Prenatal factors and offspring risk of adult multiple sclerosis

A large population-based cohort study suggests that susceptibility to multiple sclerosis (MS) may begin as early as the prenatal period, with certain adverse pregnancy-related factors linked to MS risk in adulthood. The findings come from an analysis of more than 1.3 million individuals born in Norway and followed into adulthood, recently published in JAMA.

Examining pregnancy outcomes and MS risk

Although MS concordance rates are higher among dizygotic twins than among non-twin siblings—hinting at a role for prenatal or perinatal factors—few large-scale studies have systematically evaluated how maternal pregnancy outcomes may influence MS risk later in life. To address this gap, researchers examined whether several adverse pregnancy outcomes were associated with adult-onset MS in offspring.

The study included 1,303,802 live births recorded in the Medical Birth Registry of Norway between 1967 and 1989. MS cases were identified through the National Patient Register, with follow-up beginning in January 2009 and continuing through December 2019.

Study design and exposures

Using Cox proportional hazards models, investigators assessed associations between MS and the following prenatal and perinatal exposures:

• Preterm birth (before 37 completed weeks)
• Being born small for gestational age (SGA; birth weight <10th percentile)
• Being born large for gestational age (LGA; birth weight >90th percentile)
• Maternal hypertensive disorders of pregnancy (including preeclampsia, eclampsia, gestational hypertension, and chronic hypertension)
• Placental abruption
• Maternal diabetes (type 2, unspecified pregestational diabetes, gestational diabetes, or use of antidiabetic medication during pregnancy)

Participants were required to be aged 18 years or older at the start of follow-up and free of MS during the year prior to follow-up.

Key findings from more than one million births

Among 1,166,731 infants, including 597,330 (51.2%) male participants, researchers identified 4295 MS cases from 2009 onward. After adjusting for confounders, several prenatal factors showed statistically significant associations with MS risk, including:

• Being born large for gestational age:
  • Hazard ratio (HR), 1.13
  • 95% CI, 1.03–1.25
• Being born small for gestational age:
  • HR, 0.88
  • 95% CI, 0.78–0.98
• Exposure to maternal diabetes:
  • HR, 2.15
  • 95% CI, 1.37–3.37

In contrast, preterm birth, placental abruption, and maternal hypertensive disorders of pregnancy were not associated with MS risk.

Implications for understanding MS origins

The findings suggest that biological processes influencing MS susceptibility may begin well before birth. While high childhood body mass index and diabetes are already recognized MS risk factors, the observed associations with LGA birth and maternal diabetes indicate that early-life metabolic environments may play a role in shaping long-term neurologic risk.

Reference:

Wolfova K, Engdahl BL, Horn J, et al. Maternal Pregnancy Outcomes and Offspring Risk of Adult-Onset Multiple Sclerosis. JAMA Neurol. Published online January 12, 2026. doi:10.1001/jamaneurol.2025.5255