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. 2026 Feb 1;83(2):153-160.
doi: 10.1001/jamaneurol.2025.5255.

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

Katrin Wolfova  1   2 , Bo Lars Engdahl  3 , Julie Horn  4   5 , Claire S Riley  1 , Natalie A Bello  6   7 , Eliza C Miller  8 , Sarah E Tom  1   9
Affiliations

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

Katrin Wolfova et al. JAMA Neurol. .

Abstract

Importance: 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.

Objective: 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.

Design, setting, and participants: 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.

Exposures: 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).

Main outcomes and measures: MS diagnosis defined by International Classification of Diseases and Related Health Problems, Tenth Revision, code G35.

Results: 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.

Conclusions and relevance: 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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Wolfova reported travel scholarships from the Czech Alzheimer’s Foundation, the Americas Committee for Treatment and Research in Multiple Sclerosis, and the European Committee for Treatment and Research in Multiple Sclerosis outside the submitted work. Dr Horn reported speaker fees from Boehringer Ingelheim outside the submitted work. Dr Riley reported personal fees from TG Therapeutics, EMD Serono, Viracta, Novartis, Amgen, Roche, Genentech, Cabaletta Bio, Immunic AG, Bristol Myers Squibb, EMD Serono, Alumis, PTC Bio, and AstraZeneca outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Associations Between Maternal Adverse Pregnancy Outcomes and the Risk of Multiple Sclerosis in the Offspring Accounting for Mortality (N = 1 166 731)
Models were adjusted for sex, birth cohort (1967-1977 vs 1978-1989), mother’s age at the time of delivery, previous children, birth plurality, maternal education, and maternal country of origin. AGA indicates appropriate for gestational age; HDP, hypertensive disorders of pregnancy; HR, hazard ratio; IPW, inverse-probability weighted; LGA, large for gestational age; SGA, small for gestational age.
See this image and copyright information in PMC

References

    1. Jacobs BM, Noyce AJ, Bestwick J, Belete D, Giovannoni G, Dobson R. Gene-environment interactions in multiple sclerosis: a UK Biobank study. Neurol Neuroimmunol Neuroinflamm. 2021;8(4):e1007. doi: 10.1212/NXI.0000000000001007 - DOI - PMC - PubMed
    1. Kuusisto H, Kaprio J, Kinnunen E, Luukkaala T, Koskenvuo M, Elovaara I. Concordance and heritability of multiple sclerosis in Finland: study on a nationwide series of twins. Eur J Neurol. 2008;15(10):1106-1110. doi: 10.1111/j.1468-1331.2008.02262.x - DOI - PubMed
    1. Willer CJ, Dyment DA, Risch NJ, Sadovnick AD, Ebers GC; Canadian Collaborative Study Group . Twin concordance and sibling recurrence rates in multiple sclerosis. Proc Natl Acad Sci U S A. 2003;100(22):12877-12882. doi: 10.1073/pnas.1932604100 - DOI - PMC - PubMed
    1. Shah TJ, Walsh SW. Activation of NF-kappaB and expression of COX-2 in association with neutrophil infiltration in systemic vascular tissue of women with preeclampsia. Am J Obstet Gynecol. 2007;196(1):48.e1-48.e8. doi: 10.1016/j.ajog.2006.08.038 - DOI - PubMed
    1. Ragsdale HB, Kuzawa CW, Borja JB, Avila JL, McDade TW. Regulation of inflammation during gestation and birth outcomes: inflammatory cytokine balance predicts birth weight and length. Am J Hum Biol. 2019;31(3):e23245. doi: 10.1002/ajhb.23245 - DOI - PMC - PubMed