The Efficacy of Zinc Supplementation Alone or in Combination for Improving Pregnancy and Infant Outcomes: A Systematic Review and Meta-Analysis.

Objective: To evaluate zinc supplementation's efficacy in pregnancy, addressing gaps in previous reviews regarding high-risk subgroups and combination therapies.

Methods: Systematic review of six databases through March 27, 2025 for randomized controlled trials (RCTs) on prenatal zinc supplementation. Risk of bias was assessed using the Cochrane Risk of Bias 2. Stratified analyses was conducted by participant or intervention characteristics, with meta-analysis or qualitative synthesis when appropriate. Sensitivity analyses was conducted by excluding studies with high risk of bias. The systematic review was registered in PROSPERO (CRD42023440314).

Results: 77 RCTs were included. Compared with no zinc, zinc monotherapy among healthy pregnant women resulted in higher serum zinc level (standard mean difference (SMD) _{the second trimester} = 0.32, 95% confidence interval (CI) 0.20 to 0.44; SMD_{the third trimester} = 0.51, 95% CI 0.27 to 0.76), lower fetal intrauterine retardation rate (risk ratio = 0.23, 95% CI 0.16 to 0.35), longer neonatal birth length (SMD = 0.66, 95% CI 0.21 to 1.12), bigger birth head circumference (SMD = 0.58, 95% CI 0.08 to 1.09), higher 1-min Apgar score (SMD = 0.28, 95% CI 0.06 to 0.49) and cord blood zinc level (SMD = 0.36, 95% CI 0.17 to 0.56). No additional benefits observed with zinc-iron-folate combinations versus iron-folate alone. Qualitative synthesis of limited evidence suggested potential benefits for high-risk groups (anemia, gestational diabetes, zinc deficiency or impaired intravenous glucose tolerance test).

Conclusions: Zinc monotherapy may benefit healthy pregnancies and high-risk groups, but combination regimens show no additional advantages. Further research should confirm these findings.