Maternal Pregnancy Outcomes and Offspring Risk of Adult-Onset Multiple Sclerosis

Although concordance rates for multiple sclerosis (MS) are higher among dizygotic twins than among nontwin siblings-suggesting a potential influence of prenatal and perinatal factors-few large-scale studies have systematically investigated the role of maternal adverse pregnancy outcomes in risk of MS in offspring.

To explore whether preterm birth, being born small or large for gestational age (SGA and LGA, respectively), maternal hypertensive disorders of pregnancy (HDP), placental abruption, and maternal diabetes are associated with the risk of adult-onset MS in offspring.

A closed cohort study with a follow-up beginning in January 2009 and continuing until the first event, death, emigration, or end of follow-up (December 2019). Data were derived from Norwegian national registers. All live births (N = 1 303 802) in the Medical Birth Registry of Norway from 1967 to 1989 were identified. MS cases were identified through the National Patient Register. Cox models were used to estimate the association between adverse pregnancy outcomes and MS among participants aged 18 years and older at the beginning of the follow-up and MS-free during the previous year. Data were analyzed from February to October 2025.

Primary exposures included preterm birth (before gestational age of 37 completed weeks), SGA (birth weight <10th percentile), LGA (birth weight >90th percentile), HDP (preeclampsia, eclampsia, gestational hypertension, and chronic hypertension), placental abruption, and maternal diabetes (type 2, unspecified pregestational diabetes, gestational diabetes, and use of antidiabetic medication during pregnancy).

MS diagnosis defined by International Classification of Diseases and Related Health Problems, Tenth Revision, code G35.

Among 1 166 731 infants (597 330 [51.2%] male), 4295 MS cases were identified in 2009 and onwards. Adjusting for confounders, the hazard ratio [HR] for LGA was 1.13 (95% CI, 1.03-1.25), while the HR for SGA was 0.88 (95% CI, 0.78-0.98). The HR for maternal diabetes was 2.15 (95% CI, 1.37-3.37). Preterm birth, placental abruption, and HDP were not associated with MS.

In this cohort study, being born LGA and being exposed to maternal diabetes were associated with a higher risk of adult-onset MS, whereas begin born SGA was associated with a lower risk. While high childhood body mass index and diabetes are known MS risk factors, these findings suggest susceptibility may begin as early as the prenatal period.