Busy clinicians cannot readily keep abreast of the evidence from individual trials. Moreover, neonatology is a rapidly changing field where there are frequent shifts in the weight of accumulating evidence. Therefore, there is a pressing need for continuously updated reviews of the results of randomized trials. These can provide efficient access to current evidence and avoid a long gap between the time when the efficacy of a treatment has in fact been established and the time when the treatment is routinely recommended.A systematic review of the results of randomized, controlled trials employs explicit, systematic methods designed to produce unbiased and precise estimates of the effect of a treatment on each of the major outcomes of clinical importance. The term “systematic review” is used to distinguish its explicit methodology from that of a non-systematic review where the methodology of the review process is not made explicit and opinion may be mixed with evidence. The use of statistical methods to aggregate and summarize the results of independent studies (meta-analysis) increases the power to detect treatment effects and can provide more precise estimates of the size of treatment effects than are provided by an individual trial.The Cochrane Collaboration is an international collaboration of individuals and entities with a mandate to prepare, maintain and disseminate systematic reviews of the effects of health care. Collaborative Review Groups (CRG) is composed to individuals sharing an interest in an area of health-related care practice. The Neonatal CRG is composed of approximately 60 neonatologists in five countries</sec><sec id="sec001"><title>Interpretation of meta-analysis

JNNFI

Journal of Neonatology

0973-21870973-2179

National Neonatology Forum

jn-17-4-009

Cochrane meta-analyses on respiratory disorders in neonates

Agarwal

Ramesh

Upadhyay

Amit

Division of Neonatology, Department of Pediatrics all india institute of medical sciences, New Delhi-110 029

10–122003

1746165

Busy clinicians cannot readily keep abreast of the evidence from individual trials. Moreover, neonatology is a rapidly changing field where there are frequent shifts in the weight of accumulating evidence. Therefore, there is a pressing need for continuously updated reviews of the results of randomized trials. These can provide efficient access to current evidence and avoid a long gap between the time when the efficacy of a treatment has in fact been established and the time when the treatment is routinely recommended.A systematic review of the results of randomized, controlled trials employs explicit, systematic methods designed to produce unbiased and precise estimates of the effect of a treatment on each of the major outcomes of clinical importance. The term “systematic review” is used to distinguish its explicit methodology from that of a non-systematic review where the methodology of the review process is not made explicit and opinion may be mixed with evidence. The use of statistical methods to aggregate and summarize the results of independent studies (meta-analysis) increases the power to detect treatment effects and can provide more precise estimates of the size of treatment effects than are provided by an individual trial.The Cochrane Collaboration is an international collaboration of individuals and entities with a mandate to prepare, maintain and disseminate systematic reviews of the effects of health care. Collaborative Review Groups (CRG) is composed to individuals sharing an interest in an area of health-related care practice. The Neonatal CRG is composed of approximately 60 neonatologists in five countries</sec><sec id="sec001"><title>Interpretation of meta-analysis

Generally the pooled results of the included studies are expressed as relative risk (RR) and risk difference and their confidence interval. A relative risk of one would mean that proposed therapy is equally efficacious than the control therapy. A RR of less or more than one would mean that proposed therapy is more or less efficacious respectively than control therapy. If confidence interval (CI) of RR includes 1 in its range than the difference in effects of proposed and control therapies are not significant. For example in prophylactic versus selective surfactant replacement therapy (Table 1), RR for mortality is 0.61 with CI of 0.48–0.77. Since the CI does not include 1, it signifies that there is statistically significant reduction in mortality with use of prophylactic SRT compared to selective use of SRT.

The present article briefly summarizes the Cochrane meta-analyses related to various therapies of respiratory disorders in preterm neonates. These meta-analysis can be accessed in full details on the NICHD website (http://www.nichd.nih.gov/cochrane/cochrane.htm) at no cost.

Surfactant Replacement Therapy (SRT)

A total of eight meta-analyses have been conducted on SRT (Table 1) (1–8). The comparison of prophylactic versus selective use of SRT revealed the former approach is definitely superior than later in terms of decreased airleak, pulmonary interstitial emphysema (PIE) and mortality (1). However this approach results in overuse of the drug thus increasing the cost. Secondly eligibility for prophylactic SRT have been variable all through the included studies.

