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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Effect of case management on neonatal mortality due to sepsis and pneumonia

AK Zaidi, HA Ganatra, S Syed, S Cousens, AC Lee, R Black, ZA Bhutta, and JE Lawn.

Review published: 2011.

CRD summary

This review concluded that oral or injectable antibiotics, administered in the community or in hospital, were effective in preventing neonatal deaths from pneumonia. Given the quality of the evidence available, the conclusions seem overly strong.

Authors' objectives

To evaluate the effectiveness of pneumonia or sepsis management in the community, with injectable or oral antibiotics or both, and hospital-based case management, to prevent neonatal deaths from severe infection.


PubMed, The Cochrane Library, and the World Health Organization (WHO)'s regional databases were searched, without language restrictions, for articles from 1990 to April 2009; search terms were reported. Investigators and programme managers were contacted to identify unpublished studies or data.

Study selection

Observational studies, randomised controlled trials (RCTs), systematic reviews, and meta-analyses that included neonates and primarily evaluated the management of serious neonatal infections, were eligible for inclusion. Studies had to report mortality from all causes; from sepsis, meningitis, or pneumonia; as case-fatality ratios; or any combination of these.

There was no standard definition of clinical neonatal sepsis or pneumonia across the studies; most defined them using the WHO Integrated Management of Childhood Illnesses criteria. All studies were from regions with high neonatal mortality. The participants received a range of co-interventions that varied considerably across studies.

The authors did not state how many reviewers selected studies.

Assessment of study quality

Study quality was assessed using GRADE. The authors did not state how many reviewers assessed quality.

Data extraction

Two reviewers independently extracted the data to calculate risk ratios and 95% confidence intervals. Study authors were contacted for missing data.

Methods of synthesis

Pooled risk ratios and 95% confidence intervals were calculated using the Mantel-Haenzsel fixed-effect model, or where there was evidence of heterogeneity, the DerSimonian and Laird random-effects model. Heterogeneity was assessed using Ι². Where insufficient data were available, expert opinion was sought using a Delphi process.

Results of the review

Sixty-four studies met the inclusion criteria (the number of patients was unclear); one was a RCT, five were non-randomised controlled trials, and the remainder were observational studies. The evidence was considered to be of low-to-moderate quality.

For community-based management (seven studies), oral antibiotics were associated with reductions in all-cause mortality (RR 0.75, 95% CI 0.64 to 0.89; four studies), and pneumonia-related mortality (RR 0.58, 95% CI 0.41 to 0.82; three studies). No studies were identified on the effect of oral antibiotics on sepsis-related mortality.

For community-based injected antibiotics, the RCT reported a significant reduction in all-cause mortality with a perinatal care package (RR 0.66, 95% CI 0.47 to 0.93), in domiciliary settings, where referral to hospital was not possible. A non-randomised controlled study reported a significant reduction in mortality, in a similar situation (RR 0.56, 95% CI 0.41 to 0.77). An observational study of children from the RCT reported a case-fatality rate of 4.4%. One uncontrolled study reported a case-fatality rate of 3.3%.

Across 55 observational studies evaluating hospital management of sepsis, the case-fatality rate ranged from 6.7% to 67%. Two observational studies evaluated hospital management of pneumonia, and found case-fatality rates of 14.4% and 30.8%. The results of the Delphi processes were reported.

Authors' conclusions

Oral antibiotics administered in the community were effective in reducing neonatal mortality from pneumonia. Expert opinion suggested a much higher impact from injectable antibiotics, in the community or in primary care, and an even higher impact in facility-based care.

CRD commentary

The review addressed a clear question, supported by reproducible inclusion criteria. Relevant sources were searched, with no language restrictions, and attempts were made to identify unpublished studies. The data were extracted by two people independently; it was unclear whether similar methods were used to reduce the risk of error and bias in study selection and quality assessment. Appropriate methods were used to assess study quality and the results were reported in full. Most of the analyses and conclusions were based on a few studies.

Given the quality of the evidence available, the conclusions seem overly strong.

Implications of the review for practice and research

Practice: The authors stated that despite feasibility and low cost, the interventions were not widely available in many low-income countries. Oral or injectable antibiotics could reduce the one million neonatal deaths each year, if community and facility-based interventions were implemented and linked by a functioning referral system.

Research: The authors did not state any implications for research.


Supported by the Bill and Melinda Gates Foundation, USA.

Bibliographic details

Zaidi AK, Ganatra HA, Syed S, Cousens S, Lee AC, Black R, Bhutta ZA, Lawn JE. Effect of case management on neonatal mortality due to sepsis and pneumonia. BMC Public Health 2011; 11(Supplement 3): S13. [PMC free article: PMC3231886] [PubMed: 21501430]

Indexing Status

Subject indexing assigned by NLM


Anti-Bacterial Agents /therapeutic use; Case Management; Controlled Clinical Trials as Topic; Humans; Infant Mortality; Infant, Newborn; Pneumonia /drug therapy /mortality; Sepsis /drug therapy /mortality; Treatment Outcome



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 21501430