RESUMEN
Preeclampsia (PE) is a multiorgan disorder that complicates around 2-8% of pregnancies and is a major cause of perinatal and maternal morbidity and mortality. PE is a clinical syndrome characterized by hypertension secondary to systemic inflammation, endothelial dysfunction, and syncytiotrophoblast stress leading to hypertension and multiorgan dysfunction. The uterine arteries are the main blood vessels that supply blood to the uterus. They give off branches and plays an important role in maintaining blood supply during pregnancy. The arcuate artery originates from the uterine artery and runs medially through the myometrium. The arcuate arteries divide almost directly into anterior and posterior branches, from which the radial artery leads directly to the uterine cavity during their course. Near the endometrium-myometrium junction, the radial artery generates spiral arteries within the basal layer and functional endometrium. The walls of radial and spiral arteries are rich in smooth muscle, which is lost when trophoblast cells invade and become large-caliber vessels. This physiological transformation of uteroplacental spiral arteries is critical for successful placental implantation and normal placental function. In normal pregnancy, the luminal diameter of the spiral arteries is greatly increased, and the vascular smooth muscle is replaced by trophoblast cells. This process and changes in the spiral arteries are called spiral artery remodeling. In PE, this genetically and immunologically governed process is deficient and therefore there is decreased vascular capacitance and increased resistance in the uteroplacental circulation. Furthermore, this defect in uteroplacental spiral artery remodeling is not only associated with early onset PE, but also with fetal growth restriction, placental abruption, and spontaneous premature rupture of membranes. Doppler ultrasound allows non-invasive assessment of placentation, while the flow impedance decreases as the pregnancy progresses in normal pregnancies, in those destined to develop preeclampsia the impedance is increased.
Asunto(s)
Hipertensión , Preeclampsia , Embarazo , Femenino , Humanos , Placenta/diagnóstico por imagen , Arteria Uterina/diagnóstico por imagen , Arteria Uterina/fisiología , Preeclampsia/diagnóstico por imagen , Placentación , Ultrasonografía DopplerRESUMEN
This practice guideline follows the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation, bringing together groups and individuals throughout the world, with the goal of improving the management of preterm labor. In fact, this document provides further guidance for healthcare practitioners on the appropriate use of examinations with the aim to improve the accuracy in diagnosing preterm labor and allow timely and appropriate administration of tocolytics, antenatal corticosteroids and magnesium sulphate and avoid unnecessary or excessive interventions. Therefore, it is not intended to establish a legal standard of care. This document is based on consensus among perinatal experts throughout the world in the light of scientific literature and serves as a guideline for use in clinical practice.
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Trabajo de Parto Prematuro , Nacimiento Prematuro , Tocolíticos , Recién Nacido , Femenino , Embarazo , Humanos , Trabajo de Parto Prematuro/diagnóstico , Trabajo de Parto Prematuro/prevención & control , Tocolíticos/uso terapéutico , Sulfato de Magnesio/uso terapéuticoRESUMEN
OBJECTIVE: This study aimed to: (1) identify all relevant studies reporting on the diagnostic accuracy of maternal circulating placental growth factor) alone or as a ratio with soluble fms-like tyrosine kinase-1), and of placental growth factor-based models (placental growth factor combined with maternal factors±other biomarkers) in the second or third trimester to predict subsequent development of preeclampsia in asymptomatic women; (2) estimate a hierarchical summary receiver-operating characteristic curve for studies reporting on the same test but different thresholds, gestational ages, and populations; and (3) select the best method to screen for preeclampsia in asymptomatic women during the second and third trimester of pregnancy by comparing the diagnostic accuracy of each method. DATA SOURCES: A systematic search was performed through MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform databases from January 1, 1985 to April 15, 2021. STUDY ELIGIBILITY CRITERIA: Studies including asymptomatic singleton pregnant women at >18 weeks' gestation with risk of developing preeclampsia were evaluated. We included only cohort or cross-sectional test accuracy studies reporting on preeclampsia outcome, allowing tabulation of 2×2 tables, with follow-up available for >85%, and evaluating performance of placental growth factor alone, soluble fms-like tyrosine kinase-1- placental growth factor ratio, or placental growth factor-based models. The study protocol was registered on the International Prospective Register Of Systematic Reviews (CRD 42020162460). METHODS: Because of considerable intra- and interstudy heterogeneity, we computed the hierarchical summary receiver-operating characteristic plots and derived diagnostic odds ratios, ß, θi, and Λ for each method to compare performances. The quality of the included studies was evaluated by the QUADAS-2 tool. RESULTS: The search identified 2028 citations, from which we selected 474 studies for detailed assessment of the full texts. Finally, 100 published studies met the eligibility criteria for qualitative and 32 for quantitative syntheses. Twenty-three studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the second trimester, including 16 (with 27 entries) that reported on placental growth factor test alone, 9 (with 19 entries) that reported on the soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 6 (16 entries) that reported on placental growth factor-based models. Fourteen studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the third trimester, including 10 (with 18 entries) that reported on placental growth factor test alone, 8 (with 12 entries) that reported on soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 7 (with 12 entries) that reported on placental growth factor-based models. For the second trimester, Placental growth factor-based models achieved the highest diagnostic odds ratio for the prediction of early preeclampsia in the total population compared with placental growth factor alone and soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 63.20; 95% confidence interval, 37.62-106.16 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 6.96; 95% confidence interval, 1.76-27.61 vs placental growth factor alone, 5.62; 95% confidence interval, 3.04-10.38); placental growth factor-based models had higher diagnostic odds ratio than placental growth factor alone for the identification of any-onset preeclampsia in the unselected population (28.45; 95% confidence interval, 13.52-59.85 vs 7.09; 95% confidence interval, 3.74-13.41). For the third trimester, Placental growth factor-based models achieved prediction for any-onset preeclampsia that was significantly better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 27.12; 95% confidence interval, 21.67-33.94 vs placental growth factor alone, 10.31; 95% confidence interval, 7.41-14.35 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 14.94; 95% confidence interval, 9.42-23.70). CONCLUSION: Placental growth factor with maternal factors ± other biomarkers determined in the second trimester achieved the best predictive performance for early preeclampsia in the total population. However, in the third trimester, placental growth factor-based models had predictive performance for any-onset preeclampsia that was better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio. Through this meta-analysis, we have identified a large number of very heterogeneous studies. Therefore, there is an urgent need to develop standardized research using the same models that combine serum placental growth factor with maternal factors ± other biomarkers to accurately predict preeclampsia. Identification of patients at risk might be beneficial for intensive monitoring and timing delivery.
