Summary: Women who have experienced pregnancy were diagnosed with their first multiple sclerosis symptoms an average of 3.3 years later than women with MS who had never been pregnant.
Source: Monash University
An international, multicenter study led by researchers at Monash University provides strong evidence that pregnancy is associated with a significant delay in the first clinical signs of multiple sclerosis (MS).
Multiple sclerosis affects more women than men, and this large-scale analysis—drawing on the MSBase global registry—offers new insight into how reproductive history may influence disease timing. Using data from tens of thousands of patients worldwide, the research team investigated whether pregnancy and childbirth are linked to later onset of clinically isolated syndrome (CIS), the first clinical episode suggestive of MS.
MS is estimated to affect more than 2.5 million people globally, with women roughly four times more likely than men to develop the condition. Because MS often first appears during the years when women may become pregnant, understanding the relationship between pregnancy and disease onset is important for both basic science and potential therapeutic strategies.
The study was led by Dr Vilija Jokubaitis from the Department of Neuroscience at Monash University and published in JAMA Neurology. Researchers combined reproductive histories gathered from patients at four tertiary MS clinics with long-term clinical data from MSBase, the international registry coordinated by Professor Helmut Butzkueven at Monash University.
In the primary analysis, the investigators assessed reproductive and clinical data from 2,557 women treated at MS clinics in the Czech Republic and Australia. The study evaluated whether prior pregnancy (gravidity) and childbirth (parity) before the onset of CIS were associated with a delayed first clinical event, and whether the number of pregnancies or births had a cumulative effect on timing.
The main finding was a clear association between prior pregnancy and later CIS onset. Women who had been pregnant before their first clinical episode experienced a median delay of 3.3 years (95% CI, 2.5–4.1) in the timing of CIS onset compared with women who had never been pregnant. Similarly, women who had given birth showed a median delay of 3.4 years (95% CI, 1.6–5.2) compared with those who had never given birth. Statistical analysis reported a hazard ratio of 0.68 (95% CI, 0.62–0.75; P < .001) for gravidity and a comparable hazard ratio for parity, indicating a substantially lower instantaneous risk of CIS onset among women with prior pregnancy or childbirth.
The researchers did not find evidence of a dose–response effect; having more pregnancies or more births was not associated with an additional delay in CIS onset. The average age at CIS onset in the cohort was 31.5 years (SD 9.7). Before CIS onset, 1,188 women (46%) had experienced at least one pregnancy and 1,100 (43%) had at least one childbirth. The mean ages at first pregnancy and first childbirth were 23.3 and 23.8 years, respectively.
Dr Jokubaitis and colleagues propose that pregnancy may induce lasting changes in immune function that reduce the abnormal immune activity that underlies MS. She noted that epigenetic changes—modifications to gene expression—could play a role and that follow-up studies are needed to explore biological mechanisms. The team is seeking funding to investigate these possibilities further.
MSBase, the registry used for this research, has tracked patients with multiple sclerosis across 35 countries since 2001 and operates as an Australian not-for-profit foundation. Managed by Professor Helmut Butzkueven at Monash University’s Department of Neuroscience, MSBase coordinates data from more than 160 clinics and follows over 71,000 patients, supporting numerous investigator-initiated and registry studies worldwide. The large, long-term dataset enables analyses of disease onset, relapses, disability progression, and treatment effects—outputs that have informed more than 50 peer-reviewed publications in leading neurology journals.
Professor Butzkueven emphasized that answers to major questions about MS causes and long-term treatment outcomes often require decades of systematic data collection. Registries like MSBase make it possible to detect patterns—such as the link between pregnancy and delayed CIS—that shorter studies cannot reliably identify. He also highlighted ongoing efforts to develop new biomarkers and a next-generation care platform to accelerate clinical trials and improve access to care, especially in remote and regional communities.
Dr Julia Morahan, Head of Research at MS Research Australia, welcomed the study, noting that rising MS incidence—particularly among women—makes it important to investigate factors that influence disease development and timing. Better understanding of how pregnancy affects disease biology could inform prevention strategies and future therapies.
MSBase and Monash University are building an integrated care and research platform intended to speed discovery and make clinical trials more equitable. Future tools will enable remote patient self-management and broader participation in research, increasing both knowledge and access to potential therapies.
About this multiple sclerosis research article
Source:
Monash University
Contacts:
Tania Ewing – Monash University
Image Source:
The image is in the public domain.
Original Research:
“Association of Pregnancy With the Onset of Clinically Isolated Syndrome” by Helmut Butzkueven et al. JAMA Neurology. (Closed access)
Abstract
Association of Pregnancy With the Onset of Clinically Isolated Syndrome
Importance
Multiple sclerosis is most often diagnosed in women during their childbearing years. Until now, there has been no consensus on whether pregnancy can delay the first demyelinating episode (clinically isolated syndrome, CIS).
Objective
To evaluate the association between pregnancy and the timing of CIS onset.
Design, Setting, and Participants
This multicenter cohort study gathered detailed reproductive histories (pregnancy durations, delivery dates, breastfeeding) from adult women attending MS outpatient clinics between September 1, 2016, and June 25, 2019. Participants were recruited from four tertiary hospitals in the Czech Republic and Australia. Clinical data, including the date of CIS onset and disability scores, were retrieved from MSBase, an international registry of prospectively collected long-term data on patients with MS. Data analysis took place from June 1, 2019, to February 3, 2020.
Exposures
Gravidity (any pregnancy, including miscarriages and induced abortions) and parity (childbirth after >20 weeks gestation, including livebirth and stillbirth) before CIS onset.
Main Outcomes and Measures
Time to CIS onset. The study assessed whether women with prior pregnancies or childbirths had delayed CIS onset compared with women who had never been pregnant or given birth, and whether a higher number of pregnancies or births was associated with later onset.
Results
Among 2,557 women included, the mean (SD) age at CIS onset was 31.5 (9.7) years. Before CIS onset, 1,188 women (46%) had at least one pregnancy and 1,100 (43%) had at least one childbirth. Mean age at first pregnancy was 23.3 (4.5) years and at first childbirth was 23.8 (4.5) years. Prior pregnancy and childbirth were each associated with later CIS onset compared with never being pregnant (hazard ratio [HR], 0.68; 95% CI, 0.62–0.75; P < .001), with a median delay of 3.3 years (95% CI, 2.5–4.1) for pregnancy and 3.4 years (95% CI, 1.6–5.2) for childbirth. A greater number of pregnancies or births was not associated with additional delay in CIS onset.
Conclusions and Relevance
These results indicate an association between prior pregnancies or childbirths and later timing of CIS onset, but do not support a dose relationship with higher gravidity or parity. Further research is needed to clarify the biological mechanisms linking pregnancy and MS onset.