APRIL 2008
VOLUME 5 NO. 4

ADVANCES in MEDICINE

Test predicts 94% of miscarriages

High levels of endocannabinoid spell trouble for pregnancy, says study


A team of British scientists have figured out a way to predict miscarriage in pregnant women — with 94% accuracy. The striking early results of their study are published in the March 12 issue of JAMA.

"The aim of this study was to investigate the mechanisms involved in unexplained miscarriages and how these could be modulated to improve outcomes," explains lead author Dr Justin Konje, head of the clinical division of obstetrics and gynecology at the University of Leicester, via email to NRM. But finding that one little molecule can predict miscarriage so well opened up a whole other avenue of study, namely the development of a miscarriage test.

Up to 25% of all pregnancies end in miscarriages, according to some Canadian estimates. Some diseases, like diabetes, or lifestyle habits such as smoking raise the risk. But for many women, there's no explanation for their miscarriages.

The key molecule to look for happens to be an endogenous "cannabis" called anandamide. "Anandamide is crucial to various stages in pregnancy," says Dr Konje. It acts as a communicator between the embryo and the endometrium, ensuring that the embryo is developed enough for implantation and that the endometrium is prepped to receive it, he adds.

STRONG PREDICTOR
The researchers gleaned that information partly from animal studies and decided to look at anandamide levels in 45 pregnant women who were at risk of miscarriage. These are women who presented with bleeding in early pregnancy but still had a viable baby. They tested the women's blood for anandamide and found that the women who miscarried had twice as much of the molecule than those who went on to have a healthy, full-term pregnancy — 3.47 nM versus 1.7 nM.

"The pilot data we've generated has a 100% negative predictive value for miscarriage, so any woman with a low level can be reassured that she will have a live birth," says Dr Konje. And that's even if she has some subsequent bleeding. Armed with this knowledge, the need for repeat scans and extra visits to the doctor can be minimized, which will cut the overall healthcare cost, he points out.

As for the high level women, the anandamide test pinpointed the doomed pregnancies with 94% accuracy. Although two of the high anandamide women went on to have a live birth, one of them developed pre-eclampsia and delivered at 33 weeks.

"For some women, knowing that the pregnancy is destined to fail may help them come to terms with the eventual outcome," Dr Konje suggests. And though science has no tools now to alter that outcome, Dr Konje and his team are starting to look at how anandamide levels can be changed to favour a live delivery — but he's keeping quiet until more data is available.

THE ITALIAN JOB
The British team wasn't the first to figure out a connection between anandamide and miscarriages. An April 2000 Lancet study by Italian researchers found that women who had low levels of fatty acid amide hydrolase (FAAH) — an enzyme that breaks down anandamide — went on to miscarry.

But no predictor test came of that study, partly because of the difficulties in measuring FAAH levels, speculates Dr Konje. "The enzyme was quantified from peripheral mononuclear blood cells. The process is laborious and will be difficult to apply in clinical practice," he says.

Dr Konje and colleagues decided to go straight to the source: anandamide. Right now, isolating it from blood samples can take up to 12 hours, but the team hopes to develop a test that will spit out results in 10 to 15 minutes. "The next step is to confirm the observations [via a larger study]," says Dr Konje. Once that's done, the plan is to investigate the best way to test within the next three years.

 

 

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