It's a common occurrence: Inflammatory arthritis sufferers often experience a temporary break from pain during pregnancy. Yet little is known about the mechanisms involved in this clinically important phenomenon. A study led by Dr. Zhen Yan, a postdoctoral research fellow in Dr. Lee Nelson's lab, sheds light on the subject in the July 2006 issue of Arthritis & Rheumatism.
Prenatal diagnostic tests have recently established that fetal cells and cell-free DNA routinely flow into the mother's bloodstream during normal pregnancy. On the strength of these findings, Yan and colleagues from the Center's Clinical Research Division set out to investigate whether changes in serum fetal DNA levels correlate with changes in arthritis activity during and after pregnancy.
The researchers studied 25 pregnant women with inflammatory arthritis. Ranging in age from 23 to 43, 17 of the women were classified as having adult-onset rheumatoid arthritis (RA) and six were classified as having juvenile idiopathic arthritis (JIA). In the six months prior to pregnancy, 24 had active disease, and one experienced RA onset in her first trimester. Seven of the women were in their first pregnancy, seven were in their second pregnancy and 11 had been pregnant at least twice before. None of the patients took a disease-modifying antirheumatic drug during pregnancy, and patients taking prednisone took no more than 10 milligrams per day, with one exception. Each pregnancy resulted in a single live birth.
Samples of peripheral venous blood were taken from all of the subjects — three times or more during the course of pregnancy, for most, as well as during the first few months postpartum. Levels of cell-free fetal DNA were measured using real-time quantitative polymerase-chain reaction targeting the fetus-specific genetic markers. Women were evaluated for changes in disease activity in each trimester and three to four months after giving birth.
Remission and recurrence
During pregnancy, 21 of the 25 women — 79 percent of the RA patients and 100 percent of the JIA patients — experienced improvement or remission of inflammatory arthritis symptoms. Among these women, 62 percent showed signs of disease improvement in the first trimester. Once improvement occurred, it was sustained or progressively increased until delivery. Among these women, levels of serum fetal DNA also progressively rose throughout pregnancy. As fetal DNA quantities doubled, the likelihood of arthritis improvement increased 1.2 fold. However, the improvement, even remission from arthritis, was short-lived. By the third or fourth month after delivery, disease recurrence was observed in 90 percent of these patients, coinciding with a drop of serum fetal DNA to very low or undetectable levels.
The remaining four women, including the one who had RA onset during the first trimester, did not experience significant reduction of disease symptoms during or after pregnancy. For the women with active disease, serum levels of fetal DNA were dramatically lower — and even undetectable in two — throughout pregnancy, especially in the third trimester, compared with those women who experienced arthritis improvement.
The study, the first to focus on fetal DNA in women with RA during pregnancy, found a significant inverse correlation between arthritis activity and serum fetal DNA concentration over the course of pregnancy and postpartum. Researchers acknowledge the study's limitations, including its small size and inability to determine whether serum fetal DNA has any direct biologic effect on inflammatory arthritis or any therapeutic value.
"Whether the dynamic changes in fetal DNA reflect the potential for immune modulation of maternal arthritis, are a result of disease activity changes or are not casually related cannot be determined from these studies," Nelson said. "If the former, further studies could generate new therapeutic strategies for RA."
Funding for the study came from grants from the Washington Women's Foundation and the National Institutes of Health. Study co-authors include Drs. Kristina Adams and Katherine Guthrie of the Clinical Research Division; Nathalie Lambert, INSERM, Marseille, France; and Dr. Monika Ostensen, University Hospital in Bern, Switzerland.