Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system that concerns ~2.8 million individuals worldwide (1) and 110,000 people in France (2, 3). Although there is genetic susceptibility, MS is not a hereditary disease (4). MS mostly affects women (three-fourths of patients) and usually starts at a young age, mainly 25–35-year-old adults (5). Therefore, MS has consequences on their personal, family, and professional life. MS does not affect fertility or pregnancy issues (6), and pregnancy is not contraindicated in women with MS.

One of the primary goals of prenatal care in the general population is to prevent pregnancy-related risks (7). Personalized antenatal care allows the early identification of obstetric complications through prenatal visits with physicians (e.g., gynecologists, obstetricians, and midwives) and ultrasound exams to assess fetal anatomy and monitor fetal growth and health. This optimizes delivery preparation and reduces the associated morbidity. Prenatal care also ensures that patients are educated about safe behaviors during pregnancy and the treatment of comorbidities, and it provides emotional support during what may be perceived as a stressful period by some women (8). The initiation of prenatal care before the second trimester of pregnancy is considered essential to identify pregnant women at risk of giving birth to a preterm or low-birth weight baby and to put in place medical, nutritional, educational, or psychosocial measures for promoting positive pregnancy outcomes (9).

Prenatal care should be individualized to take into account each woman's specific risk factors. The French National Authority for Health recommends the general population to make seven antenatal visits to a gynecologist/obstetrician, midwife, or general practitioner (GP) and three ultrasound exams (10, 11). The first visit should take place before the end of the third month of pregnancy (12). The same recommendations are also valid for women with MS but regular follow-up by a gynecologist–obstetrician is advisable (10).

Several studies have investigated pregnancy issues in MS (6, 13–15), but to date, no study assessed prenatal healthcare patterns in women with MS or adherence to follow-up recommendations (16). However, it is important to identify those women with MS at risk of low adherence to such recommendations to remind them about the importance of these visits/exams and to support them. Therefore, the objective of the present study was to measure the level of compliance to prenatal care recommendations and associated factors in pregnant women with MS, using data from the French National Health Insurance Database.

In the present study, among the 5,448 pregnancies that ended in a live birth in women with MS in France during the 2010–2015 period, 41.8–66.9% had an adequate follow-up according to the French antenatal care recommendations. In other words, 33.1% (index with GPs) to 58.2% (index without GPs) had an inadequate follow-up, i.e., did not reach the minimal number of visits and/or ultrasounds.

No visits, ultrasound exams, and laboratory tests were recorded in 87 pregnancies (1.6%). These women had slightly different characteristics from the whole sample: higher age at pregnancy, more recent MS identification, no DMT for at least 1 year before pregnancy, and different socio-economic distributions of the area of residence. This lack of follow-up may be due to denial of pregnancy [1 in 500 pregnancies in the general population in France (24)]. It may also be related to the woman's socio-economic status and her insurance scheme. We identified some explanatory factors for the level of compliance with pregnancy-related care recommendations. Women with multiple pregnancy and living in areas with higher medical density had better adherence to recommendations. Conversely, women in the 25–29 and >40 years age groups had lower adherence, as well as women with specific insurance schemes (CMU and agricultural and self-employed workers). Thus, our findings may have direct implications for the management of women with MS and may be helpful to raise awareness among healthcare providers about the risk of inadequate pregnancy follow-up and the need to remind the expected care to some insurance schemes specifically.

To the best of our knowledge, the present study was first specifically dedicated to the pregnancy-related healthcare follow-up of women with MS. We only identified a qualitative study on nine women in the United Kingdom that explored the experiences, expectations, and needs of women with MS in relation to childbearing (25).

Several countries, such as Belgium and the United Kingdom (26, 27), recommend more medical visits for pregnant women in the general population than France but fewer ultrasound exams. We found a French study that assessed the risk of antenatal care overutilization in the general population as well as predictive factors (28). The authors used data from the 2016 national cross-sectional perinatal survey that was performed in all maternity units in France and included 7,029 women. The number of visits was adequate for 36.8% of women but indicated high use for 44.0% and overuse for 19.2%. They found that primiparity, medium to high income, and poor psychological wellbeing were associated with prenatal care overutilization. Moreover, pregnancy care management by gynecologists–obstetricians was associated with the overutilization of ultrasound exams. This may be explained by their easier access to an ultrasound scanner, compared with other healthcare professionals.

In a systematic review (29), the late initiation or inadequate use of prenatal care in the general population was often associated with smoking, low maternal age, low education level, non-marital status, ethnic minority, planned patterns of prenatal care, hospital type, planned place of delivery, uninsured status, high parity, prior premature birth, obstetric risk factors, late recognition of pregnancy, and living in deprived neighborhoods. Unfortunately, most of these variables are not available in the SNDS, although we also identified extreme ages in the present study.

