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NEON A TO L OG Y
S.No Topic Page No.
1. WHO definitions and Vital statistics of Neonates 1
2. General Examination of NB 3
3. Neonatal reflexes 10
4. Examination of cranial nerves in NB 11
5. Routine NB care after birth 12
6. Umbilical cord care 14
7. Neonatal Resuscitation 17
8. Prematurity / Late Preterm 24
9. IUGR/SGA 29
10. Post-term infants 31
11. Large-for-gestational-age infants 32
12. Neonatal Sepsis 32
13. Neonatal Hyperbilirubinemia 39
14. Physiological jaundice 41
15. ABO incompatibility 43
16. Rh incompatibility 44
17. Exchange transfusion 48
18. Phototherapy 49
19. Kernicterus 50
20. Breast milk jaundice 51
21. Hereditary spherocytosis 53
22. G-6 PD deficiency 53
23. Crigler-Najjar syndrome 54
24. Gilbert Syndrome 56
25. Lucy - Driscol Syndrome 56
26. Dubin-Jhonson Syndrome 57
27. Rotor Syndrome 57
28. Direct Hyperbilirubinemia 57
29. Neonatal Hepatitis Syndrome 59
30. Respiratory Distress In New-Born 61
31. Transient Tachypnea Of The Newborn- RDS II 63
32. Hyaline Membrane Disease – RDS I 63
33. Meconium Aspiration Syndrome 67
34. Hypoxia-Ischemia in Neonate 69
35. Haemorrhagic Disease of Newborn 74
36. High risk neonate & its causes 75
37. Neonatal seizures 76
38. Multiple pregnancy 80
39. Infant of a Diabetic Mother 80
40. Vertical Transmission (Mother To Child Or Perinatal) 83
41. Congenital Rubella 84
42. Oral Candidiasis 85
43. Infant Of Hepatitis B Positive Mother 85
44. High risk neonate 86
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NEONATOLOGY
WHO definitions and Vital statistics of Neonates
Intramural baby: A baby born within premises of your centre
Extramural baby: Baby not born within premises of your centre
Fetus: Fetus is a product of conception, irrespective of the duration of pregnancy, which is not completely
expelled or extracted from its mother
BIRTH: Birth is the process of complete expulsion or extraction of a product of conception from its mother.
LIVE BIRTH:
A live birth is complete expulsion or extraction from its mother of a product of conception,
irrespective of duration of pregnancy, which after separation, breathes or shows any other evidence
of life, such as beating of the heart, pulsation of the umbilical cord, or definite movements of
voluntary muscles. This is irrespective of whether the umbilical cord has been cut or the placenta is
attached. [Includes all live births >500 grams birth weight or >22 weeks of gestation or a crown heel
length of >25 cm]
STILL BIRTH:
Death of a foetus having birth weight >500 g (or gestation >22 weeks or crown heel length >25 cm) or
more.
BIRTH WEIGHT:
Birth weight is the first weight (recorded in grams) of a live or dead product of conception, taken after
complete expulsion or extraction from its mother. This weight should be measured within 24 hours of
birth; preferably within its first hour of live itself before significant postnatal weight loss has occurred.
Low birth weight (LBW):
Birth weight of less than 2500 gm; Very low birth weight (VLBW): Birth weight of less than 1500 gm;
Extremely low birth weight (ELBW): Birth weight of less than 1000 gm
Embryonic period:
0-8 weeks of gestation
Fetal period:
9 weeks of gestation till the expulsion
PERINATAL PERIOD
Commences from 22 weeks (154 days) of gestation (the time when the birth weight is 500 g), and ends
at 7 completed days after birth.
The neonatal period:
It commences at birth and ends 28 completed days after birth.
Early neonatal period refers to 0-7 days of life and
Late neonatal period refers to 8-28 of life;
Post neonatal refers to 29-365 days of life.
Gestational age:
Full term: Child born after completion of 37 weeks and before competition of 42 weeks
Preterm: Born before completion of 37 weeks (and after 22 weeks of gestation)
Late preterm: Born between 34 completed to before completion of 37 weeks
Post term: Born after completion of 42 weeks
Birth weight:
Appropriate for gestational age AFGA: birth weight between 2.5 to 4 kg
Heavy for gestational age HFGA: birth weight between more than 4 kg
Light for gestational age: Birth weight less than 2.5 kg
Intra uterine growth restriction IUGR:
1. Definition: weight less than 10th percentile for gestational age.
2. Types:
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i. Symmetrical (type I):

1. All parameters (length + HC + wt) .
2. Reflects long-term nutrition.
3. Chromosomal and genetic causes
ii. Asymmetrical (type II): reflects short-term nutrition.
i. HC remains normal while length and weight are decreased.
ii. Maternal anemia, PIH etc
Combined classification:
I. Preterm
a. LFGA : light for gestational age
b. AFGA : Appropriate for gestational age
c. HFGA: Heavy for gestational age
II. Term
a. LFGA : light for gestational age
b. AFGA : Appropriate for gestational age
c. HFGA: Heavy for gestational age
III. Post term
a. LFGA : light for gestational age
b. AFGA : Appropriate for gestational age
c. HFGA: Heavy for gestational age
Normal birth definition (WHO):
Normal birth is defined as one which is spontaneous in onset, low-risk at the start of labour and
remaining so throughout labour and delivery. The infant is born spontaneously in the vertex position
between 37 and 42 completed weeks of pregnancy. After birthmother and infant are in good health.
Normal Newborn - definition:
1. Normal newborn refers to infant with full term gestation (between 37 completed and before
completion of 42 weeks)
2. AFGA-birth weight between 2.5 to < 4 kg
3. No risk factors in antenatal period
4. Normal Apgar at birth: 7-10 at 1st minute
5. No major congenital anomalies
6. O/E: infant has rosy pink colour, lusty cry and normal feeding, activities and muscle tone
Maternal death:
A maternal death is the death of a woman known to be pregnant within 42 days of termination of
pregnancy, irrespective of the duration or site of the pregnancy from any cause related to or
aggravated by the pregnancy or its management, but not from accident or incidental causes.
Prolonged rupture of membranes:
Rupture of membranes or leaking for > 18 hours.
Antepartum hemorrhage:
Bleeding per vaginum after 20 weeks of gestation
HYPOTHERMIA:
Skin temperature <36.0C
HYPOGLYCEMIA:
Whole blood glucose of less than 45mg/dL (some textbooks say 40)
HYPOCALCEMIA:
Any one of the following:
1. Serum total calcium <7 mg/dl. or
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2. Serum ionized calcium <4 mg/dl.

3. QOTC >0.2 seconds on ECG which normalizes after calcium therapy.
Neonatal mortality rate:
Definition: Number of deaths during the first 28 completed days of life per 1,000 live births in a given
year or period.
Neonatal deaths may be subdivided into early neonatal deaths, occurring during the first seven days of
life, and late neonatal deaths, occurring after the seventh day but before the 28 completed days of
life.
Number of infant deaths during the year
Infant mortality rate
------------------------------------------------------ x 1000
(IMR)
Number of live births during the year

Number of infant deaths of < than 29 days during the year

Neo-natal mortality
--------------------------------------------------------- x 1000
rate (NMR)
Number of live births during the year

Number of still births and infant deaths of < than 7 days during the year
Peri-natal mortality
------------------------------------------------------------- x 1000
Rate (PMR)
Number of live births and still births during the year

India: SRS 2013-14

1. Birth rate: 21.4/1000 population
2. Death rate: 7/1000 population
3. Infant mortality rate:
a. India 40/live births
b. Tamilnadu 21
c. Pondicherry 17
4. India: U5MR is at 49 deaths per 1000 live births
5. MMR status at all India level is at 167/1000 000 live births in 2011-13.
6. NMR 28/1000 live births (2013)
7. PMR 26/1000 total births (2013)
Values of IMR from Director of Public Health, Chennai:
Tamilnadu: SRS 2008-09 statistics per thousand live births
NNMR 23
Post Neonatal DR 12
Perinatal MR 8.4
U5 mortality 26

GENERAL EXAMINATION OF NB
Timing of examination:
1. 1st : soon after delivery.
2. 2nd : detailed examination within 24 hours
3. 3rd : discharge examination
General Appearance:
Physiological States:
NB normally passes through five different physiological states as described by Prechtl and Beintema.
NB spends about 20 hr. in stage 1& 2
Prechtl and Beintema staging:
1. Deep sleep(REM)
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2. Light sleep (non REM)

3. Awake, light peripheral movements
4. Awake, large movements, not crying
5. Awake, crying
Posture
1. Universal flexion: full term
2. Universal extension: preterm
3. Asymmetric tonic neck reflex in later neonatal period
4. Lower limbs flexed over abdomen in extended breech presentation.
Respiratory Rate and Heart Rate
1. The normal respiratory rate is 30 to 60 inspirations per minute in a term infant, some normal infants
breathe shallowly and then rapidly.
2. The heart rate is 110 to 160 beats per minute in healthy term infants, but it may vary significantly
during deep sleep or active awake states.
3. Preterm infants have resting heart rates at the higher end of the normal range.
Blood Pressure
1. The flush method for obtaining mean pressure is easier in an active infant and requires only a
sphygmomanometer.
2. Normal BP at birth: (90th percentile) 87/68
Facies
Unusual facial appearance represents malformation, deformation, a syndrome, or merely familial
appearance. Odd or funny looking facies may have:
Head and Neck
FEATURE CONDITIONS
Hypertelorism DiGeorge syndrome; Crouzon syndrome; Mucoploysachharidoses; Wardenburg;
Cri du chart etc
Hypotelorism craniostenosis; Trisomy 13; microcephaly etc
Mangoloid slant: Down and Noonan; Prader willi
Antmangoloid slant: Treacher-Collins syndrome; Apert; Cerebral gigantism
Low set ears: Down syndrome; Turner syndrome; Beckwith-Wiedemann syndrome; Potter
syndrome; Rubinstein-Taybi syndrome; Smith-Lemli-Opitz syndrome; Treacher
Collins syndrome; Trisomy 13; Trisomy 18
Upturned nose William syndrome; Fetal alcohol syndrome
Corenelia de lange syndrome
Beaking of nose Crouzan syndrome; Rubinstein-Taybi
Downturned mouth Cri du chart; Prader willi
Syntrichosis Corenelia de lange syndrome
Saddle nose Congenital syphilis; Chr 7 p deletion
Long filtrum Williams; Digeorge
Upslanting palpebral Down syndrome; Alagille syndrome; Ck syndrome; Prader-willi syndrom
fissures

Downslanting palpebral Apert syndrome; Beckwith-wiedemann syndrome; Muenke syndrome

fissures Noonan syndrome; Oral-facial-digital syndrome; Treacher collins syndrome

1. HC (Occipito Frontal Circumference - OFC): 35 cm

2. Size of the head is appropriate for the size of the face
3. Abnormal occipital prominence found in posterior fossa masses (e.g., Dandy-Walker malformation),
4. Frontal prominence due to increased cranial volume- hydrocephalus
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5. The boat-shaped scaphocephaly is synostosis of the sagittal suture

6. Right-sided flattening (plagiocephaly) occurs more often than left due to the more common left
occiput anterior descent during birth
Hair and Scalp
1. Reddish or blond hair in a dark-skinned infant may indicate albinism
2. White forelocks with other pigment defects and anomalies are associated with deafness and
retardation Eg. Waardenburg syndrome
3. In 97.5% of newborns, there is a single parietal hair whorl, located in or just to the right of the midline
approximately 80% of the time. Nearly 90% of these whorls have a clockwise rotation. More than two,
an isolated frontal or a significantly abnormally positioned whorl may be a sign of abnormal
development of underlying structures.
4. Hair unruliness: genetic syndromes, including Cornelia de Lange and Down syndromes.
5. Transillumination of the skull may detect large fluid collections: Hydrocephalus.
Palpation of the Head
1. There are six bony plates to the cranial vault; one frontal, two parietal, two temporal, and one
occipital.
2. Sutures: Normally at birth, these bones are separated by suture lines of which there are also six:
metopic, sagittal, and paired coronal and lambdoid.
3. Craniostenosis: Growth of the skull plates is perpendicular to the suture lines. If the sutures fuse
prematurely, growth is impaired, giving rise to the various forms of Cranio Stenosis.
4. Craniotabes: softer areas of skull; occur most often pathologic craniotabes occurs in syphilis and
rickets
5. Fontanels:
a. At birth,an infant has six fontanels: the anterior and posterior, two mastoid, and two
sphenoid
b. Anterior Fontanelle
i. Junction of coronal Suture and sagittal Suture
ii. Mean newborn size: 2.1 cm
iii. Often enlarges in first few months of life
iv. Closes between 4 to 26 months (median 13.8 months)
v. Closes by 3 months in 1% of infants
vi. Closes by 24 months in 96% of infants
c. Posterior Fontanelle
i. Junction of lambdoidal Suture and sagittal Suture
ii. Mean newborn size: 0.5 to 0.7 cm
iii. Closes by 2 months
d. Causes of abnormal Anterior Fontanelle
i. Bulging Fontanelle causes
1. Crying, coughing or Vomiting
2. Increased Intracranial Pressure
3. Hydrocephalus
ii. Sunken Fontanelle causes
1. Decreased Intracranial Pressure (dehydration)
iii. Large Fontanelle or delayed closure
1. Congenital Hypothyroidism
2. Trisomy 21 (Down Syndrome)
3. Rickets
4. Achondroplasia
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5. Increased Intracranial Pressure

iv. Small Fontanelle or early closure
1. Early closure may be normal
2. Always evaluate for Microcephaly
3. See Craniosynostosis
d. A third fontanel between the anterior and posterior fontanels is associated with
hypothyroidism and Down syndrome
Caput succedaneum:
a. Presents at birth with pitting edema and initially is most prominent over the presenting area.
b. It represents fluid accumulation within and under the scalp.
c. Although a caput initially may be limited to overlying a single bone, it will shift to dependent regions
and be more apparent in crossing sutures.
d. Any non-fluctuant swelling that is palpable in the delivery suite is more likely a caput.
Cephalohematoma:
a. Develops after delivery and expands during the first few hours as blood accumulates between the
surface of a calvarial bone and its pericranial membrane.
b. Boundaries limited by suture lines.
c. Feels fluctuant.
d. The blood may take several weeks to resorb and prolong neonatal jaundice.
Subgaleal hematoma:
a. Occur most often after vacuum or difficult forceps extractions but may develop spontaneously even in
cesarean or unassisted vaginal deliveries.
b. Tracking of the swelling towards the nape of the neck and bluish discoloration will confirm the
diagnosis.
Eyes
1. Rocking gently back and forth may encourage spontaneous eye opening in dim light;
2. Synophrys (fusion of eye brows) is a sign of Cornelia de Lange or others.
3. Absent eyelashes may be a clue to Ectodermal dysplasia
4. Subconjunctival hemorrhages may be present following vaginal delivery.
5. Tearing or persistent eye crusting after the first 2 days calls for evaluation for glaucoma, infection,
corneal abrasion, mass lesions with obstruction of the nasolacrimal duct, or absence of the puncta.
6. The signs of congenital glaucoma include photophobia, excessive tearing, cloudy cornea, or eyes that
appear large.
7. Cornea: clouding indicates mucopolyscchridosis or glaucoma.
8. Iris: look for coloboma a defect in circular shape of pupil
9. Congenital Cataract: Down syndrome; Rubella syndrome
Ears
1. Posteriorly rotated or low-set ears occur when cephalad migration and anterior rotation fail to
complete. At least 30% of the pinna should be above a line extended between the medial canthi
2. A behavioural reaction (eg. Moro or blinking) to a sound excludes gross bilateral hearing deficits.
Nose
1. Nasal patency:
a. It is assessed by free passage of a small catheter through both nares and into the stomach.
b. Absence of nasal canal is called choanal atresia which may be unilateral or bilateral.
Mouth and Throat
a. Asymmetry on crying occurs with facial nerve paresis,
b. One to six pairs of small benign midline cysts known as “Epstein pearls” may be present at the
junction of the hard and soft palates. These cysts are benign and often resolve by 3 months of age.
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c. Natal teeth, often in pairs, may be found most commonly along the mandibular alveolar ridge. These
fairly mobile teeth are present in 1:2,000 to 3,000 live births and are often removed due to concerns
of aspiration. Despite the probable low risk of aspiration, removal should be considered due to
ulceration of the ventral surface of the tongue, which may occur if they are retained
d. A prominent tight frenulum (ankyloglossia or “tongue tie”) may cause poor breast-feeding.
Skin:
Skin Colour:
a. Normal: rosy pink, pale in anemia ans sepsis and Plethoric in polycythemia and prematurity, babies of
Diabetic mother,
b. Icterus progresses in a cephalocaudal pattern and is best appreciated in natural light. Detection may
be improved by gently blanching the skin to remove the bloodfrom the dermal capillaries.
c. Areas of hypo- or hyperpigmentation such as café au lait spots are important to document as they
may be associated with neurologic disorders.
d. Harlequin colour change:
a. A rare but dramatic vascular event, harlequin color change occurs in the immediate
newborn period and is most common in low birthweight (LBW) infants.
b. It probably reflects an imbalance in the autonomic vascular regulatory mechanism.
c. When the infant is placed on one side, the body is bisected longitudinally into a pale upper
half and a deep red dependent half.
d. The color change lasts only for a few minutes and occasionally affects only a portion of the
trunk or face.
e. Changing the infant's position may reverse the pattern.
f. Muscular activity causes generalized flushing and obliterates the color differential. Repeated
episodes may occur but do not indicate permanent autonomic imbalance.
e. Cutis marmorata: Another frequent skin pattern is marbling of the extremities from vasoconstriction
(cutis marmorata) occurring when the infant undergoes hypothermic stress.
f. Mangolian spots:
a. Slate-blue, well-demarcated areas of pigmentation are seen over the buttocks, back, and
sometimes other parts of the body in more than 50% of black, Native American, or Asian
infants and occasionally in white ones.
b. These patches have no known anthropologic significance despite their name, Mangolian
spots; they tend to disappear within the 1st year.
c. Mongolian spot results from entrapment of melanocytes in the dermis during their
migration from the neural crest into the epidermis.
d. Large area of mangolian spots is an early marker of Hurler syndrome
(Mucopolysaccharidosis)
e. D.D: blue nevi
f. Treatment: usually not necessary.
g. Erythema toxicum:
a. Erythema toxicum may be noted occasionally at birth, although it is more common in the
next day or two. These papular lesions with an erythematous base are found more on the
trunk than on the extremities and fade without treatment by 1 week of age.
b. Occurs in ≈50% of full-term infants; preterm infants are affected less commonly. Incidence
more male infants
c. The lesions are 1–2 mm papules or pustules with a surrounding erythematous flare. At
times, splotchy erythema is the only manifestation.
d. Palms and soles are usually spared.
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e. Peak incidence occurs on the 2nd day of life, but new lesions may erupt during the 1st few
days as the rash waxes and wanes.
f. The pustules form below the stratum corneum or deeper in the epidermis and represent
collections of eosinophils
g. These papular lesions with an erythematous base are found more on the trunk than on the
extremities and fade without treatment by 1 week of age.
h. The cause of erythema toxicum is unknown.
i. D.D: The lesions can mimic pyoderma, candidosis, herpes simplex, transient neonatal
pustular melanosis, Incontinentia pigmenti and miliaria
j. The course is brief, and no therapy is required. and eosinophilic pustular folliculitis also have
eosinophilic infiltration but can be distinguished by their distribution, histologic type, and
chronicity.
k. The exact cause of Erythema Toxicum development remains unknown.
i. ? less severe form of graft versus host disease could act as stimuli for the condition
t
ii. It could be a normal inflammatory reaction or a normal response of the body’s
immune system
iii. It could be a newborn child’s immune response to harmless microorganisms, which
may have penetrated the infant’s skin during birth
h. Melia:
a. A rash in which tiny sebaceous retention (of keratin) cysts are seen. The whitish yellow
pinhead-size concretions are usually on the chin, nose, forehead, and cheeks without
erythema.
b. These are seen in ~33% of infants, and these benign cysts disappear within a few weeks
after birth.
Lymph Nodes
Lymph nodes are palpable in more than one-third of all neonates, most commonly in the inguinal region.
Abdomen
a. The liver is usually palpable, sometimes as much as 2 cm below the rib margin.
b. In diaphragmatic hernia abdomen is scaphoid and chest is full
c. In duodenal atresia there is gastric distension (double bubble)
d. Distension of the urinary bladder suggests posterior urethral valve
Umbilicus
a. The umbilicus normally is positioned approximately halfway between the xiphoid and pubis.
b. The cord is a uniform ivory color ranging in length from 30 to 100 cm; a shorter cord suggests
decreased fetal movement and a reason for fetal distress.
c. Deep green staining of the cord is a sign of prior fetal distress reflecting the passage of meconium at
least several hours prior to delivery. Superficial staining reflects very recent passage of meconium.
d. If the base of the umbilical cord itself is especially broad or remains fluctuant after vascular pulsations
have stopped, there may be a herniation of abdominal contents into the cord (omphalocoel).
e. At birth, the presence of two arteries and a single vein should be identified. Single umbilical arteries
occur in approximately 1% of pregnancies with nearly 10% of identified cases having another
congenital malformation. A single umbilical artery increases the risk for an occult renal anomaly.
f. After the cord falls off, the umbilicus should be examined for granuloma or continued leakage through
a patent urachus.
g. Omphalitis is an acute local inflammation of the periumbilical tissue that may extend to the abdominal
wall, the peritoneum, the umbilical vein or portal vessels, or the liver and may result in later portal
hypertension.
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Genitals:
a. The genitals respond to transplacentally acquired maternal hormones to produce prominence of the
genitals in females, often with considerable non purulent discharge. A normal scrotum at term is
relatively large
b. The testes should be in the scrotum or should be palpable in the canals in term infants.
c. The prepuce is normally tight and adherent. Severe hypospadias or epispadias may indicate that
abnormal sex chromosomes are present.
d. The prepuce of a newborn infant is tight and adherent. Severe hypospadias or epispadias may
indicate either abnormal sex chromosomes or adrenogenital syndrome.
Anus:
a. Passage of meconium usually occurs within the 1st 12 hr after birth; 99% of term infants and 95% of
premature infants pass meconium within 48 hr of birth.
b. Imperforate anus if not visible requires examination by gentle insertion of the examiner’s little finger
or a rectal tube.
Chest
a. In term neonates, the chest circumference is 1 to 2 cm less than the head circumference; it is relatively
smaller with lower GA.
b. Mild subcostal and intercostal retractions are common even in healthy neonates because of their
compliant chest walls. This is seen commonly in laryngotracheomalacia. Supraclavicular retractions are
never normal.
c. Neonatal lung sounds are relatively more bronchial than vesicular because of better transmission of
large airway sounds across a small chest.
d. Benign inspiratory stridor is due to congenital laryngotracheomalacia.
Clavicles
a. Clavicular fracture is the most common form of birth trauma. Most clavicular fractures are
asymptomatic and are incidental findings ona chest radiographs. When symptomatic, the most
frequent findings are swelling from hematoma, crepitations, asymmetrical bone contour, and crying
with passive movement.
Nipples
a. The breasts of term infants vary in diameter from 0.5 cm to several intercostal, with clinically
insignificant differences between genders.
e. Mastitis neonatorum:
a. Usually 1 cm in diameter in term male and female infants and may be abnormally enlarged
(3–4 cm) secondary to the effects of maternal estrogens. This effect, which lasts <1 week, is
of no clinical concern.
b. A usually white discharge, commonly referred to as “neonatal milk” or “witch’s milk,” may be
present and is normal. It is seen in full-term infants with larger than average breast nodules
and may continue for up to 2 months of age.
c. Unless there are specific signs of inflammation, enlarged breasts should be left alone.
b. Supernumerary nipples occur in 1.2% to 1.6% of darkly pigmented infants but are more unusual in
lightly pigmented infants. These supernumerary nipples, seen in the milk line below and lateral to the
true breast, are rudimentary, occasionally only distinguishable because of the presence of a small
pigmented mark or dimple.
Cardiovascular System
a. Resting rate 120-130 bpm (range 100-150);
b. Apical impulse: fourth or fifth intercostal space in the midclavicular line.
c. The femoral pulse is located just lateralto the femoral triangle beneath the inguinal ligament. The
absent or typical radial-femoral delay is observed in coarctation of the aorta.
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d. A systolic murmur from a closing PDA will be present in the first 24 to 48 hours of life.
e. Infants with the most serious forms of congenital heart disease may have no murmur
Genitourinary System
1. Normal penile length at term is at least 2.5cm.
2. The presence of both testes indicates term gestation. Archidometer is one used for measuring the size
of testes
Musculoskeletal System
a. A pilonidal sinus may be present at the bottom of a sacral pit
b. Long tufts of hair over sacrum: spina bifida occulta
Hand examination:
a. The creases of the fifth digit should be parallel. If there is shortening ofthe mid phalanx, the
nonparallel creases mark a radial deviation, clinodactyly. Any curve lessthan 10 to 15 degrees is
normal.
b. Extra digits that are postaxial or on the ulnar side are most often equivalent to skin tags and of no
significance; they may be familial, most often in families of color.
c. Extra digits on the preaxial or radial side are often enough associated with hematologic and cardiac
abnormalities to warrant further evaluation.
Nervous System
1. A neonate with facial asymmetry while crying and who has a flattened or absent nasolabial fold has a
facial palsy.
2. The most common peripheral nerve injury associated with vaginal delivery is a brachial plexusinjury.
Injuries may be incurred secondary to traction on an arm during birth. The upperroots, C-5 and C-6,
are most commonly damaged, leaving the infant with a prone adductedarm at his or her side.
3. Jitteriness, characterized by rhythmic tremors of equal amplitude around a fixed axis in an extremity
or the jaw, may occur in 41% to 44% of healthy newborns. If it fails to cease during sucking, it may be
a sign of hypoglycemia, hypocalcemia, or drug withdrawal. Jitteriness may persist in some infants for
many months with the infants having more severe accompanying CNS symptoms having longer
persistence.

