Effect of prenatal multiple micronutrient supplementation compared with iron and folic acid supplementation on size at birth and subsequent growth through 24 mo of age: a systematic review and meta-analysis

Background Prenatal multiple micronutrient supplementation (MMS), in comparison to iron and folic acid supplementation (IFA), improves pregnancy outcomes, but less is known about their effect on infant growth. Objectives We conducted a systematic review of trials comparing maternal MMS to IFA and assessed the effect on infants’ anthropometric outcomes at birth, 3, 6, 12, 18, and 24 mo of age. Methods We included trials from a Cochrane review and new studies identified through systematic literature searches in 3 databases. We calculated the pooled effect estimates with 95% confidence intervals (CIs) using a generic inverse variance method, with fixed (primary analysis) and random-effects, and assessed subgroup differences. Results The 19 included trials showed that MMS, compared to IFA, led to significantly greater length and weight from birth to 6 mo, head circumference (HC) from birth to 12 mo, and mid-upper arm circumference (MUAC) through 3 mo. Infants born to pregnant women consuming MMS were longer at birth (mean difference: 0.05 cm; 95% CI: 0.02, 0.08 cm) and had higher length-for-age z-score at birth (0.09; 95% CI: 0.06, 0.12), 3 mo (0.09; 95% CI: 0.06, 0.12), and 6 mo (0.04; 95% CI: 0.01, 0.07) of age but not thereafter. MMS resulted in significantly higher weight-for-age z-score and HC-for-age z-score until 6 mo and higher weight-for-length z-score and MUAC-for-age z-score until 3 mo. MMS reduced risk of stunting (risk ratio [RR]: 0.86; 95% CI: 0.82, 0.91), underweight (RR: 0.86; 95% CI: 0.81, 0.90), small HC (RR: 0.84; 95% CI: 0.79, 0.90), and low MUAC (RR: 0.90; 95% CI: 0.82, 0.99) at 3 mo and wasting (RR: 0.90; 95% CI: 0.85, 0.96) at birth. For some outcomes, effects were greater when MMS was continued postpartum and in settings with higher prevalence of low birthweight. Conclusions Prenatal MMS improves size at birth and subsequent infant growth through 6 mo of age but not thereafter. These results strengthen the evidence on MMS benefits beyond birth outcomes.