Maternal exposure to volatile organic compounds and the risk of congenital anomalies: A systematic review and meta-analysis

Volatile organic compounds (VOCs) are widespread environmental and occupational pollutants with potential teratogenic effects. Growing evidence indicates that maternal exposure to VOCs during pregnancy may increase the risk of congenital anomalies in offspring. This systematic review aims to evaluate and synthesize the association between maternal exposure to benzene, toluene, xylene, and formaldehyde during pregnancy and the occurrence of congenital anomalies, including neural tube defects (NTDs), congenital heart defects (CHDs), and cleft lip and/or palate (CL/P). A systematic search was conducted across six electronic databases and grey literature for studies published between January 1, 2002, and January 1, 2025. We used a random-effects models to assess the associations. Sensitivity and publication bias analyses were also conducted. Nineteen studies met the inclusion criteria. Meta-analysis revealed a significant association between prenatal VOCs exposure and increased risk of NTDs (pooled OR = 1.63, 95 % CI: 1.32-1.95) and CHDs (pooled OR = 1.33, 95 % CI: 1.09-1.56). Studies using objective exposure assessment methods such as biomonitoring, residential GIS modelling, and environmental air measurements reported more consistent and robust associations. Maternal exposure to VOCs during pregnancy is associated with an increased risk of NTDs and CHDs. These findings highlight the importance of environmental health interventions, regulatory oversight, and prenatal risk mitigation strategies. Further prospective studies using standardized exposure assessments are needed to strengthen causal inference.