Maternal periconceptional exposure to cigarette smoking and alcohol consumption and congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) is a major birth defect that occurs when abdominal organs herniate through a diaphragmatic opening into the thoracic cavity and is associated with high mortality (>50%). The etiology of CDH is not well understood.

Using data from the National Birth Defects Prevention Study, we examined associations between CDH and maternal periconceptional exposure (1 month before through the third month of pregnancy) to cigarette smoking and alcohol. Interview reports of exposures were provided by mothers of CDH (n = 503) and unaffected control (n = 6703) infants delivered from October 1997 through December 2005. Any exposure (yes/no), as well as quantity (average number of cigarettes or drinks), type (active/passive smoking; beer, wine, distilled spirits), and duration (e.g., number of months exposed) were examined. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated for all CDH cases combined, selected subtypes (Bochdalek, Morgagni, not otherwise specified), and phenotypes (infants with/without additional major birth defects).

The aOR for any smoking was nonsignificantly elevated for all CDH cases combined. Odds of any smoking was significant for isolated Bochdalek CDH (aOR, 1.9; 95% CI, 1.2-3.0). The aORs associated with all measures of alcohol consumption were near unity for each CDH category examined. Stratification of smoking exposure by alcohol consumption and stratification of alcohol consumption by smoking exposure did not appreciably change the aORs.

These findings identified periconceptional smoking exposure as a potential risk factor for CDH. Future studies need to confirm our findings and explore possible pathways accounting for the teratogenic effect of smoking.