Biomarkers May Predict Miscarriage Likelihood

A combination of vaginal bleeding score and human chorionic gonadotropin levels may predict the possibility of miscarriage by up to 77%, and the possibility of ongoing pregnancy by 94%.

The "pregnancy viability index" could help physicians reassure women who present with threatened miscarriage that the pregnancy is likely to continue and prepare those who may face miscarriage. Additionally, the score might help channel medical interventions more appropriately, Dr. Kaltum Adam said at the annual meeting of the European Society of Human Reproduction and Embryology.

"It will enable us to provide targeted management and counseling for the affected women and reassure those who are likely to achieve a live birth," said Dr. Adam, an honorary clinical research fellow at St. Mary’s Hospital in Manchester, England.

Her prospective longitudinal study included 112 women who presented with threatened miscarriage at 6-10 weeks’ gestation and with a confirmed intrauterine pregnancy. They were followed for 5 weeks, during which time they completed daily charts of pain and vaginal bleeding; had a weekly ultrasound and physical exam; and contributed weekly blood samples that were analyzed for progesterone, human chorionic gonadotropin (hCG), hemoglobin, and other standard blood chemistry factors. Baseline screening also included maternal demographics, educational, and socioeconomic status. At the final visit, there was an ultrasound exam to confirm the pregnancy’s outcome.

Of the 112 women, 22 (20%) miscarried. Time of first vaginal bleeding to miscarriage was available for 20 women: 11 miscarried in the first 7 days, 15 within 14 days, and 18 within 21 days. All of the miscarriages occurred within 28 days of the first bleed.

Dr. Adam determined that six baseline biomarkers were significantly associated with miscarriage at the 20th percentile: history of subfertility, bleeding score of two on a five-point scale, gestational age of the fetus, fetal crown-rump length of 4 mm, and serum levels of progesterone and hCG (32 nmol/L and 1,500 iU/L, respectively).

"All of these had good positive predictive values, indicating that a pregnancy had a good chance of surviving," Dr. Adam said, "but the negative predictive values were not useful for clinical practice or research."

A multivariate regression analysis, however, did identify that a combination of baseline bleeding score (two on a five-point scale) and baseline hCG level (1,500 iU/L) exhibited excellent positive and negative predictive values (94% and 77%, respectively). The equation used for computing the pregnancy viability index was hCG level/bleeding score × 1.87 × 10, where the bleeding score odds ratio for miscarriage is 1.87.

"This research has, for the first time, offered us a tool to begin to attempt to rescue pregnancies threatening to miscarry when, currently, all we can do is fold our hands and hope for the best," Dr. Adam said.

Dr. Adam plans to carry out a validation study on at least 1,000 women in the near future.

The study was funded by the Central Manchester Foundation Trust Biomedical Research Center. Dr. Adam said she had no relevant financial disclosures.

A combination of vaginal bleeding score and human chorionic gonadotropin levels may predict the possibility of miscarriage by up to 77%, and the possibility of ongoing pregnancy by 94%.

The "pregnancy viability index" could help physicians reassure women who present with threatened miscarriage that the pregnancy is likely to continue and prepare those who may face miscarriage. Additionally, the score might help channel medical interventions more appropriately, Dr. Kaltum Adam said at the annual meeting of the European Society of Human Reproduction and Embryology.

"It will enable us to provide targeted management and counseling for the affected women and reassure those who are likely to achieve a live birth," said Dr. Adam, an honorary clinical research fellow at St. Mary’s Hospital in Manchester, England.

Her prospective longitudinal study included 112 women who presented with threatened miscarriage at 6-10 weeks’ gestation and with a confirmed intrauterine pregnancy. They were followed for 5 weeks, during which time they completed daily charts of pain and vaginal bleeding; had a weekly ultrasound and physical exam; and contributed weekly blood samples that were analyzed for progesterone, human chorionic gonadotropin (hCG), hemoglobin, and other standard blood chemistry factors. Baseline screening also included maternal demographics, educational, and socioeconomic status. At the final visit, there was an ultrasound exam to confirm the pregnancy’s outcome.

