ULTRASOUND Fetal Anomaliesdocx

BRAIN: Topics in this section
• Acrania
• Arachnoid cyst
• Blake's pouch cyst
• Brain teratoma
• Cerebellar dysplasias
• Choroid plexus cysts
• Corpus callosum agenesis
• Dandy-Walker malformation
• Dural sinus thrombosis
• Encephalocele
• Hemimegalencephaly
• Holoprosencephaly
• Hydranencephaly
• Lissencephaly
• Macrocephaly
• Megacisterna magna
• Microcephaly
• Porencephalic cyst
• Schizencephaly
• Septo-optic dysplasia
• Tuberous sclerosis
• Vein of Galen aneurysm
• Ventriculomegaly
Acrania
Prevalence:
•1 in 1,000 at 12 weeks’ gestation.
Ultrasound diagnosis:
• Absence of cranial vault and cerebral hemispheres.
• At 12 weeks acrania is suspected by absence of the normally ossified skull and
distortion of the brain (exencephaly). At >16 weeks the brain is destroyed
(anencephaly).
Associated abnormalities:
• Chromosomal defects in isolated acrania are rare.
• CNS or other defects are found in about 50% of cases, including spina bifida in
25%.
Investigations:
• Detailed ultrasound examination.
Follow up:
• If the pregnancy continues, follow-up should be standard.
Delivery:
• Standard obstetric care and delivery.
Prognosis:
• Lethal condition with death within the first week of life.
Recurrence:
• One previous affected sibling: 5%.
• Two previous affected siblings: 10%.
• Supplementation of the maternal diet with folate (5 mg/day) for 3 months before
and 2 months after conception reduces the risk of recurrence by about 75%.
Arachnoid cyst
Prevalence:
•1 in 100 births. However, only 1% are large enough to be detectable prenatally.
• Unilocular, avascular cyst that does not communicate with the lateral ventricles.
• They are usually found in the midline between the cerebral hemispheres but about
10% are in the posterior fossa behind the vermis.
• Arachnoid cysts are usually isolated. There are rare associations with
chromosomal defects, mainly trisomy 18 or 12, and agenesis of the corpus
callosum.
Investigations:
• Detailed ultrasound examination, including neurosonography.
• Fetal brain MRI may be useful if ultrasound suggests the presence of other brain
abnormalities.
Follow up:
• Ultrasound scans every 4 weeks to monitor the size of the cyst and possible
compression resulting in ventriculomegaly.
Delivery:
• Place: hospital with neonatal intensive care and pediatric neurosurgery.
• Time: 38 weeks.
• Method: cesarean section if the fetal head circumference is >40 cm.
Prognosis:
• Isolated small cyst: normal neurodevelopment.
• Large and compressing cyst: surgery is required to prevent long term sequelae,
including seizures, headache, motor deficit or neurodevelopmental delay.
Recurrence:
• No increased risk of recurrence.
Blake's pouch cyst

Prevalence:
•1 in 1,000 births.
th
• Expansion of the 4 ventricle into the cisterna magna resulting in a unilocular,
avascular cyst in the posterior fossa – ‘key-hole’ sign in the transverse cerebellar
view.
• Vermis: normal size with mild to moderate upward rotation.
• Cisterna magna: normal.
• Differential diagnosis: mega cisterna magna (>10 mm; normal vermis), arachnoid
cyst (cyst in the cisterna magna with mass effect on surrounding structures;
normal vermis).
• It is usually an isolated finding.
• Risk of chromosomal abnormalies, mainly trisomy 21, in up to 5% of cases but
usually in the presence of other suggestive markers.
Investigations:
• Fetal brain MRI may be useful if other brain abnormalities are suspected.
• Invasive testing and array is recommended in non-isolated cases.
Follow up:
• Ultrasound scans every 4 weeks to monitor the size of the cyst and possible
compression resulting in ventriculomegaly.
• Spontaneous resolution by 24-26 weeks in 50% of cases.
Delivery:
Prognosis:
• Neurodevelopment: good in 90% of cases, mild impairment in 10%.
• Small risk of postnatal hydrocephalus with the need to shunt.
Recurrence:
• Isolated: no increased risk of recurrence.
• Part of trisomies: 1%.
Brain teratoma
Prevalence:
•1 in 1,000,000 births.
• Teratomas are the most common brain tumors.
• Irregular solid mass, with cystic and/or calcified components, distorting the brain
anatomy.
• The incidence of chromosomal abnormalities and genetic syndromes is not
increased.
Investigations:
Follow up:
• Ultrasound scans every 4 weeks to monitor the size of the tumor: brain teratoma
presents rapidly growing, and may be associated with progressive hydrocephalus
and polyhydramnios.
Delivery:
• Time: 38 weeks.
Prognosis:
• Survivalrate: <10%.
Recurrence:
Cerebellar dysplasias
Prevalence:
•1 in 100,000 births.
th
• Transcerebellar diameter <5 percentile for gestational age.
• The small cerebeum is due to disruption in the white matter of either the vermis
(vermian dysplasia) or the cerebellar hemispheres (hemispheric dysplasia).
• The two most common vermian dysplasias are:
• Joubert syndrome: autosomal recessive mutation of chromosome 9q34; absence
or underdevelopment of cerebellar vermis with cleft between cerebellar
th
hemispheres and communication between the 4 ventricle and cisterna magna.
The condition is associated with neurodevelopmental delay.
• Rombencephalosynapsis: sporadic abnormality; complete absence of the vermis
with fusion of the cerebellar hemispheres, absent cavum septum pellucidum,
ventriculomegaly and migration disorders. The condition is associated with
severe neurodevelopmental delay.
Investigations:
• Invasive testing for karyotyping and array.
• TORCH test for fetal infections (CMV can cause a hypoplastic cerebellum).
• Fetal brain MRI at ≥32 weeks’ gestation for diagnosis of abnormalities that are not
detectable by ultrasound, such as migration anomalies.
Follow up:
• Follow-up should be standard.
Delivery:
• Standard obstetric care, but delivery in a hospital with neonatal intensive care.
Prognosis:
• Death in childhood.
Recurrence:
• Joubert syndrome: 25%.
• Rombencephalosynapsis: no increased risk of recurrence.
Choroid plexus cysts

Prevalence:
•1 in 50 fetuses at 20 weeks’ gestation.
• More than 90% resolve by 26 weeks.
• Single or multiple cystic areas (>2 mm in diameter) in one or both choroid plexuses
of the lateral cerebral ventricles.
• Associated with increased risk for trisomy 18 and possibly trisomy 21.
Investigations:
• Detailed ultrasound examination for presence of other markers of trisomies 18 and
21. In the absence of other markers there is no need for invasive testing.
Follow up:
Delivery:
Prognosis:
• Good.
Recurrence risk:
Corpus callosum agenesis

Prevalence:
•1 in 300 births.
• Absence of the septum cavum pellucidum and tear-drop appearance of dilated
posterior part of the lateral ventricles (‘tear drop’) in the standard transverse view
of the brain at >18 weeks’ gestation.
• Complete or partial (usually of the posterior part) absence of the corpus callosum
in a mid-sagittal view of the brain.
• Abnormal course of the pericallosal artery.
• The normal length of the corpus callosum at 20 weeks’ gestation is 18-20 mm.
• Chromosomal abnormalities (trisomies 8, 13 or 18, deletions and duplications) are
found in 20% of cases.
• In about 50% of cases there is an association with any one of 200 genetic
syndromes, defects in the central nervous system (mainly abnormal gyration,
midline arachnoid cysts, Dandy-Walker complex and encephalocele) or defects in
other systems (mainly cardiac, skeletal and genitourinary).
Investigations:
• TORCH test for fetal infections.
• Fetal brain MRI at ≥32 weeks for diagnosis of abnormalities that are not detectable
by ultrasound, such as grey matter heterotopias, late sulcation and migration
anomalies.
Follow up:
Delivery:
Prognosis:
• Isolated: neurodevelopmental delay in 30% of cases.
• Other defects: prognosis could be poor depending on the type of defect.
Recurrence:
• Isolated: 3-5%.
Dandy-Walker malformation
Prevalence:
• Cystic dilation of the fourth ventricle that fills the posterior fossa and extends into
the cisterna magna.
• Hypoplasia or complete agenesis of the cerebellar vermis.
• Chromosomal defects, mainly trisomies 13 or 18, are found in about 30% of cases.
• Genetic syndromes (most common: Walker–Warburg syndrome, Meckel–Gruber
syndrome, Aicardi syndrome, Neu–Laxova syndrome) and defects (brain,
heart, gastrointestinal and genitourinary) are found in >50% of cases.
• Severe ventriculomegaly is common and postnatally develops in >80% of cases.
Investigations:
• Fetal brain MRI at ≥32 weeks’ gestation for the diagnosis of neuronal migration
disorders.
Follow up:
• Ultrasound scans every 4 weeks to monitor possible development of severe
ventriculomegaly.
Delivery:
• Standard obstetric care, but delivery in a hospital with neonatal intensive care.
• Cesarean section if the fetal head circumference is >40 cm.
Prognosis:
• Isolated: neurodevelopmental delay in >50% of cases.
• Severe ventriculomegaly: mortality rate >50% and neurodevelopmental delay in
most survivors.
Recurrence:
• Isolated: 3-5%.
Dural sinus thrombosis

Prevalence:
•1 in 200,000 births.
• Avascular, supratentorial, hyperechogenic mass in the posterior fossa above the
cerebellum, surrounded by a triangular sonolucent area (the dilated venous
sinus).
increased.
Investigations:
• Fetal brain MRI is necessary to confirm the diagnosis and describe its location and
size.
Follow up:
• Ultrasound scans every 4 weeks to monitor the evolution of the lesion.
• Repeat MRI after 6-8 weeks to exclude infarction and hemorrhage of the cerebral
parenchyma.
Delivery:
Prognosis:
• Normal head size with decreasing thrombus size indicate a favourable prognosis.
Postnatally, management is usually non-interventional.
Recurrence:
Encephalocele
Prevalence:
• Cranial bone defect with herniated fluid-filled or brain-filled cyst.
• Usuallyoccipital (85%), but can be parietal (15%) and rarely frontal.
• Chromosomal defects, mainly trisomies 13 or 18, are found in about 10% of cases.
• Cerebral and non-cerebral defects and genetic syndromes are found in >60% of
cases. The most common genetic syndromes are: Meckel-Gruber
syndrome(autosomal recessive; polydactyly, multicystic kidneys, occipital
cephalocele), Walker-Warburg syndrome (autosomal recessive; type II
lissencephaly, agenesis of corpus callosum, cerebellar malformations,
cataract) and amniotic band syndrome (sporadic; single or multiple
abnormalities of the extremities, craniofacial region and trunk due to the
presence of amniotic bands).
Investigations:
Follow up:
Delivery:
• Time: 38 weeks.
• Method: cesarean section at 38 weeks to avoid trauma to the exposed brain tissue.
Prognosis:
• Depends on the size, content and location of the encephalocele.
• Mortality for posterior encephalocele is >50% and for posterior meningocele and
anterior encephalocele is about 20%.
• Neurologicalhandicap in >50% of survivors.
Recurrence:
• Isolated: 3-5%.
• Part of an autosomal recessive conditions: 25%.
Hemimegalencephaly
Prevalence:
•1 in 100,000 births.
• There is cerebral overgrowth and ventriculomegaly of one hemisphere resulting in
shift in the midline in the standard transverse view of the fetal head. The
diagnosis is usually made >26 weeks' gestation.
• There are always abnormalities of sulcation, including agyria, pachygyria, or
polymicrogyria.
• Chromosomal abnormalities: no increased risk.
• Genetic syndromes are very common:
• Proteus syndrome: sporadic; hemimegalencephaly, disproportional overgrowth of
hands and feet.
• Klippel–Trenaunay syndrome: sporadic; hemimegalencephaly, hemangiomatosis
of one or more limbs, heart defects, renal agenesis, laryngeal atresia.
Investigations:
• Fetal brain MRI especially for the differential diagnosis with brain tumors.
Follow up:
• Ultrasound scans every 4 weeks to monitor the evolution of head circumference.
Delivery:
• Cesarean section if the head circumference is >40 cm.
Prognosis:
• Very poor: severe neurodevelopmental delay, hemiplegia and intractable seizures.
Recurrence:
Holoprosencephaly
Prevalence:
•1 in 1,300 fetuses at 12 weeks’ gestation.
• Abnormalities from incomplete cleavage of the forebrain observed in the standard
transverse sections of the brain.
• There are 4 types:
• Alobar: fusion of the cerebral hemispheres with a single ventricle.
• Semilobar: cerebral hemispheres and lateral ventricles are fused anteriorly but
separated posteriorly.
• Lobar: cerebral hemispheres are separated both anteriorly and posteriorly, but
there is partial fusion of the frontal horns of the lateral ventricles, absence of
septum pellucidum and abnormalities of the corpus callosum, cavum septum
pellucidum and olfactory tract. The main differential diagnosis is septo-optic
dysplasia and therefore an attempt should be made to examine optic chiasm and
optic nerves by MRI.
• Syntelencephaly, the anterior and occipital areas of the brain are fully cleaved as
in the lobar type, but unlike this, there is no parietal cleavage and therefore the
Silvian fissures are vertically oriented and abnormally connected across the
midline over the vertex of the brain.
• Lobar holoprosencephaly is detectable at >18 weeks’ gestation, but the other three
types can be detected at the 11-13 weeks scan.
• Chromosomal defects, mainly trisomies 13 or 18, are found in >50% of cases at 12
weeks’ gestation.
• Genetic syndromes are found in 20% of cases.
• Alobar and lobar holoprosencephaly are associated with microcephaly and
midfacial defects in 80% of cases. Extracerebral defects are particularly common
in fetuses with trisomies 13 and 18 and those with genetic syndromes.
Investigations:
• Fetal MRI may be useful for confirmation of diagnosis in cases of suspected lobar
holoprosencephaly.
Follow up:
• If pregnancy continues, follow-up should be standard.
Delivery:
Prognosis:
• Alobar and semilobar: usually lethal within the first year of life.
• Lobar: life expectancy may be normal but usually with severe developmental delay
and visual impairment.
Recurrence:
• Isolated: 6%.
• Part of genetic syndromes: 25-50%.
Hydranencephaly
Prevalence:
• The cranial cavity is fluid filled and there is no remaining cortex. The falx cerebri
and posterior fossa are normal.
increased.
• The causes are vascular occlusion in the internal carotid artery, fetal infection or
prolonged ventriculomegaly.
Investigations:
• Detailed ultrasound examination including neurosonography.
Follow up:
Delivery:
• If the head is circumference is >40cm, cephalocentesis may be needed before
vaginal delivery.
Prognosis:
• Death in early infancy.
Recurrence:
Lissencephaly
Prevalence:
•1 in 100,000 births.
• The whole or parts of the surface of the brain appear smooth with lack of
development of brain folds (gyri) and grooves (sulci).
• Prenatal diagnosis is very difficult but suspicion could be raised >24 weeks’
gestation. The parieto-occipital and Sylvian fissures appear flat and the
subarachnoid space is usually increased.
• In all cases of apparently isolated brain abnormalities, such as ventriculomegaly
and agenesis of the corpus callosum, a detailed follow-up scan should be
arranged at around 26 weeks to exclude an underlying lissencephaly.
• There are 2 types of lissencephaly:
• Type I: agyria with lack of neuronal migration. The cortex is smooth and thick.
• Type II: extensive and anarchic migration with lack of layering. The cortex is
described as “cobblestone”.
• The condition can occur on its own, but it is commonly associated with genetic
syndromes:
• Miller-Dieker: sporadic; type I lissencephaly, microcephaly, heart defects,
polydactyly.
• Walker-Warburg: autosomal recessive; type II lissencephaly, agenesis of corpus
callosum, cerebellar malformations, cataract.
Investigations:
• Fetal brain MRI at ≥32 weeks’ gestation for the diagnosis of neuronal migration
disorders.
• Fetal karyotyping: for diagnosis of Miller-Dieker syndrome (deletion 17p13.3).
• Parental karyotyping: to detect possible balance translocations involving 17p.
Follow up:
• Follow-up every 4 weeks.
Delivery:
Prognosis:
• Life expectancy is about 10 years with severe neurodevelopmental delay.
Recurrence:
• Parental translocations: up to 25%.
Macrocephaly
Prevalence:
•1 in 100 births.
• More common in males than females: 4 to 1.
• Head circumference >2 standard deviations.
• Types of macrocephaly:
• Familial (majority of cases): benign, normal neurological development.
• Secondary: due to an underlying disorder (e.g. hydrocephalus, brain tumor).
• Megalencephaly: disorder of neuronal and glial proliferation which causes
overgrowth of cells and results in severe neurodevelopmental delay. Over 100
syndromes with prenatal or postnatal overgrowth have been described. The most
common is Sotos syndrome (autosomal dominant but 95% of cases are due
to de novo mutations; macrocephaly, frontal bossing, hypertelorism).
Investigations:
• Fetal MRI.
• Invasive testing for karyotyping and array. Megalencephaly is associated with large
deletion of various chromosomes as well as microdeletions.
Follow up:
Delivery:
Prognosis:
• Familial macrocephaly: normal neurological development.
• Secondary macrocephaly: depends on underlying condition.
• Unilateral or bilateral megalencephaly: developmental delay and intractable
seizures.
Recurrence:
• Familial macrocephaly (autosomal dominant inheritance pattern): 50%.
• Secondary: no increased risk of recurrence.
• Most syndromes have an autosomal dominant inheritance pattern but more than
95% are due to de novo mutations.
Megacisterna magna
Prevalence:
• The cisterna magna is >10 mm in the transverse cerebellar view.
• Vermis: normal.
th
• Differential diagnosis: Blake’s pouch cyst (expansion of the 4 ventricle into the
cisterna magna resulting in a unilocular, avascular cyst in the posterior fossa;
vermis normal in size with upward rotation), arachnoid cyst (cyst in the cisterna
magna with mass effect on surrounding structures; normal vermis).
• It is usually an isolated finding, but in up to 10% of cases there is ventriculomegaly.
Investigations:
Follow up:
• Ultrasound scans every 4 weeks to monitor the size of the cisterna magna and
possible development of ventriculomegaly.
Delivery:
Prognosis:
• Normal neurodevelopment.
Recurrence:
Microcephaly
Prevalence:
• 80% of affected infants have a normal head circumference at birth and 90% of
affected individuals had a normal head circumference in the second trimester.
• Ultrasound diagnosis is made usually in the late second and third trimesters.
• The fetal head circumference to abdominal circumference ratio is below the
rd
3 percentile (2 standards deviations below the normal mean for gestational age).
• There is slopping forehead due to the disproportion of the frontal lobes and the
face.
• In most cases presenting in the second trimester there is associated
holoprosencephaly or encephalocele and in those presenting in the third
trimester there are abnormalities of sulcation or neuronal migration.
• Chromosomal abnormalities are rare and the most common are trisomies 13, 18
and 21.
• Genetic syndromes are very common, most of them being caused by single gene
defects with either autosomal recessive or X linked patterns of inheritance. The
most common are: Meckel-Gruber, Walker-Walburg, Miller-Diecker, Smith-Lemli-
Opitz, Seckel syndrome.
Investigations:
• Fetal brain MRI at ≥32 weeks’ gestation for diagnosis of abnormalities of neuronal
migration, such as lissencephaly and polymicrogyria.
Follow up:
• Ultrasound scans every 4 weeks to monitor the evolution of head circumference.
Delivery:
Prognosis:
• Isolated: the risk of neurodevelopmental delay inreases with decreasing head
circumference from 10% if the circumference is 2 to 3 standard deviations (SD)
below the normal mean for gestational age, to 100% if >4 SD's.
• Syndromic: the prognosis depends on the underlying condition.
Recurrence:
• No associated structural defects: 5-10%.
• Familial form of isolated microcephaly: 25%.
Porencephalic cyst
Prevalence:
• One or multiple cystic lesions in the brain that communicate with the ventricles,
subarachnoid space or both. The cysts are either in the fissures or in the midline.
• There are two types of porencephaly:
• Type I: unilateral, due to hemorrhage or ischemia.
• Type II: bilateral, due to neuronal migration disruption.
• Incidence of chromosomal defects is not increased.
• Structural defects: mainly ventriculomegaly.
Investigations:
• Fetal brain MRI at ≥32 weeks’ gestation for diagnosis of grey matter heterotopias,
late sulcation and migration anomalies.
Follow up:
• Ultrasound scans every 4 weeks to monitor the evolution of the lesion and that of
ventriculomegaly.
Delivery:
Prognosis:
• Depends on the size and location of the lesion but neurodevelopment is often
normal.
Recurrence:
Schizencephaly
Prevalence:
•1 in 100,000 births.
• Unilateral or bilateral cleft between the ventricular system and the subarachnoid
space.
• In about 70% of cases the lesion is in the parietal lobe.
• In 50-90% of cases there are other associated brain abnormalities, including
agenesis of the cavum septum pellucidum, septo-optic dysplasia and severe
ventriculomegaly.
increased.
Investigations:
• Fetal brain MRI is necessary to distinguish schizencephaly, which is a migration
disorder, from porencephaly which is a vascular insult. MRI is also important for
detection of polymicrogyria (excessive folding of the brain) which is an invariable
finding in schizencephaly.
Follow up:
Delivery:
Prognosis:
• Very poor: severe developmental delay and intractable epilepsy. Additionally, there
is blindness if the condition is associated with septo-optic dysplasia.
Recurrence:
Septo-optic dysplasia
Prevalence:
• Absent cavum septum pellucidum with communicating frontal horns.
increased.
• In septo-optic dysplasia, in addition to absent cavum septum pellucidum, there is
hypoplasia of the optic nerves and / or hypothalamic-pituitary abnormalities.
Investigations:
• Fetal brain MRI to assess optic nerves and chiasm, hypothalamic-pituitary
gland, and to demonstrate possible associated cortical abnormalities
(polymicrogyria and schizencephaly).
Follow up:
Delivery:
Prognosis:
• Isolated absent cavum septum pellucidum: usually asymptomatic.
• Septo-optic dysplasia: visual disturbances may range from blindness to almost
normal vision. Hormone insufficiencies can be treated with hormone replacement
therapy.
Recurrence:
Tuberous sclerosis
Prevalence:
• Multiple echogenic nodules in the heart (rabdomyoma, usually >20 weeks’
gestation) and brain (cortical tubers and subependymal nodules, usually >30
weeks’ gestation).
• Differential diagnosis: cardiac fibroma, which are single, large and often associated
with pericardial effusion.
• Tuberous sclerosis is found in 50% of cases of rabdomyoma (in the other 50% of
cases the cardiac tumor is an isolated finding). When there are multiple
rabdomyomas the risk of tuberous sclerosis is >90%.
• Mutations in either the TSC1 or TSC2 gene, are found in 90% of cases.
• The tumors most often affect the brain, heart, skin, kidneys, eyes and lungs.
However, prenatal diagnosis is confined to detection of the lesions in the heart
and brain.
Investigations:
• Search for the mutations in the TSC1 and TSC2 genes.
Follow up:
• Ultrasound scans every 4 weeks to monitor the evolution of cardiac tumors and
development of arrhythmias and hydrops.
Delivery:
• Place: hospital with neonatal intensive care.
• Time: 38 weeks, but ealier if there are arrhythmias or hydrops.
• Method: cesarean section if there is hydrops.
Prognosis:
• Arrhythmias, hydrops, and stillbirth in about 20% of cases.
• The cardiac tumors usually regress in early life, whereas the brain tumors usually
increase in size and number.
• Prognosis depends on the number, size and location of the tumors.
• Wide spectrum ranging from normal life expectancy with mild symptoms to severe
neurodevelopmental delay, epilepsy, autism and renal or pulmonary failure.
Recurrence:
• Autosomal dominant: 50% if one of the parents is affected.
• De novo mutations (65% of cases): no increased risk.
Vein of Galen aneurysm

