Friday, February 19, 2016

Serum Biomarkers to predict outcome in women with threatened abortion: A systemic review and diagnostic accuracy meta-analysis.




Threatened abortion approximately affect 20% of pregnancies and 50% of those will end up in miscarriage.  It has also been associated with poor obstetric outcome such as preterm labor, low lying placenta, low birth weight and PROM.

The uncertainty of prognosis makes it a challenging task for healthcare professionals.Various biomarkers have been used, with variable results to predict the prognosis of bleeding in early pregnancy.

This systemic review and meta-analysis was published in the forthcoming issue of Human Reproduction update, it aims to determine the diagnostic accuracy of various biomarkers.

A total of 19 studies were found after electronic searching of databases to determine outcomes for women with threatened abortion at 5–23 weeks gestational age.

15 studies (including 1263 women) were found eligible using QUADAS-2 (Quality Assessment for Diagnostic Accuracy Studies-2: A Revised Tool) to include in the qualitative data assessment.

The biomarkers that were looked into included serum progesterone, hCG, pregnancy associated plasma protein A, estradiol and cancer antigen 125 (CA 125).

Interestingly, serum CA 125 appeared to be the most promising marker (n = 648 women, 7 studies), whereas serum progesterone and hCG are less useful once fetal viability is established.

CA-125 is a glycoprotein and its origin is uncertain during pregnancy. It arises during the first trimester and return to a non-pregnancy range in late pregnancy.

CA 125 showed a sensitivity of 90% (95% confidence interval (CI) 83–94%), specificity of 88% (95% CI 79–93%), positive likelihood ratio of 7.86 (95% CI 4.23–14.60) and negative likelihood ratio of 0.10 (95% CI 0.06–0.20). The inverse of negative likelihood ratio was 9.31 (95% CI 5–17.1) indicating that a negative test is likely to identify those who are likely to continue with the pregnancy.

Nevertheless, when vaginal bleeding had been present for 3 days or more and there was high maternal serum CA125 activity, the abortion risk was found to be 100%.

Since this was a qualitative analysis, no cut-off value for CA125 was determined but in most studies patients who eventually aborted had values of CA-125 more than 125 IU/ml while the control had a value not more than 93 IU/ml.

A rising value of CA 125 combined with gestational sac diameter that does not correspond to the pregnancy dating is highly significant in predicting the prognosis.

Serum estradiol was the next best marker with a sensitivity of 45% (95% CI 6–90%), a specificity of 87% (95% CI 81–92%), a positive likelihood ratio of 3.72 (95% CI 1.01–13.71) and a negative likelihood ratio of 0.62 (95% CI 0.20–1.84).


References:

https://humupd.oxfordjournals.org/content/22/2/228.abstract 

https://www.researchgate.net/publication/21703609_The_prognostic_significance_of_maternal_serum_CA125_measurement_in_threatened_abortion.





http://www.ncbi.nlm.nih.gov/pubmed/12235698



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