Population Attributable Fractions of Modifiable Risk Factors for Nonsyndromic Orofacial Clefts: A Prospective Cohort Study From the Japan Environment and Children's Study

Background: Population impact of modifiable risk factors on orofacial clefts is still unknown. This study aimed to estimate population attributable fractions (PAFs) of modifiable risk factors for nonsyndromic cleft lip with or without cleft palate (CL +/- P) and cleft palate only (CP) in Japan. Methods: We conducted a prospective cohort study using data from the Japan Environment and Children's Study, which recruited pregnant women from 2011 to 2014. We estimated the PAFs of maternal alcohol consumption, psychological distress, maternal active and passive smoking, abnormal body mass index (BMI) (<18.5 and >= 25 kg/m(2)), and non-use of a folic acid supplement during pregnancy for nonsyndromic CL +/- P and CP in babies. Results: A total of 94,174 pairs of pregnant women and their single babies were included. Among them, there were 146 nonsyndromic CL +/- P cases and 41 nonsyndromic CP cases. The combined adjusted PAF for CL +/- P of the modifiable risk factors excluding maternal alcohol consumption was 34.3%. Only maternal alcohol consumption was not associated with CL +/- P risk. The adjusted PAFs for CL +/- P of psychological distress, maternal active and passive smoking, abnormal BMI, and non-use of a folic acid supplement were 1.4% (95% confidence interval [CI], -10.7 to 15.1%), 9.9% (95% CI, -7.0 to 26.9%), 10.8% (95% CI, -9.9 to 30.3%), 2.4% (95% CI, -7.5 to 14.0%), and 15.1% (95% CI, -17.8 to 41.0%), respectively. We could not obtain PAFs for CP due to the small sample size. Conclusions: We reported the population impact of the modifiable risk factors on CL +/- P, but not CP. This study might be useful in planning the primary prevention of CL +/- P.