Vitamin A Supplementation in Newborns Study

I. Background

A variety of studies over the past 15 years have demonstrated that clinical vitamin A deficiency is associated with increased mortality in pre-school aged children (1,2) and that supplementation of populations with endemic sub-clinical vitamin A deficiency can significantly reduce total mortality (3-8). A recent meta-analysis of 8 clinical trials showed that vitamin A supplementation of children 6 months through 5 years of age reduced mortality by an average of 23% (9). While the average impact was 23%, there was significant variation in the results of these studies. The impact was as high as 54% among children in an underprivileged area of Tamil Nadu supplemented with small weekly doses of vitamin A (4).

While the story of the impact of vitamin A supplementation in children 6 months and older is clear, such is not the case for younger infants. Traditionally, it has been thought that the full-time breast feeding practices associated with early infancy protected the infant from becoming vitamin A deficient. It was not until the onset of weaning or the misuse of bottle-feeding that clinical signs of xerophthalmia appeared (1). Recent evidence from a variety of locations suggests that these traditional assumptions about the adequacy of breast -feeding in assuring adequate vitamin A nutriture are suspect and likely unfounded. It is well known that infants are born with very low body stores of vitamin A and they depend on regular breast feeding or other sources to build body stores (13, 14). Therefore, if the mother's breast milk has a lower than normal concentration of vitamin A, the infant will not be able to meet daily requirements and increase body reserves. It has become clear that many women in developing countries have poor vitamin A status themselves and that their breast milk concentrations may be only half that found among women with adequate vitamin A status (15). In addition, it has been shown in Indonesia that supplementation of women post-partum can improve the vitamin A concentration in their blood and breast milk (16).

While it is becoming clearer that young infants in developing countries with endemic vitamin A deficiency are at significant risk of being vitamin A deficient in spite of adequate breast feeding behaviour, there is little data concerning the impact of supplementing this group with vitamin A. Two major studies have addressed this issue, both done by the same group at Johns Hopkins University, with opposite findings. Humphrey et al. have reported, in a randomized clinical trial of 2067 infants born in a hospital in Bandung, Indonesia, that direct supplementation of newborn infants within 24 hours of birth with 50,000 IU of vitamin A was safe (10) and associated with a 64% reduction in infant mortality (11). In contrast, West et al. studied over 11,000 infants under six months of age in their large intervention trial in southern Nepal (17). They found no difference in mortality between those supplemented with vitamin A versus those given placebo (relative risk =1.11, 95% CI 0.86 - 1.42). However, there were significant and potentially important differences between these two studies. First, the time of dosing was different. The Indonesian study dosed infants within 24 hours of birth whereas the Nepal study dosed infants when they were first identified to the study during their distribution rounds every four months. On average then, the age at first dosing was 2 months after the highest risk period and exposure to dietary and other environmental factors. It may be that the time of dosing is critically important for the development of early immune function or other protective mechanisms. Support for the Indonesian findings has come from a recently discussed study in Bangladesh where supplementation of mothers' post-partum was associated with a reduction in infant mortality (12).

Given the apparent controversy in the scientific literature on early infant dosing with vitamin A and the fact that this remains the highest risk period for mortality during childhood, more data are urgently needed to resolve this confusion. If the Indonesian findings can be replicated, the policy implications for developing countries are clear. An expansion of the "safe delivery" concept to include supplementation of the infant and mother with vitamin A would enhance nutrition and safe motherhood program impact in an extremely cost-efficient fashion. As practices in India move increasingly in the direction of attended childbirth, the opportunity to intervene becomes easier with significant potential for having a dramatic impact on infant mortality.