Micronutrient Supplementation Before and During 1st Pregnancy to Improve Birth Outcomes (JiVitA-5)

Johns Hopkins Bloomberg School of Public Health

Status: Terminated

Conditions: Birth Weight; Miscarriage; Preterm Birth; Small-for-gestational Age

Treatments: Dietary Supplement: Multiple micronutrient supplement; Drug: Placebo Oral Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT03921177

IRB 7841

Details and patient eligibility

About

The purpose of this cluster-randomized trial is to evaluate the efficacy of daily, multiple micronutrient (MM) supplement versus identical placebo use among nulligravid, recently married women, starting preconceptionally through the 1st trimester of pregnancy, in reducing low birth weight and other adverse pregnancy outcomes in rural Bangladesh.

Full description

Micronutrient deficiencies are common among women of reproductive age in rural South Asia, including Bangladesh. Antenatal multiple micronutrient (MM) supplementation, usually starting toward the end of the 1st trimester, has been shown to reduce low birth weight in many cultures. In northern Bangladesh, where the current study will be conducted, MM versus iron-folic acid supplementation has been shown to extend gestational age, thereby reducing risks of preterm birth 15% and low birth weight by 12%, and reduce risk of stillbirth by 11% (West KP et al. JAMA 2014), and to reduce risk of micronutrient deficiencies (Schulze KJ et al J Nutr 2019). Since it is plausible that women of reproductive age conceive in a state of lower micronutrient nutriture, it remains unknown the degree to which MM supplementation, starting preconceptionally through the 1st trimester (covering the periconceptional and embryonic period) can benefit pregnancy outcome. Further, there is concern that newlywed, nulligravid women in rural South Asia are at high risk, and may be at particular health and pregnancy risks due to micronutrient deficiencies resulting from dietary inadequacy.

The investigators propose to conduct a double-masked, cluster-randomized, placebo-controlled trial among recently married women in 18 rural unions of Gaibandha District, Bangladesh, that will provide a daily tablet containing either (a) a MM formulation containing a US Institute of Medicine (IOM) Recommended Dietary Allowance (RDA) for pregnancy for 15 essential vitamins and minerals (and closely approximates the UNIMAP formula), or (b) a placebo tablet of identical appearance containing no micronutrients, during a period extending from at least one-month prior to last menstrual period through the 1st trimester of pregnancy (~12 weeks' gestation). The study area will comprise 566 rural clusters (sectors) each with 250-400 households, serving as units of randomization. Consenting, recently married women will be detected through routine community surveillance and start to receive coded, double-masked supplements, resupplied during monthly home visits. Participating women will receive coded supplements for daily consumption until the end of the trial or until determined to be pregnant. On detection of pregnancy by a history of amenorrhea confirmed by urine test, irrespective of randomized allocation, all women will be switched to receive an open-labeled MM supplement, expected to occur toward the end of the 1st trimester, which will continue through 3 months post-partum. This switch is in response to previous positive effects shown on pregnancy outcomes with a MM supplement starting at the end of the 1st trimester.

Participating married women will be periodically interviewed for socioeconomic, morbidity, dietary and lifestyle risk factors and assessed by anthropometry. Pregnancies will be followed for miscarriage, abortion, live birth and still birth outcomes. Newborn anthropometry will be assessed to determine birth weight and size. Infants and mothers will be eligible for additional breast feeding, dietary, morbidity and growth assessments at 8 days, and 1, 3 and 6 months after delivery. Participating women resident in a predefined subset of the study area (n~68 sectors) will receive enhanced assessments, including blood draw in the end of the 1st trimester for subsequent laboratory assessment of micronutrient status, and body composition, among other measures.

Enrollment: 9,859 patients

Sex: Female

Ages: Under 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Resident of 566 rural sectors (clusters) in Gaibandha district
• Recently-married woman
• Nulligravid

Exclusion criteria

• Women with a history of previous pregnancy
• Women who refuse consent for participation

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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9,859 participants in 2 patient groups, including a placebo group

Multiple micronutrient supplement

Experimental group

Description:

Daily micronutrient supplement

Treatment:

Dietary Supplement: Multiple micronutrient supplement

Placebo

Placebo Comparator group

Description:

Daily identifcal placebo tablet

Treatment:

Drug: Placebo Oral Tablet