The effect of neonatal vitamin A supplementation on morbidity and mortality at 12 months: a randomized trial.

Emily R Smith,Salum Mshamu,Roger L Shapiro,Donna Spiegelman,Alfa Muhihi,Ramadhani Abdallah Noor,Christopher R Sudfeld,Wafaie Fawzi,Honorati Masanja

doi:10.1093/ije/dyw238

Abstract

Background: Neonatal vitamin A supplementation (NVAS) is an intervention hypothesized to reduce infant morbidity and mortality. The objective of this study was to assess the efficacy of neonatal vitamin A supplementation in reducing infant morbidity and mortality and assess potential sources of heterogeneity of the effect of NVAS. Methods: We completed an individually randomized, double-blind, placebo-controlled trial in Tanzania. Infants were randomized within 3 days of birth to a single dose of vitamin A (50 000 IU) or placebo. We assessed infants at 1 and 3 days after supplementation, as well as 1, 3, 6 and 12 months after supplementation. We included all live births in the analysis and used relative risks (RR) and 95% confidence intervals (CI) to assess the risks of mortality and hospitalization by 12 months. We used general estimating equations to assess the incidence of morbidities during infancy. Results: A total of 31 999 infants were enrolled in the study between August 2010 and March 2013. At 12 months, vitamin A did not reduce all-cause infant mortality (RR 1.04; 95% CI 0.92-1.16), nor affect hospitalization (RR 1.09; 95% CI 0.97-1.22) or all-cause morbidity (RR 1.00; 95% CI 0.96-1.05). Postpartum maternal vitamin A supplementation modified the effect of neonatal vitamin A supplementation on mortality at 12 months (P-value, test for interaction = 0.04). Among infants born to women who received a mega-dose of vitamin A after delivery, NVAS appeared to increase the risk of death (RR 1.12; 95% CI 0.98-1.29), whereas the risk of death among infants born to women who did not receive a mega-dose was reduced (RR 0.86; 95% CI 0.70-1.06). We noted no modification of the effect of NVAS by infant gender, birthweight or maternal HIV status. Conclusion: NVAS did not affect the risk of death or incidence of common childhood morbidities. However, this study sheds light on potential sources of heterogeneity of the effect of neonatal vitamin A supplementation which should be further examined in a pooled analysis of all NVAS trials.

Highlights

Despite improvements in child survival in the past four decades, an estimated 6.3 million children under the age of five died in 2013.1 child mortality continues to decline, there has been slower progress in reducing infant mortality
This study sheds light on potential sources of heterogeneity of the effect of neonatal vitamin A supplementation which should be further examined in a pooled analysis of all Neonatal vitamin A supplementation (NVAS) trials
The recent completion and analysis of the three largest neonatal vitamin A supplementation trials (NEOVITA) found conflicting results regarding the efficacy of this intervention in reducing infant morbidity and mortality

Summary

Introduction

Despite improvements in child survival in the past four decades, an estimated 6.3 million children under the age of five died in 2013.1 child mortality continues to decline, there has been slower progress in reducing infant mortality. Interventions to reduce neonatal and infant mortality are needed, and there is evidence that vitamin A supplementation can reduce morbidity and mortality among children aged 6 to 59 months.[2] A number of trials to assess the efficacy of neonatal vitamin A supplementation have had conflicting findings. Neonatal vitamin A supplementation (NVAS) is an intervention hypothesized to reduce infant morbidity and mortality. The objective of this study was to assess the efficacy of neonatal vitamin A supplementation in reducing infant morbidity and mortality and assess potential sources of heterogeneity of the effect of NVAS. We noted no modification of the effect of NVAS by infant gender, birthweight or maternal HIV status

Objectives

Methods

Results

Discussion

Conclusion