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Preeclampsia , Femenino , Humanos , Embarazo , Biomarcadores , Estudios Transversales , Factor de Crecimiento Placentario , Preeclampsia/epidemiología , Tercer Trimestre del Embarazo , Factor A de Crecimiento Endotelial Vascular , Receptor 1 de Factores de Crecimiento Endotelial VascularRESUMEN
Background: During the COVID-19 pandemic, different non-validated tests were proposed to simplify the diagnosis of gestational diabetes (GDM). Aim: To analyse the effects of replacing the two-step approach for Early-GDM and GDM diagnosis, with a fasting plasma glucose test. Material and Methods: This is a cohort study consisting of 3200 pregnant women: 400 with Early-GDM, 800 with GDM and 2000 with Non-GDM diagnosed using the two-step approach. Using fasting plasma glucose for Early-GDM and GDM diagnosis, according to the recommendations of Spain, Australia, Italy and the UK during the pandemic, the rates of missed and new Early-GDM and GDM were calculated and perinatal outcomes were analysed. Results: Using fasting plasma glucose in the first trimester >100 mg/dL for Early-GDM diagnosis, the rates of post-COVID missed and new Early-GDM were 79.5% and 3.2%, respectively. Using fasting plasma glucose at 24−28 weeks <84 or >92, 95 or 100 mg/dL for GDM diagnosis, the rates of missed GDM were 50.4%, 78%, 82.6% and 92.4%, respectively, and 8.6%, 5.6% and 2.3% women with Non-GDM were diagnosed with new GDM. Conclusion: Fasting plasma glucose is not a good test for the diagnosis of GDM either in the first trimester or at 24−28 weeks.
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COVID-19 , Diabetes Gestacional , Glucemia , COVID-19/diagnóstico , COVID-19/epidemiología , Prueba de COVID-19 , Estudios de Cohortes , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiología , Ayuno , Femenino , Glucosa , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Pandemias , EmbarazoRESUMEN
Volumetric placental measurement using 3-D ultrasound has proven clinical utility in predicting adverse pregnancy outcomes. However, this metric cannot currently be employed as part of a screening test due to a lack of robust and real-time segmentation tools. We present a multiclass (MC) convolutional neural network (CNN) developed to segment the placenta, amniotic fluid, and fetus. The ground-truth data set consisted of 2093 labeled placental volumes augmented by 300 volumes with placenta, amniotic fluid, and fetus annotated. A two-pathway, hybrid (HB) model using transfer learning, a modified loss function, and exponential average weighting was developed and demonstrated the best performance for placental segmentation (PS), achieving a Dice similarity coefficient (DSC) of 0.84- and 0.38-mm average Hausdorff distances (HDAV). The use of a dual-pathway architecture improved the PS by 0.03 DSC and reduced HDAV by 0.27 mm compared with a naïve MC model. The incorporation of exponential weighting produced a further small improvement in DSC by 0.01 and a reduction of HDAV by 0.44 mm. Per volume inference using the FCNN took 7-8 s. This method should enable clinically relevant morphometric measurements (such as volume and total surface area) to be automatically generated for the placenta, amniotic fluid, and fetus. The ready availability of such metrics makes a population-based screening test for adverse pregnancy outcomes possible.