NEONATAL REFLEXES
1. Moro reflex (or startle reflex). Symmetrical extension of arms and legs on startling. Usually tested by
allow the baby’s head to fall backwards suddenly. Loud sudden noises will precipitate the reflex.
Observe for any asymmetry (abnormal). Inhibited at 3-6 months.
2. Asymmetrical tonic neck reflex. As the head turns to one side, the ipsilateral arm and leg extends
while the contralateral limbs flex (‘fencer pose’). Inhibited by 4-6 months.
3. Symmetrical tonic neck reflex. Extension of the neck produces arm extension and leg flexion. Vice
versa with neck flexion. Inhibited at 6 months.
4. Grasping reflex. Palmar reflex. An object or finger placed in the palm is automatically grasped.
Inhibited at 4-6 months.
5. Rooting reflex. Head is turned with mouth open towards a stimulus on the cheek or at the corner of
the mouth. Triggered by the nipple to prompt breast feeding. Inhibited 3-4 months.
6. Sucking reflex. Forceful rhythmic sucking on an item placed in the mouth with coordinated
swallowing. Inhibited 3-4 months.
7. Babinski or plantar reflex. Dorsiflexion of toes on stimulation of sole of foot from heel to toes.
Inhibited 6-9 months.
8. Blink reflex. Stimulated by bright light in eyes. Not inhibited.
9. Pupillary reflex. Pupillary constriction with light stimulus. Not inhibited.
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10. Galant reflex. Neonate held or lying prone. Trunk curves towards the stimulated side when stroked
along one side of spinal column from head to buttocks. Inhibited 1-3 months.
11. Stepping reflex. Held upright, the neonate makes stepping movements when a foot touches a flat
surfaces or an edge. Disappears by 2-3 months but returns as a voluntary movement at 10-15 months
as the child begins to walk.
12. Downward Parachute: protective response develops at 4-6 months.
13. Glabellar reflex (blink reflex). Tap gently over the forehead and the eyes will blink.
14. Neck-righting reflex. Turn the infant’s head to the right or left and movement of the contralateral
shoulder should be obtained in the same direction.
15. Moro reflex. Support the infant behind the upper back with one hand, and then drop the infant back 1
cm or more to¾but not on¾the mattress. This should cause abduction of both arms and extension of
the fingers. Asymmetry may signify a fractured clavicle, hemiparesis, or brachial plexus injury. Absence
in upper limb may be due to clavicular fracture; absence in lower limb may be due to congenital
dislocation of hip, septic arthritis etc
Abnormal patterns:
a. Most reflexes are present at birth and disappear by 3-4 months when cerebral cortex takes control
over spinal cord
b. Persistence of these primitive reflexes beyond the expected period indicates conditions like cerebral
palsy
c. Diminished response may be due to hypoglycemia, sepsis, HIE, Cretinism etc
d. Exagerated response may be due to cerebral irritability, hypocalcemia, hyperthyroidism etc

EXAMINATION OF CRANIAL NERVES IN NB

Cranial Nerve Assessment

I Withdrawal or grimace to strong odor (e.g.,
peppermint,oil of cloves) Presence of routing refles by
smell of breast.
II Behavioural response to light (i.e., blinking fixing, follwing,
turning to light source);
III, IV, VI Ocular movement, doll's eyes, oculovestibular response,
pupil size, gemini red reflex
VII Facial muscle tone at rest and during crying
V, VII, XII Sucking strength, rooting reflex
VIII auditory a portion Behavioural response to horn (i.e., blinking widened
eyes); quieting to voice
IX, X Swallowing with normal gag
VII, IX Facial expression to strong flavour
XII Tongue fasciculation, thrust, ability to shape around
nipple

ROUTINE NB CARE AFTER BIRTH

In delivery room:
1. Nursery personnel should use chlorhexidine or iodophor-containing antiseptic soaps for routine hand
washing before caring for each infant. Rigid enforcement of hand-to elbow washing for 2 min in the
initial wash and 15-30 sec in the 2nd wash is essential for staff. Equally thorough washes between
handling infants are also required.
2. Birth weight and tagging for identification are done as soon as possible.
 12

3. WHO guidelines:
a. Do not wipe off vernix if present.
b. Bathing should be delayed until 24 hours after birth. If this is not possible due to cultural
reasons, bathing should be delayed for at least six hours (WHO- 2013)
Air ways:
1. Low-risk infants may initially be placed head downward after delivery to allow gravity to clear the
secretions from airways; wiping of the mouth with a cloth or gentle suction with a bulb syringe or soft
catheter may also be helpful.
2. Healthy infants should be given directly to their mothers for immediate bonding and nursing.
3. In a vigorous baby ther is no need for air way suctioning.
Temperature:
1. Normal: 36.5 to 37.5; Cold stress 36.5 to 36; Hypothermia< 36 C
2. To reduce heat loss, it is desirable to ensure that infants are dried and either wrapped in blankets or
placed under radiant warmers.
3. The postnatal room should be kept at a room temperature of at least 25.0 C.
4. Rooming in: Mother and her baby should be kept together from birth - together in bed or very near to
each other.
5. Small babies (i.e. low birth weight) should ideally be kept in skin-to-skin contact position (Kangaroo
mother care)
6. The steps to keep the newborn warm are called the warm chain.
a. Warm the delivery room.
b. Immediate drying.
c. Skin-to-skin contact at birth.
d. Breastfeeding.
e. Bathing and weighing postponed.
f. Appropriate clothing/bedding.
g. Mother and baby together.
h. Warm transportation for a baby that needs referral.
Skin care:
1. Skin and cord should be cleansed with warm water or a mild non medicated soap solution to reduce
the incidence of skin and periumbilical colonization with pathogenic bacteria.
2. One application of triple dye followed by twice-daily alcohol swabbing (until the cord falls off) reduces
colonization
Eye care:
1. The eyes must be protected against ophthalmia neonatorum by instillation of 1% silver nitrate drops
or erythromycin (0.5%) or tetracycline (1.0%) sterile ophthalmic ointments.
2. This procedure may be delayed during the initial short-alert period after birth to promote bonding.
Cord care:
1. Tie the cord two fingers’ length ( from the baby’s abdomen and make another tie two fingers from
the first one. Cut the cord between the first and second tie.
2. Do not put anything on the cord stump.
3. The umbilical stump should be left dry; should not apply anything on the stump.
4. Look for any possible signs of infection of the umbilical stump such as pus discharge from the
stump and redness around the cord.
Vit.K:
1. An intramuscular injection of 1 mg of water-soluble vitamin K1 (phytonadione) is recommended for all
infants immediately after birth to prevent hemorrhagic disease of the newborn. (within 6 hours)
2. Oral vitamin K may also be useful but is not as effective as the parenteral dosage.
 13

Neonatal screening:
1. It is available for various genetic, metabolic, hematologic, and endocrine disorders.
2. The most commonly identified disorders include hypothyroidism (52/100,000 births), cystic fibrosis
(30/100,000), hemoglobinopathies (26/100,000), medium-chain acyl–coenzyme A dehydrogenase
deficiency (6/100,000), galactosemia (5/100,000), and phenylketonuria (5/100,000), and adrenal
hyperplasia (5/100,000).
3. Universal screening of infants is recommended to ensure early detection of hearing loss
Breastfeeding:
1. Colostrum feeding as within 1 hour after birth and exclusive breastfeeding upto 6 mo. of life should
be encouraged.
2. The mother should be advised to breastfeed on demand, day and night as long as the baby wants.
3. No prelacteal feedings like sugar water; donkey milk etc should be given.
4. Weight gain pattern: 30 g, 20g and 10g during the first, second and third, 4-month periods respectively
during the first year of life.
Hygiene:
1. The baby need not be bathed daily; (s)he should be washed only if necessary.
2. However, the face, neck, and underarms should be wiped daily. The gluteal region should be wiped
whenever it gets soiled.
Danger signs:
Early recognition of these signs will help in identifying those babies who need urgent care and treatment.
The important danger signs are given below:
1. Not feeding well
2. Less active than before
3. Fast breathing (more than 60 breaths per minute)
4. Moderate or severe chest in-drawing
5. Grunting / moaning
6. Convulsions
7. Floppy or stiff
8. Temperature >37.50C or <35.50C
9. Umbilicus draining pus or umbilical redness extending to skin.
10. More than 10 skin pustules or bullae, or swelling, redness, hardness of skin
11. Bleeding from stump or cut
Immunization: All babies should receive the following 3 vaccines within the first week of life:
a. BCG,
b. OPV-0,
c. Hepatitis B immunization is recommended for newborns with weight >2 kg irrespective of
maternal hepatitis status.
Follow up:
Each baby should be followed up in the well-baby clinic for assessment of growth and development,
immunization, early diagnosis and management of illnesses, and health education of parents.
Follow up visits should be made to coincide with immunization schedule as far as possible.

UMBILICAL CORD
1. Umbilical cord has a potential danger of neonatal problems:
a. Neonatal tetanus
b. Umbilical sepsis (omphalitis)
c. Bleeding from the stump
 14

2. The umbilical cord is a unique tissue, consisting of two arteries and one vein covered by a mucoid
connective tissue called Wharton's jelly and a thin mucous membrane, the sheath of the umbilical cord
derived from the amnion.
3. The instrument used cuts through living tissue and vessels that are still connected to the infant's blood
stream; it therefore needs to be sterile to avoid infection.
4. The devitalized tissue of the cord stump can be an excellent medium for bacterial growth, especially if the
stump is kept moist and unclean substances are applied to it. The umbilical vessels are still patent for a few
days following birth, thus providing direct access to the bloodstream. Keeping the stump clean and dry is
therefore very important if infection is to be prevented.
5. The umbilicus is colonized by bacteria from environmental sources such as the mother's vagina, her skin
flora, and the hands of caregivers. In hospital nurseries, S. aureus is the most common colonizing organism
and is acquired mostly from the hands of nursery personnel. Once colonized, the umbilicus acts as a
reservoir of bacteria that may cause cross-infection in the nursery
6. If a baby is kept with its mother (by rooming-in), the bacteria colonizing the baby come mostly from its
mother's normal skin flora and are predominantly non-pathogenic and hence rooming in protects the
stump.
7. Separation of the umbilical cord stump is mediated by inflammation of the junction of the cord and the
skin of the abdomen with leucocyte infiltration and subsequent digestion of the cord. The cord normally
falls off between 5 and 15 days after birth; Delayed cord separation with antiseptics may be due to
destruction of the normal flora around the umbilicus.
8. Cord infection is called omphapitis; S.areus, E. coli and group B streptococci are common infections.
9. Cord clamping:
a. cord is traditionally clamped after cessation of pulsation
b. Early clamping: < 1 mt;
i. Avoids polycythemia in preterm and IUGR
ii. There is some evidence that early clamping reduces the duration of the third stage of
labour & decreases the chance of PPH
iii. Early clamping may deprive extra blood received by the child and lower haematocrit and
haemoglobin levels
iv. Early cord clamping should be avoided in Rh negative women as it increases the risk of
feto-maternal transfusion
c. Delayed clamping: >1- 3 mts
i. Results in a shift of blood from the placenta to the infant. The volume transfused varies
between 20% and 50% of neonatal blood volume.
ii. Could result in overload of the heart and respiratory difficulties in polycythemic babies.
10. Choice of ties:
a. The tie should be at least 15 cm in length to allow effective tying
b. Cord clamp if used should be sterile; hands should be washed with clean water and soap before
delivery, after any vaginal examination, and again before tying and cutting the cord.
c. A sterile and sharp instrument, such as a new razor blade or scissors, is recommended for cutting
the cord
11. Length of the cord stump:
a. The recommended length of the stump after cutting is usually 2 or 3 cm.
b. Some authors recommend clamping the cord 3-4 cm clear of the abdominal wall to avoid pinching
the skin or clamping a portion of the gut which, in very rare instances, may be inside the cord.
12. Care of the cord stump:
a. the cord should be kept dry and exposed to air or loosely covered with clean clothes
 15

b. cleaning the cord should it become sticky or soiled by using clean water and soap; Cleaning with
alcohol is not recommended as it delays healing and drying of the wound
c. no applicant is necessary esp harmful substances like cow dung and ash; antiseptic use is also not
necessary as a routine
d. rooming in encourages colonization with benign maternal skin flora
e. Early and frequent breast-feeding will provide the newborn with antibodies to help fight
infections.
f. Omphalitis require parenteral antibiotic therapy.
13. Umbilical cord vessels
1. The cord contains the two umbilical arteries, the vein, the rudimentary allantois, the remnant of the
omphalomesenteric duct, and a gelatinous substance called Wharton jelly.
2. The sheath of the umbilical cord is derived from the amnion.
3. The muscular umbilical arteries contract readily, but the vein does not. The vein retains a fairly large
lumen after birth
4. The blood vessels are functionally closed, but anatomically patent for 10–20 days. The arteries
become the lateral umbilical ligaments; the vein, the ligamentum teres; and the ductus venosus, the
ligamentum venosum.
5. During this interval, the umbilical vessels are potential portals of entry for infection. The umbilical cord
usually sloughs within 2 wk.
6. Delayed separation of the cord, after more than 1 mo, has been associated with neutrophil
chemotactic defects and overwhelming bacterial infection
14. Single umbilical artery:
1. A single umbilical artery is present in about 5–10/1,000 births; the frequency is about 35–70/1,000 in
twin births.
2. Approximately 30% of infants with a single umbilical artery have congenital abnormalities; usually
more than one; many such infants are stillborn or die shortly after birth.
3. Trisomy 18 is one of the more frequent abnormalities.
4. The number of arteries present should be recorded as an aid to the early suspicion and identification
of abnormalities in such infants.
5. For infants with a single umbilical artery, many recommend renal ultrasonography
15. Congenital omphalocele
1. An omphalocele is a herniation or protrusion of the abdominal contents into the base of the umbilical
cord.
2. In contrast to the more common umbilical hernia, the sac is covered with peritoneum without
overlying skin. The size of the sac that lies outside the abdominal cavity depends on its contents.
3. Herniation of intestines into the cord occurs in about 1/5,000 births and herniation of liver and
intestines in 1/10,000 births.
4. The abdominal cavity is proportionately small.
5. Immediate surgical repair, before infection has taken place and before the tissues have been damaged
by drying (saline-soaked sterile dressings should be applied immediately) or by rupture of the sac, is
essential for survival. Mersilene mesh or similar synthetic material may be used to cover the viscera if
the sac has ruptured or if excessive mobilization of the skin would be necessary to cover the mass and
its intact sac.
6. The risk of associated congenital anomalies/syndromes, including Beckwith-Wiedemann syndrome
(omphalocele, macrosomia, hypoglycemia), trisomies 13 and 18, and cardiac anomalies, is increased in
patients with omphalocele
16. Umbilical granuloma
 16

1. The umbilical cord usually dries and separates within 6–8 days after birth. The raw surface becomes
covered by a thin layer of skin; scar tissue forms, and the wound is usually healed within 12–15 days.
2. The presence of saprophytic organisms delays separation of the cord and increases the possibility of
invasion by pathogenic organisms.
3. Mild infection or incomplete epithelialization may result in a moist granulating area at the base of the
cord with a slight mucoid or mucopurulent discharge. Good results are usually obtained by cleansing
with alcohol several times daily.
4. Persistence of granulation tissue at the base of the umbilicus is common. The tissue is soft, 3–10 mm
in size, vascular and granular, and dull red or pink, and it may have a seropurulent secretion.
5. Treatment is cauterization with silver nitrate, repeated at intervals of several days until the base is
dry.
6. Umbilical granuloma must be differentiated from umbilical polyp, a rare anomaly resulting from
persistence of all or part of the omphalomesenteric duct or the urachus. The tissue of the polyp is firm
and resistant, is bright red, and has a mucoid secretion. If the polyp is communicating with the ileum
or bladder, small amounts of fecal material or urine may be discharged intermittently. Histologically,
the polyp consists of intestinal or urinary tract mucosa. Treatment is surgical excision of the entire
omphalomesenteric or urachal remnant.
17. UMB.SEPSIS (omphalitis)
1. Although aseptic delivery and routine cord care (daily application of triple dye to the umbilical stump
and surrounding skin= brilliant green, crystal violet, and proflavine hemisulfate.) decrease the risk of
umbilical infection, the necrotic tissue of the umbilical cord is an excellent medium for bacterial
growth.
2. Omphalitis may remain localized or may spread to the abdominal wall, the peritoneum, the umbilical
or portal vessels, or the liver.
3. Infants with abdominal wall cellulitis or those with necrotizing fasciitis have a high incidence of
associated bacteremia. Portal vein phlebitis may develop and result in the later onset of extrahepatic
portal hypertension.
4. The general manifestations may be minimal (periumbilical erythema), even when septicemia or
hepatitis has resulted.
5. Treatment:
a. antibiotic therapy effective against Staphylococcus aureus and Escherichia coli and,
b. if abscess formation has occurred, surgical incision and drainage.
c. Necrotizing fasciitis is often polymicrobial and has a high mortality.
d. Changes in newborn bathing practices that replace antiseptics with nonantiseptic pH-
balanced soap may be associated with increased risk of omphalitis.
18. UMBILICAL HERNIA
1. Often associated with diastasis recti, an umbilical hernia is due to imperfect closure or weakness of
the umbilical ring.
2. Predisposing factors include:
a. Black race and
b. Low birthweight.
3. The hernia appears as a soft swelling covered by skin that protrudes during crying, coughing, or
straining and can be reduced easily through the fibrous ring at the umbilicus.
4. The hernia consists of omentum or portions of the small intestine. The size of the defect varies from
<1 cm in diameter to as much as 5 cm, but large ones are rare.
5. Treatment:
a. Most umbilical hernias that appear before the age of 6 mo disappear spontaneously by 1 yr of
age.
 17

b. Even large hernias (5–6 cm in all dimensions) have been known to disappear spontaneously
by 5–6 yr of age.
c. Strangulation is extremely rare.
d. It is generally agreed that “strapping” is ineffective.
e. Surgery is not advised unless the hernia persists to the age of 4–5 yr, causes symptoms,
becomes strangulated, or becomes progressively larger after the age of 1–2 yr.
f. Defects exceeding 2 cm are less likely to close spontaneously.
19. Prune belly syndrome.
a. Usually seen in males (97%) and of unknown genetic origin, it consists of a large, thin, wrinkled
abdominal wall, genitourinary malformations, and cryptorchidism.
b. Surgery may be required, and survival rate has improved.

NEONATAL RESUSCITATION
1. Birth is beautiful, miraculous, but the single most dangerous event that most of us will ever encounter in
our lifetimes. Our bodies are required to make more radical physiologic adjustments immediately following
birth than they will ever have to do again. It is remarkable that more than 90% of babies make the
transition from intrauterine to extrauterine life perfectly smoothly, with little to no assistance required.
The most gratifying aspect of becoming a doctor is that you could provide skillful assistance to a
compromised newborn. The time that you devote to learning how to resuscitate newborns is time very
well spent
2. CIRCULATORY TRANSITION
a. Intrauterine to natural environment
b. FETAL  TRANSITIONAL  NEONATAL
c. Placenta to innate organs: Lung, liver, GIT and kidney take over the functions of placenta
d. Parallel circulation comes to an end by functional followed by anatomical closure of RT to LT
shunts
e. Establishment of pulmonary circulation and gas exchange
3. PERINATAL PHYSIOLOGY
LUNG EXPANSIONCLEARING OF LUNG FLUID AIR EXCHANGE PO2 FROM 25 TO 60 mm Hg
DECREASE IN PULMONARY VASCULAR RESISTANCE INCREASE IN LT ATRIAL FLOW  INCREASE IN
SYSTEMIC BP
4. Causes for perinatal asphyxia:
Fetal factors
1. Premature delivery
2. Post maturity
3. Pulmonary hypoplasia
4. Intra uterine infections
5. CHD
6. Hydrops fetalis
7. Chromosomal anomalies
8. Maternal sedation
Placental
1. Infections
2. Premature separation
3. Nuchal cord
4. Cord prolapse
5. True knots
Maternal
 18

1. CPD
2. Prolonged labour:
• combined duration of the first and second stage of labour is more 18 hours
• delayed dilatation of the cervix
• inadequate descent of the presenting part
3. Ante partum hemorrhage
4. Diabetes
5. PIH
6. PROM
2. Primary vs. secondary apnoea:
Primary apnea:
When infant is asphyxiated:
 Responds with an increased respiratory rate.
 Becomes apnic, followed by a drop in heart rate
 Increase in blood pressure.
 Responds to stimulation and 02 therapy with spontaneous respiration
Secondary apnea:
When asphyxia is allowed to continue:
• The infant responds with a period a gasping respirations,
• Falling heart rate, and blood pressure.
• Takes a last breath and then enters the secondary apnea period.
• Will not respond to stimulation and death will occur unless resuscitation begins
immediately.
3. Apgar score:

Test 0 Points 1 Point 2 Points

Activity (Muscle Tone) Absent Arms & legs Active movement with
extended flexed arms & legs

Pulse (Heart Rate) Absent Below 100 BPM Above 100 BPM
Grimace (reflex) No Response Facial grimace Sneeze, cough, pulls away

Appearance (Skin Blue-gray, pale all Pink body and Normal over entire body –
Color) over blue extremities Completely pink

Respiration Absent Slow, irregular Good, crying

(Breathing)
Normal 7-10; mild asphyxia 4-7; severe asphyxia 0-3
4. A vigorous infant who do not require resuscitation:
a. Baby with strong respiratory efforts,
b. Good muscle tone, and
c. A heart rate >100 beats per minute .
d. Towel dry and wrap;
e. No need for any resuscitation
5. Baby who need resuscitation:
f. Cyanosed baby
g. Meconium smeared baby
h. Pale baby: sepsis & anemia
i. Preterm- hypoxic baby
 19

6. Difficult resuscitation:
1. Diaphragmatic Hernia
2. Choanal atresia
3. Pierre Robin
4. Meconium in deep airway
7. Steps of resuscitation: 4 Steps x 30 sec
1. Block A (Assessment) - Initial steps in stabilization
2. Block B (Breathing) - ventilation
3. Block C (circulation) - Chest compressions.
4. Block D (Drugs) - Administration of epinephrine and/or volume expansion.

I. Initial steps of resuscitation:

1. Places baby on preheated radiant warmer
2. Positions baby with neck slightly extended.
3. Suctions mouth, then nose.
4. Dries amniotic fluid from body and head and stimulates baby to breathe.
5. Removes wet linen from contact with baby.
6. Evaluate:
1. Infant breathing or crying
2. Good muscle tone
3. The infant can be dried, placed directly on the mother's chest, and covered with dry linen to
maintain temperature.
4. babies who do not cry : Stimulation
a. Acceptable methods of stimulating a baby to breath
1. 1 or 2 slaps or flicks to the soles of the feet, or
2. rubbing the back once or twice, should be sufficient
3. Improvement is indicated by the following 4 signs:
1. Increasing heart rate.
2. Improving color.
3. Spontaneous breathing.
4. Improving muscle tone.
5. Reflex irritability
b. Give O2 Therapy if there is cyanosis despite breathing:
1. Connect a blender to control O2 delivery
2. Connect pulse oxymetry
3. Keep sp O2 < 95 % for longer durations
4. Oxygen can be delivered by tubing held in cupped hand over baby’s face or
5. Oxygen mask held close to the baby’s face
O2 Treatment
Apparatus L/Mt % of available Oxygen
Room Air 21%
Hood 10-12 80-90%
Nasal tube 5-8 Held at distance:
0.5” : 80%
1” : 60%
2” : 40%
Mask 5-8 Tightly over the face 60-80%
Loosely over the face 40%
 20

Ambu Bag 6 Without reservoir 40%

With reservoir 80-90%

iii. Subsequent steps

7. Babies who dot cry after stimulation and oxygen:
c. Further steps are:
1. Manual ventilation
2. Chest compressions
3. Endotracheal intubation and mechanical ventilation
4. Medications
5. Treatment of shock
6. Special situations
7. Ethics of babies who could not be revived
8. Manual ventilation:
Indications:
1. The baby is not breathing or is gasping; The heart rate is less than 100 /mt
2. The colour remains cyanotic despite supplemental oxygen
Ventilation:
1. Volume: One tenth of a 240-ml self-inflating Ambu bag.
2. Pressure: initial pressures of 30 to 40 cm H2O; Maintenance :15-20 cm H2O
3. Frequency: Breaths should be delivered at a rate of 40 to 60 breaths per minute
9. Chest compressions:
Indications for chest compressions: The heart rate remains less than 60 bpm, despite 30 seconds
of effective positive-pressure ventilation
Technique of chest compressions:
Thumb Technique of Chest compression:
2 thumbs are used to depress the sternum, while the hands encircle the torso and
the fingers support the spine
2-finger technique:
The tips of the middle finger and index finger are used to compress the sternum,
while the other hand is used to support the baby's back;
9. Endotracheal Intubation:
a. Indications:
1. If there is meconium and the baby has depressed respirations, muscle tone, or heart rate
2. If positive-pressure ventilation is not resulting in adequate clinical improvement
3. To administer the epinephrine is directly into the trachea
4. Extreme prematurity, surfactant administration, and suspected diaphragmatic hernia.
b. Procedure:
1. Slide the laryngoscope over the right side of the tongue;
2. Insert the tube into the right side of the mouth
3. Connect ET to bag
c. Checking that the tube is in the trachea:
1. Improvement in heart rate and color.
2. Breath sounds audible over both lung fields but decreased or absent over the stomach
d. Difficult intubation
1. Large tongue, small jaw,
2. Facial features consistent with Down syndrome;
3. Pierre Robin syndrome
 21

10. Medications:
Intravenous access
The umbilical vein
Through ET
Intra osseous
Epinephrine
1. Is indicated when the heart rate remains below 60 bpm:
2. Intravenous dose in new-born is 0.1 to 0.3 ml/kg of a 1:10,000 solution
3. Endotracheal: higher dose (0.3 to 1 mL/kg, or 0.03 to 0.1 mg/kg
4. follow the drug with a 0.5- to 1-mL flush of normal saline
5. Give rapidly—as quickly as possible
Naloxone Hydrochloride
1. Dose—0.1 mg/kg IV with either the 0.4 mg/mL or 1.0 mg/mL solution.
Bicarbonate
1. Not indicated in routine neonatal resuscitation, given for documented metabolic acidosis
after establishment of adequate ventilation and circulation. Dose is 2 m Eq /kg of an 0.5-
mEq/ mL solution infused over at least 2 minutes.
The baby in shock:
i. Give Normal Saline: 10 ml/kg through Umbilical vein Over 5-10 minutes
ii. Dopamine drip: 5-20 mic.g/kg/mt
11. Contraindications for intubation and bag and mask ventilation:
1. Endotracheal intubation:
 Congenital lobar emphysema
2. Bag and mask ventilation:
 Diaphragmatic hernia
 Meconium aspiration
12. Resuscitation of Babies Born Preterm
1. Increase the temperature in the delivery room
2. Preheat the radiant warmer
3. place, below the neck, in a polyethylene bag (< 28 weeks)
4. An oxygen blender and a pulse oximeter to vary the amount of oxygen being given ( < 90-
95%)
5. Administering continuous positive airway pressure (CPAP)
6. Consider giving prophylactic surfactant
7. Monitor blood sugar
13. Resuscitation involving meconium aspiration:
1. If the baby has a normal respiratory effort, simply clear secretions and any meconium from
the mouth and nose.
2. If the baby has depressed respirations:
i. Insert an endotracheal tube and apply suction to clear the meconium using
meconium aspirator tube
14. Discontinuing Resuscitative Efforts
i. After 10 minutes of continuous and adequate resuscitative efforts, discontinuation of
resuscitation may be justified if there are no signs of life.
ii. Resuscitation is not indicated in:
1. Gestational age of less than 23 weeks or weight of less than 400 gm.
2. Anencephaly. And Confirmed Trisomy 13 or Trisomy 18 syndrome.
15. Neonatal Resuscitation Algorithm:
22
23
 24

PREMATURITY
1. Definitions: Preterm: Infants delivered before 37 completed wks of gestation
2. Incidence: 10-12% of deliveries
3. Causes of prematurity:
1) Fetal:
i. multiple gestation;
ii. Erythroblastosis
iii. Chromosomal defects – Trisomy syndromes
2) Placental:
i. Placental dysfunction
ii. Placenta previa
iii. Abruptio placentae
3) Utrine:
i. Bicornuate uterus;
ii. Cx incompetence
4) Maternal:
i. Anemia
ii. Preterm labor- medically induced
iii. Preeclampsia
iv. Chronic illness: CHD, Renal disease
v. Infection: Listeria; GBS; UTI; Chorioamnionitis
vi. Drug abuse: Cocaine; Alcohol; Smoking
vii. PROM
viii. Polyhydramnios
4. Assessment of Gestational age
1. Post natal assessment:
a. Rapid delivery room assessment: By Farr and later elaborated by Finnstrom

