Clinical trial NCT00860470: Antenatal Micronutrient Supplementation and Infant Survival
Official title: Antenatal Multiple Micronutrient Supplementation to Improve Infant Survival and Health in Bangladesh
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infant Mortality
Preterm Birth
Low Birth Weight
Neonatal Mortality
Perinatal Mortality
Keywords: micronutrients
deficiency
pregnancy
birth outcomes
infant mortality
neonatal mortality
malnutrition
antenatal
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
name: United States Agency for International Development (USAID)
name: Mahidol University
name: Johns Hopkins University
name: Beximco Pharmaceuticals Ltd.
name: DSM Nutritional Products, Inc.
First posted: 2009-03-12
Enrollment: 44567
Sex: FEMALE
Minimum age (years): 12
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this community-based randomized trial is to examine whether a daily antenatal and postnatal multiple micronutrient supplement given to women will enhance newborn and infant survival and health and other birth outcomes in a rural setting in northwestern Bangladesh.

Detailed description: Maternal deficiency in multiple essential micronutrients is likely to be a major public health problem in low-income countries. Supplementing mothers with certain individual micronutrients has been shown to confer health benefits, although the evidence is not clear for multiple micronutrients. We aim to test, in a cluster-randomized, double-masked, controlled trial whether giving a daily multiple micronutrient supplement (similar in composition to the UNICEF antenatal supplement) will enhance infant survival and birth outcomes such as birth weight and gestational duration in a rural population in Bangladesh. Over the duration of 2-3 years a community-surveillance in the northwestern, rural Districts of Gaibandha and Southern Rangpur, the trial plans to identify and recruit 45,000 pregnant women based on 5-weekly histories of amenorrhea confirmed by urine-testing, and supplement them with either a multiple micronutrient supplement or an iron-folic acid supplement (as the standard of care control for pregnancy) and monitor pregnancy health, birth outcomes and vital status and health of liveborn infants through 6 months of age. In a \~3% sub-sample of mothers, additional measures of nutritional and health status will be evaluated in the 1st and 3rd trimesters of pregnancy, and at 3 months postpartum (with infants), that include anthropometric and body composition (bioelectrical impedance) assessment, collection of biospecimens (eg, phlebotomy and breast milk sampling for micronutrient and other analyte concentration determinations), and other clinical assessments. The trial will generate evidence from which to examine the safety and efficacy of an antenatal through postnatal maternal micronutrient supplement intervention in order to inform and guide antenatal nutrition policies and programs in South Asia.

Eligibility criteria: Inclusion Criteria:

* Pregnant and consents to participate

Exclusion Criteria:

* Not interviewed for consent within 12 consecutive weeks after being ascertained as pregnant by urine testing

