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NICHD Cochrane Neonatal Home Page


These systematic reviews were provided by the Cochrane Neonatal Review Group, and are the result of activity sponsored, by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

NICHD has placed a high priority on making the work of this collaboration available because of the importance of relaying this information to health care professionals and to the public.

For more information concerning this site, please contact:

Mrs. Diane Haughton, Cochrane Neonatal Review
Group Coordinator
Department of Pediatrics, Room 3N11F
McMaster University
1200 Main Street West
Hamilton, Ontario L8N 3Z5
Telephone: 1 905 525-9140 ext. 22897
Fax: 1 905 521 5007


Introduction to Neonatal Systematic Reviews


  1. What are systematic reviews, and why do we need them?
  2. Who prepared these systematic reviews?
  3. Methods used in preparing these systematic reviews
  4. Assessing validity
  5. Combining results of independent studies
  6. Making inferences
  7. Viewing and printing analyses from a systematic review
  8. Contact Details

  1. What are systematic reviews, and why do we need them?

    The practice of evidence-based neonatology requires efficient access to up to date, valid evidence concerning the efficacy and safety of treatments. In the field of therapy, effects of only moderate size can be clinically very important and, to be able to detect them, all the available studies must be considered. Avoidance of bias is essential, so assessments of benefits and risks of therapy must be based primarily on evidence from randomized controlled trials.

    Busy clinicians, policymakers or patients 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 results of such systematic reviews are of importance in informing providers and consumers about the effect of treatments and in identifying priorities for new research.

  2. Who prepared these systematic reviews?

    The compendium of systematic reviews which is presented here is the work of members of the Cochrane Neonatal Review Group (CNRG) of the Cochrane Collaboration.

    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 are composed of individuals sharing an interest in an area of health-related care practice. The CNRG is composed of hundreds of individuals (neonatologists, pediatricians, physiotherapists, nursing, nutritionists, statisticians, health science librarians) from many countries around the world. Contact details for the members of the CNRG editorial team are given below. Contact details for the authors of specific reviews are given in the review itself.

    Reviews appearing on these web pages are Cochrane Collaboration Reviews which have been or will be published electronically in The Cochrane Library, Cochrane Database of Systematic Reviews.

  3. Methods used in preparing these systematic reviews

    Reviewers used a systematic, explicit method in preparing these reviews. The general approach is described in detail by Mulrow and Oxman in "How to Conduct a Cochrane Systematic Review", in the Cochrane Collaboration Handbook (1). The following brief description focuses on five essential elements: specifying the objectives of the review, identifying and selecting studies, assessing validity, combining results of independent studies, and making inferences.


    1. Specifying the objectives of the review

      The objectives of the review are formulated a priori as an explicit, focused research question which specifies the population, the intervention, and the outcomes (both beneficial and harmful) of interest. The reviewer frequently will set not only a main objective but also secondary objectives - for example, subgroup analyses or analyses of sources of variation in the results of the primary studies. A protocol is developed which states the objectives of the review, and specifies the methods that will be used at each stage of the review.

    2. Identifying and selecting studies

      The Cochrane Neonatal Group maintains a Register of controlled trials of interventions involving the baby during the first month after birth. The Register incorporates neonatal trials registered in the Oxford Database of Perinatal Trials which contains reports of virtually all neonatal trials up to 1992. The Register has been continuously updated since then as described below. Photocopies are obtained of all reports. The bibliographic details and, if need be, the full report, are supplied to the relevant reviewers. All controlled trials of interventions involving the baby during the first month after birth are potentially eligible for inclusion in the Neonatal Specialized Register. Controlled trials of interventions beyond the first month are also included if they involve the later management of neonatal diseases and would be of interest to neonatologists. Allocation to the treatment groups being compared must be random or quasi-random (e.g. alternate) for the trial to be registered in the Neonatal Specialized Register.

      The search for eligible controlled trials is done as follows:

      1. Electronic search of bibliographic databases

        The National Library of Medicine database Medline has been searched electronically back to 1966 and this search is updated monthly. The search strategy has been adjusted over time (2,3). At present we search for neonatal trials by relying on publication types: randomized controlled trial (PT) or controlled clinical trial (PT), as follows:

        Access via Entrez PubMed: Database, MEDLINE

        1. Search: infant, newborn OR infant, newborn, diseases OR neonat* Limits: publication type - randomized controlled trial Retrievals are reviewed by title and abstract to identify reports which qualify for the neonatal database. Final decision is based on the full report.
        2. Search: infant, newborn OR infant, newborn, diseases OR neonat* NOT randomized controlled trial [pt]
          Limits: publication type - clinical trial
      2. Handsearch of journals

        Over 700 journals are presently being handsearched through the combined efforts of handsearchers throughout the Cochrane Collaboration. Randomized controlled trials and controlled clinical trials which are identified by handsearching are sent to the US Cochrane Center and tagged as publication type RCT or CCT (Medline upgrade project). Reports of RCTs or CCTs which are eligible for inclusion in the Neonatal Specialized Register are ascertained by electronic searching of Medline as described previously.

        The Neonatal Group contributes to the overall effort in hand-searching journals by hand-searching 26 specialty journals in the fields of Pediatrics and neonatology.

      3. Ad hoc notification

        Ad hoc notification results in additional reports of eligible trials being added to the Neonatal register. These reports may be detected through the reviewer's personal knowledge or contacts. We solicit such notification from anyone who knows of an eligible trial that appears to have been overlooked in a review (see Contact details).