Prevalence:
• Supratentorial mid-line translucent elongated cyst with active arteriovenous flow
within the cyst demonstrated by color Doppler.
• The defect develops in the early first trimester, but the aneurysm becomes
sonographically apparent just in the third trimester.
• In 90% of cases there is high-output heart failure with secondary hydrops.
• The incidence of chromosomal abnormalities or genetic syndromes is not
increased.
Investigations:
• Neurosonography to exclude secondary brain lesions (ischemia and leukomalacia).
• Echocardiography for detection of early signs of heart failure.
Follow up:
• Follow-up scans should be arranged every 1 week, mainly to determine the time of
delivery depending on the risk of developing heart failure.
Delivery:
• Place: hospital with neonatal intensive care and pediatric surgery.
• Time: 38 weeks.
• Method: cesarean section.
Prognosis:
• One third have a good outcome after postnatal intervention by embolization. One
third die during the procedure and one third survive but with neurodevelopmenal
delay.
• If there is hydrops fetalis at the time of diagnosis then the prognosis is poor.
Recurrence risk:
Ventriculomegaly
Prevalence:
•1 in 100 fetuses at 20 weeks’ gestation.
• Bilateral or unilateral dilation of the lateral cerebral ventricles observed in the
standard transverse section of the brain.
• Subdivided according to the diameter of the lateral ventricle into mild (10-12 mm),
moderate (13-15 mm) and severe (>15 mm).
• Chromosomal defects, mainly trisomies 21, 18 or 13, are found in 10% of cases. In
isolated ventriculomegaly there is a 4-fold increase in risk for trisomy 21. The risk
is inversely related to the severity of ventriculomegaly.
• Cerebral and non-cerebral defects and genetic syndromes are found in 50% of
cases.
Investigations:
• Maternal blood testing for antiplatelet antibodies in cases with evidence of brain
hemorrhage.
• Fetal brain MRI at ≥32 weeks for diagnosis of abnormalities of neuronal migration,
such as lissencephaly.
Follow up:
• Ultrasound scans every 4 weeks to monitor the evolution of ventriculomegaly.
Delivery:
Prognosis:
• Isolated mild / moderate: neurodevelopmental delay in 10% of cases, this may not
be higher than in the general population.
• Isolatedsevere: 10 year survival 60%, severe mental handicap 50%.
Recurrence:
• Isolated <1%. Increases to 5% if there is a history of affected fetus or sibling.
• Part of infection: no increased risk.
• X-linked hydrocephaly: 50% of males.
• Associated with alloimmune thrombocytopenia and no treatment: 100%.
SPINE: Topics in this section

• Hemivertebra
• Open spina bifida

• Sacrococcygeal teratoma
Hemivertebra
Prevalence:
•1 in 200 births.
• More common in females than males: 3 to 1.
• After 12 weeks’ gestation: the spine is distorted in the sagittal or coronal view
resulting in scoliosis.
• The hemivertebra appears as a triangular bony structure, smaller than a regular
vertebra, acting like a wedge against the adjacent normal vertebras.
• The incidence of chromosomal abnormalities is not increased.
• Associated syndromes are common: Jarcho-Levin (autosomal recessive; fused
vertebrae, scoliosis, abnormal rib alignment) Klippel-Feil (autosomal recessive
or dominant; fusion of cervical vertebrae), VACTERL association (sporadic;
vertebral and ventricular septal defects, anal atresia, tracheoesophageal fistula,
renal anomalies, radial dysplasia and single umbilical artery), OEIS
complex(sporadic; omphalocele, exstrophy of the cloaca, imperforate anus, and
spinal defects).
• Structural abnormalities, mainly musculoskeletal, genitourinary and cardiac are
found in >70% of cases.
Investigations:
• 2D and 3D ultrasound examination of the spine to define the extent of the
hemivertebra and exclude a lesion of the spinal cord.
Follow up:
• Ultrasound scans every 4-6 weeks to monitor the evolution of scoliosis.
Delivery:
Prognosis:
• Isolated: good. In 75% of cases there is no or slow progression of scoliosis, but in
25% there is rapid progression at 2-3 years of age.
• Associated with other structural defects: poor with increased risk of perinatal death.
Recurrence:
• Single vertebra, isolated: no increased risk.
• Multiple vertebras isolated: 5-10%.
• Part of an autosomal recessive condition: 25%.
Open spina bifida

Prevalence:
• Diagnosis of spina bifida requires the systematic examination of each neural arch,
from the cervical to the sacral region, both transversely and longitudinally. In the
transverse scan, the normal neural arch appears as a closed circle with an intact
skin covering, whereas in spina bifida the arch is ‘U’-shaped and there is an
associated bulging meningocele (thin-walled cyst) or myelomeningocele. The
extent of the defect and any associated kyphoscoliosis are best assessed in the
sagittal scan.
• Site of open spina bifida: lumbosacral (65%), sacral (24%), thoracolumbar (10%),
cervical (1%).
• Open spina bifida is associated with the Arnold-Chiari II malformation with
caudal displacement of the brain stem and obliteration of the cisterna magna.
• At 11-13 weeks’ gestation, in the mid-sagittal view of the head the lower part of the
brain between the sphenoid bone anteriorly and the occipital bone posteriorly can
be divided into the brain stem in the front and a combination of the fourth
ventricle and cisterna magna in the back. In most cases of open spina bifida the
diameter of the brain stem is increased, the distance between the brain stem and
the occipital bone (BSOB) is decreased and the ratio of the brain stem to BSOB
is >1.0.
• In the second-trimester, more than 95% of fetuses have frontal bone scalloping
(lemon sign), and obliteration of the cisterna magna with either an ‘absent’
cerebellum or abnormal anterior curvature of the cerebellar hemispheres
(banana sign). A variable degree of ventricular enlargement is present in virtually
all cases of open spina bifida at birth, but in only about 70% of cases in the mid-
trimester.
• Chromosomal abnormalities (mainly trisomy 18), single mutant genes, and
maternal diabetes mellitus or ingestion of antiepileptic drugs, are implicated in
about 10% of the cases.
• Risk of non-chromosomal syndromes is low.
Investigations:
• Fetal karyotyping in the presence of associated anomalies.
Follow up:
• Follow-up scans every 4 weeks to monitor evolution of ventriculomegaly, possible
kyphoscoliosis and development of talipes.
Fetal therapy:
• In utero closure of spina bifida (open surgery requiring hysterotomy or by
fetoscopy), reduces the need for postnatal shunt placement and may improve
motor and urologic function.
Delivery:
• Standard obsetric care and delivery. There is no evidence that delivery by
cesarean section reduces handicap.
Prognosis:
• The 5-year mortality rate is about 35%, with 20% dying during the first 12 months
of life. About 25% of fetuses with spina bifida are stillborn
• The surviving infants usually have paralysis in the lower limbs and double
incontinence; despite the associated hydrocephalus requiring surgery,
intelligence is often normal.
Recurrence:
• Affected parent or one sibling: 5%.
• Two affected siblings: 10%.
• Supplementation of the maternal diet with folate (5 mg/day) for 3 months before
and 2 months after conception reduces the risk of recurrence by about 75%.
Sacrococcygeal teratoma
Prevalence:
• It is the most frequent fetal teratoma.
• Usually mixed solid and cystic (multiple cysts irregular in shape and size).
• The tumors may be entirely external, partially internal and partly external, or mainly
internal.
• Most teratomas are extremely vascular, which is easily shown using color Doppler
ultrasound.
• The incidence of chromosomal defects or genetic syndromes is not increased.
• Hydronephrosis due to ureteric compression in the case of internal tumors.
• Large tumours may result in fetal anemia and thrombocytopenia (due to
sequestration of red blood cells and platelets by the tumor), fetal heart failure,
hydrops and placentomegaly (due to a hyperdynamic circulation as a result of
arteriovenous shunting), polyhydramnios (due to direct transudation into the
amniotic fluid and due to fetal polyuria, secondary to the hyperdynamic
circulation) and maternal mirror syndrome (generalized fluid overload and
preeclampsia).
Investigations:
• Detailed ultrasound examination, including echocardiography for assessment
of cardiac function and measurement of fetal middle cerebral artery peak systolic
velocity (MCA PSV) for diagnosis of fetal anemia.
Follow-up:
• Follow-up scans every 2 to 3 weeks to monitor growth of the tumor, heart function,
MCA PSV and amniotic fluid volume.
• Ultrasound guided laser coagulation of vessels within the tumor, fetal blood
transfusions and amniodrainage may become necessary.
Delivery:
• Time: 38 weeks. Earlier if there is evidence of poor growth, fetal hypoxia or
hydrops.
• Method: cesarean section if the tumor is very large and there is evidence of heart
failure.
Prognosis:
• Perinatal mortality: about 50%, mainly due to the preterm birth (the consequence of
polyhydramnios) of a hydropic infant requiring major neonatal surgery.
• Difficult surgery, especially with tumors that extend into the pelvis and abdomen,
can result in nerve injury and incontinence.
• The tumor is invariably benign in the neonatal period but delayed surgery or
incomplete excision can result in malignant transformation (about 10% before 2
months of age to about 80% by 4 months).
Recurrence:
FACE: Topics in this section

• Anophthalmia
• Cataract
• Dacryocystocele
• Epignathus
• Facial cleft
• Hypertelorism
• Hypotelorism
• Micrognathia
• Nose anomalies
Anophthalmia
Prevalence:
• In microphthalmia there is decrease in the size of the eyeball and in anophtalmia
there is absence of the eyeball, optic nerve and chiasma. Both can be unilateral
or bilateral.
• Chromosomal defects, mainly trisomy 13, are found in >50% of cases.
• Genetic syndromes are found in >50% of cases. The most common
are Goldenhar syndrome (sporadic; anophthalmia, ear defects, facial cleft,
facial macrosomia), Fraser syndrome (autosomal recessive; microphthalmia,
facial cleft, tracheal atresia, bilateral renal agenesis, heart defects, syndactyly or
polydactyly), Fryns syndrome (autosomal recessive; anophthalmia, facial cleft,
micrognathia, ventriculomegaly, diaphragmatic hernia).
Investigations:
• Fetal brain MRI for diagnosis of abnormalities such as absence of the optic nerve.
Follow up:
• Standard follow-up in isolated cases. If there is an underlying syndrome antenatal
care should be adjusted according to the risks of the condition.
Delivery:
Prognosis:
• Isolated: good.
• Syndromic: very poor.
Recurrence:
• Isolated: no increased risk.
• Part of trisomy 13: 1%.
Cataract
Prevalence:
• Unilateral or bilateral opacity of the lens.
• Bilateral lesions are usually syndromic, whereas unilateral are usually related to
fetal infection.
• The incidence of chromosomal defects is not increased.
• Genetic syndromes are found in about 10% of cases. The most common
include: Walker-Warburg (autosomal recessive; type II lissencephaly, agenesis
of corpus callosum, cerebellar malformations, cataract) and Chondrodysplasia
punctata(X-linked recessive; cataract, symmetric rhizomelic shortening and
epiphyseal calcifications).
• Congenital infection (especially rubella, toxoplasmosis, CMV) found in 30% of
cases.
Investigations:
• TORCH for fetal infection.
Follow up:
• Standard follow-up in isolated cases.
• If suspected fetal infection, then follow-up every 2 weeks.
Delivery:
Prognosis:
• Isolated: generally good. Ophathmologic intervention after birth has good results
with an unaffected quality of life.
• Syndromic: prognosis is generally poor.
Recurrence:
• Part of syndroms: 25%.
Dacryocystocele
Prevalence:
• Cyst (75% unilateral and 25% bilateral) between the lower part of the orbit and the
nose.
• About 90% of dacrocystoceles are due to delayed canalization of the lacrimal duct
beyond 32 weeks’ gestation.
• Differential diagnosis includes anterior encephaloceles (they are often associated
with intracranial abnormalities, such as hydrocephalus), hemangiomas (they are
usually solid or multiseptated), and dermoid cysts(these are usually located
superolaterally).
increased.
Investigations:
Follow up:
Delivery:
Prognosis:
• They resolve spontaneously either in the 3rd trimester or within the first 6 months
of life.
• Occasionally,nasolacrimal duct probing may be required to open the obstruction.
Recurrence:
Epignathus
Prevalence:
•1 in 200,000 births.
• Solid tumor arising from the sphenoid bone, hard and soft palate, the pharynx, the
tongue and jaw.
• The tumor grows into the oral or nasal cavity or intracranially.
• Differential diagnosis includes neck teratomas, encephaloceles, and other tumors
of the facial structures.
• Polyhydramnios (due to pharyngeal compression) is usually present.
increased.
Investigations:
Follow-up:
• Follow-up scans every 4 weeks to monitor growth of the tumor and assess
amniotic fluid volume. If polyhydramnios develops, monitor cervical length every
1 week to determine the need for amniodrainage.
• Fetal MRI at 32 weeks to assess the relation to adjacent structures.
Delivery:
• Time: 38 weeks.
• Method: cesarean section with EXIT procedure.
Prognosis:
• Depends on the size of the lesion and the involvement of vital structures.
• Polyhydramnios has been associated with poor prognosis. The major cause of
neonatal death is asphyxia due to airway obstruction.
• Surgical resection with a normal postoperative course is possible.
Recurrence:
Facial cleft
Prevalence:
•1 in 700 births.
• More common in males than females and in Whites than Blacks.
• In 50% of cases, both the lip and palate are affected, in 25% only the lip and in
25% only the palate.
• Unilateralin 75% of cases (more common on the left side) and bilateral in 25%.
• The typical cleft lip appears as a linear defect extending from one side of the lip
into the nostril. Cleft palate associated with cleft lip may extend through the
alveolar ridge and hard palate, reaching the floor of the nasal cavity or even the
floor of the orbit.
• Both transverse and coronal planes are necessary for the diagnosis. Color Doppler
may be useful to demonstrate flow across the palate in the case of cleft palate.
• Diagnosis of isolated cleft palate is difficult.
• Diagnosis of cleft lip and palate at 11-13 weeks’ gestation can be achieved by
targeted examination of the retronasal triangle in a coronal view and the maxillary
gap in the standard mid-sagittal view of the face used routinely in screening for
chromosomal abnormalities.
• Chromosomal abnormalities, mainly trisomies 13 and 18, are found in 1–2% of
cases. Unilateral cleft lip is not associated with chromosomal abnormalities.
• Associated with any one of >400 syndromes in 30% of cases. The most common
are: Goldenhar syndrome (sporadic; anophthalmia, ear defects, facial cleft,
facial macrosomia), Treacher–Collins syndrome (autosomal recessive or
autosomal dominant with 60% de novo mutations; hypoplasia of the maxilla and
zygomatic bone, micrognathia, cleft palate, malformed or absent ears), Pierre–
Robin anomalad (micrognathia or retrognathia, cleft palate and glossoptosis. In
half of cases this a sporadic isolated finding and in the other half it is associated
with other anomalies or with recognized genetic and non-genetic syndromes).
Investigations:
Follow-up:
• Prenatal consultation with multidisciplinary team.
Delivery:
Prognosis:
• This primarily depends on the presence and type of associated anomalies.
• Isolated: Good prognosis and normal survival.
• Surgical repair is at 3-6 months of age.
• Long-term issues in children with cleft lip and palate include dental abnormalities,
hearing and olfactory problems, midface hypoplasia, and psychological
problems. About 25% have speech abnormalities requiring secondary palate
surgery and speech therapy. Dental anomalies include missing, extra, or
malpositioned teeth and they require braces on their permanent teeth. Most
children have hearing abnormalities and may require myringotomy with
placement of bilateral tympanotomy tubes to improve hearing. Regular
psychological screening is recommended to assess the child’s cognitive
development, behavior, and self-image.
Recurrence:
• Isolated: 5% if one sibling or parent is affected and 10% if two siblings are affected.
• Syndromic: all forms of inheritance have been described, including autosomal
dominant, autosomal recessive, X-linked dominant and X-linked recessive.
Hypertelorism
Prevalence:
th
• Increased interorbital diameter >95 percentile.
• Chromosomal defects, mainly trisomy 13, are very rare.
• Genetic syndromes are found in >50% of cases. The most common
are frontonasal dysplasia (sporadic; hypertelorism, midline facial cleft,
abnormalities of the nose, cranium bifidum
ocultum), craniosynostosis (including Apert, Carpenter, Crouzon) and Neu-
Laxova syndrome (autosomal recessive; hypertelorism, microcephaly, agenesis
of corpus calosum, contractures in the upper and lower limbs, fetal growth
restriction).
• Associated defects: frontal encephalocele and agenesis of the corpus calosum.
Investigations:
Follow up:
• Isolated: follow-up should be standard.
• Syndromic: antenatal care should be adjusted according to the risks of the
condition.
Delivery:
Prognosis:
• Isolated: generally good but in severe cases the cosmetic implications are
important. There might be impaired stereoscopic binocular vision.
• Syndromic: generally poor with high risk of neurodevelopmental delay.
Recurrence:
Hypotelorism
Prevalence:
th
• Decreased interorbital diameter <5 percentile.
• Hypotelorism is part of the midline migration defects together with
holophrosecephaly (which is almost always present). The degree of hypotelorism
can be extreme as in cyclopia.
• Chromosomal abnormalities, mainly trisomy 13, are found in 50% of cases.
• Genetic syndromes are very frequent and the most common is Meckel-Gruber
syndrome (autosomal recesive, lethal condition characterized by occipital
encephalocele, multicystic kidneys and post-axial polydactyly).
Investigations:
Follow up:
Delivery:
Prognosis:
• Part of trisomy 13: lethal.
• Normal karyotype: high risk of neurodevelopmental delay depending on the degree
of holoprosencephaly.
Recurrence:
Micrognathia
Prevalence:
• Subjective finding of prominent upper lip and receding chin in the mid-sagittal view
of the face. These findings may be due to micrognathia (short mandible) or
retrognathia (backward displacement of the mandible).
• Severe micrognathia is associated with polyhydramnios (>25 weeks’ gestation),
due to glossoptosis (normal tongue obstructing small oral cavity).
• Chromosomal abnormalities, mainly trisomy 18 and triploidy, are found in about
30% of cases.
• Associated with >50 genetic syndromes, including:
• Pierre–Robin anomalad: micrognathia or retrognathia, cleft palate and
glossoptosis. In half of cases this a sporadic isolated finding and in the other half
it is associated with other anomalies or with recognized genetic and non-genetic
syndromes).
• Treacher Collins syndrome: autosomal recessive or autosomal dominant with
60% de novo mutations; hypoplasia of the maxilla and zygomatic bone,
micrognathia, cleft palate and malformed or absent ears.
• Otocephaly: sporadic: severe micrognathia or agnathia, and mid-line defects,
including holoprosencephaly, anterior encephalocele, cyclopia, aglossia, and
mid-facial location of the ears.
Investigations:
Follow up:
• Ultrasound scans every 4 weeks to monitor growth and amniotic fluid.
Delivery:
• Place: hospital with facilities for neonatal intensive care.
• Time: 38 weeks.
• Method: induction of labor aiming for vaginal delivery. A pediatrician should be
present in the delivery room and be prepared to intubate the neonate.
Prognosis:
• Neonatal mortality: >80% due to associated abnormalities.
• In Pierre–Robin anomalad survival is good.
Recurrence:
• Part of genetic syndromes: 25% to 50%.
Nose anomalies
Prevalence:
• There is a spectrum of midline abnormalities of the nose in association with
holoprosencephaly, including: arhinia (complete absence of the nasal
structures), proboscis (soft tissue appendage projecting from just below the
forehead) and single nostril (usually central).
• Holoprosencephaly in all cases. Genetic syndromes are found in 20% of cases.
Investigations:
Follow-up:
Delivery:
Prognosis:
• Very poor due to the associated holoprosencephaly and chromosomal
abnormalities.
Recurrence:
• Isolated: 6%
• Part of trisomy 13: 1%
• Part of genetic syndromes: 25% to 50%.
NECK: Topics in this section

