SCIENTISTS ON TRAIL OF MISCARRIAGE MYSTERY

By Luma Muhtadie Globe and Mail 
Update AT 8:43 PM EST Thursday, Jan. 8, 2004

Pregnant women who have low concentrations of an important protein early in their pregnancies may be at greater risk of miscarriage, a new study suggests.

A group of Australian scientists who measured a protein called Macrophage Inhibitory Cytokine 1, or MIC 1, in blood taken from a group of women during the first trimester of pregnancy discovered the women who miscarried had lower concentrations of MIC 1 than those who didn't. Concentrations of the protein were a third lower in 100 women who went on to miscarry than in a control group of 200 women who delivered normally. In most of the samples taken in women from six- to 13-months pregnant, low MIC 1 concentrations preceded miscarriage by several weeks.

MIC 1 is found in several tissues, including macrophages, or white blood cells, where it plays a role in the body’s response to infection. The protein is found in high concentrations at the interface between mother and fetus during pregnancy.

"It is produced by cells on both sides that are in contact with each other very early on in pregnancy," Dr. Euan Wallace, one of the researchers. "Based on where MIC 1 is, it may have roles in regulating the dialogue between the mother and the fetus very early on," Dr. Wallace said. "We think its job is to control the way the placenta develops and invades into the lining of the uterus."

On this basis, "it is tempting to speculate that changed production of MIC 1 in the placenta is part of the mechanism initiating spontaneous pregnancy loss," Stephen Tong, Dr. Wallace’s colleague and the lead researcher in the study writes in this week’s issue of The Lancet:

While between 10 and 15 per cent of pregnancies result in miscarriage, there are still no tests to identify at-risk women and no treatments for prevention. But proving a causal link between low MIC 1 concentrations and miscarriage could lead to the possibility of screening in the future. It could also lead to the use of MIC 1, or its synthetic analogues, in preventative treatments.

The majority of miscarriages are the inevitable consequence of improper development and little can be done to prevent them, Dr. Wallace said.

Still, he says, "having a test of the reliability of a pregnancy just opens so many new doors," including identifying women with potentially viable pregnancies for treatment.

The crucial question remains whether low concentrations of the protein in women who miscarry is an epiphenomenon or an important part of the pathological mechanism that causes miscarriage, Dr. Galit Sarig and Dr. Benjamin Brenner of the Rambam Medical Centre in Haifa, Israel, point out in an accompanying commentary in The Lancet.