Women whose rheumatoid arthritis is carefully managed before and during pregnancy have a significantly lower risk of adverse pregnancy outcomes, including miscarriage or perinatal death, new research suggests.

Doctor and pregnant woman in consultation. zoranm/Getty Images

A study published in Arthritis Care & Research presents the outcomes of a retrospective, observational study examining health care data from 443 first pregnancies in women with RA and 6,097 women without the disease.

First author Alessandra Bortoluzzi, MD, PhD, from the Rheumatology Unit at the University of Ferrara (Italy) and coauthors looked at seven diagnostic, therapeutic, and follow-up health care quality indicators during the prepregnancy and perinatal period. They included having at least one blood test in the 18 months before conception and during pregnancy, preconception musculoskeletal imaging, no exposure or wash-out from teratogenic drugs, and no exposure to biologic drugs between conception and delivery or end of pregnancy.

An ideal clinical pathway included at least one element from each of the diagnostic, therapeutic, and prenatal follow-up quality indicators.

Overall, women with RA had a significantly higher rate of thyroid diseases, adverse pregnancy outcomes, and miscarriage or perinatal death when compared with controls. However, those who followed the ideal clinical pathway for management of their disease during pregnancy had a 40% lower odds of adverse pregnancy outcomes (odds ratio, 0.60; 95% confidence interval, 0.39-0.94) and a 60% lower odds of miscarriage or perinatal death (OR, 0.40; 95% CI, 0.24-0.69) in comparison with women with RA who were not managed to the same standard. The researchers adjusted both comparisons for age, Charlson comorbidity index, and thyroid diseases.

Women with RA who met diagnostic, therapeutic, and prenatal follow-up quality indicators showed no significant differences from the general population in terms of the risk of adverse pregnancy outcomes, miscarriage, or perinatal death after adjusting for hypertension in addition to the same variables as before.

When researchers looked at some of the individual health care quality indicators, they found that testing for antiphospholipid (aPL) antibodies within 18 months of conception or pregnancy was associated with a 44% lower rate of adverse pregnancy outcomes. Similarly, antinuclear antibody or anti–extractable nuclear antigen antibody testing was associated with 36% lower odds of adverse pregnancy outcomes.

Dr. Bortoluzzi and her coauthors wrote that their findings pointed to the value of testing for aPL antibodies in women with RA who wish to get pregnant.

“In fact, despite the absence of formal recommendation or validated health care quality indicators focused on stratification of preconceptional obstetric risk in patients with RA, we started from the basic and universally accepted assumption that aPL antibodies are pathogenic autoantibodies and therefore recognized risk factors for adverse pregnancy outcome,” they wrote.

Women with RA who had either no exposure to methotrexate or leflunomide or who had a washout period from 6 months prior to conception had 72% lower odds of adverse pregnancy outcomes.

The authors also looked at the effects of drugs such as aspirin, glucocorticoids, and low-molecular-weight heparin that are used during pregnancy. They found that the relative risk of adverse pregnancy outcomes was 40% higher in women with RA who were taking glucocorticoids, compared with those with the disease but not taking that type of medication. However, low-molecular-weight heparin use was associated with an 80% lower relative risk of miscarriage or perinatal death in comparison with those not taking it. Researchers saw no significant effects of aspirin or conventional synthetic disease-modifying antirheumatic drugs on either adverse pregnancy outcomes or the risk of miscarriage or perinatal death.

“This reinforces the importance of adjustment of therapy for RA before conception and throughout pregnancy, because medication use could affect pregnancy course not only influencing maternal disease activity but also the gestational outcome,” the authors wrote. “Although this is a study conducted on administrative data, we can hypothesize that exposure to therapy represents a marker of high RA disease activity and severity. In our setting, it is possible that, the more active the disease, the greater the probability of being included in the ideal clinical pathway, but in any case, this resulted in a lower odds ratio of adverse pregnancy outcome and miscarriage/perinatal death.”

The study was supported by the Italian Society for Rheumatology. No conflicts of interest were declared.

SOURCE: Bortoluzzi A et al. Arthritis Care Res. 2020 Jan 8. doi: 10.1002/ACR.24116.