• Cervical teratoma
• Cystic hygroma
• Thyroid goitre
Cervical teratoma
Prevalence:
• 5% of all fetal teratomas.
• Vascular solid mass with cystic components, located anterior or anterolateral to the
fetal neck. The tumor grows rapidly (especially >26 weeks' gestation due to
materal estrogens) and can extend inwards producing hyperextension of the
neck and polyhydramnios.
• Calcifications are found in about 50% of cases.
• The incidence of chromosomal defects and genetic syndromes is not increased.
preeclampsia).
Investigations:
• FetalMRI at 32 weeks to assess the relation to adjacent structures.
Follow-up:
Delivery:
hydrops.
• Delivery:cesarean section with EXIT procedure.
Prognosis:
• Fetal or neonatal death (due to airway obstruction) in about 80% of cases.
• Survival after surgery is >80% however, extensive neck dissection and multiple
additional procedures are necessary to achieve complete resection of the tumor
with acceptable functional and cosmetic results.
Recurrence:
Cystic hygroma
Prevalence:
•1 in 800 pregnancies.
•1 in 8,000 live births.
• Bilateral symmetrical cystic structures located in the occipital-cervical region of the
fetal neck. They are differentiated from nuchal edema by the presence of the
nuchal ligament (midline septum).
• Cystic hygroma is caused by defects in the formation of the neck lymphatics. It is
the most common form of lymphangioma (75% are located on the neck, 20% in
the axillary region and 5% on the chest wall, abdominal wall and extremities).
• Chromosomal abnormalities, mainly Turner syndrome, are found in about 50% of
cases.
• Genetic syndromes are found in about 40% of cases. The most common
are Noonan syndrome (autosomal dominant but >90% are due to de
novomutations; cystic hygromas, hypertelorism, pulmonary stenosis, fetal growth
restriction), Multiple-pterygium syndrome (autosomal recessive; cystic
hygromas, contractures in all joints, microcephaly and micrognathia), Fryns
syndrome (autosomal recessive; anophthalmia, facial cleft, micrognathia,
ventriculomegaly, diaphragmatic hernia) and Neu-Laxova syndrome (autosomal
recessive; hypertelorism, microcephaly, agenesis of corpus calosum,
contractures in the upper and lower limbs, fetal growth restriction).
• Hydrops (in addition to cystic hygromas there is generalized edema, ascites,
pericardial or pleural effusions) occurs in 60-80% of cases.
Investigations:
• Detailed ultrasound examination, including echocardiography.
Follow-up:
• Follow-up scans every 4 weeks to assess the evolution of the hygromas and
development of hydrops.
Delivery:
• Time: 38 weeks, ealier if hydrops develops.
• Method: cesarean section if there is hydrops or large cystic hygromas preventing
flexion of the head.
Prognosis:
• Fetal death: 90%.
• In 10% of cases the fetal karyotype is normal, there are no other obvious defects
and the hygromas resolve during pregnancy. In these cases the prognosis is
good.
Recurrence:
• Isolated or part of Turner syndrome: no increased risk of recurrence.
• Part of autosomal recessive syndroms: 25%.
Thyroid goitre
Prevalence:
• Anterior cervical echogenic mass of variable size. The fetal head may be
hyperextended and polyhydramnios is common due to mechanical obstruction of
the esophagus.
• Most cases of fetal thyroid goitre are the consequence of fetal hypothyroidism due
to transplacentally derived anti-thyroid drugs used for the treatment of maternal
hyperthyroidism. A less common cause of hypothyroid goitre is congenital
dyshormonogenesis due to defects in genes involved in the pathway of thyroid
hormone production. In hypothyroidism the fetus may have impaired growth and
bradycardia.
• Hyperthyroid goitre is rare and it is caused by transplacentally derived maternal
thyroid stimulating immunoglobulins in recently diagnosed Graves’ disease. The
fetus may have impaired growth, tachycardia, heart failure and decreased
movements.
increased.
Investigations:
• In most cases assessment of the maternal condition can help decide whether the
cause is fetal hypothyroidism or hyperthyroidism. In uncertain cases,
cordocentesis and measurement of fetal blood thyroid hormones and TSH can
help distinguish between hypothyroidism, with low thyroid hormones and high
TSH, due to antithyroid drugs or congenital dyshormonogenesis, and
hyperthyroidism, with high thyroid hormones and low TSH, due to thyroid
stimulating immunoglobulins
Therapy:
• Fetal hyporthyroid goitre: reduce or even discontinue maternal antithyroid
medication aiming to maintain maternal blood thyroxine levels in the upper level
of the normal range. The second-line of treatment is intra-amniotic injection of
levothyroxine (100 μg / kg) every 1-2 weeks until delivery at term. The goitre
usually decreases in size within a few days after the first course of treatment.
Subsequent injections are given depending on sonographic evidence of re-
enlargement of the gland or serial measurements of levels of thyroid hormones in
amniotic fluid or fetal blood.
• Fetal hyperthyroid goitre: administration of antithyroid drugs to the mother. The
fetal goitre usually decreases in size within a few days, but if this does not occur
measurement of levels of thyroid hormones in fetal blood may be needed and the
dose of antithyroid drugs given to the mother adjusted as necessary.
Follow-up:
• Every 4 weeks to monitor fetal growth, size of the tumor, fetal heart rate, amniotic
fluid volume and cervical length.
Delivery:
• Time: 38 weeks.
• Method: cesarean section and EXIT if there is hyperextension of the neck and
polyhydramnios
Prognosis:
• Good.
• Untreated congenital hypothyroidism is associated with neurodevelopmental delay.

Recurrence:
• Thyroid dyshormonogenesis is autosomal recessive: 25%.
• The rest of cases: no increased risk of recurrence.
THORAX: Topics in this section

• Bronchial atresia
• Bronchogenic cyst
• Congenital high airway obstruction syndrome
• Congenital pulmonary airway malformation
• Diaphragmatic hernia
• Lung agenesis-hypoplasia
• Pleural effusion
• Pulmonary sequestration
Bronchial atresia
Prevalence:
•1 in 100,000 births.
• Enlarged hyperechogenic lung with dilated bronchial tree resulting in mediastinal
shift to the contralateral side.
• Presence of ascites (resulting from central venous compression) is a bad
prognostic factor.
increased.
Investigations:
Follow up:
• Ultrasound scans every 4 weeks to monitor the evolution of the condition.
Delivery:
• Time: 38 weeks.
• Method: cesarean section because of need for immediate postnatal resuscitation
and intubation.
Prognosis:
• High rate of perinatal mortality.
Recurrence:
Bronchogenic cyst
Prevalence:
• Single cyst in a central position with no signs of compression and no associated
altered echogenicity of the adjacent lung.
increased.
Investigations:
Follow up:
• Ultrasound scans every 4 weeks to monitor the evolution of the lesion.
Delivery:
• Time: 38 weeks.
• Method: if there is evidence of bronchial obstruction delivery should be by
cesarean section with EXIT procedure.
Prognosis:
• The cysts are usulally asymptomatic except in cases of tracheobronichal
obstruction.
Recurrence:
Congenital high airway obstruction syndrome

Prevalence:
• Agenesis or stenosis of a segment of the upper airways at the level of the trachea
or larynx. In a few cases the condition results from the presence of laryngeal
cysts or laryngeal web.
• Ultrasound features become evident ≥16 weeks’ gestation. The lungs are
massively enlarged and hyperechogenic resulting in compression of the heart
and development of ascites. The bronchial tree is dilated and the diaphragm
inverted.
• Genetic syndromes are found in >50% of cases. The most common is Fraser
syndrome (autosomal recessive; microphthalmia, facial cleft, tracheal atresia,
bilateral renal agenesis, heart defects, syndactyly or polydactyly).
Investigations:
• Fetal MRI could help identify the location and type of obstruction.
Follow up:
• If the pregnancy continues, serial scans should be carried out to define the best
time for delivery based on evolution of hydrops.
Delivery:
• Time: 38 weeks.
• Method: cesarean section with EXIT procedure and tracheostomy.
Prognosis:
• Highly lethal condition with almost all cases dying in the neonatal period.
• There are a few case reports of spontaneous resolution in utero, either because of
dilatation of a stenotic segment between the larynx and the trachea or even
development of a tracheoesophageal fistula with drainage of the bronchial fluid
into the esophagus.
Recurrence:
• Fraser syndrome: 25%.
Congenital pulmonary airway malformation

Prevalence:
Ultrasound diagnosis.
• Hyperechogenic tumor in the fetal chest, usually presenting at >16 weeks’
gestation. Divided into solid or microcystic, macrocystic with one or more large
cysts (>2 cm) and mixed with areas that are solid intermixed with areas
containing multiple cysts <2 cm in diameter.
• The lesion is unilateral in >95% of cases and usually involves one lobe or segment
of the lung.
• Hydrops is found in <10% of cases.
• Polyhydramnios, due to compressed and obstructed esophagus, may present
at >26 weeks’ gestation.
increased.
• Defects in other systems, mainly cardiac, renal and tracheo-esophageal fistulas,
are found in 10% of cases.
Fetal therapy:
• Thoraco-amniotic shunting may be useful in cases of a large cyst causing major
mediastinal shift and / or ascites.
• In a few cases of hydrops open fetal surgery with excision of the lesion has been
carried out with relatively good results.
• There is some evidence that maternal administration of steroids may cause
shrinkage of the lesion and resolution of hydrops.
Follow up:
• Ultrasound scans every 4 weeks to monitor growth, lung lesion and amniotic fluid
volume.
• During the early third trimester >80% of the microcystic lesions resolve, but in
>80% of these cases this is not a true resolution but purely inability to detect the
lesion by ultrasound because the normal lungs also become echogenic. The
lesion can be detected postnatally by chest X-ray or even better by CT scan.
Delivery:
hydrops.
• Method: induction of labor aiming for vaginal delivery.
Prognosis:
• No hydrops: survival >95%.
• Hydrops: usually lethal.
Recurrence:
Diaphragmatic hernia
Prevalence:
• Abdominal viscera herniated into the thorax through defect in the diaphragm with
associated deviation of the heart from its normal position.
• Bowel, stomach and / or liver in the thorax.
• Left (80%), right (15%) and posterolateral or anterior retrosternal (5%).
• Polyhydramnios at >26 weeks in most cases.
• Chromosomal defects, mainly trisomies 18 or 13 and occasionally tetrasomy 12p
or Pallister–Killian syndrome, are found in 20% of cases.
• Genetic syndromes are found in 10% of cases. The most common is Fryns
syndrome (autosomal recessive; anophthalmia, facial cleft, micrognathia,
ventriculomegaly, diaphragmatic hernia).
• Defects in other systems, mainly craniofacial and cardiac, are found in 20% of
cases.
Investigations:
• Amniocentesis for karyotyping (CVS not appropriate for Pallister–Killian syndrome)
and array.
• Assessment of severity is by measurement of contralateral lung area in a
transverse section of the chest to head circumference ratio (LHR). The measured
LHR is compared to the LHR in normal babies and the disease is classified as
severe if the ratio is <25%, moderate if 26-45% and mild if >45%.
• Ultrafast MRI may be useful for accurate assessment of the proportion of the liver
found in the thorax.
Fetal therapy:
• FETO (fetoscopic endoluminal tracheal occlusion). This involves the endoscopic
insertion of an inflatable balloon into the trachea with consequent retention of
fluid produced by the lungs which may stimulate lung growth. The balloon is
inserted at 26 weeks’ gestation and removed endoscopically at 34 weeks.
• An international randomized study is investigating the effectiveness of FETO,
compared to expectant management, in reducing mortality and morbidity.
Follow up:
• Ultrasound scans every 4 weeks to monitor lung growth and amniotic fluid volume.
Amniodrainage may be necessary if there is polyhydramnios and cervical
shortening.
• Risk of fetal death about 5%.
Delivery:
• Time: 38 weeks. Earlier if there is evidence of poor growth or fetal hypoxia.
Prognosis:
• Part of trisomy 18: lethal.
• Isolated: survival is <15% for severe disease, 50% for moderate disease and >90%
for mild disease.
• Morbidity in survivors includes developmental delay in up to 30% of cases
(especially in those requiring ECMO), gastro-esophageal reflux in 50% of cases,
and scoliosis in 10% of cases.
Recurrence:
• Part of syndromes: 25%.
Lung agenesis-hypoplasia
Prevalence:
• Complete absence or hypoplasia of one lung, usually the right one, with major
mediastinal shift.
• The association of hypoplastic right lung with hypoplastic right pulmonary artery
and partial pulmonary venous drainage of the right lung into the inferior vena
cava is referred to as Scimitar syndrome.
Investigations:
Follow up:
Delivery:
• Time: 38 weeks.
Prognosis:
• Prognosis is worse for right than left lung agenesis probably because of greater
degree of heart and mediastinal displacement. In Scimitar syndrome, mortality is
about 10% due to severe pulmonary hypertension.
Recurrence:
Pleural effusion
Prevalence:
• Isolated congenital chylothorax is found in about 1 in 10,000 births.
• Usually presents with polyhydramnios at around 26 weeks’ gestation.
• Unilateral (25% of cases) or bilateral anechoic area surrounding the lung.
Subjectively classified as mild, moderate or severe and in the latter case if
unilateral there is mediastinal shift.
• In half of the cases the effusion is isolated and in the other half there is associated
hydrops with skin edema and / or ascites.
• Chromosomal defects, mainly trisomy 21 and monosomy X, are found in 10% of
cases.
• Noonan syndrome (autosomal dominant but >90% are due to de novomutations;
cystic hygromas, hypertelorism, pulmonary stenosis, fetal growth restriction),
is found in <5% of cases of isolated hydrothorax.
• In the case of associated hydrops there is a wide range of genetic conditions,
especially if there are other defects.
Investigations:
• Specialist investigations, including infection screen and assessment for anemia
and metabolic disorders, may be necessary in the case of hydrops.
Fetal therapy:
• In severe unilateral or bilateral pleural effusions placement of thoraco-amniotic
shunts restores the normal intrathoracic anatomy and results in resolution of
associated hydrops and polyhydramnios. An alternative to shunting is
pleurodesis in which a sclerosant substance is injected in the pleural cavity.
Follow up:
• Ultrasound scans every 2 weeks to monitor the evolution of the pleural effusions
and associated hydrops. Insertion of new shunts may become necessary if these
are blocked or displaced.
Delivery:
• Time: 38 weeks.
• Method: cesarean section, if there is severe hydrops. In fetuses with shunts, these
need to be clamped at delivery to prevent the development of pneumothorax.
Prognosis:
• Isolated effusion: survival is >90%.
• Effusions with hydrops: in 50% of cases the hydrops resolves after thoraco-
amniotic shunting and in these cases the prognosis is good. If there is no
resolution of hydrops, there may be an underlying genetic syndrome or infection
and in these cases the prognosis is poor.
Recurrence:
• Isolated or associated with infection: no increased risk.
• Part of trisomy: 1%.
• Part of genetic syndrome: up to 25%.
Pulmonary sequestration
Prevalence:
•1 in 15,000 births
• Hyperechogenic mass in the lung, mostly in the left lower lobe.
• Color Doppler demonstrates a feeding vessel that arises from the descending
aorta.
• In 75% of cases it is intralobar, making it indistinguishable in appearance from
microcystic CPAM.
• In 25% of cases it is extralobar, located outside the normal lung with its own
visceral pleura; in most of these cases there is an associated pleural effusion.
increased.
• Defects in other systems, mainly diaphragmatic hernia and cardiac or vertebral
anomalies are found in up to 50% of cases with extralobar sequestration.
Fetal therapy:
• Ultrasound guided laser coagulation of the feeding vessel in cases of severe
hydrothorax or hydrops.
Follow up:
• Ultrasound scans every 4 weeks to monitor growth of the tumor and hydrothorax or
hydrops.
• In >30% of cases there is regression or disappearance of the tumor during the 3rd
trimester.
Timing and route of delivery:
• Time: 38 weeks.
Prognosis:
• Survival: >95%.
• Postnatal therapy: endoscopic removal of mass or selective embolization of the
feeding artery.
Recurrence:
ABDOMINAL WALL: Topics in this section

• Bladder exstrophy
• Body stalk anomaly
• Cloacal exstrophy
• Exomphalos
• Gastroschisis
Bladder exstrophy
Prevalence:
• More common in males than in females: 2 to 1.
• Abdominal wall mass in the suprapubic region below a low insertion of the
umbilical cord.
• Non-visible bladder with normal volume of amniotic fluid.
• Widely separated pubic bones, short and broad penis in males, hemiclitoris on
either side of the bladder in females.
increased.
Investigations:
• Invasive testing to determine the genetic sex of the fetus.
Follow up:
Delivery:
• Time: 38 weeks.
Prognosis:
• Survival rate is >95%. Surgery aims to achieve bladder closure and urinary
continence, and epispadias repair.
Recurrence:
Body stalk anomaly

Prevalence:
•1 in 10,000 pregnancies.
• More often in a younger age group and cocaine abuser.
• Presence of a major abdominal wall defect, severe kyphoscoliosis and short or
absent umbilical cord. Typically, the liver is directly attached to the placenta
without interposed umbilical cord and there is major distortion of the spine.
• The incidence of chromosomal abnormalities and genetic syndroms is not
increased.
• Exencephaly or encephalocoele, facial cleft, and limb amputations are common.
Investigations:
Follow up:
• If the pregnancy continues then follow-up should be standard.
Delivery:
• Routine obstetric care and delivery.
Prognosis:
• Lethal condition either in utero or in early neonatal period.
Recurrence:
Cloacal exstrophy
Prevalence:
•1 in 300,000 births.
• Low exomphalos, non-visible bladder and sacral spina bifida (in 50% of cases) with
normal volume of the amniotic fluid.
• The anatomy of cloacal exstrophy is complex but essentially there is a low
exomphalos at the superior margin of the defect, small or large bowel protruding
through the middle of two widely separated hemi-bladders, hypoplasia of the
colon and anal atresia, splaying of the pubic bones, bifid penis in males,
hemiclitoris on either side of the bladder in females, and spina bifida.
• Other defects, mainly renal and vertebral, talipes, single umbilical artery,
ambiguous genitalia (in males, the penis is divided and duplicated) are often
found.
Investigations:
• Invasive testing to determine the genetic sex of the fetus.
Follow up:
Delivery:
• Place: hospital with neonatal intensive care and facilities for pediatric surgery.
• Time: 38 weeks.
Prognosis:
• Survival: >90% after extensive reconstructive bladder, bowel and genital surgery.
• Both males and females with this condition are capable of normal lifestyle and both
sexes are fertile after surgery. Some form of urinary tract diversion is required for
all.
Recurrence:
Exomphalos
Prevalence:
• Only bowel in the sac: 1 in 100 at 11 weeks’ gestation, 1 in 800 at 12 weeks, 1 in
2,000 at 13 weeks.
• Liver in the sac: 1 in 3,500 fetuses at 11 to 13 weeks.
• Midline sac containing bowel and / or liver with umbilical cord at the apex.
• High exomphalos may contain the heart (pentalogy of Cantrell).
• Low exomphalos may be associated with cloacal abnormality and spina bifida
(OEIS complex).
• Exomphalos containing bowel only at 11-13 weeks resolves by 20 weeks in 90% of
cases.
• Chromosomal defects, mainly trisomies 18 or 13, are found in 30-50% of cases.
• Genetic syndromes, mainly Beckwith-Wiedemann syndrome, are found in 10%
of cases.
• Defects in other systems, mainly cardiac, are found in 30-50% of cases.
Investigations:
• Invasive testing for karyotyping and molecular testing for Beckwith-Wiedemann
syndrome.
Follow up:
• Ultrasound scans every 4 weeks to monitor fetal growth and amniotic fluid. It is
best to monitor growth through estimation of fetal weight by the Sieme formula
which uses biparietal diameter, occipitofrontal diameter and femur length, rather
than formulas using abdominal circumference.
Delivery:
• Time: 38 weeks. Earlier if there is evidence of poor growth or fetal hypoxia.
• Method: induction of labor aiming for vaginal delivery. Cesarean section reserved
for obstetric indications, such as breech presentation and for giant exomphalos
(sac containing >75% of liver) to avoid rupture and hemorrhage.
Prognosis:
• Isolated small / moderate exomphalos: survival >90%.
• Isolated giant exomphalos: survival 80%.
• Other defect: depends on defect, e.g. trisomy 18 is lethal.
Recurrence:
• Part of Beckwith-Wiedemann syndrome: up to 50%.
Gastroschisis
Prevalence:
• Increased risk in young women and in those with cocaine abuse.
• Paraumbilical abdominal wall defect, usually to the right side, with associated
evisceration of bowel, floating freely in the amniotic fluid with a normally inserted
umbilical cord.
increased.
Investigations:
• Detailedultrasound examination.
Associated complications:
• Bowel atresias or obstruction secondary to volvulus and/or ischemia at the hernial
orifice in about 10-30% of cases.
• Fetal growth restriction in 30-60% of cases.
• Spontaneous preterm birth in about 30% of cases.
• Fetal death in 2-4% of cases.
Follow up:
• Ultrasound scans every 4 weeks to monitor growth, amniotic fluid, fetal
oxygenation (UA-PI, MCA-PI and DV-PI) and intra-abdominal bowel dilatation.
• In fetuses with abdominal wall defects it is best to monitor growth through
estimation of fetal weight by the Sieme formula which uses biparietal diameter,
occipitofrontal diameter and femur length, rather than formulas using abdominal
circumference.
Delivery:
dilatation of intrabdominal bowel (>20 mm).
• Method: induction of labor aiming for vaginal delivery. There is no good evidence
that cesarean section is beneficial.
Prognosis:
• Survival: >90%
• Main cause of death: short bowel syndrome.
Recurrence:
• 3%.
GASTROINTESTINAL TRACT: Topics in this section

