Abstract Title Prenatal Exposure to Tetrachloroethylene and Adverse Birth Outcomes: Systematic Review & Meta- Analysis Background Tetrachloroethylene (PCE) is a chemical widely used in dry cleaning, metal degreasing, and textile processing. Occupational activities and improper waste management may lead to PCE contamination in indoor air and/or drinking water. Several studies have assessed associations between prenatal exposure to PCE and adverse birth outcomes, but a comprehensive review is needed to establish the strength and quality of these results. The aim of this study was to synthesize evidence and meta-analyze the associations between prenatal exposure to PCE and specific adverse birth outcomes: spontaneous abortions, stillbirths, CNS defects, oral cleft defects, neural tube defects, birthweight, preterm birth, and small-for-gestational-age. Methods Search Methods Six electronic databases were searched to identify relevant studies with no restrictions on date, publication type or geographic location. Reference lists of included studies were also hand searched. Selection Criteria Studies were included if they were observational studies that statistically quantified the association between PCE and the adverse birth outcomes of interest. Participants included pregnant women with infants exposed to PCE in the antenatal period. Comparator groups were unexposed. Studies in which effects of PCE were not disaggregated were excluded. Data Collection and Analysis Main results and study characteristics were extracted from each relevant study. Critical appraisal was performed using the Newcastle–Ottawa Scale (NOS) for case-control and cohort studies and the Agency for Healthcare Research and Quality (AHRQ) for cross-sectional studies. Risk ratios were calculated for each outcome using David Wilson’s Online Effect Size Calculator. Effect sizes were then pooled using random effects meta-analyses. Subgroup analyses by exposure pathway, country, and study design were also conducted when possible. Sensitivity to risk of bias was also conducted where possible. Results Eighteen studies were included. Risk of bias was high in one, moderate in seven, and low in ten studies. Meta-analyses found that prenatal PCE exposure correlated significantly with any adverse birth outcome (RR=1.16, p=0.049, I2=60%) and spontaneous abortions (RR=1.38, p < 0.01, I2=1.7%). While elevated risk ratios were found for PCE exposure and other outcomes (any congenital anomaly, stillbirths, CNS defects, oral cleft defects, neural tube defects, low birthweight, preterm birth, and small-for-gestational- age), they were not significant. Conclusion

Overall, prenatal exposure to PCE is significantly associated with higher risk of any adverse birth outcome and spontaneous abortions. This highlights the importance of minimizing PCE through policy measures and monitoring of water and air samples. Future research should address limitations in the evidence base and potential biological mechanisms.