Keith P West1, Abu Ahmed Shamim2, Sucheta Mehra1, Alain B Labrique1, Hasmot Ali2, Saijuddin Shaikh2, Rolf D W Klemm1, Lee S-F Wu1, Maithilee Mitra1, Rezwanul Haque3, Abu A M Hanif3, Allan B Massie4, Rebecca Day Merrill5, Kerry J Schulze1, Parul Christian1. 1. Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 2. Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland2The JiVitA Project, Gaibandha, Bangladesh. 3. The JiVitA Project, Gaibandha, Bangladesh. 4. Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland3Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland. 5. Centers for Disease Control and Prevention, Atlanta, Georgia.
Abstract
IMPORTANCE: Maternal micronutrient deficiencies may adversely affect fetal and infant health, yet there is insufficient evidence of effects on these outcomes to guide antenatal micronutrient supplementation in South Asia. OBJECTIVE: To assess effects of antenatal multiple micronutrient vs iron-folic acid supplementation on 6-month infant mortality and adverse birth outcomes. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized, double-masked trial in Bangladesh, with pregnancy surveillance starting December 4, 2007, and recruitment on January 11, 2008. Six-month infant follow-up ended August 30, 2012. Surveillance included 127,282 women; 44,567 became pregnant and were included in the analysis and delivered 28,516 live-born infants. Median gestation at enrollment was 9 weeks (interquartile range, 7-12). INTERVENTIONS: Women were provided supplements containing 15 micronutrients or iron-folic acid alone, taken daily from early pregnancy to 12 weeks postpartum. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause infant mortality through 6 months (180 days). Prespecified secondary outcomes in this analysis included stillbirth, preterm birth (<37 weeks), and low birth weight (<2500 g). To maintain overall significance of α = .05, a Bonferroni-corrected α = .01 was calculated to evaluate statistical significance of primary and 4 secondary risk outcomes (.05/5). RESULTS: Among the 22,405 pregnancies in the multiple micronutrient group and the 22,162 pregnancies in the iron-folic acid group, there were 14,374 and 14,142 live-born infants, respectively, included in the analysis. At 6 months, multiple micronutrients did not significantly reduce infant mortality; there were 764 deaths (54.0 per 1000 live births) in the iron-folic acid group and 741 deaths (51.6 per 1000 live births) in the multiple micronutrient group (relative risk [RR], 0.95; 95% CI, 0.86-1.06). Multiple micronutrient supplementation resulted in a non-statistically significant reduction in stillbirths (43.1 vs 48.2 per 1000 births; RR, 0.89; 95% CI, 0.81-0.99; P = .02) and significant reductions in preterm births (18.6 vs 21.8 per 100 live births; RR, 0.85; 95% CI, 0.80-0.91; P < .001) and low birth weight (40.2 vs 45.7 per 100 live births; RR, 0.88; 95% CI, 0.85-0.91; P < .001). CONCLUSIONS AND RELEVANCE: In Bangladesh, antenatal multiple micronutrient compared with iron-folic acid supplementation did not reduce all-cause infant mortality to age 6 months but resulted in a non-statistically significant reduction in stillbirths and significant reductions in preterm births and low birth weight. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00860470.