S.No Physical criteria < 37 weeks > 37 weeks

1 Creases in sloe of
feet
2 Breast nodule
3 Scalp hair
4 Ear lobe
Male: Testes and
scrotum
5 of scrotum
Female:
Present in anterior 1/3 only
< 4mm
Fine and woolly
Less cartilage
Testes partially descended; few
rugosity and less pigmentation
prominent clitoris; labium
minora exposed
Present over entire surface
>7 mm
Coarse and silky
Thick cartilage
Testes fully descended; fully
pigmented; full rugacity
Majora cover clitoris and
minora

2. New Ballard scale: The New Ballard Score is an extension of the above to include extremely pre-term
babies i.e. up to 20 weeks.
a. Consists of six physical and six neuromuscular criteria
b. Score 10 corresponds to 20 weeks and score 50 corresponds to 44 weeks
c. Accuracy is + or – 2 weeks
d. Performed in < 12 hours after birth for < 26 weeks preterm
e. Gives allowance to sick neonates
f. Neurological criteria:
i. Posture
 25

ii. Square window

iii. Arm recoil
iv. Popliteal angle
v. Scarf sign
vi. Heel to ear
g. Physical criteria:
i. Skin color and texture
ii. Lanugo hair
iii. Plantar creases
iv. Breast nodule and areola
v. Eye lids and ear
vi. Genitalia
5. Management:
1. Referral for intensive care:
1. Birth weight less than 1800 gm
2. Gestation less than 34 weeks
3. Neonate who is not able to take feeds from the breast
4. A sick neonate (irrespective of the birth weight or gestation)
2. Management of Hypothermia:
1. Hypothermia: body temperature below 36.5°C.
2. Optimal temperature is to maintain infant core temp between 36.5 to 37 ˚C
3. Mechanisms of Heat Loss and Preventive measures:
i. Evaporation:
1. Loss of heat when water evaporates from the skin and respiratory tract
2. Highest immediately after birth and with bathing
3. Dry baby quickly and remove wet towels/blankets
4. Humidify 02
ii. Convection:
1. Heat lost to surrounding moving air
2. Depends on difference in air temperature, speed of movement of the air, and
amount of skin exposure
3. Cover baby’s head
4. Dress baby
5. Keep out of drafts
6. Warm 02
7. Raise surrounding (ambient) temperature
iii. Radiation:
1. Heat lost to surrounding colder solid objects (not in direct contact) independent of
air temperature
2. Keep incubator, warmer, cot away from outside walls and windows
3. Dress baby
4. Use double walled incubator or Plexiglas heat shield in the incubator
5. For infants with temperature control problems, cover three sides of the incubator
with aluminium foil (shiny side in)
iv. Conduction
1. Heat loss to cold solid objects in direct contact
2. Baby will gain heat if placed on warm surface
3. Prewarm incubator/radiant warmer to ensure warm mattress
 26

4. Cover x-ray plates and scales

5. Pre warm hands, stethoscopes, blankets and other equipment
3. Kangaroo mother care (KFC)
1. Kangaroo mother care is care of preterm infants carried skin-to-skin with the mother. It is a
powerful, easy-to-use method to promote the health and well-being of infants born preterm as
well as full-term. Its key features are:
1. Early, continuous and prolonged skin-to-skin contact between the mother and the baby;
2. Exclusive breastfeeding (ideally);
3. It is initiated in hospital and can be continued at home;
4. Small babies can be discharged early;
5. Mothers at home require adequate support and follow-up;
6. It is a gentle, effective method that avoids the agitation routinely experienced in a busy
ward with preterm infants.
2. Position:
1. The baby should be placed between the mother’s breasts in an upright position.
2. The head should be turned to one side and in a slightly upturned position. This position
helps in breathing of and allows eye-to-eye contact between the mother and her baby.
3. The legs and arms should be folded.
4. Baby’s abdomen should be at the level of the mother’s upper abdomen.
5. Support the baby bottom with a sling/binder.
3. Feeding
1. Holding the baby near the breast stimulates milk production.
2. Mother should express milk while the baby is still in KMC position.
3. The baby could be fed with paladai, cup, spoon or tube, depending on the condition of
the baby.
4. Monitoring of Preterm/LBW
1. Pulseoximetry for Pa O2, HR
2. Transcutaneous PO2 and PCO2
3. Electrolytes, glucose, Ca, bilirubin from umb. artery sampling of blood
5. Feeding:
Nutrition
1. Desired weight gain is 15 gm/week;
2. Calories: 120 Kcal/kg/day;
3. IV:
1. GDW 10% (>1500 gm) or 5% (<1500 gm) 80-100ml/day
2. Amino acid solution 3 g/kg/day via umb. vein
4. Trophic feeds: breast feed/EBM/donor BM/ formula <10 ml/kg/day in day 1 with slow increments
to full requirement in 1 week
5. Mode of Feeding:
1. < 28 weeks: No proper sucking; No gut motility  Intravenous fluids
2. 28-31 weeks: No coordination between suck/swallow  NG tube feeding
3. 32-34 weeks: Slightly mature sucking pattern; Coordination begins Feeding by spoon
4. >34 weeks: Mature sucking pattern; more coordination between breathing and swallowing 
Breastfeeding
6. Nutrient supplement:
1. Calcium and phosphorus (140-160 mg/kg/d & 70-80 mg/kg/d)
2. Vitamin D (400 IU/day), vitamin B complex and zinc (0.5mg/day) – Multivitamin drops
3. Folate (50 mcg/kg/day)
 27

4. Iron (2 mg/kg/day
6. Complications of Prematurity:
1. Hyaline membrane disease
2. Apnea of prematurity
3. PDA
4. NEC (Necrotizing enterocolitis)
5. Intraventricular hemorrhage
6. Retinopathy of prematurity
7. Sepsis
8. Jaundice leading to kernictreus at lower threshold
9. Cerebral palsy
1. Apnea of prematurity
1. Definition: respiratory pause lasting for more than 20 sec or long enough to produce cyanosis and
bradycardia.
2. Apnea of prematurity:
1. Immaturity of respiratory centre
2. Immaturity of mechanisms that maintain airway patency
3. Occurs in the first 2 weeks of life
4. Treatment:
1. Caffeine citrate: 20 mg/kg loading; 5-10 mg/kg/day maintenance
2. Nasal CPAP
2. PDA
1. Persists in those who have:
1. <28 weeks of gestation
2. RDS
2. Clinical:
1. Hyperdynamic precardium
2. Wide pulse pressure
3. Systolic murmur
4. Medical management of PDA
i. Indomethacin:
1. Prophylaxis: 0.1mg/kg/iv q 24 hr for 3-5 days from day 1
2. Therapeutic: 0.2mg/kg/iv q 12 hr up to 3 doses; closure in 2/3 cases
3. Side effect: oliguria
4. Contrindicvations:
1. Hyperkalemia
2. Creatinine >2mg/dl
3. Thrombocytopenia
ii. Alternate drug: Ibuprofen 10 mg/kg loading and 5 mg/kg 2 doses /daily
3. NEC (Necrotizing enterocolitis)
1. Emergency in NB;
2. 10% in less than 1500 gm;
3. Mortality rates of 50% or more depending on severity.
4. Multifactorial:
1. ischemic insult damages the intestinal lining,
2. bacterial invasion,
3. proliferation of luminal bacteria, which can penetrate the damaged
intestinal wall, producing hydrogen gas - Pneumatosis intestinalis
 28

5. Treatment
a. Stoppage of feedings
b. NGT
c. Fluid resuscitation
d. Broad-spectrum antibiotics
e. TPN
f. surgery
4. Intraventricular hemorrhage
1. 20-30% incidence in < 31 weeks of GA; < 1500 gm
2. Bleeding commonly occurs in lateral ventricles
3. Ischemic damage to capillaries lead to rupture and hemorrhage
4. Most within 24 hours and all before 4 days
5. Symptoms:
1. Coma,
2. Decerebrate posturing,
3. Fixed pupils,
4. Bulging fontanelle,
5. Hypotension, acidosis, apnea.
6. Treatment:
a. Volue and blood replacement
b. O2
c. Ventilation
d. Shunt for hydrocephalus
5. Retinopathy of prematurity
1. Incompletely vascularised and premature retina
2. 60% in those weighing <1250 gm
3. Injury to developing retinal vessels
1. Abnormal vasularization,
2. Fibrovascular tissue growth into vitreous,
3. Scarring,
4. Folding and detachment of retina
4. Routine eye exam in <1500 gms at 4 weeks
5. Laser therapy
LATE PRETERM
1. Refers to babies born at 34 to 37 weeks of gestation
2. Incidence: 12.8% of all births; 70% of preterms
3. Causes:
1. Obstetric induction of labour
2. Increase in Caesarean section
3. Multiple births
4. Significance of late preterm:
1. Late–preterm infants often are mistakenly believed to be as physiologically and metabolically
mature as term infants. But, compared with term infants, those born between the 34th and
37th week of gestation suffer from higher rates of morbidity and mortality.
1. Developmental and physiologic immaturity of late preterm infants:
i. Delayed intrapulmonary fluid absorption TTN
ii. Decreased central chemosensitivity to carbon dioxide  apneic spells
iii. Delayed ductus arteriosus closure and persistent pulmonary hypertension.
 29

iv. Late-preterm infants are likely to lose heat more readily than term infants
v. Increased risk of developing hypoglycemia after birth
vi. Jaundice and hyperbilirubinemia occur more commonly and are more prolonged among
late-preterm infants than term infants
vii. Late-preterm infants also have immature gastrointestinal function and feeding difficulties
5. Morbidity and mortality among late-preterm infants:
1. Small clinical reports that compared late-preterm infants with term infants suggested a
higher risk of:
1. Cerebral palsy
2. Speech disorders,
3. Neurodevelopmental handicaps,
4. Behavioural abnormalities,
5. Competence (behavioural, scholastic, social, and global).
6. Other Issues:
1. RDS
2. Feeding problems
3. Hyperbilirubinemia and kernicterus
4. Apnea
5. Hypoglycaemia
6. Seizures
7. Sepsis
8. Hypothermia
6. Management:
1. Extended hospitalization
2. EBM

Parenteral Nutrition

Indications of parenteral nutrition

1. Birth weight less than 1000 g
2. Birth weight 1000-1500 g not on significant feeds for 3 or more days
3. Birth weight more than 1500 g not on significant feeds for 5 or more days
4. Surgical conditions in neonates: Necrotizing enterocolitis, Gastroschisis, Omphalocele,
Tracheoesophageal fistula, Intestinal atresia, Mal-rotation, Short bowel syndrome, and Meconium
ileus
Energgy requirements:
1. 110-120 kcal/kg/day for preterm ; 90-100 kcal/kg/day for term neonate
2. Sources:
a. 10% dextrose solution provides 0.34 kcal/ml.
b. 10% lipid solution provides 0.9 Kcal/ml and 20% lipid solution provides 2.2 Kcal/ml.
c. If sufficient amount of non-protein energy is not provided, amino acids are catabolized for
energy production. Adequate balance between nitrogen and non-protein energy sources
(Protein/Energy ratio: 3-4 g/100 kcal) is needed to promote protein accretion.
d. Balance between carbohydrates and fat is needed to prevent excessive fat deposition and
excessive production of CO2
e. The ideal distribution of calories should be 50-55% carbohydrate, 10-15% proteins and 30-
35% fats
Amino acids:
a. PN should provide 2.5 to 3.5 g/kg/day of AA.
 30

b. An optimal AA solution should contain essential (valine, leucine, isoleucine, methionine,

phenylalanine, threonine, lysine and histidine) and conditionally essential (cysteine, tyrosine,
glutamine, arginine, proline, glycine and taurine)
c. AAs should not have excess of glycine and methionine and should not contain sorbitol.
d. Depending on practical feasibility, AA infusion should be started on the first day of birth preferably
soon after birth. To avoid negative protein balance, one should start with at least 1.5 g/kg/d and then
increase by 1 g/kg/d to maximum of 3.5 g/kg/d. AA solutions are available as 10% and 20%
preparations.
e. Early provision of protein is critical to attain positive nitrogen balance and accretion, as premature
babies lose about 1% of their protein stores daily.
Carbohydrates
a. Carbohydrates are the main energy substrate for the neonates receiving PN.
b. Excessive carbohydrate delivery can lead to an increase in basal metabolic rate, fat deposition,
cholestasis or hepatic steatosis.
c. Use of insulin to achieve higher glucose infusion rate and promote growth has been associated with
lactic acidosis.
d. The amount of carbohydrate delivered in the form of dextrose is 4 to 6 mg/kg/min. This provides
energy intake of 40-50 kcal/kg/d and preserves carbohydrate stores. It is advanced in a gradual,
stepwise fashion (2 mg/kg/min/day) to a suggested maximum glucose rate for neonates of 12-13
mg/kg/min.
e. If infant is developing high glucose levels despite glucose infusion rate of 4-6 mg/kg/minute, insulin
infusion can be started. Glucose is available as 5%, 10%, 25% and 50% solution
Lipids
a. Lipids can be started on first day at dose of 1.0 g/kg/d and then increased gradually in stepwise
fashion to 3.0 g/kg/d.
b. In preterm neonates with hyperbilirubinemia in range of exchange transfusion threshold, lipids may be
restricted to minimum amounts (1 g/kg/d) that will provide only the essential fatty acids.
c. IVL emulsions are available in two strengths: 10% and 20%. Use of 20% lipid emulsion is preferable to
a 10% solution to decrease the risk of hypertriglyceridemia, hypercholesterolemia, and
hyperphospholipidemia.
d. When lipids are exposed to light, they form potentially toxic lipid hydroperoxides. Hence lipid syringes
and tubing should be covered by wrapping it in aluminum foil.
Minerals:
a. Sodium, potassium, and chloride are essential to life and requirements are dependent on obligatory
losses, abnormal losses, and amounts necessary for growth. Calcium, phosphorus, and magnesium are
the most abundant minerals in the body.
b. Mineral Requirement
a. Sodium 0-3 meq/kg/d (1st week of life) 2-3 meq/kg/d (beyond 1st week in term neonates) 3-5
meq/kg/d (beyond 1st week in preterm neonates)
b. Potassium 0-2 meq/kg/d (1st week of life) 1-3 meq/kg/d (beyond 1st week)
c. Chloride 2-3 meq/kg/d
d. Calcium 150-200 mg/kg/day
e. Magnesium 15-25 mg/d
f. Phosphate 20-40 mg/kg/d
Vitamins
a. Vitamins are added in PN solution to meet the daily requirement. Separate preparations of fat-soluble
and water-soluble vitamins suitable for neonates are not available in India.
b. Multivitamin injection (MVI), when added in a dose of 1.5 mL/kg to lipid solution meets the need of
vitamin A and most other vitamin.
c. Furthermore, intravenous vitamin delivery may be less due to photodegradation of vitamins A, D, E, K,
B2, B6, B12, C, and folic acid and adsorption of vitamins A, D, and E into the vinyl delivery bags and
tubing.
 31

d. Vitamin K needs to be given separately as weekly intramuscular injections.

e. Although vitamin B12 is not present in MVI, its deficiency is not manifested unless the neonate is on
long-term PN.
f. Vitamin requirement: Term (daily dose) Preterm (dose/kg/day)
a. Vitamin A (IU) 2300 1640
b. Vitamin D (IU) 400 160
c. Vitamin E (IU) 7 2.8
d. Vitamin K (µg) 200 80
e. Vitamin B6 (µg) 1000 180 Vitamin
f. B12 (µg) 1 0.3
g. Vitamin C (mg) 80 25
h. Biotin (µg) 20 6
i. Folic acid (µg) 140 56
j. Niacin (mg) 17 6.8
k. Pantothenic acid (mg) 5 2
l. Riboflavin (µg) 1400 150
m. Thiamin (µg) 1200 350
Trace elements
a. Trace elements like zinc, copper, manganese, selenium, fluorine and iodine should be provided in PN
solutions.
b. Zinc is universally recommended from day one of TPN, whereas the other trace minerals are generally
provided after 2 weeks of TPN without any appreciable enteral feeding.
c. Copper, selenium, molybdenum, and iron can be delivered separately also.
d. Dosage of zinc to be provided is 150-400 microgram/kg/d even with short-term PN, but a suitable
preparation is difficult to find in Indian market.
Fluids:
a. Intravenous fluid is the carrying medium for PN. It is started at 60-80 mL/kg/d and advanced by 15- 20
mL/kg/d to maximum of 150 mL/kg/d by end of first week of life.
b. Fluid therapy is regulated by monitoring hydration status of the infant (weight gain/loss, serum
sodium, urinary specific gravity, urine output and osmolality of plasma and urine).
Evidence-based recommendations for parenteral nutrition
Component Recommendations
Fluids Day 1: 60-80 mL/kg/d.
Postnatal weight loss up to 3% per day to a maximum of 10 to 15% is
acceptable. This is achieved by progressively increasing the fluid intake to 120-
150 mL/kg/d by one week of age.
Energy: An intake of 50 kcal/kg/d is sufficient to match ongoing expenditure, but it does
not meet additional requirements of growth. The goal energy intake is 100-120
kcal/kg/d (higher in infants with chronic lung disease)
Protein: Optimal parenteral amino acid intake is 3.5 g/kg/d.
Parenteral amino acids can begin from day 1 at 1-1.5 gm/kg/d
Carbohydrates: From day one, 6 mg/kg/min can be infused, increased by 2 mg/kg/min/d to 12-
14 mg/kg/min and adjusted to maintain euglycemia
Insulin: is only used in infants who continue to have hyperglycemia associated
with glycosuria and osmotic dieresis even after the glucose intake has been
reduced to 4 to 6 mg/kg/min. Insulin is given as a continuous infusion commencing
at a rate of 0.05 units/kg/h, increasing as required for persistent hyperglycemia.
Fat: Intravenous fat, 1 g/kg/d can be started from day 1, at the same time as when
intravenous amino acids are started. This is increased to 2 g/kg/d and 3 g/kg/d over
the next two days. It is delivered as a continuous infusion of 20% intravenous fat via
a syringe pump, separate from the infusate containing the amino acids and glucose.
The syringe and infusion line should be shielded from ambient light.
 32

Minerals: sodium, chloride, potassium, calcium, phosphorus, magnesium.

Trace elements: zinc, copper, selenium, manganese, iodine, chromium, and molybdenum.
Vitamins: Vitamins must be added to the fat emulsion to minimize loss during administration
due to adherence to tubing and photo-degradation.
Dispensing PN solution: In developed countries PN solution is prepared by central pharmacy and delivered
ready to be used. But this facility is usually not available in most of Indian hospitals
and physicians and nurses have to chart and prepare PN.
Steps for calculation and preparing PN are as follows (a PN chart is provided in appendix):
1. Determine total fluid requirement for the day
2. Subtract amount of fluid to be used for medications (e.g. diluting and infusing antibiotics) and
enteral feeds
3. Plan AA, IVL and glucose to be given over 24 h
4. Take IVL suspension in one syringe and add MVI in to it.
5. In second syringe mix AA, dextrose, electrolytes and trace elements
6. IVL+MVI suspension is infused separately from AA-glucose-minerals solution, although they can
be mixed at the site of infusion using a three-way adapter.
7. For calculating amount of each PN component, use following formula:
𝐴𝐴𝐴𝐴𝐴𝐴 𝐴𝐴 𝐴𝐴 𝐴𝐴𝐴𝐴𝐴 𝐴𝐴𝐴 𝐴𝐴 𝐴𝐴𝐴𝐴 𝐴𝐴𝐴𝐴𝐴 × 𝐴𝐴𝐴𝐴 𝐴𝐴𝐴𝐴𝐴
𝐴𝐴𝐴𝐴𝐴𝐴𝐴h 𝐴𝐴 𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴
8. For example, for a baby weighing 1.5 kg to be given 3 mEq/kg of sodium, amount of 3% NaCl to be
used is:
𝐴𝐴𝐴𝐴𝐴𝐴 𝐴𝐴 3% 𝐴𝐴𝐴𝐴 = 3 𝐴𝐴𝐴/𝐴𝐴 × 1.5 𝐴𝐴 0.5 𝐴𝐴𝐴/𝐴𝐴 = 9 𝐴𝐴
Route of administration
1. PN can be delivered through peripheral or central venous lines. Short-term PN can be given
through peripheral venous line. Peripheral access offers the advantage of a lower risk of infection
due to the greater distance of the catheter from the central circulation as well as a smaller risk of
mechanical complications. However, nutrition delivery is limited with peripheral lines due to
constraints created by a solution's osmolarity.
2. The limiting factor in deciding route of delivery is osmolarity of the AA-glucose solution
which is dependent on dextrose concentration. A dextrose concentration greater than 12.5% has
an acidic pH and can be irritating to the peripheral veins. In addition to dextrose, electrolytes and
minerals added to the solution increase the osmolarity of the solution.
3. Hypertonic solution need to be administered through central venous line.
4. Increasing use of peripherally inserted central catheters (PICC) has facilitated administration of PN
while avoiding many potential complications of surgically inserted central lines.
5. Another attractive option in neonates is central line inserted through umbilical vein. Umbilical
venous catheter can be used for up to 14 days after which risk of complications increases.
6. Position of central line should be confirmed by X-ray before starting infusion through it. To avoid
risk of pericardial tamponade, tip of the central catheter should lie outside the pericardial sac (on
the chest x-ray is at least 0.5 cm outside the cardiac outline). In comparison to catheters made of
stiffer material (polyvinylchloride, polypropylene, polyethylene), softer catheters (silicone and
polyurethane) are less thrombogenic and less traumatic, and are, therefore, preferable for long-
term use. The venous access used for PN should not be interrupted for giving antibiotics or other
medications. For this a separate intravenous line should be established.
Monitoring and complications
1. Meticulous monitoring is needed in a neonate receiving PN. Monitoring should be more frequent
in the initial stages. Once a steady metabolic stage has been achieved, monitoring can be reduced
to once a week.
Complications of PN
1. It can be nutrient-related or venous access-related.
2. Nutrient related complications include hypoglycemia (plasma sugar < 54 mg%) and hyperglycemia
(plasma sugar >150 mg/dL) (glucose-related), azotemia and metabolic acidosis (protein-related),
 33

hypertriglyceridemia (triglyceride >200 mg/dL) (lipid-related), cholestasis and trace element

deficiency. Most of these complications can be avoided by proper monitoring and provision of
nutrients.
3. PN-related cholestasis is usually complication of long-term PN and can be avoided by provision of
at least minimal-enteral nutrition. Catheter-related complications include occlusion, dislodgement
and infection.
Monitoring schedule for a neonate on parenteral nutrition
Parameter Frequency
Blood sugar 2-3 times a day while increasing glucose infusing rate Once a day
while on stable glucose infusion rate
Urine sugar once per nursing shift
Serum electrolytes Twice a week initially, then weekly
Blood urea Twice a week initially, then weekly
Calcium, magnesium and phosphorous Weekly
Serum albumin Weekly
Packed cell volume Weekly
Liver function tests Weekly
Serum triglycerides Weekly
Anthropometry
Weight Daily
Head circumference weekly
Length Weekly
Prevention of infection
1. Hospital-acquired infection (HAI) is a major complication of PN. All efforts should be made to
avoid HAI.
2. Aseptic precautions during preparation of PN
 Use of laminar flow
 No compromise on disposables
 Trained staff
 No reuse of the PN solutions
 No interruption of the venous line carrying PN
 Use of bacterial filter

IUGR or SGA
1. Definition:
a. Incidence. About 3-10% of all pregnancies are associated with IUGR
b. Birth weight below the 10th percentile or
c. > 2 SD below the mean for gestational age;
2. Causes of IUGR:
1. Fetal factors:
a. Genetic disorders such as achondroplasia, Russell-Silver syndrome, present with IUGR
b. Chromosomal defects: Trisomies 13, 18, and 21
c. Congenital malformations.
i. Anencephaly, gastrointestinal atresia, Potter's syndrome
ii. CHDs except TGV
d. TORCH infections
2. Inborn errors of metabolism. Transient neonatal diabetes, galactosemia, and phenylketonuria
3. Maternal factors:
i. Poor nutritional status of the mother
 34

ii. Anemia,
iii. Frequent pregnancies
iv. Maternal hypertension,
v. Pre-eclampsia,
vi. Post-maturity,
vii. Smoking
viii. Alcoholism
ix. Heroin
x. Malaria
xi. Mothers with hemoglobinopathies
xii. Chronic maternal diseases of heart, kidneys, lungs or liver
4. PLACENTAL FACTORS:
i. Hemangioma
ii. Single umbilical artery
iii. Infarction
iv. Aberrant cord insertion
v. Umbilical vessel thrombosis
4. Classification of IUGR:
1. Symmetric IUGR:
a. Head circumference, length, and weight are equally affected- <10%
b. Ealier onset and associated with diseases affecting cell number : chromosomal, genetic,
malformations, tretogenic, infectious, PIH etiologies
2. Asymmetric IUGR:
a. Only weight is reduced - <10%
b. Relative sparing of head growth
c. Late onset
d. Associated with poor maternal nutrition or late onset PET, PIH
5. Clinical assessment:
1. Reduced birth weight for gestational age
2. Infants in general are thin, with loose, peeling skin because of loss of subcutaneous tissue, a scaphoid
abdomen, and a disproportionately large head.
3. More alert than their premature counterparts.(wiseman look)
6. Problems of IUGR:
1. Chronic Hypoxia: infants frequently have birth asphyxia and meconium aspiration
2. Persistent pulmonary hypertension.
3. Hypothermia: due to diminished subcutaneous fat insulation and lack adequate brown fat
4. Metabolic:
a. Hypoglycemia: due to diminished glycogen reserves and decreased capacity for gluconeogenesis.
5. Hematologic disorders.
a. Hyperviscosity and polycythemia may result from increased erythropoietin levels secondary to
fetal hypoxia
6. Altered immunity.
i. IUGR infants have decreased IgG levels; the thymus is reduced in size by 50% and peripheral
blood lymphocytes are decreased.
i. More likely to have malformations
ii. Feeding difficulties as in preterm babies.
6. Hyaline membrane disease is less frequent
7. Management: (as in preterm care)
 35

a. Mannagement of correctable factors in AN period

b. Timing delivery after lung maturity
c. Skilled resuscitation should be available because birth asphyxia is common.
d. care should be taken to prevent heat loss
e. Hypoglycemia should be treated promptly with parenteral dextrose and early feeding
f. Polycythemia needs attention
g. Mangement of Con. Defects, cong.infections and genetic anamalies.
8. Outcome: minimal brain dysfunction, including hyperactivity, short attention span, and learning problems are
common with IUGR babies.

