Antenatal and postnatal iron supplementation and childhood mortality in rural Nepal: a prospective follow-up in a randomized, controlled community trial

Abstract

The long-term benefits of antenatal iron supplementation in child survival are not known. In 1999-2001, 4,926 pregnant women in rural Nepal participated in a cluster-randomized, double-masked, controlled trial involving 4 alternative combinations of micronutrient supplements, each containing vitamin A. The authors examined the impact on birth weight and early infant mortality in comparison with controls, who received vitamin A only. They followed the surviving offspring of these women at approximately age 7 years to study effects of in utero supplementation on survival. Of 4,130 livebirths, 209 infants died in the first 3 months and 8 were lost to follow-up. Of those remaining, 3,761 were followed, 150 died between ages 3 months and 7 years, and 152 were lost to follow-up. Mortality rates per 1,000 child-years from birth to age 7 years differed by maternal supplementation group, as follows: folic acid, 13.4; folic acid-iron, 10.3; folic acid-iron-zinc, 12.0; multiple micronutrients; 14.0; and controls, 15.2. Hazard ratios were 0.90 (95% confidence interval (CI): 0.65, 1.22), 0.69 (95% CI: 0.49, 0.99), 0.80 (95% CI: 0.58, 1.11), and 0.93 (95% CI: 0.66, 1.31), respectively, in the 4 supplementation groups. Maternal iron-folic acid supplementation reduced mortality among these children by 31% between birth and age 7 years. These results provide additional motivation for strengthening antenatal iron-folic acid programs.

Figure 1.

Population follow-up and participation in a controlled trial involving alternative combinations of antenatal micronutrient supplements, Nepal, 1999–2008. Excluded women were those who had a false-positive pregnancy test result, an unknown pregnancy outcome, or an induced abortion.

Figure 2.

Effects of antenatal micronutrient supplementation on offspring mortality from birth to age 7 years, expressed as hazard ratios (HR) and 95% confidence intervals (CI), by supplementation group, Nepal, 1999–2008. A) Folic acid-iron supplementation versus vitamin A alone (control group); B) multiple micronutrient supplementation versus vitamin A alone (control group). For interaction between preterm birth and multiple micronutrient supplementation, P < 0.1 (Cox proportional hazards model with a robust variance estimate). Body mass index is calculated as weight (kg)/height (m)².

Figure 3.

Kaplan-Meier curve for probability of survival among children of women who received antenatal micronutrient supplements, by supplementation group, Nepal, 1999–2008.