A total of 44
646 women were recruited, 36
847 at the outset and 7799 newly married women during the trial (fig ). In all, 1136 (2.5%) women were excluded because they emigrated before becoming pregnant or dying or because they declined to be recruited. Overall, 20
119 (45%) women were pregnant 22
189 times. Maternal survival was known after all pregnancy outcomes, but 157 women were lost to follow up during the postpartum period (their median follow up time post partum was around 2 weeks in each group). As the women lost to follow up had completed pregnancies they were included in the denominators for estimating mortality.
At the time of their first study pregnancy, the three groups of women were comparable in age, arm circumference, and weekly dietary intakes. Small differences were evident with respect to cigarette smoking, alcohol consumption, and literacy. A smaller percentage of the placebo group were of low Hindu caste or were not Hindus. Only 3% of pregnancies were delivered at a health post, clinic, or hospital (table ).
Characteristics of mothers during their first study pregnancy by supplement group. Values are numbers (percentages) unless stated otherwise
Women who were pregnant more than once during the trial received a greater percentage of their total eligible supplements than those who were never pregnant (fig ). For example, half of the women who were ever pregnant and 44% of those who were never pregnant received
80% of their intended supplements. Over 75% of the pregnant women received at least half of their eligible doses—that is, more than half of a dietary allowance for those receiving vitamin A or β carotene—compared with around 62% of those who were never pregnant. Compliance was about 3% lower in the β carotene group in the mid-range of supplement intake.
Minimum percentages of all eligible weekly supplements (to the end of the trial or death) taken by percentages of women who were ever or never pregnant during the trial by supplement group
Among 1446 women who had their first pregnancy in the 27 substudy wards between September 1994 and July 1996, 1025 (71%) were seen at the clinic, of whom 978 (95%) were confirmed pregnant by urine test. From these women, serum samples were available for 935 (96%) and 916 (94%) mid-pregnancy determinations of retinol and β carotene concentrations, respectively. The mean serum retinol concentration was lowest in the placebo group (1.02 μmol/l), highest among vitamin A recipients (1.30
μmol/l), and between these two values in the β carotene group (1.14
μmol/l) (table ). The percentage of women by supplement group with serum retinol concentrations <0.70
μmol/l followed the same pattern. The mean β carotene concentration was significantly higher (0.20
μmol/l) and the percentage of women with concentrations <0.09
μmol/l lower (26.5%) in the β carotene than in the vitamin A and placebo groups (around 0.14
μmol/l and about 42% in both groups). Thus, compliance with taking supplements seems to have been adequate to change biochemical variables.
Serum retinol and β carotene concentrations in women during mid-pregnancy
Mortality related to pregnancy up to 12 weeks post partum was 704, 426, and 361 maternal deaths per 100
000 pregnancies in the placebo, vitamin A, and β carotene groups, yielding relative risks of 0.60 (0.37 to 0.97) (P=0.04) and 0.51 (0.30 to 0.86) (P=0.01) in the vitamin A and β carotene groups, respectively (table ). Mortality among women receiving β carotene was not significantly different from that in the vitamin A group (relative risk 0.85 (0.48 to 1.49), P=0.57). We therefore combined the effects to obtain a relative risk of 0.56 (0.37 to 0.84), reflecting a 44% reduction in mortality related to pregnancy associated with vitamin A or β carotene supplementation (P=0.005). This survival effect was evident after 1½ years of the trial, reflected by a relative risk of 0.54 (0.32 to 0.90) (P=0.02), which remained stable during the last part of the trial (relative risk 0.61 (0.31 to 1.19), P=0.15, data not shown). The relative risk was protective for both nutritional supplements during pregnancy, from the end of pregnancy to 6 weeks post partum, and from 6 to 12 weeks post partum (table ).
Impact of supplementation on mortality related to pregnancy up to 12 weeks post partum
Impact of supplementation on mortality in women during and after pregnancy
Analysis of cause specific mortality, based on interviews with relatives, showed protective but non-significant effects of supplementation against risk of death from obstetric causes and infection (table ). Point estimates of relative risk are stronger for β carotene than for vitamin A. Supplementation was associated with protection from death attributed to injuries and other miscellaneous causes.
Impact of supplementation on cause related mortality in women during pregnancy up to 12 weeks post partum. Values are numbers of women unless stated otherwise
The maternal mortality ratio was 645 (42 deaths/6670 live births), 407 (29/7074), and 361 (23/6643) per 100
000 live births in the placebo, vitamin A, and β carotene groups, respectively (P=0.08 for vitamin A and 0.04 for β carotene v
placebo). The ratio for women receiving either vitamin A or β carotene was 385, yielding a relative risk of 0.60 (0.39 to 0.93), representing a 40% reduction in mortality by this measure (P=0.02).