POST-TERM INFANTS
1. Post-term infants are those born after 42 completed weeks of gestation, as calculated from the mother’s
last menstrual period, regardless of weight at birth. Historically, about 12% of pregnancies ended after the
294th day.
2. The cause of post-term birth or postmaturity is unknown.
Clinical Manifestations
1. Post-term infants have normal length and head circumference but may have decreased weight if there
is placental insufficiency.
2. Infants born post-term in association with presumed placental insufficiency may have various physical
signs.
3. Desquamation, long nails, abundant hair, pale skin, alert faces, and loose skin, especially around the
thighs and buttocks, give them the appearance of having recently lost weight; meconium-stained nails,
skin, vernix, umbilical cord, and placental membranes may also be noted.
4. Common complications of postmaturity include perinatal depression, meconium aspiration, persistent
pulmonary hypertension, hypoglycemia, hypocalcemia, and polycythemia.
Prognosis
1. When delivery is delayed 3 wk or more beyond term, mortality is significantly increased and, in some
series, has been approximately three times that of a control group of infants born at term. Mortality
has been lowered markedly through improved obstetric management.
Management
1. Careful obstetric monitoring, including nonstress testing, biophysical profile, or Doppler velocimetry,
usually provides a rational basis for choosing one of three courses:
i. nonintervention,
ii. induction of labor, or
iii. cesarean section.
b. Induction of labor or cesarean section may be indicated in older primigravidas more than 2-4 wk
beyond term, particularly if evidence of fetal distress is present.
c. Medical problems in the newborn are treated if they arise.

LARGE-FOR-GESTATIONAL-AGE INFANTS
1. Infants with birthweight > the 90th percentile for gestational age are called large for gestational age (LGA).
Neonatal mortality rates decrease with increasing birthweight until approximately 4,000 g, after which
they increase.
2. These oversized infants are usually born at term, but preterm infants with weights high for gestational age
also have a significantly higher mortality than infants of the same size born at term; maternal diabetes and
obesity are predisposing factors.
3. Some infants are constitutionally large because of large parental size.
4. Complications:
 36

a. LGA infants have a higher incidence of birth injuries, such as:

i. cervical and brachial plexus injuries,
ii. phrenic nerve damage with paralysis of the diaphragm,
iii. fractured clavicles,
iv. cephalohematomas,
v. subdural hematomas, and
vi. ecchymoses of the head and face.
vii. LGA infants are also at increased risk for hypoglycemia and polycythemia.
viii. The incidence of congenital anomalies, particularly congenital heart disease, is also
higher in LGA infants.
ix. Intellectual and developmental retardation is more common in high birthweight term
and preterm infants.
NEONATAL SEPSIS
Definition: Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of infection with or
without accompanying bacteremia in the first month of life. It encompasses various systemic infections of the
newborn such as septicemia, meningitis, pneumonia, arthritis, osteomyelitis, and urinary tract infections.
Introduction:
1. Infections are important cause of neonatal morbidity and mortality. 2% of fetuses are infected in
utero, and up to 10% of infants have infections in the 1st mo of life.
2. Preterm LBW infants have a 3- to 10-fold higher incidence of infection than full-term normal birth
weight infants.
3. Infectious agents can be transmitted from:
a. The mother to the fetus
b. Nursery: person to person
c. Ventilators
d. Indwelling devices
e. Invasive procedures
4. Newborn infants are less capable of responding to infection because of immunologic deficiencies.
5. Coexisting conditions complicate sepsis: prematurity, LBW, MAS, post maturity etc.
6. Etiologic agents include bacteria, viruses, fungi, protozoa, and mycoplasmas.
Modes of Transmission and Pathogenesis:
1. Intrauterine infection:
a. Intrauterine infection is due to cytomegalovirus [CMV], Treponema pallidum, Toxoplasma
gondii, rubella virus, varicella virus, parvovirus B19 etc.
b. Ascending bacterial infection: Chorioamnionitis results from prolonged rupture (>18 hours)
of the chorioamniotic membrane - Gr.B.Streptococcus(GBS)
2. Intranatal:
a. Resuscitation, endotracheal intubation or insertion of an umbilical vessel catheter is
associated with an increased risk of bacterial infection.
b. Lack of 5 cleans: clean surface, clean hands, clean tie, clean knife and no applicants on
umbilical stump.
3. Postnatal infections
a. Postnatal infections may be transmitted by direct contact with hospital personnel, the
mother, or other family members;
b. Breast milk (HIV, CMV);
c. Contaminated equipment.
d. Ventilators
e. Indwelling catheters
 37

f. IV fluids and stock solutions

4. Meningitis may result from contamination of open neural tube defects, congenital sinus tracts, or
penetrating wounds from fetal scalp sampling or internal fetal electrocardiographic monitors
5. Immunity:
a. Immunoglobulin (Ig) G is levels are directly proportional to gestational age. IgG provides
protection against GBS
b. Newborn infants lack antibody-mediated (IgM) protection against Escherichia coli
c. No transplacental passage of complement from the maternal circulation necessary for
bactericidal activity against E. coli and as an opsonin in the phagocytosis of GBS
d. Opsonization of Staphylococcus aureus is normal in neonatal sera, but various degrees of
impairment have been noted with GBS and E. coli.
e. Quantitative and qualitative deficiencies of the phagocyte system contribute to the
newborn’s susceptibility to infection.
a. Neutrophil migration (chemotaxis) is abnormal at birth in both term and preterm
infants.
b. chemo taxis of monocytes is impaired; this impairment affects the inflammatory
response in tissues and the results of delayed hypersensitivity skin tests
c. Neonatal NK cells have decreased cytotoxic activity and herpes simplex virus (HSV)
may predispose to disseminated HSV infection in newborns
d. Several adverse neonatal outcomes, including brain injury, necrotizing enterocolitis
(NEC), and bronchopulmonary dysplasia, may be mediated by the cytokine response
to infection in the mother, fetus, or newborn
Definition:
Sepsis is defined as SIRS resulting from a suspected or proven infectious etiology.
Clinical Types:
1. Early Onset Sepsis- within 72 hours of life: pathogens in the maternal genital tract colonize on
skin, umbilical cord, respiratory and GIT mucosa or through placenta in the perinatal period
2. Late onset Sepsis – after 72 hours of life; pathogens acquired through human contacts or
nosocomial in NB nurseries.

Early Onset Sepsis (EOS) Late Onset Sepsis (LOS)

Period of onset Presents within the first 72
hours of life.
Source of infection: Maternal genital tract
Pathogens Group B streptococcus;
Escherichia coli; Listeria
monocytogenes
Clinical presentation Respiratory distress&
pneumonia.
Usually presents after 72 hours of life.
Nosocomial or communityacquired
Staphylococcus aureus, coagulase-
negative staphylococci,GBS, Enterococcus,
and gram-negative organisms
Septicaemia, pneumonia, meningitis.

Risk Factors for EOS:

a. Preterm and LBW
b. Rupture of membranes
c. Maternal infection
d. Resuscitation
e. Invasive monitoring
f. Galactosemia: E.coli sepsis
Etiology of Fetal and Neonatal Infection
 38

a. Early onset sepsis:

1. Transplacental (TORCHS)
2. Trans vaginal:
a. Chorioamnionitis due to: PROM (>24 hrs);
b. Foul smelling and/or meconium stained liquor
c. Single unclean or > 3 sterile vaginal examination(s) during labor
d. Prolonged labor (sum of 1st and 2nd stage of labor > 24 hrs)

a. Postnatal:
i. Perinatal asphyxia (Apgar score <4 at 1mt)
ii. Resuscitation procedures
a. Endotracheal tube
b. Suction apparatus
c. Umbilical catheterization
b. Etiology of Late onset sepsis:
i. Nursery:
1. Nosocomial
2. Cross infection in nursery
3. Ventilator associated
4. Procedures and devices
ii. Breastfeeding: HIV
iii. Community acquired
Pathogens:
a. Intrauterine transplacental infections:
1. Syphilis,
2. Rubella,
3. CMV,
4. Toxoplasmosis,
5. Parvovirus b19
6. Varicella
b. Intrapartum:
1. HIV
2. HSV
3. HBV
4. GBS
5. E.Coli
6. Gonococci
7. Chlamydiae
8. CMV
c. Nosocomial infection:
1. Coagulase-negative staphylococci,
2. Gram-negative bacilli (E. coli,Klebsiella pneumoniae, Salmonella, Enterobacter,
Citrobacter,Pseudomonas aeruginosa, Serratia),
3. Enterococci,
4. S. Aureus,
5. Candida.
6. Enteroviruses,
7. Cmv,
 39

8. Hepatitis a,
9. Adenoviruses,
10. Influenza,
11. Respiratory syncytial virus (RSV),
12. Rhinovirus,
13. Parainfluenza,
14. HSV,
15. Rotavirus
Differences between early and late onset sepsis:

CHARACTERISTICS EARLY ONSET LATE ONSET VERY LATE ONSET

(NOSOCOMIAL)
Age at onset Birth to 7 days usually <72 hr 7-30 days >30 days
Maternal obstetric Common Uncommon Varies
complications
Prematurity Frequent Varies Usual
Organism source Maternal genital tract Maternal genital Environment/comm
tract/environment unity
Manifestation Multisystem Multisystem or focal Multisystem or
focal
Place Maternal genital tract; Normal NICU, community NICU, community
nursery, NICU, community
Pathogens Group B streptococcus; Staphylococcus aureus, coagulase-negative
Escherichia coli; Listeria staphylococci,GBS, Enterococcus, and gram-
monocytogenes negative organisms
Clinical presentation Respiratory distress& Septicaemia, pneumonia, meningitis.
pneumonia.
Signs and symptoms:
1. Vague and nonspecific; subtle or insidious
2. Hypothermia more common than fever
3. Hyperthermia in viral infection like Herpes
4. Lethargy and poor suck
5. Pallor and circumoral cyanosis
6. Skin mottling
7. Jaundice
8. Poor Feeding:
Signs:
a. General
1. Respiratory distress,
2. Apnoea
3. Gasping respiration
4. Poor perfusion-pallor
5. Prolonged capillary refill time
6. Hypotonia,
7. Absent neonatal reflexes
8. Brady/tachycardia
9. Hypo / hyperglycaemia
10. Metabolic acidosis
 40

11. Icterus: direct/indirect

b. In NICU:
1. Hypotension
2. Hypo/ hyperglycaemia
3. Increased pre-feed aspirates
4. Unexplained metabolic acidosis
c. Criteria of IMNCI:
1. Convulsions
2. Respiratory rate ≥60/minute
3. Severe chest in drawing
4. Nasal flaring
5. Grunting
6. Bulging fontanel
7. 10 or more pustules/a big boil
8. Redness around umbilicus extending to the skin
9. Lethargic or unconscious
10. Reduced movements
11. Not able to feed
Systemic inflammatory response syndrome: SIRS
a. The systemic inflammatory response syndrome (SIRS) is an inflammatory cascade that is initiated
by the host response to an infectious or non-infectious trigger
b. Shock can lead to hypovolemia, cardiac and vascular failure, acute respiratory distress syndrome
(ARDS), insulin resistance, decreased cytochrome P450 activity (decreased steroid synthesis),
coagulopathy, and unresolved or secondary infection.
c. Tumor necrosis factor (TNF) and other inflammatory mediators increase vascular permeability,
causing diffuse capillary leak, decreased vascular tone, and an imbalance between perfusion and
metabolic demands of the tissues.
d. TNF and interleukin-1 (IL-1) stimulate the release of proinflammatory and anti-inflammatory
mediators, causing fever and vasodilatation.
e. Arachidonic acid metabolites lead to the development of fever, tachypnea, ventilation-perfusion
abnormalities, and lactic acidosis.
f. Nitric oxide, released from the endothelium or inflammatory cells, is a major contributor to
hypotension.
g. Myocardial depression is caused by myocardium-depressant factors, TNF, and some interleukins
through direct myocardial injury, depleted catecholamine, increased β-endorphin, and production
of myocardial nitric oxide.
h. In neonates SIRS manifests as temperature instability, respiratory dysfunction (altered gas
exchange, hypoxemia, acute respiratory distress syndrome [ARDS]), cardiac dysfunction
(tachycardia, delayed capillary refill, hypotension), and perfusion abnormalities (oliguria,
metabolic acidosis) (Table 103-13). Increased vascular permeability results in capillary leak into
peripheral tissues and the lungs, with resultant pulmonary and peripheral edema. DIC results in
the more severely affected cases. The cascade of escalating tissue injury may lead to multisystem
organ failure and death.
Severe EOS: Neonate may be symptomatic in utero (foetal tachycardia, poor beat-to-beat variability) or
presents with signs within a few hours after birth.
D.D of neonatal sepsis:
1. RDS
2. Transient tachypnea
 41

3. Intra cerebral haemorrhage

4. Inborn errors of metabolism
5. GI perforation
Septic screening: > two is positive for evidence of sepsis
1. Gastric aspirate > 5 polys per HPF; C/S
2. Maternal vaginal swap For GPS; C/S
3. TC < 5000 / cml
4. Bandemia > 20 %
5. Micro ESR > 15 mm
6. CRP > 1 mg/dL
Other Tests:
1. Cytokins and procalcitonin: elevated
2. CSF C/S; microscopy
3. Thrombocytopenia < 1 L / cml
4. Acidosis Present
Culture:
1. Organisms that are part of the skin flora (e.g., Diphtheroids, non-haemolytic streptococci,
Coag.NS) suggest contamination
2. Culture is positive with clinical deterioration
3. Multiple site cultures are positive
4. Urine culture:
5. Suprapubic puncture or bladder
6. Catheterization
7. >10 ⁴ organisms/ml in urine obtained by catheterization
8. Any organism in the urine obtained by suprapubic aspiration
CSF:
1. Leucocyte count >30/ mm3
2. Protein concentration >150 mg/ dL
3. CSF to blood glucose ratio <50%
4. Positive Gram stain/ culture
CXR: shows
1. Hyperventilation
2. Thymic atrophy
3. Pear shaped heart
4. Distended abdomen
Treatment
1. Supportive treatment:
a. Thermo-neutral environment
b. Maintain oxygen saturation
c. Initiate mechanical ventilation, if necessary.
d. Administer i.V. Fluids/ crystalloids/ colloids and inotropes to maintain normal tissue
perfusion and blood pressure
e. Monitor for hypo/hyperglycaemia.
f. Avoid enteral feeding till the infant is hemodynamically stable.
g. To manage anaemia/bleeding diathesis, use packed red cells and fresh frozen plasma.
h. IV fluids : glucose and electrolytes
1. Antibiotics:
Situation Medication
 42

1. EOS Ampicillin (piperacillin) + gentamicin

2. EOS not improving Third-generation cephalosporin + amikacin

3. LOS Third-generation cephalosporin + amikacin

4. LOS not improving Ciprofloxacin/piperacillin-tazobactam/cefperazone-sulbactam

5. Suspect Gram-negative Meropenem

6. VLBW neonates not improving- Consider antifungal agents

7. Associated NEC Use metronidazole

2. Duration of treatment:
Term Preterm
1. Culture-negative, sick baby- 5 days 7 days
2. Culture-positive, sick neonate 7–10 days 10–14 days
4. Adjuvants in treatment:
1. Fresh blood: provides polys, thrombocytes, complements and opsonins
2. Exchange blood transfusion: to remove toxins
3. IV Gamma Globulins: 500 to 1000 mg/kg
4. Granulocyte-Monocyte Colony Stimulating Factors (GM-CSF)
5. Pentoxifylline showed a reduction in TNF-alpha, IL and IL-10 levels
Prognosis:
1. Mortality is > 20 %
2. Mortality increases with coexisting complications:
1. Tracheo esophegeal fistula
2. Meningo myelocoel
3. Meconium aspiration
4. Respiratory Distress syndrome
Prevention:
a. Maternal screening for GBS, HSV, HIV, Syphilis,Gono
b. Antibiotic prophylaxis to antenatal mother
c. Antibiotic prophylaxis to neonate
d. Hand washing
e. Barrier nursing
f. Aseptic techniques in resuscitation and nursery care
g. Colostrum and exclusive breast feeding
h. Caesarean section for proved vaginal sepsis like HSV
i. Presence of risk factors (MRO, PROM, Vaginal exam etc)
j. Three of the risk factors warrant initiation of antibiotic treatment.
k. Infants with two risk factors should be investigated with a septic screen and then treated
accordingly.

NEONATAL HYPERBILIRUBINEMIA
Bilirubin:
a. It is an end product of heme catabolism
b. Anti-oxidants like Vit.E, Catalase, superoxide dismutase are deficient in NB. Bilirubin is a powerful
antioxidant and a peroxyl scavenger. It protects NB from oxygen toxicity
 43

c. But elevations of indirect, unconjugated bilirubin are potentially neurotoxic. Conjugated form is not
neurotoxic, but may indicate a potentially serious hepatic disorders or a systemic illness.
2. Bilirubin metabolism:
a. Sources of Heme:
i. Hemoglobin: 80% from senile RBC and ineffective erythropoiesis
ii. Myoglobin
iii. Cytochrome P450
iv. Other Hemoproteins: catalase, heme peroxidase, and endothelial nitric oxide
synthase.
b. Fate of Hemoglobin:
Hemoglobin Heme + Globin+ (by lysosomal enzymes of RE cells)
Heme------------------ Biliverdin+ Iron+ CO
Heme oxygenase
Biliverdin--------------Bilirubin
Biliverdin reductase
c. Fate of bilirubin:
i. Transported to blood stream and bound to albumin
ii. Carried to liver and released; carried by ligandin in hepatocytes to mitochodria
iii. Conjugated with 2 molecules of glucuronic acid to bilirubin diglucuronide and
excreted to bile
3. Indirect or unconjugated bilirubin:
a. The lemon yellow color jaundice results from the accumulation of unconjugated, nonpolar, lipid-
soluble bilirubin pigment in the skin.
b. This unconjugated bilirubin (indirect-acting in Van den Bergh reaction) is an end product of
hemeprotein catabolism from a series of enzymatic reactions by hemeoxygenase and biliverdin
reductase and nonenzymatic reducing agents in the reticuloendothelial cells.
c. Unconjugated hyperbilirubinemia is increased by any factor that
i. Increases the load of bilirubin to the liver (haemolytic anemias, polycythemia, bruising or
internal hemorrhage, shortened red blood cell life as a result of immaturity or
transfusion of cells, increased enterohepatic circulation, infection);
ii. Reduces the activity of the transferase enzyme (genetic deficiency, hypoxia, infection,
thyroid deficiency);
iii. Competes for or blocks the transferase enzyme (drugs and other substances requiring
glucuronic acid conjugation);
iv. Leads to an absence or decreased amounts of the enzyme or to reduction of bilirubin
uptake by liver cells (genetic defect, and prematurity).
4. Clinical assessment of jaundice:
a. Jaundice usually becomes apparent in a cephalocaudal progression, starting on the face and
progressing to the abdomen and then the feet, as serum levels increase.
b. Dermal pressure may reveal the anatomic progression of jaundice by Kramer Rule but clinical
examination cannot be depended on to estimate serum levels:
i. face, ≈5 mg/dL;
ii. mid-abdomen, ≈15 mg/dL;
iii. soles, ≈20 mg/dL
c. Jaundice to the midabdomen, signs or symptoms, high-risk factors that suggest
nonphysiologic jaundice, or hemolysis must be evaluated further.
d. Noninvasive techniques like transcutaneous bilirubinometer that correlate with serum levels
may be used to screen infants.
 44

e. Infants with severe hyperbilirubinemia may present with lethargy and poor feeding and,
without treatment, can progress to acute bilirubin encephalopathy (kernicterus)
5. Direct Jaundice:
a. Conjugated bilirubin is the end product from indirect, unconjugated bilirubin that has undergone
conjugation in the liver cell microsome by the enzyme uridine diphosphoglucuronic acid (UDP)–
glucuronyl transferase to form the polar, water-soluble glucuronide of bilirubin (direct-reacting).
The water-soluble conjugated form is excreted from hepatic cells into the biliary system and
gastrointestinal tract.
b. Whereas jaundice from deposition of indirect bilirubin in the skin tends to appear bright yellow or
orange, jaundice of the obstructive type (direct bilirubin) has a greenish or muddy yellow cast.
6. Classification of Hyperbilirubinemia
1) Physiological: appear after 24 hour and always indirect hyperbilirubinemia
2) Pathological: appear witn in 24 hours plus direct hyperbilirubinemia
1. Indirect:
I. Hemolytic
1. ABO
2. Rh
3. Enzyme defect- G6PD
4. Membrane defect: Spherocytosis
5. Hemoglobin defect: Thalasemia
II. Non Hemolytic
1. Breast milk jaundice
2. Criggler najar I&II
3. Gilbert
4. Infection
2. Direct:
1. Familial:
a. Dubin Jhonson
b. Rotar
2. Infection
a. Neonatal hepatitis (TORCHS)
a. Neonatal sepsis
b. Giant cell hepatitis
3. Obstructive:
a. Biliary Obstruction
b. Choledochal cyst
4. Metabolic:
a. Cystic fibrosis
b. Galactosemia
c. Alpha1-antitrypsin deficiency
d. Tyrosinemia
6. Differential diagnosis:
a. Jaundice, consisting of either indirect or direct bilirubin, that is present at birth or appears
within the 1st 24 hr of life:
a. Erythroblastosis fetalis,
b. Concealed hemorrhage,
c. Sepsis,
d. Congenital infections, including syphilis, cytomegalovirus, rubella, and toxoplasmosis
 45

e. Infants who have received intrauterine transfusions for erythroblastosis fetalis

b. Jaundice that first appears on the 2nd day:
a. Physiologic jaundice
b. Crigler-Najjar syndrome
c. Early-onset breast-feeding jaundice
c. Jaundice appearing after the 3rd day and within the first week:
a. Bacterial sepsis or
b. Urinary tract infection;
c. It may also be due to TORCHS infection
d. jaundice first recognized after the 1st wk of life:
a. Breast milk associated jaundice,
b. Septicemia,
c. Congenital atresia or paucity of the bile ducts,
d. Hepatitis,
e. Galactosemia,
f. Hypothyroidism,
g. Cystic fibrosis, and
h. Congenital hemolytic anemia crises related to red blood cell morphology and enzyme
deficiencies.
e. Persistent jaundice during the first month of life:
a. Hyperalimentation-associated cholestasis,
b. Hepatitis, TORCHS
c. Congenital atresia of the bile ducts,
d. Galactosemia, and
e. Inspissated bile syndrome following hemolytic disease of the newborn.
f. Rarely, physiologic jaundice may be prolonged for several weeks, as in infants with
hypothyroidism or pyloric stenosis.

PHYSIOLOGICAL JAUNDICE or ICTERUS NEONATORUM

a) Criteria for physiologic jaundice:
a. Under normal circumstances, the level of indirect-reacting bilirubin in umbilical cord serum is 1-3
mg/dL and rises at a rate of less than 5 mg/dL/24 hr; thus,
b. jaundice becomes visible on the 2nd-3rd day,
c. usually peaking between the 2nd and 4th days at 5-6 mg/dL and
d. Decreasing to below 2 mg/dL between the 5th and 7th days of life.
e. Direct bilirubin level is normal
b) Causes:
a. Increased Hb% in NB with increased bilirubin production after the breakdown of fetal red blood
cells
b. Low UDPGT: Transient insufficiency in the conjugation of bilirubin by the liver.
c. Increased enterohepatic circulation
i. Increased b-glucoridase activity
ii. Decreased intestinal flora
iii. Decreased intestinal motility
d. Early and frequent feeding decreases, whereas breast-feeding and dehydration increase, serum
levels of bilirubin.
e. Delay in passage of meconium, which contains 1 mg bilirubin/dL, may contribute to jaundice by
enterohepatic recirculation after deconjugation by intestinal glucuronidase
 46

f. Drugs such as oxytocin (in the mother) and chemicals used in the nursery such as phenolic
detergents may also produce unconjugated hyperbilirubinemia.
c) Risk factors:
a. Maternal diabetes,
b. Prematurity,
c. Polycythemia,
d. Male sex,
e. Asian children
f. Trisomy 21,
g. Cephalohematoma,
h. Oxytocin induction,
i. Drugs: vitamin K3, novobiocin
d) Premature infants:
a. longer duration
b. results in higher levels,
c. peak being reached between the 4th and 7th days;
d. Peak levels of 8-12 mg/dL
e) Diagnosis:
a. The diagnosis of physiologic jaundice can be established only by precluding known causes of
jaundice
b. In general, it is unlikely to be physiological if there is:
i. A family history of hemolytic disease,
ii. Pallor,
iii. Hepatomegaly, splenomegaly,
iv. Failure of phototherapy to lower bilirubin,
v. Vomiting, lethargy, poor feeding, excessive weight loss, apnea, bradycardia, abnormal
vital signs (including hypothermia),
vi. Light-colored stools,
f) Treatment: No specific treatment is required for physiologic jaundice
g) Predicting risk for exaggerated physiologic jaundice in the 1st 24-72 hr of life based on hour-specific
bilirubin levels by graph of Bhutani VK, Johnson L, Sivieri EM:

h) Differences between physiological and pathological jaundice:

 47

Physiological jaundice Pathological jaundice

1) Jaundice after 24 hrs of life Jaundice appear within 24 hours of life
2) Increase by less than 5 mg/dl/day Increase by morethan 5 mg/dl/day
3) Reaches a maximum 12 mg/dl in term and 15 mg in May cross threshold level for developing kernicterus
preterm
4) Peak in 3-5 days and subside in 7 days in term and Rapid rise and produce any time depending on the
14 days in preterm severity and type
5) Includes only indirect hyperbilirubinemia Includes both indirect and direct hyperbilirubilemia
6) Causes of physiological jaundice: Causes of pathological jaundice: Eg:
1) Increased Hb% 1) Immune hemolysis-Rh and ABO
2) Low UDPGT 2) RBC membrane defect: Spherocytosis
3) Decreased intestinal flora 3) Hemoglobin defect: Thallasemia
4) Decreased intestinal motility 4) Enzyme defect: G6PD
5) Increased enterohepatic circulation 5) Biliary atresia
7) Pronosis is good Kernicterus is possible
8) No need for treatment Phototherapy and exchange blood transfusions are
indicated depending on type and severity

ABO INCOMPATIBILITY
Incidence
1) Approximately 15% of live births are at risk, but manifestations of disease develop in only 0.3-
2.2%.
2) Even first pregnancy can be affected
3) Usually, the mother is type O and the infant is type A or B. O mothe - A1 infant severe
incompatibility due to more Ig.G production which crosses the placenta
4) Although ABO incompatibility occurs in 20-25% of such pregnancies, haemolytic disease develops
in only 10% of the offspring, and the infants are generally type A1, which is more antigenic than
A2. Overall incidence is 1-2 %
5) ABO incompatibility is usually mild because of low antigenicity of the ABO system
6) First pregnancy can be affected as the antibodies are already existing in the mother
7) Less jaundice but anemia may be significant
8) < 10% may go for exchange transfusion
Pathophysiology
1) Transplacental transport of maternal isoantibody results in an immune reaction with the A or B
antigen on fetal erythrocytes, which produces microspherocytes.
2) This results in hemolysis of the spherocyte.
3) Due to less no. of A or B antigenic sites on the fetal erythrocytes and more competitive binding
sites in other tissues produce only mild hemolysis.
Risk factors:
1) A1 antigen
2) Antepartum intestinal parasitism or third-trimester immunization with tetanus toxoid
3) Birth order is not a risk factor in contrast to Rh disease.
Clinical presentation:
1) The onset is usually within the first 24 h of life.
2) The jaundice evolves at a faster rate than physiologic jaundice.
3) Anemia: Because of the effectiveness of compensation by reticulocytosis, anemia is less severe.
Diagnosis:
1) Blood type and Rh factor in the mother and the infant.
2) Increase in reticulocyte count will support the diagnosis of hemolytic anemia.
3) Direct Coombs' test: weakly positive
 48

4) Blood smear: microspherocytosis, polychromasia and normoblastosis.

