EBM

Evidence Based Medicine In Neonatology

Definition:
Evidence-Based Pediatrics is the practice of child health care based on the best available
evidence that we are doing more good than harm .It is the integration of best research
evidence with clinical experience and patient values to facilitate clinical decision making.
Good doctors use both individual clinical experience and the best available external
evidence, and neither alone is enough
It is a life long self-directed and problem-based learning process.
There is an average of 19 new articles appearing in pediatric journals every day, so, it is very
difficult for practicing pediatricians to keep up to date
The question that faces the neonatal community in the 21st century is
"How will we continue to improve the outcome of newborns, and yet avoid repeating medical
disasters?".
Clinical Decision-Making
Clinical Experience , Clinical state and circumstances , Patient preferences and actions , Health
care resources , Research evidence
Steps of EBM:
1 Formulate an answerable relevant question
2. Conduct an efficient literature search for the best external evidence
3. Critically appraise the evidence for validity and applicability
4. Apply the results in health care decisions and clinical practice
5. Evaluate the performance and outcome
(I) Framing the Question
P opulation / Situation
I ntervention / Exposure
C ounter intervention
O utcome
Example of a Question
Is water as effective as alcohol in preventing umbilical cord infections in newborn infants?
P opulation: Newborn infants
I ntervention: Water
C ounter intervention: Alcohol
O utcome: Umbilical infections
(II) Conduct an efficient literature search for the best external evidence
Hierarchy of an efficient literature search

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1- Single Studies
It is important to learn how to search the medical literature and to become familiar with two
bibliographic databases, EMBASE and MEDLINE.
EMBASE (Elsevier Science) is the short format of the Expert Medica database. EMBASE
covers the biomedical literature from 110 countries and is particularly strong in
pharmaceutical and toxicological studies.
MEDLINE, the National Library of Medicine's database. It includes indexes information's
from over 3900 biomedical journals published in the United States and 70 foreign countries.
- A variety of MEDLINE search engines are widely available including OVID, PUBMED, etc.
2- Synopses of Single Studies
Encapsulate the key methodological details and results of a single study that are required to
apply the evidence to individual patient care.
- Used only when a systematic review does not exist or when the review is outdated
- Example: Evidence-Based Abstraction Journals
3- Systematic Reviews (Syntheses)
Systematic consolidation of the literatures on a specific topic : Sources :
- The Cochrane Library
- Agency for Healthcare Research and Policy
- Health care journals
RCTs and Systematic Reviews
RCTs are considered to be the best method for evaluating the effectiveness of an
intervention, and therefore are considered the best available evidence.
The methodology of RCTs seeks to minimize bias at all points of the study and thereby,
gives the most accurate estimates of effects.
Random allocation of study subjects is essential to minimize bias at the time of study entry
(selection bias)
Appropriate trial methodology seeks to reduce bias in all aspects of the study.
It provides the basis for all traditional statistical comparisons used in analysis of the trial
results.
Qualitative systematic reviews summarize the cumulative data, but do not perform further
statistical analyses.
Quantitative systematic reviews, or meta-analysis are systematic reviews that use
statistical methods to combine the results of multiple RCTs.
Meta-analysis = The results of multiple RCTs.
- It has its criticism.
- Any trial for pooling results from various studies will not only incorporate the biases of the
primary studies, but will add additional bias attributable to study selection and the inevitable
heterogeneity of the selected studies.
The Cochrane Collaboration is an international effort to prepare, maintain, and
disseminate systematic reviews of the main health care topics.
The Neonatal Collaborative Review Group oversees the creation and updating of
systematic overviews of RCTs of interventions in the field of neonatal-perinatal medicine.
The neonatal reviews also appear on a Web site maintained by the National Institute of Child Health
and Human Development
4- Synopses of Syntheses
Encapsulate the key methodological details and the results of a systematic reviews. - Example:
Evidence-Based Abstraction Journals
Look for the articles labeled Review
5 - Systems
1- Clinical practice guidelines
2- Evidence-based textbooks

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Clinical Practice Guidelines

