Facial Dysmorphism in Infants Following Combined Prenatal Exposure to Alcohol and Tobacco

OBJECTIVES Alcohol and smoking have well-established teratogenic effects; however, despite their frequent co-use during pregnancy, the combined impact on fetal development remains less understood. Facial dysmorphism is a sensitive marker of embryonic disruption. This study investigated whether concomitant prenatal exposure to alcohol and tobacco exerts synergistic effects on infant facial dysmorphism, facial size, and growth trajectories. METHODS This longitudinal study included 634 infants from a high-risk population in South Africa. Prenatal alcohol and smoking behaviors were assessed using a modified timeline follow-back interview at each visit, capturing frequency and quantity. Three-dimensional facial images were obtained at 1 month and 1 year postnatally. Infants were categorized into 5 exposure groups: control, continuous alcohol only, continuous smoking only, continuous coexposure, and continuous smoking with any alcohol. Group differences were evaluated using anthropometric measurements and dense surface modeling to assess facial dysmorphism, size, and growth trajectories. RESULTS Continuous prenatal coexposure to smoking and alcohol was associated with the greatest facial dysmorphism and reduced facial size compared to controls and single-exposure groups. Effects were largely sex specific, with stronger alterations in girls. Coexposure was also associated with ocular changes, including reduced palpebral fissure length and increased canthal index. Single exposures showed more limited effects, and facial growth trajectories were not significantly influenced by exposure. CONCLUSIONS Combined prenatal exposure to alcohol and tobacco is associated with greater facial dysmorphism than single exposures. These findings highlight the importance of interventions targeting alcohol and smoking cessation during pregnancy to reduce teratogenic risk.