Early neonatal Vitamin A supplementation and infant mortality: An individual participant data meta-analysis of randomised controlled trials

Keith P. West, Lee S.F. Wu, Hasmot Ali, Rolf D.W. Klemm, Karen Margaret Edmond, Lisa Hurt, Betty Kirkwood, Sam Newton, Caitlin Shannon, Sunita Taneja, Sarmila Mazumder, Kiran Bhatia, Nita Bhandari, Joanne Katz, James M. Tielsch, Jean Humphrey, Tina Agoestina, Sajid Bashir Soofi, Shabina Ariff, Zaid BhattiSimon Cousens, Zulfiqar A. Bhutta, Robert Ntozini, Honorati Masanja, Emily R. Smith, Alfa Muhihi, Wafaie Fawzi, Rajiv Bahl, Jose Martines, Sachiyo Yoshida

Research output: Contribution to journalArticlepeer-review

Abstract

Biannual vitamin A supplementation is a well-established survival tool for preschool children 6 months and older in vitamin A deficient populations but this schedule misses the opportunity to intervene on most young infant deaths. Randomised trials of neonatal vitamin A supplementation (NVAS) in the first few days of life to assess its impact on under 6-month mortality in low/middle-income countries have had varying results. Methods Investigators of 11 published randomised placebo-controlled NVAS trials (n=163 567 children) reanalysed their data according to an agreed plan and pooled the primary outcomes of mortality from supplementation through 6 and 12 months of age using random effects models and meta-regression. One investigator withdrew but allowed use of the data. Findings Overall there was no effect of NVAS on infant survival through 6 (risk ratio (RR) 0.97; 95% CI 0.89 to 1.06) or 12 months of age (RR 1.00; 95% CI 0.93 to 1.08) but results varied by study population characteristics. NVAS significantly reduced 6-month mortality among the trials conducted in Southern Asia (RR 0.87; 95% CI 0.77 to 0.98), in contexts with moderate or severe vitamin A deficiency (defined as 10% or higher proportion of women with serum retinol <0.7 μmol/L or 5% or more women with night blindness) (RR 0.87; 95% CI 0.80 to 0.94), early infant mortality was 30 or more per 1000 live births (RR 0.91; 95% CI 0.85 to 0.98), 75% or more of infant mortality occurred in the first 6 months of life (RR 0.92; 95% CI 0.84 to 1.01), or where >32% mothers had no schooling (RR 0.88; 95% CI 0.80 to 0.96). NVAS did not reduce mortality in the first 6 months of life in trials conducted in Africa, in contexts characterised by a low prevalence of vitamin A deficiency, lower rates of infant mortality and where maternal education was more prevalent. There was a suggestion of increased infant mortality in trials conducted in Africa (RR 1.07; 95% CI 1.00 to 1.15). Individual-level characteristics such as sex, birth weight, gestational age and size, age at dosing, parity, time of breast feeding initiation, maternal education and maternal vitamin A supplementation did not modify the impact of NVAS. Conclusion NVAS reduced infant mortality in South Asia, in contexts where the prevalence of maternal vitamin A deficiency is moderate to severe and early infant mortality is high; but it had no beneficial effect on infant survival in Africa, in contexts where the prevalence of maternal vitamin A deficiency is lower, early infant mortality is low.

Original languageEnglish (US)
Pages (from-to)217-226
Number of pages10
JournalArchives of disease in childhood
Volume104
Issue number3
DOIs
StatePublished - Mar 1 2019

Keywords

  • infant mortality
  • neonatal Vitamin A supplementation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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