Vitamin A Supplementation of Breast Feeding Mothers and Their Neonates at Delivery: Impact on Mother to Child Transmission of HIV During Lactation, HIV Infection Among Women During the Postpartum Year, and Infant Mortality.

The Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) project was a placebo-controlled randomized trial, which enrolled 14,110 mothers and their infants within 96 hours of delivery from one of 14 hospitals and clinics in greater Harare between November 25, 1997 and January 29, 2000. Mother-baby pairs were eligible if neither had an acutely life threatening condition, the baby was a singleton with birth weight >1500 g, and the mother planned to stay in Harare after delivery. Written informed consent was obtained from the mother. Socio-economic and demographic characteristics were collected by interview and obstetric details of the pregnancy and delivery were transcribed from hospital records. Gestational age was estimated. Infant birth weight was measured using an electronic scale. Infant length, infant head circumference, and maternal arm circumference were measured. Arm circumference was measured as an indicator of maternal nutritional status rather than Body Mass Index because it is less influenced by fluid fluctuations during the immediate post partum period. Addresses were recorded for the mother's urban and rural residences (it is common for urban Zimbabweans to travel frequently to extended family rural homesteads), her place of work, her husband's place of work, and that of relative who would always know her whereabouts.

At recruitment, study nurses collected plasma and serum from mothers and babies. Maternal plasma was stored at room temperature (~20° C) and other samples in a cool box (~ 10-15° C) before being transferred to the laboratory within 2 hr of collection.

Mother-baby pairs were randomized to one of four treatment groups: mother received 400,000 IU vitamin A (as retinyl palmitate) and baby received 50,000 IU vitamin A (Aa group); mother received 400,000 IU vitamin A and baby received placebo (Ap group); mother received placebo and baby received 50,000 IU vitamin A (Pa group); and both mother and baby received placebo (Pp group). Treatment and placebo capsules appeared identical and both contained a soy oil base with vitamin E as a preservative (50 IU per maternal capsule; 10 IU per infant capsule) (Tishcon Corporation, Westbury, NY, USA).

A separate team at Johns Hopkins University prepared the study capsule packets. Study identification numbers were randomly allocated to the treatment groups by computer in blocks of 12. The numbers were printed on adhesive labels and affixed to amber-colored zip-lock plastic bags that were packed with the assigned capsules. Capsule packets were prepared separately for each of the four treatment groups, and then merged into numeric order before shipping to Zimbabwe where series of packets were distributed to each recruitment site. As each mother-baby pair was recruited, the capsules in the next sequential bag were administered, and the associated study number assigned to the pair. Lists linking the study number to the treatment were kept in sealed envelopes and encrypted computer files that were not accessible to the Zimbabwe-based study team.

Pairs were followed at 6 wk, 3 mo, and then 3 monthly up to 24 months at one of three study clinics. Home visits were attempted for defaulting pairs to either their urban or rural home anywhere within the Zimbabwe borders. We initially planned to follow all HIV-positive mothers and their infants and a ~50% random sample of HIV-negative mothers and their infants for 24 months. However, in June 2000, economic conditions necessitated discontinuing the second year of follow up. This meant that 24%, 48% and 100% of the pairs were reassigned to 24 months, >18 month, and >12 month follow up, respectively. Follow up visits included assessment of recent illness, sick clinic visits, and hospitalizations by the mother or infant; anthropometric measures, infant dietary history, maternal sexual and reproductive health practices, and blood and breast milk sampling. Free clinical care included treatment of acute infections with appropriate antimicrobial drugs, referral to government treatment facilities for suspect tuberculosis, counseling and antibiotic treatment for mastitis, and oral rehydration solution education for diarrhea. HIV-related and psychosocial counseling was available throughout the study.