Long-term neuropsychiatric outcomes in offspring of mothers with multiple sclerosis and neuromyelitis optica spectrum disorder: A nationwide cohort study.

BACKGROUND

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) predominantly affect women of childbearing age, yet the impact of maternal disease status on long-term offspring outcomes remains unclear.

METHODS

Using the Korean National Health Insurance Service database (2005-2019), we conducted a nationwide cohort study. Live-born offspring of mothers diagnosed with MS or NMOSD before childbirth were identified and matched 1:4 to controls using propensity scores. Neuropsychiatric outcomes were defined using ICD-10 codes.

RESULTS

Among 3,524,987 live births, 257 were born to mothers with MS and 26 to mothers with NMOSD. Neither group showed increased risks of major congenital malformations or adverse short-term neonatal outcomes. However, offspring of mothers with MS had an elevated risk of any neuropsychiatric disorder (HR 1.64; 95% CI 1.06-2.54); in exploratory analyses, possible associations were observed with neurotic, stress-related, and somatoform disorders (2.44; 1.16-5.09) and behavioral and emotional disorders (1.91; 1.07-3.40). In offspring of mothers with NMOSD, the HR for any neuropsychiatric disorder was 1.95 (0.63-6.06). In exploratory analyses, possible associations were observed with epileptic and febrile seizures (2.90; 1.04-8.09) and attention-deficit hyperactivity disorder (14.22; 1.53-132.12; 4 and 2 events).

CONCLUSIONS

Maternal MS was associated with a higher long-term risk of neuropsychiatric disorders in offspring, whereas congenital and short-term neonatal outcomes were not increased in either group. In offspring of mothers with NMOSD, the overall risk estimate was also elevated but statistically inconclusive. These findings support long-term monitoring of neuropsychiatric development in these offspring.