Proportion of Orofacial Clefts Attributable to Recognized Risk Factors

Abstract

Objective: Estimate the population attributable fraction (PAF) for a set of recognized risk factors for orofacial clefts. Design: We used data from the National Birth Defects Prevention Study. For recognized risk factors for which data were available, we estimated crude population attributable fractions (cPAFs) to account for potential confounding, average-adjusted population attributable fractions (aaPAFs). We assessed 11 modifiable and 3 nonmodifiable parental/maternal risk factors. The aaPAF for individual risk factors and the total aaPAF for the set of risk factors were calculated using a method described by Eide and Geffler. Setting: Population-based case–control study in 10 US states. Participants: Two thousand seven hundred seventy-nine cases with isolated cleft lip with or without cleft palate (CL±P), 1310 cases with isolated cleft palate (CP), and 11 692 controls with estimated dates of delivery between October 1, 1997, and December 31, 2011. Main Outcome Measures: Crude population attributable fraction and aaPAF. Results: The proportion of CL±P and CP cases attributable to the full set of examined risk factors was 50% and 43%, respectively. The modifiable factor with the largest aaPAF was smoking during the month before pregnancy or the first month of pregnancy (4.0% for CL±P and 3.4% for CP). Among nonmodifiable factors, the factor with the largest aaPAF for CL±P was male sex (27%) and for CP it was female sex (16%). Conclusions: Our results may inform research and prevention efforts. A large proportion of orofacial cleft risk is attributable to nonmodifiable factors; it is important to better understand the mechanisms involved for these factors.