US air pollution is associated with increased incidence of non-syndromic cleft lip/palate

Maternal cigarette use is associated with the fetal development of orofacial clefts. Air pollution should be investigated for similar causation. We hypothesize that the incidence of non-syndromic cleft lip with or without palate (NSCLP) and non-syndromic cleft palate (NSCP) would be positively correlated with air pollution concentration.

The incidence of NSCLP and NSCP per 1000 live births from 2016 to 2020 was extracted from the Centers for Disease Control and Prevention Vital Statistics Database and merged with national reports on air pollution using the Environmental Protection Agency Air Quality Systems annual data. The most commonly reported pollutants were analyzed including benzene, sulfur dioxide (SO₂), particulate matter (PM) 2.5, PM 10, ozone (O₃), and carbon monoxide (CO). Multivariable negative binomial and Poisson log-linear regression models evaluated the incidence of NSCLP and NSCP as a function of the pollutants, adjusting for race. All p-values are reported with Bonferroni correction.

The median NSCLP incidence was 0.22/1000 births, and isolated NSCP incidence was 0.18/1000 births. For NSCLP, SO₂ had a coefficient estimate (CE) of 0.60 (95% CI [0.23, 0.98], p < 0.007) and PM 2.5 had a CE of 0.20 (95% CI [0.10, 0.31], p < 0.005). Among isolated NSCP, no pollutants were found to be significantly associated.

SO₂ and PM 2.5 were significantly correlated with increased incidence of NSCLP. The American people and perinatal practitioners should be aware of the connection to allow for risk reduction and in utero screening.