A Comparative Evaluation of Multiple Micronutrient and Iron–Folic Acid Supplementation during Pregnancy in Pakistan: Impact on Pregnancy Outcomes

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Abstract
Background: Maternal micronutrient deficiencies are widespread in Pakistan and are potentially associated with maternal undernutrition and intrauterine growth retardation. Intervention strategies largely consist of administration of iron–folic acid supplements during pregnancy. Objective: We evaluated the acceptability of multiple micronutrient supplementation and its potential benefits on pregnancy outcomes and maternal micronutrient status in a cohort of pregnant women in rural and urban Sindh through a cluster-randomized design. Methods: We randomly assigned 2,378 pregnant women to receive either iron–folic acid or multiple micronutrient supplements. The supplements were administered fortnightly by community health workers who performed home visits to assess tolerance and observe the mothers. Results: The women in both groups consumed about 75% of the supplements provided, and few reported adverse effects such as vomiting, abdominal pain, etc. There was a small (70 g) but significant increase in birthweight among infants of mothers receiving multiple micronutrients as compared with infants of mothers receiving iron–folic acid supplements (2.95 ± 0.6 vs. 2.88 ± 0.5 kg, p = .01). This translated into a 10% reduction (p < 0.17) in the proportion of low-birthweight infants among infants of mothers receiving multiple micronutrients. Although stillbirth rates were comparable in the two groups, the early neonatal mortality rate in the group receiving multiple micronutrients was higher, although not significantly, than that in the group receiving iron– folic acid (43.2 vs. 23.5 deaths per 1,000 live births; RR = 1.64; 95% CI, 0.94 to 2.87). Comparable reductions in anemia (hemoglobin < 11 g/dL) were observed, although the proportion with low iron stores (assessed by serum ferritin) was lower in the iron–folic acid group in the postnatal period. Although the proportion of women with subclinical vitamin A deficiency after supplementation did not differ between the two groups, the iron–folic acid group had a higher proportion with lower serum zinc levels in the immediate postpartum period. Conclusions: These data suggest that multiple micronutrient supplements are well tolerated during pregnancy, but the effect on birthweight is modest. The observed effect on early neonatal mortality suggests the need for further studies and careful assessment of the intervention in health system settings.