CHICAGO — Women who have low blood levels of the peptide kisspeptin during their first trimester of pregnancy are significantly more likely to miscarry, a new study shows.

"Even in women with no symptoms of miscarriage, a single blood test for kisspeptin more accurately predicted the risk of miscarriage compared with [human chorionic gonadotropin] hCG levels that were measured at the same time," said lead investigator Ali Abbara, MBBS, a clinical research fellow at Imperial College London, United Kingdom.

Speaking at a press conference here at ICE/ENDO 2014, where he presented the research, Dr. Abbara said their study is the first to show that a plasma kisspeptin test early in pregnancy can identify the risk for miscarriage before 26 weeks' gestation in asymptomatic women.

Asked by Medscape Medical News to comment on the work, Ann Nardulli, PhD, a researcher at the University of Illinois Urbana-Champaign, said: "It looks like we may have another marker to tell us whether there's a healthy pregnancy."

It looks like we may have another marker to tell us whether there's a healthy pregnancy.

Currently, serial measurements of hCG are used to determine whether a pregnancy is progressing normally, said Dr. Nardulli, who moderated the press conference but did not participate in the study.

Kisspeptin: A Biomarker for Pregnancy Complications?

Miscarriage affects 1 in 5 pregnancies, and most occur early in pregnancy, often accompanied by symptoms of abnormal vaginal bleeding or pain.

Kisspeptin, which is critical for reproduction, is found in the placenta and is believed to play an important role in placental development, according to Dr. Abbara. During a healthy pregnancy, kisspeptin levels increase up to several thousand times those of women who are not pregnant, he said.

Because miscarriage is commonly associated with an abnormal placenta, Dr. Abbara and colleagues decided to look at levels of this peptide among pregnant women attending their first routine antenatal visit at Imperial College's obstetric center between 2010 and 2012.

They recruited 993 women who had no symptoms of miscarriage. Their mean gestation was 11.2 weeks. A total of 949 women with a single pregnancy completed the observational study ― the women provided a single blood sample, and the researchers measured serum hCG and used radioimmunoassay to determine plasma kisspeptin levels. Pregnancy outcomes were recorded prospectively.

Of the study participants, 50 women later miscarried and 899 did not, Dr. Abbara reported.

Compared with the women who did not miscarry, women who had a miscarriage had 60.4% lower kisspeptin levels (corrected for gestational age) and 36.1% lower hCG levels, a significant difference (P < .001 each). And kisspeptin level predicted miscarriage better than hCG did, with a receiver operating characteristic area under the curve of 0.899 vs 0.775 for hCG.

A kisspeptin level greater than 1306 pmol/L was strongly associated with a reduced risk for miscarriage, Dr. Abbara said. Even after adjustment for patient age, body mass index, gestational age, blood pressure, and smoking status, the odds ratio was 0.13 (P < .0001).

Among the 50 women whose pregnancy resulted in miscarriage, this occurred less than 8 days after the blood tests in 16 women and at 10 days or more after testing in 34 women. Those who miscarried earlier had lower levels of kisspeptin than did women whose miscarriage occurred later in pregnancy, Dr. Abbara told Medscape Medical News.

Test Still in Research Stage; Further Work Needed

For kisspeptin measurement, Dr. Abbara said they used an in-house radioimmunoassay, which "we think is better than the commercially available kits."

However, he said the setup costs for this test are high.

"This [test] is still at the research stage," Dr. Abbara said. "Future work will assess whether enhanced surveillance of women [with low blood kisspeptin levels] would make it possible to intervene to prevent miscarriage."

He told Medscape Medical News that kisspeptin levels may also prove to be an indicator for other pregnancy complications, such as preeclampsia and intrauterine growth restriction.

Dr. Nardulli called the study results interesting. "The levels of kisspeptin stay higher for longer [in pregnancy] than hCG, so kisspeptin may be quite sensitive," she said.

This study was funded by the Medical Research Council UK, the United Kingdom's National Institute for Health Research, and the Wellcome Trust in London. Dr. Abbara and Dr. Nardulli have disclosed no relevant financial relationships.

Joint Meeting of the International Society of Endocrinology and the Endocrine Society: ICE/ENDO 2014;  June 21, 2014. Abstract OR04-2.



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