Clinical utility of thrombophilia, anticoagulant treatment, and maternal variables as predictors of placenta-mediated pregnancy complications: an extensive analysis

Abstract

Objective: The objective of this study is to analyze the usefulness of thrombophilia and antithrombotic drugs in combination with materno-fetal characteristics to generate a predictive model of placenta-mediated pregnancy complications (PMPC) for counseling treatment.

Methods: A retrospective analysis was performed in women with singleton pregnancy that required a thrombophilia study, including 222 patients with unknown cause PMPC and 151 women with no complications at current pregnancy in Hospital Clínico Universitario, Lozano, Blesa, Zaragoza, Spain. Chi-squared and Mann–Whitney test were applied to analyze univariate risk factors. Multivariate analysis was performed using logistic regression model with candidate variables: maternal characteristics, obstetric history, thrombophilia, and treatment with low-molecular-weight heparin (LMWH) and/or with acid acetylsalicylic (ASA). The calibration, discrimination, and best cutoff point for the clinical application of the model was analyzed.

Results: Maternal characteristics showed differences in median body mass index (BMI), odds ratio (OR): 0.4, smoking habit, OR: 8.5, and hypertension, OR: 11.4, appearing all of them as risk factors. In our study, a prior pregnancy that ended in a child alive was a protective factor OR: 0.02–0.4, and having a previous preterm child was a strong risk factor OR: 4.2. Thrombophilia was not a risk factor. Patients under LMWH treatment (15%) and/or ASA (6.2%) had better pregnancy outcomes, showing both as protective factors: ASA OR: 0.32 and LMWH OR: 0.16. The model has an AUC value of 0.847, with good calibration. A nomogram and an app is provided for this adjusted model with high discrimination ability in internal validation (AUC = 0.833). Our clinical utility analysis guide us to choose 40% as the best threshold probability.

Conclusions: We found risk and protective factors associated with PMPC, but our data were not conclusive to demonstrate its relation with maternal thrombophilia. However, the challenger finding is the clinical utility of antithrombotic drugs as a protective factors in PMPC prevention. It is possible to identify patients with high risk of PMPC through a combined predictive model, for counseling treatment.

Keywords:

• Antithrombotic treatment
• growth restriction
• placental abruption
• preeclampsia
• pregnancy
• stillbirth
• thrombophilia

Acknowledgements

We would like to thank Concepción Orna for helping in language edition. Luis Mariano Esteban, Gerardo Sanz and Ángel Borque-Fernando are members of the research group “Modelos Estocásticos”, supported by Gobierno de Aragón. Gerardo Sanz also received support from Grant MTM2017-83812-P of MINECO.

Disclosure statement

No potential conflict of interest was reported by the authors.