Paternal Risk Factors for Oral Clefts in Northern Africans, Southeast Asians, and Central Americans.

While several studies have investigated maternal exposures as risk factors for oral clefts, few have examined paternal factors. We conducted an international multi-centered case-control study to better understand paternal risk exposures for oral clefts (cases = 392 and controls = 234). Participants were recruited from local hospitals and oral cleft repair surgical missions in Vietnam, the Philippines, Honduras, and Morocco. Questionnaires were administered to fathers and mothers separately to elicit risk factor and family history data. Associations between paternal exposures and risk of clefts were assessed using logistic regression adjusting for potential confounders. A father's personal/family history of clefts was associated with significantly increased risk (adjusted OR: 4.77; 95% CI: 2.41-9.45). No other significant associations were identified for other suspected risk factors, including education (none/primary school v. university adjusted OR: 1.29; 95% CI: 0.74-2.24), advanced paternal age (5-year adjusted OR: 0.98; 95% CI: 0.84-1.16), or pre-pregnancy tobacco use (adjusted OR: 0.96; 95% CI: 0.67-1.37). Although sample size was limited, significantly decreased risks were observed for fathers with selected occupations. Further research is needed to investigate paternal environmental exposures as cleft risk factors.