BACKGROUND AND OBJECTIVES:Sex steroid hormones have been demonstrated to affect the immune system in multiple sclerosis (MS), and puberty may trigger MS activity. We aimed to evaluate the association between menarche and disease course in pediatric MS through comparison of relapse rates across premenarche, perimenarche, and postmenarche periods. METHODS:This is a retrospective analysis of a prospectively followed female cohort with pediatric-onset MS in the US Network of Pediatric MS Centers database. Perimenarche was considered the period from 1 year before to 1 year after the estimated menarche date based on menarche integer age. Relapses were collected prospectively. Negative binomial and repeated-measures Cox regression models were used to assess the association of pubertal development stage with relapse rate, adjusted for race, body mass index, and disease-modifying therapy (DMT). RESULTS:Of 736 participants (all female; mean onset age 14.4 ± 2.8 years; mean menarche age 11.6 ± 1.4 years), onset was in premenarche in 73, perimenarche in 112 (± 1 year of menarche), and postmenarche in 551. The median time of MS onset was 2.8 years after menarche. Most (86%) were exposed to DMT in follow-up. In adjusted negative binomial analysis, the annualized relapse rate during premenarche was 0.43, perimenarche was 0.65, and postmenarche was 0.43 (premenarche rate ratio [RR] 1.00 (95% CI 0.70-1.43) and perimenarche RR 1.52 (95% CI 1.16-1.99), compared with reference of postmenarche, p = 0.0049. In adjusted repeated-events Cox regression analysis, there was increased hazard to relapse in perimenarche and postmenarche compared with premenarche (perimenarche hazard ratio [HR] 1.78 [95% CI 1.17-2.70] and postmenarche HR 1.67 [95% CI 1.12-2.50], compared with reference of premenarche, p = 0.025). In this analysis, use of oral and infusion DMTs significantly lowered the relapse hazard compared with periods of no DMT use (injectable HR 0.98 [95% CI 0.83-1.15], oral HR 0.48 [95% CI 0.37-0.61], and infusion HR 0.24 [95% CI 0.18-0.31], compared with no DMT, p < 0.001). DISCUSSION:Onset of puberty may be a time of increase in disease activity and may require consideration of a change in therapeutic approach. Menarche age was used as a surrogate for puberty, and future studies measuring sex steroid hormones may be informative.

BACKGROUND:Mothers with MS face an increased incidence and prevalence of peripartum mental illness as compared to mothers without MS. OBJECTIVE:To determine the factors associated with the risk of peripartum mental illness among mothers with MS. METHODS:We identified mothers with MS with live births between 2002 and 2019 using linked population-based administrative data from Ontario, Canada. Using validated definitions, we estimated the incidence of mental illness (depression, anxiety, bipolar disorder) from conception through the first post-partum year (peripartum period). We used multivariable Poisson regression to assess the association between age, delivery year, area-level deprivation (Ontario Marginalization Index), disease duration, disability, and comorbidity and incidence of peripartum mental illness. RESULTS:Among 1745 mothers with MS, the mean (SD) age at conception was 31.2 (4.8) years. Mothers living in communities that lacked cohesion had increased rates of peripartum depression (incidence rate ratio [IRR] 1.25; 1.11-1.42) and anxiety (IRR 1.20; 1.07-1.33). Elevated MS disability level was associated with elevated peripartum depression rates (IRR 1.51; 1.12-2.04). CONCLUSION:Higher area-level deprivation and disability levels are associated with an increased incidence of peripartum mental illness. These findings may assist clinicians in identifying women with MS who may benefit from peripartum mental health support.

BACKGROUND AND OBJECTIVES:Peripartum mood and anxiety disorders constitute the most frequent form of maternal morbidity in the general population, but little is known about peripartum mental illness in mothers with multiple sclerosis (MS). We compared the incidence and prevalence of peripartum mental illness among mothers with MS, epilepsy, inflammatory bowel disease (IBD), and diabetes and women without these conditions. METHODS:Using linked population-based administrative health data from ON, Canada, we conducted a cohort study of mothers with MS, epilepsy, IBD, and diabetes and without these diseases (comparators) who had a live birth with index dates, defined as 1 year before conception, between 2002 and 2017. Using validated definitions, we estimated the incidence and prevalence of mental illness (any, depression, anxiety, bipolar disorder, psychosis, substance use, suicide attempt) during the prenatal (PN) period (from conception to birth) and 3 years postpartum. We compared incidence and prevalence estimates between cohorts using simple incidence ratios (IRs) and prevalence ratios with 95% CIs and using Poisson regression models adjusting for confounders. RESULTS:We included 894,852 mothers (1,745 with MS; 5,954 with epilepsy; 4,924 with IBD; 13,002 with diabetes; 869,227 comparators). At conception, the mean (SD) maternal age was 28.6 (5.7) years. Any incident mental illness affected 8.4% of mothers with MS prenatally and 14.2% during the first postpartum year; depression and anxiety were the most common incident disorders. The first postpartum year was a higher risk period than the PN period (any mental illness IR 1.27; 95% CI 1.08-1.50). After adjustment, mothers with MS had an increased incidence of any mental illness during the PN (IR 1.26; 95% CI 1.11-1.44) and postpartum (IR 1.33; 95% CI 1.20-1.47, first postpartum year) periods than comparator mothers. Similarly, mothers with MS had an increased incidence of all specific mental illnesses except suicide attempt during the PN period vs comparator mothers. Any prevalent mental illness affected 42% of mothers with MS prenatally and 50.3% in the first postpartum year. DISCUSSION:Mothers with MS had an elevated incidence and prevalence of peripartum mental illness compared with comparator mothers, although residual confounding cannot be excluded. These findings emphasize the need for preventive interventions and early treatment of mental illness.

