Exposure to drinking water pollutants and non-syndromic birth defects: a systematic review and meta-analysis synthesis
Authors: Jauniaux Eric , Jeremiah Lydia , Richardson Biba , Rogozińska Ewelina 
Published: November 2024

Objectives
To evaluate the association between drinking water pollutants and non-syndromic birth defects.

Design
Systematic review and meta-analysis synthesis.

Data sources
A search of MEDLINE, EMBASE and Google Scholar was performed to review relevant citations reporting on birth defects in pregnancies exposed to water pollutants between January 1962 and April 2023.

Eligibility criteria
Prospective or retrospective cohort, population studies and case–control studies that provided data on exposure to drinking water pollutants around conception or during pregnancy and non-syndromic birth defects. We included studies published in the English language after the Minamata Bay disaster to reflect on contemporary concerns about the effect of environmental pollution and obstetric outcomes.

Data extraction and synthesis
Two reviewers independently read the retrieved articles for content, data extraction and analysis. The methodological quality of studies was assessed using the Newcastle-Ottawa Scale. Included studies were assessed for comparability when considered for meta-analysis.

Results
32 studies met inclusion criteria including 17 cohorts (6 389 097 participants) and 15 case–control studies (47 914 cases and 685 712 controls). The most common pollutants investigated were trihalomethanes (11 studies), arsenic (5 studies) and nitrates (4 studies). The studies varied in design with different estimates of exposure, different stages of gestation age and different durations of exposure to pollutants. 21 articles reported data on any birth defects in their population or study groups and the others on specific birth defects including congenital heart defects, neural tube defects, orofacial defects and hypospadias. An increased risk or higher incidence of overall birth defects was reported by 9 studies and for specific birth defects by 14 studies. Eight studies compared the risk or incidence of birth defects with exposure to different concentrations of the pollutants. The analysis showed an association between higher levels of trihalomethanes (TTMs) and arsenic increase in major birth defects (lower vs higher exposure (OR 0.76, 95% CI 0.65 to 0.89; p<0.001 and OR 0.56, 95% CI 0.39 to 0.82; p<0.005, respectively).

Conclusion
The evidence of an association between exposure to average levels of common drinking water chemical pollutants during pregnancy and an increased risk or incidence of birth defects is uncertain. Available evidence indicates that some common chemical pollutants currently found in drinking water may have a direct teratogenic effect at high maternal exposure, however, wide variation in methodology limits the interpretation of the results. Future prospective studies using standardised protocols comparing maternal levels during all three trimesters of pregnancy and cord blood levels at birth are needed to better understand the placental transfer of water pollutants and accurately evaluate individual fetal exposure to drinking water pollutants.

PROSPERO registration number
CRD42018112524.