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A protein found in the placenta is present in much smaller amounts in women who suffer miscarriages than in those who go on to have a normal healthy baby, Australian scientists have found.
The role of the protein is to control the immune response between the woman and her baby, which carries genes from its father and would therefore normally be identified as foreign by the mother’s immune system. If this happened, the baby would be rejected by the immune system and pregnancy could not continue, so there are systems that turn down the immune response during pregnancy. This is the reason why women with some auto-immune diseases such as arthritis may suffer relief from symptoms while they are pregnant.
The new finding, published in The Lancet by a team from Monash University, in Victoria, and the University of New South Wales, suggests that the relative lack of the protein, called macrophage inhibitory cytokine 1 (MIC 1), could be the cause of many unexplained miscarriages.
Many pregnancies end in miscarriage, usually before the woman realises she is pregnant. As many as half of pregnancies miscarry before the fertilised egg is implanted in the wall of the womb. Others occur after implantation but before the pregnancy is detected.
The Australian team looked at miscarriages only after pregnancy had been clinically confirmed, from seven weeks of gestation onwards. After this time, they say, miscarriage is much less common but still occurs in 10-15 per cent of all pregnancies. Others put the figures higher, at 25 per cent.
Three years ago three of the authors of the latest study published evidence that MIC 1 — identified in 1997 — is present in high levels in the placenta, blood and amniotic fluid of pregnant women. It is a cytokine, one of a class of growth factors that control the immune response. They suggested then that its role might be to suppress the inflammatory process triggered in the mother’s body by the presence of foreign tissue: the baby.
In the latest study a team led by Stephen Tong and Euan Wallace measured levels of MIC 1 in blood samples taken from 100 women who had miscarriages and 200 who completed their pregnancies. These were routine samples, taken at 7 to 13 weeks of pregnancy.
They found that levels in the women who miscarried were less than a third of those in women who completed their pregnancies. They also show that these low levels can be detected several weeks before the miscarriage occurs.
This suggests that levels of MIC 1 might be measured and used to assess the risk of miscarriage, especially in women who have already suffered one. In such cases, the risk of a second miscarriage is about 20 per cent.
The team concludes: “It is tempting to speculate that changed production of MIC 1 in the placenta is part of the mechanism initiating spontaneous pregnancy loss. If a causal link between low MIC 1 and miscarriage is confirmed, then MIC 1, or its synthetic analogues, might be useful in prevention of miscarriage.”
In a commentary in The Lancet, Garit Sarig and Benjamin Brenner, of Rambam Medical Centre, Haifa, say the crucial question is whether a lowered level of MIC 1 is the mechanism that causes miscarriage or is simply an event that happens at the same time.
They add that if the results can be confirmed, the way is open to develop novel therapies to prevent pregnancy loss.
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