RCT Entities:
IMPORTANCE: Maternal micronutrient deficiencies may adversely affect fetal and infant health, yet there is insufficient evidence of effects on these outcomes to guide antenatal micronutrient supplementation in South Asia. OBJECTIVE: To assess effects of antenatal multiple micronutrient vs iron-folic acid supplementation on 6-month infant mortality and adverse birth outcomes. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized, double-masked trial in Bangladesh, with pregnancy surveillance starting December 4, 2007, and recruitment on January 11, 2008. Six-month infant follow-up ended August 30, 2012. Surveillance included 127,282 women; 44,567 became pregnant and were included in the analysis and delivered 28,516 live-born infants. Median gestation at enrollment was 9 weeks (interquartile range, 7-12). INTERVENTIONS:Women were provided supplements containing 15 micronutrients or iron-folic acid alone, taken daily from early pregnancy to 12 weeks postpartum. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause infant mortality through 6 months (180 days). Prespecified secondary outcomes in this analysis included stillbirth, preterm birth (<37 weeks), and low birth weight (<2500 g). To maintain overall significance of α = .05, a Bonferroni-corrected α = .01 was calculated to evaluate statistical significance of primary and 4 secondary risk outcomes (.05/5). RESULTS: Among the 22,405 pregnancies in the multiple micronutrient group and the 22,162 pregnancies in the iron-folic acid group, there were 14,374 and 14,142 live-born infants, respectively, included in the analysis. At 6 months, multiple micronutrients did not significantly reduce infant mortality; there were 764 deaths (54.0 per 1000 live births) in the iron-folic acid group and 741 deaths (51.6 per 1000 live births) in the multiple micronutrient group (relative risk [RR], 0.95; 95% CI, 0.86-1.06). Multiple micronutrient supplementation resulted in a non-statistically significant reduction in stillbirths (43.1 vs 48.2 per 1000 births; RR, 0.89; 95% CI, 0.81-0.99; P = .02) and significant reductions in preterm births (18.6 vs 21.8 per 100 live births; RR, 0.85; 95% CI, 0.80-0.91; P < .001) and low birth weight (40.2 vs 45.7 per 100 live births; RR, 0.88; 95% CI, 0.85-0.91; P < .001). CONCLUSIONS AND RELEVANCE: In Bangladesh, antenatal multiple micronutrient compared with iron-folic acid supplementation did not reduce all-cause infant mortality to age 6 months but resulted in a non-statistically significant reduction in stillbirths and significant reductions in preterm births and low birth weight. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00860470.
Authors: Paulo A R Neves; Marcia C Castro; Clariana V R Oliveira; Maira B Malta; Bárbara H Lourenço; Marly A Cardoso Journal: Eur J Nutr Date: 2018-12-17 Impact factor: 5.614
Authors: Brietta M Oaks; Christine P Stewart; Kevin D Laugero; Seth Adu-Afarwuah; Anna Lartey; Stephen A Vosti; Per Ashorn; Kathryn G Dewey Journal: Matern Child Nutr Date: 2016-12-27 Impact factor: 3.092
Authors: Christopher D Heaney; Brittany Kmush; Ana Navas-Acien; Kevin Francesconi; Walter Gössler; Kerry Schulze; DeLisa Fairweather; Sucheta Mehra; Kenrad E Nelson; Sabra L Klein; Wei Li; Hasmot Ali; Saijuddin Shaikh; Rebecca D Merrill; Lee Wu; Keith P West; Parul Christian; Alain B Labrique Journal: Environ Res Date: 2015-07-15 Impact factor: 6.498
Authors: Mary K Quinn; Emily R Smith; Paige L Williams; Willy Urassa; Joy Shi; Gernard Msamanga; Wafaie W Fawzi; Christopher R Sudfeld Journal: J Nutr Date: 2020-02-01 Impact factor: 4.798
Authors: Olukunmi O Balogun; Katharina da Silva Lopes; Erika Ota; Yo Takemoto; Alice Rumbold; Mizuki Takegata; Rintaro Mori Journal: Cochrane Database Syst Rev Date: 2016-05-06
Authors: Brittany L Kmush; Alain Labrique; Wei Li; Sabra L Klein; Kerry Schulze; Saijuddin Shaikh; Hasmot Ali; Ronald E Engle; Lee Wu; Robert H Purcell; Sucheta Mehra; Parul Christian; Keith West; Kenrad Nelson Journal: Am J Trop Med Hyg Date: 2015-11-30 Impact factor: 2.345
Authors: Alison D Gernand; Kerry J Schulze; Christine P Stewart; Keith P West; Parul Christian Journal: Nat Rev Endocrinol Date: 2016-04-01 Impact factor: 43.330