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Procesamiento de Imagen Asistido por Computador , Placenta , Líquido Amniótico/diagnóstico por imagen , Femenino , Humanos , Redes Neurales de la Computación , Placenta/diagnóstico por imagen , Embarazo , UltrasonografíaRESUMEN
BACKGROUND: In women with a singleton pregnancy and sonographic short cervix in midgestation, vaginal administration of progesterone reduces the risk of early preterm birth and improves neonatal outcomes without any demonstrable deleterious effects on childhood neurodevelopment. In women with twin pregnancies, the rate of spontaneous early preterm birth is 10 times higher than that in singletons, and in this respect, all twins are at an increased risk of preterm birth. However, 6 trials in unselected twin pregnancies reported that vaginal administration of progesterone from midgestation had no significant effect on the incidence of early preterm birth. Such apparent lack of effectiveness of progesterone in twins may be due to inadequate dosage or treatment that is started too late in pregnancy. OBJECTIVE: The early vaginal progesterone for the prevention of spontaneous preterm birth in twins, a randomized, placebo-controlled, double-blind trial, was designed to test the hypothesis that among women with twin pregnancies, vaginal progesterone at a dose of 600 mg per day from 11 to 14 until 34 weeks' gestation, as compared with placebo, would result in a significant reduction in the incidence of spontaneous preterm birth between 24+0 and 33+6 weeks. STUDY DESIGN: The trial was conducted at 22 hospitals in England, Spain, Bulgaria, Italy, Belgium, and France. Women were randomly assigned in a 1:1 ratio to receive either progesterone or placebo, and in the random-sequence generation, there was stratification according to the participating center. The primary outcome was spontaneous birth between 24+0 and 33+6 weeks' gestation. Statistical analyses were performed on an intention-to-treat basis. Logistic regression analysis was used to determine the significance of difference in the incidence of spontaneous birth between 24+0 and 33+6 weeks' gestation between the progesterone and placebo groups, adjusting for the effect of participating center, chorionicity, parity, and method of conception. Prespecified tests of treatment interaction effects with chorionicity, parity, method of conception, compliance, and cervical length at recruitment were performed. A post hoc analysis using mixed-effects Cox regression was used for further exploration of the effect of progesterone on preterm birth. RESULTS: We recruited 1194 women between May 2017 and April 2019; 21 withdrew consent and 4 were lost to follow-up, which left 582 in the progesterone group and 587 in the placebo group. Adherence was good, with reported intake of ≥80% of the required number of capsules in 81.4% of the participants. After excluding births before 24 weeks and indicated deliveries before 34 weeks, spontaneous birth between 24+0 and 33+6 weeks occurred in 10.4% (56/541) of participants in the progesterone group and in 8.2% (44/538) in the placebo group (odds ratio in the progesterone group, adjusting for the effect of participating center, chorionicity, parity, and method of conception, 1.35; 95% confidence interval, 0.88-2.05; P=.17). There was no evidence of interaction between the effects of treatment and chorionicity (P=.28), parity (P=.35), method of conception (P=.56), and adherence (P=.34); however, there was weak evidence of an interaction with cervical length (P=.08) suggestive of harm to those with a cervical length of ≥30 mm (odds ratio, 1.61; 95% confidence interval, 1.01-2.59) and potential benefit for those with a cervical length of <30 mm (odds ratio, 0.56; 95% confidence interval, 0.20-1.60). There was no evidence of difference between the 2 treatment groups for stillbirth or neonatal death, neonatal complications, neonatal therapy, and poor fetal growth. In the progesterone group, 1.4% (8/582) of women and 1.9% (22/1164) of fetuses experienced at least 1 serious adverse event; the respective numbers for the placebo group were 1.2% (7/587) and 3.2% (37/1174) (P=.80 and P=.06, respectively). In the post hoc time-to-event analysis, miscarriage or spontaneous preterm birth between randomization and 31+6 weeks' gestation was reduced in the progesterone group relative to the placebo group (hazard ratio, 0.23; 95% confidence interval, 0.08-0.69). CONCLUSION: In women with twin pregnancies, universal treatment with vaginal progesterone did not reduce the incidence of spontaneous birth between 24+0 and 33+6 weeks' gestation. Post hoc time-to-event analysis led to the suggestion that progesterone may reduce the risk of spontaneous birth before 32 weeks' gestation in women with a cervical length of <30 mm, and it may increase the risk for those with a cervical length of ≥30 mm.
Asunto(s)
Embarazo Gemelar , Nacimiento Prematuro/prevención & control , Atención Prenatal , Progesterona/uso terapéutico , Administración Intravaginal , Adulto , Método Doble Ciego , Europa (Continente) , Femenino , Humanos , Embarazo , Trimestres del Embarazo , Progesterona/administración & dosificación , Resultado del TratamientoRESUMEN
INTRODUCTION: This study aimed to evaluate the quality of the brain volumes acquired following an evidence-based guideline for the acquisition of brain volumes. MATERIAL AND METHODS: This was a prospective multicenter study. Five centers recruited five cases each, acquiring two volumes per case, at different gestational age ranges. From the collected volumes, 10 operators performed an advanced neurosonography of each case. The evaluable anatomic structures were counted in each volume and expressed as a percentage. The results were compared with those obtained in a previous study where no recommendations had been made for the acquisition of the volumes. RESULTS: Five hundred evaluations were included in the study. In the axial plane, 91.5% of the structures were satisfactorily evaluated, 81.8% in the coronal plane and 89.9% in the sagittal plane. These results were significantly better than those obtained in a previous study where the volumes had been acquired without any guidelines and the percentage of evaluable structures were 80% (P < .001), 67.1% (P < .001) and 55.1% (P < .001) in the axial, coronal and sagittal planes, respectively. CONCLUSIONS: The application of an evidence-based guideline for the acquisition of brain volumes improves the quality of these by increasing the number of evaluable structures in the volume.
