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

Vitamin A Deficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00198822
• Other study ID #: GHS-A-00-03-00019-00
• Status: Completed
• Phase: Phase 3
• First received: September 12, 2005
• Last updated: March 5, 2012
• Start date: August 2001
• Est. completion date: March 2008

Study information

• Verified date: March 2012
• Source: Johns Hopkins Bloomberg School of Public Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardBangladesh: Bangladesh Medical Research Council
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59666
• Est. completion date: March 2008
• Est. primary completion date: January 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 15 Years to 49 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Infant Mortality
• Maternal Death
• Maternal Mortality
• Night Blindness
• Vitamin A Deficiency

Intervention

Dietary Supplement:
• Vitamin A or Beta-Carotene Supplements
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

Locations

Country	Name	City	State
Bangladesh	JiVitA Bangladesh Project	Rangpur	Rajshahi Division
Bangladesh	JiVitA Project Office	Rangpur	Rangpur District
United States	Johns Hopkins School of Public Health	Baltimore	Maryland

Sponsors (6)

Lead Sponsor	Collaborator
Johns Hopkins Bloomberg School of Public Health	Access Business Group, Bill and Melinda Gates Foundation, Canadian International Development Agency, The Sight and Life Research Institute, United States Agency for International Development (USAID)

Countries where clinical trial is conducted

United States,  Bangladesh, 

References & Publications (9)

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. — View Citation

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. — View Citation

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. — View Citation

Gunnsteinsson S, Labrique AB, West KP Jr, Christian P, Mehra S, Shamim AA, Rashid M, Katz J, Klemm RD. Constructing indices of rural living standards in Northwestern Bangladesh. J Health Popul Nutr. 2010 Oct;28(5):509-19. — View Citation

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. — View Citation

Labrique AB, Christian P, Klemm RD, Rashid M, Shamim AA, Massie A, Schulze K, Hackman A, West KP Jr. A cluster-randomized, placebo-controlled, maternal vitamin A or beta-carotene supplementation trial in Bangladesh: design and methods. Trials. 2011 Apr 21 — View Citation

West KP Jr, Christian P, Labrique AB, Rashid M, Shamim AA, Klemm RD, Massie AB, Mehra S, Schulze KJ, Ali H, Ullah B, Wu LS, Katz J, Banu H, Akhter HH, Sommer A. Effects of vitamin A or beta carotene supplementation on pregnancy-related mortality and infan — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause, Pregnancy-related Mortality	Mortality evaluated on intent-to-treat basis	Deaths during pregnancy through 12 weeks postpartum	No
Secondary	All-cause 3-month Infant Mortality		Deaths through the 1st 12 weeks of life	No
Secondary	Maternal Morbidity, Including Obstetric Complications		through the 1st 24 weeks following termination of pregnancy	No
Secondary	Gestational Age at Birth		within 24 weeks after birth	No
Secondary	Fetal Growth and Postnatal Infant Growth Through Three Months of Age		through the 1st 12 weeks after birth	No
Secondary	Infant Morbidity Through 3 Months of Age		within 24 weeks after birth	No
Secondary	Plasma Beta-carotene in the Third Trimester of Pregnancy(Nutritonal Status of the Mother)		Third trimester of pregnancy (about the 32nd week of gesatation)	No
Secondary	Plasma Retinol at the Third Trimester of Pregnancy (Nutritional Status of the Mother)		Third trimester of pregnancy (about the 32nd week of gestation)	No

External Links

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