Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system that often affects women of reproductive age. The impact of MS on obstetric and neonatal outcomes remains unclear, particularly in women of advanced maternal age.
Objectives:
We aimed to evaluate obstetric and neonatal outcomes in women with MS using data extracted from the National Health Screening Examination (NHSE) and the National Health Screening Program for Infants and Children (NHSPIC) in Korea.
Methods:
Women with singleton live births between 2011 and 2020 who underwent the NHSE within 4 years before pregnancy were identified. Women with MS (n = 481) were matched 1:10 to women without MS (n = 4810) based on age and comorbidity indices. Outcomes were compared using multivariate logistic regression considering maternal age.
Results:
Women with MS had a higher risk of preterm birth (odds ratio [OR] = 2.50; 95% confidence interval [CI] = 1.38–4.52) and placenta previa (OR = 1.83; 95% CI = 1.05–3.20) compared with controls. The association between MS and preterm birth was particularly pronounced in women of advanced age. Other obstetric outcomes did not differ significantly according to MS status, and neonatal outcomes were similar between the two groups.
Conclusions:
Most obstetric and neonatal outcomes were comparable between women with and without MS. However, for pregnant women with MS, age ⩾ 35 years was associated with an increased risk of preterm birth, highlighting the importance of careful prenatal monitoring in this population. Further studies are warranted to elucidate the mechanisms underlying this risk.
HakiMAl-BiatiHAAl-TameemiZS, et al. Review of multiple sclerosis: Epidemiology, etiology, pathophysiology, and treatment. Medicine2024; 103: e37297.
2.
SiriratnamPHudaSButzkuevenH, et al. Risks and outcomes of pregnancy in neuromyelitis optica spectrum disorder: A comprehensive review. Autoimmun Rev2024; 23(2): 103499.
3.
KryskoKMDobsonRAlroughaniR, et al. Family planning considerations in people with multiple sclerosis. Lancet Neurol2023; 22(4): 350–366.
4.
AndersenJBKoppTISellebjergF, et al. Pregnancy-related and perinatal outcomes in women with multiple sclerosis: A nationwide Danish cross-sectional study. Neurol Clin Pract2021; 11(4): 280–290.
5.
van der KopMLPearceMSDahlgrenL, et al. Neonatal and delivery outcomes in women with multiple sclerosis. Ann Neurol2011; 70(1): 41–50.
6.
AndersenMLJølvingLRIachinaM, et al. Neonatal outcomes in women with multiple sclerosis—influence of disease activity: A Danish nationwide cohort study. Mult Scler Relat Disord2024; 85: 105549.
7.
RahmatiSGalaviZKavyaniB, et al. Maternal and neonatal outcomes in pregnant women with multiple sclerosis disease: A systematic review and meta-analysis. Midwifery2024; 134: 104004.
8.
RamagopalanSVValdarWDymentDA, et al. No effect of preterm birth on the risk of multiple sclerosis: A population based study. BMC Neurol2008; 8: 30.
9.
BoveRMHoutchensMK.Pregnancy management in multiple sclerosis and other demyelinating diseases. Continuum2022; 28: 12–33.
10.
MaillartERollotFLerayE, et al. Pregnancy and birth outcomes in women with multiple sclerosis: Comparison of the RESPONSE study to the general French population. Mult Scler2025; 31(3): 324–337.
11.
MacDonaldSCMcElrathTFHernández-DíazS.Pregnancy outcomes in women with multiple sclerosis. Am J Epidemiol2019; 188: 57–66.
12.
CaoJXuWLiuY, et al. Trends in maternal age and the relationship between advanced age and adverse pregnancy outcomes: A population-based register study in Wuhan, China, 2010-2017. Public Health2022; 206: 8–14.
13.
KooYJRyuHMYangJH, et al. Pregnancy outcomes according to increasing maternal age. Taiwan J Obstet Gynecol2012; 51(1): 60–65.
14.
AradhyaSTegunimatakaAKravdalØ, et al. Maternal age and the risk of low birthweight and pre-term delivery: A pan-Nordic comparison. Int J Epidemiol2023; 52: 156–164.
15.
LeanSCDerricottHJonesRL, et al. Advanced maternal age and adverse pregnancy outcomes: A systematic review and meta-analysis. PLoS ONE2017; 12(10): e0186287.
16.
CarolanMFrankowskaD.Advanced maternal age and adverse perinatal outcome: A review of the evidence. Midwifery2011; 27(6): 793–801.
17.
Guarga MontoriMÁlvarez MartínezALuna ÁlvarezC, et al. Advanced maternal age and adverse pregnancy outcomes: A cohort study. Taiwan J Obstet Gynecol2021; 60: 119–124.
18.
SparićRStojkovićMPlešinacJ, et al. Advanced maternal age (AMA) and pregnancy: A feasible but problematic event. Arch Gynecol Obstet2024; 310(3): 1365–1376.
19.
