The WHO has estimated that 19 million (15.3%) pregnant women and 190 million (33.3%) of preschool aged children in the world’s poorest countries are vitamin A deficient. [1, 2] In Bangladesh, one in five preschool-age children are vitamin A deficient. This deficiency contributes to morbidity and mortality from severe infections and is the main cause of blindness in undernourished children. 
This innovation was provided as antenatal and newborn vitamin A supplementation in two large cluster-randomized controlled trials to reduce maternal and infant mortality in the JiVitA project site from 2001-2017. [3, 4, 5] The interventions included weekly supplementation of vitamin A capsules or placebo to pregnant mothers from the first trimester through 12 weeks after delivery and/or a single dose of vitamin A (50,000 IU) at birth or a placebo to newborns using a 2×2 factorial design.
The beneficial effect of vitamin A on child mortality has been established,  but the long-term benefits of early vitamin A supplementation are unclear. The GCC funded follow-up study assesses the effects of maternal and newborn vitamin A supplementation on cognitive development of children at 8 years of age.
- 60,000 women were supplemented with vitamin A during pregnancy.
- Supplementation with vitamin A in 17,116 live-born infants reduced all-cause mortality by 15%. 
- Follow-up assessments are conducted on 1600 children and their mothers.
Scaling up the supplementation with Vitamin A is very easy... The information from this study will help the governments and policy-makers make necessary decisions about Vitamin-A supplementation in relation to children’s cognitive function.
-- Jena Hamadani
Variation in vitamin A nutrition in embryo-fetal and early postnatal life can profoundly affect viability, neural development and morphology of the offspring.
The initial innovation carried out two large community-based nutrition intervention trials. The first trial assessed the effects of maternal supplementation with weekly retinol or beta-carotene from the first trimester through 12 weeks on maternal mortality, fetal loss and infant mortality4. A total of ~60,000 pregnant women were enrolled from 2001 to 2007, among which approximately 70% gave birth to live infants. Nested in this intervention was a second trial, which assessed the efficacy of a newborn vitamin A supplementation (single oral dose) on all-cause infant mortality during the first 6 months of life.  This study was carried out from January 2004 to January 2007 and involved a total of ~16,000 newborns.
The effects of embryo-fetal and early postnatal life Vitamin A supplementation in human populations are most well-defined in terms of their impact on mortality, with reductions shown at ~20%. [5, 7] Impacts on neurodevelopmental function and protective effects through sensitive developmental stages would be expected consequences of vitamin A supplementation, but have not been adequately studied to date. In fact, few newborn vitamin A supplementation studies have assessed the long term consequences of this at-birth intervention on developmental outcomes.
One study in Indonesia in which newborn vitamin A supplementation was done followed up children when they were three years of age to assess the long term safety of providing vitamin A at birth and some cognitive outcomes.  This study showed improved Bayley scores in those who had received vitamin A at birth compared to the placebo group.
Currently, the study team is undertaking a follow-up study, to comprehensively evaluate the effects of antenatal and newborn vitamin A dosing on a cohort of children originally involved in the above intervention studies. The study team will follow 1,600 children, at 8 years of age, who received vitamin A supplementation (in utero via maternal supplementation and/or in the first few days of life) or placebo. The team will examine the impact of supplementation on developmental outcomes including general intellectual function, gross and fine motor function, memory, aspects of executive function, behavior, and school achievement at 8 years of age.
- Grand Challenges Canada
- The JiVitA project and investigators
- Johns Hopkins Bloomberg School of Public Health
- Northwestern Bangladesh
- Enrollment of the estimated sample size of children in the study was completed. Cognitive tests were successfully administered. Results will be discussed at the Grand Challenges meeting in Seattle.
- The successful collaboration between icddr,b, the JiVitA field site and Johns Hopkins School of Public Health made the implementation highly successful.
Sociopolitical climate: Political unrest, strikes and roadblocks have at times hindered the ability of the study team to reach participants and carry out work; however enrollment in the follow-up study was successfully completed.
Newborn vitamin A supplementation as a strategy is currently being considered by the WHO for recommendation in low income countries, or settings where vitamin A deficiency is common.
The study team followed up 1600 children and their mothers from across four vitamin A supplementation groups in the present study. The four groups included the maternal and newborn vitamin A supplementation or placebo provided using a 2×2 factorial design. Both individual and combined effects of maternal and newborn vitamin A supplementation is being evaluated.
Through a home visit, the team assessed child morbidity, behaviour and home environment, including care-giving behaviours. A detailed history of schooling including years attended was obtained. Child anthropometry was assessed and the HOME inventory administered. Child cognition assessments were conducted at a central clinic, via tests of intelligence, motor control including fine motor skills, behavior and school achievement. Maternal IQ was also assessed.
The study team will also use extant data from the original interventions including household socioeconomic status, supplement compliance, complications and morbidity at birth, and breastfeeding patterns in the first 6 months of life.
Impact of Innovation
Newborn vitamin A dosing improved infant survival through the first 6 months of life, with a 15% reduction in all-cause mortality. In line with two previous trials in South Asia, [8, 9] these data revealed an efficacy period of 4 months for Vitamin A dosing in reducing mortality, where infant survival in the vitamin A–supplemented group began to improve beyond the first week of life until week 16 of life. The estimated reduction in mortality risk in the first and next 5 months of life were 11% and 23%, respectively.
Use of weekly vitamin A or beta carotene in pregnant women did not reduce all-cause maternal, fetal, or infant mortality compared with placebo. Vitamin A supplementation, compared with either placebo or beta carotene supplementation, did however reduce maternal gestational night blindness.
The anticipated impact of the follow-up study recently completed is the quantification of antenatal and newborn vitamin A supplementation effects on child cognitive, motor and school function and thereby on human capital among children aged 8 years.
- Alam, M. J. et al. (2012) Meeting Micronutrient Requirements for Health and Development: An Update. Bangladesh J Child Health 2012; VOL 36 (1): 36-45.
- Global prevalence of vitamin A deficiency in populations at risk 1995–2005. WHO Global Database on Vitamin A Deficiency. Geneva: World Health Organization; 2009
- Rotondi, M. A. et al. (2010) Vitamin A supplementation and neonatal mortality in the developing world: a meta-regression of cluster-randomized trials. Bulletin of the World Health Organization.
- Effects of Vitamin A or Beta Carotene SupplementationonPregnancy-RelatedMortality and Infant Mortality in Rural Bangladesh JAMA, May 18, 2011—Vol 305, No. 19
- Klemm et al (2008) Newborn vitamin A supplementation reduced infant mortality in rural Bangladesh. Pediatrics, 122: 242-250.
- Humphrey JH et al. (1998) Neonatal vitamin A supplementation: Effect on development and growth at 3 y of age. Am J Clin Nutr. 1998;68:109-117.
- Fawzi WW, et al. Vitamin A supplementation and child mortality. A meta-analysis.
- Humphrey JH et al. (1996) Impact of neonatal vitamin A supplementation on infant morbidity and mortality. J Pediatr. 1996;128(4):489–496
- Rahmathullah L et al. (2003) Impact of supplementing newborn infants with vitamin A on early infant mortality: community based randomised trial in Southern India. BMJ. 2003;327(7409):254–259
Instruments & Batteries