Pregnancy May Offer Protective Benefits in Multiple Sclerosis, Study Suggests

In a sensitivity analysis that excluded women with evidence of possible demyelinating events before MS diagnosis, the associations between pregnancy-related ICD-10 code recording and disease risk were even more pronounced.

After identifying several less pregnancy-related International Classification of Diseases, 10th Revision (ICD-10) codes among women with multiple sclerosis (MS) than those without autoimmune disorders, results from a retrospective case-control study showed that pregnancies were associated with a lower risk of the disease and may offer protective benefits.

Lead author Christiane Gasperi, MD, physician and researcher, TUM School of Medicine, Technical University of Munich, and colleagues aimed to determine the relationships between pregnancies and gynecological diagnoses with MS risk by observing differences in gynecological ICD-10 code recording rates. The sample included women with MS (n = 5720), Crohn disease (n = 6280), or psoriasis (n = 40,555) and women without these autoimmune diseases (n = 26,729) in the 5 years before diagnosis.

In a previous study, investigators observed higher recording rates for 43 ICD-10 codes for patients with MS compared with controls in the 5 years before diagnosis. In the new analysis, 28 ICD-10 codes were recorded less frequently during the same time period, whereas no ICD-10 codes appeared to be more frequent. Eighteen of these 28 ICD-10 codes were related to pregnancies, of which Supervision of normal pregnancy (Z34) and Supervision of high-risk pregnancy (Z35) showed the strongest negative relations to MS.

"With an increase of the maternal age at first childbirth and decreasing birth rates in the last decades, a protective effect of pregnancies on disease risk could, at least in part, explain the increasing gender gap in MS incidence,” Gasperi et al concluded.

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Other less frequently recorded ICD-10 codes in women with MS included Encounter for contraceptive management (Z30) and Encounter for procreative management (Z31). Three ICD-10 codes associated with disorders of the menstrual cycle as well as Female infertility (N97) were also associated with lower ORs of MS. Four other gynecological diagnoses—Other inflammation of vagina and vulva (N76), Noninflammatory disorders of ovary, fallopian tube and broad ligament (N83), Erosion and ectropion of cervix uteri (N86), and Other noninflammatory disorders of vagina (N89)—were recorded less frequently in the MS cohort.

In the same analysis adjusting for pregnancy occurrences, all 10 gynecological ICD-10 codes unrelated to pregnancies were still significantly associated with lower odds ratios (ORs) of MS; however, the associations were less pronounced.

A separate sensitivity analysis excluding all women with ICD-10 codes suggestive of possible demyelinating events before diagnosis was performed to assess the possibility of a reverse causality between MS risk and pregnancies or gynecological disorders. Here, all ICD-10 codes with significant results in the primary analysis, except for 2 pregnancy-related ICD-10 codes, were still negatively associated with MS. When investigating a dose effect of pregnancies on MS diagnosis, investigators found lower ORs for women who had multiple pregnancies, although these differences were not significant.

"We also observed previously not reported associations of gynecological disorders unrelated to pregnancies with lower MS risk. Whether these observations are explained by the observed lower gynecologist encounters rates in women with MS in the years before first diagnosis or whether they represent truly independent associations of gynecological disorders and MS risk, needs further investigation. The observed associations might, to some degree, be shared by different autoimmune disorders," the study investigators wrote.

In the 5 years before diagnosis, women with MS had an average of 1.66 gynecologist encounters per year compared with 1.91 encounters among those without autoimmune disorders. This difference was even more pronounced in the sensitivity analysis, demonstrated by 1.21 and 1.75 gynecological visits, respectively. In a regression analysis, the number of gynecological visits were negatively associated with MS diagnosis (OR, 0.79; 95% CI, 0.77-0.81; P = 2.12x10-51). Women with MS also had fewer gynecologist encounters as compared to women with CD or psoriasis (1.66 vs 1.77 and 1.69 per person and years, respectively).

REFERENCE
1. Gasperi C, Hapfelmeier A, Schneider A, et al. Association of pregnancies with risk of multiple sclerosis. Multiple Sclerosis Journal. Published online March 18, 2022. doi:10.1177/13524585221080542.