Adverse pregnancy outcomes linked to adult-onset MS risk

medwireNews: Being born large for gestational age (LGA) and being exposed to maternal diabetes significantly increase the risk for adult-onset multiple sclerosis (MS), suggests a study in JAMA Neurology.

The researchers analyzed data from Norwegian population registries on 1,166,731 individuals (51.2% male) born between 1967 and 1989, of whom 4295 developed MS as adults between 2009 and 2019. The median age of MS diagnosis was 37 years.

The link between future MS and six adverse pregnancy outcomes was studied – preterm birth (before 37 weeks of gestation), being born small for gestational age (SGA; birthweight <10th percentile based on national data), LGA (birthweight >90th percentile), maternal hypertensive disorders of pregnancy (HDP), placental abruption, and maternal diabetes.

Maternal diabetes doubles the risk for future MS development in offspring

Maternal diabetes was found to significantly increase the risk for later MS with a hazard ratio (HR) of 2.15, compared with no maternal diabetes exposure, after adjustment for confounders such as sex, maternal age at time of delivery, and birth plurality. Of 2662 infants exposed to maternal diabetes, 19 (0.7%) developed later MS, compared with 4293 (0.4%) of 1,165,552 who were not.

The category of maternal diabetes in the study included women with type 2 diabetes, gestational diabetes, and those who used any antidiabetic medication during pregnancy, but excluded women with type 1 diabetes “due to its potential genetic association with MS,” explain Sarah Tom (Columbia University, New York, USA) and colleagues.

Further analysis showed that maternal gestational diabetes alone was not significantly linked to future risk for MS in the offspring, but this was “potentially due to a small sample of only 5 MS cases in this group,” suggest Tom et al.

Birthweight influences later risk for MS

Being LGA at birth increased the risk for adult-onset MS with a significant HR of 1.13 after adjustment for confounders, compared with being born an appropriate weight for age (AGA), with MS developing in 474 (0.4%) of 114,025 participants who were born LGA and 3469 (0.4%) of 939,324 who were born AGA.

Conversely, being born SGA was associated with a significantly lower risk for adult-onset MS, with an adjusted HR of 0.88 compared with being born AGA. In all, 369 (0.3%) out of 114,865 individuals born SGA developed MS.

Neither preterm birth, placental abruption, nor HDP (including preeclampsia, eclampsia, gestational hypertension, and chronic hypertension) were associated with the later development of MS.

“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 prenatal period,” the study authors say. “Early metabolic exposures may influence immune system programming and future growth trajectories.”

The team concludes: “Future epidemiologic studies should examine markers of neonatal adiposity and growth to better understand how early-life factors shape MS risk.”

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JAMA Neurol 2026; doi:10.1001/jamaneurol.2025.5255