Impact of Maternal Vitamin A or Beta-Carotene Supplementation on Maternal and Infant Mortality in Bangladesh

Study Overview
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Brief Summary
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The purpose of this trial is to determine whether providing women with a weekly oral supplement of vitamin A, either preformed or as beta-carotene, at a dosage equivalent to a recommended intake from early pregnancy through three months postpartum, can reduce the risk of maternal mortality, fetal loss, or infant mortality.

Detailed Description
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Maternal mortality and vitamin A deficiency coexist in rural South Asia. In Nepal, weekly supplementation with vitamin A or beta-carotene during the child-bearing years reduced all-cause maternal mortality and, in night blind women, also infant mortality. The present trial is testing the efficacy of the same supplements from  9 weeks' gestation to 12 weeks postpartum. The planned sample size is 68,000 pregnancies. It is being conducted in 19 rural unions, covering an area of  750 sq km with a population of  580,000 in Gaibandha and Southern Rangpur Districts in Northern Bangladesh. The study area was mapped as 596 sectors (unit of randomization), each comprising 200-275 households;  135,000 houses were numerically addressed and, at the outset, 103,000 women were listed. Women are visited at home every 5 weeks by 596 trained female staff to detect pregnancy by a combination of menstrual history and urine testing. Newly married women are prospectively enlisted for pregnancy surveillance. Following informed consent urine-positive (pregnant) women detected during surveillance are enrolled to receive weekly a capsule containing 7000 retinol equivalents of preformed vitamin A, 42 mg of beta-carotene or placebo. Vital events are recorded weekly through 3 months postpartum. Trained interviewers conduct maternal nutritional and health and household socioeconomic assessments in the 1st trimester. At 3 months postpartum, interviewers assess both mother and infant for health and nutritional status, including apparent birth defects that are later physician-confirmed. An additional home health assessment occurs at 6 months post partum, and vital status is recorded for mother and infant at one year postpartum. A  3% subsample of enrolled pregnant women participate in a substudy involving enhanced clinical, anthropometric, biochemical, body compositional, morbidity and interview-based assessment protocols in the 1st, 2nd and 3rd trimesters, and at 3 months post-partum. Reported maternal and infant deaths are verified and causes ascertained during verbal autopsy interviews with family members of the deceased.

Official Title
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Impact of Maternal Vitamin A or Beta-Carotene Supplementation on Maternal and Infant Mortality in Bangladesh

Conditions
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Vitamin A Deficiency, Maternal Mortality, Infant Mortality

Intervention / Treatment
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* Dietary Supplement: Vitamin A or Beta-Carotene Supplements


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Married women of reproductive age First pregnancy during time period of trial Exclusion Criteria: Premenarchial girls Married women with a previous pregnancy enrolled into the trial Previously married women who have moved into the study area Single women (never married, widowers) Women who are sterilized (or whose husbands are sterilized) Menopausal women

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Weekly oral supplement with 7000 µg retinol equivalents from early pregnancy through 12 weeks following termination of pregnancy | Dietary Supplement: Vitamin A or Beta-Carotene Supplements<br>* weekly dosage of either 7000 µg retinol equivalents as preformed vitamin A or 42 mg of beta-carotene from 1st trimester of pregnancy through 12 weeks after termination of pregnancy<br>|
| Experimental: 2<br>Weekly oral supplement with 42 mg of beta-carotene from early pregnancy through 12 weeks following termination of pregnancy | Dietary Supplement: Vitamin A or Beta-Carotene Supplements<br>* weekly dosage of either 7000 µg retinol equivalents as preformed vitamin A or 42 mg of beta-carotene from 1st trimester of pregnancy through 12 weeks after termination of pregnancy<br>|
| Placebo Comparator: 3<br>Weekly oral supplement with placebo from early pregnancy through 12 weeks following termination of pregnancy | Dietary Supplement: Vitamin A or Beta-Carotene Supplements<br>* weekly dosage of either 7000 µg retinol equivalents as preformed vitamin A or 42 mg of beta-carotene from 1st trimester of pregnancy through 12 weeks after termination of pregnancy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause, Pregnancy-related Mortality | Mortality evaluated on intent-to-treat basis | Deaths during pregnancy through 12 weeks postpartum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause 3-month Infant Mortality |  | Deaths through the 1st 12 weeks of life | 
| Maternal Morbidity, Including Obstetric Complications |  | through the 1st 24 weeks following termination of pregnancy | 
| Gestational Age at Birth |  | within 24 weeks after birth | 
| Fetal Growth and Postnatal Infant Growth Through Three Months of Age |  | through the 1st 12 weeks after birth | 
| Infant Morbidity Through 3 Months of Age |  | within 24 weeks after birth | 
| Plasma Beta-carotene in the Third Trimester of Pregnancy(Nutritonal Status of the Mother) |  | Third trimester of pregnancy (about the 32nd week of gesatation) | 
| Plasma Retinol at the Third Trimester of Pregnancy (Nutritional Status of the Mother) |  | Third trimester of pregnancy (about the 32nd week of gestation) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Maternal mortality, Infant mortality, Vitamin A, Beta-carotene, Micronutrients, Bangladesh, Neonatal mortality