Systematically developed statements to assist practitioners for taking decisions about
specific clinical conditions.
A trial to distill a large body of knowledge into a convenient readily usable format.
(III) Critically appraise the evidence for validity and applicability
The Critically Appraised Topic (CAT ) is a practical, evidence-based evaluation and teaching
tool.
In the neonatal intensive care units, questions often arise about the validity of old and new
therapies and diagnostic tests.
(VI) Apply the results in health care decisions and clinical practice
Applying the results in health care decisions and clinical practice
Evidence can also be used in the creation of clinical policies or guidelines.
In creating clinical policies, one must consider the evidence regarding the impact of the
disease, barriers to implementing, safety, acceptability, societal values and cost
effectiveness.
Even in situations where the evidence is extensive, formulating a clinical policy is a
difficult task.
(V) Evaluate the performance and outcome
To gain experience in the practice of evidence-based medicine, it is recommended that one
should evaluate his own performance and commitment to the principles of evidence-based
medicine.
Levels of Evidence and Grades of Recommendations
Intervention Level of evidence Grade of recommendation
Systematic review of RCTs 1a
A
Individual randomized controlled trial 1b
Systematic review of cohort studies 2a
Individual cohort study 2b
B
Systematic review of case-control studies 3a
Individual case-control study 3b
Case series 4 C
Expert opinion 5 D

Examples of EBM in Neonatology

1- Antenatal steroids
Antenatal betamethazone decreases RDS and neonatal mortality
A total of 18 RCTs studied the effect of antenatal steroids on promoting lung maturity .
A systematic review was conducted for those 18 RCTs which included more than 3700
newborns.
The meta-analysis demonstrated a significant decrease in the risk of RDS, intracranial
hemorrhage and neonatal death .
The evidence from the systematic review recommends the use of antenatal betamethazone
steroids .
Avoid antenatal dexamethazone
A well-conducted retrospective study has indicated that antenatal dexamethazone is associated with
a greater risk of periventricular leukomalacia than antenatal betamethazone
2- Postnatal Steroids
Use Postnatal Dexamethazone Judiciously
Avoid early use of postnatal dexamethazone
as several studies indicated that early use of postnatal dexamethazone is associated with a
higher incidence of cerebral palsy or significant neuro developmental handicapping.

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Avoid prolonged courses of postnatal dexamethazone In a recent RCTs of treatment

of CLD, long-term neurological complications were significantly worse with prolonged
dexamethazone treatment.
3- Surfactant Replacement Therapy
In the last decade, 33 RCTs involving more than 6000 infants have been conducted.
The systematic review of these trials demonstrated that surfactant, whether used
prophylactically in the delivery room to prevent RDS or in the rescue treatment of
established RDS, leads to a significant decrease in the risk of pneumothorax and the risk of
mortality.
A systematic review of the seven RCTs that have evaluated the use of prophylactic
surfactant therapy compared with selective therapy of infants with established RDS
suggests that there are important clinical benefits associated with prophylactic surfactant
administration.
4- Prophylactic indomethacin
Prophylactic indomethacin has been evaluated both in the prevention of PDA and in the
prevention of IVH.
Animal studies and clinical trials have suggested that indomethacin, a cyclooxygenase
inhibitor of prostaglandin synthesis, lowers the risk of intraventricular hemorrhage in very
low birth weight infants.
A systematic overview of 14 RCTs of prophylactic indomethacin involving 1000 infants
suggests a decrease in the risk of PDA.
However, use of prophylactic indomethacin is not widespread because of concern regarding
possible side effects of treatment including cerebral ischemia and necrotizing enterocolitis

In the case of prophylactic indomethacin, there are three treatment alternatives:

1) Prophylactic indomethacin for all at-risk infants after cranial ultrasound screening for
baseline IVH.
2) Indomethacin administration for at-risk infants without severe IVH.
3) Indomethacin administration only to infants with symptomatic PDA.
5- Necrotizing Enterocolitis
Question:
Could stool pattern affect the diagnosis of NEC?
Conclusion & Comment:
-Presence of blood in the stool (macroscopic or started by microscopic then changed to
macroscopic) of a newborn increases the possibility of NEC diagnosis.
-0ccult (microscopic) blood has no significance correlation with NEC.
Question:
Could abdominal ultrasonography help in the diagnosis of NEC?
Conclusion & Comment:
Abdominal_ultrasonography helps in the diagnosis mainly through detection of :
-Portal vein gas which usually missed by routine plain X ray while easily
detected by US, its presence is highly indicative of NEC.
-Intestinal perforation via detection of intra peritoneal fluid debris level and
ascites.

