Reproductive history of the Danish multiple sclerosis population: A register-based study.

BACKGROUND: A diagnosis of multiple sclerosis (MS) may impact the choice of parenthood. OBJECTIVE: To investigate the number of live births, abortions and ectopic pregnancies among persons with MS. METHODS: From the Danish Multiple Sclerosis Registry, we extracted data from all persons diagnosed with MS from 1960 to 1996 and matched each MS person with four reference persons. We used a negative binomial regression model for the live births and Poisson regression model for abortions and ectopic pregnancies. The total fertility rate (TFR) during 1960-2016 and the annual number of live births in the MS population were analysed. RESULTS: Persons with MS had fewer children than reference persons. Fewer women with MS had elective abortions after diagnosis (incidence rate ratio (IRR) = 0.88; 95% confidence interval (CI) = 0.78-1.00) than reference persons. There was no difference regarding the number of elective abortions, spontaneous abortions or ectopic pregnancies after onset. The TFR was lower for women with MS than for reference persons, and the number of annual live births by MS persons increased during 1960-2016. CONCLUSION: MS seems to considerably impact reproductive choices, especially after clinical diagnosis, resulting in the MS population having fewer children than the general population.

Pregnancy Outcomes in Men and Women Treated With Teriflunomide. A Population-Based Nationwide Danish Register Study.

Background: The majority of persons diagnosed with multiple sclerosis (MS) experience their first MS symptoms in the reproductive age. Teriflunomide (TFL, Aubagio), was first released in Denmark for relapsing-remitting MS in December 2013. TFL treatment is contraindicated in women of childbearing potential who are not using reliable contraception. TFL can be transmitted via semen and a low risk of male-mediated embryo-fetal toxicity is described. Objective: To report pregnancy outcomes of TFL-treated women and partners to TFL-treated men: gestation week. Methods: Prospective cohort study comparing pregnancy outcomes of TFL-treated men and women, matched on age at conception, 1:4 with controls from the general population. Data on TFL-treated patients treated 1st of January 2014-31st of December 2016 for at least 30 consecutive days prior to conception, and with conception occurring latest 2 years after treatment discontinuation were extracted from The Danish Multiple Sclerosis Registry and merged with several national reproductive registries. Logistic regression was used to analyse the association between TFL exposure and any adverse event. Results: A total of 31 pregnancies were recorded, 13 women and 18 of partners to a TFL-treated man. All 18 partners of TFL-treated men completed their pregnancies: livebirth (18), gestation time >37 weeks (17), gestation time 33-36 weeks (1), normal birth weight (18), spontaneous and elective abortion (0), congenital malformation (plagiocephali) (1), normal delivery (14), induced delivery (2), cesarean section (2), Apgar score ≥7 (18). Among the 13 pregnancies in women exposed to TFL: elective abortion (11), spontaneous abortion (0), livebirth (2), gestation time >37 weeks (2), normal birth weight (2), congenital malformations (0), normal delivery (1), induced delivery (1), Apgar score ≥7 (2). The TFL group was associated with a 22% reduction in the odds of any adverse event relative to controls, although this association was not significant (OR 0.78; 95% CI 0.16-3.72, p = 0.753). Conclusion: Pregnancy outcomes were consistent with those of the general population. The malformation reported of the partner to a TFL-treated man is comparable to the rate of plagiocephaly reported in Denmark.

Mental health among children of mothers with multiple sclerosis: A Danish cohort and register-based study.

