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

Diao et al., 2025 | J Evid Based Med | Meta Analysis

Citation

Diao Sha, Feng Yuan, ... Zhang Lingli. The Efficacy of Zinc Supplementation Alone or in Combination for Improving Pregnancy and Infant Outcomes: A Systematic Review and Meta-Analysis. J Evid Based Med. 2025-Sep;18(3):e70061. doi:10.1111/jebm.70061

Abstract

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; SMDthe 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.

Key Findings

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; SMDthe 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),

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population healthy pregnant
Sample Size 77
Age Range See abstract
Condition diabetes

MeSH Terms

  • Pregnancy
  • Humans
  • Female
  • Zinc
  • Dietary Supplements
  • Pregnancy Outcome
  • Infant, Newborn
  • Randomized Controlled Trials as Topic
  • Pregnancy Complications

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Systematic Review, Meta-Analysis
  • Vertical: folate

Provenance


Source extracted via PubMed E-utilities API on 2026-04-09