Of the 112 women, 22 (20%) miscarried. Time of first vaginal bleeding to miscarriage was available for 20 women: 11 miscarried in the first 7 days, 15 within 14 days, and 18 within 21 days. All of the miscarriages occurred within 28 days of the first bleed.

Dr. Adam determined that six baseline biomarkers were significantly associated with miscarriage at the 20th percentile: history of subfertility, bleeding score of two on a five-point scale, gestational age of the fetus, fetal crown-rump length of 4 mm, and serum levels of progesterone and hCG (32 nmol/L and 1,500 iU/L, respectively).

"All of these had good positive predictive values, indicating that a pregnancy had a good chance of surviving," Dr. Adam said, "but the negative predictive values were not useful for clinical practice or research."

A multivariate regression analysis, however, did identify that a combination of baseline bleeding score (two on a five-point scale) and baseline hCG level (1,500 iU/L) exhibited excellent positive and negative predictive values (94% and 77%, respectively). The equation used for computing the pregnancy viability index was hCG level/bleeding score × 1.87 × 10, where the bleeding score odds ratio for miscarriage is 1.87.

"This research has, for the first time, offered us a tool to begin to attempt to rescue pregnancies threatening to miscarry when, currently, all we can do is fold our hands and hope for the best," Dr. Adam said.

Dr. Adam plans to carry out a validation study on at least 1,000 women in the near future.

The study was funded by the Central Manchester Foundation Trust Biomedical Research Center. Dr. Adam said she had no relevant financial disclosures.

A combination of vaginal bleeding score and human chorionic gonadotropin levels may predict the possibility of miscarriage by up to 77%, and the possibility of ongoing pregnancy by 94%.

The "pregnancy viability index" could help physicians reassure women who present with threatened miscarriage that the pregnancy is likely to continue and prepare those who may face miscarriage. Additionally, the score might help channel medical interventions more appropriately, Dr. Kaltum Adam said at the annual meeting of the European Society of Human Reproduction and Embryology.

"It will enable us to provide targeted management and counseling for the affected women and reassure those who are likely to achieve a live birth," said Dr. Adam, an honorary clinical research fellow at St. Mary’s Hospital in Manchester, England.

Her prospective longitudinal study included 112 women who presented with threatened miscarriage at 6-10 weeks’ gestation and with a confirmed intrauterine pregnancy. They were followed for 5 weeks, during which time they completed daily charts of pain and vaginal bleeding; had a weekly ultrasound and physical exam; and contributed weekly blood samples that were analyzed for progesterone, human chorionic gonadotropin (hCG), hemoglobin, and other standard blood chemistry factors. Baseline screening also included maternal demographics, educational, and socioeconomic status. At the final visit, there was an ultrasound exam to confirm the pregnancy’s outcome.

Of the 112 women, 22 (20%) miscarried. Time of first vaginal bleeding to miscarriage was available for 20 women: 11 miscarried in the first 7 days, 15 within 14 days, and 18 within 21 days. All of the miscarriages occurred within 28 days of the first bleed.

Dr. Adam determined that six baseline biomarkers were significantly associated with miscarriage at the 20th percentile: history of subfertility, bleeding score of two on a five-point scale, gestational age of the fetus, fetal crown-rump length of 4 mm, and serum levels of progesterone and hCG (32 nmol/L and 1,500 iU/L, respectively).

"All of these had good positive predictive values, indicating that a pregnancy had a good chance of surviving," Dr. Adam said, "but the negative predictive values were not useful for clinical practice or research."

A multivariate regression analysis, however, did identify that a combination of baseline bleeding score (two on a five-point scale) and baseline hCG level (1,500 iU/L) exhibited excellent positive and negative predictive values (94% and 77%, respectively). The equation used for computing the pregnancy viability index was hCG level/bleeding score × 1.87 × 10, where the bleeding score odds ratio for miscarriage is 1.87.

"This research has, for the first time, offered us a tool to begin to attempt to rescue pregnancies threatening to miscarry when, currently, all we can do is fold our hands and hope for the best," Dr. Adam said.

Dr. Adam plans to carry out a validation study on at least 1,000 women in the near future.

The study was funded by the Central Manchester Foundation Trust Biomedical Research Center. Dr. Adam said she had no relevant financial disclosures.