Ambient Ozone and Cadmium as Risk Factors For Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) results from a defect in the diaphragm through which abdominal contents enter the thorax displacing the heart and the lungs. This causes lung hypoplasia and varying degrees of pulmonary hypertension resulting in high rates of morbidity and mortality. Though CDH has a prevalence rate of 2.61 per 10,000 live births it is an expensive birth defect with an estimated annual cost of nearly $250 million for all CDH survivors. Maternal exposure to air pollutants have not been studied as risk factors for CDH in humans. Ambient ozone has been found to be risk factors for certain birth defects including congenital heart defects, chromosomal anomalies, and limb reduction defects. Cadmium, however, has been found to be a risk factor for diaphragmatic hernia, cleft palate, renal defects, anopthalmia, microphthalmia, anal atresia, undescended testes, and dysplastic ears in animal studies only. The objectives of this study were to: 1) examine the prevalence, temporal trends, and correlates of CDH among live-born infants during 1998–2012; 2) investigate the association between sociodemographic and perinatal characteristics and neonatal and one-year survival among infants with CDH and its subtypes, isolated and complex; 3) examine the role of ambient ozone as a risk factor for CDH; and 4) determine the association between maternal exposure to ambient cadmium in air and CDH and assess if maternal smoking during pregnancy is an effect modifier of the cadmium-CDH association. To answer these questions we used a population-based, retrospective cohort study using data from the 1998–2012 Florida Birth Defects Registry. We classified CDH cases into isolated and complex. A case that was associated with other anomalies listed on the National Birth Defects Prevention Network list of major structural reportable defects was classified as complex CDH. We used Poisson and joinpoint regression models to compute prevalence ratios and assess temporal trends, respectively. Kaplan-Meier survival curves and Cox proportional hazards regression were used to describe neonatal and one-year survival and estimate hazard ratios of neonatal and one-year mortality. We then used multilevel Poisson regression models to examine the association between maternal exposure to ambient ozone and CDH as well as cadmium and CDH. We conducted stratified analyses to test for effect measure modification by maternal smoking status. The study population to answer the first two questions consisted of 3,209,775 live-born infants (including 1,025 cases). To answer the third and fourth questions, the study population consisted of 3,039,685 and 2,591,395 live-born infants (including 981 and 840 cases), respectively. We found a 4% increase in the annual prevalence of CDH among complex cases, but no trend for isolated cases. We observed higher prevalence of CDH among infants born to mothers with high school or less maternal education and for multiple births. Female sex and maternal obesity were found to be associated with decreased risk for CDH. The most important predictor of neonatal and one-year mortality was gestational ag