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

Condition(s) targeted: Vitamin A Deficiency

Intervention: Vitamin A or Beta-Carotene Supplements (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Johns Hopkins Bloomberg School of Public Health

Official(s) and/or principal investigator(s):
Keith P West, Jr., Dr.P.H., Principal Investigator, Affiliation: Johns Hopkins Bloomberg School of Public Health
Parul Christian, Dr.P.H., Study Director, Affiliation: Johns Hopkins Bloomberg School of Public Health
Rolf DW Klemm, Dr.P.H., Study Director, Affiliation: Johns Hopkins Bloomberg School of Public Health
Mahbubur Rashid, MBBS, MSc, Study Director, Affiliation: JiVitA Bangladesh Project
Alain B Labrique, MSc, Study Director, Affiliation: Johns Hopkins Bloomberg School of Public Health
Alfred Sommer, M.D., Study Director, Affiliation: Johns Hopkins Bloomberg School of Public Health

Overall contact:
Keith P West, Jr., Dr.P.H., Phone: 410-955-2061, Email: kwest@jhsph.edu

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.

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

Study design: Prevention, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Efficacy Study

Primary outcome:

All-cause pregnancy-related maternal mortality

Perinatal and neonatal mortality

Three-month infant mortality

Secondary outcome:

Maternal morbidity, including obstetric complications

Gestational age at birth

Fetal and postnatal growth through three months of age

Infant morbidity through three months of age

Maternal and infant nutritional status

Detailed description: 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.

Minimum age: 15 Years. Maximum age: 49 Years. Gender(s): Female.

Criteria:

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

Keith P West, Jr., Dr.P.H., Phone: 410-955-2061, Email: kwest@jhsph.edu

JiVitA Bangladesh Project, Rangpur, Rajshahi Division, Bangladesh; Recruiting
Alain B Labrique, MSc, Phone: 880-521-63391, Email: alabriqu@jhsph.edu
Keith P West, Jr., Dr.P.H., Phone: 410-955-2061, Email: kwest@jhsph.edu
Joanne Katz, Sc.D., Sub-Investigator
Ahmed Shamim, M.Sc., Sub-Investigator
Emorn Wasantwisut, Ph.D., Sub-Investigator

Micronutrient research at the Center for Human Nutrition at Johns Hopkins Bloomberg School of Public Health

Related publications:

West KP Jr, Katz J, Khatry SK, LeClerq SC, Pradhan EK, Shrestha SR, Connor PB, Dali SM, Christian P, Pokhrel RP, Sommer A. Double blind, cluster randomised trial of low dose supplementation with vitamin A or beta carotene on mortality related to pregnancy in Nepal. The NNIPS-2 Study Group. BMJ. 1999 Feb 27;318(7183):570-5.

Katz J, West KP Jr, Khatry SK, Pradhan EK, LeClerq SC, Christian P, Wu LS, Adhikari RK, Shrestha SR, Sommer A. Maternal low-dose vitamin A or beta-carotene supplementation has no effect on fetal loss and early infant mortality: a randomized cluster trial in Nepal. Am J Clin Nutr. 2000 Jun;71(6):1570-6.

Christian P, West KP Jr, Khatry SK, LeClerq SC, Kimbrough-Pradhan E, Katz J, Shrestha SR. Maternal night blindness increases risk of mortality in the first 6 months of life among infants in Nepal. J Nutr. 2001 May;131(5):1510-2.

Christian P, West KP Jr, Khatry SK, Katz J, LeClerq SC, Kimbrough-Pradhan E, Dali SM, Shrestha SR. Vitamin A or beta-carotene supplementation reduces symptoms of illness in pregnant and lactating Nepali women. J Nutr. 2000 Nov;130(11):2675-82.

Christian P, West KP Jr, Khatry SK, Kimbrough-Pradhan E, LeClerq SC, Katz J, Shrestha SR, Dali SM, Sommer A. Night blindness during pregnancy and subsequent mortality among women in Nepal: effects of vitamin A and beta-carotene supplementation. Am J Epidemiol. 2000 Sep 15;152(6):542-7.

West KP Jr. Extent of vitamin A deficiency among preschool children and women of reproductive age. J Nutr. 2002 Sep;132(9 Suppl):2857S-2866S. Erratum in: J Nutr 2002 Nov;132(11):3432.

Starting date: August 2001
Ending date: May 2007
Last updated: September 6, 2006