Primary outcomes:
measure: Infant Mortality Through 6 mo of Age
timeFrame: 6-months post-birth
Secondary outcomes:
measure: Neonatal Mortality
timeFrame: 1 month post-birth
measure: Post-neonatal Mortality
timeFrame: 1-6 months post-birth
measure: Still Birth Rates
timeFrame: 24 weeks gestation to delivery
measure: Preterm Birth
timeFrame: Up to 37 weeks of gestation
measure: Extremely Pre-term
timeFrame: Up to 28 weeks of gestation
measure: Very Pre-term
timeFrame: Between 27 and 33 weeks of gestation
measure: Moderate to Late Preterm
timeFrame: Between 31 and 38 weeks of gestation
measure: Low Birth Weight
timeFrame: Measured at delivery/birth
measure: Small for Gestation Age
timeFrame: At delivery/birth
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins School of Public Health
state: Maryland
city: Rangpur
country: Bangladesh
facility: JiVitA Project Office
state: Gaibandha District
Study officials:
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Keith P West, Jr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Parul Christian
role: PRINCIPAL_INVESTIGATOR
References:
citation: Christian P, Khatry SK, Katz J, Pradhan EK, LeClerq SC, Shrestha SR, Adhikari RK, Sommer A, West KP Jr. Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial. BMJ. 2003 Mar 15;326(7389):571. doi: 10.1136/bmj.326.7389.571.
citation: Christian P. Micronutrients and reproductive health issues: an international perspective. J Nutr. 2003 Jun;133(6):1969S-1973S. doi: 10.1093/jn/133.6.1969S.
citation: Christian P, Shrestha J, LeClerq SC, Khatry SK, Jiang T, Wagner T, Katz J, West KP Jr. Supplementation with micronutrients in addition to iron and folic acid does not further improve the hematologic status of pregnant women in rural Nepal. J Nutr. 2003 Nov;133(11):3492-8. doi: 10.1093/jn/133.11.3492.
citation: Christian P, West KP, Khatry SK, Leclerq SC, Pradhan EK, Katz J, Shrestha SR, Sommer A. Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal. Am J Clin Nutr. 2003 Dec;78(6):1194-202. doi: 10.1093/ajcn/78.6.1194.
citation: Katz J, West KP Jr, Khatry SK, Christian P, LeClerq SC, Pradhan EK, Shrestha SR. Risk factors for early infant mortality in Sarlahi district, Nepal. Bull World Health Organ. 2003;81(10):717-25. Epub 2003 Nov 25.
citation: Jiang T, Christian P, Khatry SK, Wu L, West KP Jr. Micronutrient deficiencies in early pregnancy are common, concurrent, and vary by season among rural Nepali pregnant women. J Nutr. 2005 May;135(5):1106-12. doi: 10.1093/jn/135.5.1106.
citation: Christian P, Osrin D, Manandhar DS, Khatry SK, de L Costello AM, West KP Jr. Antenatal micronutrient supplements in Nepal. Lancet. 2005 Aug 27-Sep 2;366(9487):711-2. doi: 10.1016/S0140-6736(05)67166-8. No abstract available.
citation: Christian P, Jiang T, Khatry SK, LeClerq SC, Shrestha SR, West KP Jr. Antenatal supplementation with micronutrients and biochemical indicators of status and subclinical infection in rural Nepal. Am J Clin Nutr. 2006 Apr;83(4):788-94. doi: 10.1093/ajcn/83.4.788.
citation: Katz J, Christian P, Dominici F, Zeger SL. Treatment effects of maternal micronutrient supplementation vary by percentiles of the birth weight distribution in rural Nepal. J Nutr. 2006 May;136(5):1389-94. doi: 10.1093/jn/136.5.1389.
citation: West KP Jr, Christian P. Antenatal micronutrients in undernourished people. Lancet. 2008 Feb 9;371(9611):452-4. doi: 10.1016/S0140-6736(08)60214-7. No abstract available.
citation: Christian P, Darmstadt GL, Wu L, Khatry SK, Leclerq SC, Katz J, West KP Jr, Adhikari RK. The effect of maternal micronutrient supplementation on early neonatal morbidity in rural Nepal: a randomised, controlled, community trial. Arch Dis Child. 2008 Aug;93(8):660-4. doi: 10.1136/adc.2006.114009.