In selective SRT, early usage (within 2 hours) is better that delayed use (2). Natural surfactants have many proteins also, which enhance the activity of surfactant, and have been shown to be more effective than artificial surfactant (3). Multiple doses of surfactant (two to four) are better than single dose of surfactant (4). SRT has been evaluated for meconium aspiration syndrome also (8). However the number of patients included in studies are not enough to recommend its routine use.

Use of continuous positive pressure (CPAP)

The meta-analyses on CPAP have revealed that use nasal CPAP (nCPAP) in respiratory distress syndrome (RDS) is associated with reduced respiratory failure and mortality with higher risk of pneumothorax (Table 2)(9). The early use of nCPAP is associated with higher benefits compared to delayed institution (10).

A brief period of prior to extubation trial of endotracheal CPAP compared to direct extubation from low rate is associated with increased adverse outcomes, so it should not be practiced (11).

Meta-analysis comparing synchronized nasal IPPV with CPAP has shown superiority of the former for apnea of prematurity (12) and for preventing extubation failure in ventilated preterm babies (13). However this modality has not been tested on sufficient number of babies to warrants its routine clinical use.

Similarly use of prophylactic NCPAP in preterms has been shown to do more harm than good and so it should not be used till more evidence is available (5). Use of short binasal prong devices are more effective than single nasal or nasopharyngeal prong for preventing extubation failure in preterm ventilated babies (14) Infant flow driver (IFD) has been shown to be a better device for delivery of CPAP to babies (14).

Use of postnatal steroids for prevention/treatment of chronic lung disease

All the different schedules of use for postnatal steroids usage (early (15) moderately early (16) and delayed 19) are associated with some reduction in CLD at 28 days and 36 weeks of post conceptional age (Table-3). However, this results in significant increase in both short and long term adverse effects, which prohibit its routine use. It is pertinent here to mention the result of another meta-analysis, which reported long-term effects of steroid use in preterm neonates with CLD (22). Use of either inhaled corticosteroids for bronchodilat or has also not been associated with any benefit in treatment of CLD (18, 19). The postnatal steroid was associated with 2–3 times higher risk of major neurodevelopment disability 22. It is therefore recommended that postnatal steroids for this purpose should not be used in clinical practice.

Apnea of prematurity (AOP)

Theophylline and oral caffeine are equally efficacious in preterm babies in first 2–7 days for treatment of AOP (25). However there were lesser adverse events with use of caffeine in preterm babies. Prophylactic methylxanthines should not be used in preterm at risk of AOP (22). Doxapram has similar efficacy to methylxanthines in treatment of AOP, but should not be used as primary drug for AOP due to more adverse effects (23).

Kinesthetic stimulation was evaluated in two meta-analysis for prevention and treatment of AOP (24, 25). The numbers of patients included were too small to make any conclusive comment about their usages.

High frequency ventilation

High frequency oscillatory ventilation (HFOV) was studied in three different meta-analyses compared with conventional ventilator (CV). Elective HFOV compared to CV has not been shown any superiority in preterm with acute pulmonary dysfunction (26). HFOV used, as rescue modality was also not superior to CV in preterm babies with respiratory insufficiency (27). Rescue HFOV has also not been shown to be superior to CV in term/near term neonates with respiratory dysfunction (28).

In one meta-analysis high frequency jet ventilation (HFJV) is also found to be no different than CV (29).

Meta-analyses on ventilation and other adjunct treatment

In a meta-analysis, synchronized ventilation was superior to CV in terms of decreased air leaks (30). Melhylxanthines have been found to be efficacious if given before extubation to prevent extubation failure in preterm ventilated babies (31) While prophylactic doxapram for the same purpose was having deleterious effects (32). Infant position during ventilation was studied in meta-analysis (33). Prone position was superior than the other positions Nasal intubation compared to oral intubation was studied in a meta-analysis. Nasal intubation was having higher side effects than oral intubation in preterm babies (34). There was insufficient evidence for use of neuromuscular paralysis in ventilated babies (35). Similarly practice of permissive hypercapnia in ventilated babies had insufficient evidence (36).

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