• Abdominal cysts
• Anorectal atresia
• Duodenal atresia
• Esophageal atresia
• Hepatic calcifications
• Hirschsprung's disease
• Liver tumors
• Meconium peritonitis
• Not-visible gallbladder
• Small bowel obstruction
Abdominal cysts
Abdominal cystic masses are frequent findings at ultrasound examination. Renal
tract anomalies or dilated bowel are the most common explanations, although
cystic structures may arise from the biliary tree, ovaries, mesentery or uterus.
The correct diagnosis of these abnormalities may not be possible by ultrasound
examination, but the most likely diagnosis is usually suggested by the position of
the cyst, its relationship with other structures and the normality of other organs.
Choledochal cysts:
Choledochal cysts represent cystic dilatation of the common biliary duct.
Prenatally, the diagnosis may be made ultrasonographically by the demonstration
of a cyst in the upper right side of the fetal abdomen. There is communication
between the bile duct and the cyst. Absence of polyhydramnios or peristalsis
may help to differentiate the condition from bowel disorders. Postnatally, early
diagnosis and removal of the cyst may avoid the development of biliary cirrhosis,
portal hypertension, calculi formation or adenocarcinoma. The operative mortality
is about 10%.
Mesenteric or omental cysts:
These cysts may represent obstructed lymphatic drainage. The fluid contents
may be serous, chylous or hemorrhagic. Antenatally, the diagnosis is suggested
by the finding of a multiseptate or unilocular, usually mid-line, cystic lesion of
variable size; a solid appearance may be secondary to hemorrhage. Antenatal
aspiration may be considered in cases of massive cysts resulting in thoracic
compression. Postnatal management is conservative and surgery is reserved for
cases with symptoms of bowel obstruction or acute abdominal pain following
torsion or hemorrhage into a cyst. Complete excision of cysts may not be
possible because of the proximity of major blood vessels and in up to 20% of
cases there is recurrence after surgery. Although malignant change in mesenteric
cysts has been described, this is rare.
Hepatic cysts:
Hepatic cysts are typically located in the right lobe of the liver. They are quite rare
and result from obstruction of the hepatic biliary system. They appear as
unilocular, intrahepatic cysts, and they are usually asymptomatic, although rarely
may show complications such as infections or hemorrhages. Hepatic cysts are
found in 30% of the cases of adult polycystic kidney disease.
Intestinal duplication cysts:
These are quite rare, and may be located along the entire gastrointestinal tract.
They sonographically appear as tubular or cystic structures of variable size. They
may be isolated or associated with other gastrointestinal
malformations. Thickness of the muscular wall of the cysts and presence of
peristalsis may facilitate the diagnosis. Postnatally, surgical removal is carried
out.
Anorectal atresia
Prevalence:
• Overdistention of the rectum and sigmoid colon in the third trimester.
• Normal amount of the amniotic fluid.
• Occasionally, intraluminal calcifications (meconium) can be visualised.
• Chromosomal defects, mainly trisomy 21 and 18, are found in 3-4% of cases.
• Other defects, mainly urogenital malformations, vertebral anomalies and CNS, are
found in up to 70% of cases.
• Non-genetic syndromes: VACTERL association (sporadic; vertebral and
ventricular septal defects, anal atresia, tracheoesophageal fistula, renal
anomalies, radial dysplasia and single umbilical artery), Caudal regression
syndrome (sporadic; sacral agenesis or hypoplasia, hypoplastic veretebral
bodies, anal atresia), OEIS complex (sporadic; omphalocele, exstrophy of the
cloaca, imperforate anus, and spinal defects).
Investigations:
Follow up:
Delivery:
• Time: 38 weeks.
Prognosis:
• In isolated cases the overall survival is good.
• In cases presenting with multiple abnormalities the prognosis is poor.
Recurrence:
Duodenal atresia
Prevalence:
• ‘Double bubble’ sign as a result of an enlarged stomach and duodenal cap. Usually
found >24 weeks’ gestation.
• Polyhydramnios >24 weeks’ gestation in 50% of cases.
• Chromosomal defects, mainly trisomy 21, are found in 30% of cases.
• Other defects, mainly cardiac, renal, vertebral, are found in 10-20% of cases.
Investigations:
Follow up:
• Ultrasound scans every 2-3 weeks to monitor growth and assess amniotic fluid
volume. Amniodrainage may be necessary if there is polyhydramnios and
cervical shortening.
Delivery:
• Time: 38 weeks.
Prognosis:
• Survivalrate >95%.
Recurrence:
Esophageal atresia
Prevalence:
• Small or ‘absent’ stomach in the presence of polyhydramnios >25 weeks’
gestation.
• Esophageal atresia may be suspected prenatally in only about 40% of cases
because if there is an associated tracheoesophageal fistula (found in >80% of
cases), the stomach may look normal.
• Chromosomal defects: trisomy 18 found in 20% of cases and trisomy 21 in 1% of
cases.
• Other defects, mainly cardiac, found in 50% of cases.
• Tracheoesophageal fistulae may be seen as part of the VACTERL
association(sporadic; vertebral and ventricular septal defects, anal atresia,
tracheoesophageal fistula, renal anomalies, radial dysplasia and single umbilical
artery).
Investigations:
Follow up:
Delivery:
• Time: 38 weeks.
Prognosis:
• Survival is primarily dependent on gestation at delivery and the presence of other
anomalies. For babies with an isolated tracheoesophageal fistula, born after 32
weeks' gestation without aspiration pneumonitis, postoperative survival is >95%.
Recurrence:
Hepatic calcifications
Prevalence:
• Presence of solitary or multiple echogenic foci (1-2 mm in diameter) within the
substance of the liver or in the capsule.
increased.
• Parenchymal calcifications may be due to intrauterine infection.
Investigations:
Follow up:
• In isolated cases follow-up should be standard.
Delivery:
Prognosis:
• Good.
Recurrence:
Hirschsprung's disease
Prevalence:
• The condition is characterized by congenital absence of intramural
parasympathetic nerve ganglia in a segment of the colon. The aganglionic
segment is unable to transmit a peristaltic wave, and therefore meconium
accumulates and causes dilatation of the lumen of the bowel. The ultrasound
appearance is similar to that of anorectal atresia, when the affected segment is
colon or rectum.
• Polyhydramnios and dilatation of the loops are present in the case of small bowel
involvement; on this occasion, it is not different from other types of obstruction.
Investigations:
• Amniocentesis for karyotyping or analysis of cfDNA in maternal blood.
Follow up:
• Ultrasound scans every 2-3 weeks to monitor the evolution of the condition and
assess amniotic fluid volume. Amniodrainage may be necessary if there is
polyhydramnios and cervical shortening.
Delivery:
• Time: 38 weeks.
Prognosis:
• Postnatal surgery is aimed at removing the affected segment and this may be a
two-stage procedure with temporary colostomy. Neonatal mortality is
approximately 20%.
Recurrence:
Liver tumors
Prevalence:
•1 in 100,000 births.
• The most common are hemangioma, mesenchymal hamartoma and
hepatoblastoma.
• They can be cystic, echogenic, mixed solid and cystic or they may just present with
hepatomegaly.
• Hemangiomas and hepatoblastomas may be associated with evidence of high-
output heart failure, hydrops and polyhydramnios.
• Color Doppler studies may be helpful in distinguishing hemangioma from the other
tumors.
• Hepatoblastoma can be associated with the Beckwith–Wiedemann
syndromewith evidence of organomegaly and macroglossia.
Investigations:
• Doppler ultrasound to define the vascular anatomy of the liver.
• Fetal MRI to define the extent of the tumor and its relationship with intrahepatic
structures and adjacent organs.
Follow up:
• Ultrasound scans every 2-3 weeks to monitor the size of the tumor and
development of heart failure and polyhydramnios.
Fetal therapy:
• In the case of large hemangiomas associated with high-output heart failure
maternal administration of steroids may arrest the growth of the tumor.
Delivery:
• Time: 38 weeks.
• Method: cesarean section for large vascular tumors to avoid rupture at the time of
delivery.
Prognosis:
• Hemangiomas: survival of about 80% after treatment with steroids. However,
occasionally, they are associated with arteriovenous shunting, congestive heart
failure and hydrops, resulting in intrauterine or neonatal death. After infancy the
tumors regress spontaneously.
• Mesenchymal hamartoma: surgical resection with 70% survival.
• Hepatoblastoma: surgical resection with 60% survival. Prior to resection several
cycles of chemotherapy may be necessary to shrink the tumor and make it
resectable.
Recurrence:
• In general there is no increased risk of recurrence.
• In hepatoblastoma in association with Beckwith–Wiedemann syndrome (autosomal
dominant) and familial adenomatous polyposis (autosomal dominant condition
that predisposes to colonic adenomas and carcinomas) the risk is increased.
Further information:
• https://rarediseases.info.nih.gov/diseases/3343/beckwith-wiedemann-syndrome
Meconium peritonitis
Prevalence:
• Presence of intra-abdominal hyperechogenic areas (peritoneal calcifications).
Results from intrauterine perforation of the bowel which leads to a local sterile
chemical peritonitis.
• Additionally: dilated bowel loops, ascites and meconium pseudocyst.
• The incidence of chromosomal abnormalities and genetic syndroms is
not increased.
• Risk of cystic fibrosis: 75%.
Investigations:
• Amniocentesis: DNA studies for cystic fibrosis if both parents are carriers.
• TORCH test for fetal infections
Follow up:
Delivery:
• Time: 38 weeks.
Prognosis:
• In case of simple peritonitis the outcome is good and surgical intervention is not
necessary.
• In case of complex peritonitis (associated with bowel dilatation, ascites) the
prognosis is poor and neonatal mortality is >50%.
Recurrence:
Not-visible gallbladder
Prevalence:
• Small or absent gallbladder.
• In most cases this is a transient finding (75%), but some are due to isolated
gallbladder agenesis (15%), cystic fibrosis (10%) and rarely biliary atresia (3%).
• In about 25% of cases of biliary atresia there associated heterotaxy syndrome,
which includes situs inversus, polysplenia, malrotation of the gut intestinal atresia
and heart defects.
Investigations:
• Limited data suggest that in biliary atresia there are very low levels of digestive
enzymes in amniotic fluid at <24 weeks’ gestation.
Follow up:
Delivery:
Prognosis:
• Biliary atresia is a serious condition requiring liver transplantation.
• Gallbladderagenesis is a benign condition.
Recurrence:
Small bowel obstruction

Prevalence:
• Multiple fluid-filled loops of the bowel in the abdomen >7 mm in diameter
presenting >25 weeks’ gestation.
• Distension of the abdomen with active peristalsis.
• If bowel perforation occurs, transient ascites, meconium peritonitis and meconium
pseudocysts may ensue.
• Polyhydramnios >25 weeks’ gestation, especially in proximal obstructions.
increased.
• Other bowel anomalies: malrotation, gastroschisis, duplication and meconium
ileus.
• 10% risk of cystic fibrosis (up to 90% in case of associated meconium peritonitis).
Investigations:
Follow up:
Delivery:
• Time: 38 weeks.
Prognosis:
• The prognosis is related to the gestational age at delivery, the presence of
associated abnormalities and site of obstruction. In those born after 32 weeks
with isolated obstruction requiring resection of only a short segment of bowel,
survival is >95%. Loss of large segments of bowel can lead to short gut
syndrome, which is a lethal condition.
Recurrence:
URINARY TRACT: Topics in this section

• Horseshoe kidney
• Hydronephrosis
• Kidney tumors
• Multicystic kidneys
• Pelvic kidney
• Autosomal dominant polycystic kidneys
• Autosomal recessive polycystic kidneys
• Renal agenesis
• Uretero-pelvic junction obstruction
• Urethral obstruction
• Uretero-vesical junction obstruction
Horseshoe kidney
Prevalence:
•1 in 400 births.
• More common in male fetuses.
• Fusion of the lower poles of both kidneys in front of the descending aorta.
• Horseshoe kidney is best demonstrated on the coronal and transverse scans when
renal tissue will be seen crossing the midline.
• Normal bladder and amniotic fluid volume.
• Chromosomal abnormalities: horseshoe kidney is found in 30% of cases of Turner
syndrome and in 20% of trisomy 18.
• Associated syndromes are found in 15% of cases. The most common is Caudal
regression syndrome (sporadic; sacral agenesis or hypoplasia, hypoplastic
veretebral bodies, anal atresia).
• Other defects include hydronephrosis, and genital anomalies.
• Extra-renal defects, mainly CNS, cardiac or skeletal, are found in 30% of cases.
Investigations:
Follow up:
• Ultrasound scans every 4 weeks to detect possible late-onset hydronephrosis.
Delivery:
Prognosis:
• In isolated forms, the prognosis is good. Postnatal follow-up is advised because of
significant risk of infections, hydronephrosis and nephrolithiasis (70%).
Recurrence:
• Isolated or part of Turner syndrome: no increased risk.
Hydronephrosis
Prevalence:
•1 in 500 births.
• Dilatation of the collecting system of the kidney observed in the standard
transverse view of the abdomen. Ureters and bladder are normal.
• On the basis of the anteroposterior diameter of the pelvis the condition is divided
into:
nd rd
• Mild (only renal pelvis): 4-7 mm in the 2 trimester; 7-9 mm in the 3 .
nd rd
• Moderate (pelvis and calyces): 8-10 mm in the 2 trimester; 10-15 mm in the 3 .
nd rd
• Severe (cortical thinning): >10 mm in the 2 trimester; >15 mm in the 3 .
• Chromosomal defects: low risk in isolated forms.
• Abnormalities of the contralateral kidney: multicystic kidney, ectopia, renal
agenesis.
• Associated syndromes are found in 5% of cases.
Investigations:
• Detailed ultrasound examination (especially of the contralateral kidney).
• Karyotyping should be offered only if other markers are present.
Follow up:
• Ultrasound scans every 4 weeks to monitor the evolution of hydronephrosis and
assess amniotic fluid volume.
Delivery:
Prognosis:
• In the majority of cases, the condition remains stable or resolves in the neonatal
period. In about 20% of cases, there may be an underlying ureteropelvic junction
obstruction or vesicoureteric reflux that requires postnatal follow-up and possible
surgery. Moderate hydronephrosis is usually progressive and in more than 50%
of cases surgery is necessary during the first 2 years of life.
Recurrence:
Kidney tumors
Prevalence:
•1 in 200,000 births.
• Mesoblastic nephroma (renal hamartoma) is the most frequent renal tumor, while
Wilms’ tumor (nephroblastoma) is extremely rare.
• In both tumors there is a solitary mass replacing the normal architecture of the
whole or part of the kidney.
• Cystic areas may appear due to hemorrhagic necrosis.
• In most cases, there is associated polyhydramnios.
• Nephroblastoma can be associated with the Beckwith–Wiedemann
syndromewith evidence of organomegaly and macroglossia.
Investigations:
Follow up:
• Ultrasound scans every 2-3 weeks to monitor the size of the tumor and
development of heart failure and polyhydramnios.
Delivery:
• Place: hospital with facilities for neonatal intensive care. In about 20% of neonates
there is hypertension due to overproduction of renin by the affected or normal
kidney.
• Method: vaginal delivery.
Prognosis:
• Mesoblastic nephromas are benign, and nephrectomy is curative in the majority of
cases. In a few cases there is local recurrence or distant metastases in the first
year of life.
• Wilms’ tumor is malignant and about 50% are associated with genetic syndromes
(such as Beckwith– Wiedemann syndrome). Treatment of the tumor requires
nephrectomy, chemotherapy and sometimes radiotherapy; Survival is >90%.
Recurrence:
• Mesoblastic nephroma: no increased risk of recurrence.
• In nephroblastoma associated with Beckwith–Wiedemann syndrome (autosomal
dominant) the risk is increased.
Multicystic kidneys
Prevalence:
• The kidneys are replaced by multiple irregular cysts of variable size with
intervening hyperechogenic stroma.
• Renal pelvis cannot be visualised.
• The disorder can be unilateral (80% of cases), bilateral or segmental; if bilateral,
there is associated anhydramnios and the bladder is ‘absent’.
• Abnormalities of the contralateral kidney (25%): duplex system, pelvico-uretric
obstruction, agenesis, ectopic or affected by vesico-ureteric reflux.
• Chromosomal defects, mainly trisomy 18, are found in 3% of unilateral lesions and
15% of bilateral ones.
• Associated syndromes are found in 10% of cases. The most common
are: Brachio-otorenal syndrome (autosomal dominant; brachial cyst presenting
as anterolateral neck cyst, multicystic kidneys), VACTERL
association (sporadic; vertebral and ventricular septal defects, anal atresia,
artery), Short-rib polydactyly syndrome (autosomal recessive; short limbs,
hypoplastic thorax, polydactyly, heart and brain defects, multicystic
kidneys), Meckel-Gruber syndrome (autosomal recessive; polydactyly,
multicystic kidneys, occipital cephalocele).
.
Investigations:
• Karyotyping might be useful in case of bilateral form or associated with other
abnormalities
to estimate the risk of recurrence.
Follow up:
• Unilateral: Ultrasound scans every 4 weeks to detect possible late-onset
hydronephrosis.
• Bilateral:if the pregnancy continues then follow-up should be standard.
Delivery:
Prognosis:
• Bilateral: lethal either in utero or in the neonatal period due to pulmonary
hypoplasia.
• Unilateral: normal prognosis. Postnatally, most urologists adopt an expectant
approach because the kidney gradually shrinks and may disappear. The parents
and family should also be scanned to exclude autosomal dominant branchio-
otorenal syndrome.
Recurrence:
• Isolated: 1-2%.
Pelvic kidney
Prevalence:
• Visualisation of the kidney in the pelvis above the bladder.
• Empty renal fossa on the affected side with the adrenal gland filling the space.
• Color Doppler might be useful to locate the hilum of the ectopic kidney.
• Normal bladder and amniotic fluid volume.
• The incidence of chromosomal defects and genetic syndromes is not increased.
Investigations:
Follow up:
• Ultrasound scans every 4 weeks to detect possible late-onset hydronephrosis.
Delivery:
Prognosis:
• Good prognosis. Vesico-ureteral reflux and uretero-pelvic junction obstruction may
occur.
Recurrence:
Autosomal dominant polycystic kidneys

Prevalence:
•1 in 1,000 people carry the mutant gene.
• Clinical onset of this disorder is typically in the third to fifth decade of life.
• The kidneys are enlarged and hyperechogenic, but smaller than in autosomal
recessive disease.
• Renal pelvises can be visualised.
• Bladder and amniotic fluid volume are normal.
increased.
• Associated with hepatic, pancreatic or ovarian cysts.
Investigations:
• Genetic testing: the disease is caused by mutations in the PKD1 gene (85% of
cases) on chromosome 16p13.13 and PKD2 gene (15% of cases) on
chromosome 4q13.23. Prenatal diagnosis in affected families can be carried out
by first-trimester chorion villous sampling.
Follow up:
• Ultrasound scans every 4 weeks to assess amniotic fluid volume.
• Ultrasound examination of parents’ kidneys.
Delivery:
Prognosis:
• In counselling affected parents with ADPKD, it should be emphasized that the
prenatal demonstration of sonographically normal kidneys does not necessarily
exclude the possibility of developing polycystic kidneys in adult life.
• Dialysis and transplant are the treatment options when the pathology becomes
symptomatic in the third to fifth decades of life.
Recurrence:
• Risk of recurrence: 50%.
Autosomal recessive polycystic kidneys
Prevalence:
• The disease has a wide spectrum of renal and hepatic involvement and it is
subdivided into perinatal, neonatal, infantile and juvenile types on the basis of the
age of onset of the clinical presentation.
• Bilaterally enlarged and homogeneously hyperechogenic kidneys. Usually found
>24 weeks’ gestation.
• Renal pelvises cannot be visualised.
• Gradual onset of oligohydramnios from the second trimester.
increased.
• Cystic fibrosis of the liver: the liver appearances are normal, despite the presence
of cysts, portal fibrosis and proliferation of bile ducts. The more severe the renal
disease, the less severe is the hepatic fibrosis.
Investigations:
• Genetic testing: the disease is caused by mutations in the PKHD1 gene on
chromosome 6p21. Prenatal diagnosis in families at risk can be carried out by
first-trimester chorion villous sampling (reliable prenatal diagnosis in 80% of
affected families).
Follow up:
• Ultrasound scans every 4 weeks to monitor growth and assess amniotic fluid
volume.
Delivery:
• Time: 38 weeks.
Prognosis:
• The prenatal type is lethal either in utero or in the neonatal period due to
pulmonary hypoplasia.
• The infantile and juvenile types result in chronic renal failure, hepatic fibrosis and
portal hypertension; many cases survive into their teens and require renal
transplant.
Recurrence:
• Risk of recurrence: 25%.
Renal agenesis
Prevalence:
• Unilateral: 1 in 2,000 births.
• Bilateral: 1 in 5,000 births.
• Unilateral: nonvisualisation of one kidney with normal bladder and amniotic fluid.
Color Doppler demonstrates single renal artery. There may be compensatory
hypertrophy of the contralateral kidney.
• Bilateral: nonvisualisation of the kidneys and bladder in combination with
anhydramnios >17 weeks’ gestation. Failure to visualise renal arteries with colour
Doppler. Adrenal glands assume discoid shape and move laterally and inferiorly.
Small fetal chest, cardiac hypertrophy and talipes are seen.
• In the majority of cases, renal agenesis is a sporadic and isolated abnormality.
• Chromosomal defects, mainly trisomy 18, are found in 1-2% of cases.
• Associated syndromes are found in 10% of cases. The most common are: Fraser
syndrome (autosomal recessive condition characterized by renal agenesis,
laryngeal atresia, cryptophthalmos, syndactyly) and VACTREL
association(vertebral and ventricular septal defects, anal atresia,
artery), MURCS association (sporadic; hypoplastic or bicornuate uterus, renal
agenesis or dysplasia, vertebral and rib abnormalities).
Investigations:
• Karyotyping in cases with additional abnormalities.
Follow up:
• In isolated cases follow-up should be standard.
Delivery:
Prognosis:
• Bilateral is lethal, usually in the neonatal period due to pulmonary hypoplasia.
• Unilateral has normal prognosis. In some patients there may be vesicoureteric
reflux. Girls should have a pelvic ultrasound to look for abnormalities in the
Müllerian structures postnatally.
Recurrence:
• Non-syndromic: 3%.
• In 15% of cases, one of the parents has unilateral renal agenesis and in these
families the risk of recurrence is increased.
Uretero-pelvic junction obstruction