Question: Could culture studies (from blood, stool, duodenal aspirate and peritoneal
aspirate) affect the diagnosis of NEC?
Conclusion and Comment:
Culture studies (from blood, stool, duodenal aspirate and peritoneal aspirate) correlates
poorly with NEC diagnosis because no specific organism associated with NEC.
Question: Could breast milk protect against NEC more than artificial milk?
Conclusion and Comments:

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-There is an excellent evidence that breast milk decreases the incidence of NEC .
-No evidence of full complete protection of breast milk against NEC.
-The partial protective effect of breast milk against NEC is more in the preterm babies.
Question: Could feeding pattern (delayed rather than early, slow rather than rapid and no
feeding rather than trophic feeding protect against NEC?
Conclusion and Comments:
-Delayed feeding has no proved evidence to have NEC protective effect.
-Slow feeding has no proved evidence to have NEC protective effect.
-Early trophic feeding with breast milk or half strength formula is highly accepted .
-The relation of rapid advancement with NEC occurrence is still unproved but the
available studies can not absolutely exclude this.
- Ideal rate of feeding advancement is still unclear.
- Larger volumes and early full strength formulae seem to be associated with increased
incidence of NEC.
Question: In preterm 35w gestation or less and at risk of NEC. Is antenatal corticosteroid
protect against NEC?
Comments and Conclusion:
-Excellent evidence of the protection effect of antenatal corticosteroid given to pretems
35w gestation or less against NEC.
-A single course of antenatal corticosteroids is a rare example of a treatment that yields
both a health benefit and a cost saving.
-The protection effect is more with intact membranes but still present also with PROM.
6- Hand Hygiene
Hand washing is considered a key aspect of hand hygiene (elimination of organisms from
hands).
- Because spread of organisms by hand contact is universally accepted as the leading means of
dissemination of infectious agents.
Initial wash
The traditional practice was to perform a 3- 5-minute scrub using a brush on entry to the
unit.
Then evidence proved that an initial wash of 15 to 60 seconds replaced the former practice.
Brushes were recommended only for staff or parents who had heavily soiled hands.
Interval wash
This became the primary focus because it represented the area with the greatest
noncompliance due to skin breakdown from repeated friction and application of antiseptic
agents, lack of time and human nature.
Strategies to overcome these barriers included introduction of new antiseptic agents as 2%
instead of 4% chlorhexidine and use of lotions and waterless alcohol gels at the bedside to
enhance compliance .
7- Line Management
Epidemiologic studies indicate that sepsis particularly those of CONS, are frequently associated
with indwelling catheters.
Organisms that colonize catheter hubs are often the same as those isolated from catheter
tips in cases with catheter-related sepsis.
De-contaminating hubs with alcohol will decrease colonization and result in lower rates of
bacteremia.
The evidence strongly suggests that this practice can play a significant role in lowering the
risk of nosocomial bacteremia.
lipid infusions should be changed only once every 24 hours.
Parenteral fluids with amino acids should be changed once every 48 to 72 hours.

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8- Avoid early lumbar puncture

There is evidence that performing a lumbar puncture has adverse effects on heart rate and
oxygen saturation.
There is also evidence of lack of diagnostic benefit of early lumbar puncture. Although there is
no direct evidence of neurological effects, the consensus was to avoid this procedure in the first
three days of life.
9- Maintain neutral head position with bed elevated 30 degrees
- Studies have shown that turning the infants head to the side affects jugular venous return and
may affect intracranial pressure and cerebral blood flow.
- The lowest rate of ICH was observed in the units used this neutral elevated head practice.
10- Avoid routine chest physiotherapy
There is evidence of a strong link between chest physiotherapy and ICH in preterm LBW infants.
This procedure can be devastating, especially in the first days of life.
11- Avoid routine suctioning
-It is well documented that repeated unnecessary suctioning could lead to changes in blood
pressure, cerebral blood flow, and intracranial pressure which might result in ICH..
- It is logical to think that these changes may be harmful to the infant, and the consensus therefore
was to eliminate this noxious activity from routine care.
12- Use of Sodium Bicarbonate
Although the use of bicarbonate for metabolic acidosis is widespread, there is little evidence
of its efficacy and a vast body of literature on its side effects.
The American Heart Association recognizes only 3 situations in which NaHCO3 is useful:
hyperkalemia, urinary bicarbonate loss, and prolonged cardiac arrest.
There is substantial evidence that diluting the bicarbonate and infusing it slowly is
preferable to rapid concentrated infusions.
Treatment of the basic problem causing the metabolic acidosis is still the best therapy.
Conclusion
The field of neonatal-perinatal medicine has developed significant resources to support the
practice of evidence-based medicine.
To begin to use these resources, we must prepare ourselves to become practitioners of
evidence-based medicine.
This includes mastering the five steps of practicing evidence-based medicine.
Although evidence-based practice can be successfully practiced on an individual level,
institutional approaches will help reinforce the practice of evidence-based medicine.