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

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.

Efecto del ácido levofolínico sobre las concentraciones de homocisteína plasmática en la mujer joven y sana en la consulta preconcepcional / Effects of levofolinic acid on plasma homocysteine concentrations in healthy and young women in preconceptional care

FUNDAMENTO: El aumento de la homocisteína plasmática total (tHcy) es un factor de riesgo para los defectos del tubo neural. Se estudia el efecto de la suplementación con ácido levofolínico (l,5-formil-tetrahidrofólico) sobre los valores de la tHCy plasmática en la mujer en edad reproductiva. PACIENTES Y MÉTODO: Treinta mujeres sanas de 18 a 35 años recibieron 5 mg/día de ácido levofolínico por vía oral durante 30 días. La tHcy y los folatos intraeritrocitarios se determinaron antes de la suplementación (día 0), los días 2, 5, 10 y 30 durante el tratamiento, y 30 (día 60) y 60 días (día 90) después de finalizado. La tHcy plasmática se determinó por inmunoanálisis de polarización de fluorescencia (coeficiente de variación [CV] intraanálisis e interanálisis < 8 por ciento) y el ácido fólico intraeritrocitario, mediante inmunoanálisis quimioluminiscente (CV intraanálisis e interanálisis < 5 por ciento). RESULTADOS: La tHCy plasmática disminuye a partir del segundo día de tratamiento (día 0 frente a 2: media de la diferencia, -1,24 µmol/l; intervalo de confianza [IC] del 95 por ciento, -0,84 a -1,63; p < 0,001). El descenso máximo (32,3 por ciento) se observa a los 30 días (media de la diferencia, -2,72 µmol/l; IC del 95 por ciento, -2,20 a -3,24; p < 0,001). Tras finalizar el tratamiento el efecto hipohomocisteinémico persiste el día 60 (media de la diferencia, -2,67 µmol/l; IC del 95 por ciento, -2,07 a -3,26; p < 0,001) y 90 (media de la diferencia, -1,49 µmol/l; IC del 95 por ciento, -0,94 a -2,03; p < 0,001). La respuesta fue mayor cuando la tHcy plasmática fue de 9 µmol/l o más. CONCLUSIONES: El ácido levofolínico provoca un descenso temprano, intenso y persistente de las concentraciones de tHcy plasmática (AU)