Prevalence:
• More common in males.
• Pelvicalyceal dilatation without ureteral dilatation. The degree of pelvicalyceal
dilatation is variable and, occasionally, perinephric urinomas (encapsulated
collection of urine due to a tear in the renal pelvis or calyces or the ureter) and
urinary ascites may be present.
• Unilateral in 80% of cases.
increased.
• Abnormalities of the contralateral kidney: multicystic kidney, ectopia, renal
agenesis.
Investigations:
Follow up:
Delivery:
Prognosis:
• The majority of infants have moderate or good function and can be managed
expectantly. Pyeloplasty is performed if there is deterioration of renal function.
Recurrence:
Urethral obstruction
Prevalence:
•1 in 1,500 males
• Urethral obstruction can be caused by urethral agenesis, persistence of the cloaca,
urethral stricture or posterior urethral valves.
• With posterior urethral valves, there is usually incomplete or intermittent
obstruction of the urethra, resulting in an enlarged and hypertrophied bladder
with varying degrees of hydroureters, hydronephrosis, a spectrum of renal
dysplasia (echogenic renal parenchyma with peripherally placed cysts),
oligohydramnios and pulmonary hypoplasia.
• In some cases, there is associated urinary ascites from rupture of the bladder.
• Reduced amount of the amniotic fluid >17 weeks’ gestation.
• In the first trimester the condition presents as megacystis (longitudinal bladder
diameter of ≥7 mm). If the bladder diameter is 7-15 mm there is spontaneous
resolution of the megacystis in about 90% of cases. If the bladder diameter is
≥15 mm the condition is invariably associated with progressive obstructive
uropathy leading to hydronephrosis and dysplastic kidneys.
• Chromosomal defects, mainly trisomies 21, 18 or 13, are found in about 10% of
cases.
• Other defects, mainly cardiac and gastrointestinal are found in up to 40% of cases.
Investigations:
• Amniocentesis for karyotyping or analysis of cfDNA from maternal blood.
Fetal therapy:
• Decompression of the urinary tract has been achieved by ultrasound-guided
insertion of suprapubic vesico-amniotic catheters and cystoscopic ablation of
urethral valves. Although these techniques demonstrated the feasibility of
intrauterine surgery, they did not provide conclusive evidence that such
intervention improves renal or pulmonary function.
Follow up:
• If pregnancy continues, ultrasound scans every 4 weeks to monitor the evolution of
the condition and assess amniotic fluid volume.
• Antenatal evaluation of renal function relies on a combination of ultrasonographic
findings and analysis of fetal urine obtained by urodochocentesis. Poor
prognostic signs are:
• The presence of bilateral multicystic or severely hydronephrotic kidneys with
echogenic or cystic cortex;
• Anhydramnios implying complete urethral obstruction;
• High urinary sodium (more than 100 mg/dL), calcium (more than 8 mg/dL) and ß2
microglobulin (more than 40 mg/L).
Delivery:
• Time: 38 weeks.
Prognosis:
• Severe: high perinatal mortality due to pulmonary hypoplasia secondary to severe
oligohydramnios. Even in those that survive, about 30% develop renal failure
necessitating dialysis and / or transplantation before the age of 5 years.
Recurrence:
Uretero-vesical junction obstruction

Prevalence:
• Presence of hydroureter and hydronephrosis with normal bladder.
• The dilated ureter is tortuous and appears as a collection of cysts of variable size,
localized between the dilated renal pelvis and the bladder.
•The etiology is diverse, including ureteric stricture or atresia, vascular obstruction,
diverticulum, or ureterocele. Ureteroceles (visible as a thin-walled and fluid-filled
small circular area inside the bladder) are usually found in association with
a duplex kidney and collecting system. The upper pole characteristically
obstructs and the lower one refluxes.
increased.
Investigations:
Follow up:
Delivery:
Prognosis:
• Postnatal intervention is indicated if the vesico-uretric reflux is associated with
abnormal renal function.
Recurrence:
GENITAL TRACT: Topics in this section

• Ambiguous genitalia
• Ovarian cyst
• Urogenital sinus
Ambiguous genitalia
Prevalence:
• Female fetus: clitoromegaly with normal labia.
• Male fetus: micropenis, hypospadias, undescended testes, bifid scrotum.
• On the basis of the cause, the condition is divided into:
• True hermaphrodite: both ovarian and testicular tissue are found within the same
gonad. The karyotype is female 46,XX, but there is a chromatinic material from
the Y chromosome.
• Female pseudohermaphrodite: virilized females with normal female karyotype
and ovarian gonadal tissue. The causes include congenital adrenal hyperplasia
(1 in 15,000), ingestion of androgens by the mother and maternal virilizing
tumors.
• Male pseudohermaphrodite: undervirilized males with normal male karyotype
and testicular tissue. The causes include inadequate synthesis of testosterone or
the presence of an androgen receptor defect.
• Chromosomal abnormalities, mainly trisomy 13, triploidy and 13q syndrome, are
found in a few cases.
• The condition is commonly associated with genetic syndromes:
• Smith-Lemli-Opitz syndrome: autosomal recessive; ambiguous
genitalia, microcephaly, cardiac, renal and gastrointestinal defects, syndactyly
and polydactyly.
• WAGR syndrome: sporadic; Wilms tumor, aniridia (absence of the iris),
geniturinary malformations, neurodevelopmental delay.
• Other defects, mainly facial clefts and cardiac defects are often found.
Investigations:
• Look for maternal signs of hyperandrogenism (acne, deep voice, development of
hirsuitism during pregnancy) and enquire about ingestion of androgens during
the first trimester and family history of ambiquous genitalia.
• Determine genetic sex by invasive testing or cfDNA in maternal blood.
• Families at risk of congenital adrenal hyperplasia: invasive testing for DNA
analysis.
• Cases suspected of Smith–Lemli–Opitz syndrome: amniocentesis and
measurement of 7-dehydrocholesterol; high levels suggest the diagnosis.
Follow up:
• In families with congenital adrenal hyperplasia, administering dexamethasome to
the pregnant woman from 6 weeks’ gestation can minimize the effect of
androgens on the genitalia and the developing brain. If the fetus is male, steroids
should be discontinued.
• Follow-up scans every 4 weeks to monitor growth and evolution of genitalia.
Delivery:
• Standard obstetric care but delivery should be in a tertiary center.
Prognosis:
• Treatment of a neonate with ambiguous genitalia should be performed by a
multidisciplinary team, including geneticists, pediatric endocrinologists, and
pediatric urologist. There is controversy concerning sex assignment and the need
or not of reconstructive surgery.
Recurrence:
• Congenital adrenal hyperplasia: 25%
Ovarian cyst
Prevalence:
• Most common intra-abdominal cyst in female fetuses.
• Unilateral, unilocular cyst, sometimes containing a ‘daughter cyst’, in the abdomen
of a female fetus >26 weeks’ gestation.
• If the cyst undergoes torsion (40% of cases) or hemorrhage the appearance is
complex or solid. Rupture can result in ascites.
• Fetal ovarian cysts are sensitive to placental hormones and are more common in
diabetic or rhesus isoimmunised mothers as a result of placental hyperplasia.
• Large ovarian cysts (>6 cm in diamater) can cause polyhydramnios due to
compression of the bowel.
• Most cases are sporadic and there is no association with chromosomal
abnormalities.
• A few cases are associated with genetic syndromes. The most common
is McKusick - Kaufman syndrome (automosomal recessive; hydrometrocolpos,
polydactyly, heart defects).
• Other defects, mainly genitourinary (renal agenesis, polycystic kidneys) and
gastrointestinal (esophageal atresia, duodenal atresia and imperforate anus), are
often found.
Investigations:
Follow up:
• Ultrasound scans every 4 weeks to monitor the evolution of the cyst. If the cyst is
>6 cm ultrasound guided aspiration should be considered.
Delivery:
• Place: hospital with neonatal intensive care and facilities for pediatric surgery
• Time: 38 weeks.
Prognosis:
• The majority of cysts are benign and resolve spontaneously in the neonatal period.
Surgery may be necessary if there is torsion.
Recurrence:
Urogenital sinus
Prevalence:
•1 in 250,000 births.
• Presacral cystic mass in the pelvis of a female fetus, due to a common channel for
urinary and genital tracts. The mass represents hydrometrocolpos, distended
vagina and a compressed, anteriorly located bladder with varying degrees of
urinary obstruction. The contents may be clear (urine) or turbid (hemorrhage).
Ascites may result from escape of urine through the Fallopian tubes into the
abdomen.
• Normal amount of the amniotic fluid.
increased.
• Other defects, mainly of the genitourinary tract (bicornuate uterus, cervical atresia,
vaginal atresia or duplication, hydronephrosis, renal agenesis, multicystic
kidneys) gastrointestinal tract (imperforate anus, esophageal atresia) and
cardiovascular system, are often found.
Investigations:
Follow up:
Delivery:
• Time: 38 weeks.
Prognosis:
• Neonatal evaluation of the exact anatomical picture and investigation for other
anomalies of the genital and urinary tracts. Reconstructive surgery is necessary.
Most patients are continent and fertile, but about 50% require intermittent
catheterization.
Recurrence:
EXTREMITIES: Topics in this section

• Limb deficiency or amputation
• Amniotic band syndrome
• Arthrogryposis
• Clinodactyly
• Clubfoot
• Clubhands
• Ectrodactyly
• Polydactyly
• Syndactyly
Limb deficiency or amputation

Prevalence:
General principles:
• In 50% of cases there are transverse reduction deficiencies of one forearm or hand
without associated anomalies.
• In 50% of cases there are multiple reduction deficiencies and in 25% of these there
are additional anomalies of the internal organs or craniofacial structures.
• Amputation of the upper extremity is usually an isolated anomaly, whereas
amputation of the leg or bilateral amputations of all limbs are usually part of a
genetic syndrome.
• Isolated amputation of an extremity can be due to amniotic band syndrome,
exposure to a teratogen or a vascular accident.
• If the defect is unilateral, it may correspond to the femur–fibula–ulna or femur–
tibia–radius complex. The former is non-familial, while the second has a strong
genetic component.
Phocomelia:
• Hands and feet are present (may be normal or abnormal), but the intervening arms
and legs are absent.
• Three syndromes must be considered in the differential diagnosis of phocomelia:
• Roberts syndrome: autosomal recessive; tetraphocomelia, bilateral facial cleft,
micrognathia, hypertelorism, ear and nose malformations.
• Thrombocytopenia with absent radius (TAR) syndrome: autosomal recessive;
absence of radius bilaterally associated with thrombocythopenia,
• Grebe syndrome: autosomal recessive disorder described in the inbred Indian
tribes of Brazil. Characterized by marked hypomelia of upper and lower limbs,
increasing in severity from proximal to distal segments. In contrast to Roberts
syndrome, the lower limbs are more affected than the upper extremities.
Congenital short femur:
Classified into five groups:
1. Simple hypoplasia of the femur
2. Short femur with angulated shaft
3. Short femur with coxa vara: this is the most common and is due to deformity of the
hip, whereby the angle between the head and the shaft of the femur is reduced to
less than 120 degrees.
4. Absent or defective proximal femur.
5. Absent or rudimentary femur.
• One or both femurs can be affected but the right one is more frequently involved.`
• Femoral hypoplasia–unusual facies syndrome, which is sporadic, consists of
bilateral femoral hypoplasia and facial defects, including short nose with broad
tip, long philtrum, micrognathia and cleft palate.
Amniotic band syndrome

Prevalence:
• Spectrum of features involving extremities, craniofacial region and trunk, which
may be isolated or appear in combination. Demonstration of bands in not
necessary for the diagnosis of amniotic band syndrome.
• Extremities: absent digits or portions of limbs, swollen distal arm or leg resulting
from constrictive amniotic bands.
• Craniofacial region: facial cleft, asymmetric microphthalmia, severe nasal
deformity, encephalocele.
• Trunk: severe spinal deformities, large abdominal wall defects with herniated
intestine. The most extreme manifestation is body stalk anomaly.
increased.
Investigations:
Follow up:
• Ultrasound scans every 2-3 weeks to assess the evolving consequences of the
bands.
Fetal therapy:
• In a few cases fetoscopic lysis of the bands has been used in cases of constriction
of the umbilical cord or threatened limb amputations.
Delivery:
Prognosis:
• Prognosis and treatment depends on the nature of amniotic band syndrome and
the severity of deformation. Facial deformities often require extensive
reconstructive procedures.
• Body stalk anomaly is lethal.
Recurrence:
Arthrogryposis
Prevalence:
• Malposition of the limbs and limited fetal movements, resulting from contractures in
≥2 joints.
• Onset of arthrogryposis varies: from 12 to 30 weeks’ gestation.
• The condition is commonly associated with polyhydramnios (>25 weeks' gestation),
narrow chest, micrognathia and nuchal edema (or increased nuchal translucency
at 11-13 weeks).
• Fixed abnormal contractures of muscles can be:
• Regional: only the lower or upper limbs are affected. If the lower region is affected,
the legs are hyperextended and crossed. If the upper region is affected, the arms
are flexed lying on each side of the thorax.
• Generalized: all muscles are affected as in fetal akinesia deformation sequence.
• Chromosomal abnormalities: a few cases have trisomy 8 or 18.
• More than 150 genetic syndromes are associated with arthrogryposis. The most
common are:
• Fetal akinesia deformation sequence: group of abnormalities of different
causes characterized by decreased fetal movements, multiple
joint contractures, fetal growth restriction, facial anomalies, pulmonary hypoplasia
and occasionally hydrops.
• Cerebro-oculo-facio-skeletal syndrome: autosomal recessive; severely reduced
muscle tone, distinctive facial features (low-set ears, microphthalmia,
micrognathia) and abnormalities of the skull, limbs, heart, and kidneys.
• Neu-Laxova syndrome: autosomal recessive; hypertelorism, microcephaly,
agenesis of corpus calosum, contractures in the upper and lower limbs, fetal
growth restriction.
• Multiple pterygium syndrome: autosomal recessive; cystic hygromas,
contractures in all joints, microcephaly and micrognathia.
Investigations:
• Detailed medical history should be obtained concerning infection, fever or
hypothermia and exposure to teratogens such as phenytoin and ethanol.
• Myotonic dystrophy or myastenia gravis should be ruled out.
Follow up:
• Ultrasound scans every 2-3 weeks to monitor growth, movements in all joints and
amniotic fluid volume. Amniodrainage may be necessary if there is
Delivery:
• Place: hospital with facilities for neonatal intensive care.
• Delivery by elective cesarean section due to possible complications resulting from
abnormal fetal position and lack of flexibility of the limbs.
Prognosis:
• If multiple organs are affected there is high mortality within the first months of life.
• If only limbs are affected, surgery and physiotherapy aim to achieve the maximum
function for each involved joint.
Recurrence:
• Depends on the underlying condition.
• Distal arthrogryposis: 50%.
Clinodactyly
Prevalence:
•1 in 100 births.
• Medial deviation or radial curving of the finger at the distal interphalangeal joint
usually affecting the fifth finger.
• Chromosomal abnormalities: bilateral clinodactyly is found in 60% of newborns
with trisomy 21.
• The condition is usually isolated.
Investigations:
• Invasive testing and array is recommended in non-isolated cases.
Follow up:
Delivery:
Prognosis:
• Isolated cases: good prognosis. No need for postnatal surgery.
Recurrence:
• Isolated familial: 50%.
• Part of trisomy 21: 1%
Clubfoot
Prevalence:
• Bilateral in 50% of cases.
• Demonstration that the sole of the foot is not perpendicular to the lower leg bones.
• In >50% of cases the condition is isolated.
• Chromosomal abnormalities: common finding in trisomies 18 and 13.
• Commonly associated with prolonged oligohydramnios, brain abnormalities, spina
bifida, skeletal and neuromuscular disorders.
• More than 250 genetic syndromes include clubfoot as one component.
Investigations:
• Non-isolated cases: invasive testing and array.
Follow up:
• Isolated: standard follow-up.
Delivery:
Prognosis:
• Isolated: good prognosis.
• In 90% of cases good long-term function is achieved by manipulation and serial
application of casts, supported by limited operative intervention.
• Surgery is necessary in about 10% of cases and in one third more than one
operation is needed.
Recurrence:
• One sibling with clubfoot: 3%.
• Parent and one child with clubfoot: 25%.
Clubhands
Prevalence:
• Bilateral in 50% of cases.
• Clubhand deformities are subdivided into radial and ulnar:
• Radial clubhand: radial aplasia, acute radial deviation of the hand and absent or
hypoplastic thumb.
• Ulnar clubhand: ranges from mild deviation of the hand on the ulnar side of the
forearm to complete absence of the ulna.
• Ulnar clubhand is usually an isolated anomaly, whereas, radial clubhand is
frequently syndromatic:
• Trisomy 18: radial clabhand is a common finding in this chromosomal abnormality.
• Thrombocytopenia - absent radius (TAR) syndrome: radial aplasia, thumb
present, heart defects, micrognathia.
• Holt - Oram syndrome: radial aplasia, syndactyly, heart defects.
• Roberts syndrome: radial aplasia, phocomelia, facial cleft, heart defects.
• VACTER association: radial aplasia or hypoplasia, vertebral abnormalities,
ventricular septal defect, tracheoesophageal fistula, anal atresia, renal defects,
and single umbilical artery.
Investigations:
Follow up:
• Follow-up scans every 4 weeks.
• In families with history of TAR syndrome: cordocentesis for diagnosis of
hematologic abnormalities.
Delivery:
• Standard obstetric care, but delivery should be in a hospital with neonatal intensive
care..
Prognosis:
• Depends on the associated condition.
• Surgical treatment and physiotherapy aim to improve mobility, strength, and
stability of the forearm and wrist.
Recurrence:
• Part of genetic syndromes: 25% or 50%.
Ectrodactyly
Prevalence:
• Spectrum of hand and foot defects with missing digits, median cleft and fusion of
the remaining digits resulting in clawlike extremities.
• Chromosomal abnormalities: found in trisomy 18.
• High incidence of genetic syndromes. The most common are:
• Roberts syndrome: autosomal recessive; ectrodactyly, phocomelia, facial cleft.
• Ectrodactyly - ectodermal dysplasia (EEC): autosomal dominant; deferomities of
all four extremities but more severe in the hands, and ectodermal defects (dry
skin, sparse hair, dental defects and defects of the tear ducts).
• Nager syndrome: autosomal dominant but in most cases de novo
mutations; ectrodactyly, micrognathia, external ear anomalies.
• Split hand and foot malformation: ectrodactyly presenting as ‘lobster claw’
anomaly.
Investigations:
Follow up:
• Standard follow-up.
• Consultation by a clinical geneticist.
Delivery:
Prognosis:
• Isolated: good prognosis.
• Surgical treatment and physiotherapy reduce functional impairment of the hands.
Recurrence:
Polydactyly
Prevalence:
•1 in 100 births in Blacks and 1 in 700 births in Whites.
• More common in males than in females: 2 to 1.
• More than 5 digits with or without bony phalanx in the hand or foot.
• There are 2 types of polydactyly:
• Postaxial (more common): sixth digit is on the ulnar or fibular side, after the fifth
digit.
• Preaxial (rare): sixth digit is on the radial or tibial side, before the thumb or toe.
• Chromosomal abnormalities: found in 75% of fetuses with trisomy 13.
• In most cases it is an isolated finding, with an autosomal dominant mode of
inheritance. In some cases there is an association with genetic syndromes:
• Meckel - Gruber syndrome: autosomal recessive; polydactyly, polycystic kidneys,
occipital cephalocele.
• Bardet - Biedl syndrome: autosomal recessive; postaxial polydactyly, enlarged
hyperechogenic kidneys. Postnatally: obesity, retinopathy, hypogonadism,
neurological disorders.
• Short - rib polydactyly syndrome: autosomal recessive; short limbs, hypoplastic
thorax, polydactyly, heart and brain defects, polycystic kidneys.
• Ellis – van Creveld syndrome: autosomal recessive; short limbs, postaxial
polydactyly, narrow chest, heart defects.
Investigations:
• Invasive testing and array in non-isolated cases.
• Consultation with clinical geneticist.
Follow up:
• In isolated cases, follow-up should be standard.
Delivery:
Prognosis:
• Isolated cases: good prognosis.
Recurrence:
• Part of autosomal recessive syndromes: 25%.
Syndactyly
Prevalence:
• Two or more digits (bone or soft tissue) are fused together.
• Chromosomal abnormalities: common finding in triploidy.
• In most cases it is an isolated finding, but there is a common association with
genetic syndromes:
• Apert syndrome: autosomal dominant; brachysyndactyly of hands and feet,
craniosynostosis, hypertelorism, heart defects.
• Carpenter syndrome: autosomal recessive; polysyndactyly, craniosynostosis.
• Fraser syndrome: autosomal recessive; microphthalmia, facial cleft, tracheal
atresia, bilateral renal agenesis, heart defects, syndactyly or polydactyly.
Investigations:
Follow up:
Delivery:
Prognosis:
• Isolatedcases: good prognosis.
Recurrence:
• Isolated familial polysyndactyly: 50%.
• Part of Apert syndrome: 50%.
• Part of Carpenter and Fraser syndrome: 25%.
• Part of triploidy: no increased risk.
SKELETON: Topics in this section

