Neurodevelopmental delays in children born after medically assisted reproduction: a national population cohort study

Importance: The neurodevelopmental outcomes of children born after medically assisted reproduction remain incompletely characterized on a population level. We were to assess the incidence and relative risk of neurodevelopmental delay in the children of infertile women born after unassisted conception, intrauterine insemination (IUI), and in vitro fertilization (IVF).

We conducted a retrospective cohort study using the National Health Insurance Service database of South Korea from October 2017 through December 2023. The study included 115 839 singleton, full-term, non-low-birthweight children born to women aged 20-49 years with a diagnosis of female infertility. The exposure was mode of conception-spontaneous, IUI, or IVF-balanced by propensity score matching on preconceptional maternal factors. Outcome measure was neurodevelopmental delay, defined as scoring below the cutoff in any of six functional domains on the Korean Developmental Screening Test across six consecutive rounds. Crude incidence rate ratios (IRRs) and adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards models.

Among 115 839 children, 6 575 (5.7%) exhibited delay in at least one domain. Crude IRRs for any delay were 1.19 (95% confidence interval [CI]: 1.07, 1.61) for IUI and 1.10 (95% CI: 1.03, 1.17) for IVF versus unassisted conception. In the survival models, higher risks persisted for both IUI (aHR = 1.19; 95% CI: 1.06, 1.34) and IVF (1.09, 95% CI: 1.02, 1.06) compared with unassisted conception. When comparing IVF and IUI, IVF conferred a lower risk of fine motor delay than IUI (0.84, 95% CI: 0.72, 0.99). Among IVF births, risk of developmental delay was similar across all six domains for frozen and fresh embryo transfers.

Children conceived via IUI or IVF demonstrated a modest but significant increase in screen-positive neurodevelopmental delay compared with those conceived spontaneously. These findings highlight the need for neurodevelopmental monitoring in this population.