New evidence that maternal micronutrient status modifies the effect of neonatal vitamin A supplementation

headshotEmily Rose Smith


Although the World Health Organization (WHO) recommends vitamin A supplementation for infants and preschool children aged 6 to 59 months to reduce morbidity and mortality, the debate about whether or not to supplement newborns has been controversial.  (Note that an exchange in IJE 44:1 in 2015 also demonstrated some controversy about whether or not to continue supplementation for preschool-aged children). In an attempt to inform global policy, three large clinical trials were conducted in Tanzania, Ghana, and India. However, these trials found conflicting results. The trial conducted in India—consistent with previous trials in the region—found that supplementation reduced the risk of infant death, while the other two trials in Ghana and Tanzania found no effect of supplementation.

Inconsistency between the trials might indicate that some, but not all, children benefit from neonatal vitamin A supplementation (NVAS). Our study, published in the IJE, examines data from the Neovita trial in Tanzania, the largest NVAS study ever conducted in sub-Saharan Africa. We looked to see if there were any subgroups of infants in this trial who benefited from supplementation.

We found that maternal vitamin A status might explain why some infants benefited from NVAS and others did not. It is common (standard of care) for women in Tanzania to receive vitamin A supplementation right after childbirth. Our analysis indicates that NVAS reduced the risk of infant mortality only among infants whose mothers had not received supplemental vitamin A. In fact, the biggest reduction in mortality was found among the subgroup of infants whose mothers had not received supplemental vitamin A and also had inadequate vitamin A in their diets.

We did not see this reduction in risk of death associated with NVAS when we looked at the infants of mothers who received the usual postpartum vitamin A supplementation and, in fact, we found some evidence that neonatal supplementation might be harmful in this case. Furthermore, infants born to women who received the postpartum maternal vitamin A supplement and who had an adequate amount of vitamin A in their diets did not benefit from NVAS, and again there was some indication that neonatal supplementation might be harmful for these infants born to mothers with better vitamin A status.

Similarly, regional differences in NVAS trial results are hypothesized to be caused by differences in the prevalence of maternal vitamin A deficiency (VAD). In South Asia, where vitamin A deficiency is more common among mothers, trials have shown neonatal supplementation reduced infant mortality at six months by 13%. In Africa, where vitamin A deficiency is less common, trials have shown a 10% increased risk of infant mortality at six months. Our individual-level findings from one study are consistent with these population-level findings. However, this hypothesis should be explored further in an analysis including data from all NVAS trials.

While our results suggest that some infants might benefit from NVAS, it also raises the possibility that supplementation can be harmful in some cases. A decision to implement a neonatal vitamin A supplementation programme in any context should therefore be considered with caution.

Read More

Smith, ER, Muhihi A, Mshamu S, et al. The effect of neonatal vitamin A supplementation on morbidity and mortality at 12 months: A randomized trial. Int J. Epidemiol. 2016; doi: 10.1093/ije/dyw238.

 Haider BA, Bhutta ZA. Neonatal vitamin A supplementation: time to move on. Lancet. 2014; doi: 10.1016/S0140-6736(14)62342-4 .

Masanja H, Smith ER, Muhihi A, Briegleb C, Mshamu S, Ruben J, Noor RA, Khudyakov P, Yoshida S, Martines J, et al. Effect of neonatal vitamin A supplementation on mortality in infants in Tanzania: a randomized, double-blind, placebo-controlled trial. Lancet. 2014; doi: 10.1016/S0140-6736(14)61731-1 .

Bahl R, Bhandari N, Dube B, Edmond K, Fawzi W, Fontaine O, Kaur J, Kirkwood BR, Martines J, Masanja H, et al. Efficacy of early neonatal vitamin A supplementation in reducing mortality during infancy in Ghana, India and Tanzania: study protocol for a randomized controlled trial. Trials . 2012;13 (22).

World Health Organization (WHO). Guideline: Vitamin A supplementation in infants and children 6-59 months of age. Geneva, Switzerland: World Health Organization, 2011.


Emily R. Smith is a fourth-year doctoral student in the Department of Global Health and Population at the Harvard T. H. Chan School of Public Health. Her research is focused on generating, analyzing, and interpreting epidemiological data needed to improve maternal and child health in low and middle income countries. Ms. Smith has implemented both clinic-based and population-based randomized control trials to evaluate the efficacy of interventions to improve health. Her experience includes analysis of clinical trial data, utilizing methods for causal inference with observational data, and conducting meta-analyses. Ms. Smith completed her Master of Public Health (MPH) in Global Environmental Health at the Rollins School of Public Health at Emory University. She received a Bachelor of Arts (BA) from Northwestern University in Anthropology and International Studies. Follow Emily Smith on Twitter: @emily_ers.

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