• Skeletal dysplasia
• Achondrogenesis
• Achondroplasia
• Asphyxiating thoracic dystrophy

• Atelosteogenesis
• Campomelic dysplasia
• Craniosynostosis
• Diastrophic dysplasia
• Ellis-Van Creveld syndrome
• Hypophosphatasia
• Jarcho-Levin syndrome
• Osteogenesis imperfecta
• Short rib polydactyly syndrome
• Thanatophoric dysplasia
Skeletal dysplasia
Prevalence:
• 25% are stillborn and 30% die in the neonatal period.
Approach to prenatal diagnosis:
• There is a wide range of rare skeletal dyplasias, each with a specific recurrence
risk, dysmorphic expression, and implications for neonatal survival and quality of
life.
• The incidental discovery of a skeletal dysplasia on routine ultrasound screening, in
a pregnancy not known to be at risk of a specific syndrome, necessitates a
systematic examination of the limbs, head, thorax and spine to arrive at the
correct diagnosis.
Assessment of long bones:
• Shortening of the extremities can involve the entire limb (micromelia), the
humerus or femur (rhizomelia), the radius, ulna, tibia or fibula (mesomelia) or the
hands and feet (acromelia). The femur is abnormally short even in mesomelic
dwarfism and, therefore, in routine fetal abnormality screening the femur is
measured and compared subjectively to all long bones. Severe limb reductions,
as in thanatophoric dwarfism and achondrogenesis can be detected from 16
weeks’ gestation, whereas in achondroplasia limb shortening becomes obvious
>22 weeks.
• Abnormal shape. In some conditions there is pronounced bowing (e.g.
campomelic dysplasia, thanatophoric dwarfism), and in others fractures and
callus formation may also be detected (e.g. osteogenesis imperfecta,
achondrogenesis and hypophosphatasia).
• Reduced echogenicity of bones due to hypomineralization is seen in some
disorders (e.g. hypophosphatasia, osteogenesis imperfecta and
achondrogenesis). Virtual absence of ossification of the spine in
achondrogenesis, may lead to the erroneous diagnosis of complete spinal
agenesis. Poor mineralization of the skull in hypophosphatasia, may result in the
misdiagnosis of hydrocephalus.
• Absence of extremities, such as amelia (complete absence of extremities),
acheiria (absence of the hand), phocomelia (seal limb) or aplasia–hypoplasia of
the radius or ulna, are often inherited as part of a genetic syndrome (Holt–Oram
syndrome, thrombocytopenia with absent radii syndrome). Another cause of focal
limb loss is the amniotic band syndrome.
Evaluation of hands and feet:
• Several skeletal dysplasias are associated with alterations of the hands and feet.
• Polydactyly: presence of more than five digits. It is classified as postaxial if the
extra digits are on the ulnar or fibular side and preaxial if they are located on the
radial or tibial side.
• Syndactyly: soft tissue or bony fusion of adjacent digits.
• Clinodactyly: deviation of a finger(s).
• Disproportion between hands and feet and the other parts of the extremity may
also be a sign of a skeletal dysplasia.
Examination of fetal movements:
• Arthrogryposis and multiple pterygium syndrome are characterized by limitation of
flexion or extension of the limbs.
Evaluation of the fetal thorax:
• Several skeletal dysplasias are associated with a small thorax, which leads to
pulmonary hypoplasia and neonatal death. The diagnosis of a small thorax can
be made by examining the thoracic-to-abdominal circumference ratio or the
thoracic-to-head circumference ratio. The thoracic circumference is measured at
the level of the four-chamber view of the heart.
Evaluation of the fetal head:
• Several skeletal dysplasias are associated with reduced ossification of the skull
bones. The face should also be examined for the diagnosis of hypertelorism,
micrognathia, short upper lip, and abnormalities of the ears.
Diagnostic tests complementary to sonography:
• Prenatal or postnatal evaluation includes DNA analysis for an increasing number of
skeletal dysplasia. Some can now be diagnosed by cfDNA testing of maternal
blood. Postnatally, examination of skeletal radiographs is of particular
importance, since the classification of skeletal dysplasias is largely based on
radiographic findings.
Achondrogenesis
Prevalence:
• Second most common lethal skeletal dysplasia, after thanatophoric dysplasia.
• Severe shortening of the limbs, narrow thorax, short trunk length and large head.
• Associated with micrognathia, nuchal edema and polyhydramnios.
• There are 2 types of achondrogenesis:
• Type I (20%): autosomal recessive; there is poor mineralization of the skull and
vertebral bodies, as well as rib fractures.
• Type II (80%): sporadic; there is poor mineralization of the vertebral bodies but not
the skull and there are no rib fractures.
Investigations:
• Achondrogenesis is due to mutations in SLC26A2, COL2A1 and TRIP11 genes.
Follow up:
Delivery:
Prognosis:
• The condition is lethal due to severe pulmonary hypoplasia.
Recurrence:
• Type I: 25%
• Type II: no increased risk.
Achondroplasia
Prevalence:
• Short limbs, short hands and fingers, large head with frontal bossing and
depressed nasal bridge, and lumbar scoliosis.
• Limb shortening and typical facial features become apparent >22 weeks’ gestation.
Investigations:
• Achondroplasia is due to a mutation in the FGFR3 gene and has autosomal
dominant inheritance pattern. The diagnosis can be made by invasive testing or
cfDNA analysis of maternal blood.
Follow up:
• Follow-up scans every 4 weeks to monitor growth of the fetal head.
Delivery:
Prognosis:
• Homozygotic type: lethal due to severe pulmonary hypoplasia.
• Heterozygotic type: intelligence and life expectancy are normal. Respiratory
limitations due to small thorax and development of stenotic vertebral canal
(peripheral neurologic deficits) may decrease the quality of life.
Recurrence:
• One affected parent: 50%.
• If both parents are affected: 50% risk of heterozygous achondroplasia, 25% risk of
homozygous achondroplasia and 25% chance of unaffected child.
• De novo mutation: low recurrence risk.
Asphyxiating thoracic dystrophy

Prevalence:
• Phenotypic expression varies. Characteristic features are short narrow chest with
short ribs and mild to moderate rhizomelic (femur and humerus) limb shortening,
which may become apparent >22 weeks’ gestation.
• The condition is also referred to as Jeune syndrome.
• Renal anomalies.
Investigations:
• Mutations in >10 genes have been identified, but 50% of cases are due to mutation
in the DYNC2H1 gene.
Follow up:
Delivery:
Prognosis:
• Neonatal mortality: 60% due to pulmonary hypoplasia.
• Surviving neonates have normal intelligence but rarely live beyond their teens
because renal and cardiovascular problems.
Recurrence:
• Autosomal recessive inheritance: 25%.
Atelosteogenesis
Prevalence:
•1 in 500,000 births.
• Severe shortening of the limbs, narrow thorax, clubfeet, dislocations of the hips,
knees, and elbows.
• Associated with prominent forehead, hypertelorism, micrognathia and cleft palate
and ‘hitchhiker thumbs’’. The features are similar, but more severe, to those of
diastrophic dysplasia.
Investigations:
• Atelosteogenesis is due to mutations in the FLNB and SLC26A2 genes.
• If the mutation in the family is known, prenatal diagnosis is best performed by
chorion villus sampling and DNA analysis.
Follow up:
Delivery:
Prognosis:
• Lethal in utero or shortly after birth due to respiratory failure.
Recurrence:
• In the majority of cases (de novo mutations): no increased risk.
• In the rare cases of autosomal recessive inheritance: 25%.
Campomelic dysplasia
Prevalence:
•1 in 200,000 births.
• Shortening and bowing of the long bones of the legs (bilateral acute femoral
angulation), narrow chest, hypoplastic scapulas, large calvarium with
disproportionately small face, micrognathia.
• Nuchal edema, clubfeet, hydrocephalus (due to atlanto-occipital occlusion).
Polyhydramnios is common.
Investigations:
• There is sex reversal in about 70% of male fetuses and invasive testing is
necessary to determine the genetic sex.
• Campomelic dysplasia is caused by mutations in or near the SOX9 gene.
Follow up:
Delivery:
• Standard obstetric care and delivery should be in a tertiary center.
Prognosis:
• Mortality in the first year of life: 95%, due to severe laryngeotracheomalacia.
Recurrence:
• In the majority of cases (de novo mutations): no increased risk.
• In the rare cases of autosomal recessive inheritance: 25%.
Craniosynostosis
Prevalence:
• Associated with advanced paternal age.
• Premature fusion of cranial sutures resulting in abnormal shapes of the cranium.
• In 90% of cases, craniosynostosis is an isolated finding.
• In 10% of cases, there is an association with any one of 150 syndromes, including,
Crouzon syndrome, Muenke syndrome, Saethre-Chotzen syndome, Apert
syndrome, Pfeiffer syndrome
Investigations:
• Detailed ultrasound examination. Special attention should be paid to fetal hands,
midface, heart and central nervous system.
• Fetal MRI provides useful information.
• Detailed family history and consultation with geneticist: if the family history is
negative for isolated craniosynostoses, prenatal karyotyping to rule out
chromosomal abnormalities is recommended.
• Craniosynostosis is caused by mutations in the FGFR-2, FGFR-3,
TWIST, and EFNB-1 genes.
Follow up:
Delivery:
• Standard obstetric care and delivery in tertiary center,
Prognosis:
• Newborns might have difficulties with breathing, feeding and vision.
• Increased intracranial pressure, which is present in one third of the newborns,
might affect intelligence and neurodevelopment. Optimal timing for surgical repair
should be planned.
Recurrence:
• De novo mutations: no increased risk of recurrence.
• Syndromic forms with positive family history: 25% and 50% risk of recurrence
depending on the associated syndrome.
Crouzon syndrome
Prevalence:
• Variable craniosynostosis (most often bicoronal), midface hypoplasia with “beaked”
nasal tip, mandibular prognathism, and exorbitism (protrusion of the eyeballs as
a result of shallow orbits).
• Normal hands and feet.
Investigations:
• Autosomal dominant inheritance of mutation in the FGFR2 gene. The diagnosis
can be made by invasive testing.
Prognosis:
• Most affected individuals are of normal intelligence.
• Bulging eyes and vision problems.
Muenke syndrome
Prevalence:
• Coronal craniosynostosis.
• Mild abnormalities of the hands and feet, including carpal and tarsal fusion,
brachydactyly, thimble-like middle phalanges and cone-shaped epiphyses.
Investigations:
Prognosis:
• Most affected individuals are of normal intelligence, but some have delayed
development and learning difficulties.
Saethre-Chotzen syndrome
Prevalence:
• Uni- or bicoronal craniosynostosis, facial asymmetry, deviation of the nasal septum,
a low frontal hairline, and small, low set, and posteriorly rotated ears.
• Brachydactyly and partial cutaneous syndactyly of the toes.
Investigations:
• Autosomal dominant inheritance of mutation in the TWIST1 gene. The diagnosis
Prognosis:
• Most affected individuals are of normal intelligence, but some have delayed
development and learning difficulties.
Apert syndrome
Prevalence:
• Bicoronal craniosynostosis resulting in brachycephaly, ‘towering skull deformity’,
hypertelorism, frontal bossing.
• Brachysyndactyly of hands and feet.
• Other abnormalities: ventricular septal defect, fusion of cervical vertebrae,
agenesis of corpus callosum, hydronephrosis and cryptorchidism.
Investigations:
Prognosis:
• 50% chance of mental retardation.
• Need for surgery for synostosis and syndactyly.
Pfeiffer syndrome
Prevalence:
• Multisutural craniosynostosis (cloverleaf-shaped skull) and midface hypoplasia with
associated hypertelorism and exorbitism.
• Broad, radially deviated thumbs, broad great toes,
Investigations:
• Autosomal dominant inheritance of mutation in the FGFR1 and FGFR2 genes. The
diagnosis can be made by invasive testing.
Prognosis:
• Type I: favourable prognosis, normal intelligence.
• Type II: poor neurologic prognosis.
Diastrophic dysplasia
Prevalence:
•1 in 500,000 births.
• Phenotypic expression varies. Characteristic features include severe shortening
and bowing
of all long bones, multiple joint flexion contractures and scoliosis, clubfeet, and
abducted position of the thumbs referred to as ‘hitchhiker thumb’.
• Micrognathia, cleft palate and thickened deformed ‘cauliflower’ ears.
Investigations:
• Diastrophic dysplasiais one of several skeletal disorders caused by mutations in
the SLC26A2 gene.
Follow up:
Delivery:
Prognosis:
• This disease is not lethal and neurodevelopment is normal.
• Long-term medical problems include short stature, progressive scoliosis and joint
deformities making it difficult to walk.
Recurrence:
Ellis-Van Creveld syndrome

Prevalence:
•1 in 100,000 births.
• Acromelic and mesomelic shortness of limbs, postaxial polydactyly, narrow chest,
ectodermal dysplasia and heart defects.
• Heart defects are present in >50% of cases: single atrium, large atrioseptal defect,
aortic atresia, hypoplastic ascending aorta, hypoplastic left ventricle
Investigations:
• Ellis-vanCreveld syndrome is caused by mutations in the EVC or EVC2 gene.
Follow up:
Delivery:
Prognosis:
• Neonatal mortality: 50% due to pulmonary hypoplasia and cardiac problems.
• The overall prognosis for affected patients is related to the presence or absence of
cardiac abnormalities. Intelligence is normal.
Recurrence:
Hypophosphatasia
Prevalence:
• Hypophosphatasiais an inherited disorder that affects the development of bones
and teeth. It can appear any time from before birth to adulthood.
• Prenatal type: 1 in 100,000 births.
• Postnatal type: 1 in 10,000 births
• In the prebatal type there is severe micromelia, severe thoracic hypoplasia, diffuse
hypomineralization (decreased echogenicity) involving all the bones except for
clavicles.
Investigations:
• Hypophosphatasia is due to mutations in the ALPL gene which lead to the
production of an abnormal version of alkaline phosphatase that cannot
participate effectively in the mineralization process. The degree of malfunction
varies: the severity ranges from unapparent cases diagnosed on the basis of
biochemical features to the lethal cases detected in the fetus.
• If the mutation in the family is known, prenatal diagnosis is best performed by
chorion villus sampling and DNA analysis.
Follow up:
Delivery:
Prognosis:
• Prenatal type: lethal due to severe pulmonary hypoplasia.
• Postnatal type: can appear in childhood or adulthood. Affected children may have
short stature with bowed legs or knock knees, enlarged wrist and ankle joints,
and an abnormal skull shape. In adults, there is premature loss of teeth and
recurrent fractures in the foot and thigh bones causing chronic pain.
Recurrence:
• Prenatal type is autosomal recessive: 25%.
• Postnatal type is either autosomal recessive or autosomal dominant: 25% or 50%
Jarcho-Levin syndrome
Prevalence:
•1 in 200,000 births.
• Also referred to as spondylothoracic dysostosis and short trunk dwarfism.
• Fusion of several vertebral bodies and misalignment with the ribs which are also
fused at the part nearest the spine. The trunk is short, but the arms and legs are
of normal length.
Investigations:
• Jarcho-levin syndrome is due to mutations in the MESP2 gene.
Follow up:
Delivery:
• Standard obstetric care and delivery in a tertiary center, because the neonate may
require resuscitation in the delivery room due to pulmonary hypoplasia.
Prognosis:
• About 40% die in the first few months due to pulmonary hypoplasia and
hypertension. After the second year of life the condition improves.
Neurodevelopment is normal.
Recurrence:
Osteogenesis imperfecta
Prevalence:
• The most common are types I and IV.
• Spectrum of the defects characterized by fragile bones.
• There are at least eight recognized forms of osteogenesis imperfecta, designated
type I through type VIII with overlapping characteristic features. Type I is the
mildest form and type II is the most severe; signs and symptoms of the other
types fall somewhere between these two extremes.
• Most cases that present prenatally are types II and III:
• Type I: fragile bones, blue sclerae and progressive deafness. Ultrasonography in
the second and third trimesters may demonstrate fractures of long bones.
• Type II: short limbs and ribs with multiple fractures, hypomineralization of the skull.
• Type III: multiple fractures, usually present at birth, resulting in scoliosis and very
short stature.
Investigations:
• Detailed family history and consultation with geneticist.
• Osteogenesis imperfecta is caused by mutations in
the COL1A1, COL1A2, CRTAP, and P3H1 genes.
• Prenatal diagnosis of types II, III, and IV can be made by invasive testing.
Follow up:
Delivery:
• Standard obstetric care and delivery in a tertiary center.
Prognosis:
• Type I: normal life expectancy.
• Type II: lethal.
• Type III: motor disability (kyphoscoliosis, fractures), hearing loss in adulthood.
Recurrence:
• De novo Most cases of osteogenesis imperfecta have an autosomal dominant
pattern of inheritance, but most infants with more severe forms of the condition
(types II and III) are caused by new mutations.
Short rib polydactyly syndrome

Prevalence:
•1 in 500,000 births.
• Micromelia, short ribs with hypoplastic thorax, polydactyly (usually preaxial).
• There are four types of short-rib polydactyly syndrome:
• Type I (Saldino-Noonan): narrow metaphyses.
• Type II (Majewski): facial cleft and disproportionally shortened tibiae.
• Type III (Naymoff): wide metaphyses with spurs.
• Type IV (Beemer-Langer): median cleft lip and ambiguous genitalia in some
46,XY individuals.
• Heart defects, polycystic kidneys, brain malformations and intestinal atresia.
Investigations:
Follow up:
Delivery:
Prognosis:
Recurrence:
Thanatophoric dysplasia
Prevalence:
• Most common lethal skeletal dysplasia.
• Severe shortening of the limbs, narrow thorax, normal trunk length and large head
with prominent forehead.
• There are 2 types of thanatophoric dysplasia:
• Type I (more common): sporadic, the femurs are curved (telephone receiver).
• Type II (rare): sporadic, the femurs are straight but the skull is cloverleaf-shaped.
Investigations:
• Thanatophoric dysplasia is due to a mutation in the FGFR3 gene. The diagnosis
can be made by invasive testing or cfDNA analysis of maternal blood.
Follow up:
Delivery:
• Pregnacies are often complicated by polyhydramnios, prematurity, malpresentation
and cephalopelvic dysproporion. The presence of the cloverleaf deformity and
hydrocephalus may require cephalocentesis and assisted delivery.
Prognosis:
Recurrence:
• No increased risk.
HYDROPS FETALIS: Topics in this section
Overview
Prevalence:
• Abnormal accumulation of serous fluid in at least two of the following: skin (edema)
and body cavities (pericardial, pleural, or ascitic effusions).
• Placentomegaly (placental thickness >6 cm) is often present.
Etiology:
• Non-specific finding in a wide variety of fetal and maternal disorders, including
hematological, chromosomal, cardiovascular, renal, pulmonary, gastrointestinal,
hepatic and metabolic abnormalities, congenital infection, neoplasms,
malformations of the placenta or umbilical cord and genetic syndromes.
• Classically divided into:
• Immune: 10% of cases and it is due to maternal hemolytic antibodies.
• Non-immune: 90% of cases and it is due to all other etiologies.
Investigations:
• In many instances, the underlying cause may be determined by maternal antibody
and infection screening, fetal ultrasound scanning, including echocardiography,
Doppler studies, fetal blood sampling and amniocentesis for karyotyping and
array.
• Often the abnormality remains unexplained even after expert post mortem
examination.
Fetal therapy:
• Fetal anemia: intrauterine blood transfusions.
• Pleural effusions or large pulmonary cyst: insertion of thoracoamniotic shunts.
• Fetal tachyarrhythmias: transplacental or direct fetal administration of
antiarrhythmic drugs.
• Teratomas, chorioangiomas, pulmonary sequestration: ultrasound-guided laser
coagulation of feeding vessel.
• Recipient fetus in twin-to-twin transfusion syndrome: endoscopic laser coagulation
of the communicating placental vessels.
Follow up:
• Scans every 2-3 weeks to monitor the evolution of hydrops.
• There is a risk of maternal morbidity due to the ‘mirror syndrome’ (combination of
fetal hydrops with generalized fluid overload and a preeclamptic state in the
mother).
Delivery:
• Timing and method of delivery depend on the cause of hydrops.
Prognosis:
• Depends on the cause of hydrops.
• Progressive unexplained hydrops is often lethal before or soon after birth.
Recurrence:
• Fetal defects, infection: no increased risk of recurrence.
• Red blood cell isoimmunisation: high.
• Metabolic disorders: 25%.
CHROMOSOMAL DEFECTS: Topics in this section

