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. This study was registered in PROSPERO as CRD42024551864.