Maternal low-dose vitamin A or beta-carotene supplementation has no effect on fetal loss and early infant mortality: a randomized cluster trial in Nepal.
ABSTRACT The effect of vitamin A supplementation on the survival of infants aged <6 mo is unclear. Because most infant deaths occur in the first few month of life, maternal supplementation may improve infant survival.
The objective was to assess the effect of maternal vitamin A or beta-carotene supplementation on fetal loss and survival of infants <6 mo of age.
Married women of reproductive age in 270 wards of Sarlahi district, Nepal, were eligible to participate. Wards were randomly assigned to have women receive weekly doses of 7000 microg retinol equivalents as retinyl palmitate (vitamin A), 42 mg all-trans-beta-carotene, or placebo. Pregnancies were followed until miscarriage, stillbirth, maternal death, or live birth of one or more infants, who were followed through 24 wk of age.
A total of 43559 women were enrolled; 15832 contributed 17373 pregnancies and 15987 live born infants to the trial. The rate of fetal loss was 92.0/1000 pregnancies in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.06 (95% CI: 0.91, 1.25) and 1.03 (95% CI: 0.87, 1.19), respectively. The 24-wk mortality rate was 70.8/1000 live births in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.05 (95% CI: 0.87, 1.25) and 1.03 (95% CI: 0.86, 1.22), respectively.
Small weekly doses of vitamin A or beta-carotene given to women before conception, during pregnancy, and through 24 wk postpartum did not improve fetal or early infant survival in Nepal.
Article: Effects of Vitamin A or Beta Carotene Supplementation on Pregnancy-Related Mortality and Infant Mortality in Rural BangladeshA Cluster Randomized Trial[show abstract] [hide abstract]
ABSTRACT: Context Maternal vitamin A deficiency is a public health concern in the developing world. Its prevention may improve maternal and infant survival.Objective To assess efficacy of maternal vitamin A or beta carotene supplementation in reducing pregnancy-related and infant mortality.Design, Setting, and Participants Cluster randomized, double-masked, placebo-controlled trial among pregnant women 13 to 45 years of age and their live-born infants to 12 weeks (84 days) postpartum in rural northern Bangladesh between 2001 and 2007.Interventions Five hundred ninety-six community clusters (study sectors) were randomized for pregnant women to receive weekly, from the first trimester through 12 weeks postpartum, 7000 μg of retinol equivalents as retinyl palmitate, 42 mg of all -trans beta carotene, or placebo. Married women (n = 125 257) underwent 5-week surveillance for pregnancy, ascertained by a history of amenorrhea and confirmed by urine test. Blood samples were obtained from participants in 32 sectors (5%) for biochemical studies.Main Outcome Measures All-cause mortality of women related to pregnancy, stillbirth, and infant mortality to 12 weeks (84 days) following pregnancy outcome.Results Groups were comparable across risk factors. For the mortality outcomes, neither of the supplement group outcomes was significantly different from the placebo group outcomes. The numbers of deaths and all-cause, pregnancy-related mortality rates (per 100 000 pregnancies) were 41 and 206 (95% confidence interval [CI], 140-273) in the placebo group, 47 and 237 (95% CI, 166-309) in the vitamin A group, and 50 and 250 (95% CI, 177-323) in the beta carotene group. Relative risks for mortality in the vitamin A and beta carotene groups were 1.15 (95% CI, 0.75-1.76) and 1.21 (95% CI, 0.81-1.81), respectively. In the placebo, vitamin A, and beta carotene groups the rates of stillbirth and infant mortality were 47.9 (95% CI, 44.3-51.5), 45.6 (95% CI, 42.1-49.2), and 51.8 (95% CI, 48.0-55.6) per 1000 births and 68.1 (95% CI, 63.7-72.5), 65.0 (95% CI, 60.7-69.4), and 69.8 (95% CI, 65.4-72.3) per 1000 live births, respectively. Vitamin A compared with either placebo or beta carotene supplementation increased plasma retinol concentrations by end of study (1.46 [95% CI, 1.42-1.50] μmol/L vs 1.13 [95% CI, 1.09-1.17] μmol/L and 1.18 [95% CI, 1.14-1.22] μmol/L, respectively; P < .001) and reduced, but did not eliminate, gestational night blindness (7.1% for vitamin A vs 9.2% for placebo and 8.9% for beta carotene [P < .001 for both]).Conclusion Use of weekly vitamin A or beta carotene in pregnant women in Bangladesh, compared with placebo, did not reduce all-cause maternal, fetal, or infant mortality.Trial Registration clinicaltrials.gov Identifier: NCT00198822 Figures in this Article Maternal vitamin A deficiency appears to be widespread in low-income countries. Currently, the World Health Organization estimates nearly 20 million pregnant women to be vitamin A deficient, exhibiting a serum retinol concentration below 0.70 μmol/L, of whom nearly 9 million have gestational night blindness, an ocular manifestation of deficiency.1 Night blindness during pregnancy is associated with increased risks of maternal anemia, morbidity, and mortality,2- 3 suggesting that preventing vitamin A deficiency could improve maternal survival. Evidence of such an effect has been reported in rural Nepal, where a randomized controlled trial demonstrated a decrease of approximately 44% in mortality related to pregnancy following continuous, weekly receipt of vitamin A or beta carotene during the reproductive years at dosages approximating a recommended daily allowance.4 The reduction was most apparent in women with night blindness,3 and causes of death attenuated in risk were those involving infectious, obstetric, and miscellaneous causes as determined by interviews with family members.4 Supplementation also modestly decreased reported symptoms of morbidity.5 