Multiple-micronutrient supplementation in pregnant adolescents in low- and middle-income countries: a systematic review and a meta-analysis of individual participant data

Context: Approximately 7.3 million births occur annually among adolescents in low- and middle-income countries. Pregnant adolescents constitute a nutritionally vulnerable group that could benefit from intervention to mitigate the mortality and adverse birth outcomes associated with adolescent pregnancy. Objective: The aim of this systematic review and meta-analysis was to assess the following: (1) the effect of multiple-micronutrient (MMN) supplementation vs iron and folic acid (IFA) supplementation among adolescents on maternal morbidity, birth outcomes, and mortality outcomes, (2) the effects of MMN supplementation in adolescents compared with the effects in adult women, and (3) the effect modification, if any, of MMN supplementation by baseline and geographic characteristics of adolescents. Data Sources: MEDLINE and Cochrane databases were searched, along with the reference lists of relevant reviews. Study Selection: Multiple-micronutrient supplementation trials in pregnancy that were conducted in a low- or middle-income country and had included at least 100 adolescents (10–19 years of age) were eligible for inclusion. Two independent reviewers assessed study eligibility. Data Extraction: Thirteen randomized controlled trials conducted in Africa and Asia were identified from 1792 reviews and 1578 original trials. Individual-level data was shared by study collaborators and was checked for completeness and extreme values. One- and two-stage individual participant data meta-analyses were conducted using data from randomized controlled trials of MMN supplementation. Results: A total of 15 283 adolescents and 44 499 adult women with singleton births were included in the individual participant data meta-analyses of MMN supplementation vs IFA supplementation. In adolescents, MMN supplementation reduced low birth weight (1-stage OR = 0.87, 95%CI 0.77–0.97; 2-stage OR = 0.81; 95%CI 0.74–0.88), preterm birth (1-stage OR = 0.88, 95%CI 0.80–0.98; 2-stage OR = 0.86, 95%CI 0.79–0.95), and small-for-gestational-age births (1-stage OR = 0.90, 95%CI 0.81–1.00; 2-stage OR = 0.86, 95%CI 0.79–0.95) when compared with IFA supplementation. The effects of MMN supplementation did not differ between adolescents and older women, although a potentially greater reduction in small-for-gestational-age births was observed among adolescents. Effect modification by baseline characteristics and geographic region was inconclusive. Conclusions: Multiple-micronutrient supplementation can improve birth outcomes among pregnant adolescents in low- and middle-income countries. Policy related to antenatal care in these settings should prioritize MMN supplementation over the currently recommended IFA supplementation for all pregnant women, especially adolescents.