This study aims to investigate the correlation between exposure to disinfection byproducts of chlorination and preterm birth (PTB) through evidence-based medicine Meta-analysis and Mendelian randomization (MR) analysis. Meta-analysis was conducted on 17 studies involving 1,251,426 neonates, revealing a higher risk of PTB with exposure to total trihalomethanes (TTHMs) and chloroform. Mendelian randomization (MR) analysis confirmed a causal relationship between chlorides and PTB. TTHMs and chloroform were associated with increased PTB risk, while haloacetic acids showed no significant association. TTHMs were linked to small gestational age. Ethnicity and study design influenced heterogeneity. Exposure to chlorination byproducts, particularly TTHMs and chloroform, poses a significant risk for PTB. MR analysis supports a causal relationship between chlorides and PTB, highlighting the importance of water disinfection byproduct control in preventing PTB.
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