Rheumatic, Immune-Mediated Diseases Increase Risk of Childbearing Problems, Adverse Pregnancy Outcomes

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An analysis of data from more than 5 million people suggests rheumatic and immune-mediated diseases were associated with increased rates of childlessness and elevated risk of adverse pregnancy outcomes.

An analysis of data from more than 5.3 million citizens in Finland provides new insight into how the presence of inflammatory rheumatic disease and immune-mediated diseases could contribute to difficulties in childbearing.

A deep dive into data from all patients born in Finland from 1964 through 1984, the results of the study provide evidence of increased prevalence of childlessness and adverse pregnancy outcomes among those with rheumatic or immune-mediated diseases

“Despite seeing an elevated risk for diverse childbearing problems in rheumatic and other immune-mediated diseases, many of the complications are still fairly rare,” said lead investigator Anne Kerola, MD, PhD, a resident in rheuamtology at the University of Helsinki.2 “Family planning should actively be discussed between patients, both men and women, with rheumatic diseases and their healthcare providers. Pregnancies in women with rheumatic diseases are carefully followed up to tailor medications appropriately, which helps reduce risks.”

Citing an interest in learning more about the influence of rheumatic and immune-mediated diseases on reproductive success and pregnancy outcomes, Kerola and colleagues at the University of Helsinki designed the current research endeavor as an analysis of data from within the FinRegistry. A nationwide registry, the database provided investigators with information related to a cohort of 5,339,804 individuals alive on January 1, 2010, for inclusion in their study.1

A total of 19 immune-mediated diseases were identified for inclusion in the study. These included, but were not limited to, juvenile idiopathic arthritis, psoriatic arthritis, rheumatoid arthritis (both seropositive and seronegative), type 1 diabetes, asthma, multiple sclerosis, ulcerative colitis, and vitamin B12 deficiency anemia. For the purpose of analysis, reproductive years were defined as before 35 years of age for men and before 30 years for women. For each case identified, protocol dictated investigators identify 20 sex-, birth year-, and education level-matched controls.1

Among the 5,339,804 individuals born in Finland between 1964 and 1984, 7.9% of the women and 7.8% of the men had an autoimmune disease diagnosed before or during reproductive years. Among women, the case count ranged from 147 in myasthenia gravis to 21,878 in asthma. Among men, the case count ranged from 65 in myasthenia graves to 28,441 in asthma.1

Upon analysis, results pointed to elevated variability in prevalence of childlessness and the number of children between diseases. Overall, women with immune-mediated disease experienced a greater prevalence of childlessness than controls, with a mean difference of 3.6%. The greatest differences were observed for Addison’s disease (23.9% more childlessness), juvenile idiopathic arthritis (9.3%), and vitamin B12 deficiency anemia (8.6%). Among men, rheumatic conditions also had a greater prevalence of childlessness than controls (mean difference, 4.7%), but most diseases showed no difference. The greatest differences in prevalence of childlessness among men were observed for myasthenia gravis (20.1% more childlessness), Addison’s disease (16.4%), and vitamin B12 deficiency anemia (13.7%).1

When estimating associations with adverse outcomes, 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 multiple immune-mediated diseases. Investigators called specific attention to the increased risk observed with systemic lupus erythematosus, systemic sclerosis, type 1 diabetes, and Addison’s disease, which were associated with a more than doubling in risk of some of these outcomes.1

Investigators highlighted multiple important limitations to consider within their study. These included an ability to account for disease-specific factors, using an ever-never approach for pregnancy outcomes, and the age criteria used in case definition may have results in pregnancies occurring prior to diagnosis. Investigators also pointed out their hope the results be viewed as exploratory.1

“Considering the widespread impact of rheumatic diseases on reproductive health, our results emphasize the recommendation to discuss family planning early and often in women of reproductive age who have rheumatic diseases, and may aid in forming recommendations for pregnancy monitoring in women with rheumatic diseases,” investigators wrote. “Future research is warranted on male reproductive health in [immune-mediated diseases], and determinants and prevention of adverse pregnancy outcomes in each [immune-mediated disease].”


Kerola AM, Palomäki A, Laivuori H, et al. Patterns of reproductive health in inflammatory rheumatic diseases and other immune-mediated diseases: a nationwide registry study. Rheumatology (Oxford). Published online March 20, 2024. doi:10.1093/rheumatology/keae122

Rheumatic diseases associated with childbearing problems. EurekAlert! March 20, 2024. Accessed March 20, 2024.