Patterns of reproductive health in inflammatory rheumatic diseases and other immune-mediated diseases: a nationwide registry study

Abstract

Objectives: Rheumatic diseases may impair reproductive success and pregnancy outcomes, but systematic evaluations across diseases are lacking. We conducted a nationwide cohort study to examine the impact of rheumatic diseases on reproductive health measures, comparing the impacts with those of other immune-mediated diseases (IMDs).

Methods: Out of all of the 5 339 804 Finnish citizens, individuals born 1964-1984 and diagnosed with any of the 19 IMDs before age 30 (women) or 35 (men) were matched with 20 controls by birth year, sex, and education. We used data from nationwide health registers to study the impact of IMDs on reproductive health measures, such as reproductive success and, for women, ever having experienced adverse maternal and perinatal outcomes.

Results: Several of the rheumatic diseases, particularly SLE, JIA, and seropositive RA, were associated with higher rates of childlessness and fewer children. The risks for pre-eclampsia, newborns being small for gestational age, preterm delivery, non-elective Caesarean sections, and need of neonatal intensive care were increased in many IMDs. Particularly, SLE, SS, type 1 diabetes, and Addison's disease showed >2-fold risks for some of these outcomes. In most rheumatic diseases, moderate (1.1-1.5-fold) risk increases were observed for diverse adverse pregnancy outcomes, with similar effects in IBD, celiac disease, asthma, ITP, and psoriasis.

Conclusion: Rheumatic diseases have a broad impact on reproductive health, with effects comparable with that of several other IMDs. Of the rheumatic diseases, SLE and SS conferred the largest risk increases on perinatal adverse event outcomes.

Keywords: autoimmune diseases; inflammatory rheumatic diseases; male reproductive health; maternal health; reproductive health.

Graphical abstract

Figure 1.

Number of children and reproductive window. (A) Prevalence of childlessness in men and women. In the population, the prevalence was 21.3% in women and 30.7% in men. (B) Difference in the mean number of children by sex, and reproductive age range in women. For the reproductive age range, the bar represents mean age at first child to mean age at last child. For the reproductive age range, the population mean for age at first child was 27.4 years and for the last child 31.8 years. The whiskers represent 95% CIs. P-value categories: ***: <0.001, **: 0.001–0.01, *: 0.01–0.05. Detailed numbers and exact P-values for the plot are shown in Supplementary Table S3, available at Rheumatology online. The population datasets represent individuals born 1964–1984, in line with the study cohort

Figure 2.

Associations with maternal and perinatal outcomes. (A) Gestational diabetes, adjusted for BMI, and intrahepatic cholestasis of pregnancy. (B) Hypertensive disorders of pregnancy. (C) Child small for gestational age (weight below the 10th percentile for gestational age) at birth. (D) Preterm birth (≤37 ^0/7 weeks). (E) Elective and non-elective caesarean section. (F) Phototherapy and neonatal intensive care unit (ICU). Outcomes with no association (P > 0.05) are displayed with a hollow box, and results are shown for diseases with over 20 cases for the outcome. The outcomes are defined as ever having experienced the outcome, compared with individuals who have never had the outcome. Analyses on gestational diabetes were not performed for T1D. In panels A–C, in analyses for other IMDs than T1D the individuals with comorbid T1D were excluded. In panels D–F, analyses for IMDs other than T1D were adjusted for comorbid T1D. The detailed association results are shown in Supplementary Table S8, available at Rheumatology online. T1D: type 1 diabetes

Figure 3.

Prevalence of maternal and perinatal outcomes. Prevalences are shown for diseases with an association P-value below 0.05 in Fig. 2. The outcomes are defined as ever having experienced the outcome, compared with individuals who have never had the outcome. The detailed counts for the prevalences are in Supplementary Table S8, available at Rheumatology online