BACKGROUND: Multiple sclerosis is associated with an increased risk of developing physical, cognitive, and mental health problems. Current studies have demonstrated variating outcomes of parental multiple sclerosis mental health problems and their children's mental health development. OBJECTIVE: The purpose of this study was to investigate whether maternal multiple sclerosis is associated with the mental health status of their child. METHODS: Data from the Danish National Birth Cohort (DNBC) were merged with information from the Danish Multiple Sclerosis Registry. Two proxies, total difficulties score and prediction of any psychiatric diagnosis based on the strengths and difficulties questionnaire, were used to measure the mental health status of the children. The two groups were compared using Mann-Whitney and logistic regression analyses. RESULTS: For the total difficulties score the control and exposed group consisted of respectively n = 42,016 and n = 40, and for the prediction of any psychiatric diagnosis respectively n = 16,829 and n = 17. We found no statistically significant association between maternal multiple sclerosis and mental health status on neither of the proxies. CONCLUSION: Maternal multiple sclerosis did not show any association with the mental health status of their children at age eleven. On the contrary, other studies conclude that there is an association between maternal multiple sclerosis and the child's mental health status, one especially mediated by the maternal mental health status.

Patient awareness about family planning represents a major knowledge gap in multiple sclerosis.

BACKGROUND: The purpose of the survey was to assess the knowledge of family planning issues associated with disease modifying therapies (DMTs) among patients diagnosed with multiple sclerosis (MS). METHODS: 590 Danish MS patients responded to an online questionnaire about family planning in MS, collecting demographics, disease characteristics, disease modifying treatment, knowledge of potential teratogenic effects in DMTs, number of children, occurrence of unplanned pregnancies and outcome, and sources of information. RESULTS: 488 females and 102 males, mean age 40 years, responded. On average, it was 6.5 and 10.9 years since diagnosis and first symptoms, respectively. 16% of female and 19% of male respondents did not receive DMT at the time of responding to the survey. 30% of all had received only one DMT, 37%, 19%, 8%, and 5% had received two, three, four, and five different treatments, respectively. 42% of female and 74% of male respondents said they did not know if the medication they were taking had teratogenic risks. 83% of females and 85% of males responded that they did not know, whether DMT in male MS patients may expose healthy partners to teratogenic risks; hereto, 13% and 10%, respectively, answered that no transmission occurs. On average respondents had two children; three of four children reported in the study were born prior to the respondents being diagnosed with MS. 50% of both female and male respondents without children wanted a family and 25% of females and 16% of males wanted to start a family within the next two years. 91% of female respondents would discontinue DMT during pregnancy. Among male respondents 32% would continue treatment during a partner's pregnancy and 47% did not know whether they would continue or discontinue treatment. 10% of the female patients had had unplanned pregnancies during MS treatment, of these 49% chose to have an abortion. 53% of all felt they were well informed about MS treatment and family planning. 22% and 41% of the respondents received information from the neurologist about teratogenic risks in female MS patients and about teratogenic risks in women with male MS patients as partners, respectively; 27% and 34%% retrieved information from the internet on these two issues. CONCLUSION: This survey uncovered a low level of knowledge about DMTs' teratogenic risks among MS patients irrespective of sex. Knowledge about potential teratogenic risks for male MS patients receiving DMTs while planning to start a family was largely absent. 10% of female patients had experienced unplanned pregnancies on MS treatment. In general, patients use the internet and their neurologist to the same extent for information on parenthood planning.

Life course of children with parental multiple sclerosis.

