Purpose To compare the risk of neurodevelopmental disorders in children conceived via intracytoplasmic sperm injection (ICSI) and those conceived naturally. Materials and methods A population-based cohort study using data retrieved from the Taipei Medical University Research Database (TMURD) from January, 2004 to August, 2016. The data included maternal pregnancy history, perinatal history and developmental follow up of their babies up to 5 years of age. The study included 23885 children, of whom 23148 were naturally conceived and 737 were conceived via ICSI. Neurodevelopmental disorders defined by 21 ICD-9-CM codes. Results Of the 23885 children enrolled for analysis, 2778 children were included for further sub-grouping analysis after propensity matching to reduce bias from maternal factors. The single-birth group included 1752 naturally conceived (NC) children and 438 ICSI children. The multiple-birth group included 294 NC and 294 ICSI children. The risk of neurodevelopmental disorders was not increased for ICSI children in both groups (single birth: adjusted hazard ratio aHR = 0.70, 95% CI = 0.39–1.27, p = 0.243; multiple-birth group aHR = 0.77, 95% CI = 0.43–1.35, p = 0.853). In the single-birth group, multivariate analyses showed that male sex (aHR = 1.81, 95% CI = 1.29–2.54, p < 0.001), and intensive care unit (ICU) admission (aHR = 3.10, 95% CI = 1.64–5.86, p < 0.001) were risk factors for neurodevelopmental disorders. In the multiple-birth group, multivariate analyses demonstrated that ICU admission (aHR = 3.58, 95% CI = 1.82–7.04, p < 0.001), was risk factor for neurodevelopmental disorders. Conclusion Our study indicated that the use of ICSI does not associated with higher risk of neurodevelopmental disorders in the offspring. But male sex, and ICU admission do have increased risk of neurodevelopmental disorders. However, long term follow up of this cohort on health outcomes in adolescence and adulthood will strengthen the conclusions that ICSI is safe regarding offspring long term outcome.
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