Pregnant women taking oral corticosteroids for rheumatoid arthritis may be at increased risk of preterm birth, according to research published online Sept. 30 in.
A study of 528 pregnant women with rheumatoid arthritis enrolled in the MotherToBaby Pregnancy Studies found that those taking a daily dose of 10 mg or more of prednisone equivalent – representing a mean cumulative dose of 2,208.6 mg over the first 139 days of pregnancy – had 4.77-fold higher odds of preterm birth, compared with those not taking oral corticosteroids. Women on medium doses – with a mean cumulative dose of 883 mg – had 81% higher odds of preterm birth, while those on low cumulative doses of 264.9 mg showed a nonsignificant 38% increase in preterm birth risk.
Women who did not use oral corticosteroids before day 140 of pregnancy had a 2.2% risk of early preterm birth. Among women with low use of oral corticosteroids, the risk was 3.4%, among those with medium use the risk was 3.3%, but among those with high use the risk was 26.7%.
After day 140 of gestation, there was a nonsignificant 64% increase in the risk for preterm birth with any use of oral corticosteroids, compared with no use. But among women taking 10 mg or more of prednisone equivalent per day, the risk was 2.45-fold higher, whereas those taking under 10 mg showed no significant increase in risk.
“Systemic corticosteroid use has been associated with serious infection in pregnant women and serious and nonserious infection in individuals with autoimmune diseases, independent of other immunosuppressive medications, especially for doses of 10 mg of prednisone equivalent per day and greater,” wrote, a research investigator with HealthPartners Institute in Minneapolis, Minn., and coauthors.
Given that intrauterine infection is believed to contribute to preterm birth, some have suggested that the immunosuppressive effects of oral corticosteroids could be associated with an increased risk of preterm birth because of subclinical intra-amniotic infection, they wrote.
However, they noted that there was a lack of information on the effect of dose and timing of oral corticosteroids during pregnancy on the risk of preterm birth.
The authors acknowledged that dosage of oral corticosteroids during pregnancy was linked to disease activity, which was itself associated with preterm birth risk. They adjusted for self-assessed rheumatoid arthritis severity at enrollment, which was generally during the first trimester, and found that this did attenuate the association with preterm birth.
“Ideally, we would have measures of disease severity at the time of every medication start, stop, or dose change to account for time-varying confounding later in pregnancy,” they wrote.
The study did not find any effect of biologic or nonbiologic disease-modifying antirheumatic drugs, either before or after the first 140 days of gestation.
The authors also looked at pregnancy outcomes among women with inflammatory bowel disease and asthma who were taking corticosteroids for those conditions.
While noting that these estimates were “imprecise,” they did see the suggestion of an increase in preterm birth among women taking oral corticosteroids for asthma, especially when used in the first half of pregnancy. There was also a suggestion of increased preterm birth risk associated with high oral corticosteroid use for inflammatory bowel disease, but these estimates were unadjusted, they noted.
“Overall, IBD and asthma exploratory analyses align with the direction of the associations in the RA analysis despite limitations of precision and inability to adjust for IBD severity,” they wrote.
The conclusions to be drawn from the study are limited by its small size, the investigators noted, as well as a lack of information on the type of rheumatoid arthritis and longitudinal disease severity. They added that while the hypothesized mechanism of action linking oral corticosteroid use to preterm birth was subclinical intrauterine infection, they did not have access to placental pathology to confirm this.
The study was supported by the National Institutes of Health, and the MotherToBaby Pregnancy Studies are supported by research grants from a number of pharmaceutical companies. No other conflicts of interest were declared.