• Features
• Management
Features
The commonest chromosomal defects are trisomies 21, 18 or 13, sex
chromosomal defects (45,X, 47,XXX, 47,XXY, 47,XYY) and triploidy.
In the first trimester, a common feature of many chromosomal defects is
increased nuchal translucency thickness. In later pregnancy, each chromosomal
defect has its own syndromal pattern of abnormalities.
• Trisomy 21:
Nasal hypoplasia, increased prenasal and nuchal fold thickness, cardiac defects,
intracardiac echogenic foci, duodenal atresia and echogenic bowel, mild
hydronephrosis, shortening of the femur, sandal gap and clinodactyly or mid-
phalanx hypoplasia of the fifth finger.
• Trisomy 18:
Strawberry-shaped head, choroid plexus cysts, absent corpus callosum,
enlarged cisterna magna, facial cleft, micrognathia, nuchal edema, heart defects,
diaphragmatic hernia, esophageal atresia, exomphalos, single umbilical artery,
renal abnormalities, echogenic bowel, myelomeningocoele, growth restriction
and shortening of the limbs, radial aplasia, overlapping fingers and talipes or
rocker bottom feet.
• Trisomy 13:
Holoprosencephaly, microcephaly, facial abnormalities, cardiac abnormalities,
enlarged and echogenic kidneys, exomphalos and post axial polydactyly.
• Triploidy:
When there is double paternal contribution (diandric) there is a molar placenta
and the pregnancy rarely persists beyond 20 weeks. When there is a double
maternal contribution (digynic) the placenta is thin but of normal consistency and
the pregnancy may persist into the third trimester; the fetus demonstrates severe
asymmetrical growth restriction, mild ventriculomegaly, micrognathia, cardiac
abnormalities, myelomeningocoele, syndactyly, and 'hitch-hiker' toe deformity.
• Turner syndrome:
Large cystic hygromas, generalised edema, mild pleural effusions and ascites,
cardiac abnormalities and horseshoe kidneys.
• 47,XXX, 47,XXY or 47,XYY:
These are not associated with an increased prevalence of sonographically
detectable defects.
Management
When an abnormality suggestive of a chromosomal defect is detected a
thorough check should be made for the other features of the chromosomal defect
known to be associated with that marker.
• Multiple abnormalities:
The risk for chromosomal defects is substantially increased and fetal karyotyping
should be considered.
• Isolated abnormalities:
The decision of whether to carry out an invasive test depends on whether the
abnormality is major or minor.
• If there is a major abnormality it is advisable to offer fetal karyotyping, even if
these abnormalities are apparently isolated. This is because: first, if the
abnormalities are either lethal or they are associated with severe handicap (e.g.
holoprosencephaly), fetal karyotyping constitutes one of a series of investigations
to determine the possible cause and thus the risk of recurrence, and second, if
the abnormality is potentially correctable by intrauterine or postnatal surgery (e.g.
diaphragmatic hernia), it is important to exclude an underlying chromosomal
defect – especially because, for many of these conditions, the usual defect is
trisomy 18 or 13.
• If there is a minor abnormality the estimated risk can be derived by multiplying
the a priori risk (based on the results of previous screening) by the likelihood ratio
of the specific abnormality or marker. The likelihood ratio for trisomy 21 is about 1
(therefore the a priori risk is not increased in the case of choroid plexus cysts,
echogenic endocardiac focii, mild hydronephrosis and short femur) and about 10
(therefore there is a 10-fold increase in the a priori risk for nuchal or prenasal
edema and hypoplastic nasal bone).
TUMORS: Topics in this section
• Lymphangioma
• Neuroblastoma
Lymphangioma
Prevalence:
• Multiseptated, multicystic irregular mass, which is usually located on the neck
(75%), axillary region (20%), chest wall, abdominal wall and extremities (5%); in
<1% of cases the tumor is in the mesentery or retroperitoneum.
increased.
Investigations:
• In case of cervical and thoracic lymphangioma, there is an increased risk of central
venous compression leading to hydrops and esophageal compression resulting
in polyhydramnios.
Follow-up:
• Ultrasound scans every 2-3 weeks to monitor the size of the tumor and assess
amniotic fluid volume. Amniodrainage may be necessary if there is
Delivery:
• Time: 38 weeks.
• Method: cesarean section with EXIT procedure if there is polyhydramnios and
hyperextension of the neck due to a large cervical tumor.
Prognosis:
• Prognosis is favourable, unless there is associated cardiac failure, hydrops or high
airway compression.
• Some mesenchymal lesions may partially regress spontaneously after birth. The
treatment of choice is surgical excision.
Recurrence:
Neuroblastoma
Prevalence:
• Arises from undifferentiated neural tissue of the adrenal medulla (90%) or
sympathetic ganglia in the abdomen, thorax, pelvis, or head and neck (10%).
• Cystic, solid, or complex mass in the region of the adrenal gland, usually in the
third trimester. Occasionally, calcifications are present.
• Tumors arising from the sympathetic ganglia may appear in the abdomen, thorax
or neck.
• The tumor can metastasize in utero to the placenta, umbilical cord or liver.
• There may be associated polyhydramnios and fetal hydrops.
• No increased risk of chromosomal abnormalities or genetic syndromes.
Investigations:
• MRI to detect possible intraspinal extension of the tumor.
Follow up:
• Ultrasound scans every 4 weeks to monitor the size of the tumor and development
of development of hepatomegaly, placentomegaly, heart failure and
polyhydramnios.
Delivery:
• Time: 38 weeks.
Prognosis:
• Survival is >90% if the diagnosis is made in utero or in the first year of life, but
<20% for those diagnosed after the first year. Treatment requires surgical
excision of the tumor and chemotherapy.
Recurrence:
PLACENTA, UMBILICAL CORD: Topics in this section

• Chorioangioma
• Morbid adherent placenta

• Single umbilical artery
• Umbilical cord cyst
• Umbilical cord knot
• Vasa previa
Chorioangioma
Prevalence:
• Hypo- or hyperechoic, well-circumscribed mass, which is usually located
underneath the chorionic plate near the umbilical cord insertion, and often
protrudes into the amniotic cavity.
• Color Doppler demonstrates large vascular channels around and within the tumor.
preeclampsia).
Investigations:
Follow up:
Delivery:
hydrops.
• Method: induction of labor aiming for vaginal delivery, unless the fetus is hydropic
and hypoxic.
Prognosis:
• Symptomatic chorioangiomas carry a high risk of perinatal death. The neonate may
have severe microangiopathic hemolytic anemia and thrombocytopenia.
Recurrence risk:
Morbid adherent placenta

Prevalence:
• Placenta previa with history of previous cesarean section (CS): 3% for 1 CS, 10%
for 2 CS, >50% for ≥3 CS.
• A morbidly adherent placenta includes placenta accreta (chorionic villi attach to
myometrium), increta (chorionic villi invade into the myometrium) and percreta
(chorionic villi invade through the myometrium).
• Multiple vascular lacunae (spaces) within the placenta (‘Swiss cheese’
appearance) with turbulent flow (peak systolic velocity >15 cm/s),
• Retroplacental myometrial thickness of <1 mm.
• Loss of normal retroplacental hypoechogenic zone.
• Blood vessels and placental tissue bridging uterine-placental margin, myometrial-
bladder interface, or crossing uterine serosa. Exophytic masses invading the
urinary bladder.
• Irregular vascularization involving the whole uterine serosa–bladder junction,
visualised with 3-dimensional power Doppler.
Investigations:
• MRI is recommended if ultrasound findings are inconclusive.
• Fetal antenatal surveillance should be standard.
Follow up:
Delivery:
• Place: hospital with expertise in the management of this condition and a blood
bank that can facilitate transfusion of large amounts of various blood products.
There is a high chance of hysterectomy and major hemorrhage.
• Time: 36 to 37 weeks.
• Method: cesarean section.
Prognosis:
• Maternal mortality 5-10%, morbidity 75%.
• Early diagnosis reduces mortality and morbidity by 50%.
Single umbilical artery

Prevalence:
• Visualizationof only one artery around the fetal bladder.
• Chromosomal abnormalities, mainly trisomy 18, 13 and triploidy, are found in 5% of
cases.
• Fetal growth restriction (<5th percentile) occurs in 10% of cases. Stillbirth, usually
in association with growth restriction is twice as common as in the general
population.
• Abnormalities affecting cardiovascular, skeletal, gastrointestinal, genitourinary and
central nervous systems, are found in 20% of cases.
Investigations:
• Fetal karyotyping in non-isolated cases.
Follow up:
• Serial scans at 28, 32 and 36 weeks’ gestation to assess fetal growth and well-
being.
Delivery:
Prognosis:
• In isolated cases the prognosis is normal.
Recurrence risk:
Umbilical cord cyst

Prevalence:
• True cysts are derived from the embryological remnants of either the allantois or
the omphalomesenteric duct and are typically located towards the fetal insertion
of the cord.
• Pseudocysts are more common than true cysts and are located anywhere along
the cord. They have no epithelial lining and represent localized edema and
liquefaction of Wharton’s jelly.
• Single cysts are usually transient with no adverse effect.
• Multiple cysts are associated with increased risk of miscarriage, trisomies 18 and
13, omphalocele, VACTREL association and fetal growth restriction.
Investigations:
• Fetal karyotyping for non-isolated cases.
Prognosis:
• Isolated cases: normal prognosis.
Recurrence risk:
• Isolated cases: no increased risk of recurrence.
Umbilical cord knot

Prevalence:
• Visualisation of a transverse section of the umbilical cord surrounded by a loop of
umbilical cord: ‘hanging noose sign’.
• Predisposing factors include: long cord, small fetus, polyhydramnios,
monoamniotic twins.
Investigations:
• Routine surveillance of the umbilical cord for knots may not be justifiable because it
is time consuming and of uncertain sensitivity or benefit.
Follow up:
• The detection of an umbilical cord knot is not an indication for delivery unless
associated with evidence of fetal compromise, such as abnormal fetal heart rate
pattern.
• Closer fetal surveillance by fetal Dopplers and cardiotocography should be
considered.
Prognosis:
• Risk of stillbirth is increased by 5 times.
Recurrence risk:
Vasa previa
Prevalence:
• Umbilical vessels, unsupported by either the umbilical cord or placental tissue,
traverse the fetal membranes of the lower segment above the cervix.
• Use of transvaginal ultrasound and color Doppler are necessary to make the
diagnosis.
• Vasa previa usually occurs in association with velamentous cord insertion, bipartite
placenta, or succenturiate lobe, where vessels run through the membranes to
join the separate lobes.
• Risk factors are multiple pregnancies, IVF conceptions (1 in 300) and low lying
placenta in the second trimester.
Investigations:
• Detailed ultrasound examination, including transvaginal sonography with color
Doppler.
Follow up:
• Serial scans every 2 weeks after 26 weeks to monitor cervical length. If there is
cervical shortening (<25 mm) hospitalization should be considered.
Delivery:
• Deliveryby cesarean section at 34 to 36 weeks, depending on cervical length.
Prognosis:
• Fetal death: >60% if not diagnosed prenatally and <3% if diagnosed prenatally.
Recurrence risk:
AMNIOTIC FLUID: Topics in this section

• Oligohydramnios
• Polyhydramnios
Oligohydramnios
Prevalence:
•1 in 100 pregnancies at <24 weeks’ gestation.
• The vertical measurement of the deepest pocket of amniotic fluid free of fetal parts
is <2 cm or the amniotic fluid index (sum of vertical pockets in the four quadrants)
is <5 cm.
• There are essentially three major causes of oligohydramnios at <24 weeks’
gestation:
1. Urinary tract abnormalities: bilateral renal agenesis, multicystic or polycystic
kidneys and urethral obstruction.
2. Preterm prelabor rupture of the membranes: normal fetal growth, anatomy
and fetal Doppler, with maternal history of vaginal loss of clear or blood
stained amniotic fluid.
3.Uteroplacental insufficiency: Fetal growth restriction with Doppler evidence
of high impedance to flow in the uterine and / or umbilical arteries and
redistribution in the fetal circulation.
Investigations:
• In cases of unexplained oligohydramnios, amnioinfusion may be useful in allowing
detailed examination of the fetus and in some cases to demonstrate that the
cause was rupture of membranes.
• Invasive testing for karyotyping should be undertaken if there are relevant fetal
abnormalities.
Follow up:
• Ultrasound scans every 1-3 weeks to monitor fetal condition and assess amniotic
fluid volume. In cases of rupture of the membranes assessment of lung growth
may be useful in predicting pulmonary hypoplasia.
• Therapeutic amnioinfusion is not useful.
• In uteroplacental insufficiency assessment of fetal growth and Doppler in the
umbilical artery, ductus venosus and middle cerebral artery will help decide the
best time for delivery.
Delivery:
• Fetal urinary tract abnormalities: standard obstetric care and delivery.
• Rupture of the membranes: expectant management and vaginal delivery if cephalic
presentation.
• Uteroplacental insufficiency: cesarean section or vaginal delivery depending on
gestational age, fetal size and degree of fetal compromise as defined by Doppler
and or cardiotocography.
Prognosis:
• Depends on gestational age at diagnosis, cause and gestational age at delivery. In
oligohydramnios <24 weeks’ gestation the prognosis is generally poor.
• Bilateral renal agenesis, multicystic or polycystic kidneys are lethal abnormalities,
usually in the neonatal period due to pulmonary hypoplasia.
• Preterm rupture of membranes at ≤20 weeks’ gestation is associated with a poor
prognosis; about 40% miscarry within 5 days of membrane rupture due to
chorioamnionitis, and, in the remaining 60% of pregnancies, more than 50% of
neonates die due to pulmonary hypoplasia.
• Uteroplacental insufficiency resulting in oligohydramnios at ≤24 weeks’ gestation is
very severe and the most likely outcome is intrauterine death.
Recurrence:
• Renal abnormalities: agenesis or multicystic 1-3%, infantile polycystic 25%.
• Preterm rupture of membranes: 10-25%, but can be reduced by cervical cerclage
and progesterone
• Uteroplacental insufficiency: 10% but can be reduced by aspirin (150 mg/day) from
12 weeks’ gestation.
Polyhydramnios
Prevalence:
• The vertical measurement of the deepest pocket of amniotic fluid free of fetal
parts is used to classify polyhydramnios into mild (8–11 cm), moderate (12–15
cm) and severe (≥16 cm).
• In about 80% of cases the polyhydramnios is mild, in 15% moderate and in 5%
severe.
• Most cases of mild polyhydramnios are idiopathic, but most cases with moderate or
severe polyhydramnios are due to maternal or fetal disorders.
• In most cases, polyhydramnios develops late in the second or in the third trimester
of pregnancy. Acute polyhydramnios at 16–22 weeks is mainly seen in
association with twin-to-twin transfusion syndrome.
• There are essentially two major causes of polyhydramnios:
1. Reduced fetal swallowing: due to brain abnormalities (e.g anencephaly,
Dandy-Walker malformation), facial tumors, gastrointestinal obstruction (e.g.
esophageal or duodenal atresia, small bowel obstruction), compressive
pulmonary disorders (e.g. pleural effusions, diaphragmatic hernia, CPAM,
CHAOS), narrow thoracic cage due to skeletal dysplasias), and fetal akinesia
deformation sequence (due to neuromuscular impairment of fetal swallowing).
2.Increased fetal urination: maternal diabetes mellitus and maternal uremia
(increased glucose and urea cause osmotic diuresis), hyperdynamic fetal
circulation due to fetal anemia (e.g. red blood cell isoimmunization or
congenital infection), fetal and placental tumors (e.g. sacrococcygeal
teratoma, placental chorioangioma), or twin-to-twin transfusion syndrome.
Investigations:
• Invasive testing for karyotyping and array if there are fetal abnormalities or growth
restriction. DNA testing for the myotonic dystrophy mutation if there is abnormal
posturing of the extremities.
• Glucose tolerance test if there is associated macrosomia.
• TORCH test if there are fetal features suggestive of infection.
Follow up:
• Ultrasound scans every 1-3 weeks to monitor fetal condition, amniotic fluid volume
and cervical length.
Prenatal therapy:
• Maternal diabetes mellitus: good glycemic control.
• Hydrops due to dysrhythmias: antiarrhythmic medication.
• Hydrops due to fetal anemia: intrauterine blood transfusion.
• Pulmonary cysts or pleural effusions: thoracoamniotic shunting.
• Twin-to-twin transfusion syndrome: laser occlusion of placental anastomoses.
• Fetal or placental tumors: laser occlusion of feeding vessels.
• Defects resulting in reduced fetal swallowing or severe idiopathic polyhydramnios:
serial amniodrainages if there is cervical shortening. However, the procedure
itself may precipitate premature labor. An alternative and effective method of
treatment is maternal administration of indomethacin; however, this drug may
cause fetal ductal constriction, and close monitoring by serial fetal
echocardiographic studies is necessary.
Delivery:
• Standard obstetric care and delivery in most cases.
• Fetal abnormalities: induction of labor at 38 weeks’ gestation in a hospital with
neonatal intensive care and facilities for pediatric surgery.
• Fetral tumors: consideration for cesarean section and EXIT procedure.
• Severe polyhydramnios: controlled induction and membrane rupture at 38 weeks’
gestation to avoid risk of umbilical cord prolapse.
Prognosis:
• This depends on the cause of polyhydramnios and the gestational age at delivery.
Recurrence:
• Idiopathic: no increased risk.
• Associated maternal or fetal conditions: depends on the cause.
MULTIPLE PREGNANCIES: Topics in this section

• Protocol for ultrasound scans
• MC twins: conjoined twins
• MC twins: death of one fetus
• MC twins: monoamniotic
• MC twins: selective fetal growth restriction
• MC twins: twin anemia-polycythemia sequence
• MC twins: twin reversed arterial perfusion sequence
• MC twins: twin-to-twin transfusion syndrome
• Structural abnormalities
• Triplet pregnancies
Protocol for ultrasound scans

Background:
• Multiple births account for 2-3% of all live births and the incidence is increasing due
to assisted conception and increasing maternal age.
• Perinatal mortality and morbidity is higher with multiple pregnancies than
singletons and therefore these pregnancies require additional support.
• The risk of pregnancy complications is much higher in monochorionic (MC) than
dichorionic (DC) pregnancies.
• Two-thirds of twins are dizygotic (non-identical) and one-third monozygotic
(identical). One-third of monozygotic twins are dichorionic (DC) and two-thirds
are monochorionic (MC). Therefore, all MC twins are monozygotic and 6 of 7 DC
twins are dizygotic.
• In DC pregnancies the inter-fetal membrane is composed of a central layer of
chorionic tissue sandwiched between two layers of amnion, whereas in MC
pregnancies there is no chorionic layer.
Determination of chorionicity:
• The best way to determine chorionicity by ultrasound at 11-13 weeks’ gestation is
to examine the junction between the inter-fetal membrane and the placenta. In
DC pregnancies there is a triangular placental tissue projection (λ sign) into
the base of the In MC pregnancies there is no placental tissue projection into
the base of the membrane (T sign).
• With advancing gestation, there is regression of the chorion laeve and the ‘lambda’
sign becomes progressively more difficult to identify. Thus by 20 weeks only 85%
of DC pregnancies demonstrate the λ sign.
Pregnancy dating:
• Spontaneous conception: use the crown-rump length of the longest fetus at 11-13
weeks.
• IVF conception: use the embryonic age from fertilization.
Measurements:
• In each scan assess fetal growth (head circumference, abdominal circumference,
femur length), amniotic fluid (deepest vertical pool), pulsatility index by
Doppler (umbilical artery, middle cerebral artery and ductus venosus) and in
monochorionic twins middle cerebral artery peak systolic velocity to detect
possible twin anemia–polycythemia sequence (TAPS).
• At 20 weeks measure cervical length. If <20 mm give vaginal progesterone 400 mg
in the morning and 400 mg at night and repeat the scan in 1 week. If there is
progressive cervical shortening to <5 mm give prophylactic steroids for fetal lung
maturity. There is no evidence that bed rest or cervical cerclage is beneficial.
Dichorionic twins:
• Scans at 12, 20 weeks and then every 4 weeks until delivery.
• If there is discordance in fetal size of >15%, discordance in amniotic fluid or any
abnormal Dopplers then review every 1 week.
• If there is no complication, consider delivery at 37 weeks.
Monochorionic diamniotic twins:
• Scans at 12 and 16 weeks and then every 2 weeks until delivery.
• If there is no complication, consider delivery at 36 weeks.
Monochorionic monoamniotic twins:
• If there is discordance in fetal size of >15% or any abnormal Dopplers then review
every 1 week.
• If there is no complication, delivery by cesarean section at 32 weeks.
Trichorionic triplets:
• 12 weeks: counsel concerning options of expectant management or embryo
reduction.
• Scans at 12, 20, 24, 28 and 32 weeks.
• If there is no complication, consider delivery by cesarean section at 34 weeks.
Monochorionic or dichorionic triplets:
• 12 weeks: counsel concerning options of expectant management or embryo
reduction.
• If there is no complication, delivery by cesarean section at 32-34 weeks
MC twins: conjoined twins

