Mode of conception and future neurologic morbidity of the offspring: a sibling analysis

Abstract Study question To investigate the risk of long-term neurological morbidity among children born following fertility treatments while employing sibling matched analysis to maximize confounder control. Summary answer Fertility treatments appear to be an independent risk factor for long-term neurological morbidity of the offspring up to 18 years of age. What is known already Controversy exists regarding the association between fertility treatments and long-term morbidity of the offspring. Study design, size, duration A retrospective population-based cohort analysis was performed, including all sibling deliveries occurring between 1991 and 2021 at a tertiary medical center. Offspring were followed-up until the age of 18 years. Participants/materials, setting, methods The study population included 10,810 siblings of women who had at least one spontaneous pregnancy and at least one pregnancy following fertility treatments - in vitro fertilization (IVF) and ovulation induction (OI). A Kaplan–Meier survival curve was used to compare the cumulative neurologic morbidity incidence and a multivariable Cox survival hazards regression model was used to control for confounders. Main results and the role of chance There were 5,935 siblings (54.9%) conceived following fertility treatment and 4875 spontaneously conceived siblings (45.1%). Gestational diabetes mellitus and hypertensive disorders were more common in the fertility treatment group (9.9% vs. 5%, and 7.7% vs. 4.7%, respectively, p < 0.001). Likewise, the rates of Cesarean delivery (33.6% vs. 2.3%, p < 0.001), preterm delivery (11.9% vs 7.6%, p < 0.001) and low birth weight (12.1% vs.7.2%, p < 0.001) were higher in the fertility treatments group, as compared with the spontaneous pregnancy group. Neurological morbidity was significantly higher among siblings born following fertility treatments as compared with those conceived spontaneously (10.2% vs. 8.2%; p < 0.001). In particular, psychiatric emotional disorders were more common in the fertility treatment group (4.4% vs. 3.3% p = 0.002). Using a Kaplan-Meier survival curve, siblings conceived following fertility treatments had higher cumulative incidence rates of neurological morbidity (Log-Rank, p = 0.012). After controlling for confounders, such as maternal age, diabetes mellitus, preterm delivery and hypertensive disorders, using a Cox regression model, being born following fertility treatments was associated with long term neurological morbidity (adjusted HR = 1.2, 95% CI 1.02-1.32, p = 0.027). Limitations, reasons for caution This retrospective cohort study can only provide evidence of association but not causation. Also, our study results are hospital-based diagnoses which most likely represent acute and severe disease. Wider implications of the findings In this large retrospective cohort study of siblings, a significant and independent association was found between fertility treatments and long-term neurological morbidities. Trial registration number N/A