Increased risk of orofacial clefts associated with maternal obesity: case-control study and Monte Carlo-based bias analysis.

Our objective was to evaluate whether infants born to obese or diabetic women are at higher risk of non-syndromic orofacial clefting. We conducted a population-based case-control study using Washington State birth certificate and hospitalisation data for the years 1987-2005. Cases were infants born with orofacial clefts (n = 2153) and controls infants without orofacial clefts (n = 18 070). The primary exposures were maternal obesity (body mass index > or =30) and diabetes (either pre-existing or gestational). We estimated adjusted odds ratios (ORs) to compare, for mothers of cases and controls, the proportions of obese vs. normal-weight women and diabetic vs. non-diabetic women. We additionally performed Monte Carlo-based simulation analysis to explore possible influences of biases. Obese women had a small increased risk of isolated orofacial clefts in their offspring compared with normal-body mass index women [adjusted OR 1.26; 95% confidence interval 1.03, 1.55]. Results were similar regardless of type of cleft. Bias analyses suggest that estimates may represent underlying ORs of stronger magnitude. Results for diabetic women were highly imprecise and inconsistent. We and others have observed weak associations of similar magnitude between maternal obesity and risk of non-syndromic orofacial clefts. These results could be due to bias or residual confounding. However, it is also possible that these results represent a stronger underlying association. More precise exposure measurement could help distinguish between these two possibilities.