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

Abstract

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 randomized, controlled trials.

Methods: Original data from 12 randomized, controlled 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. Outcomes included birthweight, other birth measurements, gestation, and incidence of low birthweight (LBW) (< 2500 g), small-for-gestational age birth (SGA, birthweight below the within-each-population 10th percentile), 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 micronutrients 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 supplementation 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.

FIG. 1

Scatterplots of birthweight according to gestational age, for each of the 12 trials, showing (open circles) data removed because of implausible combinations of birthweight and gestational age (all based on the “restricted sample”)

FIG. 1

Scatterplots of birthweight according to gestational age, for each of the 12 trials, showing (open circles) data removed because of implausible combinations of birthweight and gestational age (all based on the “restricted sample”)

FIG. 2

Mean (95% CI) birthweight for multiple micronutrient (filled circles) and control (open circles) groups in each center

FIG. 3

Random-effects model forest plots for effects of MMN supplementation compared with controls on (a) birthweight, (b) low birthweight, (c) SGA births, (d) LGA births, (e) gestation and (f) pre-term delivery

FIG. 3

Random-effects model forest plots for effects of MMN supplementation compared with controls on (a) birthweight, (b) low birthweight, (c) SGA births, (d) LGA births, (e) gestation and (f) pre-term delivery

FIG. 3

Random-effects model forest plots for effects of MMN supplementation compared with controls on (a) birthweight, (b) low birthweight, (c) SGA births, (d) LGA births, (e) gestation and (f) pre-term delivery

FIG. 4

Effect on birthweight of MMN supplementation relative to the control group according to maternal BMI. The lines are truncated to the 5th and 95th percentiles for BMI for each dataset

FIG. 5

Random effects model showing the interaction between maternal BMI and supplement effect. The effect size indicates the change in birthweight (g) in the MMN group relative to the control groups per unit increase in maternal BMI