5) Bilirubin levels: Indirect hyperbilirubinemia provides an index of the severity of disease.
6) Maternal IgG titer: Elevated IgG titers against the infant's blood group
Management:
1) Antepartum treatment: not indicated.
2) Postpartum treatment
a. Phototherapy: may entirely obviate the need for exchange transfusion
b. Exchange transfusion for jaundice crossing threshold values.
c. Packed cells for anemia
d. Intravenous immunoglobulin (IVIG). high-dose IVIG (1 g/kg over 4 h) has been shown to
reduce serum bilirubin levels and the need for blood exchange transfusion with ABO or Rh
hemolytic diseases.
e. Synthetic blood group trisaccharides: There is decrease in exchange transfusion rates when
A or B trisaccharides were administered.
Prognosis: the overall prognosis is excellent.

Rh INCOMPATIBILITY
Introduction:
1) Inheritance:
a. The Rh antigenic determinants are genetically transmitted from each parent (Autosomal
recessive), determine the Rh type;
b. A child will be Rh negative if both its parents are Rh negative. Otherwise the child may be Rh
positive or Rh negative.
c. Thus an Rh+ individual may be homozygous (+/+) or heterozygous (+/-), while an Rh-
individual must be homozygous (-/-).
d. <15% of population is Rh negative; 55% of Rh-positive fathers are heterozygous (D/d)
2) Antigens in RBC:
a. Rh factor has many antigens: D, C, E, Kell, Kidd, K, M, Duffy
b. 90 % Rh disease due to D antigen; C&E 10%
3) Rh incompatibility develops between an Rh-negative mother previously sensitized to the Rh (D)
antigen and her Rh positive fetus.
4) Only about 5% of Rh –ve mothers with Rh +ve fetus has babies with hemolytic disease.
5) Reasons for reduced incidence
a. If ABO incompatibility is coexisting, the mother is partially protected against sensitization by
the rapid removal of Rh-positive cells from her circulation by her preexisting anti-A or anti-B
antibodies
b. The onset of disease begins in utero; first pregnancy is usually not affected and severity will
increase with each successive Rh incompatible pregnancy. In restricred familysize Rh
incompatibility may not manifest.
c. The use of Rh immunoglobulin (RhoGAM) prophylaxis has reduced the incidence of Rh
sensitization to <1% of Rh-incompatible pregnancies.
d. 10-15% of Rh-negative mothers (10-50%) fail to develop specific IgG-Rh antibody despite
repeated exposure to Rh antigen.
Pathophysiology:
1. Exposure of the mother to the Rh antigen occurs in the following situations:
a. Parturition,
b. Miscarriage,
c. Abortion,
 49

d. Ectopic pregnancy.
e. Invasive investigative procedures such as amniocentesis, chorionic villus sampling,
2. Re exposure to the Rh antigen will induce a maternal anamnestic response and elevation of specific
IgG-Rh antibody.
Risk factors
1. Birth order. The first-born infant is at minimum risk (<1%) and subsequent pregnancies are at a
progressive risk for fetal disease.
2. Fetomaternal hemorrhage. The volume of fetal erythrocytes entering the maternal circulation
correlates with the risk of sensitization.
3. ABO incompatibility. Coexistent ABO incompatibility will reduce the risk of maternal Rh sensitization
to 1.5-3.0%.
4. Obstetric factors. Cesarean section increases the risk of significant fetomaternal transfusion
5. Gender. Male infants are reported to have an increased risk
6. Maternal immune response. A significant proportion of Rh-negative mothers (10-50%) fail to develop
specific IgG-Rh antibody despite repeated exposure to Rh antigen.
Clinical presentation
1. The severity of the disease may range from mild hemolysis (15% of cases) to severe anemia with
massive enlargement of the liver and spleen.
2. Jaundice.
a. Jaundice may be absent at birth because of placental clearance but unconjugated
hyperbilirubinemia appears within the first 24 h of life;
b. In severe cases, bilirubin pigments stain the amniotic fluid, cord, and vernix caseosa yellow
c. The level of bilirubin may rapidly reach high levels with the risk of bilirubin encephalopathy.
The risk is aggravated by hypoxia and acidosis.
3. Anemia.
a. Low cord blood hemoglobin reflects the relative severity of the haemolytic process.
b. Profound anemia results in pallor, signs of cardiac decompensation (cardiomegaly,
respiratory distress), massive anasarca, and circulatory collapse.
4. Petechiae, purpura, and thrombocytopenia may also be present in severe cases as a result of
decreased platelet production or the presence of concurrent disseminated intravascular coagulation.
5. Hypoglycemia occurs frequently and may be related to hyperinsulinism and hypertrophy of the
pancreatic islet cells
6. Hydrops fetalis.
a. Severe Rh disease can lead to hydrops fetalis
b. Clinical features in the fetus include progressive hypoproteinemia with ascites or pleural
effusion, or both; severe chronic anemia with secondary hypoxemia; and cardiac failure.
c. Pulmonary edema or bilateral pleural effusions results in birth asphyxia
d. severe respiratory distress may develop after birth
e. There is an increased risk of late fetal death& stillbirth.
f. Other causes of Hydrops:
i. α-Thalassemia
ii. Severe CHD with fetal CCF
iii. Chylothorax, chylous ascites
iv. Congenital infections
v. Congenital nephrosis
vi. Chromosome abnormalities
g. Management:
 50

i. Intrauterine exchange transfusion with type O Rh-negative packed erythrocytes will

raise the hematocrit and improve the oxygen-carrying capacity
ii. Therapeutic paracentesis or thoracentesis may be performed to remove pleural
fluid.
iii. Drug treatment may include diuretics such as furosemide for pulmonary edema and
pressor agents such as dopamine
7. Preterm labour can occur and may be spontaneous or induced.
Laboratory Data:
1. Blood type and Rh type (mother and infant) to establish incompatibility.
2. The cord blood hemoglobin is proportional to the severity of the disease; with hydrops fetalis it may
be as low as 3-4 g/dL.
3. The white blood cell count is usually normal but may be elevated; thrombocytopenia may develop in
severe cases.
4. Cord bilirubin is generally between 3 and 5 mg/dL; the directreacting (conjugated) bilirubin content
may also be elevated
5. Direct antiglobulin (Coombs') test. A strongly positive direct Coombs' test indicates that fetal RBCs are
coated with antibodies and is diagnostic of Rh incompatibility.
6. If Rh immunoglobulin was given at 28 weeks' gestation a false-positive direct Coombs' test occurs but
without reticulocytosis.
7. Blood smear. Polychromasia and normoblastosis are present. Spherocytes are not usually present. The
nucleated RBC (Normoblast) count will often be >10 per 100 white blood cells.
8. Bilirubin levels.
a. Progressive elevation of unconjugated bilirubin
b. Bilirubin-binding capacity tests: Measurements of serum albumin
9. Indirect Coombs' test. This test detects the presence of antibodies in the maternal serum. Rh-positive
RBCs are incubated with the maternal serum. The RBCs now coated with anti-D are agglutinated by an
antihuman globulin serum and gives positive Coomb’s reaction.
10. Carbon monoxide (CO). CO Hb levels are increased in neonates with hemolysis.
Antenatal diagnosis:
1. Maternal titer of IgG antibodies to D antigen should be assayed at 12-16, 28-32, and 36 wk of
gestation. A rapid rise in titer, or a titer of 1:64 or greater suggests significant hemolytic disease.
2. Fetal Rh status can be determined by isolating fetal cells or fetal DNA (plasma) from the maternal
circulation
3. Real-time ultrasonography:
a. Skin or scalp edema, pleural or pericardial effusions, and ascites.
b. organomegaly (liver, spleen, heart), the double–bowel wall sign (bowel edema), and placental
thickening.
4. Doppler ultrasonography:
a. Demonstration of an increase in the peak velocity of systolic blood flow in the middle
cerebral artery indicates severe anemia.
b. Assesses fetal distress by demonstrating increased vascular resistance in fetal middle cerebral
arteries;
5. Spectrophotometric scanning of amniotic fluid wavelengths demonstrates a positive optical density
(OD) deviation of absorption for bilirubin from normal at 450 nm.
6. Percutaneous umbilical blood sampling (PUBS) is performed to determine fetal hemoglobin levels and
to transfuse packed RBCs in those with serious fetal anemia
Postnatal diagnosis:
 51

1. Blood from the umbilical cord should be examined for ABO blood group, Rh type, Hct and hemoglobin,
and reaction to the direct Coombs test.
2. If the Coombs test result is positive, a baseline serum bilirubin level should be measured, and a
commercially available RBC panel should be used to identify RBC antibodies present in the mother’s
serum.
Management
1. Antepartum management:
a. Maternal antibody titer should be determined antenatally. Usual range is 1:16- 1:32
b. RhoGAM. Current obstetric guidelines suggest giving immunoprophylaxis at 28 weeks' gestation
c. Intrauterine transfusion. Intrauterine transfusion may be indicated to prevent fetal death or fetal
hydrops. Intravascular (umbilical vein) transfusion of packed by slow-push infusion after being
cross-matched against the mother’s serum.
d. Reduction of maternal antibody level. Maternal plasma exchange and high-dose IVIGs have been
of value in pregnant woman to reduce circulating maternal antibodies levels by >50%.
e. Delivery: indications are pulmonary maturity, fetal distress, complications of PUBS, and 35-37 wk
of gestation.
2. Postpartum treatment
1. Resuscitation:
i. Anemic infants may require immediate single-volume exchange blood transfusion at
delivery to improve oxygen-carrying capacity.
ii. Correction of acidosis with 1-2 meq/kg of sodium bicarbonate;
iii. Assisted ventilation for respiratory failure.
2. Phototherapy: decreases bilirubin levels and reduces the number of total exchange transfusions
required.
3. Exchange transfusion indications:
i. Cord hemoglobin value of 10 g/dL or less and bilirubin concentration of 5 mg/dL or more
ii. previous kernicterus or severe erythroblastosis in a sibling,
iii. reticulocyte counts >15%,
iv. prematurity
v. A rise of >5 mg/dL over 24 h within the first 2 days of life or more than 20 mg/dL in term
and > infants and > 15 mg in preterm are indications for exchange transfusion.
4. Heme oxygenase inhibitors (metalloporphyrins) are currently investigational. The enzyme heme
oxygenase catalyzes the rate-limiting step in bilirubin production, the conversion of heme to
biliverdin.
5. IVIG. Early administration of intravenous immunoglobulin (IVIG) may reduce hemolysis, peak
serum bilirubin levels, and the need for exchange transfusions. Postnatal treatment decreases
hemolysis of the antibody-coated Rh-positive RBCs. dose 0.5-1 gm/kg.
3. Prevention Rh disease: RhoGAM prophylaxis.
1. The risk of initial sensitization of Rh-negative mothers has been reduced to less than 1% by the
intramuscular injection of 300 μg of human anti-D globulin (1 mL of RhoGAM) within 72 hr of
delivery of an Rh-positive infant, ectopic pregnancy, abdominal trauma in pregnancy,
amniocentesis, chorionic villus biopsy, or abortion.
2. RhoGAM Administration of human anti-D globulin at 28-32 wk and again at birth (40 wk) is more
effective than a single dose.
3. Large fetal-to-maternal transfers of blood may require proportionately more human anti-D
globulin. The amount of fetal blood entering the maternal circulation may be estimated using the
Kleihauer-Betke acid elution technique during the immediate postpartum period.
Complications:
 52

1. Anemia
2. Cholestasis: Inspissated bile syndrome
3. Portal vein thrombosis and portal hypertension and a mild GVH reaction may manifest as diarrhea,
rash, hepatitis, or eosinophilia may occur in children who have been subjected to exchange
transfusion
4. Kernicterus
Prognosis:
a. Antenatal immune prophylaxis and improved management techniques, including amniotic fluid
spectrophotometry, intrauterine transfusion, and advances in neonatal intensive care, have been
largely responsible for a significant reduction in mortality.

EXCHANGE TRANSFUSION

1. Indications for Exchange transfusion:

a. To treat hyperbilirubinaemia when bilirubin reaches toxic levels in:-
i. rhesus haemolytic disease,
ii. ABO incompatibility,
b. babies with severe anaemia at birth (single volume exchange)
c. To reduce packed cell volume in polycythemia
d. Severe sepsis in NB
2. Types of exchange transfusion:
a. Partial exchange transfusion: is typically performed for Polycythemia. It consists of removing
whole blood and replacing it with albumin, plasma, or normal saline to lower the HCT to
approximately 55%.
b. Single blood volume exchange: using (85 ml/Kg ) and usually performed for anemia with heart
failure (i.e. hydrops fetalis)
c. Double volume exchange: (170 ml/ Kg of blood). Usually performed for severe hemolytic disease
of newborn.
3. Indications in hyperbilirubinemia:
1. Previous kernicterus or severe erythroblastosis in a sibling,
2. reticulocyte counts >15%, and
3. Bilirubin >20 mg in term baby
4. > 15 mg in preterm
5. Cord Hb% <10
6. Cord bilirubin > 5mg
4. Exchange transfusion:
1. O –ve fresh blood cross matched with infant and mother’s sera
2. Double volume: 85 X 2 / kg ml
3. 20 ml exchanged each time via umbilical venous catheter placed at IVC or hepatic vein
4. Removes 80% sensitized cells and mat. antibodies and 50 % of bilirubin
5. Potential complications from exchange transfusion are not trivial and include metabolic acidosis,
electrolyte abnormalities, hypoglycemia, hypocalcemia, thrombocytopenia, volume overload,
arrhythmias, NEC, infection, graft versus host disease, and death.

PHOTOTHERAPY
Principle:
1. Bilirubin absorbs light maximally in the blue range (420-470 nm). Broad-spectrum white, blue, and
special narrow-spectrum (super) blue lights have been effective in reducing bilirubin levels.
 53

2. Bilirubin in the skin absorbs light energy, causing several photochemical reactions.
3. One major product from phototherapy is a result of a reversible photo-isomerization reaction
converting the toxic native unconjugated 4Z,15Z-bilirubin into an unconjugated configurational
isomer, 4Z,15E-bilirubin, which can then be excreted in bile without conjugation.
4. The other major product from phototherapy is lumirubin, which is an irreversible structural isomer
converted from native bilirubin that can be excreted by the kidneys in the unconjugated state.
5. Phototherapy includes using “special blue” fluorescent tubes, placing the lamps within 15-20 cm of the
infant, and putting a fiberoptic phototherapy blanket under the infant’s back to increase the exposed
surface area.
Precautions:
1. Conventional phototherapy is applied continuously, and the infant is turned frequently for maximal skin
surface area exposure.
2. Before phototherapy is initiated, the infant’s eyes should be closed and adequately covered to prevent
light exposure and corneal damage.
3. Body temperature should be monitored, and the infant should be shielded from bulb breakage.
4. Irradiance should be measured directly. In infants with hemolytic disease, care must be taken to monitor
for the development of anemia, which may require transfusion.
5. Anemia may develop despite lowering of bilirubin levels.
Indications:
1. Aggressive phototherapy may improve neurodevelopmental outcome in infants <1,000 g.
2. Phototherapy may reduce the need for repeated exchange transfusions.
Contraindication:
1. Phototherapy is contraindicated in the presence of porphyria.
Complications
1. Clinical experience suggests that long-term adverse biologic effects of phototherapy are absent,
minimal, or unrecognized.
2. Common problems associated with phototherapy include:
a. Loose stools,
b. Erythematous macular rash,
c. Purpuric rash associated with transient porphyrinemia,
d. Overheating,
e. Dehydration (increased insensible water loss, diarrhea),
f. Hypothermia from exposure, and
i. A benign condition called bronze baby syndrome (which occurs in the presence of
direct hyperbilirubinemia).
3. Bronze baby syndrome:
a. It refers to a sometimes-noted dark, grayish brown skin discoloration in infants undergoing
phototherapy. Almost all infants observed with this syndrome have had significant
elevation of direct-reacting bilirubin and other evidence of obstructive liver disease. The
discoloration may be due to photo-induced modification of porphyrins, which are often
present during cholestatic jaundice and may last for many months.
b. Despite the bronze baby syndrome, phototherapy can continue if needed.

KERNICTERUS
1. Kernicterus, or bilirubin encephalopathy, is a neurologic syndrome resulting from the deposition of
unconjugated (indirect) bilirubin in the basal ganglia and brainstem nuclei. Neuronal loss occurs due
damage to cell membrane and interference to O2 utilization.
1. The pathogenesis of kernicterus is multifactorial and involves the following factors:
 54

a. Unconjugated bilirubin levels,

b. Albumin binding and unbound bilirubin levels,
c. Passage across the blood-brain barrier: increased in asphyxia and maturational changes in blood-
brain barrier permeability.
d. Neuronal susceptibility to injury.
2. Kernicterus occurs in full term infants with a bilirubin >20 mg/dL.and >15 mg/dL. in preterm. The more
immature the infant is, the greater the susceptibility to kernicterus.
Clinical manifestations
1. The early signs may be subtle and indistinguishable from those of sepsis, asphyxia, hypoglycemia,
intracranial hemorrhage, and other acute systemic illnesses in a neonate.
2. Lethargy, poor feeding, and loss of the Moro reflex are common initial signs.
3. Subsequently, the infant may appear gravely ill and prostrate, with diminished tendon reflexes and
respiratory distress.
4. Opisthotonos with a bulging fontanel, twitching of the face or limbs, and a shrill high-pitched cry may
follow.
5. In advanced cases, convulsions and spasm occur, with affected infants stiffly extending their arms in an
inward rotation with the fists clenched. Rigidity is rare at this late stage.
6. Many infants who progress to these severe neurologic signs die; the survivors are usually seriously
damaged but may appear to recover and for 2-3 mo show few abnormalities.
7. Later in the 1st yr of life, opisthotonos, muscle rigidity, irregular movements, and convulsions tend to
recur.
8. In the 2nd yr, the opisthotonos and seizures abate, but irregular, involuntary movements, muscle
rigidity, or, in some infants, hypotonia increase steadily.
9. By 3 yr of age, the complete neurologic syndrome is often apparent; it consists of bilateral
choreoathetosis with involuntary muscle spasms, extrapyramidal signs, seizures, mental deficiency,
dysarthric speech, high-frequency hearing loss, squinting, and defective upward eye movements.
Pyramidal signs, hypotonia, and ataxia occur in a few infants. In mildly affected infants, the syndrome
may be characterized only by mild to moderate neuromuscular incoordination, partial deafness, or
“minimal brain dysfunction,” occurring singly or in combination; these problems may be inapparent
until the child enters school.
10. Mental retardation, deafness, and spastic quadriplegia are common among survivors. .
11. Stages of Kernicterus:
Early Late Chronic
Lethargy Irritability Athetoid cerebral palsy
Poor feeding Opisthotonos High-frequency hearing loss
High-pitched cry Seizures Paralysis of upward gaze
Hypotonia Apnea Dental dysplasia
convulsions Oculogyric crisis Mild mental retardation
Bulging fontanel Hypertonia
Death Fever
12. Prevention
a. The only effective way at preventing kernicterus is to lower the serum bilirubin levels either
by phototherapy or exchange transfusion.
b. All pregnant women should be tested for ABO and Rh (D) blood types and have a serum
screen for unusual isoimmune antibodies
c. Visual inspection is never sufficient; therefore it is best to use a bilimeter or blood test to
determine a baby's risk for developing kernicterus.
d. These numbers can then be plotted on the Bhutani Nomogram.
 55

13. Treatment
a. Currently no effective treatment exists for kernicterus. Future therapies may include
neuroregeneration. A handful of patients have undergone deep brain stimulation, and
experienced some benefit.
b. Drugs such as Baclofen, Clonazepam, and Artane are often used to manage movement
disorders associated with kernicterus.
c. Proton Pump Inhibitors are also used to help with reflux. Cochlear Implants and hearing aids
have also been known to improve the hearing loss that can come with kernicterus (Auditory
Neuropathy - ANSD).

BREASTMILK AND JAUNDICE:

1. Jaundice associated with breast-feeding develops in 2% of breast-fed term infants after the 7th day of life,
with maximal concentrations as high as 10-30 mg/dL reached during the 2nd-3rd week. If breast-feeding is
continued, the bilirubin gradually decreases but may persist for 3-10 wk at lower levels.
2. If nursing is discontinued, the serum bilirubin level falls rapidly, reaching normal range within a few days.
With resumption of breast-feeding, bilirubin seldom returns to previously high levels. Phototherapy may
be of benefit.
3. Although uncommon, kernicterus can occur in patients with breast milk jaundice.
4. The etiology of breast milk jaundice is not entirely clear but may be attributed to the presence of
glucuronidase in some breast milk.
5. Breast milk related jaundice is of two types:
1. Early-Onset Breastfeeding Jaundice
a. It occurs in the 1st week of life in breast-fed infants (>12 mg/dL)
b. It may be due to decreased milk intake with dehydration and/or reduced caloric intake.
c. Prophylactic supplements of glucose water to breast-fed infants are associated with higher
bilirubin levels, in part because of reduced intake of the higher–caloric density breast milk.
d. Decreased volume and frequency of feedings may result in mild dehydration and the delayed
passage of meconium.
e. Inadequate breast milk with starvation leads to increased enterohepatic circulation &
Bilirubin in meconium is absorbed due to lack of meconium clearance.
f. Management:
i. The frequency of feedings needs to be increased to more than 10 per day and
rooming-in with night feeding should be encouraged.
ii. If the infant has a decline in weight gain, delayed stooling, and continued poor
caloric intake, formula supplementation may be necessary, but breastfeeding should
be continued
2. Late-Onset Breast Milk Jaundice
a. Breast milk jaundice occurs later in the newborn period, with the bilirubin level usually
peaking in the sixth to 14th days of life. This late-onset jaundice may develop in up to one
third of healthy breastfed infants. Total serum bilirubin levels vary from 12 to 20 mg per dL
and are nonpathologic.
b. The bilirubin level may remain persistently elevated for one to three months.
c. If the diagnosis of breast milk jaundice is in doubt or the total serum bilirubin level becomes
markedly elevated, breastfeeding may be temporarily interrupted, although the mother
should continue to express breast milk to maintain production.
d. With formula substitution, the total serum bilirubin level should decline rapidly over 48
hours. Breastfeeding may then be resumed.
 56

e. Etiology:
1. The underlying cause of breast milk jaundice is not entirely understood.
2. Gilbert syndrome may be associated in some- Defects in uridine diphosphate-glucuronyl
transferase activity
3. An unusual metabolite of progesterone (pregnane-3-alpha 20 beta-diol), a substance in
the breast milk that inhibits uridine diphosphoglucuronic acid (UDPGA) glucuronyl
transferase
4. Increased concentrations of nonesterified free fatty acids that inhibit hepatic glucuronyl
transferase
5. Increased enterohepatic circulation of bilirubin due to
a. Increased content of beta glucuronidase activity in breast milk and, therefore,
the intestines of the breastfed neonate and
b. Delayed establishment of enteric flora in breastfed infants
6. Reduced hepatic uptake of unconjugated bilirubin due to a mutation in the solute carrier
organic anion transporter protein SLCO1B1.
7. Inflammatory cytokines in human milk, especially interleukin (IL)-1 beta and IL-6, are
increased in individuals with breast milk jaundice and are known to be cholestatic and
reduce the uptake, metabolism, and excretion of bilirubin.

HEREDITARY SPHEROCYTOSIS
1. Etiology:
a. Autosomal dominant and, less frequently, autosomal recessive disorder.
b. Abnormalities of spectrin or ankyrin, which are major components of the cytoskeleton responsible
for RBC shape.
c. The loss of membrane surface area without a proportional loss of cell volume causes sphering of
the RBCs and an associated increase in cation permeability, cation transport, adenosine
triphosphate use, and glycolysis.
d. The decreased deformability of the spherocytic RBCs impairs cell passage from the splenic cords
to the splenic sinuses, and the spherocytic RBCs are destroyed prematurely in the spleen.
e. Splenectomy markedly improves RBC life span and cures the anemia.
2. Clinical features:
a. In Neonates: May present as anemia and hyperbilirubinemia
3. Laboratory findings:
1. Evidence of hemolysis includes reticulocytosis and indirect hyperbilirubinemia.
2. The hemoglobin level usually is 6–10 g/dL, but it can be in the normal range.
3. The reticulocyte percentage often is increased to > 10%.
4. The mean corpuscular volume is normal, although the mean corpuscular hemoglobin
concentration often is increased.
5. The RBCs on the blood film vary in size and include polychromatophilic reticulocytes and
spherocytes.
4. TREATMENT.
1. Splenectomy is the cure for this disorder.

G-6 PD DEFICIENCY

1. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most frequent disease involving enzymes of
the hexose monophosphate pathway, is responsible for 2 clinical syndromes:
a. episodic haemolytic anemia, and
 57

b. chronic nonspherocytic hemolytic anemia.

2. The most common manifestations of this disorder are neonatal jaundice and episodic acute hemolytic
anemia, which is induced by infections, certain drugs, and, rarely, fava beans.
3. This X-linked deficiency affects more than 400 million people worldwide, representing an overall 4.9%
global prevalence. The global distribution of this disorder parallels that of malaria.
Episodic or induced hemolytic anemia:
1. Etiology
a. G6PD catalyzes the conversion of glucose 6-phosphate to 6-phosphogluconic acid. This reaction
produces NADPH, which maintains glutathione in the reduced, functional state.
b. Reduced glutathione provides protection against oxidant threats from certain drugs and infections
that would otherwise cause precipitation of hemoglobin (Heinz bodies) or damage the RBC
membrane.
2. Clinical Manifestations:
a. Most individuals with G6PD deficiency are asymptomatic
b. Drugs that elicit hemolysis in these individuals include aspirin, sulfonamides, rasburicase, and
antimalarials, such as primaquine & favism
c. Neonates with coinheritance of G6PD deficiency and a mutation of the promoter of
uridinediphosphate-glucuronyl transferase, seen in Gilbert syndrome, have more severe neonatal
jaundice
3. Lab:
a. Unstained or supravital preparations of RBCs reveal precipitated hemoglobin, known as Heinz
bodies.
b. blood film may contain red cells with what appears to be a bite taken from their periphery
c. polychromasia (evidence of bluish, larger RBCs), representing reticulocytosis
d. The diagnosis depends on direct or indirect demonstration of reduced G6PD activity in RBCs
4. Prevention and Treatment
a. Prevention of hemolysis: ethnic groups with a significant incidence of G6PD deficiency should be
tested for the defect before known oxidant drugs are given.
b. Infants with severe neonatal jaundice who belong to these ethnic groups also require testing for
G6PD deficiency because of their heightened risk for this defect.
c. If severe hemolysis has occurred, supportive therapy may require blood transfusions, although
recovery is the rule when the oxidant agent is discontinued.
Chronic nonspherocytic hemolytic anemia:
1. This has been associated with profound deficiency of G6PD caused by enzyme variants. Persons with
G6PD B− enzyme deficiency occasionally have chronic hemolysis, and the haemolytic process may
worsen after ingestion of oxidant drugs.
2. Splenectomy is of little value in these types of chronic hemolysis.

