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

Abstract

Background: Each year almost one million newborns die from infections, mostly in low-income countries. Timely case management would save many lives but the relative mortality effect of varying strategies is unknown. We have estimated the effect of providing oral, or injectable antibiotics at home or in first-level facilities, and of in-patient hospital care on neonatal mortality from pneumonia and sepsis for use in the Lives Saved Tool (LiST).

Methods: We conducted systematic searches of multiple databases to identify relevant studies with mortality data. Standardized abstraction tables were used and study quality assessed by adapted GRADE criteria. Meta-analyses were undertaken where appropriate. For interventions with biological plausibility but low quality evidence, a Delphi process was undertaken to estimate effectiveness.

Results: Searches of 2876 titles identified 7 studies. Among these, 4 evaluated oral antibiotics for neonatal pneumonia in non-randomised, concurrently controlled designs. Meta-analysis suggested reductions in all-cause neonatal mortality (RR 0.75 95% CI 0.64- 0.89; 4 studies) and neonatal pneumonia-specific mortality (RR 0.58 95% CI 0.41- 0.82; 3 studies). Two studies (1 RCT, 1 observational study), evaluated community-based neonatal care packages including injectable antibiotics and reported mortality reductions of 44% (RR = 0.56, 95% CI 0.41-0.77) and 34% (RR = 0.66, 95% CI 0.47-0.93), but the interpretation of these results is complicated by co-interventions. A third, clinic-based, study reported a case-fatality ratio of 3.3% among neonates treated with injectable antibiotics as outpatients. No studies were identified evaluating injectable antibiotics alone for neonatal pneumonia. Delphi consensus (median from 20 respondents) effects on sepsis-specific mortality were 30% reduction for oral antibiotics, 65% for injectable antibiotics and 75% for injectable antibiotics on pneumonia-specific mortality. No trials were identified assessing effect of hospital management for neonatal infections and Delphi consensus suggested 80%, and 90% reductions for sepsis and pneumonia-specific mortality respectively.

Conclusion: Oral antibiotics administered in the community are effective for neonatal pneumonia mortality reduction based on a meta-analysis, but expert opinion suggests much higher impact from injectable antibiotics in the community or primary care level and even higher for facility-based care. Despite feasibility and low cost, these interventions are not widely available in many low income countries.

Funding: This work was supported by the Bill & Melinda Gates Foundation through a grant to the US Fund for UNICEF, and to Saving Newborn Lives Save the Children, through Save the Children US.

Figure 1

Searches and screening for community based management of sepsis and pneumonia.

Figure 2

Searches and screening for hospital management of sepsis

Figure 3

Searches and screening for hospital management of pneumonia.

Figure 4

Meta-analysis of observational studies comparing oral antibiotics versus none in the community setting for babies: All cause mortality. Legend: Heterogeneity chi-squared = 1.17 (d.f. = 3) p = 0.760 I-squared (variation in RR attributable to heterogeneity) = 0.0% Test of RR=1 : z= 3.32 p = 0.001

Figure 5

Meta-analysis of observational studies comparing oral antibiotics versus none in the community setting for babies: Pneumonia mortality. Legend: Heterogeneity chi-squared = 2.16 (d.f. = 2) p = 0.339 I-squared (variation in RR attributable to heterogeneity) = 7.5% Test of RR=1: z= 3.06 p = 0.002

Figure 6

Box plot of Delphi expert opinion estimates of reduction in neonatal cause specific mortality due to pneumonia and sepsis/meningitis

Figure 7

Plot of neonatal sepsis CFR versus percent skilled delivery as a marker of access to facility care. Model fitted: outcome = log(CFR) Covariates = Skilled attendant coverage and % babies vLBW Fitted line is predicted CFR for settings with % VLBW<30%. Predicted CFR at 0% skilled attendance is 30%. Predicted CFR at 100% skilled attendance is 9.5%. % reduction = 68.5% Coefficient skilled attendance is 0.12 on the log scale (95% CI -0.02 to -0.007); i.e. for each 1% increase in skilled attendance rate CFR is reduced by 1.1% (95% CI: 0.7% to 1.6%)