Estudio doppler de las arterias uterinas y del equilibrio angiogénico para estimar el riesgo de complicaciones maternas y perinatales en las gestantes diagnosticadas de preeclampsia

El objetivo de las tres publicaciones que componen esta Tesis Doctoral fue evaluar la capacidad del Índice de pulsatilidad medio de las arterias uterinas (IPm-AUt) y de los factores de equilibrio angiogénico sFlt-1 (soluble fms-like tyroxin kinase-1) y PlGF (placental growth factor) para P1. La predicción de Preeclampsia (PE) en gestantes de alto riesgo.P2. La confirmación o exclusión del diagnóstico de PE cuando existe sospecha clínica.P3. La predicción del riesgo de aparición de complicaciones maternas y neonatales y del intervalo de tiempo que transcurre hasta el parto en mujeres con PE. Métodos.P1, Estudio prospectivo observacional de 135 gestaciones únicas con al menos un criterio de alto riesgo. Se evaluó el rendimiento de un modelo cuantitativo y otro semi-cuantitativo previamente descritos para la predicción de la PE, basados en la evaluación secuencial del IPm-AUt entre las semanas 11positivo 0 - 13 positivo 6 y 19 positivo 0 - 22 positivo 0.P2, Se incluyeron gestantes con sospecha (n igual a 32) o diagnóstico confirmado (n igual a 60) de PE. Se evaluó el IPm-AUt y del cociente sFlt-1 PlGF de forma adicional al protocolo convencional de estudio ante un caso de PE.P3, Se incluyeron 51 gestaciones con PE precoz (mayor 34 semanas). Se evaluó el IPm-AUt y el cociente sFlt-1 PlGF en el momento del diagnostico y la asociación individual y en combinación de dichos marcadores con la aparición de resultados maternos y perinatales adversos y su asociación con el tiempo restante desde el diagnóstico de la PE hasta el parto. Conclusiones. P1. la evaluación de la evolución secuencial de las resistencias en las arterias uterinas entre el primer y segundo trimestre de la gestación es de utilidad para predecir el riesgo de padecer PE precoz en gestantes de alto riesgo.P2. La PE precoz se asocia de forma prácticamente invariable con valores elevados del cociente sFlt-1 PlGF y del IPm-AUt. La utilidad clínica tanto del IPm-AUt como del ratio sFlt-1 PlGF más allá de la semana 34 es limitada. En el contexto de una sospecha de PE, solamente la obtención de un cociente sFlt-1 PlGF elevado podría tener utilidad diagnóstica, mostrando una elevada especificidad pero una baja sensibilidad.P3. En la PE precoz, la edad gestacional y los valores de IPm-AUt y del cociente sFlt-1 PlGF obtenidos en el momento del diagnóstico se relacionan con los resultados perinatales adversos pero no con la aparición de complicaciones maternas. El cociente sFlt-1 PlGF está inversamente relacionado con el intervalo de tiempo que transcurre hasta el parto y cuando es menor 655 se asocia a la aparición de complicaciones maternas y o perinatales en las siguientes 48 hora

Prediction of perinatal survival in early‐onset fetal growth restriction: role of placental growth factor

Objective To analyze the ability to predict perinatal survival and severe neonatal morbidity of cases with early-onset fetal growth restriction (eoFGR) using maternal variables, ultrasound parameters and angiogenic markers at the time of diagnosis. Methods This was a prospective observational study in a cohort of singleton pregnancies with a diagnosis of eoFGR (< 32 weeks of gestation). At diagnosis of eoFGR, complete assessment was performed, including ultrasound examination (anatomy, biometry and Doppler assessment) and maternal serum measurement of the angiogenic biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). Logistic regression models for the prediction of perinatal survival (in cases diagnosed at < 28 weeks) and severe neonatal morbidity (in all liveborn cases) were calculated. Results In total, 210 eoFGR cases were included, of which 185 (88.1%) survived perinatally. The median gestational age at diagnosis was 27 + 0 weeks. All cases diagnosed at ≥ 28 weeks survived. In cases diagnosed < 28 weeks, survivors (vs non-survivors) had a higher gestational age (26.1 vs 24.4 weeks), estimated fetal weight (EFW; 626 vs 384 g), cerebroplacental ratio (1.1 vs 0.9), PlGF (41 vs 18 pg/mL) and PlGF multiples of the median (MoM; 0.10 vs 0.06) and lower sFlt-1/PlGF ratio (129 vs 479) at the time of diagnosis (all P < 0.001). The best combination of two variables for predicting perinatal survival was provided by EFW and PlGF MoM (area under the receiver-operating-characteristics curve (AUC), 0.84 (95% CI, 0.75–0.92)). These were also the best variables for predicting severe neonatal morbidity (AUC, 0.73 (95% CI, 0.66–0.80)). Conclusions A model combining EFW and maternal serum PlGF predicts accurately perinatal survival in eoFGR cases diagnosed before 28 weeks of gestation. Prenatal prediction of severe neonatal morbidity in eoFGR cases is modest regardless of the model used. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology

Prediction of perinatal survival in early‐onset fetal growth restriction: role of placental growth factor

Fondos FEDERObjective To analyze the ability to predict perinatal survival and severe neonatal morbidity of cases with early-onset fetal growth restriction (eoFGR) using maternal variables, ultrasound parameters and angiogenic markers at the time of diagnosis. Methods This was a prospective observational study in a cohort of singleton pregnancies with a diagnosis of eoFGR (< 32 weeks of gestation). At diagnosis of eoFGR, complete assessment was performed, including ultrasound examination (anatomy, biometry and Doppler assessment) and maternal serum measurement of the angiogenic biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). Logistic regression models for the prediction of perinatal survival (in cases diagnosed at < 28 weeks) and severe neonatal morbidity (in all liveborn cases) were calculated. Results In total, 210 eoFGR cases were included, of which 185 (88.1%) survived perinatally. The median gestational age at diagnosis was 27 + 0 weeks. All cases diagnosed at ≥ 28 weeks survived. In cases diagnosed < 28 weeks, survivors (vs non-survivors) had a higher gestational age (26.1 vs 24.4 weeks), estimated fetal weight (EFW; 626 vs 384 g), cerebroplacental ratio (1.1 vs 0.9), PlGF (41 vs 18 pg/mL) and PlGF multiples of the median (MoM; 0.10 vs 0.06) and lower sFlt-1/PlGF ratio (129 vs 479) at the time of diagnosis (all P < 0.001). The best combination of two variables for predicting perinatal survival was provided by EFW and PlGF MoM (area under the receiver-operating-characteristics curve (AUC), 0.84 (95% CI, 0.75–0.92)). These were also the best variables for predicting severe neonatal morbidity (AUC, 0.73 (95% CI, 0.66–0.80)). Conclusions A model combining EFW and maternal serum PlGF predicts accurately perinatal survival in eoFGR cases diagnosed before 28 weeks of gestation. Prenatal prediction of severe neonatal morbidity in eoFGR cases is modest regardless of the model used. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.European CommissionMinisterio de Economía, Industria y Competitividad (España)Instituto de Salud Carlos III (España)Depto. de Salud Pública y Materno - InfantilFac. de MedicinaTRUEpu

Angiogenesis-Related Biomarkers (sFlt-1/PLGF) in the Prediction and Diagnosis of Placental Dysfunction: An Approach for Clinical Integration

Placental dysfunction is involved in a group of obstetrical conditions including preeclampsia, intrauterine growth restriction, and placental abruption. Their timely and accurate recognition is often a challenge since diagnostic criteria are still based on nonspecific signs and symptoms. The discovering of the role of angiogenic-related factors (sFlt-1/PlGF) in the underlying pathophysiology of placental dysfunction, taking into account that angiogenesis-related biomarkers are not specific to any particular placental insufficiency-related disease, has marked an important step for improving their early diagnosis and prognosis assessment. However, sFlt-1/PlGF has not been yet established as a part of most guidelines. We will review the current evidence on the clinical utility of sFlt-1/PlGF and propose a new protocol for its clinical integration

Predictors of adverse perinatal outcome up to 34 weeks, a multivariable analysis study

The objective was to evaluate the best predictors of adverse perinatal outcome (APO) in foetuses examined up to 34 weeks and delivered by spontaneous or induced labour. This was a retrospective study of 129 pregnancies that underwent an ultrasound Doppler examination at 23–34 weeks and entered into labour within 30 days. Cerebroplacental ratio (CPR) and mean uterine artery pulsatility index (mUtA PI) were converted into multiples of the median (MoM) and estimated foetal weight (EFW) into centiles to adjust for gestational age (GA). Sonographic and clinical parameters were evaluated using logistic regression analysis. The multivariable model for the prediction of APO presented a notable accuracy: Detection rate (DR) was 39.5% for a false positive rate (FPR) of 5% and 56.8% for a FPR of 10%, AUC 0.82, p < .0001. Significant predictors were GA, EFW centile, and CPR MoM, but not mUtA PI MoM. Moreover, the type of labour onset did not exert any influence on APO. In conclusion, up to 34 weeks, prediction of APO after spontaneous or induced labour may be done measuring CPR and EFW.IMPACT STATEMENT What is already known on this subject? Earlier in pregnancy, foetal growth restriction is caused by placental disease causing progressive hemodynamic changes. These changes have been exhaustively described. Conversely, information about the best predictors of adverse outcome is scarce. What do the results of this study add? The findings of this study show that prior to 34 weeks and up to 1 month before labour, labour outcome might be predicted by gestational age, foetal cerebroplacental ratio (CPR) and estimated foetal weight (EFW). What are the implications of these findings for clinical practice and/or further research? If CPR behaves as a good marker of outcome not only at the end of pregnancy but also earlier in gestation, it might be interrogated along with EFW in foetuses attempting vaginal delivery to determine the risk of adverse outcome