CRIGLER-NAJJAR SYNDROME

Crigler-najjar syndrome type I (glucuronyl transferase deficiency)

1. This is inherited as an autosomal recessive trait. Enzyme bilirubin uridine diphospho glucuronate
glucuronosyltransferase is completely absent (UGT1A1). CN type II is due to decreased UGT1A1 activity.
1. CN type I is inherited as an autosomal recessive trait.
2. Clinical Manifestations
a. Severe unconjugated hyperbilirubinemia develops in homozygous affected infants in the 1st 3
days of life, and without treatment, serum unconjugated bilirubin concentrations of 25-35 mg/dL
are reached in the 1st month.
 58

b. Kernicterus, an almost universal complication of this disorder, is usually 1st noted in the early
neonatal period; some treated infants have survived childhood without clinical sequelae.
c. Stools are pale yellow.
d. Persistence of unconjugated hyperbilirubinemia at levels >20 mg/dL after the 1st wk of life in the
absence of hemolysis should suggest the syndrome.
3. Diagnosis
a. The diagnosis of CN type I is based on the early age of onset and the extreme level of bilirubin
elevation in the absence of hemolysis.
b. In the bile, bilirubin concentration is <10 mg/dL compared with normal concentrations of 50-100
mg/dL; there is no bilirubin glucuronide.
c. Definitive diagnosis is established by measuring hepatic glucuronyl transferase activity in a liver
specimen obtained by a closed biopsy; open biopsy should be avoided because surgery and
anesthesia can precipitate kernicterus.
d. DNA diagnosis is also available and may be preferable. Identification of the heterozygous state in
parents also strongly suggests the diagnosis.
4. Treatment
a. The serum unconjugated bilirubin concentration should be kept to <20 mg/dL for at least the 1st
2-4 wk of life; in low birthweight infants, the levels should be kept lower by repeated exchange
transfusions and phototherapy.
b. Phenobarbital therapy should be considered to determine responsiveness and differentiation
between type I and II.
c. The risk of kernicterus persists into adult life (serum bilirubin usually >35 mg/dL).
d. Adjuvant therapy using agents that bind photobilirubin products such as calcium phosphate,
cholestyramine, or agar can be used to interfere with the enterohepatic recirculation of bilirubin.
e. Prompt treatment of intercurrent infections, febrile episodes help prevent the later development
of kernicterus
f. Orthotopic liver transplantation cures the disease and has been successful in a small number of
patients; isolated hepatocyte transplantation has been reported in fewer than 10 patients, but all
patients eventually required orthotopic transplantation.
g. Other therapeutic modalities have included plasmapheresis and limitation of bilirubin production.
The latter option, inhibiting bilirubin generation, is possible via inhibition of heme oxygenase
using metalloporphyrin therapy.

CRIGLER-NAJJAR SYNDROME TYPE II

(PARTIAL GLUCURONYL TRANSFERASE DEFICIENCY)

1. CN type II is an autosomal recessive disease; it is caused by homozygous missense mutations in UGT1A1,

resulting in reduced (partial) enzymatic activity
2. Type II disease can be distinguished from type I by the marked decline in serum bilirubin level that occurs
in type II disease after treatment with phenobarbital secondary to an inducible phenobarbital response
element on the UGT1A1 promoter.
Clinical Manifestations
1. When this disorder appears in the neonatal period, unconjugated hyperbilirubinemia usually occurs in the
1st 3 days of life; serum bilirubin concentrations can be in a range compatible with physiologic jaundice or
can be at pathologic levels. The concentrations characteristically remain elevated into and after the 3rd wk
of life, persisting in a range of 1.5-22 mg/dL; concentrations in the lower part of this range can create
uncertainty about whether chronic hyperbilirubinemia is present.
2. Development of kernicterus is unusual.
 59

3. Stool color is normal, and the infants are without clinical signs or symptoms of disease. There is no
evidence of hemolysis.
Diagnosis
1. Concentration of bilirubin in bile is nearly normal in CN type II.
2. Jaundiced infants and young children with type II syndrome respond readily to 5 mg/kg/24 hr of oral
phenobarbital, with a decrease in serum bilirubin concentration to 2-3 mg/dL in 7-10 days.
Treatment
1. Long-term reduction in serum bilirubin levels can be achieved with continued administration of
phenobarbital at 5 mg/kg/24 hr.
2. Orlistat, an irreversible inhibitor of intestinal lipase, induces a mild decrease in plasma bilirubin levels
(~10%) in patients with CN I and II.

GILBERT SYNDROME

1. Gilbert's syndrome is usually an autosomal recessive disorder and is a common cause of unconjugated
hyperbilirubinaemia. There have been some reports of heterozygous cases, mainly within Asian
populations.
2. Gilbert's syndrome affects 5-10% of people in Western Europe. The worldwide prevalence of Gilbert's
syndrome varies considerably depending on which diagnostic criteria are used. Men are more commonly
affected than women.
3. Gilbert syndrome is caused by mutation in the promoter region of UGT1A1 that leads to decreased
glucuronyl transferase activity to < 30%.
4. Gilbert's syndrome is characterised by unconjugated hyperbilirubinemia, no evidence of haemolysis,
normal liver enzyme levels and no evidence of liver disease.
5. It is usually diagnosed around puberty, and aggravated by intercurrent illness, stress, fasting or after
administration of certain drugs.
6. The increase in serum concentrations of unconjugated bilirubin can lead to intermittent episodes of non-
pruritic jaundice, which can be precipitated by fasting, infections, dehydration, surgery, physical exertion
and lack of sleep. Symptoms, including tiredness, that occur during episodes of jaundice are caused by the
precipitating factor and do not result directly from Gilbert's syndrome.
7. It can remain unnoticed for many years, but usually presents in adolescence with:
1. Intermittent jaundice noticed after fasting, lack of sleep, vigorous exercise or during an
intercurrent illness.
2. Exposure to certain medications which may precipitate jaundice - eg, chemotherapy. Adverse
effects of anticancer agents have been observed in Gilbert's syndrome patients due to reduced
drug or bilirubin glucuronidation.

LUCY - DRISCOL SYNDROME

1. Lucey Driscoll syndrome is characterized by severe jaundice in the first 4 days of life.
2. It is a transient condition and is due to presence of an inhibitor substance in the mother's blood that
prevents the action of an enzyme in the baby's liver that conjugates the bilirubin (the pigment that
accumulates in access in jaundice).
3. As a result of high bilirubin, the child has jaundice and sometimes even convulsions. Since, this inhibitor is
present only for a limited time, the condition is transient.
4. The treatment is light in the form of photo therapy, drugs such as phenobarbitone and even blood
transfusion in the form of exchange transfusion.
 60

DUBIN-JHONSON SYNDROME

1. Dubin-Johnson syndrome is an autosomal recessive inherited defect with variable penetrance in

hepatocyte secretion of bilirubin glucuronide.
2. The defect in hepatic excretory function is not limited to conjugated bilirubin excretion but also involves
several organic anions normally excreted from the liver cell into bile.
3. Bile acid excretion and serum bile acid levels are normal.
4. Total urinary coproporphyrin excretion is normal in quantity but coproporphrin I excretion increases to
∼80% with a concomitant decrease in coproporphyrin III excretion. Normally, coproporphyrin III is >75% of
the total.
5. Cholangiography fails to visualize the biliary tract and x-ray of the gallbladder is also abnormal.
6. Liver histology demonstrates normal architecture, but hepatocytes contain black pigment similar to
melanin.
ROTOR SYNDROME

1. Patients with Rotor syndrome have an additional deficiency in organic anion uptake; however, the genetic
defect has not yet been elucidated.
2. Unlike Dubin-Johnson syndrome, total urinary coproporphyrin excretion is elevated, with a relative
increase in the amount of the coproporphyrin I isomer.
3. The gallbladder is normal by roentgenography, and liver cells contain no black pigment.
4. In Dubin-Johnson and Rotor syndromes, sulfobromophthalein excretion is often abnormal.

DIRECT HYPERBILIRUBINEMIA
1) Normal value:
a. A value < 2.0 mg/dL is normal
b. A value >5.0 mg/dL is considered severe
2) Risk factors:
1. Infant receiving total parenteral nutrition (TPN) for >2 weeks
2. Infection may cause hepatocellular damage, leading to increased direct bilirubin levels.
3. direct hyperbilirubinemia occurs after feedings in galactosemia
3) Differential diagnosis:
a. More common causes of direct hyperbilirubinemia.
I. Idiopathic neonatal hepatitis: most common
II. Biliary atresia is the second most common
III. Bacterial infection (sepsis or urinary tract infection).
IV. Intrauterine infection (TORCH)
V. Inspissated bile (bile plug) from hemolytic disease.
VI. Choledochal cyst.
VII. Alpha-antitrypsin deficiency is the most common genetic cause of cholestasis.
VIII. Galactosemia
B. Less common causes of direct hyperbilirubinemia:
i. Cystic fibrosis.
ii. Hypothyroidism.
iii. Rotor's syndrome.
iv. Dubin-Johnson syndrome, a genetic defect in the canalicular transport system.
v. Storage disease (eg, Niemann-Pick disease or Gaucher's disease).
 61

vi. Metabolic disorders (eg, tyrosinemia, fructosemia).

vii. Trisomy 21 or 18.
4) History:
a. The clinical hallmarks of the disease include icterus (Greenish yellow), acholic stools, and dark
urine.
5) Physical examination:
a. Enlarged liver or spleen. Splenomegaly is more common in neonatal hepatitis but can be a late
sign in biliary atresia.
6) Laboratory studies:
a. Elevated levels of AST and ALT signify hepatocellular damage. Elevated alkaline phosphatase
levels may signify biliary obstruction. Elevated GGTP is a sensitive but nonspecific indicator of
early cholestatic change.
b. A complete blood cell count with differential may help to determine whether infection is
present.
c. Coombs' test may indicate the possibility of hemolytic disease.
d. Prothrombin time, partial thromboplastin time, and serum albumin level
e. Blood and urine culture. If sepsis is suspected.
f. Testing for viral disease.
i. Determine the serum total immunoglobulin M for test for TORCH infections.
ii. Urine is tested for cytomegalovirus, and a
iii. Serum hepatitis profile is obtained (hepatitis surface antigen and IgM hepatitis A
antibody). Hepatitis B markers should be tested in both the mother and the infant.
g. Serum alpha1-antitrypsin levels. These levels are obtained to rule out alpha1-antitrypsin
deficiency.
h. Urine-reducing substance should be determined if galactosemia is suspected.
i. Serum thyroxine (T4) and thyroid-stimulating hormone (TSH) levels should be
obtained if hypothyroidism is suspected.
j. Sweat chloride test. A quantitative sweat chloride test should be done to rule out cystic fibrosis.
k. Urine metabolic screen.
7. Radiologic and other studies:
a. Ultrasonography. Ultrasound examination of the liver and the biliary tract will rule out
choledochal cyst, stones, tumor, and masses and will also provide information on the gallbladder.
The absence of the gallbladder may suggest biliary atresia.
b. Radionuclide scans allow evaluation of the biliary anatomy.
c. Liver biopsy is usually performed after all other laboratory tests have been performed and a
definitive diagnosis is still needed.
8. Exploratory laparotomy and operative cholangiography should be done if biliary atresia is
suspected or the medical evaluation is inconclusive.
9. Management:
1. Biliary atresia.
a. Hepatic portoenterostomy (the Kasai procedure) is currently the initial procedure of choice
in infancy;
b. Hepatic transplantation offers improved survival and quality of life to those for whom the
Kasai operation has not been successful.
2. Idiopathic neonatal hepatitis. Supportive care
3. Alpha1-antitrypsin. The only curative therapy is liver transplantation.
4. Bacterial infection. If signs of sepsis are present, appropriate cultures should be performed and
empiric antibiotic therapy initiated.
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5. Intrauterine infection. Appropriate antiviral agents or other medications should be started, if

indicated.
6. Inspissated bile secondary to hemolytic disease is treated with supportive management. The use
of phenobarbital is controversial.
7. Choledochal cyst. The treatment is surgical removal.
8. Galactosemia. Immediate elimination of lactose- and galactose-containing products from the diet
is required.

NEONATAL HEPATITIS SYNDROME

The neonatal hepatitis syndrome is the term given to non-specific hepatic inflammation, which develops
secondary to many different aetiologies, including:
i. Infectious hepatitis: 20 %; it occurs only in early infancy, usually between one and two months after
birth. These include cytomegalovirus, rubella (measles), and hepatitis A, B or C viruses.
ii. Idiopathic neonatal hepatitis: In the remaining 80 percent of the cases no specific virus can be
identified as the cause, and it develops secondary to many different aetiologies as follows:
1. Disorders of membrane transport and secretion
a. Disorders of canalicular secretion
b. Bile acid transport—BSEP(bile salt export pump) deficiency
c. Phospholipid transport— (PFIC progressive familial intrahepatic cholestasis)
d. Ion transport—cystic fibrosis
2. Complex/multi-organ disorders
a. FIC1 deficiency
b. Neonatal sclerosing cholangitis
c. Arthrogryposis–renal dysfunction–cholestasis syndrome
3. Disorders of bile acid biosynthesis and conjugation
4. Disorders of embryogenesis
a. Ductal plate malformation ( eg. Caroli disease)
b. Alagille syndrome (Jagged1 defect, syndromic bile duct paucity)
5. Unclassified (idiopathic “neonatal hepatitis”)-mechanism unknown
iii. Biliary atresia :
a. The most common form of biliary atresia is obliteration of the entire extrahepatic biliary tree
at or above the porta hepatis. This presents a much more difficult problem in surgical
management.
b. Most patients with biliary atresia (85–90%) have a postnatal onset; embryonic fetal onset
presents at birth and is associated with other congenital anomalies within the polysplenia
spectrum (biliary atresia splenic malformation [BASM])
c. Incidence. 1/10,000-15,000 live births
d. Differentiation of idiopathic neonatal hepatitis from biliary atresia.
Idiopathic neonatal hepatitis Biliary atresia
Familial Not familial
More common in premature or small Increased incidence polysplenia syndrome with
for gestational age infants. abdominal heterotaxia, malrotation, levocardia
Transient impairment of bile excretion Persistently acholic stools
Less severe hepatomegaly liver may find an abnormal size or consistency
US: abdominal polysplenia micro-gallbladder; Ultrasonographic triangular cord (TC)
sign, which represents a cone-shaped fibrotic mass cranial
to the bifurcation of the portal vein.
 63

iv. Lab evaluation to differentiate biliary atresia from neonatal hepatitis:

a. Hepatobiliary scintigraphy with technetium-labeled iminodiacetic acid derivatives is used to
differentiate biliary atresia from nonobstructive causes of cholestasis. The hepatic uptake of the
agent is normal in patients with biliary atresia, but excretion into the intestine is absent. Although
the uptake may be impaired in neonatal hepatitis, excretion into the bowel will eventually occur.
Obtaining a follow-up scan after 24 hr is of value to determine the patency of the biliary tree.
b. The administration of phenobarbital (5 mg/kg/day) for 5 days before the scan is recommended
because it may enhance biliary excretion of the isotope.
c. Percutaneous liver biopsy: Biliary atresia is characterized by bile ductular proliferation, the
presence of bile plugs, and portal or perilobular edema and fibrosis, with the basic hepatic lobular
architecture intact. In neonatal hepatitis, there is severe, diffuse hepatocellular disease, with
distortion of lobular architecture, marked infiltration with inflammatory cells, and focal
hepatocellular necrosis; the bile ductules show little alteration. Giant cell transformation is found
in infants with either condition and has no diagnostic specificity.
d. The histologic changes seen in patients with idiopathic neonatal hepatitis can occur in other
diseases, including α1-antitrypsin deficiency, galactosemia, and various forms of intrahepatic
cholestasis. Although paucity of intrahepatic bile ductules may be detected on liver biopsy even in
the 1st few weeks of life, later biopsies in such patients reveal a more characteristic pattern.
Other conditions of neonatal hepatitis like syndromes:
a. Aagenaes syndrome is a form of idiopathic familial intrahepatic cholestasis associated with
lymphedema of the lower extremities.
d. Zellweger (cerebrohepatorenal) syndrome is a rare autosomal recessive genetic disorder marked
by progressive degeneration of the liver and kidneys
e. Neonatal hemochromatosis is a rapidly progressive disease characterized by increased iron
deposition in the liver, heart, and endocrine organs without increased iron stores in the
reticuloendothelial system.
f. Alagille syndrome (arteriohepatic dysplasia) is the most common syndrome with intrahepatic bile
duct paucity.
g. Caroli disease and Caroli syndrome are rare congenital disorders of the intrahepatic bile ducts.
They are both characterized by dilatation of the intrahepatic biliary tree. The term Caroli disease
is applied if the disease is limited to ectasia or segmental dilatation of the larger intrahepatic
ducts. This form is less common than Caroli syndrome, in which malformations of small bile ducts
and congenital hepatic fibrosis are also present. This process can be either diffuse or segmental
and may be limited to one lobe of the liver, more commonly the left lobe. Caroli disease is
sporadic, whereas Caroli syndrome is generally inherited in an autosomal recessive manner. As
with congenital hepatic fibrosis, Caroli syndrome is often associated with autosomal recessive
polycystic kidney disease (ARPKD).
ii. Management of patients with suspected biliary atresia.
a. All patients suspected of having biliary atresia should undergo exploratory laparotomy and direct
cholangiography to determine the presence and site of obstruction
b. For patients in whom no correctable lesion is found, the hepatoportoenterostomy (Kasai)
procedure should be performed.
iii. Treatment of neonatal cholestasis:
a. Decreased delivery of bile acids to the proximal intestine leads to inadequate digestion and
absorption of dietary long-chain triglycerides and fat-soluble vitamins.
b. Impairment of hepatic metabolic function can alter hormonal balance and utilization of nutrients.
c. Progressive liver damage can lead to biliary cirrhosis, portal hypertension, and liver failure.
d. Management:
 64

CLINICAL IMPAIRMENT MANAGEMENT

Malnutrition resulting from malabsorption of Replace with dietary formula or supplements containing
dietary long-chain triglycerides medium-chain triglycerides

Vitamin A deficiency (night blindness, thick skin) Replace with 10,000–15,000 IU/day as Aquasol A

Vitamin E deficiency (neuromuscular degeneration) Replace with 50–400 IU/day as oral α-tocopherol or
TPGS

Vitamin D deficiency (metabolic bone disease) Replace with 5,000–8,000 IU/day of D2 or 3–5 μg/kg/day
of 25-hydroxycholecalciferol

Vitamin K deficiency (hypoprothrombinemia) Replace with 2.5–5.0 mg every other day as water-
soluble derivative of menadione

Deficiency of water-soluble vitamins Supplement with twice the recommended daily

allowance

Retention of biliary constituents such as cholesterol Administer choleretic bile acids and ursodeoxycholic
(itch or xanthomas) acid, 15–20 mg/kg/day

Progressive liver disease; portal hypertension Interim management (control bleeding; salt restriction;
(variceal bleeding, ascites, hypersplenism) spironolactone)

End-stage liver disease (liver failure) Transplantation

RESPIRATORY DISTRESS IN NEW-BORN

Definition:
Respiratory rate of more than 60 per minute, with:
a. Dyspnea, intercostal or subcostal indrawing, sternal retraction,
b. Predominantly diaphragmatic breathing pattern.
c. A characteristic expiratory grunt
d. Cyanosis in room air
Causes of respiratory distress in NB
1. Pulmonary:
1. Common
i. Respiratory distress syndrome
ii. Transient tachypnea
iii. Pneumonia
iv. Meconium Aspiration syndrome
v. Pneumothorax and air leaks
vi. Pulmonary edema
vii. Pleural effusion
viii. Pulmonary hemorrhage
2. Uncommon
3. Diapragmatic hernia
4. Tracheoesophageal fistula
5. Cysts and tumors
6. Congenital lobar emphysema
7. Pulmonary hypoplasia
8. Accessory or sequestered lobes
9. Pulmonary lymphangiectasia
 65

10. Pulmonary arteriovenous fistula

2. Cardiac:
1. Persistent fetal circulation
2. Cyanotic congenital heart disease
3. Congestive heart failure
3. Abdominal:
1. Ascites
2. Necrotizing enterocolitis
3. Abdominal mass
4. Omphalocele
5. Gastroschisis
4. Haematological:
1. Anemia
2. Polycythemia
3. Hypotension
4. Hypovolemia
5. CNS
a. Asphyxia
b. Intracranial hemorrhage
c. Neuromuscular disorders
d. Drugs
6. Others:
a. Sepsis
b. Acidosis
c. Hypothermia,
d. cold stress
e. Hyperthermia
f. Hypoglycemia
g. Methemoglobinemia

TRANSIENT TACHYPNEA OF THE NEWBORN

(RDS type II- wet lung syndrome)

1. Transient tachypnea may follow uneventful preterm or term vaginal delivery or cesarean delivery.
2. It is characterized by the early onset of tachypnea, sometimes with retractions, or expiratory grunting and,
occasionally, cyanosis that is relieved by minimal oxygen supplementation (<40%).
3. Most infants recover rapidly, within 3 days.
4. Pathogenesis: Delayed clearance of fetal lung fluid via the circulation and pulmonary lymphatics. Improper
squeezing of lung fluid during vaginal passage.
5. The chest generally sounds clear without rales or rhonchi, and the chest radiograph shows prominent
pulmonary vascular markings, fluid in the intralobar fissures, overaeration, flat diaphragms, and, rarely,
small pleural effusions.
6. Hypercapnia and acidosis are uncommon.
7. Distinguishing the disease from RDS and other respiratory disorders (e.g., pneumonia) may be difficult, and
transient tachypnea is frequently a diagnosis of exclusion; the distinctive features of transient tachypnea
are rapid recovery of the infant and the absence of radiographic findings for RDS (hypoaeration, diffuse
reticulogranular pattern, air bronchograms) and other lung disorders.
 66

8. In severe cases, retained fetal lung fluid may interfere with the normal postnatal fall in PVR, resulting in
persistent pulmonary hypertension.
9. X-ray of the chest
a. There are prominent peirhilar vascular markings, edema of the interlobar septae and fluid in the
fissures.
b. Treatment is supportive. There is no evidence supporting the use of oral furosemide in this
disorder.
10. Severe respiratory morbidity and mortality have been reported in infants born by elective cesarean section
who initially present with signs and symptoms of transient tachypnea. These infants demonstrate
refractory hypoxemia due to pulmonary hypertension and require ECMO support. The term “malignant
TTN” has been used to describe this condition.
11. AAP STUDIES:
a. It is more common in newborns of mothers with asthma. Newborns with TTN have a greater risk
of developing asthma in childhood; in one study, this association was stronger in patients of lower
socioeconomic status, nonwhite race, and males whose mothers did not have asthma.TT N results
from delayed reabsorption and clearance of alveolar fluid. Postdelivery prostaglandin release
distends lymphatic vessels, which removes lung fluid as pulmonary circulation increases with the
initial fetal breath. Cesarean delivery without labor bypasses this process and is therefore a risk
factor for TTN.
b. Surfactant deficiency may play a role in TTN. Research indicates a decreased count of lamellar
bodies in the gastric aspirate and decreased surfactant phospholipid concentrations in the
tracheal aspirate in cases of TTN. However, treating TTN with surfactant is not indicated.
c. Antenatal corticosteroids given 48 hours before elective cesarean delivery at 37 to 39 weeks'
gestation reduce TTN incidence, although it is unclear whether delaying cesarean delivery until 39
weeks' gestation is preferable.

HYALINE MEMBRANE DISEASE (RDS type I)

1. Definition:
a. A preterm neonate showing progressive respiratory difficulty including tachypnea >60/mt, chest
retractions, and cyanosis within 48-96 hours of life
b. Chest radiograph shows uniform reticulogranular pattern and peripheral air bronchogram
2. Incidence:
a. It occurs in 60-80% of infants <28 wk of gestational age, in 15-30% of those between 32 and 36
wk, and rarely in those >37 wk.
b. The risk increases with:
i. Maternal diabetes,
ii. Multiple births,
iii. Cesarean delivery,
iv. Precipitous delivery,
v. Asphyxia,
vi. Cold stress,
vii. Maternal history of previously affected infants.
viii. Preterm male or white infants.
c. The risk of RDS is reduced in pregnancies with:
i. Chronic or pregnancy-associated hypertension,
ii. Maternal heroin use,
iii. Prolonged rupture of membranes, and
 67

iv. Antenatal corticosteroid prophylaxis.

d. Accounts for 6% neonatal deaths prior to surfactant era
3. Inherited causes of surfactant deficiency:
Abnormalities in surfactant protein B and C genes and gene responsible for transporting
surfactant across membranes (ABC transporter 3 [ABCA3])
4. Pathophysiology:
1. Surfactant synthesis begins at 24 weeks. It appears in amniotic fluid between 28 and 32 wk.
Mature levels of pulmonary surfactant are present after 35 wk.
2. Surfactant is a complex system of lipids, proteins and glycoproteins produced in type II
pneumocytes. The surfactant is packaged by the cell in lamellar bodies, and extruded into the air-
spaces.
3. Synthesis of surfactant depends in part on normal pH, temperature, and perfusion. Asphyxia,
hypoxemia, and pulmonary ischemia, particularly in association with hypovolemia, hypotension,
and cold stress, may suppress surfactant synthesis.
4. In preterm, immature type II alveolar cells produce less surfactant, causing an increase in alveolar
surface tension and a decrease in compliance.
5. The resultant atelectasis causes pulmonary vascular constriction, hypoperfusion, and lung tissue
ischemia.
6. Pulmonary blood flow is reduced and ischemic injury both to the cells producing surfactant and to
the vascular bed results in an effusion of proteinaceous material into the alveolar spaces.
7. Hyaline membrane is formed through the combination of sloughed epithelium, protein, and
edema
5. Clinical presentation:
1. Signs of RDS usually appear within minutes of birth, although they may not be recognized for
several hours
2. Characteristically, tachypnea, prominent (often audible) grunting, intercostal and subcostal
retractions, nasal flaring, and cyanosis are noted.
3. RDS is characterized by progressive worsening of cyanosis and dyspnea
4. If the condition is inadequately treated, blood pressure may fall; cyanosis and pallor increase, and
grunting decreases or disappears, as the condition worsens.
5. Patients may also have a mixed respiratory-metabolic acidosis, edema, ileus, and oliguria.
6. Respiratory failure may occur in infants with rapid progression of the disease.
7. In most cases, the symptoms and signs reach a peak within 3 days, after which improvement is
gradual. Improvement is often heralded by spontaneous diuresis and improved blood gas values
at lower inspired oxygen levels and/or lower ventilator support.
8. Death can be due to severe impairment of gas exchange, alveolar air leaks (interstitial
emphysema, pneumothorax), pulmonary hemorrhage, or IVH.
6. Diagnosis:
a. The lecithin/sphingomyelin ratio was less than 2 ; phosphatidylglycerol was not present in
amniotic fluid or tracheal fluids at birth; negative bubble stability test
b. CXR:
i. Uniform reticular pattern or ground glass appearance
ii. Air bronchogram
7. D.D:
a. Early-onset sepsis:
i. It may be indistinguishable from RDS.
ii. In pneumonia manifested at birth, the chest roentgenogram may be identical to that
for RDS.
 68

iii. Maternal group B streptococcal colonization, identification of organisms on gram

staining of gastric or tracheal aspirates or a buffy coat smear, and/or the presence of
marked neutropenia may suggest the diagnosis of early-onset sepsis.
b. Cyanotic heart disease (total anomalous pulmonary venous return) can also mimic RDS both
clinically and radiographically. Echocardiography with color-flow imaging should be
performed in infants who show no response to surfactant replacement, to rule out cyanotic
congenital heart disease as well as ascertain patency of the ductus Arteriosus and assess
pulmonary vascular resistance (PVR).
c. Persistent pulmonary hypertension, aspiration (meconium, amniotic fluid) syndromes,
spontaneous pneumothorax, pleural effusions, and congenital anomalies such as cystic
adenomatoid malformation, pulmonary lymphangiectasia, diaphragmatic hernia, and lobar
emphysema must be considered in patients with an atypical clinical course but can generally
be differentiated from RDS through radiographic evaluation.
d. Transient tachypnea may be distinguished by its short and mild clinical course and is
characterized by low or no need for oxygen supplementation.
8. Management:
Prevention:
1. Avoidance of unnecessary or poorly timed cesarean section, appropriate management of high-risk
pregnancy and labor, and prediction of pulmonary immaturity with possible in utero acceleration of
maturation
2. Antenatal corticosteroids:
1. Administration of antenatal corticosteroids to women between 24 and 34 wk of gestation
significantly reduces the incidence and mortality of RDS as well as overall neonatal mortality.
2. Repeated weekly doses of betamethasone until 32 wk may reduce neonatal morbidities and
the duration of mechanical ventilation.
3. Antenatal steroid given to mother reduces neonatal deaths in first 48 hours due to:
i. RDS
ii. Intraventricular hemorrhage
iii. Necrotising enterocolitis
4. Betamethasone and dexamethasone have been used antenatally. Dexamethasone may result
in a lower incidence of IVH than betamethasone, but further research is needed to determine
whether one of these steroids is superior for antenatal treatment.
5. For unbooked cases: 12 mg betamethazone Im two doses 24 hour apart.
6. Early supportive care of premature infants, especially in the treatment of acidosis, hypoxia,
hypotension, and hypothermia, may lessen the severity of RDS.
7. Calories and fluids should initially be provided intravenously. For the 1st 24 hr, 10% glucose
and water should be infused through a peripheral vein at a rate of 65-75 mL/kg/24 hr.
8. Warm humidified oxygen should be provided at a concentration initially sufficient to keep
arterial oxygen pressure between 40 and 70 mm Hg (85-95% saturation)
9. CPAP prevents collapse of surfactant-deficient alveoli and improves both FRC and ventilation-
perfusion matching. Early use of CPAP for stabilization of at-risk VLBW infants beginning as
early as in the delivery room reduces ventilatory needs.
10. Infants with respiratory failure or persistent apnea require assisted mechanical ventilation.
11. Many ventilated neonates receive sedation or pain relief with benzodiazepines or opiates
(morphine, fentanyl), respectively. Midazolam is approved for use in neonates and has
demonstrated sedative effects.
12. Premature infants requiring ventilator support after 1 wk of age
 69