Prevalence:
• 1% of monochorionic twins.
• Results from incomplete splitting of the embryonic mass after day 12 of
fertilization.
• Fused twins in monochorionic monoamniotic pregnancy.
• Classified according to the site of fusion followed by pagus (Greek word for 'what
is fixed'). Most common type is thoracopagus (75% of cases) with fusion in the
thorax and abdomen and often conjoined hearts, livers and intestines.
• Other types include pygopagus (fetuses fused at the rump), ischiopagus (fetuses
fused at the lower half of the bodies with spines conjoined end to end at
o
180 angle), craniophagus (fused skulls and separate bodies), omphalopagus
(fused at the lower abdomen, with shared liver and intestines).
increased.
Investigations:
• Detailed ultrasound examination and assessment by multidisciplinary team.
Management:
• Pregnancy termination, stillbirth or neonatal death in >90% of cases.
• If the pregnancy continues, delivery should be by cesarean section in a centre with
expertise in the management of such pregnancies.
Prognosis:
• Very high risk of handicap in survivors.
Recurrence:
MC twins: death of one fetus

Prevalence:
• Spontaneous death of one fetus occurs in 1% of monochorionic twins.
Implications:
• Death of one twin is associated with acute hemorrhage from the co-twin into the
fetoplacental unit of the dead one. In the co-twin there is a 15% risk of death and
≥ 25% of the survivors have severe neurological injury. There is also a high risk
(60-70%) of preterm birth.
• If death of a fetus occurs at <24 weeks' gestation the co-twin is more likely to also
die but if it survives, neurologic damage may be less; if death occurs >24 weeks
the co-twin is more likely to survive but also more likely to suffer brain damage.
Management:
• Ultrasound examination to estimate whether the death of the fetus occurred within
the previous 48 hours or earlier (mild generalized edema, ascites and pleural
effusions), and assessment of the survivor for evidence of brain hemorrhage,
heart failure and hyperdynamic circulation with high middle cerebral artery peak
systolic velocity (MCA PSV).
• Death at <48 hours and MCA PSV ≥1.5 multiple of the median: intrauterine
blood transfusion and repeat Doppler 5-10 hours later. If the PSV is again >1.5
multiple of the median another transfusion is necessary. If there is
polyhydramnios and the cervical length is <20 mm consider amniodrainage.
• Death at <48 hours and MCA PSV <1.5 multiple of the median: repeat Doppler
studies within 24 hours. If the PSV becomes >1.5 multiple of the median an
intrauterine blood transfusion is necessary. If there is polyhydramnios and the
cervical length is <20 mm consider amniodrainage.
• Death at >48 hours and no evidence of fetal heart failure: expectant
management irrespective of MCA PSV. If there is polyhydramnios and the
cervical length is <20 mm consider amniodrainage.
• If the fetus survives: neurosonography should be carried out in 2 and 4 weeks
and MRI at 32 weeks to determine if there is evidence of brain damage. If brain
development, fetal growth and Dopplers are normal there is no need for early
delivery. If there is evidence of brain damage, in some countries pregnancy
termination would be a legal option.
MC twins: monoamniotic
Prevalence:
• 5% of monochorionic twins.
• Results from splitting of the embryonic mass after day 9 of fertilization.
• Absence of inter-twin membrane. The two umbilical cords insert close to each
other with large-caliber anastomoses between the two fetal circulations.
• Color Doppler demonstrates cord entanglement in most cases and this is usually
present from the first trimester of pregnancy. Cord entanglement does not
contribute to fetal death or brain damage.
• The number of yolk sacs does not accurately predict amnionicity, because a
few monoamniotic twins have two yolk sacs and a few diamniotic twins
have only one yolk sac.
increased.
• Risk of discordance for structural abnormalities (20%) is higher than in
monochorionic diamniotic twins (8%)
Investigations:
• Scans at 12 and 16 weeks and then every 2 weeks until delivery. Assessment of
growth, brain development, amniotic fluid volume and pulsatility index in the
umbilical artery, middle cerebral artery and ductus venosus of both fetuses.
• If there is discordance in fetal size of >15% or any abnormal Dopplers then review
every 1 week.
Management:
• Fetal death, usually of both twins, occurs in 70% of cases (50% at <20 weeks’
gestation, 15% at 20-32 weeks and 5% at ≥32 weeks).
• The most likely cause of fetal death, which occurs suddenly and unpredictably, is
acute exsanguination across the large anastomoses between the two cords,
probably triggered by cord compression.
• Discordance for major abnormality: one option is endoscopic cord occlusion of the
affected fetus followed by laser transection of the cord to avoid subsequent death
of the healthy twin in later pregnancy.
• TTTS occurs rarely and is suspected by the development of polyhydramnios and
the finding of small or absent bladder in the donor and large bladder in the
recipient. The proximity of cords precludes the option of endoscopic laser
ablation of communicating vessels. Alternative options are amniodrainage, early
delivery or endoscopic occlusion and transection of the cord of one of the
fetuses.
• There is no need for hospitalization. Delivery should be by elective cesarean
section at 32 weeks’ gestation.
Recurrence:
MC twins: selective fetal growth restriction

Prevalence:
• 10-15% of monochorionic twins.
• Estimated weight <5th percentile in the small fetus and ≥25% discordance
between the two fetuses.
• The amniotic fluid in the small fetus is reduced and in the other fetus is normal.
• The condition is subdivided into 3 types according to the Doppler finding of the end
diastolic flow (EDF) in the umbilical artery of the small fetus:
• Type I: EDF positive.
• Type II: EDF absent or reversed
• Type III: EDF cyclical change from positive to absent and reversed.
• If in the presence of ≥25% estimated weight discordance between the fetuses
there is polyhydramnios in the sac of the bigger twin the condition is sFGR with
superimposed TTTS.
increased.
Investigations:
• Ultrasound scans every 1 week to monitor growth, amniotic fluid volume and
pulsatility index in the umbilical artery, middle cerebral artery and ductus venosus
of both fetuses.
Management:
• Types I and II with TTTS: endoscopic laser ablation of communicating placental
vessels.
• Type I without TTTS: expectant management with close monitoring to define the
best time of delivery. If Doppler finding remain normal then elective cesarean
section at 34-35 weeks. There is intact survival of both twins in 95% of cases.
• Type II without TTTS: there is a high risk of perinatal death and handicap for both
twins.
• ≥26 weeks: the best management is close monitoring and delivery if the ductus
venosus EDF becomes negative or reversed.
• <26 weeks: the best management is endoscopic laser ablation of communicating
placental vessels. Survival of the big baby is 70% and of the small baby depends
of ductus venosus EDF: 40% if positive and 10% if negative or reversed. Risk of
neonatal cerebral lesions primarily depends on gestational age at delivery and
varies from 20% for birth at <26 weeks to 5% for birth at ≥32 weeks. An
alternative management is cord occlusion of the small fetus; the survival of the
large twin is 90%.
• Type III: the two umbilical cords are adjacent to each other and the behaviour of
the pregnancy is similar to that of monoamniotic twins; development of TTTS is
rare and sudden unexpected death could occur in 20-30% of cases. Laser
surgery may be impossible and the best management is close monitoring and
delivery on the basis of ductus venosus EDF in the small fetus. If the ductus
venosus EDF is positive elective delivery should be by cesarean section at 32
weeks’ gestation. There is a 20% risk of neonatal cerebral lesions and the risk is
greater in the larger than small fetus.
Recurrence:
MC twins: twin anemia-polycythemia sequence

Prevalence:
• Spontaneous: 5% of monochorionic twins. Usually occurs >26 weeks' gestation.
• After laser ablation of placental vessels: 2-10% of monochorionic twins.
• TAPS occurs due to a slow transfusion of blood from the donor to the recipient
through few very small arteriovenous vascular anastomoses leading to highly
discordant hemoglobin levels.
• There is no substantial difference between the twins in either size or amniotic fluid
volume.
• The placenta of the anemic fetus looks thick and hyperechogenic, whereas that of
the polycythemic fetus looks thin and translucent.
• The fetal middle cerebral artery peak systolic velocity (MCA PSV) in the anemic
fetus is increased (>1.5 multiples of median), whereas that in the polycythemic
fetus is decreased (<1 multiples of the normal median).
• The anemic fetus may have a dilated heart, tricuspid regurgitation and ascites. The
liver of the polycythemic fetus has a starry sky pattern due to diminished
echogenicity of the liver parenchyma and an increased brightness of the portal
venule walls.
• The incidence of chromosomal abnormalities, genetic syndromes or fetal defects is
not increased.
Investigations:
• Detailed ultrasound examination, including echocardiography (to assess cardiac
function) and measurement of MCA PSV (to predict degree of anemia and
polycytemia).
Management:
• <26 weeks: endoscopic laser ablation of communicating placental vessels.
Subsequently, scans every 1 week to monitor fetal growth, brain anatomy and
MCA-PSV. Fetal brain MRI at ≥32 weeks’ gestation should be considered for the
diagnosis of neuronal migration disorders. If both babies are developing normally
vaginal delivery can be carried out at 37 weeks.
• 26-30 weeks: intrauterine blood transfusions to the anemic twin and exchange
transfusion with Hartmans’ solution for the polycythemic twin. Doppler
assessment every 2-3 days because it may become necessary to undertake
interventions every 3-4 days. Delivery by cesarean section at 30-32 weeks.
• >30 weeks: delivery by cesarean section.
Prognosis:
• Neurodevelopmental delay in up to 20% of cases, which mainly depends on
gestational age at birth. The risk is higher for the recipient twin.
Recurrence:
MC twins: twin reversed arterial perfusion sequence

Prevalence:
• Monochorionic twins with one normal fetus (pump twin) and another with no
cardiac acitivity (rarely, a rudimentary heart may show slow pulsations) and
variable degrees of deficient development of the head and upper limbs and
hydrops (recipient twin).
• Color Doppler in the recipient twin demonstrates reversed pulsatile flow from an
umbilical arterioarterial anastomosis and venous return to the pump twin via a
venovenous anastomosis. Occasionally, the cord of the acardiac twin arises
directly from that of the pump twin.
• The size of the acardiac mass is prognostic value for the survival of the pump twin.
• About 50% of pump twins die before or after birth from congestive heart failure or
severe preterm birth, due to polyhydramnios.
• The incidence of chromosomal abnormalities, genetic syndromes or fetal defects is
not increased.
Investigations:
• Detailed ultrasound examination, including echocardiography to assess cardiac
function in the pump twin.
Fetal therapy:
• Prenatal treatment is by occlusion of the blood flow to the acardiac twin. Several
methods have been used, including ablation of umbilical cord vessels by laser or
diathermy, coagulation of placental anastomoses by laser, or ablation of intrafetal
vessels by monopolar diathermy, laser, or radiofrequency. When these methods
are used at 16-18 weeks’ gestation the survival rate of the pump twin is about
80%.
• The preferred management is ultrasound-guided laser coagulation or
radiofrequency of the umbilical cord vessels within the abdomen of the acardiac
twin at 11-13 weeks. The survival is 70-75%, which is less than the 80%
achieved with intervention at 16-18 weeks.
• However, delay in intervention between the diagnosis of TRAP sequence at 11-13
weeks’ gestation until 16-18 weeks is associated with spontaneous cessation of
flow in the acardiac twin in 60% of cases and in about 50% of these there is also
death or brain damage in the pump twin.
Follow up:
• Intrauterine intervention: scan in 1 week to confirm that the pump twin is alive and
that there is cessation of flow in the acardiac twin. Subsequently, standard follow-
up.
• No intrauterine intervention: scans every 2-3 weeks to monitor growth of the
acardiac twin, heart function of the pump twin and amniotic fluid volume.
Delivery:
Prognosis:
• Depends on gestational age at birth.
Recurrence:
MC twins: twin-to-twin transfusion syndrome

Prevalence:
• There is imbalance in the net flow of blood across the placental vascular
communications from one fetus, the donor, to the other, the recipient.
• 11-14 weeks: early TTTS is suspected if there is discordance in size of the amniotic
fluid sacs, ≥20% discordance in fetal nuchal translucency (NT) thickness, or
absent / reversed end diastolic flow (EDF) in the ductus venosus usually in the
fetus with higher NT.
• ≥15 weeks: oligohydramnios (deepest vertical pool of ≤2 cm) in the sac of the
oliguric or anuric donor fetus and polyhydramnios (≥6 cm at 15-17 weeks, ≥8 cm
at 18-20 weeks and >10 cm at ≥20 weeks) in the sac of the polyuric recipient.
• The condition is subdivided into 4 stages according to the Doppler finding of EDF
in the umbilical artery and ductus venosus of both fetuses:
• Stage 1: donor bladder visible, EDF positive in both vessels in both fetuses.
• Stage 2: donor bladder not visible, EDF positive in both vessels in both fetuses.
• Stage 3: EDF absent or reversed in either vessel in either fetus.
• Stage 4: presence of ascites or hydrops in either fetus; usually the recipient.
increased.
Investigations:
• Ultrasound scans every 1 week to monitor growth, amniotic fluid volume and
pulsatility index in the umbilical artery, middle cerebral artery and ductus venosus
of both fetuses.
Management:
• Discordance in amniotic fluid (but not sufficient to fulfill the oligohydramnios /
polyhydramnios sequence) with normal fetal Doppler:
• Overall survival: 95%.
• Progression to TTTS: 15%.
• Ultrasound scans every 1-2 weeks to monitor evolution.
Stage 1:
• Survival: overall 85%, at least one twin 90%.
• Progression to stages 2 to 4: 20%.
• Ultrasound scans every 1 week to monitor evolution.
• Endoscopic laser ablation of communicating placental vessels if progression to
stages 2-4 or increasing polyhydramnios and shortening of cervical length.
Stages 2-4:
• <28 weeks: the best management is endoscopic laser ablation of communicating
placental vessels; all communicating vessels should be ablated and the area
between them should also be coagulated to achieve dichorionization of the
placenta.
• ≥28 weeks: the best option is to deliver by cesarean section and the timing would
depend on the Doppler findings in the umbilical artery and ductus venosus of
both fetuses.
• Stage 2: survival overall 75%, at least one twin 85%.
• Stages 3 and 4: survival overall 60-70%, at least one twin 75-85%.
• Neurodevelopmental impairment in survivors: 5-10%.
• Follow-up after laser therapy: ultrasound scans and Doppler every 1 week until
resolution of the signs of TTTS and normalization of Doppler findings and every 2
weeks thereafter with special attention for signs of brain damage, recurrence of
TTTS and development of TAPS.
• Normalization of amniotic fluid volume occurs after 1 week. Resolution of cardiac
dysfunction in the receipient and of hydrops in stage 4 TTTS usually occurs after
3-4 weeks.
• In about 1 in 1,000 cases there may be limb amputation due to thrombotic events
or amniotic bands.
Delivery:
• Vaginallyat 37 weeks if there is normal growth and Dopplers in both babies.
Recurrence:
Structural abnormalities
Dichorionic twins:
• The prevalence of defects per fetus is the same as in singletons (2%) and
therefore the risk of a defect in at least one fetus is 2 times as high (4%) as in a
singleton pregnancy. In 10% of cases both fetuses are affected (concordance)
and in 90% only one fetus is affected (discordance).
Monochorionic twins:
• The prevalence of defects per fetus is 2 times higher than in singletons and
therefore the risk of a defect in at least one fetus is 4 times as high (8%) as in a
singleton pregnancy. In 20% of cases both fetuses are affected (concordance)
and in 80% only one fetus is affected (discordance).
Management of pregnancies discordant for abnormality:
• These pregnancies can be managed expectantly or by selective fetocide of the
abnormal twin.
• In cases where the abnormality is non-lethal but may result in serious handicap the
parents need to decide whether the potential burden of a handicapped child is
enough to risk the loss of the normal twin from fetocide-related complications.
• In cases where the abnormality is lethal it may be best to avoid the risks
associated with selective fetocide, unless the condition itself threatens the
survival of the normal twin. For example, in anencephaly or trisomy 18 (with
associated esophageal atresia or diaphragmatic hernia), there is >50% risk of
development of polyhydramnios at 24-26 weeks’ gestation placing the normal
twin at high risk of preterm birth and associated mortality and morbidity.
Selective fetocide in dichorionic twins:
• Fetocide can be carried out by intracardiac injection of potassium chloride.
• Fetocide at 11-14 weeks: risk of miscarriage 7% and risk of birth at <32 weeks 6%.
• Fetocide at ≥16 weeks: risk of miscarriage 14% and risk of birth at <32 weeks
20%.
• Fetocide at 32 weeks: this is a legal option in some countries and avoids risks of
miscarriage and early preterm birth.
Selective fetocide in monochorionic twins:
• Fetocide can be carried out by occlusion of the umbilical cord vessels through
endoscopic laser, ultrasound-guided bipolar forceps or radiofrequency.
• Fetocide at ≥16 weeks: risk of miscarriage 20% and risk of birth at <32 weeks
20%.
Triplet pregnancies
Management options at 11-13 weeks:
• In triplet pregnancies diagnosed during the first trimester management options
include continuing with the whole pregnancy or embryo reduction (ER) to twins or
singletons.
• The consequence of ER is decrease in the rate of early preterm birth, but increase
in the rate of miscarriage at <24 weeks (Table below).
• Trichorionic (TC) triplets: ER is achieved by fetal intracardiac injection of
potassium chloride (KCl).
• Dichorionic (DC) triplets: ER by KCl involves either the separate fetus or both
monochorionic (MC) twins; the injected KCl to only one of the MC twins could be
transferred to the co-twin through the inter-twin placental vascular anastomoses
or death of one fetus could lead to hemorrhage from the co-twin into the dead
fetoplacental unit with consequent death or neurodevelopmental impairment in
the survivor.
• In DC, compared to TC triplets, there is a higher rate of miscarriage both with
expectant management, and after ER to MC twins, which could, at least in part,
be attributed to subsequent development of sFGR or TTTS.
• Another option for DC triplet pregnancies is ER to DC twins by ultrasound-guided
laser ablation of the pelvic vessels of one of the MC twins. The risks of
miscarriage and early preterm birth are lower with this method than with other
options. However, with intrafetal laser half of the pregnancies will result in the
birth of one rather than two babies, because the other MC twin dies within 2
weeks of the procedure.
Management options Miscarriage Preterm birth
at 11-13 weeks 12+0 to 23+6 weeks 24+0 to 32+6 weeks
Trichorionic triplets
- Expectant management 3% 35%
- Reduction to DC twins by KCL 7% 13%
- Reduction to singleton by KCL 10% 8%
Dichorionic triplets
- Expectant management 9% 38%
- Reduction to MC twins by KCL 13% 23%
- Reduction to singleton by KCL 18% 9%
- Reduction to DC twins by laser 3% 7%
Feto-fetal transfusion syndrome (FFTS):

• In triplet pregnancies complicated by severe FFTS, the best management option is
endoscopic laser ablation of communicating placental vessels.
• DC triplets: the separate fetus can pose some technical problems in selecting the
appropriate site of entry of the fetoscope but in general these problems can
easily be overcome. Consequently, the outcome of affected pregnancies is
similar to that in MC twins but with an inevitable higher incidence of early preterm
birth.
• Survival: overall 75%, at least one baby 95%. Birth at <32 weeks: 55%.
• MC triplets: endoscopic laser surgery can be technically difficult because of the
necessity to ablate the communicating placental vessels between all three
fetuses. The fetoscope is introduced into the sac of the recipient fetus and laser
was used to coagulate the vessels between this fetus and each of the other two
fetuses. Subsequently, the fetoscope is advanced through the inter-twin
membrane into the sac of one of the other fetuses to coagulate the vascular
connections between them. As a result of such technical problems or the inability
to achieve the objective of complete separation between all fetuses the outcome
is poorer than in DC triplets.
• Survival: overall 55%, at least one twin 80%. Birth at <32 weeks: 65%.

ULTRASOUND Fetal Anomaliesdocx

Încărcat de

Informații document

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

ULTRASOUND Fetal Anomaliesdocx

Încărcat de

Drepturi de autor:

Formate disponibile

BRAIN: Topics in this section

Blake's pouch cyst

Choroid plexus cysts

Corpus callosum agenesis

Dural sinus thrombosis

Vein of Galen aneurysm

SPINE: Topics in this section

• Open spina bifida

Open spina bifida

FACE: Topics in this section

NECK: Topics in this section

• Untreated congenital hypothyroidism is associated with neurodevelopmental delay.

THORAX: Topics in this section

Congenital high airway obstruction syndrome

Congenital pulmonary airway malformation

ABDOMINAL WALL: Topics in this section

Body stalk anomaly

GASTROINTESTINAL TRACT: Topics in this section

Small bowel obstruction

URINARY TRACT: Topics in this section

Autosomal dominant polycystic kidneys

Uretero-pelvic junction obstruction

Uretero-vesical junction obstruction

GENITAL TRACT: Topics in this section

EXTREMITIES: Topics in this section

Limb deficiency or amputation

Amniotic band syndrome

SKELETON: Topics in this section

• Asphyxiating thoracic dystrophy

Asphyxiating thoracic dystrophy

Ellis-Van Creveld syndrome

Short rib polydactyly syndrome

HYDROPS FETALIS: Topics in this section

CHROMOSOMAL DEFECTS: Topics in this section

PLACENTA, UMBILICAL CORD: Topics in this section

• Morbid adherent placenta

Morbid adherent placenta

Single umbilical artery

Umbilical cord cyst

Umbilical cord knot

AMNIOTIC FLUID: Topics in this section

MULTIPLE PREGNANCIES: Topics in this section

Protocol for ultrasound scans

MC twins: conjoined twins

MC twins: death of one fetus

MC twins: selective fetal growth restriction

MC twins: twin anemia-polycythemia sequence

MC twins: twin reversed arterial perfusion sequence

MC twins: twin-to-twin transfusion syndrome

Feto-fetal transfusion syndrome (FFTS):

S-ar putea să vă placă și