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Rheumatic diseases associated with reproductive issues and adverse pregnancy outcomes, study finds

Rheumatic diseases can have a wide-ranging impact on men’s and women’s reproductive health, with effects comparable to other immune-mediated conditions, a Finnish study finds.

It was known that immune-mediated diseases (IMDs) could impair reproductive success and pregnancy outcomes, but systematic evaluations across diseases were lacking, Finnish, US and UK researchers wrote in the journal Rheumatology.

Using Finnish registry data comprising 5,339,804 citizens, individuals born from 1964 to 1984 and diagnosed with any one of 19 IMDs before age 30 (women) and 35 (men) were matched with 20 controls by birth year, sex and education.

Researchers then analysed the impact of rheumatic diseases compared with other IMDs on reproductive health measures, such as reproductive success and, for women, adverse maternal and perinatal outcomes.

‘Overall, we observed a high variability in the prevalence of childlessness and the number of children between diseases, as well as high variability in the impact of individual diseases,’ the researchers reported.

On average, women with IMDs experienced a higher prevalence of childlessness than controls (mean difference 3.6%), with women with Addison’s disease experiencing 23.9% more childlessness, those with juvenile idiopathic arthritis (JIA) 9.3% more childlessness, and those with vitamin B12 deficiency anaemia experiencing 8.6% more childlessness.

Men with an IMD also had a higher prevalence of childlessness than controls (mean difference 4.7%).

In men, most diseases made no difference to childlessness rates, but the three conditions found to have the most impact were myasthenia gravis (20.1% more childlessness), Addison’s disease (16.4% more childlessness), and vitamin B12 deficiency anaemia (13.7% more childlessness).

Several of the rheumatic diseases, particularly systemic lupus erythematosus (SLE), JIA, and seropositive rheumatoid arthritis, were associated with higher rates of childlessness and fewer children in both men and women.

‘IMDs such as psoriatic disease, asthma, alopecia areata, coeliac disease, and [immune thrombocytopenia] ITP, were not associated with an increased prevalence of childlessness or reduced number of children in either sex, although some had higher use of assisted reproductive technology,’ the researchers noted.

“Inflammatory bowel disease (IBD) was not, in contrast to the findings of previous studies, associated with an increased risk of childlessness, suggesting that treatment improvements may have positively impacted the reproductive health of these patients.’

In other findings, 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, [Sjögren‘s syndrome] SS, type 1 diabetes, and Addison’s disease showed >2-fold risks for some of these outcomes,’ the researchers reported.

‘Of the rheumatic diseases, SLE and SS conferred the largest risk increases on perinatal adverse event 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, coeliac disease, asthma, ITP and psoriasis.

Lead author Dr Anne Kerola, resident in rheumatology at the Helsinki University Hospital in Finland, said despite seeing an elevated risk for diverse childbearing problems in rheumatic and other IMDs, many of the complications were still fairly rare.

‘Family planning should actively be discussed between patients, both men and women, with rheumatic diseases and their healthcare providers,’ she said.

‘Pregnancies in women with rheumatic diseases are carefully followed up to tailor medications appropriately, which helps reduce risks.’

IMDs have also been linked to other adverse outcomes including an increased risk of atrial fibrillation (AF). In a prospective study published last year, Dutch researchers found there were elevated risks of AF for those with several autoimmune diseases including Crohn’s disease (HR = 1.23), ulcerative colitis (HR = 1.17), rheumatoid arthritis (HR = 1.39), SLE (HR = 1.82) and systemic sclerosis (HR = 2.32).