Rana Abdullah Alamoudi

Objective The coronavirus (COVID-19) pandemic presents an opportunity to study stress's effect on the development of non-syndromic orofacial clefts (NSOFCs). This study was aimed at assessing maternal stress exposure during the pregestational to first trimester pregnancy periods and the development of NSOFCs during a year of the COVID-19 pandemic. Design Cohort study of infants with NSOFCs and controls matched based on recruitment site and age. Setting Government hospitals in Saudi Arabia between November 2020 and November 2021. Main Outcome Measures Data collection included NSOFC clinical examination and maternal stress exposure assessment using the Modified Life Events Questionnaire, the Fear of COVID-19 Scale, and a focus on the lack of pregnancy planning and a threatened miscarriage. Results Of the 557 infants recruited, 191 had NSOFCs. Logistic regression analysis with adjusted odds ratios (AORs) that removed the effects of confounders showed that any of the seven stressful life events (AOR:3.78, P < .001) and the family histories of relatives with NSOFCs (AOR:9.73, P < .001) increased the AOR for NSOFC development. In contrast, maternal folic acid (AOR:0.56, P.010), threatened miscarriage (AOR:0.17, P = .001), fear of COVID-19 (AOR:0.83, P = .038), and suspected COVID-19 infection (AOR:0.43, P = .008) decreased the AOR for NSOFC development. Conclusion Along with an established risk associated with family history of birth defects, stressful life events may be a risk factor for NSOFC development. Beyond folic acid's known benefit, it may be that higher maternal health concerns contribute to increased protective health behaviors during pregnancy. Ongoing research is needed to specify the maternal risk factors for NSOFC.