US Air Pollution is Associated with Increased Incidence of Cleft Lip/Palate – A CDC Vital Statistics Investigation

PURPOSE: Air pollution has negative health effects in the adult population. With rising pollution levels, further investigation is needed to determine the effects of air pollutants on fetal health and birth outcomes. Given that maternal cigarette use increases the risk for non-syndromic orofacial clefts, air pollutants should be investigated for a similar relationship. (1) We hypothesized that incidence of cleft lip with or without palate (CLP) will be positively correlated with levels of air pollution within the US. METHOD: The incidence of non-syndromic CLP per 1000 live births from 2016 to 2020 was extracted from the Centers for Disease Control (CDC) Vital Statistics Wonder Database and merged with national reports on air pollution using the Environmental Protection Agency (EPA) Air Quality Systems (AQS) annual data. Inclusion criteria included patients born with CLP, exclusion criteria included known genetic syndrome and maternal cigarette use. Pollutants analyzed include benzene, sulfur dioxide (SO2), Particulate Matter (PM) 2.5, PM 10, Ozone, and carbon monoxide (CO). Birth records were reported at the county level. Generalized linear models with log link and gamma distribution modeled the incidence of CLP as a function of the 6 pollutant covariates. 95% confidence intervals and p-values were calculated. RESULTS: The median CLP incidence was 0.25/1000 births, interquartile range 0.19, 0.52. PM10 had a coefficient estimate (CE) of 0.06 with 95% CI [0.02, 0.1] and PM2.5 had a CE of 0.23 with 95% CI [0.11, 0.36]. Thus, PM 10 and PM 2.5 were significantly correlated with increased CLP incidence (p-value = 0.0024, p-value = 0.0008, respectively). Other pollutants were not found to be statistically significant and included: benzene with a coefficient estimate (CE) of – 0.001 with 95% CI [-0.002, 0.003], CO CE = 1.06 with 95% CI [-2.81, 4.64], Ozone CE = 15.3 with 95% CI [-40.06, 69.29], and Sulfur CE = -0.001 with 95% CI [-0.65, 0.71]. CONCLUSION: Among the 6 air pollutants assessed PM 10 and PM 2.5 were significantly correlated with increased CLP incidence. Both pollutants are inhaled and deposited in maternal lungs. PM 2.5 has an increased ability to pass from the lungs to the fetus via blood supply due to its smaller size. (2) Both PM 10 and 2.5 are produced by emissions from gasoline use, oil, diesel fuel, and combustion of wood. In addition, PM 10 is generated from construction, landfills and agriculture, wildfires, and industrial pollution. (3) This is the first study to evaluate and establish a correlation between air pollution and non-syndromic CLP on a national scale. With 70-75% of clefts being non-syndromic, this can inform policy change and preventative measures in communities with disproportionally elevated non-syndromic CLP and air pollutant levels. (4,5) Future directions of this study include investigation of the link between area deprivation index and the likelihood for increasing levels for PM 10 and PM 2.5. This will allow an investigation into the inequities in exposure and access to craniofacial care. REFERENCES: 1. Chung KC, Kowalski CP, Kim HM, Buchman SR. Maternal cigarette smoking during pregnancy and the risk of having a child with cleft lip/palate. Plast Reconstr Surg. 2000;105(2):485-491. 2. Zhu N, Ji X, Geng X, Yue H, Li G, Sang N. Maternal PM2.5 exposure and abnormal placental nutrient transport. Ecotoxicology and Environmental Safety. 2021;207:111281. 3. Inhalable Particulate Matter and Health (PM2.5 and PM10). California Air Resources Board https://ww2.arb.ca.gov/resources/inhalable-particulate-matter-and-health#:~:text=5%3F-,PM10%20and%20PM2.,a%20significant%20proportion%20of%20PM10. Accessed2022. 4. Evans K, Hing AV, Cunningham M. Chapter 95 - Craniofacial Malformations. In: Gleason CA, Devaskar SU, eds. Avery’s Diseases of the Newborn (Ninth Edition). Philadelpia: W.B. Saunders; 2012:1331-1350. 5. Khan MI, Cs P, Srinath NM. Genetic Factors in Nonsyndromic Orofacial Clefts. Glob Med Genet. 2020;7(4):101-108.