Multiple micronutrient supplementation during pregnancy in low-income countries: A meta-analysis of effects on birth size and length of gestation

Background. Multiple micronutrient deficiencies are common among women in low-income countries and may adversely affect pregnancy outcomes. Objective. This meta-analysis reports the effects on newborn size and duration of gestation of multiple micronutrient supplementation mainly compared with iron plus folic acid during pregnancy in recent rand-omized, controlled trials. Methods. Original data from 12 randomized, control-led trials in Bangladesh, Burkina Faso, China, Guinea-Bissau, Indonesia, Mexico, Nepal, Niger, Pakistan and Zimbabwe, all providing approximately 1 recommended dietary allowance (RDA) of multiple micronutrients to presumed HIV-negative women, were included. Out-comes included birthweight, other birth measurements, gestation, and incidence of low birthweight (LBW) (< 2,500g), small-for-gestational age birth (SGA, birth-weight below the within-each-population 10th percen-tile), large-for-gestational age birth (LGA, birthweight above the within-each- population 90th percentile), and preterm delivery (< 37 weeks). Results. Compared with control supplementation (mainly with iron-folic acid), multiple micronutrient supplementation was associated with an increase in mean birthweight (pooled estimate: +22.4 g [95% CI, 8.3 to 36.4 g]; p = .002), a reduction in the prevalence of LBW (pooled OR = 0.89 [95% CI, 0.81 to 0.97];p = .01) and SGA birth (pooled OR = 0.90 [95% CI, 0.82 to 0.99]; p = .03), and an increase in the prevalence of LGA birth (pooled OR = 1.13 [95% CI, 1.00 to 1.28]; p = .04). In most studies, the effects on birthweight were greater in mothers with higher body mass index (BMI). In the pooled analysis, the positive effect of multiple micro-nutrients on birthweight increased by 7.6 g (95% CI, 1.9 to 13.3 g) per unit increase in maternal BMI (p for interaction = .009). The intervention effect relative to the control group was + 39.0 g (95% CI, +22.0 to +56.1 g) in mothers with BMI of 20 kg/m² or higher compared with -6.0 g (95% CI, -8.8 to +16.8 g) in mothers with BMI under 20 kg/m². There were no significant effects of multiple micronutrient supplementation on birth length or head circumference nor on the duration of gestation (pooled effect: +0.17 day [95% CI, -0.35 to +0.70 day]; p = .51) or the incidence of preterm birth (pooled OR = 1.00 [95% CI, 0.93 to 1.09]; p = .92). Conclusions. Compared with iron-folic acid sup-plementation alone, maternal supplementation with multiple micronutrients during pregnancy in low-income countries resulted in a small increase in birthweight and a reduction in the prevalence of LBW of about 10%. The effect was greater among women with higher BMI.