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Encéfalo/diagnóstico por imagen , Imagenología Tridimensional/métodos , Ultrasonografía Prenatal/métodos , Adulto , Medicina Basada en la Evidencia , Femenino , Edad Gestacional , Adhesión a Directriz , Humanos , Interpretación de Imagen Asistida por Computador , Tamaño de los Órganos , Embarazo , Estudios ProspectivosRESUMEN
We present a new technique to fully automate the segmentation of an organ from 3D ultrasound (3D-US) volumes, using the placenta as the target organ. Image analysis tools to estimate organ volume do exist but are too time consuming and operator dependant. Fully automating the segmentation process would potentially allow the use of placental volume to screen for increased risk of pregnancy complications. The placenta was segmented from 2,393 first trimester 3D-US volumes using a semiautomated technique. This was quality controlled by three operators to produce the "ground-truth" data set. A fully convolutional neural network (OxNNet) was trained using this ground-truth data set to automatically segment the placenta. OxNNet delivered state-of-the-art automatic segmentation. The effect of training set size on the performance of OxNNet demonstrated the need for large data sets. The clinical utility of placental volume was tested by looking at predictions of small-for-gestational-age babies at term. The receiver-operating characteristics curves demonstrated almost identical results between OxNNet and the ground-truth). Our results demonstrated good similarity to the ground-truth and almost identical clinical results for the prediction of SGA.
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Aprendizaje Profundo , Imagenología Tridimensional/métodos , Placenta/diagnóstico por imagen , Ultrasonografía Prenatal/métodos , Conjuntos de Datos como Asunto , Femenino , Humanos , Tamaño de los Órganos , Placenta/anatomía & histología , Embarazo , Primer Trimestre del EmbarazoRESUMEN
BACKGROUND: Preeclampsia is a major pregnancy complication with adverse short- and long-term implications for both the mother and baby. Screening for preeclampsia at 11-13 weeks' gestation by a combination of maternal demographic characteristics and medical history with measurements of biomarkers can identify about 75% of women who develop preterm preeclampsia with delivery at <37 weeks' gestation and 90% of those with early preeclampsia at <32 weeks, at a screen-positive rate of 10%. A recent trial (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) has reported that in women identified by first-trimester screening as being at high risk for preeclampsia, use of aspirin (150 mg/d from the first to the third trimester), compared to placebo, reduced the incidence of preterm preeclampsia, which was the primary outcome, by 62% (95% confidence interval, 26-80%) and the incidence of early preeclampsia by 89% (95% confidence interval, 53-97%). The surprising finding of the trial was that despite the reduction in preeclampsia the incidence of admission to the neonatal intensive care unit, which was one of the secondary outcomes, was not significantly affected (odds ratio, 0.93; 95% confidence interval, 0.62-1.40). OBJECTIVE: We sought to examine the effect of prophylactic use of aspirin during pregnancy in women at high risk of preeclampsia on length of stay in the neonatal intensive care unit. STUDY DESIGN: This was a secondary analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial to assess evidence of differences in the effect of aspirin on length of stay in neonatal intensive care. Bootstrapping was used for the comparison of mean length of stay between the aspirin and placebo groups. Logistic regression was used to assess treatment effects on stay in the neonatal intensive care unit. RESULTS: In the trial there were 1620 participants and 1571 neonates were liveborn. The total length of stay in neonatal intensive care was substantially longer in the placebo than aspirin group (1696 vs 531 days). This is a reflection of significantly shorter mean lengths of stay in babies admitted to the neonatal intensive care unit from the aspirin than the placebo group (11.1 vs 31.4 days), a reduction of 20.3 days (95% confidence interval, 7.0-38.6; P = .008). Neonatal intensive care of babies born at <32 weeks' gestation contributed 1856 (83.3%) of the total of 2227 days in intensive care across both treatment arms. These occurred in 9 (1.2%) of the 777 livebirths in the aspirin group and in 23 (2.9%) of 794 in the placebo group (odds ratio, 0.42; 95% confidence interval, 0.19-0.93; P = .033). Overall, in the whole population, including 0 lengths of stay for those not admitted to the neonatal intensive care unit, the mean length of stay was longer in the placebo than aspirin group (2.06 vs 0.66 days; reduction of 1.4 days; 95% confidence interval, 0.45-2.81; P = .014). This corresponds to a reduction in length of stay of 68% (95% confidence interval, 20-86%). CONCLUSION: In pregnancies at high risk of preeclampsia administration of aspirin reduces the length of stay in the neonatal intensive care unit by about 70%. This reduction could essentially be attributed to a decrease in the rate of births at <32 weeks' gestation, mainly because of prevention of early preeclampsia. The findings have implications for both short- and long-term health care costs as well as infant survival and handicap.
