BACKGROUND AND PURPOSE: The effect of pregnancy on brain changes and radiological disease activity in women with multiple sclerosis (MS) is not well understood. This study was undertaken to describe the dynamics of lesion activity and brain volume changes during the pregnancy and postpartum periods. METHODS: This observational study of 62 women with relapsing-remitting MS included magnetic resonance imaging (221 scans) as well as clinical visits at baseline (<24 and >6 months before pregnancy), prepregnancy (<6 months before pregnancy), postpartum (<3 months after delivery), and follow-up (>12 and <24 months after delivery) periods. RESULTS: The majority of women had a mild disability and a short disease duration (median = 5.5 years). Eighteen (29.0%) women had a relapse during the year preceding pregnancy onset, nine (14.5%) during pregnancy, and 20 (32.3%) in the year following delivery. Disability status remained unchanged during follow-up. Women in the postpartum period (n = 62) had higher T2 lesion volume (median = 1.18 ml vs. 0.94 ml), greater annualized T2 lesion volume increase (0.23 ml vs. 0.0 ml), lower brain parenchymal fraction (85.6% vs. 86.4%), and greater annualized brain volume loss (-1.74% vs. -0.16%) compared with the prepregnancy period (all p < 0.001). At 12-24 months after delivery, women (n = 41) had higher T2 lesion volume (1.16 ml vs. 1.0 ml) and lower brain parenchymal fraction (86.0% vs. 86.5%) compared to the prepregnancy period (both p < 0.001). CONCLUSIONS: The postpartum period was associated with an increase in T2 lesion volume and accelerated brain volume loss in a considerable proportion of women. This should be considered in treatment decision-making and designing clinical trials.

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine and General University Hospital Charles University Prague Prague Czech Republic

Department of Radiology 1st Faculty of Medicine and General University Hospital Charles University Prague Prague Czech Republic

See more in PubMed

Schumacher A, Costa SD, Zenclussen AC. Endocrine factors modulating immune responses in pregnancy. Front Immunol. 2014;5:196.

Simerly RB. Wired for reproduction: organization and development of sexually dimorphic circuits in the mammalian forebrain. Annu Rev Neurosci. 2002;25:507-536.

Qiu K, He Q, Chen X, Liu H, Deng S, Lu W. Pregnancy-related immune changes and demyelinating diseases of the central nervous system. Front Neurol. 2019;10:1070.

Vukusic S, Hutchinson M, Hours M, et al. Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain. 2004;127:1353-1360.

Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998;339:285-291.

Nguyen AL, Eastaugh A, van der Walt A, Jokubaitis VG. Pregnancy and multiple sclerosis: clinical effects across the lifespan. Autoimmun Rev. 2019;18:102360.

Portaccio E, Ghezzi A, Hakiki B, et al. Postpartum relapses increase the risk of disability progression in multiple sclerosis: the role of disease modifying drugs. J Neurol Neurosurg Psychiatry. 2014;85:845-850.

Hughes SE, Spelman T, Gray OM, et al. Predictors and dynamics of postpartum relapses in women with multiple sclerosis. Mult Scler. 2014;20:739-746.

Anderson A, Krysko KM, Rutatangwa A, et al. Clinical and radiologic disease activity in pregnancy and postpartum in MS. Neurol Neuroimmunol Neuroinflamm. 2021;8:e959.

Zuluaga MI, Otero-Romero S, Rovira A, et al. Menarche, pregnancies, and breastfeeding do not modify long-term prognosis in multiple sclerosis. Neurology. 2019;92:e1507-e1516.

Koch M, Uyttenboogaart M, Heersema D, Steen C, De Keyser J. Parity and secondary progression in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2009;80:676-678.

D'Amico E, Leone C, Patti F. Offspring number does not influence reaching the disability's milestones in multiple sclerosis: a seven-year follow-up study. Int J Mol Sci. 2016;17:234.

Khalid F, Healy BC, Dupuy SL, et al. Quantitative MRI analysis of cerebral lesions and atrophy in post-partum patients with multiple sclerosis. J Neurol Sci. 2018;392:94-99.

Paavilainen T, Kurki T, Parkkola R, et al. Magnetic resonance imaging of the brain used to detect early post-partum activation of multiple sclerosis. Eur J Neurol. 2007;14:1216-1221.

van Walderveen MA, Tas MW, Barkhof F, et al. Magnetic resonance evaluation of disease activity during pregnancy in multiple sclerosis. Neurology. 1994;44:327-329.

Houtchens M, Bove R, Healy B, et al. MRI activity in MS and completed pregnancy: data from a tertiary academic center. Neurol Neuroimmunol Neuroinflamm. 2020;7:e890.

Rościszewska-Żukowska I, Podyma M, Stasiołek M, Siger M. Thalamus atrophy in the peri-pregnancy period in clinically stable multiple sclerosis patients: preliminary results. Brain Sci. 2021;11:1270.

Oatridge A, Holdcroft A, Saeed N, et al. Change in brain size during and after pregnancy: study in healthy women and women with preeclampsia. Am J Neuroradiol. 2002;23:19-26.

