Proportion of orofacial clefts attributable to recognized risk factors
Objectives: Estimate the population attributable fraction (PAF) for a set of recognized non-genetic risk factors for orofacial clefts.^ Methods: We used data on cases with cleft lip with or without cleft palate (CL±P) and cleft palate only (CP) from the National Birth Defects Prevention Study. For recognized risk factors for which data were available through existing literature, we estimated crude population attributable fractions (cPAFs) and average adjusted population attributable fractions (aaPAFs), which account for potential confounding. We assessed eleven modifiable parental/maternal risk factors: education, age, obesity, pre-gestational diabetes, gestational diabetes, previous pregnancies, dietary folate, folic acid supplementation, smoking, alcohol use, and fever. We also assessed non-modifiable factors (race/ethnicity, infant sex, family history of orofacial clefts), because non-modifiable factors may serve as markers for modifiable factors (e.g., diet) or genetic 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.^ Results: The proportion of CL±P and CP cases attributable to the set of recognized risk factors was 49% and 43%, respectively. The modifiable factor with the largest aaPAF was smoking during the month before pregnancy or the first month of pregnancy (4.4% for CL±P and 3.4% for CP). Among non-modifiable factors, the factor with the largest aaPAF for CL±P was male sex (27%), whereas it was female sex for CP (16%). ^ Discussion: For most of the individual risk factors, the cPAF was higher than the aaPAF, which may indicate the crude estimates were potentially inflated. Our results suggest a substantial proportion of orofacial risk is due to recognized, non-genetic risk factors. However, slightly more than half of the risk for orofacial cleft could not be accounted for in this study, which highlights the need to identify novel risk factors.^ Conclusions: Our results can inform research and prevention efforts (e.g., focusing on the modifiable factors responsible for the largest proportion of risk). Since a large proportion of cleft risk is attributable to non-modifiable factors, it is also important to better understand the mechanisms involved for these factors.^
Raut, Janhavi, "Proportion of orofacial clefts attributable to recognized risk factors" (2016). Texas Medical Center Dissertations (via ProQuest). AAI10182176.