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Aspirina/uso terapéutico , Unidades de Cuidado Intensivo Neonatal , Tiempo de Internación/estadística & datos numéricos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Preeclampsia/prevención & control , Adulto , Medicina Basada en la Evidencia , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Modelos Logísticos , Masculino , Oportunidad Relativa , EmbarazoRESUMEN
INTRODUCTION: We evaluated the utility of placental volume and three-dimensional (3D) vascular flow indices to predict early and late preeclampsia. MATERIAL AND METHODS: In 1,004 pregnancies attending routine care, we recorded first-trimester screening program for aneuploidy (FTSA) parameter and measured uterine artery pulsatility index (uterine-a PI). Placental volume and vascular flow indices were obtained using 3D power Doppler and VOCAL techniques. RESULTS: Placental volume was lower and uterine-a PI was higher in both early and late preeclampsia groups versus nonaffected pregnancies. The prediction rate of placental volume in late preeclampsia was higher than that of uterine-a PI (AUROC 0.707 vs. 0.581, p < 0.011). The inclusion of placental volume improved significantly the prediction rate of total and late preeclampsia in the models constructed with maternal characteristics, FTSA, and uterine-a PI (AUROC 0.745 vs. 0.818, p < 0.004, and 0.740 vs. 0.812, p < 0.012, respectively). The inclusion of vascular indices did not improve the predictive value of these models. DISCUSSION: Placental volume was an independent predictor of total, early, and late preeclampsia and its inclusion in combined predictive models significantly improved prediction rates. Reduced placental volume observed at first trimester in women with early and late preeclampsia suggests that these entities are the clinical expression of a similar pathophysiological process.
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Placenta/diagnóstico por imagen , Circulación Placentaria , Preeclampsia/diagnóstico , Primer Trimestre del Embarazo , Estudios de Cohortes , Femenino , Humanos , Placenta/irrigación sanguínea , Valor Predictivo de las Pruebas , Embarazo , Resultado del EmbarazoRESUMEN
BACKGROUND: The Aspirin for Evidence-Based Preeclampsia Prevention trial was a multicenter study in women with singleton pregnancies. Screening was carried out at 11-13 weeks' gestation with an algorithm that combines maternal factors and biomarkers (mean arterial pressure, uterine artery pulsatility index, and maternal serum pregnancy-associated plasma protein A and placental growth factor). Those with an estimated risk for preterm preeclampsia of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/d) vs placebo from 11-14 until 36 weeks' gestation. Preterm preeclampsia with delivery at <37 weeks' gestation, which was the primary outcome, occurred in 1.6% (13/798) participants in the aspirin group, as compared with 4.3% (35/822) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74). OBJECTIVE: We sought to examine the influence of compliance on the beneficial effect of aspirin in prevention of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial. STUDY DESIGN: This was a secondary analysis of data from the trial. The proportion of prescribed tablets taken was used as an overall measure of compliance. Logistic regression analysis was used to estimate the effect of aspirin on the incidence of preterm preeclampsia according to compliance of <90% and ≥90%, after adjustment for the estimated risk of preterm preeclampsia at screening and the participating center. The choice of cut-off of 90% was based on an exploratory analysis of the treatment effect. Logistic regression analysis was used to investigate predictors of compliance ≥90% among maternal characteristics and medical history. RESULTS: Preterm preeclampsia occurred in 5/555 (0.9%) participants in the aspirin group with compliance ≥90%, in 8/243 (3.3%) of participants in the aspirin group with compliance <90%, in 22/588 (3.7%) of participants in the placebo group with compliance ≥90%, and in 13/234 (5.6%) of participants in the placebo group with compliance <90%. The odds ratio in the aspirin group for preterm preeclampsia was 0.24 (95% confidence interval, 0.09-0.65) for compliance ≥90% and 0.59 (95% confidence interval, 0.23-1.53) for compliance <90%. Compliance was positively associated with family history of preeclampsia and negatively associated with smoking, maternal age <25 years, Afro-Caribbean and South Asian racial origin, and history of preeclampsia in a previous pregnancy. CONCLUSION: The beneficial effect of aspirin in the prevention of preterm preeclampsia appears to depend on compliance.
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Aspirina/uso terapéutico , Cumplimiento de la Medicación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Preeclampsia/prevención & control , Nacimiento Prematuro/epidemiología , Adulto , Método Doble Ciego , Etnicidad , Medicina Basada en la Evidencia , Femenino , Humanos , Modelos Logísticos , Edad Materna , Factor de Crecimiento Placentario/metabolismo , Preeclampsia/metabolismo , Embarazo , Primer Trimestre del Embarazo , Proteína Plasmática A Asociada al Embarazo/metabolismo , Flujo Pulsátil , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Fumar/epidemiología , Resultado del Tratamiento , Arteria Uterina/diagnóstico por imagen , Adulto JovenRESUMEN
BACKGROUND: The Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention trial demonstrated that in women who were at high risk for preterm preeclampsia with delivery at <37 weeks' gestation identified by screening by means of an algorithm that combines maternal factors and biomarkers at 11-13 weeks' gestation, aspirin administration from 11 to 14 until 36 weeks' gestation was associated with a significant reduction in the incidence of preterm preeclampsia (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). OBJECTIVE: We sought to examine whether there are differences in the effect of aspirin on the incidence of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial in subgroups defined according to maternal characteristics and medical and obstetrical history. STUDY DESIGN: This was a secondary analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial. Subgroup analysis was performed to assess evidence of differences in the effect of aspirin on incidence of preterm preeclampsia in subgroups defined by maternal age (<30 and ≥30 years), body mass index (<25 and ≥25 kg/m2), racial origin (Afro-Caribbean, Caucasian and other), method of conception (natural and assisted), cigarette smoking (smoker and non-smoker), family history of preterm preeclampsia (present and absent), obstetrical history (nulliparous, multiparous with previous preterm preeclampsia and multiparous without previous preterm preeclampsia), history of chronic hypertension (present and absent). Interaction tests were performed on the full data set of patients in the intention to treat population and on the data set of patients who took ≥ 90% of the prescribed medication. Results are presented as forest plot with P values for the interaction effects, group sizes, event counts and estimated odds ratios. We examined whether the test of interaction was significant at the 5% level with a Bonferroni adjustment for multiple comparisons. RESULTS: There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history. In participants with chronic hypertension preterm preeclampsia occurred in 10.2% (5/49) in the aspirin group and 8.2% (5/61) in the placebo group (adjusted odds ratio, 1.29; 95% confidence interval, 0.33-5.12). The respective values in those without chronic hypertension were 1.1% (8/749) in the aspirin group and 3.9% (30/761) in the placebo group (adjusted odds ratio, 0.27; 95% confidence interval, 0.12-0.60). In all participants with adherence of ≥90% the adjusted odds ratio in the aspirin group was 0.24 (95% confidence interval, 0.09-0.65); in the subgroup with chronic hypertension it was 2.06 (95% confidence interval, 0.40-10.71); and in those without chronic hypertension it was 0.05 (95% confidence interval, 0.01-0.41). For the complete data set the test of interaction was not significant at the 5% level (P = .055), but in those with adherence ≥90%, after adjustment for multiple comparisons, the interaction was significant at the 5% level (P = .0019). CONCLUSION: The beneficial effect of aspirin in the prevention of preterm preeclampsia may not apply in pregnancies with chronic hypertension. There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history.
