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Fertility & Pregnancy Channel
Reported July 12, 2012

Antibody Causes Adverse Pregnancy Outcomes

(Ivanhoe Newswire) – A new study shows that women who have a certain kind of antibody that interferes with blood vessel function are at risk for adverse pregnancy outcomes, and other antibodies in the same family that were previously thought to cause pregnancy complications do not actually put women at risk.

Many doctors may be doling out unnecessary treatment to some pregnant women who have antiphospholipid antibodies (aPLs) with anticoagulants, like expensive heparin injections which could cause bleeding and bone loss.

"This paper identifies people who are at risk for pregnancy loss and, more importantly, those who are not at risk and who therefore do not need to be treated," Michael Lockshin, M.D., director, Barbara Volcker Center for Women and Rheumatic Disease, and co-director, Mary Kirkland Center for Lupus Research at Hospital for Special Surgery (HSS), New York City, and lead author of the study, was quoted as saying.

aPLs interfere with phospholipids, a fat found in all living cells and cell membranes, like blood cells and the lining of blood vessels. Patients who have these antibodies are at risk for blood clots, stroke, and pregnancy complications, though some patients with these antibodies can be completely healthy. "Phospholipids are highly exposed in the placenta, and as a result antiphospholipid antibodies concentrate there," Jane Salmon, M.D., the study's senior author and Collette Kean Research Chair and co-director, Mary Kirkland Center for Lupus Research at HSS, was quoted as sayin. "When antibodies are deposited in a person's tissues, inflammation is initiated leading to organ damage." This is a mechanism for pregnancy complications.

Women that experience recurrent pregnancy loss are usually tested for the presence of aPLs, and up to 15% are positive. Most patients who test positive are treated with anticoagulants. There are currently no standards about which aPLs doctors test for to assess risk (there are three main ones) and interlaboratory consistency of results is poor.

The new study is the first clinical research publication of the PROMISSE study, an ongoing multicenter, prospective clinical trial that compares the pregnancies of women with aPL, lupus, both aPL and lupus, and healthy controls. Between 20% and 35% of patients with lupus and aPL have pregnancy complications and the study is attempting to identify the patients who are at risk.

"The identification of biomarkers that identify patients at high risk will allow us to select a subset of patients who we can consider in an interventional trial," Dr. Salmon, the principal investigator of PROMISSE, was quoted as saying. All aPL tests were sent to core laboratories, eliminating interlaboratory variability.

The current analysis looked at 144 patients who had aPLs, of whom 28 had adverse pregnancy outcomes. The control group consisted of 159 healthy pregnant women and was tested parallel to the group with aPLs. Women in the control group had no known illness, no prior fetal loss, no more than one miscarriage and at least one successful pregnancy.

The study analyzed the association between adverse pregnancy outcome and the presence of three different aPLs: lupus anticoagulant [LAC], anticardiolipin antibody [aCL] and antibody to ß2 glycoprotein I. Researchers defined an adverse pregnancy outcome as otherwise unexplained fetal death after 12 weeks, neonatal death prior to discharge that was associated with complications of prematurity, preterm delivery prior to 34 weeks because of gestational hypertension, preeclampsia or placental insufficiency, and birthing a child that was small for its gestational age.

It was found that LAC was the strongest predictor of an adverse pregnancy outcome; 39% of patients with LAC had an adverse outcome compared to 3% who did not have LAC. 8% of women with aCL, but not LAC, suffered an adverse outcome. Other aPLs did not increase risk. "Lupus anticoagulant is the most important predictor of risk and high titer anticardiolipin antibodies alone don't provide substantial risk," Dr. Salmon was quoted as saying. Before the study, physicians considered aCL as a strong predictor of risk.

Anticoagulant treatments are currently used for many women with aPLs, but identifying who to treat is not clear and this treatment is often ineffective. "Although many patients with aPLs are treated with heparin, pregnancy outcomes are still disappointing. We need better therapies," Dr. Salmon was quoted as saying. "This study will allow us to identify subsets of patients with the highest risk in whom to test new approaches and new drugs."

Dr. Salmon's mice studies with aPL have demonstrated that blocking inflammatory pathways can prevent miscarriages, growth restriction and preeclampsia. Further studies on PROMISSE patients and interventional trials will hopefully reveal whether this therapeutic approach will be effective in pregnant women with aPLs and/or lupus.

Source: Arthritis & Rheumatism, July 2012

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