A New Perspective On Isotretinoin In Pregnancy: Pregnancy Outcomes, Evaluation Of Complex Phenotypes, And Importance Of Teratological Counselling

BackgroundTeratogens are responsible for 5% of all known causes of congenital anomalies. Isotretinoin, a retinoic acid-derived agent, leads to congenital anomalies in 21-52% of cases when exposure occurs during pregnancy according to studies conducted before 2006. However, rates of congenital anomalies were much lower in later studies. ObjectivesTo investigate the rates of congenital anomalies in isotretinoin exposure during pregnancy, isotretinoin exposure before pregnancy, and a control group unexposed to any teratogenic agents. MethodsIn this cohort study, we divided pregnant women admitted to our center between 2009 and 2020 into two groups: isotretinoin exposure during the pregnancy (n=77) and isotretinoin exposure before the pregnancy (n=75). We selected the control group from among the non-teratogen exposed pregnant women with a simple random sampling method. Obstetricians calculated the ages of all pregnancies via ultrasound (USG) (crown-rump diameter for the first trimester; biparietal diameter and femur length for the second trimester). After birth, a pediatric genetics specialist examined all babies. ResultsAmong the isotretinoin exposure during the pregnancy, isotretinoin exposure before the pregnancy, and the control groups, there were statistically significant differences in live births (respectively, 64.3%, 88%, 93.3%), congenital anomalies (respectively, 28.6%, 6.1%, 1.4%), miscarriages (respectively, 13%, 2.7%, 4%), terminations (respectively, 32.5%, 9.3%, 2.7%), prematurities (11.9%, 16.7%, 2.9%) (respectively, p < 0.001, p<0.001, p=0.014, p<0.001). We detected novel phenotypical features in five patients. ConclusionsOur study demonstrated that study design, long-term follow-up, teratological counseling, and implementing advanced molecular analysis in complex phenotypes with novel phenotypical features are beneficial for understanding the association of congenital anomalies with isotretinoin exposure. While evaluating congenital anomalies, we detected statistically significant differences between isotretinoin exposure vs control, but we did not detect any statistical differences between isotretinoin exposure before the pregnancy and controls. This conflict between our study and previous studies might be caused by no evident differentiation between isotretinoin exposure before the pregnancy and during the pregnancy and higher termination rates in previous studies.