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Aspirina/uso terapéutico , Hipertensión/epidemiología , Sobrepeso/epidemiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Preeclampsia/prevención & control , Complicaciones del Embarazo/epidemiología , Nacimiento Prematuro , Adulto , Algoritmos , Índice de Masa Corporal , Medicina Basada en la Evidencia , Femenino , Edad Gestacional , Humanos , Incidencia , Modelos Logísticos , Edad Materna , Anamnesis , Oportunidad Relativa , Embarazo , Complicaciones Cardiovasculares del Embarazo/epidemiología , Primer Trimestre del Embarazo , Historia Reproductiva , Técnicas Reproductivas Asistidas/estadística & datos numéricos , Medición de Riesgo , Fumar/epidemiologíaRESUMEN
BACKGROUND: Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle. RESULTS: A total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants. There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events. CONCLUSIONS: Treatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo. (Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation; EudraCT number, 2013-003778-29 ; Current Controlled Trials number, ISRCTN13633058 .).
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Aspirina/uso terapéutico , Preeclampsia/prevención & control , Adulto , Aspirina/efectos adversos , Método Doble Ciego , Femenino , Humanos , Incidencia , Recién Nacido , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Preeclampsia/epidemiología , Embarazo , Complicaciones del Embarazo , Resultado del Embarazo , RiesgoRESUMEN
OBJECTIVE: To evaluate the utility of first-trimester placental volume and vascular flow indices to predict intrauterine growth retardation (IUGR). STUDY DESIGN: In 1004 singleton pregnancies attending routine care we recorded maternal characteristics, biophysical and biochemical factors included in the first trimester screening for aneuploidy (FTSA) and uterine artery pulsatility index (PI). Placental volume, Vascularization Index, Flow Index and Vascularization Flow Index were obtained. Customized curves were used to define IUGR. We compared pregnancies with and without IUGR. The performance of different predictive models was described by the areas under the receiver operator characteristic (AUROC) curve. Predictive models of IUGR were compared using a two by two approach and subset analysis was performed. RESULTS: Placental volume and all vascular indices were significantly lower (p<0.001, p≤0.01), and uterine artery PI higher (p<0.001), in pregnancies with IUGR, with and without associated pre-eclampsia. RESULTS: obtained in the analysis of homogeneous subsets showed that the effectiveness of combined predictive models for IUGR improved significantly after adding vascular indices or placental volume to maternal characteristics, FTSA variables and uterine artery PI (AUROC curve value 0.703 (95% CI 0.663-0.744) versus 0.720 (95% CI 0.681-0.759) and 0.735 (95% CI 0.696-0.733), respectively). The most effective model at first trimester was that which included only maternal characteristics, uterine a-PI and placental volume, similar to that of the most complex model built with all the factors analyzed in this study AUROC curve value 0.735 (95% CI 0.696-0.773). CONCLUSIONS: Placental volume and vascular indices were predictors factors of IUGR at first trimester. The effectiveness of combined predictive models for IUGR increased significantly after adding these factors, but the sensitivity of these models was too low for them to be considered useful in clinical practice.
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Retardo del Crecimiento Fetal/diagnóstico por imagen , Placenta/diagnóstico por imagen , Circulación Placentaria/fisiología , Arteria Uterina/diagnóstico por imagen , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Recién Nacido , Placenta/irrigación sanguínea , Preeclampsia , Valor Predictivo de las Pruebas , Embarazo , Primer Trimestre del Embarazo , Estudios Prospectivos , Curva ROC , Flujo Sanguíneo Regional , Ultrasonografía Doppler/métodos , Ultrasonografía Prenatal/métodos , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the acquisition-related factors influencing the quality of the brain volumes for further study of advanced neurosonography. METHODS: This was a prospective multicentre study. Five centres were asked to include five cases each, acquiring two volumes per case, at different gestational ages. Ten operators performed an advanced neurosonography per case. The potential influence of the following factors on the number of evaluable structures was assessed: vaginal/ abdominal acquisition, position of the head, gestational age, subjective quality of the volume and the acquiring operator itself. RESULTS: Four hundred and thirty-two evaluations were included in the study. A total of 80% of the structures were evaluated satisfactorily in the axial plane, 67.1% and 55.1% in the coronal and sagittal plane, respectively. Sagittal volumes acquired transvaginally had a better quality than those acquired transabdominally. Gestational age affected the quality of axial and sagittal volumes (p < 0.001), and the best quality was obtained between 20 and 27 weeks. In axial and sagittal volumes, the head position influenced the percentage of structures visualized (p < 0.001, p < 0.001). CONCLUSIONS: Factors affecting the quality of the volume for advanced neurosonography are gestational age, fetal head position, transvaginal acquisition in sagittal volumes, the acquiring operator and the subjective quality of the volume. © 2016 John Wiley & Sons, Ltd.
