Prediction of Recurrent Pregnancy Loss by a New Thrombophilia Based Genetic Risk Score

  • José Antonio Páramo Clinica Universidad de Navarra, Hematology, Pamplona, 31008, Spain CIBER CV, ISCIII, Spain
  • Pilar Llamas Hospital Universitario Fundacion Jimenez Dıaz, Hematology, Madrid, 28040, Spain
  • José Bellver IVI-RMA Valencia, Valencia, 46015, Spain University of Valencia, Department of Pediatric, Obstetrics and Gynecology, Valencia, 46010, Spain
  • Ramón Lecumberri Clinica Universidad de Navarra, Hematology, Pamplona, 31008, Spain CIBER CV, ISCIII, Spain
  • Arantxa García-Raso Hospital Universitario Fundacion Jimenez Dıaz, Hematology, Madrid, 28040, Spain
  • Pilar Alamá IVI-RMA Valencia, Valencia, 46015, Spain
  • César Díaz-García University of Valencia, Department of Pediatric, Obstetrics and Gynecology, Valencia, 46010, Spain IVI-RMA London, London, W1G 9RQ, United Kingdom Instituto de Investigaciones Sanitarias La Fe, Reproductive Research Group, Valencia, 46026, Spain
  • Ana Alfonso Pierola Clinica Universidad de Navarra, Hematology, Pamplona, 31008, Spain
  • Ana Carolina Miranda Hospital Universitario Fundacion Jimenez Dıaz, Hematology, Madrid, 28040, Spain
  • Víctor Hugo Gómez IVI-RMA Valencia, Valencia, 46015, Spain
  • Sergio Cabanillas IVI-RMA Valencia, Valencia, 46015, Spain
  • Sheila Vázquez IVI-RMA London, London, W1G 9RQ, United Kingdom
  • Kevin Guillén Gendiag.exe, Scientific Department, Esplugues de Llobregat, 08950, Spain
  • Sara Pich Gendiag.exe, Scientific Department, Esplugues de Llobregat, 08950, Spain
  • Oriol Casagran Gendiag.exe, Scientific Department, Esplugues de Llobregat, 08950, Spain
  • Israel Ortega Gendiag.exe, Scientific Department, Esplugues de Llobregat, 08950, Spain
  • Jose Manuel Soria Institut d´Investigacio Sant Pau (IIB-Sant Pau), Unitat de Genomica de Malalties Complexes, Barcelona, 31008, Spain
  • Eduardo Salas Gendiag.exe, Scientific Department, Esplugues de Llobregat, 08950, Spain
Keywords: , recurrent pregnancy loss, thrombophilia screening, genetic risk score, highly sensitive predictive tool.

Abstract

We  examined the predictive ability of the new thrombophilia-based genetic risk score that has been developed (TiC-RPL)  to acutely determine the risk of recurrent pregnancy loss (RPL) closely related to thrombophilia and to compare it with the ability of the classical genetic thrombophilia variants F5 rs6025 and F2 rs1799963. This is a case-control observational study, with retrospective data analysis. We included 180 healthy women with at least one uncomplicated pregnancy to term and no previous miscarriage and 184 cases of idiopathic recurrent pregnancy loss (RPL). The predictive ability was assessed in terms of discrimination (AUC), sensitivity, specificity, positive and negative predictive values (PPV, NPV), and positive and negative likelihood ratios (PLR and NLR). TiC-RPL has a better AUC (95 CI) than F5 rs6025+F2 rs1799963 [0.763 (0.715-0.811) vs 0.540 (0.514-0.567); p<0.0001], with a sensitivity of 70.65%, a specificity of 67.78%, a PPV of 69.15%, an NPV of 69.32%, a PLR of 2.19, and an NLR of 0.43. Our results show that the new score TiC-RPL is significantly better than F5 rs6025+F2 rs1799963 in identifying RPL women in whom RPL appears to be associated with thrombophilia. This identification can guide a personalized approach in the prevention of RPL.

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Published
2018-12-01
Section
Articles