LAUSR

BACKGROUND There have been concerns about potential adverse consequences of assisted reproductive technology on the development of children conceived in this way. Despite multiple studies investigating the outcomes of assisted conception, data focusing specifically on the neurodevelopmental outcomes of infants conceived with assisted reproductive technology and born preterm are limited. OBJECTIVE To evaluate and compare the neurodevelopmental outcomes at 18 to 24 months' corrected age of preterm infants born <29 weeks' gestational age who were conceived by assisted reproductive technology and those who were conceived naturally. STUDY DESIGN This retrospective cohort study included inborn, non-anomalous infants, born at <29 weeks' gestation between January 1, 2010 and December 31, 2016, who had a neurodevelopmental assessment at 18 to 24 months' corrected age at any of 10 Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment at 18 to 24 months, defined as the presence of any of the following: cerebral palsy; Bayley-III cognitive, motor, or language composite score of <85; sensorineural or mixed hearing loss; and unilateral or bilateral visual impairment. Secondary outcomes included mortality, composite of mortality or neurodevelopmental impairment, significant neurodevelopmental impairment, and each component of the primary outcome. We compared outcomes between infants conceived by assisted reproductive technology and those conceived naturally, using bivariate and multivariable analyses after adjustment. RESULTS Of the 4863 eligible neonates, 651 (13.4%) were conceived using assisted reproductive technology. Maternal age; education level; and rates of diabetes, receipt of antenatal corticosteroids, and cesarean section were higher in the assisted reproduction group compared to the natural conception group. Neonatal morbidity and death rates were similar except for intraventricular hemorrhage, which was lower in the assisted reproduction group [181/546 (33%) vs 1284/3318(39%)], P = 0.01). Of the 4176 surviving infants, 3386 (81%) had follow up outcome at 18 to 24 months' corrected age. Multivariable logistic regression adjusting for gestational age, antenatal steroids, sex, small for gestational age, multiple gestations, mode of delivery, maternal age, maternal education, pregnancy-induced hypertension, maternal diabetes, and smoking showed that infants conceived through assisted reproduction was associated with lower odds of neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.52-0.86) and the composite of death or neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.54-0.84). Being conceived through assisted reproductive technology was associated with decreased odds of a Bayley-III composite cognitive score <85 (adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.99), and composite language score <85 (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.88). CONCLUSIONS Compared with natural conception, assisted conception was associated with lower odds of adverse neurodevelopmental outcomes, especially cognitive and language outcomes, at 18 to 24 months' corrected age among preterm infants born <29 weeks' gestation. Longer-term follow up studies are required to assess the risks of learning disabilities and development of complex visual-spatial and processing skills in these children as they reach school age.