Vitamin A deficiency (VAD) is a significant public health problem in developing countries, especially in Africa and Southeast Asia, most seriously affecting the young children and pregnant women. According to the present estimates, there are 127 million pre‐school children with VAD (serum retinol < 0.70 mmo/L or displaying abnormal impression cytology) and 4.4 million preschool children with xerophthalmia in the developing world (West 2002). More than 7.2 million pregnant women in the developing world are vitamin A deficient (serum or breast‐milk vitamin A concentrations < 0.70 µmol/L) and another 13.5 million have low vitamin A status (0.70 ‐ 1.05 µmol/L) (West 2002). Annually, more than six million women develop night blindness (XN) during pregnancy West 2002.

VAD is believed to cause an increased susceptibility to infections by impeding normal regeneration of damaged mucosal barriers and by diminishing the function of neutrophils, macrophages, and natural killer cells. Vitamin A is also required for adaptive immunity and plays a role in the development of T ‐helper (Th) cells and B‐cells (Stephensen 2001). Vitamin A deficiency also diminishes antibody‐mediated responses directed by Th2 cells, although some aspects of Th1‐mediated immunity are also diminished Stephensen 2001. These factors may account for the increased mortality seen in vitamin A‐deficient infants, young children, and pregnant women. Deficiency of vitamin A causes xerophthamia and significantly increases the risk of severe illness and death from such common childhood infections as diarrhoeal disease and measles Humphrey 1992; Christian 2001. An estimated 250,000 to 500,000 vitamin A deficient children become blind every year, half of them dying within 12 months of losing their sight West 2002.

The main causes of childhood vitamin A deficiency in the developing world include maternal vitamin A deficiency resulting in low concentrations of vitamin A in breast milk, inadequate dietary intake of vitamin A during and after weaning; and repeated bouts of infectious illnesses, which further decrease vitamin A levels Miller 2002. The current U.S. recommended dietary allowance (RDA) established by the Institute of Medicine (IOM) for nonpregnant, nonlactating women, aged 19 ‐ 50 years is 700 µg of vitamin A per day IOM 2001. The recommended dietary allowance increases to only 770 µg/d during pregnancy but nearly doubles to 1300 µg/d during lactation. Mothers in developing countries are commonly vitamin A deficient because they consume diets low in vitamin A. Median dietary intake of vitamin A is 403 µg/d in rural Bangladeshi women, which provides 57% of their RDA if they are not pregnant or lactating and only 31% of their RDA during lactation Zeitlin 1992. Maternal vitamin A deficiency seems to have little effect on fetal status, because even well‐nourished women transfer very little vitamin A to the infant. Therefore, all babies are physiologically vitamin A "depleted" at birth, having little in the way of vitamin A stores in their livers. Young infants in developing countries have even less vitamin A stores. However, during lactation well‐nourished women transfer about 71,500 µg of vitamin A to their infant (130 L of breast milk consumed during the entire period of lactation containing 55 µg/dL vitamin A), whereas women in developing countries transfer only about half that amount because average milk vitamin A concentrations are about 30 µg/dL Wallingford 1986. As a result, during lactation, breast‐fed babies of well‐nourished women accrue adequate stores, whereas breast‐fed babies of vitamin A‐deficient women remain depleted. Furthermore, if weaning foods are lower in vitamin A than the breast milk they partially replace the child's risk of vitamin A deficiency increases further when breast‐feeding stops. Dietary vitamin A reference intakes for infants and young children established by IOM in the United States and by the Food and Agricultural Organization (FAO) recommend intakes from 350 to 500 µg/d for infants and from 300 to 400 µg/d for one to six year old children FAO/WHO 1988; IOM 2001. In studies of preschool children in Egypt, Mexico, Kenya, and India median intakes of animal sources of vitamin A were 174, 119, 50 and 33 µg/d, respectively, providing only 11 ‐ 58% of the RDA and leaving these children largely dependent on plant sources Calloway 1993; Ramakrishnan 1999. In a study of Bangladeshi children, virtually the only source of preformed vitamin A consumed was breast milk; weaned children consumed only negligible amounts of vitamin A from animal sources Zeitlin 1992.

There are two approaches to supplementing vitamin A intake during the first half of infancy. First, supplement all lactating mothers so that their infants can increase vitamin A intake through breast milk. Second, give vitamin A supplements to all infants when they come in contact with the health care system. Such possible contacts occur immediately after birth, during postnatal visits or during immunization visits. The International Vitamin A Consultative Group (IVACG)  recommends that three 50,000‐international unit (IU) doses of vitamin A should be given at the same time as infant vaccines during the first six months of life. Recent kinetic studies have indicated that this regimen would be safe and would maintain the infant's vitamin A stores even when the mother is also given 400,000 IU within the first six weeks after delivery Ross 2002.

The role of prophylactic vitamin A supplementation in apparently healthy children (more than six months of age) residing in developing countries in reducing childhood mortality has been the subject of several systematic and narrative reviews. For deficient children more than six months of age, vitamin A supplementation is estimated to reduce mortality by 23 ‐ 30% overall. Most of the reduction is due to the effect on diarrhea and measles mortality Beaton 1993; Fawzi 1993; Glasziou 1993. Periodic vitamin A supplementation to children over six months old is being implemented in > 70 countries and is considered by many international agencies to be one of the most effective public health interventions ever undertaken Fawzi 2006. Supplementation with a standard WHO protocol (200,000 IU to mothers early postpartum, 100,000 IU to infants at nine months, and 200,000 IU at four to six month intervals thereafter) has been adopted as national policy in most developing countries Darboe 2007. Side‐effects of vitamin A supplementation are rare in children aged six months or older but there are reports of toxic effects in the first six months of life, such as raised intracranial pressure manifested by vomiting, bulging of the anterior fontanelle and irritability Baqui 1995; Agoestina 1994; de Francisco 1993.

Because infants are at higher risk of mortality when compared to older children, improving the vitamin A status of infants could potentially save the greatest number of lives. Therefore, the available evidence on the beneficial effects on mortality and morbidity of this intervention during the first six months of life needs to be systematically reviewed. Moreover, the concern about the safety of vitamin A supplementation in young infants, particularly during the neonatal period, needs to be addressed and the optimum dose determined. Also, the differential effect on mortality and morbidity with respect to the vitamin A status of mothers, birthweight and infant mortality rate needs to be studied. Therefore, a systematic review of randomized controlled trials is being proposed to evaluate the effect of prophylactic vitamin A supplementation on mortality and morbidity in infants six months of age or less in developing countries, with particular reference to supplementation of mothers during lactation and of infants at different times during the first half of infancy.