Ai-Lan Nguyen1,2, Karolina Vodehnalova3, Tomas Kalincik1,2, Alessio Signori4, Eva Kubala Havrdova3, Jeannette Lechner-Scott5,6,7, Olga G Skibina8, Alana Eastaugh1, Lisa Taylor1, Josephine Baker1, Nicola McGuinn8, Louise Rath8, Vicki Maltby5,6,7, Maria Pia Sormani4, Helmut Butzkueven8,9,10, Anneke Van der Walt8,9,10, Dana Horakova3, Vilija G Jokubaitis8,9,10. 1. Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia. 2. CORe, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia. 3. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. 4. Department of Health Sciences (DISSAL), Biostatistics Unit, University of Genoa, Genoa, Italy. 5. Department of Neurology, John Hunter Hospital, Newcastle, New South Wales, Australia. 6. School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia. 7. Centre for Brain and Mental Health, Hunter Medical Research Institute, Newcastle, New South Wales, Australia. 8. Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia. 9. Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia. 10. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Abstract
Importance: Multiple sclerosis (MS) is usually diagnosed in women during their childbearing years. Currently, no consensus exists on whether pregnancy can delay the first episode of demyelination or clinically isolated syndrome (CIS). Objective: To investigate the association of pregnancy with time to CIS onset. Design, Setting, and Participants: This multicenter cohort study collected reproductive history (duration of each pregnancy, date of delivery, length of breastfeeding) on all participants between September 1, 2016, and June 25, 2019. Adult women being treated at the MS outpatient clinics of 4 tertiary hospitals in 2 countries (Charles University and General University Hospital in Prague, Czech Republic; Royal Melbourne Hospital in Melbourne, Australia; Alfred Hospital in Melbourne, Australia; and John Hunter Hospital in Newcastle, Australia) were recruited to participate in the study. Preexisting data (date of CIS onset, date of birth, sex, date of clinical onset, and Expanded Disability Status Scale result) were collected from MSBase, an international registry of long-term prospectively collected data on patients with MS. Data analyses were performed from June 1, 2019, to February 3, 2020. Exposures: Gravida (defined as any pregnancy, including pregnancy that ended in miscarriage and induced abortion) and parity (defined as childbirth after gestational age of more than 20 weeks, including livebirth and stillbirth) before CIS onset. Main Outcomes and Measures: Time to CIS onset. The following were assessed: (1) whether women with previous pregnancies and childbirths had a delayed onset of CIS compared with those who had never been pregnant and those who had never given birth, and (2) whether a dose response existed, whereby a higher number of gravidity and parity was associated with a later onset of CIS. Results: Of the 2557 women included in the study, the mean (SD) age at CIS onset was 31.5 (9.7) years. Of these women, before CIS onset, 1188 (46%) had at least 1 pregnancy and 1100 (43%) had at least 1 childbirth. The mean (SD) age at first pregnancy was 23.3 (4.5) years and at first childbirth was 23.8 (4.5) years. Women with previous pregnancies and childbirths had a later onset of CIS compared with those who had never been pregnant (HR, 0.68; 95% CI, 0.62-0.75; P < .001), with a median delay of 3.3 (95% CI, 2.5-4.1) years. Women who had given birth also had a later CIS onset compared with women who had never given birth (HR 0.68; 95% CI, 0.61-0.75; P < .001), with a similar median delay of 3.4 (95% CI, 1.6-5.2) years. A higher gravidity and parity number was not associated with delay in CIS onset. Conclusions and Relevance: This study suggests an association between previous pregnancies and childbirths and timing of CIS onset, but having more pregnancies or childbirths did not appear to be associated with a later CIS onset. Further studies are needed to help explain the mechanisms behind the associations between pregnancy and onset of multiple sclerosis.
Importance: Multiple sclerosis (MS) is usually diagnosed in women during their childbearing years. Currently, no consensus exists on whether pregnancy can delay the first episode of demyelination or clinically isolated syndrome (CIS). Objective: To investigate the association of pregnancy with time to CIS onset. Design, Setting, and Participants: This multicenter cohort study collected reproductive history (duration of each pregnancy, date of delivery, length of breastfeeding) on all participants between September 1, 2016, and June 25, 2019. Adult women being treated at the MS outpatient clinics of 4 tertiary hospitals in 2 countries (Charles University and General University Hospital in Prague, Czech Republic; Royal Melbourne Hospital in Melbourne, Australia; Alfred Hospital in Melbourne, Australia; and John Hunter Hospital in Newcastle, Australia) were recruited to participate in the study. Preexisting data (date of CIS onset, date of birth, sex, date of clinical onset, and Expanded Disability Status Scale result) were collected from MSBase, an international registry of long-term prospectively collected data on patients with MS. Data analyses were performed from June 1, 2019, to February 3, 2020. Exposures: Gravida (defined as any pregnancy, including pregnancy that ended in miscarriage and induced abortion) and parity (defined as childbirth after gestational age of more than 20 weeks, including livebirth and stillbirth) before CIS onset. Main Outcomes and Measures: Time to CIS onset. The following were assessed: (1) whether women with previous pregnancies and childbirths had a delayed onset of CIS compared with those who had never been pregnant and those who had never given birth, and (2) whether a dose response existed, whereby a higher number of gravidity and parity was associated with a later onset of CIS. Results: Of the 2557 women included in the study, the mean (SD) age at CIS onset was 31.5 (9.7) years. Of these women, before CIS onset, 1188 (46%) had at least 1 pregnancy and 1100 (43%) had at least 1 childbirth. The mean (SD) age at first pregnancy was 23.3 (4.5) years and at first childbirth was 23.8 (4.5) years. Women with previous pregnancies and childbirths had a later onset of CIS compared with those who had never been pregnant (HR, 0.68; 95% CI, 0.62-0.75; P < .001), with a median delay of 3.3 (95% CI, 2.5-4.1) years. Women who had given birth also had a later CIS onset compared with women who had never given birth (HR 0.68; 95% CI, 0.61-0.75; P < .001), with a similar median delay of 3.4 (95% CI, 1.6-5.2) years. A higher gravidity and parity number was not associated with delay in CIS onset. Conclusions and Relevance: This study suggests an association between previous pregnancies and childbirths and timing of CIS onset, but having more pregnancies or childbirths did not appear to be associated with a later CIS onset. Further studies are needed to help explain the mechanisms behind the associations between pregnancy and onset of multiple sclerosis.
Authors: Vera R Lezhnyova; Ekaterina V Martynova; Timur I Khaiboullin; Richard A Urbanowicz; Svetlana F Khaiboullina; Albert A Rizvanov Journal: Biology (Basel) Date: 2020-12-11
Authors: Vilija G Jokubaitis; Olga Skibina; Raed Alroughani; Ayse Altintas; Helmut Butzkueven; Sara Eichau; Yara Fragoso; Kerstin Hellwig; Stella E Hughes; Louise Rath; Anneke van der Walt; Orla Gray Journal: Ther Adv Neurol Disord Date: 2021-04-12 Impact factor: 6.570
Authors: Anders Pretzmann Mikkelsen; Pia Egerup; Astrid Marie Kolte; David Westergaard; Henriette Svarre Nielsen; Øjvind Lidegaard Journal: PLoS One Date: 2022-03-31 Impact factor: 3.240
Authors: Christiane Gasperi; Alexander Hapfelmeier; Antonius Schneider; Klaus A Kuhn; Ewan Donnachie; Bernhard Hemmer Journal: Mult Scler Date: 2022-03-18 Impact factor: 5.855