Neonatal vitamin A supplementation for prevention of mortality and morbidity among term neonates in low and middle income countries

Review question: Does vitamin A supplementation among term neonates in low and middle income countries prevent mortality and morbidity?

Background: Vitamin A is an important micronutrient that is required for maintenance of normal functioning of the human body. In the developing world, many pregnant women are vitamin A deficient. During pregnancy, additional vitamin A is required to promote growth of the baby and to provide stores in the baby's liver. Deficiency of this micronutrient in the mother may lead to its deficiency in the baby and may result in adverse effects on the baby's health. The benefits of giving vitamin A to children older than six months of age for reducing death and adverse effects on health have been established, but no available evidence shows this beneficial effect among infants one to five months of age. Potential benefits of vitamin A supplementation during the newborn period (during the first month of life) are under investigation.

Study characteristics: The present review identified 12 studies including 168,460 newborns in which the intervention group was supplemented with vitamin A during the newborn period.

Key results: Analysis of data for all infants shows no significant reduction in infant deaths at six months of age with the intervention and similar findings for infant deaths at 12 months of age.

Quality of evidence: We judged the quality of evidence as high for the most important clinical outcomes, with the exception of two outcomes that we scored as having low and very low quality: ‘diarrhoeal events during the first 48-72 hours post supplementation’ and ‘all-cause infant mortality at 6 months in term infants’, respectively.

Authors' conclusions: 

Given the high burden of death among children younger than five years of age in low and middle income countries, and the fact that mortality in infancy is a major contributory cause, it is critical to obtain sound scientific evidence of the effect of vitamin A supplementation during the neonatal period on infant mortality and morbidity. Evidence provided in this review does not indicate a potential beneficial effect of vitamin A supplementation among neonates at birth in reducing mortality during the first six months or 12 months of life. Given this finding and the absence of a clear indication of the biological mechanism through which vitamin A could affect mortality, along with substantial conflicting findings from individual studies conducted in settings with potentially varying levels of maternal vitamin A deficiency and infant mortality, absence of follow-up studies assessing any long-term impact of a bulging fontanelle after supplementation and the finding of a potentially harmful effect among female infants, additional research is warranted before a decision can be reached regarding policy recommendations for this intervention.

Read the full abstract...

Vitamin A deficiency is a major public health problem in low and middle income countries. Vitamin A supplementation in children six months of age and older has been found to be beneficial, but no effect of supplementation has been noted for children between one and five months of age. Supplementation during the neonatal period has been suggested to have an impact by increasing body stores in early infancy.


To evaluate the role of vitamin A supplementation for term neonates in low and middle income countries with respect to prevention of mortality and morbidity.

Search strategy: 

We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE via PubMed (1966 to 13 March 2016), Embase (1980 to 13 March 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 13 March 2016). We also searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.

Selection criteria: 

Randomised and quasi-randomised controlled trials. Also trials with a factorial design.

Data collection and analysis: 

Two review authors independently assessed trial quality and extracted study data. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence.

Main results: 

We included 12 trials (168,460 neonates) in this review, with only a few trials reporting disaggregated data for term infants. Therefore, we analysed data and presented estimates for term infants (when specified) and for all infants.

Data for term neonates from three studies did not show a statistically significant effect on the risk of infant mortality at six months in the vitamin A group compared with the control group (typical risk ratio (RR) 0.80; 95% confidence interval (CI) 0.54 to 1.18; I2 = 63%). Analysis of data for all infants from 11 studies revealed no evidence of a significant reduction in the risk of infant mortality at six months among neonates supplemented with vitamin A compared with control neonates (typical RR 0.98, 95% CI 0.89 to 1.07; I2 = 47%). We observed similar results for infant mortality at 12 months of age with no significant effect of vitamin A compared with control (typical RR 1.04, 95% CI 0.94 to 1.15; I2 = 47%). Limited data were available for the outcomes of cause-specific mortality and morbidity, vitamin A deficiency, anaemia and adverse events.