BACKGROUND: The majority of persons with multiple sclerosis (MS) experience onset of MS between the ages of 20 and 40. Since two-thirds of the persons with MS are young women of childbearing age, parenthood is an essential issue during this period of life. The potential influence of parental MS on children arises from the varied symptoms of the chronic illness, which affect physical and cognitive abilities. MS disabilities and fatigue can restrict daily life and result in less energy for activities or job loss and thus worse conditions for the family. OBJECTIVES AND METHODS: This PhD thesis was designed to investigate whether parental MS influences children in different areas throughout the children's life course (i.e. education, employment, disability pension, and income) as well as to explore the experiences of having a parent with MS. We investigated the research question using two distinct METHODS: A quantitative method based on nationwide population-based Danish registers comparing a group of children with one biological parent with MS (termed 'MS offspring') with a matched group of children of parents without MS (termed 'reference cohort') up to 58 years of age (Papers I-II). A qualitative method based on phenomenological face-to-face interviews with young adults with parental MS (Paper III). The nationwide register-based epidemiological method complemented by a phenomenological interview method, the long time-span and the age groups of 'children' up to age 58 are original within this area of research. RESULTS: In Paper I, we investigated the educational achievements of 4,177 MS offspring compared with 33,416 reference children. MS off-spring achieved a higher grade point average in the final class of basic school, at age 15, although they achieved similar educational levels as did the reference children at ages 15 to 58. There was a trend toward more MS offspring women attaining health-related educations than did reference women at ages 21 to 58. In Paper II, we investigated employment and income of 2,456 MS offspring compared with 19,648 reference children. At age 30, the MS offspring were less often employed, and at ages 30 and 40 MS offspring more often received disability pension than did reference children. The mean income at the age interval of 45 to 49 years was similar. Analyzing whether the MS offspring earned more than DKK 250,000 annually (~ EUR 33,650), which is approximately double the level defined as poverty in Denmark in 2012, they earned above this level in annual gross personal in-come less frequently than did reference children. This income level was only sufficient for the bare necessities. In Paper III, we explored the experiences of children growing up with a parent with MS by interviewing 14 young adults between 18 and 25 years. The results in the interview study showed two essential themes: 'Caring' and 'Restraint'. Each essential theme emerged from four subthemes. Caring: Assuming responsibility; worry and guilt; choosing health-related educations; advantage of being responsible. Restraint: Concealing feelings and desires; anxiety and depression; shame; lack of openness and knowledge. All the young adults had experiences of the essential themes of caring and restraint. Half of the participants in the interview study were enrolled in a health-related education. CONCLUSION: Growing up with a parent with MS can have both beneficial and adverse influences on children late into adulthood. On the one hand, the educational achievements of MS offspring are either better or similar to those of reference children because they attained better grades and similar educational levels. Also, some of the young adults interviewed found advantages to having learned to be responsible. On the other hand, we found an ad-verse association regarding employment, disability pension, and income. Also, the young adults interviewed had experiences of caring for and of practicing restraint toward the parent with MS, the other parent, and siblings, with most participants continuing this pattern toward friends and partners. The results of caring and restraint might partly explain some of the associations found in the register-based studies. The children might continue taking care of their parents and striving to find a balance between helping others and fulfilling their own desires. This caregiver challenge might also partly explain the beneficial association between parental MS on education and the adverse association on employment. Thus, having a parent with MS might be associated with long-term socioeconomic influence on education, employment, disability pension, income, and social relations in children's life course: Parental MS influences children far into adulthood.

Employment, disability pension and income for children with parental multiple sclerosis.

BACKGROUND: Little is known about the consequences of parental multiple sclerosis (MS) on offspring's socioeconomic circumstances. OBJECTIVE: To investigate employment, disability pension and income in offspring of parents with MS compared with matched reference persons in a nationwide register-based cohort study. METHODS: All Danish-born persons with onset of MS during 1950-1986 were retrieved from the Danish Multiple Sclerosis Registry. Their offspring were identified using the Civil Registration System. One random offspring from each sibship was matched by sex and year of birth with eight random reference persons. RESULTS: We included 2456 MS offspring and 19,648 reference persons. At age 30, employment was lower among MS offspring than reference children (odds ratio (OR): 0.89; 95% confidence interval (CI): 0.84-0.95; p = 0.0003), and they more often received disability pension (OR: 1.31; 95% CI: 1.15-1.50; p < 0.0001) at ages 30 and 40 but not at age 50. Although the mean income was not significantly lower for the MS offspring cohort, most of them attained an annual personal income below 250,000 DKK (Danish krone), that is, ~33,650 EUR (OR: 0.91; 95% CI: 0.84-0.99; p = 0.04). CONCLUSION: Having had a parent with MS may affect employment and increase the risk of disability pension and low income in adult life.