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Encéfalo/diagnóstico por imagen , Imagenología Tridimensional , Ultrasonografía Doppler Transcraneal , Ultrasonografía Prenatal , Femenino , Edad Gestacional , Humanos , Embarazo , Estudios ProspectivosRESUMEN
BACKGROUND: Preterm birth is the leading cause of neonatal death and handicap in survivors. Although twins are found in 1.5% of pregnancies they account for about 25% of preterm births. Randomized controlled trials in singleton pregnancies reported that the prophylactic use of progestogens, cervical cerclage and cervical pessary reduce significantly the rate of early preterm birth. In twin pregnancies, progestogens and cervical cerclage have been shown to be ineffective in reducing preterm birth. OBJECTIVE: The objective of this study was to test the hypothesis that the insertion of a cervical pessary in twin pregnancies would reduce the rate of spontaneous early preterm birth. STUDY DESIGN: This was a multicenter, randomized controlled trial in unselected twin pregnancies of cervical pessary placement from 20(+0)-24(+6) weeks' gestation until elective removal or delivery vs. expectant management. Primary outcome was spontaneous birth <34 weeks. Secondary outcomes included perinatal death and a composite of adverse neonatal outcomes (intraventricular haemorrhage, respiratory distress syndrome, retinopathy of prematurity or necrotizing enterocolitis) or need for neonatal therapy (ventilation, phototherapy, treatment for proven or suspected sepsis, or blood transfusion). Analysis was by intention to treat. This trial is registered in the ISRCTN registry, number 01096902. RESULTS: A total of 1,180 (56.0%) of the 2,107 eligible women agreed to take part in the trial; 590 received cervical pessary and 590 had expectant management. Two of the former and one of the latter were lost to follow up. There were no significant differences between the pessary and control groups in rates of spontaneous birth <34 weeks (13.6% vs. 12.9%; relative risk 1.054, 95% confidence interval [CI] 0.787-1.413; p=0.722), perinatal death (2.5% vs. 2.7%; relative risk 0.908, 95% CI 0.553-1.491; p=0.702), adverse neonatal outcome (10.0 vs. 9.2%; relative risk 1.094, 95% CI 0.851-1.407; p=0.524) or neonatal therapy (17.9% vs. 17.2%; relative risk 1.040, 95% CI 0.871-1.242; p=0.701). A post hoc subgroup analysis of 214 women with short cervix (≤25 mm) showed no benefit from the insertion of a cervical pessary. CONCLUSION: In women with twin pregnancy, routine treatment with cervical pessary does not reduce the rate of spontaneous early preterm birth.
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Pesarios , Embarazo Gemelar , Nacimiento Prematuro/prevención & control , Adulto , Cuello del Útero/diagnóstico por imagen , Enterocolitis Necrotizante/prevención & control , Femenino , Humanos , Recién Nacido , Análisis de Intención de Tratar , Hemorragias Intracraneales/prevención & control , Muerte Perinatal/prevención & control , Embarazo , Síndrome de Dificultad Respiratoria del Recién Nacido/prevención & control , Retinopatía de la Prematuridad/prevención & control , Ultrasonografía , Espera VigilanteRESUMEN
OBJECTIVE: To analyze placental volume and vascularization at first trimester in women with pre-eclampsia, and secondarily, the effect of maternal characteristics on placental development and perinatal outcomes. METHODS: This was a prospective cohort study including women seen between 11 and 14 weeks of pregnancy. Biophysical and biochemical markers included in the screening program for aneuploidy were recorded. Placental volume and vascularization indices were obtained using three-dimensional power-Doppler imaging and Virtual Organ Computer-aided Analysis (VOCAL) techniques. RESULTS: We compared 84 women with pre-eclampsia versus 904 non-affected. Placental volume and all vascular indices were lower in those with pre-eclampsia. Multivariate analysis showed that parity and maternal weight had a significant effect on placental volume and vascularization indices (p = 0.004 and p = 0.011). In women with pre-eclampsia, multiparity showed a negative effect on placental volume, gestational age, birth weight and Apgar test score. By contrast, in the non-affected group, multiparity had a protective effect. Low maternal weight had a significantly worse effect on placental vascularization and perinatal outcomes in women with pre-eclampsia. CONCLUSIONS: Women with pre-eclampsia showed significantly lower placental volume and vascularization indices at first trimester. Multiparity and low maternal weight independently exacerbated the negative effects of pre-eclampsia on placental characteristics and perinatal outcomes. © 2015 John Wiley & Sons, Ltd.
