MS Vulnerability May Begin In Utero: Prenatal and Perinatal Factors Influence Multiple Sclerosis Risk, Says JAMA Study
USA: Researchers have found in a Norwegian cohort study that prenatal and perinatal factors influence the risk of developing multiple sclerosis (MS) later in life. Exposure to maternal diabetes during pregnancy or being born large for gestational age increased MS risk, while being born small for gestational age was associated with a lower risk. These findings suggest that MS vulnerability may begin in utero.
In a large population-based study published in JAMA Neurology, Katrin Wolfova from the Department of Neurology, Columbia University, Presbyterian Hospital, New York, and colleagues examined whether adverse pregnancy outcomes are linked to the long-term risk of adult-onset MS in offspring. Drawing on data from national health registers in Norway, the researchers evaluated more than 1.3 million individuals born between 1967 and 1989, making this one of the most comprehensive investigations into early-life influences on MS risk to date.
The study used a closed cohort design with follow-up from January 2009 to December 2019. Participants were aged 18 years or older and MS-free in the year before follow-up. MS cases were identified through the Norwegian National Patient Register, while pregnancy and birth data came from the Medical Birth Registry of Norway. Cox proportional hazards models were applied to examine links between prenatal and perinatal factors and later MS risk.
Key exposures included preterm birth, small or large for gestational age, hypertensive disorders of pregnancy, placental abruption, and maternal diabetes, which covered pregestational and gestational diabetes as well as antidiabetic medication use during pregnancy.
Key Findings:
- The analysis included 1,166,731 eligible individuals, with males accounting for just over half of the study population.
- During the follow-up period, 4,295 participants were diagnosed with multiple sclerosis.
- After adjustment for potential confounders, being born large for gestational age was associated with a modestly higher risk of developing MS in adulthood.
- Being born small for gestational age was linked to a lower risk of adult-onset MS.
- Exposure to maternal diabetes during pregnancy showed the strongest association, with offspring having more than a twofold increased risk of MS later in life.
- Preterm birth was not associated with an increased or decreased risk of developing MS.
- Placental abruption did not show a significant association with adult-onset MS.
- Hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension, were not linked to MS risk in offspring.
The authors note that while high body mass index and diabetes during childhood or adulthood are already recognized risk factors for MS, their findings extend the timeline of susceptibility much earlier. Early metabolic exposures during fetal development may affect immune system programming, inflammatory pathways, and long-term growth patterns, potentially shaping vulnerability to autoimmune diseases such as MS.
The researchers emphasize the need for future epidemiological studies to focus on markers of neonatal growth and adiposity. A better understanding of how metabolic and growth-related factors in early life interact with immune development could offer new insights into MS prevention and risk stratification, highlighting pregnancy as a critical window for long-term neurological health.
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
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