Antenatal Micronutrient Supplementation and Infant Survival

NCT ID: NCT00860470

Last Updated: 2022-10-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

44567 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-01-31

Study Completion Date

2012-09-30

Brief Summary

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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

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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.

Conditions

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Infant Mortality Preterm Birth Low Birth Weight Neonatal Mortality Perinatal Mortality

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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1

Iron (27 mg) and folic acid (600 ug)

Group Type ACTIVE_COMPARATOR

Iron (27 mg) - folic acid (600 ug)

Intervention Type DIETARY_SUPPLEMENT

Supplement serves as the "Control" (providing the current standard of care during pregnancy). Mothers instructed to take 1 tablet per day, from the 1st trimester through 12 weeks post-partum.

2

Multiple micronutrient

Group Type EXPERIMENTAL

Multiple micronutrient

Intervention Type DIETARY_SUPPLEMENT

Containing 15 micronutrients all at an RDA including: vitamin A (770 ug retinol equivalents, vitamin D (5 ug), vitamin E (15 mg), folic acid (600 ug), thiamin (1.4 mg), riboflavin (1.4 mg), niacin (18 mg), vitamin B-12 (2.6 mg), vitamin B-6 (1.9 mg), vitamin C (85 mg), iron (27 mg), zinc (12 mg), iodine (220 ug), copper (1000 ug), selenium (60 ug).

Mothers instructed to take 1 tablet per day, from the 1st trimester through 12 weeks post-partum.

Interventions

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Iron (27 mg) - folic acid (600 ug)

Supplement serves as the "Control" (providing the current standard of care during pregnancy). Mothers instructed to take 1 tablet per day, from the 1st trimester through 12 weeks post-partum.

Intervention Type DIETARY_SUPPLEMENT

Multiple micronutrient

Containing 15 micronutrients all at an RDA including: vitamin A (770 ug retinol equivalents, vitamin D (5 ug), vitamin E (15 mg), folic acid (600 ug), thiamin (1.4 mg), riboflavin (1.4 mg), niacin (18 mg), vitamin B-12 (2.6 mg), vitamin B-6 (1.9 mg), vitamin C (85 mg), iron (27 mg), zinc (12 mg), iodine (220 ug), copper (1000 ug), selenium (60 ug).

Mothers instructed to take 1 tablet per day, from the 1st trimester through 12 weeks post-partum.

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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iron-folate one-a-day multivitamin antenatal micronutrient

Eligibility Criteria

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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
Minimum Eligible Age

12 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Bill and Melinda Gates Foundation

OTHER

Sponsor Role collaborator

United States Agency for International Development (USAID)

FED

Sponsor Role collaborator

Mahidol University

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

Beximco Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role collaborator

DSM Nutritional Products, Inc.

INDUSTRY

Sponsor Role collaborator

Johns Hopkins Bloomberg School of Public Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Keith P West, Jr.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins Bloomberg School of Public Health

Parul Christian

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins Bloomberg School of Public Health

Locations

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Johns Hopkins School of Public Health

Baltimore, Maryland, United States

Site Status

JiVitA Project Office

Rangpur City, Gaibandha District, Bangladesh

Site Status

Countries

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United States Bangladesh

References

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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.

Reference Type BACKGROUND
PMID: 12637400 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12771347 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14608063 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14668283 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14758431 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15867289 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16125578 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16600929 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16614435 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18262025 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18644934 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11304051 (View on PubMed)

de Boer M, Thorne-Lyman AL, Shamim AA, Wu LS, Shaikh S, Ali H, West KP, Christian P. Dietary diversity as a modifier of the effect of supplementation with multiple micronutrients during pregnancy on low birth weight in a randomized controlled trial in Bangladesh. Am J Clin Nutr. 2025 Sep;122(3):762-769. doi: 10.1016/j.ajcnut.2025.07.007. Epub 2025 Jul 12.

Reference Type DERIVED
PMID: 40653272 (View on PubMed)

Finkelstein JL, Cuthbert A, Weeks J, Venkatramanan S, Larvie DY, De-Regil LM, Garcia-Casal MN. Daily oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2024 Aug 15;8(8):CD004736. doi: 10.1002/14651858.CD004736.pub6.

Reference Type DERIVED
PMID: 39145520 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35155983 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32844185 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31006806 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27769295 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27604769 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26431336 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26186135 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25985774 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25536256 (View on PubMed)

Related Links

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http://www.jhsph.edu/chn/research/jivita1.html

Basic description of the JiVitA project, location and individuals

Other Identifiers

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JHU_IRB 570

Identifier Type: -

Identifier Source: org_study_id

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