13. High-frequency ventilation (HFV) achieves desired alveolar ventilation by using smaller tidal
volumes and higher rates.
14. The most current data do not support the routine administration of iNO in preterm infants
with hypoxemic respiratory failure.
15. Inhaled nitric oxide (iNO) decreases the need for extracorporeal membrane oxygenation
(ECMO) in term and near-term infants with hypoxic respiratory failure or persistent
pulmonary hypertension of the neonate.
3. Surfactant therapy:
1. Exosurf is a synthetic surfactant. Natural surfactants include Survanta (bovine), Infasurf (calf),
and Curosurf (porcine). Natural surfactants are superior because of their surfactant-
associated protein content, their more rapid onset, and their lower risk of pneumothorax and
improved survival.
2. Dosing:
i. Prophylactic: surfactants within 15 mts of birth to all preterm < 30 weeks
ii. Resque or relacement therapy: preferably within 2 hours after birth
iii. Repeated dosing is given via the endotracheal tube every 6-12 hr for a total of 2 to 4
doses
iv. Initial and subsequent dose of Survanta is 100 mg/kg
v. Initial dose of Curosurf is 100-200 mg/kg and subsequent doses of 100 mg.
3. INSURE: Start resuscitation with CPAP of at least 5–6 cm water via mask or nasal prongs to
stabilize the airway and establish functional residual volume. Intubate surfactant
extubate  CPAP (INSURE technique)
4. Side effects of surfactant therapy:
a. Small risk of pulmonary hemorrhage
b. Secondary lung infection
c. Pneumothorax
d. Transient hypoxia,
e. Hypercapnia,
f. Bradycardia
g. Hypotension,
h. Blockage of the endotracheal tube
5. Contraindications:
Congenital anomalies incompatible with life
Respiratory distress in infants with laboratory evidence of lung maturity
6. Other uses of surfactant therapy:
1. Severe pneumonias
2. Meconium aspiration syndrome
3. Persistence of pulmonary hypertension
4. Pulmonary hemorrhage and adult RDS
9. Pharmacologic Therapies:
a. Vitamin A supplementation given largely to infants < 1,000 g resulted in a decrease in death
and BPD nosocomial sepsis and retinopathy of prematurity.
b. Systemic corticosteroids or inhaled steroids have been used to treat infants who continue to
require ventilator support, and in whom BPD develops.
c. After extubation:
i. Methylaxanthines and systemic steroids reduce the need for re-intubation (from 10%
to 1%).
 70

ii. Administration of racemic epinephrine after extubation does not improve pulmonary
function or the rate of extubation failure.
d. Because of the difficulty of distinguishing group B streptococcal or other bacterial infections
from RDS, empirical antibiotic therapy is indicated until the results of blood cultures are
available.
10. Complications of RDS (HMD):
a. Complications of tracheal intubation are pneumothorax and other air leaks, asphyxia from
obstruction or dislodgment of the tube, bradycardia during intubation or suctioning, and the
subsequent development of subglottic stenosis.
b. PDA is associated with hypoxia, acidosis, increased pulmonary pressure
c. Bronchopulmonary dysplasia is a result of lung injury in infants requiring mechanical
ventilation and supplemental oxygen.
d. Noncardiorespiratory complications of BPD include growth failure, psychomotor retardation
11. Prognosis:
a. Antenatal steroids, postnatal surfactant use, and improved modes of ventilation have
resulted in low mortality from RDS (≈10%).
b. Mortality increases with decreasing gestational age.
c. Surfactant therapy has reduced mortality from RDS approximately 40%, but the incidence of
BPD has not been measurably affected.
d. The long-term prognosis for normal pulmonary function in most infants surviving RDS is
excellent.

MECONIUM ASPIRATION SYNDROME

Meconium:
i. First intestinal discharge of NB
ii. Composed of epithelial cells, fetal hair, mucus and bile
iii. Meconium inactivates surfactant
Incidence:
i. Meconium-stained amniotic fluid is found in 10-15% of births and usually occurs in term or post-
term infants.
ii. Meconium aspiration syndrome (MAS) develops in 5% of such infants; 30% require mechanical
ventilation, and 3-5% die.
Pathophysiology:
1. Intrauterine stress may cause passage meconium in amniotic fluid
2. The meconium-stained amniotic fluid may be aspirated by the foetus while gasping;
3. The presence of meconium in the trachea may cause airway obstruction as well as an
inflammatory response, resulting in severe respiratory distress.
4. Early consequences of meconium aspiration:
1. Acute upper airway obstruction and atelectasis
2. Alveolar hyper expansion.
3. Chemical pneumonitis:
4. Carbon dioxide retention and hypoxemia
5. Infants with MAS are at increased risk of persistent pulmonary hypertension. The
increase in pulmonary vascular resistance may lead to atrial and ductal right-to-left
shunting
5. Risk factors:
A. Maternal;
i. Post term pregnancy.
 71

ii. Preeclampsia-eclampsia.
iii. Maternal hypertension.
iv. Maternal diabetes mellitus.
v. Abnormal biophysical profile.
vi. Oligohydramnios.
vii. Maternal heavy smoking, chronic respiratory or cardiovascular disease.
E. Fetal:
i. Abnormal fetal heart rate.
ii. Intrauterine growth retardation.
Clinical manifestation:
a. Meconium staining of vernix, cord, skin and nails may be obvious.
b. May have respiratory distress at birth; Some infants may have a delayed presentation, with only mild
initial respiratory distress, which becomes more severe hours after delivery
c. Infants with thick meconium obstruction may be apneic or have gasping respirations, cyanosis, and
poor air exchange.
d. Air trapping and scattered atelectasis may follow
e. Tachypnea, nasal flaring, intercostal retractions, increased AP diameter of the chest
f. Auscultation often reveals decreased air exchange, rales, rhonchi, or wheezing
Treatment:
Prenatal management:
1) Identification of high-risk pregnancies.
2) Monitoring. Fetal monitoring and delivery of infant in time before fetal distress develop
3) Amnioinfusion. In mothers with moderate or thick, meconium-stained amniotic fluid, amnioinfusion
decreases the incidence and severity of meconium aspiration syndrome.
Delivery room:
a. If the baby is not vigorous :
i. Use direct laryngoscopy, intubate, and suction the trachea immediately after delivery.
Suction for no longer than 5 seconds.
ii. Pulmonary toilet. it may be advisable to leave an endotracheal tube in place in
symptomatic infants for pulmonary toilet.
iii. Mechanical ventilation.
1. Oxygen therapy via hood or positive pressure by CPAP is crucial in maintaining
adequate arterial oxygenation.
2. Patients with severe disease require mechanical ventilation or HFV (high
frequency ventilation)
3. Oxygen saturations should be maintained at 90-95%.
iv. Surfactant therapy is now commonly used to replace displaced or inactivated surfactant
and as a detergent to remove meconium.
v. Culture and Broad spectrum antibiotics (ampicillin and gentamicin)
b. If the baby is vigorous:
i. defined as normal respiratory effort, normal muscle tone, and heart rate >100
beats/min):
ii. No need for intubation.
iii. Clear secretions and meconium from the mouth and nose with a large-bore suction
catheter.
C. For Persistent pulmonary hypertension: Nitric oxide therapy is indicated for pulmonary
hypertension; high-frequency oscillation may further optimize the response to nitric oxide.
D. Surveillance for any end-organ damage is essential
 72

Prevention:
1. Identification of fetal distress and initiation of prompt delivery in the presence of late fetal heart rate
(FHR) deceleration or poor beat-to-beat FHR variability.
2. Amnioinfusion and intrapartum nasopharyngeal suctioning in infants with meconium-stained amniotic
fluid does not reduce the risk for MAS.
Prognosis:
1. Administration of exogenous surfactant, high-frequency ventilation, inhaled nitric oxide, and ECMO
have reduced the mortality to <5%.
2. Residual lung problems are rare but include symptomatic cough, wheezing, and persistent
hyperinflation for up to 5-10 yr.
3. In patients surviving severe meconium aspiration, Broncho Pulmonary Dysplasia may result from
prolonged O2
4. Those with a significant asphyxial insult may have neurologic sequelae.
HYPOXIA-ISCHEMIA IN NEONATE (HIE)
Definitions and criteria:
1. Hypoxemia refers to decreased arterial concentration of oxygen. Hypoxia refers to a decreased
oxygenation to cells or organs. Ischemia refers to blood flow to cells or organs that is insufficient to
maintain their normal function.
2. Asphyxia ( Greek "a stopping of the pulse")
3. A gold standard definition of birth asphyxia does not exist.
4. Better term is perinatal asphyxia since asphyxia may occur in utero, at birth or in the postnatal period.
5. WHO definition: “failure to initiate and sustain breathing at birth”
5. Apgar criteria
a. It could be defined as moderate asphyxia as slow gasping or an Apgar score of 4-6 at 1 minute
of age.
b. Severe asphyxia was defined as no breathing or an Apgar score of 0-3 at 1 minute of age.
6. AAP & ACOG criteria
1. Fetal acidosis (Ph. <7.0),
2. A 5th min Apgar score of 0-3,
3. Encephalopathy (altered tone, depressed level of consciousness, seizures),
4. Multi organ dysfunction.
Etiology of asphyxia
Antenatal:
1. Inadequate oxygenation of maternal blood from hypoventilation during anesthesia, cyanotic
heart disease, respiratory failure, or carbon monoxide poisoning;
2. Low maternal blood pressure from acute blood loss, spinal anesthesia, or compression of the
vena cava and aorta by the gravid uterus;
3. Inadequate relaxation of the uterus to permit placental filling as a result of uterine tetany
caused by the administration of excessive oxytocin;
4. Premature separation of the placenta;
5. Impedance to the circulation of blood through the umbilical cord as a result of compression
or knotting of the cord;
6. Placental insufficiency from toxaemia or postmaturity.
7. Prolonged labour due to CPD
After birth:
1. Failure of oxygenation as a result of severe forms of cyanotic congenital heart disease or
severe pulmonary disease;
2. Severe anemia (severe hemorrhage, hemolytic disease);
 73

3. Shock severe enough to interfere with the transport of oxygen to vital organs from
overwhelming sepsis, massive blood loss, and intracranial or adrenal hemorrhage.
Pathophysiology
1. Anaerobic metabolism leads to increased levels of
1. Lactate
2. Inorganic phosphates.
3. Excitatory and toxic amino acids, glutamate,
4. Intracellular sodium and calcium: tissue swelling and cerebral edema.
5. Free radicals and nitric oxide
2. Loss of cerebrovascular auto regulation and fall in CBF
3. Neuronal loss
4. Cerebrovascular hemorrhage esp. intraventricular
5. Term infants demonstrate neuronal necrosis of the cortex (later, cortical atrophy) and parasagittal
ischemic injury.
6. Preterm infants demonstrate PVL (later, spastic diplegia), status marmoratus of the basal ganglia, and
IVH.
7. Term more often than preterm infants have focal or multifocal cortical infarcts that manifest clinically
as focal seizures and hemiplegia.
8. Pulmonary arteriole smooth muscle hyperplasia may develop, which predisposes the infant to
pulmonary hypertension
9. Congestion and petechiae are seen in the pericardium, pleura, thymus, heart, adrenals, and meninges.
10. If fetal distress produces gasping, the amniotic fluid contents (meconium, squames, lanugo) are
aspirated into the trachea or lungs.
Clinical presentation
1. Antinatal: intrauterine growth restriction
2. Perinatal:
1. Fetal bradycardia
2. Decline in beat-to-beat variability
3. Variable or late (type II) deceleration
4. Fetal scalp blood pH <7.20
5. meconium stained liquor
3. Immediate NB period
1. At birth, affected infants may be depressed and may fail to breathe spontaneously.
2. During the ensuing hours, they may remain hypotonic or change from a hypotonic to a
hypertonic state
3. Pallor, cyanosis, apnea, a slow heart rate, and unresponsiveness to stimulation are also signs
of HIE.
4. Cerebral edema may develop during the next 24 hr and result in profound brainstem
depression. During this time, seizure activity may occur.
5. Seizures in asphyxiated newborns may also be due to hypocalcemia, hypoglycemia, or
infection
6. CNS dysfunction, heart failure and cardiogenic shock, persistent pulmonary hypertension,
respiratory distress syndrome, gastrointestinal perforation, hematuria, and acute tubular
necrosis are associated with perinatal asphyxia secondary to inadequate perfusion
4. Multi organ involvement:
Hypoxic-ischemic encephalopathy, infarction, intracranial
CNS
hemorrhage, seizures, cerebral edema, hypotonia, hypertonia
CVS Myocardial ischemia, poor contractility, cardiac stun, tricuspid
 74

insufficiency, hypotension
Pulmonary hypertension, pulmonary hemorrhage, respiratory
R.S
distress syndrome - MAS
Renal Acute tubular or cortical necrosis
Adrenal Adrenal hemorrhage
Gastrointestinal Perforation, ulceration with hemorrhage, necrosis
Inappropriate secretion of antidiuretic hormone, hyponatremia,
Metabolic
hypoglycemia, hypocalcemia, myoglobinuria
Integument Subcutaneous fat necrosis
Hematology Disseminated intravascular coagulation
Diagnosis:
1. Computed tomography (CT) scan.
1. Focal hemorrhagic lesions,
2. Diffuse cortical injury, and damage to the basal ganglia;
3. Bilateral, diffuse hypodensity reflects marked cortical neuronal injury, with associated
edema
4. CT has limited ability to identify cortical injury during the 1st few days of life.
2. Ultrasonography:
1. It is the preferred modality in evaluation of the preterm infant.
2. intraventricular hemorrhage
3. Necrosis of basal ganglia and thalamus.
4. Periventricular white matter injury.
3. Magnetic resonance imaging (MRI):
1. Identifies regions of hypoxia and ischemia
4. Evoked electrical potentials (auditory, visual)
5. Amplitude-integrated electroencephalography (aEEG) may help to determine which infants are at
highest risk for long-term brain injury. A single-channel tracing is generated from 2 electrodes
placed in the biparietal area. A filter is used to filter and attenuate the signal between 2 Hz and 15
Hz. This technique is simple to perform and correlates with standard EEG. It has good reliability, a
positive predictive value of 85%, and a negative predictive value of 91-96% for infants who will
have adverse neurodevelopmental outcome.
Sarnat and Sarnat stages of HIE:
SIGNS STAGE 1 STAGE 2 STAGE 3
1. Level of consciousness Hyperalert Lethargic Stuporous, coma
2. Muscle tone Normal Hypotonic Flaccid
3. Posture Normal Flexion Decerebrate
4. Tendon reflexes/clonus Hyperactive Hyperactive Absent
5. Myoclonus Present Present Absent
6. Pupils Mydriasis Miosis Unequal, poor light reflex
7. Seizures None Common Decerebration
8. Outcome Good Variable Death, severe deficits
Treatment
1. Immediate resuscitation.
a. Ventilation.
b. Oxygenation
c. Perfusion.
d. Correct metabolic acidosis
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2. Maintain a normal serum glucose level (~75-100 mg/dL) to provide adequate substrate for brain
metabolism.
3. Avoid hyperglycemia to prevent hyperosmolality
Control of seizures
1. Phenobarbital for 2 months. High-dose phenobarbital (20 mg/kg) reduced the incidence of
seizures and improved neurologic outcome at 3 years in term asphyxiated newborns; additional
doses of 5-10 mg/kg (up to 40-50 mg/kg total) may be needed.
2. Phenytoin (20 mg/kg loading dose) or lorazepam (0.1 mg/kg) may be needed for refractory
seizures.
Prevention of cerebral edema
1. Avoidance of fluid overload; moderate fluid restriction (eg, 60 mL/kg). If cerebral edema is
severe, further restriction of fluid intake to 50 mL/kg is imposed.
2. Observe the infant for SIADH.
3. Glucocorticoids and osmotic agents like manitol are not recommended.
Neuroprotection:
1. There is some clinical evidence that highdose prophylactic phenobarbital may decrease
neurodevelopmental impairment in infants with HIE.
2. Magnesium has an inhibitory effect on glutamate receptors and Ca2+ channels during hypoxia.
3. Prevention of free radical formation:
1. Xanthine oxidase inhibitor.
2. Allopurinol
4. Resuscitation with room air. In a trial room air-resuscitated infants recovered more quickly than
neonates resuscitated with 100% oxygen who manifest biochemical changes indicative of
prolonged oxidative stress at 4 weeks of age
5. Systemic or selective cerebral hypothermia
1. Decrease the rate of apoptosis
2. Suppresses production of glutamate, free radicals, NO, and lactate.
3. Prevent s the decline in high-energy phosphates like Phosphocreatine and adenosine
triphosphate
4. Downregulate the secondary mediators cytokines,
5. Reduce seizures.
6. Most effective when implemented within 6 hr of the event.
7. Head cooling for 72 hours starting within 6 hours of birth, with the rectal temperature
maintained at 34.5 0c
8. Whole body cooling to 33.5 o C for 72 hours
9. Systemic hypothermia may result in more uniform cooling of the brain and deeper CNS
structures
6. Hyperthermia has been found to be associated with impaired neurodevelopment.

COMPLICATIONS OF BIRTH ASPHYXIA (Short notes)

Immediate:
1. Hypoxic ischemic encephalopathy- seizures
2. Persistent pulmonary hypertension
3. Myocardial dysfunction
4. Acute renal tubular necrosis
5. Necrotizing enterocolitis
6. Adrenal hemorrhage with adrenal insufficiency
7. Disseminated intravascular coagulation
 76

8. Metabolic derangements:
a. Hypocalcemia
b. Hypoglycemia
c. Metabolic acidosis
d. hyperkalemia
9. Intracranial hemorrhage
10. Stress ulcer stomach
Delayed:
1. Cerebral palsy
2. Mental retardation
3. Epilepsy
4. Autism
5. Attention deficit hyperactive disorder
6. Dyslexia
7. Short stature (pituitary dysfunction)
8. Hydrocephalus (intracranial hemorrhage)
9. Microcephaly
PROGNOSIS
1. poor prognosis:
1. Infants with initial cord or initial blood pH <6.7 have a 90% risk for death or severe
neurodevelopmental impairment at 18 mo of age.
2. Infants with Apgar scores of 0-3 at 5 min, high base deficit (>20-25 mmol/L),
3. Decerebrate posture, and lack of spontaneous activity
4. Flaccid coma, apnea, absent oculocephalic reflexes, and refractory seizures,
5. low Apgar score at 20 min, absence of spontaneous respirations at 20 min of age, and
persistence of abnormal neurologic signs at 2 wk of age
6. Stage 2 and 3 encephalopathy
7. MRI and EEG abnormalities
8. Microcephaly and poor head growth during the 1st year
2. Better prognosis:
1. Normal MRI and EEG findings
Brain death after neonatal HIE
1. Coma unresponsive to pain, auditory, or visual stimulation;
2. Apnea with pco2 rising from 40 to over 60 mm hg without ventilatory support;
3. Absent brainstem reflexes (pupil, oculocephalic, oculovestibular, corneal, gag, sucking).
4. These findings must occur in the absence of hypothermia, hypotension, and elevated levels of
depressant drugs (phenobarbital).
5. An absence of cerebral blood flow on radionuclide scans and no electrical activity on EEG

HEMORRHAGIC DISEASE OF NEWBORN

Introduction:
1. Placental transfer is limited; cord blood levels of vitamin K1 (phylloquinone) are 30-fold lower than
maternal levels. Intestinal bacteria synthesize menaquinone (vitamin K2), which has 60% of the
activity of phylloquinone. However, neonates have a decreased number of bacteria in their gut that
manufacture vitamin K2; levels of this form of vitamin K are not found in the livers of infants until they
are 2 to 3 months old. Therefore newborn infants are deficient in vitamin K at birth and are at risk for
significant bleeding.
2. Neonate in first week of life has transient deficiency of vitamin K–dependent factors (II, VII, IX, and X)
 77

3. This deficiency between the 2nd and 7th days of life results in spontaneous and prolonged bleeding.
This is called Hemorrhagic disease of Newborn
Etiology and types:
1. Classic type:
1. Classic vitamin K deficiency bleeding is observed in infants who have not received
prophylactic vitamin K at birth.
2. Early onset:
1. Early-onset vitamin K deficiency bleeding usually occurs during first 24 hours after birth.
2. Numerous maternal medications during pregnancy are associated with vitamin K deficiency
bleeding in neonates (eg, anticonvulsants, antitubercular drugs, vitamin K antagonists [eg,
warfarin].
3. Late onset:
1. Late onset (>2 wk) is often associated with vitamin K malabsorption, as noted in neonatal
hepatitis or biliary atresia.
Management:
1. Prevention: 1 mg of vitamin K IM within 6 hours after
2. For haemorrhage 1–2 mg of vitamin K intravenously is given
3. Serious bleeding, particularly in premature infants or those with liver disease, may require a
transfusion of fresh frozen plasma or whole blood.

