Twin pregnancies conceived by assisted reproductive treatments and the risk of long-term offspring pediatric neurological morbidity.

Evidence is conflicting whether twins conceived by assisted reproductive treatment (ART(have higher rate of adverse outcomes than twins conceived spontaneously. Specifically, scarce data exist regarding the long-term neurological implications. Therefore, we studied the association between ART leading to twin pregnancy and short and long- term neurological morbidity of offspring. A retrospective cohort study including twins born between the years 1991-2021 at a tertiary medical center was conducted. Total and subtypes of neurological morbidity among twins born following in vitro fertilization (IVF) versus ovulation induction (OI) and no ART (Spontaneous) were compared. A Kaplan-Meier survival curve was used to compare cumulative neurological morbidity incidence, and a Cox proportional hazards models were constructed to adjust forconfounders. The study population included 7790 twins; 1380 (17.7%) were conceived by IVF, 696 (8.9%) by OI and 5741 (73.7%) were conceived spontaneously. An independent significant association was found between IVF and preterm delivery <37 weeks and cesarean delivery (CD). Higher rates of total neurological morbidity were noted in ART groups (30.1% in IVF, 34.4% in OI and 20.5% in spontaneous group, p < 0.001). Cumulative rates of long-term total neurological morbidity were significantly higher among offspring in ART groups. Using a Cox proportional hazards model, controlling for potential confounders, the association between IVF and the risk for neurological pediatric morbidity remained significant (Adjusted HR = 1.16, 95% CI 1.02-1.33, p = 0.029). However, no independent association was found between OI and neurological morbidity. Twins conceived by IVF are at increased risk for long-term pediatric neurological morbidity.