Trimester-Specific Blood Trihalomethane and Urinary Haloacetic Acid Concentrations and Adverse Birth Outcomes: Identifying Windows of Vulnerability during Pregnancy

BACKGROUND: Some disinfection by-products (DBPs) are reproductive, and developmental toxicants in laboratory animals. However, studies of trimester-specific DBP e,xposure, on adverse birth outcomes in humans are inconsistent. OBJECTIVE: We examined whether trimester-specific blood and urinary biomarkers of DBP were associated with small for gestational age (SGA), low birth weight (LBW), and preterm birth. METHODS: A total of 4,086 blood and 3,951 urine samples were collected across pregnancy trimesters among 1,660 mothers from Xiaogan City, China. Blood samples were quantified for biomarkers of trihalomethanes (MEMO: chloroform (TCM), bromodichloromethane, clibromochloromethane, and bromoform. Urine samples were quantified for biomarkers of haloacetic acids (HAA): clichloroacetic acid and trichloroacetic acid. Birth outcomes were abstracted at delivery from medical records. We used Poisson regression models with log link functions to estimate risk ratios (RRs) and 95% confidence intervals (Cis) for SGA, LBW, and preterm birth across terffles (or categories) of DBP biomarker concentrations measured across pregnancy trimesters. We also examined the relative exposure differences across gestation comparing adverse outcomes with normal births using mixed-effects models. RESULTS: Blood TCM concentrations in the second trimester were associate-d with an elevated risk of SGA comparing middle, vs. lowest (RR, 2.34; 955') CI: 1.02, 5.35) and highest vs. lowest (RR, 2.47; 955') CI: 1.09, 5.58) exposure groups. Third-trimester blood TCM. concentrations were also associated with an increased risk of SGA comparing the second tertile with the first (RR, 2.61; 95% CI: 1.15, 5.92). We found that maternal blood TCM concentrations were significantly higher for SGA compared with non-SGA births across the period from 23 to 34 wk gestation. Other blood and urinary DBP biomarkers examined were unrelated to SGA, LBW, or preterm birth. CONCLUSION: Blood TCM concentrations in mid to late pregnancy were associated with an Increased risk of SGA, whereas other biomarkers of DBPs examined across pregnancy were not associated with birth outcomes.