Among women with autoimmune diseases, the use of disease-modifying anti-rheumatic drugs (DMARDs) during pregnancy was associated with a slightly increased risk of preeclampsia, which may have reflected disease activity, researchers reported.
Compared with women who stopped taking DMARDs when they became pregnant, those with autoimmune disease who continued on the drugs had a nonsignificantly increased relative risk for preeclampsia of 2.29 (95% CI 0.81 to 6.44), according to Soko Setoguchi, MD, of Harvard Medical School in Boston, and colleagues.
But after excluding women using only antimalarial drugs, who were likely to have mild disease, there was no longer any increased risk for preeclampsia (RR 1.23, 95% CI 0.30 to 5.02), the researchers reported in the November Arthritis Care & Research.
This attenuation of risk when women with milder disease were excluded suggests "that the relationship between DMARD use and preeclampsia is likely due to underlying disease or severity," they wrote.
Pregnant women with some autoimmune diseases, particularly lupus and rheumatoid arthritis, are known to have an increased risk for preeclampsia, which is a serious complication that can have adverse consequences for both mother and baby.
But disease flares occurring during pregnancy also can be hazardous to both, so continuation of medications for disease control may be needed -- and may even be protective, according to Setoguchi and colleagues.
"It is possible that DMARDs may decrease the risk of preeclampsia by diminishing the maternal immune response to the placenta, which may play a role in the development of preeclampsia," they explained.
To explore this hypothesis, they examined the use of medications by women with autoimmune diseases during the first 20 weeks of pregnancy, which is the time frame that includes implantation and growth of the placenta.
Between 1997 and 2006, there were 306,831 pregnancies in British Columbia resulting in live births.
Among this cohort, 1,901 were women whose records indicated diagnoses of rheumatoid arthritis, systemic lupus erythematosus, psoriasis, inflammatory bowel disease, or multiple sclerosis.
A total of 414 of women with these autoimmune diseases had been given a prescription for a DMARD while pregnant.
The most commonly used DMARD was hydroxychloroquine, followed by chloroquine, azathioprine, and sulfasalazine; the mean duration of use was 6 weeks.
Other medications dispensed included corticosteroids in 0.8% and nonsteroidal anti-inflammatory drugs (NSAIDs) in 2.1%.
Many of the women taking corticosteroids or NSAIDs were using the drugs for reasons other than autoimmune disease, such as for osteoarthritis, the researchers noted.
Among women using DMARDs, the incidence of preeclampsia was 7.7%, while the incidence was 4.4% for women taking corticosteroids and 2.6% for NSAIDs.
When the researchers considered rates of preeclampsia according to the individual diagnoses, they found that only women with lupus had a significantly elevated risk:
- Systemic lupus erythematosus, RR 2.02 (95% CI 1.11 to 3.64)
- Rheumatoid arthritis/psoriasis, RR 1.26 (95% CI 0.87 to 1.81)
- Inflammatory bowel disease, RR 0.98 (95% CI 0.57 to 1.70)
- Multiple sclerosis, RR 1.51 (95% CI 0.67 to 3.40)
The finding that rheumatoid arthritis was associated with only a small increase in risk, contrary to previous estimates, may have reflected a lack of information in the database about disease severity, according to the researchers.
They noted that autoimmune diseases were likely to have been underreported in the medical files, and that those that were identified were likely to have been more severe cases.
"It is plausible that DMARDs may actually decrease the risk for preeclampsia among women with autoimmune disease by mitigating immune responses. Although our results did not show beneficial effects of DMARDs, a small beneficial effect cannot be ruled out," they observed.
"Future studies that evaluate the association between DMARDs and preeclampsia should consider interactions with autoimmune disease subtype and severity," the researchers wrote.
The study and researchers have been supported by the National Institutes of Health and the Agency for Healthcare Research and Quality.
The authors reported receiving fees and support from a variety of companies, including AstraZeneca, Novartis, Abbott, Amgen, Lilly, and GlaxoSmithKline.
- Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Arthritis Care & ResearchSource Reference: Palmsten K, et al "Use of disease-modifying antirheumatic drugs during pregnancy and risk of preeclampsia" Arthritis Care Res 2012; 64:1730-1738.