Prenatal metabolic factors may influence long-term susceptibility to multiple sclerosis (MS), according to a nationwide cohort study published in JAMA Neurology. Using more than 1 million births from Norwegian national registries, investigators found that individuals born large for gestational age or exposed to maternal diabetes in utero had a significantly higher risk of developing adult-onset MS decades later.
“Adverse pregnancy outcomes—encompassing preterm birth, restrictive or excessive fetal growth, hypertensive disorders of pregnancy, placental abruption, and gestational diabetes—have been associated with altered immune development and may influence long-term MS risk in the offspring,” explained the study authors.
The investigators aimed to determine whether adverse pregnancy and perinatal factors, including fetal growth (born small or large for gestational age), maternal diabetes, hypertensive disorders of pregnancy, preterm birth, and placental abruption, are associated with the risk of developing adult-onset MS.
To do so, they conducted a population-based closed cohort study using linked Norwegian national registries that included all live births from 1967 to 1989. Follow-up began in January 2009 and continued through December 2019, death, or emigration. Researchers followed participants from adulthood for incident MS identified through national patient records, and associations between predefined prenatal exposures. The study team assessed MS risk using adjusted Cox proportional hazards models.
Among 1,166,731 individuals included in the analysis, the investigators identified 4,295 cases of MS during follow-up. After adjusting for potential confounding factors, being born large for gestational age was associated with a modestly increased risk of adult-onset MS (HR, 1.13; 95% CI, 1.03–1.25), whereas being born small for gestational age was associated with a lower risk (HR, 0.88; 95% CI, 0.78–0.98). Maternal diabetes was associated with more than a twofold increase in MS risk in offspring (HR, 2.15; 95% CI, 1.37–3.37).
In contrast, the team observed no significant associations between MS risk and preterm birth, placental abruption, or maternal hypertensive disorders of pregnancy.
“While it is well established that children with high BMI and diabetes are more likely to develop MS in adulthood, our findings suggest that the roots may lie in the perinatal period,” the investigators concluded. “Early metabolic exposures may influence immune system programming and future growth trajectories. Future epidemiologic studies should examine markers of neonatal adiposity and growth to better understand how early-life factors shape MS risk.”
date:2026-02-12 20:15:00