citation: Shankar AH, Genton B, Baisor M, Paino J, Tamja S, Adiguma T, Wu L, Rare L, Bannon D, Tielsch JM, West KP Jr, Alpers MP. The influence of zinc supplementation on morbidity due to Plasmodium falciparum: a randomized trial in preschool children in Papua New Guinea. Am J Trop Med Hyg. 2000 Jun;62(6):663-9. doi: 10.4269/ajtmh.2000.62.663.
citation: Smith JW, Matchado AJ, Wu LS, Arnold CD, Burke SM, Maleta KM, Ashorn P, Stewart CP, Shaikh S, Ali H, Labrique AB, West KP Jr, Christian P, Dewey KG, Groopman JD, Schulze KJ. Longitudinal Assessment of Prenatal, Perinatal, and Early-Life Aflatoxin B1 Exposure in 828 Mother-Child Dyads from Bangladesh and Malawi. Curr Dev Nutr. 2022 Jan 7;6(2):nzab153. doi: 10.1093/cdn/nzab153. eCollection 2022 Feb.
citation: Schulze KJ, Gernand AD, Khan AZ, Wu LS, Mehra S, Shaikh S, Ali H, Shamim AA, Sungpuag P, Udomkesmalee E, Labrique AB, West KP, Christian P. Newborn micronutrient status biomarkers in a cluster-randomized trial of antenatal multiple micronutrient compared with iron folic acid supplementation in rural Bangladesh. Am J Clin Nutr. 2020 Nov 11;112(5):1328-1337. doi: 10.1093/ajcn/nqaa223.
citation: Schulze KJ, Mehra S, Shaikh S, Ali H, Shamim AA, Wu LS, Mitra M, Arguello MA, Kmush B, Sungpuag P, Udomkesmelee E, Merrill R, Klemm RDW, Ullah B, Labrique AB, West KP, Christian P. Antenatal Multiple Micronutrient Supplementation Compared to Iron-Folic Acid Affects Micronutrient Status but Does Not Eliminate Deficiencies in a Randomized Controlled Trial Among Pregnant Women of Rural Bangladesh. J Nutr. 2019 Jul 1;149(7):1260-1270. doi: 10.1093/jn/nxz046.
citation: Gernand AD, Paul RR, Ullah B, Taher MA, Witter FR, Wu L, Labrique AB, West KP Jr, Christian P. A home calendar and recall method of last menstrual period for estimating gestational age in rural Bangladesh: a validation study. J Health Popul Nutr. 2016 Oct 21;35(1):34. doi: 10.1186/s41043-016-0072-y.
citation: Christian P, Kim J, Mehra S, Shaikh S, Ali H, Shamim AA, Wu L, Klemm R, Labrique AB, West KP Jr. Effects of prenatal multiple micronutrient supplementation on growth and cognition through 2 y of age in rural Bangladesh: the JiVitA-3 Trial. Am J Clin Nutr. 2016 Oct;104(4):1175-1182. doi: 10.3945/ajcn.116.135178. Epub 2016 Sep 7.
citation: Gernand AD, Schulze KJ, Nanayakkara-Bind A, Arguello M, Shamim AA, Ali H, Wu L, West KP Jr, Christian P. Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized, Controlled Trial in Rural Bangladesh. PLoS One. 2015 Oct 2;10(10):e0137269. doi: 10.1371/journal.pone.0137269. eCollection 2015.
citation: Heaney CD, Kmush B, Navas-Acien A, Francesconi K, Gossler W, Schulze K, Fairweather D, Mehra S, Nelson KE, Klein SL, Li W, Ali H, Shaikh S, Merrill RD, Wu L, West KP Jr, Christian P, Labrique AB. Arsenic exposure and hepatitis E virus infection during pregnancy. Environ Res. 2015 Oct;142:273-80. doi: 10.1016/j.envres.2015.07.004. Epub 2015 Jul 15.
citation: Sikder SS, Labrique AB, Craig IM, Wakil MA, Shamim AA, Ali H, Mehra S, Wu L, Shaikh S, West KP Jr, Christian P. Patterns and determinants of care seeking for obstetric complications in rural northwest Bangladesh: analysis from a prospective cohort study. BMC Health Serv Res. 2015 Apr 18;15:166. doi: 10.1186/s12913-015-0832-1.
citation: West KP Jr, Shamim AA, Mehra S, Labrique AB, Ali H, Shaikh S, Klemm RD, Wu LS, Mitra M, Haque R, Hanif AA, Massie AB, Merrill RD, Schulze KJ, Christian P. Effect of maternal multiple micronutrient vs iron-folic acid supplementation on infant mortality and adverse birth outcomes in rural Bangladesh: the JiVitA-3 randomized trial. JAMA. 2014 Dec 24-31;312(24):2649-58. doi: 10.1001/jama.2014.16819.