Plausible host defenses against severe illness, which likely rely on vitamin A–regulated cell proliferation and differentiation and could be compromised by vitamin A deficiency, include multiple mechanisms of epithelial innate and adaptive immunity,6 hematopoiesis,7- 8 and coagulation,9 abnormalities of which could exacerbate infection, result in anemia, or impair wound recovery.9 Although in a trial conducted in Nepal there was no overall effect on infant mortality,10 there was evidence of a reduction in mortality among infants born to mothers with a positive history of gestational night blindness.11 Given the importance of reducing maternal mortality, additional vitamin A intervention trials have been indicated. A recent trial conducted in Ghana, West Africa,12 reported no effect of weekly supplementation on all-cause maternal mortality with a comparable dosage of vitamin A, suggesting that local nutritional, health, and vital risk contexts may influence effect of supplementation. In Bangladesh, we sought to extend the findings of the Nepal trial to another South Asian setting, delivering the same dosage of vitamin A or beta carotene to women from early pregnancy through 12 weeks postpartum to assess effects on pregnancy-related maternal, fetal, and early infant mortality.JAMA The Journal of the American Medical Association 305(19):1986-1995. · 30.03 Impact Factor
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ABSTRACT: Vitamin A deficiency (VAD) is an important nutritional problem in India, resulting in an increased risk of severe morbidity and mortality. Periodic, high-dose vitamin A supplementation is the WHO-recommended method to prevent VAD, since a single dose can compensate for reduced dietary intake or increased need over a period of several months. However, in India only 34 percent of targeted children currently receive the two doses per year, and new strategies are urgently needed. Recent advancements in biotechnology permit alternative strategies for increasing the vitamin A content of common foods. Mustard (Brassica juncea), which is consumed widely in the form of oil by VAD populations, can be genetically modified to express high levels of beta-carotene, a precursor to vitamin A. Using estimates for consumption, we compare predicted costs and benefits of genetically modified (GM) fortification of mustard seed with high-dose vitamin A supplementation and industrial fortification of mustard oil during processing to alleviate VAD by calculating the avertable health burden in terms of disability-adjusted life years (DALY). We found that all three interventions potentially avert significant numbers of DALYs and deaths. Expanding vitamin A supplementation to all areas was the least costly intervention, at $23-$50 per DALY averted and $1,000-$6,100 per death averted, though cost-effectiveness varied with prevailing health subcenter coverage. GM fortification could avert 5 million-6 million more DALYs and 8,000-46,000 more deaths, mainly because it would benefit the entire population and not just children. However, the costs associated with GM fortification were nearly five times those of supplementation. Industrial fortification was dominated by both GM fortification and supplementation. The cost-effectiveness ratio of each intervention decreased with the prevalence of VAD and was sensitive to the efficacy rate of averted mortality. Although supplementation is the least costly intervention, our findings also indicate that GM fortification could reduce the VAD disease burden to a substantially greater degree because of its wider reach. Given the difficulties in expanding supplementation to areas without health subcenters, GM fortification of mustard seed is an attractive alternative, and further exploration of this technology is warranted.PLoS ONE 01/2010; 5(8):e12046. · 4.09 Impact Factor
Article: Effect of vitamin A supplementation in women of reproductive age on cause-specific early and late infant mortality in rural Ghana: ObaapaVitA double-blind, cluster-randomised, placebo-controlled trial.[show abstract] [hide abstract]
ABSTRACT: Objectives To assess the effect of vitamin A supplementation in women of reproductive age in Ghana on cause- and age-specific infant mortality. In addition, because of recently published studies from Guinea Bissau, effects on infant mortality by sex and season were assessed. Design Double-blind, cluster-randomised, placebo-controlled trial. Setting 7 contiguous districts in the Brong Ahafo region of Ghana. Participants All women of reproductive age (15-45 years) resident in the study area randomised by cluster of residence. All live born infants from 1 June 2003 to 30 September 2008 followed up through 4-weekly home visits. Intervention Weekly low-dose (25 000 IU) vitamin A. Main outcome measures Early infant mortality (1-5 months); late infant mortality (6-11 months); infection-specific infant mortality (0-11 months). Results 1086 clusters, 62 662 live births, 52 574 infant-years and 3268 deaths yielded HRs (95% CIs) comparing weekly vitamin A with placebo: 1.04 (0.88 to 1.05) early infant mortality; 0.99 (0.84 to 1.18) late infant mortality; 1.03 (0.92 to 1.16) infection-specific infant mortality. There was no evidence of modification of the effect of vitamin A supplementation on infant mortality by sex (Wald statistic =0.07, p=0.80) or season (Wald statistic =0.03, p=0.86). Conclusions This is the largest analysis of cause of infant deaths from Africa to date. Weekly vitamin A supplementation in women of reproductive age has no beneficial or deleterious effect on the causes of infant death to age 6 or 12 months in rural Ghana. Trial registration number http://ClinicalTrials.gov: NCT00211341.BMJ open. 01/2012; 2(1):e000658.