| Summary: | Background: Despite being underreported, orofacial cleft lip/palate (CLP) remains in the top five of South Africa’s most common congenital disorders. Maternal air pollution exposure has been associated with CLP in neonates. South Africa has high air pollution levels due to domestic burning practices, coal-fired power plants, mining, industry, and traffic pollution, among other sources. We investigated air pollutant levels in geographic locations of CLP cases. Methods: In a retrospective case series study (2006–2020) from a combined dataset by a Gauteng surgeon and South African Operation Smile, the maternal address at pregnancy was obtained for 2,515 CLP cases. Data from the South African Air Quality Information System was used to calculate annual averages of particulate matter (PM) concentrations of particles < 10 µm (PM10) and < 2.5 µm (PM2.5). Correlation analysis determined the relationship between average PM2.5/PM10 concentrations and CLP birth prevalence. Hotspot analysis was done using the Average Nearest Neighbor tool in ArcGIS. Results: Correlation analysis showed an increasing trend of CLP birth prevalence to PM10 (CC = 0.61, 95% CI = 0.38–0.77, p < 0.001) and PM2.5 (CC = 0.63, 95% CI = 0.42–0.77, p < 0.001). Hot spot analysis revealed that areas with higher concentrations of PM10 and PM2.5 had a higher proclivity for maternal residence (z-score = –68.2, p < 0.001). CLP birth prevalence hotspot clusters were identified in district municipalities in the provinces of Gauteng, Limpopo, North-West, Mpumalanga, and Free State. KwaZulu-Natal and Eastern Cape had lower PM;10 and PM2.5 concentrations and were cold spot clusters. Conclusions: Maternal exposure to air pollution is known to impact the fetal environment and increase CLP risk. We discovered enough evidence of an effect to warrant further investigation. We advocate for a concerted effort by the government, physicians, researchers, non-government organizations working with CLP patients, and others to collect quality data on all maternal information and pollutant levels in all provinces of South Africa. Collaboration and data sharing for additional research will help us better understand the impact of air pollution on CLP in South Africa.
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