Carmona S, Martinez-Garcia M, Paternina-Die M, et al. Pregnancy and adolescence entail similar neuroanatomical adaptations: a comparative analysis of cerebral morphometric changes. Hum Brain Mapp. 2019;40:2143-2152.

Hoekzema E, Barba-Muller E, Pozzobon C, et al. Pregnancy leads to long-lasting changes in human brain structure. Nat Neurosci. 2017;20:287-296.

Martinez-Garcia M, Paternina-Die M, Barba-Muller E, et al. Do pregnancy-induced brain changes reverse? the brain of a mother six years after parturition. Brain Sci. 2021;11(2):168.

Mills KL, Tamnes CK. Methods and considerations for longitudinal structural brain imaging analysis across development. Dev Cogn Neurosci. 2014;9:172-190.

Peper JS, Hulshoff Pol HE, Crone EA, van Honk J. Sex steroids and brain structure in pubertal boys and girls: a mini-review of neuroimaging studies. Neuroscience. 2011;191:28-37.

Sisk CL, Foster DL. The neural basis of puberty and adolescence. Nat Neurosci. 2004;7:1040-1047.

Luders E, Gingnell M, Poromaa IS, Engman J, Kurth F, Gaser C. Potential brain age reversal after pregnancy: younger brains at 4-6 weeks postpartum. Neuroscience. 2018;386:309-314.

Lisofsky N, Gallinat J, Lindenberger U, Kuhn S. Postpartal neural plasticity of the maternal brain: early renormalization of pregnancy-related decreases? Neurosignals. 2019;27:12-24.

Kim P, Leckman JF, Mayes LC, Feldman R, Wang X, Swain JE. The plasticity of human maternal brain: longitudinal changes in brain anatomy during the early postpartum period. Behav Neurosci. 2010;124:695-700.

Frischer JM, Weigand SD, Guo Y, et al. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. Ann Neurol. 2015;78:710-721.

Uher T, Krasensky J, Malpas C, et al. Evolution of brain volume loss rates in early stages of multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2021;8:e979.

Uher T, Vaneckova M, Krasensky J, et al. Pathological cut-offs of global and regional brain volume loss in multiple sclerosis. Mult Scler. 2019;25:541-553.

Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005;58:840-846.

Zivadinov R, Reder AT, Filippi M, et al. Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis. Neurology. 2008;71:136-144.

Kalincik T, Cutter G, Spelman T, et al. Defining reliable disability outcomes in multiple sclerosis. Brain. 2015;138:3287-3298.

Uher T, Krasensky J, Vaneckova M, et al. A novel semiautomated pipeline to measure brain atrophy and lesion burden in multiple sclerosis: a long-term comparative study. J Neuroimaging. 2017;27:620-629.

Smith SM, Zhang Y, Jenkinson M, et al. Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. NeuroImage. 2002;17:479-489.

Sastre-Garriga J, Pareto D, Battaglini M, et al. MAGNIMS consensus recommendations on the use of brain and spinal cord atrophy measures in clinical practice. Nat Rev Neurol. 2020;16:171-182.

Lehmann H, Zveik O, Levin N, Brill L, Imbar T, Vaknin-Dembinsky A. Brain MRI activity during the year before pregnancy can predict post-partum clinical relapses. Mult Scler. 2021;27(14):2232-2239. doi:10.1177/13524585211002719

Yeh WZ, Widyastuti PA, Van der Walt A, et al. Natalizumab, fingolimod and dimethyl fumarate use and pregnancy-related relapse and disability in women with multiple sclerosis. Neurology. 2021;96(24):e2989-e3002.

Portaccio E, Tudisco L, Pasto L, et al. Pregnancy in multiple sclerosis women with relapses in the year before conception increases the risk of long-term disability worsening. Mult Scler. 2021:13524585211023365. doi:10.1177/13524585211023365

Meinl I, Havla J, Hohlfeld R, Kümpfel T. Recurrence of disease activity during pregnancy after cessation of fingolimod in multiple sclerosis. Mult Scler. 2018;24:991-994.

Martinelli V, Colombo B, Dalla Costa G, et al. Recurrent disease-activity rebound in a patient with multiple sclerosis after natalizumab discontinuations for pregnancy planning. Mult Scler. 2016;22:1506-1508.

Havrdova E, Arnold DL, Cohen JA, et al. Alemtuzumab CARE-MS I 5-year follow-up: durable efficacy in the absence of continuous MS therapy. Neurology. 2017;89:1107-1116.

Arnold DL, Fisher E, Brinar VV, et al. Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon beta-1a in MS. Neurology. 2016;87:1464-1472.

Cuello JP, Martinez Gines ML, Kuhle J, et al. Neurofilament light chain levels in pregnant multiple sclerosis patients: a prospective cohort study. Eur J Neurol. 2019;26:1200-1204.

Evers KS, Atkinson A, Barro C, et al. Neurofilament as neuronal injury blood marker in preeclampsia. Hypertension. 2018;71(6):1178-1184.

SARS-CoV-2 Is Linked to Brain Volume Loss in Multiple Sclerosis

Sex bias in multiple sclerosis and neuromyelitis optica spectrum disorders: How it influences clinical course, MRI parameters and prognosis