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Placenta/patología , Preeclampsia/patología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Imagenología Tridimensional , Tamaño de los Órganos , Placenta/irrigación sanguínea , Embarazo , Primer Trimestre del Embarazo , Estudios Prospectivos , Ultrasonografía Prenatal , Adulto JovenRESUMEN
La diabetes gestacional (DG), con una prevalencia de un 9%, se asocia a una elevada morbilidad materna y perinatal. El diagnóstico y el tratamiento precoz de la hiperglucemia materna reducen el riesgo de macrosomía fetal y sus complicaciones intraparto. En el primer trimestre se puede identificar factores de riesgo de DG de la historia materna (edad, obesidad, macrosomía o DG en gestaciones previas, antecedente familiar de diabetes), marcadores bioquímicos (adiponectina, sex hormone-binding globuline y otros) y marcadores biofísicos (arteriografía, adiposidad visceral). Entre los factores de riesgo de macrosomía destacan la obesidad y la diabetes en la historia materna, pregnancy associated plasma protein-A y fracción libre de la subunidad beta de la gonadotropina coriónica humana como marcadores bioquímicos y la translucencia nucal y Doppler de arterias uterinas como marcadores biofísicos. Combinando los marcadores mediante modelos de predicción, y con una tasa de falsos positivos del 10%, se puede alcanzar una tasa de detección del 65 y el 35% para DG y macrosomía, respectivamente (AU)
Gestational diabetes (GD), which has a prevalence of 9%, is associated with high maternal and perinatal morbidity. Early diagnosis and treatment of maternal hyperglycemia reduce the risk of macrosomia and the associated intrapartum complications. Risk factors for GD can be identified in the first trimester from maternal history (age, obesity, previous macrosomia or GD, family history of diabetes), biochemical markers (adiponectin, sex hormone-binding globuline and others), and biophysical markers (arteriography, visceral adiposity). Risk factors for macrosomia include obesity and diabetes in the maternal history, pregnancy associated plasma protein-A and free β subunit of human chorionic gonadotropin as biochemical markers, and nuchal translucency and uterine artery Doppler as biophysical markers. Prediction models combining maternal history, biochemical and biophysical markers can achieve a detection rate of 65% and 35% for GD and macrosomia, respectively, with a false positive rate of 10% (AU)
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Humanos , Femenino , Diabetes Gestacional/epidemiología , Diabetes Gestacional/fisiopatología , Macrosomía Fetal/complicaciones , Macrosomía Fetal/diagnóstico , Factores de Riesgo , Tamizaje Masivo/análisis , Tamizaje Masivo/métodos , Primer Trimestre del Embarazo/fisiología , Morbilidad , BiomarcadoresRESUMEN
OBJECTIVES: To find the best early predictor model for fetal growth and large for gestational age (LGA) infants considering clinical, ultrasonographic and biochemical variables. METHOD: In 2097 singleton pregnancies at first trimester, we evaluated maternal characteristics, PAPP-A and ß-HCG proteins, fetal nuchal translucency thickness and uterine artery pulsatility index (UtA-PI). At second trimester fetal ultrasound biometry and UtA-PI were then measured. The relationships between birth weight and LGA and maternal characteristics, first and second trimester variables, and all variables combined, were studied. The performance of screening was determined by receiver operating characteristic curves analysis. RESULTS: Stepwise regression analysis showed that in the prediction of birthweight percentile there were significant contributions from all maternal factors, PAPP-A and Ut-A PI in the first trimester, and fetal biometric variables in the second trimester. Maternal charateristics combined with PAPP-A, ß-hCG, fetal NT and uterine artery PI identified 30.2 % LGA (FPR 10%). The combined model reached a sensitivity of 41.2% (FPR 10%) and 56.2% (FPR 20%). CONCLUSIONS: Sensitivity of the screening for LGA improves significantly after addition of second trimester ultrasound measurements to first trimester variables and maternal characteristics.
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Macrosomía Fetal/diagnóstico por imagen , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Ultrasonografía Prenatal/métodos , Adulto , Femenino , Desarrollo Fetal , Edad Gestacional , Humanos , Recién Nacido , Estudios Longitudinales , Embarazo , Complicaciones del Embarazo/diagnóstico por imagenRESUMEN
OBJECTIVE: To determine the effect of using customized vs. standard population birthweight curves to define large for gestational age (LGA) infants. METHODS: We analyzed data obtained from 2,097 singleton pregnancies using three different methods of classifying newborn birthweight: standard population curves, British or Spanish customized curves. We recorded maternal characteristics, proportion of LGA newborns when using each method, percentage of LGA according to one method but not for the others, and concordance between the different methods. RESULTS: The proportion of LGA newborns according to Spanish customized curves was significantly lower than that calculated using either standard general population birthweight curves or British curves (p < 0.001). A third (33.9%) of the infants classified as LGA according to the general population method were adequate for gestational age (AGA) when the Spanish customized curves were used, and 18.5% of non-LGA were LGA according to customized curves (p < 0.001). Concordance between the different models high, but on excluding AGA the concordance coefficient was low (Cohen's κ <0.4). CONCLUSIONS: The use of customized curves allows differentiation between constitutional LGA and cases of fetal overgrowth, leading to a decrease in the rate of both false-positives and negatives as well as the overall proportion of LGA babies.