Association between arsenic exposure and intrauterine growth restriction: A systematic review and meta-analysis

Abstract

Several observational studies have explored the link between arsenic (As) exposure and intrauterine growth restriction (IUGR). However, epidemiological findings have been inconsistent, with a wide range of reported heterogeneity. This study aims to systematically evaluate the association between As exposure and IUGR (SGA(Small for gestational age), PTB(Preterm birth), LBW(Preterm birth)) through a meta-analysis. We searched six databases-China National Knowledge Infrastructure, Wan Fang, VIP Database, PubMed, Web of Science, and Science Direct-for studies on As exposure and IUGR up to May 2024. After screening and data extraction, a comprehensive bias risk assessment was conducted using the Newcastle-Ottawa Scale (NOS), AHRQ (the assessment tool of the Agency for Healthcare Research and Quality), and NTP/OHAT (the assessment tool of the National Toxicology Program/Office of Health Assessment and Translation). Meta-analysis was conducted using random-effects models (I2 > 50%) or fixed-effects models (I2 < 50%) to estimate effect sizes. Subgroup analysis and meta-regression analysis were performed to identify the sources of heterogeneity. Publication bias was assessed using the Egger test, Begg test, and funnel plot. Eleven studies, including 2,183,652 participants from the Americas, Europe, Asia, and Africa, were analyzed. Results showed a significant association between As exposure and SGA (OR: 1.06, 95% CI: 1.00, 1.13), particularly in Asia (OR: 1.28, 95% CI: 1.10, 1.49). Maternal exposure to higher As levels (10-100 μg/L) was also significantly associated with SGA (OR: 1.25, 95% CI: 1.04, 1.50). Although PTB (OR: 1.03, 95% CI: 0.99, 1.07) and LBW (OR: 1.03, 95% CI: 0.97, 1.09) did not show overall significant associations, subgroup analyses revealed increased risks under specific conditions. As exposure at 1-10 μg/L significantly increased PTB risk (OR: 1.13, 95% CI: 1.06, 1.21), while exposure at 0-1 μg/L significantly increased LBW risk (OR: 1.13, 95% CI: 1.06, 1.21). This study supports a link between As exposure and increased IUGR risk, particularly SGA. Stricter public health policies are needed to reduce arsenic exposure during pregnancy. However, due to heterogeneity and potential publication bias, results should be interpreted with caution.

Fig 1. PRISMA flowchart of the searching and selecting process.

Fig 2. Risk of bias summary using the OHAT framework.

++ low, + probably low, − probably high, − − high.

Fig 3. Forest plot of meta-analysis on arsenic exposure and IUGR risk.