Diagnostic accuracy of serum biomarkers in predicting the outcome in threatened miscarriages: a systematic review and diagnostic accuracy meta-analysis.

Clinical Pearls:

• According to the systemic review and meta-analysis, CA-125 is the best marker to predict the fate of patients with threatened miscarriage once viability is reached. It should be further investigated in combination with others like inhibin-A and other sonographic parameters to improve the predictive accuracy.
• The conventionally used biomarkers of serum HCG and progesterone are not useful in predicting outcome of a pregnancy with a viable fetus.

Miscarriages in pregnancy are common occurrences and associated with considerable emotional distress regarding the pregnancy outcome. Studies have shown that 8-20 percent of women with a positive pregnancy test can end up in early miscarriage. Nearly 80% of the miscarriages occur in first trimester.[1]

Various biochemical markers and ultra-sonographic predictors have been used in clinical practice to predict the outcome of threatened miscarriages. The current biomarkers under investigations are beta HCG, PAPP-A, serum estradiol and progesterone and CA 125. Various studies in the past have come up with conflicting results.

An earlier observational study by Maged A.M and Mostafa W.A concluded that serum progesterone measurement of at least 25 ng/ml carries 97% likelihood for viable intrauterine pregnancy.

A recent systemic review and meta-analysis published in the recent issue of Human Reproduction Update aims to determine the best predictor in identifying the pregnancies that are most likely progress.

The researchers Pillai R.N. et al included all the studies that met the inclusion criteria till June 2015. The quality of the study assessed by using the QUADAS-2 (Quality Assessment for Diagnostic Accuracy Studies-2: A Revised Tool)[2]  and Cochrane Systemic review software was used to perform the analysis.

Out of 19 studies included, 15 studies were eligible for the analysis comprising a total of 1263 women.

It was seen that once fetal viability is established serum CA 125 appears to be the most promising marker (n = 648 women in seven studies) with a sensitivity of 90% and specificity of 88% whereas serum progesterone and hCG are less useful.

In fact, a negative test is likely to predict highest chances of continuation of pregnancy.

CA-125 is a cell surface antigen expressed by fetal chorion, amniotic fluid, and maternal decidua in significant amounts.

Levels were significantly higher in patients presenting with bleeding and eventually ending in miscarriage then those who continued the pregnancy till term, supporting the theory of its release secondary to decidual disruption.[3] 

CA-125 is a cell surface antigen expressed by fetal chorion, amniotic fluid, and maternal decidua in significant amounts.

Few studies have tried to calculate a ‘cut-off’ value to predict miscarriage. Using the ROC curve the most likely calculated level was > 58 IU/ml at sensitivity and specificity of 80% and 100% respectively.

Serum estradiol was the second best marker with sensitivity and specificity of 45% and 87% respectively.

The authors concluded that CA-125 is the best marker to predict the fate of patients with threatened miscarriage once  viability is reached. It should be further investigated in combination with others like inhibin-A and other sonographic parameters to improve the predictive accuracy.

The conventionally used biomarkers of serum hCG and progesterone are not useful in predicting outcome of a pregnancy with a viable fetus. 

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[1] http://www.uptodate.com/contents/miscarriage-beyond-the-basics accessed on July 3, 2016

[2] http://www.bristol.ac.uk/social-community-medicine/projects/quadas/quadas-2/

[3] https://www.jscimedcentral.com/Obstetrics/obstetrics-4-1077.pdf