INTERACTION BETWEEN GESTATIONAL WEIGHT GAIN AND PRENATAL MICRONUTRIENT SUPPLEMENTATION IN DETERMINING NEONATAL ANTHROPOMETRIC OUTCOMES: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Background: Gestational weight gain (GWG) and prenatal micronutrient supplementation are both critical determinants of neonatal anthropometric outcomes. While their independent effects have been extensively studied, the interaction between these two exposures remains poorly understood. Understanding how GWG modifies the effectiveness of micronutrient supplementation could inform more targeted prenatal interventions and optimize birth outcomes across diverse populations.

Methods: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched SciSpace Deep Search, SciSpace Full Text Search, Google Scholar, and PubMed through August 2026 using comprehensive search strategies combining terms related to gestational weight gain, prenatal micronutrient supplementation, and neonatal anthropometric outcomes. Studies were eligible if they analyzed the interaction or combined effect of GWG and micronutrient supplementation on birth weight, birth length, head circumference, or small for gestational age (SGA) in pregnant human populations. Two-stage screening (title/abstract, then full-text) was conducted using six pre-defined criteria with scoring thresholds of ≥4.0 for abstract screening and ≥4.5 for full-text screening. Data extraction focused on study design, population characteristics, micronutrient types and dosages, GWG measurement methods, neonatal outcomes, and interaction effect findings.

Results: From 892 identified records, 4 studies met inclusion criteria after removing 224 duplicates and screening 500 unique records. The included studies comprised randomized controlled trials and prospective cohort studies involving diverse populations from rural Gambia and China. Studies examined interactions between GWG and various micronutrients including lipid-based nutritional supplements with multiple micronutrients, iron and folic acid, and folic acid alone. Evidence demonstrated significant effect modification, with micronutrient supplementation showing enhanced effectiveness on birth weight and head circumference among women with higher gestational weight gain. For example, protein-energy plus multiple micronutrient supplementation was associated with +0.462 z-scores (95% CI [0.097, 0.826]) in birth weight among women in the highest quartile of weight gain, compared to -0.099 z-scores (-0.459, 0.260) in the lowest quartile.

Conclusions: This systematic review provides evidence that gestational weight gain significantly modifies the effect of prenatal micronutrient supplementation on neonatal anthropometric outcomes. The synergistic relationship suggests that adequate maternal weight gain may be necessary to maximize the benefits of micronutrient interventions. However, the limited number of included studies and heterogeneity in micronutrient types and GWG measurement methods indicate the need for additional high-quality research to establish robust clinical recommendations.