BackgroundAn increasing number of women with multiple sclerosis (wMS) are considering pregnancy. Prior studies suggest increased rate of elective cesarian sections (C-sections) in wMS.MethodsThe Canadian Multiple Sclerosis Pregnancy Study (CANPREG-MS) is a prospective study on pregnant wMS. This report shows comparisons between (i) CANPREG-MS wMS delivered by C-section and the general population and (ii) C-section and vaginal deliveries in this study cohort.ResultsCANPREG-MS has resulted in 170 deliveries with 63 by C-section. The proportion with C-sections in CANPREG-MS (37.1%) was significantly higher than that for the Canadian population (28%) ( p = .0085). The majority (66.7%) of C-sections were not planned, and typically were performed for obstetrical indications. C-sections were performed at an earlier gestational age than vaginal deliveries, although birthweight did not differ by mode of delivery in wMS. MS relapses (3.2%) and pseudo-relapses (3.2%) were rare in the first month after C-section deliveries, regardless of disease modifying therapy decisions during gestation and postpartum.ConclusionsC-sections were more common in wMS than the general population, but few were because of maternal MS. CANPREG-MS provides informative data for pregnancies in wMS with well-managed and relatively mild disease. This information is helpful to obstetrical and MS healthcare providers.

Citation: Lugaresi A, Jokubaitis VG and Krysko KM (2024) Editorial: Aging in multiple sclerosis: from childhood to old age, in women and men. Front. Neurol. 15:1368420. doi: 10.3389/fneur.2024.1368420

Background/Objective(s) A significant proportion of people with multiple sclerosis (MS) are women of childbearing age and the number of those exposed to ocrelizumab (OCR) close to pregnancy is increasing. Currently, OCR labelling advises contraception during treatment and for 6–12 months thereafter; however, an increasing number of pregnancies are occurring in this interval.To report pregnancy and infant outcomes among women with MS exposed to OCR before or during pregnancy and/or breastfeeding. Material(s) and Method(s) Pregnancies from the Roche safety database were analysed. Maternal OCR exposure was defined as ≥1 infusion; in utero exposure was defined as an infusion ≤3 months (M) prior to the last menstrual period (LMP) or during pregnancy. Foetal death was termed spontaneous abortion (SA) if <22 complete gestational weeks (GW), or stillbirth if later. Live births (LB) were preterm if <37 complete GW. Major congenital anomalies (MCA) were classified via EUROCAT 1.5. Infant exposure through breastfeeding was recorded if lactating mothers received OCR postpartum. Result(s) As of 12 July 2023, 3,244 cumulative MS pregnancies were reported; 2,444 were reported prospectively, 793 retrospectively, seven unspecified. A total of 855 prospective pregnancies were considered in utero exposed; most occurred ≤3M before LMP (n=572), followed by first (n=258) and later trimesters (n=25). Amongst prospectively reported pregnancies with known outcomes (n=1,144), 83.6% resulted in LB. In utero exposed and non-exposed groups had similar proportions of LB (84.2% vs 88.3%), full-term (65.7% vs 70.9%) and preterm (9.5% vs 8.7%) LB, and SA (7.4% vs 9.1%). Elective abortions were more frequent in the exposed group (7.4% vs 1.7% in the non-exposed group). The proportion of LB with MCA was similar between the exposed and non-exposed group (2.1% vs 1.9%) and remained within epidemiological background. Of 122 infants with breastfeeding exposure, 27 were also exposed in utero. As of 28 March 2024, approximately 4,000 cumulative MS pregnancies were reported. Updated pregnancy outcomes and 1-year infant outcomes will be presented. Conclusion(s) This is the largest dataset of pregnancy outcomes for an anti-CD20 therapy in MS. In utero exposure to ocrelizumab, primarily occurring ≤3M before the LMP and first trimester, did not increase the risk of adverse pregnancy or infant outcomes compared with the epidemiological background of both MS and the general population. Counselling remains an important approach to ensure optimal outcomes for mothers and infants.

People with MS may be at heightened risk of intimate partner violence (IPV) compared to the general population; however, little is known about the prevalence of IPV among people with MS or its effects on MS-specific clinical outcomes. Additionally, while MS clinicians often discuss family planning with patients, many clinicians may have received little training in detecting and responding to IPV. Moreover, no studies have investigated how to implement IPV case-finding and resource provision in the MS clinical setting. Overall, there are several scholarly, educational, and implementation-related gaps in IPV-associated care for people with MS. This article aims to summarize the available literature on IPV in people with MS, identify future research questions, and aid MS clinicians in safely addressing IPV while awaiting vital MS-specific knowledge.