HIGH RISK NEONATE & ITS CAUSES (S.N)

1. High risk neonate:
a. Infants at risk during the neonatal period are the ones who carry increased risk of neonatal
morbidity and mortality
b. The term high-risk infant designates an infant who should be under close observation by
experienced physicians and nurses.
2. Causes of high risk neonate:
1. PREVIOUS PREGNANCY
I. Intrauterine death
II. Neonatal death
III. Prematurity
IV. Intrauterine growth restriction
V. Congenital malformation
VI. Blood group sensitization, neonatal jaundice
VII. Neonatal thrombocytopenia
VIII. Hydrops
IX. Inborn errors of metabolism
2. PRESENT PREGNANCY
I. Vaginal bleeding (abruptio placentae, placenta previa)
II. Sexually transmitted diseases (colonization: herpes simplex, group B
streptococcus), chlamydia, syphilis, hepatitis B, HIV
III. Multiple gestation
IV. Preeclampsia
V. Premature rupture of membranes
VI. Short interpregnancy time
VII. Poly-oligohydramnios
VIII. Acute medical or surgical illness
IX. Inadequate prenatal care
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X. Familial or acquired hypercoagulable states

XI. Treatment of infertility
3. LABOR AND DELIVERY
1. Fetal distress
2. Immature L:S ratio; absent phosphatidylglycerol
3. Breech presentation
4. Meconium-stained fluid
5. Nuchal cord
6. Forceps delivery
7. Apgar score <4 at 1 min
4. NEONATE
I. Birthweight <2,500 or >4,000 g
II. Birth before 37 or after 42 wk of gestation
III. Tachypnea, cyanosis
IV. Congenital malformation
V. Pallor, plethora, petechiae

NEONATAL SEIZURES
Introduction
1. The arborization of axons, dendritic processes and myelination are incomplete in the neonatal brain.
2. A seizure discharge cannot readily be propagated throughout the neonatal brain to produce a
generalized seizure.
3. Hence focal and subtle seizures are common; generalized grand mal seizures are uncommon.
Definition: A seizure is defined clinically as a paroxysmal alteration in neurologic function (ie, behavioral,
motor, or autonomic)
The incidence:
1. 1.5 to 14 in 1000 live births.
2. Neonatal seizures are rarely idiopathic in the newborn
3. It is a manifestation of a serious central nervous system disease.
Convulsions vs. Jitteriness
• Seizures:
1. Eye movements can be abnormal .eg staring, blinking, jerks, or horizontal eye deviation).
2. The hands continue to move if grasped
3. Movements are of a coarser nature.
4. EEG is abnormal
• Jitteriness:
1. Eye movements are normal.
2. The hands will stop moving if they are grasped,
3. Movements are of a fine nature.
4. EEG is normal
Subtle seizures:
1. Ocular : Tonic horizontal deviation ; Starring look ; repetitive blinking
2. Oral–facial–lingual movements: Repetitive chewing, tongue-thrusting, lip-smacking, etc.
3. Limb movements: Cycling, paddling, boxing-jabs, etc.
4. Autonomic phenomena: Tachycardia or bradycardia
5. Apnea
Major causes of seizures:
1. Perinatal asphyxia: most common cause of neonatal seizures. occur within the first 24 h of life;
 79

2. Intra cranial hemorrhages: Subarachnoid, intraventricular and subdural hemorrhage

3. Metabolic disturbances
1. Hypoglycemia: common in preterm, IUGR & infants of diabetic mothers (IDMs)
2. Hypocalcemia:
3. Hypomagnesemia
4. Hyponatremia
5. Hypernatremia:
6. Other metabolic disorders
1. Pyridoxine dependency:
2. Amino acid disorders:
3. Maple syrup urine disease (MSUD) :
4. Infections
1. Meningitis: group B streptococcus, Escherichia coli, or Listeria monocytogenes
2. Toxoplasmosis and infection with herpes simplex, cytomegalovirus, rubella, and coxsackie B
viruses lead to intracranial infection and seizures
5. Ischemic stroke
1. Polycythemia,
2. Thrombophilia due to a genetic disorder,
3. Severe hypotension
6. Pyridoxine dependency:
a. A rare disorder must be considered when generalized clonic seizures begin shortly after birth
with signs of fetal distress in utero.
b. These seizures are particularly resistant to conventional anticonvulsants, such as
phenobarbital or phenytoin.
7. Drug withdrawal
1. Passive addiction
2. Drug withdrawal seizures
1. Heroin, methadone, and propoxyphene
2. Sedative-hypnotics such as secobarbital;
3. Alcohol.
8. Toxins: Inadvertent injection of local anesthetics into the fetus at the time of delivery
9. Benign familial neonatal seizures
1. An autosomal dominant condition,
2. Begins on the 2nd–3rd day of life, with a seizure frequency of 10-20/day.
3. Patients are normal between seizures, which stop in 1–6 mo.
4. Fifth-day fits occur on day 5 of life (4–6 days) in normal-appearing neonates.
5. The diagnosis by exclusion of other causes of seizures.
6. The prognosis is good.
Evaluation:
History
1. A positive family history: metabolic errors and benign familial neonatal convulsions
2. Maternal drug: narcotic withdrawal syndrome
3. Delivery:
1. Maternal analgesia,
2. perinatal asphyxia
3. maternal infections during pregnancy
Day of birth:
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At birth: Maternal anesthetic agents: xylocaine injected to scalp; can see severe tonic seizures typically in
the first few hours of life.
Day 1: hypoglycemia, hypocalcemia, hypoxic-ischemic encephalopathy
Days 2-3: Meningitis; Drug withdrawal
> Day 5: Hypocalcemia, TORCH infections or developmental defects.
> 1-2 wks: Methadone withdrawal.
Examination:
1. Physical examination
i. Gestational age.
ii. Blood pressure.
iii. Presence of skin lesions.
iv. Presence of hepatosplenomegaly.
v. Size and "feel" of the fontanel
vi. Level of alertness,
vii. Cranial nerves,
viii. Motor function,
ix. Primary neonatal reflexes,
x. Unusual odour
Work up:
1. Blood should be obtained for determinations of glucose, calcium, magnesium, electrolytes, and blood
urea nitrogen.
2. Inborn errors of metabolism:
a. Serum ammonia: urea cycle abnormalities.
b. Urine organic acids: methylmalonic or propionic acidemia.
c. Urine screening test using 2,4- dinitrophenylhydrazine: Maple syrup urine disease (MSUD)
3. MRI or CT scan for lissencephaly and schizencephaly
4. Karyotype: Infants with chromosome abnormalities
5. lumbar puncture: The CSF findings may indicate a bacterial meningitis or aseptic encephalitis
6. Ultrasonography of the head to rule out IVH or periventricular hemorrhage
7. CT scan: infarction, hemorrhage, calcification, and cerebral malformations
8. EEG: diagnostic and prognostic
General management
1. It is an emergency
2. Nurse the baby in thermoneutral environment and ensure airway, breathing and circulation (TABC).
3. O2 ; IV Fluids
4. Monitoring:
1. Pulse oxymetry
2. Electrolytes
3. Acid base chemistry
Chemistry-Management
1. Hypoglycemia:
1. 10% dextrose in water, 2-4 mL/kg intravenously, followed by 6-8 mg/kg/min
2. Hypocalcaemia:
1. serum concentration less than 7 mg/dL;
2. Rx: (1–2 mL/kg) over 10–20 minutes,
3. Maintenance: continuous infusion 0.5–1 g/kg/d over 1–2 days
3. If serum magnesium levels are low (<1.52 mEq/L), give 0.25 ml/kg of 50% magnesium sulfate IM
Anticonvulsant therapy
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1. Phenobarbitone
1. Drug of choice for NB (>70% controlled)
2. 20 mg/kg/IV slowly over 20 minutes
3. Repeat dose of phenobarbitone 10 mg/kg may be used every 20-30 minutes till a total dose
of 40 mg/kg
4. Maintenance dose is 3-5 mg/kg/day in 1-2 divided doses
2. Phenytoin
1. Indicated if the maximal dose of phenobarbitone (40 mg/kg) fails to resolve seizures or
earlier, if adverse effects occur with phenobarb
2. 20 mg/kg IV at a rate of not more than 1 mg/kg/min under cardiac monitoring.
3. Should be diluted in normal saline as it is incompatible with dextrose solution.
4. A repeat dose of 10 mg/kg may be tried in refractory seizures.
5. The maintenance dose is 3-5 mg/kg/d (maximum of 8 mg/kg/d) in 2-4 divided doses.
6. Only IV route is preferred in neonates
3. Benzodiazepines
1. Diazepam is generally avoided due to its short duration of action, narrow therapeutic index,
and because of the presence of sodium benzoate as a preservative
2. Lorazepam is preferred over diazepam as it has a longer duration of action and results in less
adverse effects (sedation and cardiovascular effects).
3. Midazolam is faster acting than lorazepam and may be administered as an infusion.
4. Dosing
1. Diazepam: 0.25 mg/kg IV bolus (0.5 mg/kg rectal); may be repeated 1-2 times.
2. Lorazepam: 0.05 mg/kg IV bolus over 2-5 minutes; may be repeated
3. Midazolam: 0.15 mg/kg IV bolus followed by infusion of 0.1 to 0.4 mg/kg/hour.
4. Clonazepam: 0.1–0.2 mg/kg IV bolus followed by infusion 10-30 mg/kg/hr.
4. Refractory seizures:
1. Lidocaine: Start with 4mg/kg/hr IV on first day, reduce by 1mg/kg/hr on each subsequent day
2. Paraldehyde: 0.1-0.2 ml/kg/dose may be given IM or 0.3 ml/kg/dose mixed with coconut oil in 3:1
as rectal.
3. Sodium valproate: It can be used for maintenance therapy in neonates; Dose is 20-25 mg/kg/d
followed by 5-10 mg/kg every 12 hours.
5. Other drugs
1. Vigabatrin: primarily for infantile spasms; 50 mg/kg/day.
2. Topiramate: potential neuroprotective effect against injury caused by seizures; 3 mg/kg.
3. Pyridoxine: Therapeutic trial of pyridoxine is reserved as a last resort; 1 ml of neurobion has 50-
mg pyridoxine and 1 ml IM
4. Discontinuing the drugs: If neurological examination is normal discontinue all drugs on at
discharge
Prognosis
1. Depends on the primary cause
2. Hypoglycemic and hypocalcemia good prognosis
3. Poor probnosis in:
1. Severe hypoxic-ischemic encephalopathy
2. Cytoarchitectural abnormality of the brain
3. Susceptible to status epilepticus and early death

MULTIPLE PREGNANCY
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I. Incidence.
a. Vanishing twin: only half of twin pregnancies diagnosed with ultrasonography during the first
trimester are finally delivered as twins, a phenomenon that has been termed vanishing twin.
b. Twins occur in 1-2% of deliveries after 20 weeks, and the triplet rate is ~0.1%.
c. The rate of monozygotic twinning is considered a chance phenomenon, whereas dizygotic
twinning results from multiple ovulations, and may have a familial tendency.
II. Risk factors.
a. Family history of twins,
b. Maternal age (peak at 35-39 years),
c. Previous twin gestation
d. Increasing parity
III. Placentation
a. Twin placentation is classified according to the placental disk (single, fused, or separate), number of
chorions (monochorionic or dichorionic), and number of amnions (monoamniotic or diamniotic)
b. Heterosexual twins always have a dichorionic placenta.
c. Monochorionic twins are always of the same sex. All monochorionic twins are monozygotic and are
either monoamniotic or diamniotic.
IV. Mortality rates
1. Prematurity in twins. Approximately 10% of preterm deliveries are twin gestations, and they
account for 25% of perinatal deaths in preterm deliveries.
V. Morbidity
1. Prematurity.
2. Intrauterine growth retardation.
3. Uteroplacental insufficiency.
4. Congenital anomalies.
5. Twin-twin transfusion syndrome:
VI. Complications
1. The second-born twin is 2-4 times as likely to develop respiratory distress syndrome, probably
secondary to perinatal stress;
2. the first-born twin may be at risk for necrotizing enterocolitis

INFANT OF A DIABETIC MOTHER

Incidence
Insulin-dependent diabetes occurs in 0.5% of all pregnancies. In addition, 1-3% of
women exhibit biochemical abnormalities during pregnancy consistent with gestational diabetes.
Pathophysiology:
1. Macrosomia.
a. Macrosomia is the classic presentation of the infant of a diabetic mother (IDM).
2. Small for gestational age.
a. Mothers with renal, retinal, or cardiac diseases are more likely to have small for gestational
age or premature infants, poor fetal outcome, fetal distress, or fetal death.
Specific disorders frequently encountered in IDMs:
Metabolic disorders:
1. Hypoglycemia is defined as a blood glucose level <35 mg/dL in a preterm or term infant. It is present
in up to 40% of IDMs, most commonly in macrosomic infants. It usually presents within 1-2 h after
delivery.
2. Hypocalcemia. The incidence is up to 50% of IDMs. Serum calcium levels are lowest at 24-72 h of
age.
 83

3. Hypomagnesemia. A serum magnesium level <1.52 mg/dL

Cardiorespiratory disorders:
1. Perinatal asphyxia occurs in up to 25% of IDMs.
2. Hyaline membrane disease or RDS: Most cases are the result of premature delivery, delayed
maturation of pulmonary surfactant production, or delivery by elective cesarean section.
3. Transient tachypnea of the newborn occurs especially after elective cesarean section.
4. Hypertrophic cardiomyopathy occurs in up to 50% of IDMs. It occurs secondary to increased fat and
glycogen deposition in the myocardium and may lead to congestive heart failure.
Hematologic disorders:
1. Hyperbilirubinemia.
2. Polycythemia and hyperviscosity.
3. Renal venous thrombosis is a rare
Morphologic and functional problems:
a. Macrosomia is caused by fetal hyperglycemia, resulting in increased glucose uptake in insulin-sensitive
tissues.
b. Birth injury. Macrosomia may lead to shoulder dystocia, which may cause birth asphyxia. Birth injuries
include fractures of the clavicle or humerus, Erb's palsy, phrenic nerve palsy, and, rarely, central
nervous system injury.
c. Congenital malformations. It is suspected that poor diabetic control in the first trimester is associated
with a higher percentage of congenital malformations. Congenital malformations include:
i. Cardiac defects (eg, transposition of the great vessels, ventricular septal defect, or atrial
septal defect),
ii. Renal defects (eg, agenesis),
iii. Gastrointestinal tract defects (eg, small left colon syndrome or situs inversus),
iv. Neurologic defects (eg, anencephaly or meningocele syndrome),
v. Skeletal defects (eg, hemivertebrae or caudal regression syndrome),
vi. Unusual facies, and
vii. Microphthalmos.
Clinical presentation:
a. Infants of diabetic and gestational diabetic mothers often bear a surprising resemblance to each
other.
b. Usually child is large for gestational age
c. Hypoglycemia presents as lethargy, poor feeding, apnea, or jitteriness in the first 6-12 h after
birth. The infants tend to be jumpy, tremulous, and hyperexcitable during the 1st 3 days of life,
d. Jitteriness that occurs after 24 h of age may be the result of hypocalcemia or hypomagnesemia.
e. Tachypnea due to polycythemia, cardiac failure, transient tachypnea and RDS
f. Cardiomegaly is common and heart failure can
g. The incidence of congenital anomalies is increased threefold in infants of diabetic mothers:
a. Cardiac malformations (ventricular or atrial septal defect, transposition of the great
vessels, truncus arteriosus, double-outlet right ventricle, tricuspid atresia, coarctation of
the aorta)
b. Lumbosacral agenesis is most common.
c. Neural tube defects,
d. Hydronephrosis,
e. Renal agenesis and dysplasia,
f. Duodenal or anorectal atresia,
g. Situs inversus,
h. Double ureter,
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i. Holoprosencephaly.
Diagnosis
a. Laboratory studies.
i. Serum glucose levels should be checked at delivery and at 1/2, 1, 11/2, 2, 4, 8, 12, 24, 36, and 48 h
of age.
ii. Serum calcium levels should be obtained at 6, 24, and 48 h of age.
iii. If serum calcium levels are low, serum magnesium levels should be obtained because they may
also be low.
iv. The hematocrit should be checked at birth and at 4 and 24 h of age.
v. Serum bilirubin levels should be checked as indicated by physical examination.
b. Electrocardiography and echocardiography should be performed if hypertrophic cardiomyopathy or a
cardiac malformation is suspected.
Management:
1. Hypoglycemia.
1. If child is having symptomatic hypoglycaemias infuse 2 mL/kg of a 10% glucose solution
at a rate of 1.0 mL/ min. Then give a continuous infusion of glucose at a rate of 6-8
mg/kg/min, and increase the rate as needed to maintain a normal blood glucose (>40-50
mg/dL).
2. Hypocalcemia:
1. Oral calcium 4 ml/kg/day of 10% calcium gluconate for prevention
1. 2 ml/kg/dose diluted 1:1 with 5% dextrose over 10 minutes, under cardiac monitoring
followed by a continuous IV infusion of 80-mg/kg/day elemental calcium for 48 hours
3. Hypomagnesimia: given orally as magnesium sulfate 50%, 0.2 mL/kg/day (4 mEq/mL).
4. Cardiomyopathy. The treatment of choice is with propranolol.
5. Renal venous thrombosis. Treatment consists of fluid restriction and close monitoring of
electrolytes and renal status. Supportive therapy is indicated to ensure adequate blood
circulation.
Prognosis:
a. Less morbidity and mortality occur with adequate control during the diabetic pregnancy.
b. The risk of subsequent diabetes in the infants of these women is at least 10 times greater than in the
normal population.

VERTICAL TRANSMISSION (MOTHER TO CHILD OR PERINATAL)

“Vertical transmission” is a term that refers to the spread of infections from mother-to-baby. These infections
may occur while the foetus is still in the uterus, during labour and delivery, or after delivery while
breastfeeding.(Perinatal transmission)
1. Congenital infections (passed in utero)
TORCH is an acronym for several of the more common congenital infections. These are:
1. Toxoplasmosis
2. Other infections (syphilis, hepatitis B, Coxsackie virus, Epstein-Barr virus,varicella-zoster
virus (chicken pox), and human parvovirus)
3. Rubella
4. Cytomegalovirus (CMV)
5. Herpes simplex virus
6. HIV
2. Perinatal infections (during labour and delivery)
Occurs through an infected birth canal. Examples of perinatal infections are:
1. Gonorrhoea
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2. Chlamydia
3. Herpes simplex virus
4. Human Papilloma Virus (genital warts)
5. Group B Streptococci (GBS)
3. Postnatal infections (after delivery)
Infections spread from mother to baby after delivery is known as “postnatal infections.” These infections
can be spread during breastfeeding. Eg. HIV
4. Prevention:
1. Antenatal:
a) Maternal screening for GBS, HSV, HIV, Syphilis, Gonococcus
b) Antibiotic prophylaxis to antenatal mother who are identified carriers of GBS. Eg. Erythrocyn
500 mg 8th hourly
2. Antibiotic prophylaxis to neonate:
a) All initial evaluation, empiric therapy should be initiated with ampicillin and gentamicin.
b) The duration of treatment might be as short as 48 to 72 hours, depending on the culture
results and clinical course.
3. Intranatal:
a) Caesarian section for proved vaginal sepsis like HSV
4. Prevention of HIV transmission :
1. Single dose NVP 200mg given at the onset of labour and single dose of syrup NVP 2mg/kg
weight to the baby within 72 hours decreases risk of transmission by 13.1% (breast
feeding)..
2. Avoid manipulations like amniocentesis and external cephalic version increase the risk of
transmission of HIV.
3. Prevention of long duration of rupture of membranes which increases the transmission
risk. It has been estimated that with every hour, the risk of transmission increases by 2%.
4. Placental disruption and infections also adversely affect transmission. Invasive fetal
monitoring should be avoided, as should all invasive obstetric procedures.
11. Where facilities are available, elective LSCS should be offered.
12. If instrumental delivery is necessary, then forceps are a better option than vacuum
suction cup delivery.
13. Emergency LSCS is associated with high transmission as comkpared to elective LSCS
14. In India – normal delivery is recommended unless the woman has obstetric reasons
15. When replacement feeding (infant formula) is acceptable, feasible, affordable,
sustainable and clean water is available, HIV-infected mothers should avoid
breastfeeding completely.
16. Otherwise, exclusive breastfeeding is recommended during the first months of life, with
early abrupt weaning at 3-4 months or 6 months of age
4. Prevention of Hepatitis B:
a. Routine immunization of all women for HBV
b. Screening of pregnant mother for HBV
c. HB Immunoglobulin and HB vaccine to the child soon after birth followed by HbV 2 nd
and 3rd doses
5. Prevention of Rubella:
a. MMR vaccine at the age of completion of 15 months
b. Rubella vaccine to women before marriage
6. Prevention of cong.Syphilis:
a. Screen for VDRL
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b. Treat VDRL positive mothers with long acting penicillin

CONGENITAL RUBELLA
I. Definition. Rubella is a viral infection capable of causing chronic intrauterine infection and damage to the
developing fetus.
II. Pathophysiology.
a. Rubella virus is an RNA virus with epidemic seasonal pattern
b. Fetal effects is greater the earlier in gestation that infection occurs, especially at 1-11 weeks, when
90% of infected fetuses will be damaged,
III. Clinical presentation.
1. Teratogenic effects. These include
a. Intrauterine growth retardation,
b. Congenital heart disease (patent ductus arteriosus or pulmonary artery stenosis),
c. Sensorineural hearing loss,
d. Cataracts or glaucoma,
e. Neonatal purpura, and
f. Dermatoglyphic abnormalities.
1. Systemic involvement can be manifested by:
1. Adenitis,
2. Hepatitis,
3. Hepatosplenomegaly,
4. Jaundice,
5. Anemia,
6. Decreased platelets with or without petechiae,
7. Myocarditis,
8. Eye lesions (iridocyclitis or retinopathy),
9. Pneumonia.
2. Late defects.
1. Including immunologic dyscrasias,
2. Hearing deficit,
3. Psychomotor retardation,
4. Autism,
5. Brain syndromes such as subacute sclerosing panencephalitis,
6. Diabetes mellitus, and
7. Thyroid disease.
II. Diagnosis: ELISA for IgM and IgG antibodies are the most commonly performed tests.
III. Management.
1. There is no specific treatment for rubella.
2. Prevention consists of vaccination of the susceptible population (especially young children).
3. Vaccine should not be given to pregnant women.

ORAL CANDIDIASIS
1. Oropharyngeal infection with Candida albicans (thrush, moniliasis) is common in neonates from contact
with the organism in the birth canal or breast.
2. Neonatal risk factors for invasive candidiasis include very low birth weight status, broad-spectrum
antibiotic administration; OPC is also a major problem during myelosuppressive therapy
3. The lesions of oropharyngeal candidiasis (OPC) appear as white plaques covering all or part of the
oropharyngeal mucosa
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4. diagnosis is confirmed by direct microscopic examination on potassium hydroxide smears

5. Therapeutic agents in decreasing order of efficacy include miconazole gel, amphotericin B suspension,
gentian violet, and nystatin suspension
6. OPC is usually self-limited in the healthy newborn infant, but treatment with nystatin will hasten recovery
and reduce the risk of the infection spreading to other infants. Persistent infections should be treated with
fluconazole therapy.
7. Fluconazole has been shown to be safe in premature infants and effective in a single dose for HIV-infected
children with oral candidiasis.
8. In breast-fed infants, simultaneous treatment of infant and mother with topical nystatin or oral fluconazole
may be indicated.
INFANT OF HEPATITIS B POSITIVE MOTHER
1. HBsAg-positive mother.
1. If the mother is HBsAg-positive, the infant should be given hepatitis B immune globulin (HBIG), 0.5
mL IM, within 12 h after delivery.
2. Additionally, hepatitis B vaccine is given at birth and at 1 month and 6 months of age.
3. If the first dose is given simultaneously with HBIG, it should be administered at a separate site,
preferably in the opposite leg.
2. Infant born to mother whose HBsAg status is unknown.
1. Test the mother as soon as possible. While awaiting the results, give the infant hepatitis B vaccine
within 12 h of birth in the dose used for infants born to HBsAg-positive mothers.
2. If the mother is found to be HBsAg-positive, the infant should receive HBIG (0.5 mL) within 7 days
of birth.
3. If the infant is preterm and the maternal HBsAg status cannot be determined within the initial 12
h after birth, HBIG should be given as well as hepatitis vaccine.
3. Immunization program.
1. The World Health Organization recommended that all countries add HBV vaccine to their routine
childhood immunization program.
2. Two dose schedules have been proposed; each includes 3 separate doses. In option 1, these are at
birth, 1-2 months, and at 6-18 months; in option 2, doses should be given at 1-2 months, 4
months, and 6-18 months.

HIGH RISK NEONATE

All newborn infants can be classified into 1 of 3 groups:
1. Well infants.
2. High-risk infants.
3. Sick infants
Definition of high risk infant:
The high risk neonate can be defined as a newborn, regardless of gestational age or birth weight, who has
a greater than average chance of morbidity or mortality because of threats to life and health that occur
during prenatal, perinatal and postnatal period
Factors Predisposing to High-Risk Neonate:
I. Maternal Factors:
1. High-risk pregnancies as in lack of antenatal care, poor socioeconomic condition, previous history
of obstetric complications as abortion, toxemias, placental insufficiency, stillbirth.
2. Medical illness of mother as diabetes mellitus, heart and kidney diseases and severe infection.
3. Complications of labor and delivery as prolonged rupture of membranes, caesarean section and
stillbirth.
II. Neonatal Factors:
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1. As neonatal asphyxia, neonatal infection, congenital anomalies, prematurity, post-maturity, low

Apgar score, hypoglycaemia and others.
2. At birth, all infants should have a complete gestational age assessment. This assessment helps to
identify infants that are Preterm, post-term, small or large for gestational age.
3. Birth eight of the child: This includes low birth weight in pre maturity and intra uterine growth
retardation
Classification of High-risk Infants:
1. According to birth weight:
a. Appropriate for gestational age AFGA: birth weight between 2.5 to 4 kg
b. Heavy for gestational age HFGA: birth weight between more than 4 kg
c. Light for gestational age: Birth weight less than 2.5 kg
d. Intra uterine growth restriction IUGR:
i. Definition: weight less than 10th percentile for gestational age.
ii. Types:
1. Symmetrical (type I):
a. All parameters (length + HC + wt.).
b. Reflects long-term nutrition.
2. Asymmetrical (type II): reflects short-term nutrition.
a. HC remains normal while length and weight are decreased.
e. Low- birth-weight (LBW) infant: An infant whose birth weight is less than 2500 gm regardless
of gestational age.
f. Very-Low-Birth weight (VLBW): An infant whose birth weight is less than 1500 gm.
g. Very-Very-Low-Birth-Weight (VVLBW) or extremely low (ELBW): An infant whose birth
weight is less than 1000 gm.
h. Moderately-Low Birth Weight (MLBW): An infant whose birth weight is 1500- 2500 kg.
2. According to gestation:
a. Full term: Child born after completion of 37 weeks and before competition of 42 weeks
b. Preterm: Born before completion of 37 weeks (and after 22 weeks of gestation)
c. Late preterm: Born between 34 completed to before completion of 37 weeks
d. Post term: Born after completion of 42 weeks
Systemic Assessment of High-Risk Neonates:
1. General assessment:
a. Weigh daily, measure length and head circumference.
b. General body shape and size, posture at rest, presence and location of edema.
c. Any apparent deformities.
d. Any signs of distress: Poor color, mouth open, grimace-furrowed brow.
2. Respiratory assessment:
a. Shape of chest (barrel, concave), system, presence of incisions, chest tubes or other
deviation.
b. Use of accessory muscle: nasal flaring or substantial, intercostal or subclavicular retractions.
c. Determine respiratory rate and regularity.
d. Breath sounds: stridor, crackles, wheezing, and grunting, equality of breath sounds.
e. Determine whether suctioning is needed.
f. Cry if not incubated.
g. If incubated, size of tube, type of ventilator and setting, and method of securing tube.
h. Determine oxygen saturation by pulse oximetry.
3. Cardiovascular assessment:
a. Determine heart rate, heart sounds, including any murmurs.
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b. Infant’s color: cyanosis, pallor, plethora, jaundice- assess the color of the lips, nail beds,
mucous membranes.
c. Determine blood pressure and cuff size.
d. Monitors, their parameters and whether alarms are in “on position”.
4. Gastrointestinal assessment:
a. Determine presence of abdominal distention, increase in circumference, shiny skin and state
of umbilicus.
b. Determine any signs of regurgitation; time related to feeding, character and amount of
residual if gavage- fed. If nasogastric tube in place, type of suction, drainage (color,
consistency).
c. Amount, color, consistency and odor of any emesis.
d. Palpate liver margin.
e. Amount, color and consistency of stools, check for occult blood.
f. Bowel sound: presence or absence.
5. Genitourinary assessment:
a. Any abnormalities of genitalia.
b. Amount, color, ph, lab stick finding, and specific gravity of urine.
c. Check weight (the most accurate measure of hydration).
6. Neurologic- musculoskeletal assessment:
a. Infant’s movement: random, purposeful, jittery, twitching, level of activity with stimulation,
evaluation based on gestational age.
b. Infant’s position or attitude: flexed, extended.
c. Reflexes: moro, sucking, babiniski, plantar reflex and other expected reflexes.
d. Determine level of response.
e. Determine changes in head circumference: size and tension of fontanels, suture lines.
7. Temperature:
a. Determine skin and axillary temperature.
b. Determine relationship to environmental temperature.
8. Skin assessment:
a. Any discoloration, reddened area, signs of irritation, abrasions. Observe for monitoring
equipment, infusions, or other apparatus coming in contact with skin.
b. Determine texture and turgor of skin; dry, smooth.
c. Any rash, skin lesion or birthmarks.
d. Determine whether intravenous infusion device is in place and observe for sign of infiltration.
9. Monitoring physiological data:
a. Vital signs:
i. Temp: 36.5-37.3°C.
ii. Pulse: 120-150 beat /min.
iii. Respiration: 40-60 cycle/ Min.
b. Blood examination is a necessary part of the ongoing assessment and monitoring of risk
newborn’s progress. The tests most often performed are blood glucose, Bilirubin, calcium,
and hematocrit and blood gases.
c. Blood glucose ( for hypoglycemia).
Management:
The following are basic goals for care of all high-risk infants:
a. Exhibit adequate oxygenation.
b. Maintain stable body temperature.
c. Protect the infant from nosocomial infection.
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d. Receive adequate hydration and nutrition.

e. Maintain skin integrity.
f. Experience no pain.
g. Receive appropriate development care.
h. Receive appropriate family support, including, preparation for home care.
Anticipation and management of problems:
I. It is essential to identify the clinical problem that the infant is at risk of developing, so that the
problem can be anticipated.
II. Every effort should then be made to prevent this problem occurring.
III. If this is not possible then the infant must be carefully monitored so that the problem can be identified
as soon as it develops. This allows for early treatment.
IV. Once the problem occurs, it must be treated as early as possible.
a. Resuscitate the infant if needed.
b. Immediately treat the abnormal signs, e.g. give oxygen for cyanosis.
c. Attempt to make a diagnosis of the cause of the clinical signs.
d. Treat the cause if possible.
e. Give the infant general supportive care.
f. Monitor the vital signs.
g. Discuss the problem with the parents.
h. Decide whether to transfer the infant to a level 2 or 3 nursery