HamadaRHasegawaAMaedaY, et al. Maternal and neonatal outcomes in full-term pregnancies of very advanced maternal age: A Japanese single-center retrospective cohort study. BMC Pregnancy Childbirth2025; 25: 711.
20.
KimH-ESongIGChungS-H, et al. Trends in birth weight and the incidence of low birth weight and advanced maternal age in Korea between 1993 and 2016. J Korean Med Sci2019; 34: e34.
21.
KimJNamJYParkE-C.Advanced maternal age and severe maternal morbidity in South Korea: A population-based cohort study. Sci Rep2022; 12: 21358.
22.
ChenYHLinHLLinHC.Does multiple sclerosis increase risk of adverse pregnancy outcomes? A population-based study. Mult Scler2009; 15(5): 606–612.
23.
RadzikAMAmezcuaLAndersonA, et al. Disparities by race in pregnancy care and clinical outcomes in women with multiple sclerosis: A diverse multicenter cohort. Neurology2024; 102: e208100.
24.
KangHT.Current status of the national health screening programs in South Korea. Korean J Fam Med2022; 43(3): 168–173.
25.
MoonJS.Review of national health screening program for infant and children in Korea. J Korean Med Assoc2010; 53: 377–385.
26.
JoSCheonEKangH, et al. Cohort profile: The Korean National Health Examination Baseline (KNHEB) cohort for longitudinal health monitoring in South Korea. BMC Public Health2025; 25: 1777.
27.
YoonSJLimJHanJH, et al. Identification of growth patterns in low birth weight infants from birth to 5 years of age: Nationwide Korean cohort study. Int J Environ Res Public Health2021; 18: 1206.
28.
VukusicSBoveRDobsonR, et al. Pregnancy and infant outcomes in women with multiple sclerosis treated with ocrelizumab. Neurol Neuroimmunol Neuroinflamm2024; 12: e200349.
29.
HoutchensMKEdwardsNCSchneiderG, et al. Pregnancy rates and outcomes in women with and without MS in the United States. Neurology2018; 91: e1559–e1569.
30.
BastNDost-KovalskyKHabenS, et al. Impact of disease-modifying therapies on pregnancy outcomes in multiple sclerosis: A prospective cohort study from the German multiple sclerosis and pregnancy registry. Lancet Reg Health Eur2025; 48: 101137.
31.
ThielSCipleaAIGoldR, et al. The German multiple sclerosis and pregnancy registry: Rationale, objective, design, and first results. Ther Adv Neurol Disord2021; 14: 17562864211054956.
32.
CappellettiMDella BellaSFerrazziE, et al. Inflammation and preterm birth. J Leukoc Biol2016; 99: 67–78.
33.
PresiccePRolandCSenthamaraikannanP, et al. IL-1 and TNF mediates IL-6 signaling at the maternal-fetal interface during intrauterine inflammation. Front Immunol2024; 15: 1416162.
34.
BarenbrugLGroenMTHoentjenF, et al. Pregnancy and neonatal outcomes in women with immune mediated inflammatory diseases exposed to anti-tumor necrosis factor-α during pregnancy: A systemic review and meta-analysis. J Autoimmun2021; 122: 102676.
35.
GoyneCEFairAESumowskiPE, et al. The impact of aging on multiple sclerosis. Curr Neurol Neurosci Rep2024; 24: 83–93.
36.
ZhangYAtkinsonJBurdCE, et al. Biological aging in multiple sclerosis. Mult Scler2023; 29: 1701–1708.
37.
Castellanos GutierrezASFiguerasFMorales-PrietoDM, et al. Placental damage in pregnancies with systemic lupus erythematosus: A narrative review. Front Immunol2022; 13: 941586.
38.
WegmannTGLinHGuilbertL, et al. Bidirectional cytokine interactions in the maternal-fetal relationship: Is successful pregnancy a TH2 phenomenon?Immunol Today1993; 14(7): 353–356.
39.
Multifetal gestations: Twin, triplet, and higher-order multifetal pregnancies: ACOG practice bulletin, number 231. Obstet Gynecol2021; 137(6): e145–e162.
40.
MillerDHFazekasFMontalbanX, et al. Pregnancy, sex and hormonal factors in multiple sclerosis. Mult Scler2014; 20(5): 527–536.
41.
FinkKGorczycaAAlpingP, et al. Multiple sclerosis, disease-modifying drugs and risk for adverse perinatal and pregnancy outcomes: Results from a population-based cohort study. Mult Scler2023; 29(6): 731–740.
42.
CanibañoBDeleuDMesraouaB, et al. Pregnancy-related issues in women with multiple sclerosis: An evidence-based review with practical recommendations. J Drug Assess2020; 9(1): 20–36.
43.
McGeeDC.Steroid use during pregnancy. J Perinat Neonatal Nurs2002; 16: 26–39.
44.
XiaoWLLiuXYLiuYS, et al. The relationship between maternal corticosteroid use and orofacial clefts-a meta-analysis. Reprod Toxicol2017; 69: 99–105.