  4. Assessing validity

    Randomized trials, by their design, offer maximum protection against selection bias at entry. However, opportunities for bias arise at multiple points in the design, conduct, analysis and reporting of randomized trials. Therefore, the validity of each primary trial is assessed, and the methodological features of each trial are included as part of the review. Systematic attention is given to blinding of the randomization process, blinding of the intervention, completeness of follow-up, and blinding of the outcome measurement.

  5. Combining results of independent studies

    The measures of treatment effect include, for categorical dichotomous data, both relative estimators (odds ratio, relative risk) and absolute estimators (risk difference). For data measured on a continuous scale, the effect of treatment is expressed as the mean difference. For each outcome, standard statistical methods (1) are used to calculate the treatment effect (point estimate and 95% confidence interval) as shown in each trial and in the set of included trials as a whole. This latter estimate, the "typical effect", is a weighted average, the weights being the inverse of the variance of the estimate provided by each participating trial. Thus, large trials have more effect on the typical effect than do small trials. These methods are based on either fixed effect or random effects models. The neonatal reviews generally use a fixed effect model.

    The statistical significance of a treatment effect is demonstrated when the confidence interval around the point estimate of treatment effect excludes "no difference". This would occur when the confidence interval of the estimate for odds ratio or relative risk does not include one, or when the confidence interval for absolute risk reduction or mean difference does not include zero. By convention, the proportion of adverse events (rather than favorable outcomes) is tabulated. On the graphs, treatment effects which lie to the left of the no effect vertical line (e.g. to the left of an odds ratio, OR, of 1) indicate a result which favors the experimental group.

    Reviewers consider not only the direction and size of the typical treatment effect, but whether the results are reasonably consistent within a set of trials. If there is substantial heterogeneity of the results, the reviewer may elect not to calculate a typical effect.

  6. Making inferences

    The strength of inference concerning the probable effects of a treatment depends on the methodological quality of the primary trials on which the review was based, the degree of consistency of results among the trials contributing to the review, and the degree of confidence that the search for all trials relevant to the review has been comprehensive. When the methodologic quality of the included trials is high, and the results are consistent within the set of trials, and there is high confidence that all relevant trials have been detected, there is a basis for strong inference regarding the statistical significance and clinical implications of the results.

  7. Viewing and printing analyses from a systematic review

    To view the analyses tables and graphs, go to Data Tables & Graphs at the end of the review and click on the specific outcome you want to see. From there you will be able to scroll vertically and horizontally to view the table or graph on the screen. If you choose to print the analyses, changing your print options from portrait to landscape may be necessary.

  8. Contact Details

    Mrs. Diane Haughton, Review Group Coordinator
    Department of Pediatrics, Rm 3N11F
    McMaster University
    1200 Main Street West
    Hamilton, Ontario L8N 3Z5
    Telephone: 1 905 525-9140 ext. 22897
    Fax: 1 905 521 5007

    Editorial Information:
    Cochrane Neonatal Group
    Registered with the Collaboration on 1 April 1993

    Coordinating Editor:
    Dr. Roger Soll, (USA)

    Dr. John C. Sinclair (Canada)
    Professor Michael B. Bracken (USA)
    Dr. Jeffrey Horbar (USA)

    Regional Coordinators:
    Professor David J Henderson-Smart (Australasia)
    Dr. Peter Davis (Australasia)
    Professor Henry Halliday (UK and Europe)
    William McGuire (UK and Europe)

    Other Support to the Editorial Team:
    Lisa Milani (current),
    Myriam Bickle-Graz, Brenda Tan (previous)
    Tara Graham, Abigail d'Sa (previous)
    Grace Wang (previous)

    Trials Search Coordinator:
    Bharati Purohit (current)
    Sandra Costa (previous)

    The Cochrane Library can be obtained from:
    John Wiley and Sons Ltd.
    1 Oldlands Way
    Bognor Regis
    West Sussex
    PO22 9SA
    Tel: +44 (0) 1243 843397
    Fax: +44 (0) 1243 843232


    John Wiley & Sons Inc
    Subscription Department
    111 River Street
    Hoboken, NJ 07030
    Tel: Toll-free USA only: 1 866 465 3817
    Tel: Outside USA: 1 201 748 6645
    Fax: 1 201 784 5715

    Sources of Support for the Cochrane Neonatal Collaborative Review Group:
    Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA

    Other Support (past):
    David and Lucile Packard Foundation, USA
    American Academy of Pediatrics, USA
    Perinatal Clinical Epidemiology Unit, Toronto, Canada
    Dept. of Pediatrics, McMaster University, Hamilton, Canada
    Dept. of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada

  9. References
    1. Mulrow CD, Oxman AD (eds). Cochrane Collaboration Handbook [updated 21 October 1996]. Available in The Cochrane Library [database on disk and CD-ROM]. The Cochrane Collaboration; Issue 3. Oxford: Update Software; 1996. Updated quarterly. Available from: BMJ Publishing Group, London.
    2. Kirpalani H, Schmidt B, McKibbon A, Haynes B, Sinclair JC. Searching Medline for randomized clinical trials on care of the newborn. Pediatrics 85:543-546, 1988.
    3. Haynes RB, Wilczynski N, McKibbon KA, Walker CJ, Sinclair JC. Developing optimal search strategies for detecting clinically sound studies in Medline. J Amer Informatics Assoc 1994;1:447-458.