Study of fetal DNA in serum and disease activity during pregnancy in women with inflammatory arthritis

During pregnancy, women with inflammatory arthritis usually experience disease improvement or even remission, while a disease flare regularly occurs within 3 to 4 months after delivery. A study featured in the July 2006 issue of Arthritis & Rheumatism sheds light on this widely reported yet little understood phenomenon.

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, researchers in Seattle, Washington, supported in part by a grant from the Washington Women's Foundation and by grants from the National Institutes of Health, set out to investigate whether changes in serum fetal DNA levels correlate with changes in arthritis activity during and after pregnancy. They conducted a study on 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 6 were classified as having juvenile idiopathic arthritis (JIA). Of the subjects, 24 had active disease in the 6 months prior to pregnancy, with one experiencing RA onset in her first trimester. 7 of the women were in their first pregnancy, 7 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. All pregnancies resulted in a single live birth.

Samples of peripheral venous blood were taken from all subjects, most 3 times or more during the course of pregnancy, as well as postpartum, within 3 months of delivery. 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 3 to 4 months after giving birth.

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. 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 4 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 2 - throughout pregnancy, especially in the third trimester, compared with those women who experienced arthritis improvement.

This 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. Yet, 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 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 causally related cannot be determined from these studies," notes researcher J. Lee Nelson, M.D. "If the former, further studies could generate new therapeutic strategies for RA."


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