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

TL;DR

Being born large or exposed to maternal diabetes during pregnancy may increase the risk of multiple sclerosis in adulthood, while being born small may lower it.

Contribution

This large-scale study identifies prenatal factors, such as birth weight and maternal diabetes, as potential early contributors to multiple sclerosis risk.

Findings

Being born large for gestational age was associated with a higher risk of adult-onset multiple sclerosis.

Exposure to maternal diabetes during pregnancy was strongly linked to increased multiple sclerosis risk in offspring.

Being born small for gestational age was associated with a reduced risk of multiple sclerosis.

Abstract

Are preterm birth, being small or large for gestational age, maternal hypertensive disorders of pregnancy, placental abruption, or maternal diabetes associated with risk of adult-onset multiple sclerosis (MS) in offspring?

In this cohort study among 1 303 802 participants in Norway, being born large for gestational age and exposure to maternal diabetes were associated with a higher MS risk, while being born small for gestational age was associated with a lower MS risk. Preterm birth, placental abruption, and hypertensive disorders of pregnancy were not associated with MS.

The findings suggest that MS susceptibility may begin as early as in the prenatal period.

This cohort study evaluates associations between various maternal pregnancy outcomes and risk of multiple sclerosis in offspring.

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.

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