On the other hand, several risk factors of inadequate pregnancy-related healthcare utilization identified in our study (e.g., specific insurance schemes) were not found in the literature on the general population. We wonder whether this is specific to women with MS who may be needed to be reminded about the standard recommendations for antenatal care and visit timing.

Despite the existing French recommendations, it is obvious that many women consulted mainly their GP. This choice seems to be linked to the density of gynecologists. Indeed, when there are few gynecologists in the area of residence, consultations are more difficult to obtain, and this may force women to go to their GP (30, 31). It may also reflect women's preferences. Indeed, some women with MS may find reassuring to go and see their GP, whom they know and trust and who is informed about their condition. It is necessary to remember that general practitioners are not as experienced in “MS and pregnancy” recommendations as neurologists. The French National Perinatal Survey (32, 33) also found an increase in GPs as main care providers during pregnancy (from 4.7% in 2010 to 6.5% in 2016).

Regardless of the professional chosen for prenatal healthcare (GP or gynecologist), the recommendations on folic acid and vitamin D supplementation (34, 35) apply to all women, including those with MS. Here, 17.7% of women had at least one reimbursement for a folic acid prescription before pregnancy start. This number is similar to what is found in the general population by the 2010 French National Perinatal Survey (36) (14.8%, 95% CI [14.2–15.4]) but slightly lower than in the 2016 Survey (33) (23.2% of women). Moreover, for 49.8% of pregnancies, at least one vitamin D reimbursement was recorded. It is important to remember that high-dose vitamin D can prevent the creation of new lesions because it “delays immune hyperactivity” (37). Some deliveries are therefore not directly related to pregnancy. In our case, 52.9% of women received a vitamin D delivery outside the pregnancy period. The frequency of cesarean section was slightly lower in the present MS population than in the French population (32) (15.8 vs. 20.4%).

Regarding the MS follow-up, in 26.9% of pregnancies, women did not have any visit to a neurologist during pregnancy and within the 12 months after pregnancy. This finding is surprising because this consultation is useful to evaluate the postpartum period and to determine whether and when a DMT should be initiated (38, 39) or whether breastfeeding is possible. However, it is also possible to prepare for the postpartum period during the prepartum period (40). In 45.9% of pregnancies, women restarted DMT within 6 months after delivery (34.1% within 3 months and 11.7% within 3–6 months of delivery). Interferon beta was the most delivered, followed by glatiramer acetate and then natalizumab, in agreement with the study period (2010–2015).

Our study has several strengths and limitations. First, the French National Health Insurance Database (SNDS) allowed including a large sample of women with MS and live births in the whole of France between 2010 and 2015 (6 years). The French National Health Insurance Database does not allow distinguishing relapsing MS from progressive MS as no clinical data are available. For this reason, we were unable to run the analyses according to the type of MS. Although the SNDS database may contain some errors due to unreported information about visits and laboratory tests, it allowed excluding selection and information bias. Inclusion of live births only allowed comparing pregnancies and excluding premature pregnancy interruptions, whatever the reasons may be. We cannot exclude few mistakes in data collection that may have had a marginal impact on the classification of women. The use of gynecological healthcare resources during pre-pregnancy periods was not studied here. As no index on the follow-up of recommendations to pregnancy-related healthcare existed in France, we used two indices validated in the United States to construct a robust index adapted to the French recommendations. Based on the agreement obtained to access the data, we focused on people with MS and were not able to add a control group without MS.

To conclude, the present study extends the knowledge on the subject and constitutes an important step for the better controlling of pregnancy follow-up in women with MS and for minimizing the risks related to care underuse. We think that our findings may have direct implications in the management of women with MS and may be helpful to raise awareness among healthcare providers about the risk of inadequate pregnancy follow-up in this group. Particularly, it is necessary to better guide women with MS on specific health insurance coverage (CMU and schemes for agricultural and self-employed workers) because inadequate pregnancy follow-up could be linked to economic problems (despite the French universal health coverage system). It is important that women with MS manage their pregnancies as they wish and with the same support available to the general population. Moreover, a regular follow-up with a neurologist is also recommended by the French MS society (41) for women with MS during conception, pregnancy, and postpartum and is of particular importance regarding therapeutic management during this period.

The data analyzed in this study is subject to the following licenses/restrictions: According to the French data protection regulations, the authors cannot publicly release data from the French National Health Insurance database (SNDS). However, a request for data reuse may be made and would require prior approval by the French regulatory authorities. Requests to access these datasets should be directed to SNDS, https://www.snds.gouv.fr/SNDS/Processus-d-acces-aux-donnees.

EL played a major role in the acquisition of data and contributed to the study concept. MM organized the database, performed the statistical analysis, and drafted the manuscript. All authors contributed to the manuscript revision, and read and approved the submitted version.