Serum concentrations of Ang-2 and Flt-1 may be predictive of pregnancy outcome in women with pregnancies of uncertain viability: a phase I exploratory prognostic factor study

Abstract

The aim of this study was to determine whether serum concentrations of Ang-1, Ang-2, Flt-1, IL-15 and/or TRAIL can be used to predict outcome in women with pregnancies of uncertain viability (PUVs). Women presenting to the Early Pregnancy Unit at the Queen’s Medical Centre in Nottingham between 17.06.14 and 01.09.15 were prospectively recruited. Serum concentrations of Ang-1, Ang-2, Flt-1, IL-15 and TRAIL were measured in women with PUVs. Women were followed-up according to departmental protocols until viability was determined. Biomarker concentrations were correlated with pregnancy outcome. Ninety-four PUVs were studied, of which 61 (64.9%) were subsequently proven to be viable. There were statistically significant (p < .01), linear (p-value_trend <.01) associations between Ang-2 and Flt-1 concentrations and pregnancy viability such that women with lower concentrations were significantly more likely to have viable pregnancies than women with higher concentrations. In conclusion, Ang-2 and Flt-1 may be useful in predicting outcome in women with PUVs.

Impact statement

• What is already known on this subject: Predicting outcome in women with pregnancies of uncertain viability (PUVs) is challenging. There is currently no accurate and reliable method. All PUVs need to be followed-up until a definitive diagnosis of either a viable or non-viable pregnancy can be made. This takes time, utilises limited resources and generates significant anxiety. Recent studies have demonstrated serum concentrations of Ang-1, Ang-2, Flt-1, IL-15 and TRAIL in viable pregnancies are significantly different to those in non-viable or ectopic pregnancies.

• What the results of this study add: The results from this prospective study of 94 women with PUVs suggest that serum concentrations of Ang-2 and Flt-1 may be able to predict pregnancy viability in cases of uncertainty. Women with PUVs and low concentrations of Ang-2 or Flt-1 are significantly more likely to have viable pregnancies than women with high concentrations.

• What the implications are of these findings for clinical practice and/or further research: Evidence from multiple studies is necessary to appreciate the discriminating ability of these prognostic factors. Rapid clinical adoption in the absence of such evidence may lead to wasted resources. If our findings are confirmed, however, these biomarkers, either alone or as part of a prognostic model, may be capable of accurately predicting pregnancy outcome in cases of uncertainty. This would reduce the strain on limited resources and alleviate anxiety for women.

Keywords:

• Pregnancy of uncertain viability
• viable
• non-viable
• angiopoietin
• Flt-1

Acknowledgements

The authors would like to thank: Catherine Pincott-Allen for her assistance with the biomarker assays; Andrea Venn for her input with the statistical analyses; and all the staff and patients from the Early Pregnancy Assessment Unit at the Queen’s Medical Centre, Nottingham.

Disclosure statement

No conflict of interest is declared. No financial relationships with any organisation that might have interest in the submitted work in the previous 3 years are declared. No other relationship or activities that could appear to have influenced the submitted work are declared. All authors had full access to all of the data in the study and can take full responsibility for the integrity of the data and the accuracy of the data analysis. The University of Nottingham is the sponsor for the study.

Additional information

Funding

This study was supported by University of Nottingham.