Elsevier

The Lancet

Volume 385, Issue 9975, 4–10 April 2015, Pages 1324-1332
The Lancet

Articles
Effect of neonatal vitamin A supplementation on mortality in infants in Tanzania (Neovita): a randomised, double-blind, placebo-controlled trial

https://doi.org/10.1016/S0140-6736(14)61731-1Get rights and content

Summary

Background

Supplementation of vitamin A in children aged 6–59 months improves child survival and is implemented as global policy. Studies of the efficacy of supplementation of infants in the neonatal period have inconsistent results. We aimed to assess the efficacy of oral supplementation with vitamin A given to infants in the first 3 days of life to reduce mortality between supplementation and 180 days (6 months).

Methods

We did an individually randomised, double-blind, placebo-controlled trial of infants born in the Morogoro and Dar es Salaam regions of Tanzania. Women were identified during antenatal clinic visits or in the labour wards of public health facilities in Dar es Salaam. In Kilombero, Ulanga, and Kilosa districts, women were seen at home as part of the health and demographic surveillance system. Newborn infants were eligible for randomisation if they were able to feed orally and if the family intended to stay in the study area for at least 6 months. We randomly assigned infants to receive one dose of 50 000 IU of vitamin A or placebo in the first 3 days after birth. Infants were randomly assigned in blocks of 20, and investigators, participants' families, and data analysis teams were masked to treatment assignment. We assessed infants on day 1 and day 3 after dosing, as well as at 1, 3, 6, and 12 months after birth. The primary endpoint was mortality at 6 months, assessed by field interviews. The primary analysis included only children who were not lost to follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number ACTRN12610000636055.

Findings

Between Aug 26, 2010, and March 3, 2013, 31 999 newborn babies were randomly assigned to receive vitamin A (n=15 995) or placebo (n=16 004; 15 428 and 15 464 included in analysis of mortality at 6 months, respectively). We did not find any evidence for a beneficial effect of vitamin A supplementation on mortality in infants at 6 months (26 deaths per 1000 livebirths in vitamin A vs 24 deaths per 1000 livebirths in placebo group; risk ratio 1·10, 95% CI 0·95–1·26; p=0·193). There was no evidence of a differential effect for vitamin A supplementation on mortality by sex; risk ratio for mortality at 6 months for boys was 1·08 (0·90–1·29) and for girls was 1·12 (0·91–1·39). There was also no evidence of adverse effects of supplementation within 3 days of dosing.

Interpretation

Neonatal vitamin A supplementation did not result in any immediate adverse events, but had no beneficial effect on survival in infants in Tanzania. These results strengthen the evidence against a global policy recommendation for neonatal vitamin A supplementation.

Funding

Bill & Melinda Gates Foundation to WHO.

Introduction

Every year, an estimated 6·9 million children die before their fifth birthday. About 44% of deaths of children younger than 5 years occur in the neonatal period, mostly in southeast Asia and sub-Saharan Africa.1 The Millennium Development Goal for child survival will not be achieved without additional investments to address newborn baby deaths. Interest to estimate trends and causes of newborn deaths2 and to reduce mortality with safe and efficacious interventions3 has increased. Vitamin A deficiency is thought to be a major public health issue in low-income countries.4, 5 Evidence from a systematic review6 and meta-analyses7, 8 of randomised controlled trials indicate a significant benefit of periodic vitamin A supplementation for children aged 6–59 months, reducing all-cause mortality by 23–30%. This body of evidence prompted policy recommendations by WHO9 and catalysed the implementation of large-scale supplementation programmes for children younger than 5 years to improve child survival.9

Results from studies to establish whether vitamin A supplementation can provide similar benefits in children younger than 6 months have conflicting results, ranging from no benefit10 to potential benefit11, 12, 13 or possible harm, at least in subsets of children.14, 15 This conflicting evidence prompted the development of large trials to generate the necessary evidence to inform global programmes that aim to improve child survival.16

We did a trial in Tanzania to establish the effect on infant mortality of vitamin A supplementation given on the day of birth or within the next 2 days. This is one of three large trials recommended by a technical consultation team convened by WHO in December, 2008, to inform global policy for or against newborn vitamin A supplementation. Two companion studies done in India and Ghana are reported elsewhere.17, 18

Section snippets

Study design and participants

We did a randomised double-blind, placebo-controlled trial in Dar es Salaam and Morogoro regions of Tanzania. The characteristics of the study areas have been described elsewhere.16 In Dar es Salaam, we enrolled mothers and newborn babies from ten large antenatal clinics and labour wards in the catchment areas, and in the Morogoro region, the study was nested within the Ifakara Health Institute's health and demographic surveillance system (HDSS). The Ifakara HDSS covers about 2400 km2 and is

Results

Between Aug 26, 2010, and March 3, 2013, we identified and assessed 34 133 livebirths for eligibility (figure 1). 1290 were not screened because they did not consent, died before screening, or could not be contacted. 844 (3%) newborn infants were excluded (figure 1). We randomly assigned 31 999 newborn babies to receive either vitamin A (n=15 995) or placebo (n=16 004). Most (24 888; 78%) infants received vitamin A or placebo within 24 h (table 1). Maternal and infant characteristics were

Discussion

Provision of one dose of vitamin A at birth was thought to be a low-cost intervention that could have significant protective effects on development of the immune system and early infant mortality.23 In this trial we did not show a beneficial effect on survival at age 6 months in infants given vitamin A supplementation within the first 3 days after birth, although the findings do not exclude the possibility of a slight increased risk of death.

Our results are consistent with a companion trial in

References (28)

  • A Imdad et al.

    Vitamin A supplementation for preventing morbidity and mortality in children from 6 months to 5 years of age

    Cochrane Database Syst Rev

    (2010)
  • WW Fawzi et al.

    Vitamin A supplementation and child mortality. A meta-analysis

    JAMA

    (1993)
  • PP Glasziou et al.

    Vitamin A supplementation in infectious diseases: a meta-analysis

    BMJ

    (1993)
  • Vitamin A supplements. A guide to their use in the treatment and prevention of vitamin A deficiency and xerophthalmia

    (1997)
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