Fetal Left Ventricle Function Evaluated by Two-Dimensional Speckle-Tracking Echocardiography across Clinical Stages of Severity in Growth-Restricted Fetuses.

Fetal growth restriction (FGR) can result in adverse perinatal outcomes due to cardiac dysfunction. This study used 2D speckle-tracking echocardiography to assess left ventricle (LV) longitudinal strain across FGR severity stages. A prospective longitudinal cohort study measured global (GLS) and segmental LV longitudinal strain in FGR fetuses, with evaluations conducted at various time points. FGR was classified into subtypes based on published criteria using fetal weight centile and Doppler parameters. A linear mixed model was employed to analyze repeated measures and compare Z-score measurements between groups throughout gestational age. The study included 40 FGR fetuses and a total of 107 evaluations were performed: 21 from small for gestational age (SGA), 74 from the FGR stage I, and 12 from the FGR stage ≥ II. The results indicate that SGA and stage I FGR fetuses exhibit higher LV GLS than stages ≥ II. Throughout gestation, SGA and FGR stage I fetuses showed similar behavior with consistently better LV GLS values when compared to FGR stages ≥ II. No significant differences were observed in LV GLS strain behavior between SGA and FGR stage I. In conclusion, all FGRs show signs of early cardiac dysfunction, with severe cases demonstrating significantly a lower LV GLS when compared to mild cases, suggesting deterioration of cardiac dysfunction with progression of fetal compromise.

Multicentre randomised trial of screening with sFlt1/PlGF and planned delivery to prevent pre-eclampsia at term: protocol of the PE37 study.

INTRODUCTION: Pre-eclampsia affects ~5%-7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal-fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35-37 weeks' gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35-37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes. METHODS AND ANALYSIS: We propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35-37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect). ETHICS AND DISSEMINATION: The study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04766866.

Neurodesarrollo a los 2 años en cardiopatía congénita: utilidad pronóstica de los marcadores de daño cerebral / Neurodevelopmental outcomes in congenital heart disease: Usefulness of biomarkers of brain injury

Introducción: En la actualidad, las alteraciones del neurodesarrollo son la complicación más frecuente en los pacientes con cardiopatía congénita (CC) en edad escolar. Analizamos la incidencia de eventos neurológicos agudos (ENA) en pacientes con CC sometidos a cirugía cardiaca y la utilidad de los neuromarcadores para predecir el neurodesarrollo. Métodos: Estudio prospectivo observacional en recién nacidos (RN) con CC diagnosticada prenatalmente, y sometidos a cirugía el primer año de vida. Se evaluaron: 1) biomarcadores sanguíneos de lesión cerebral (S100B, enolasa neuronal específica) en sangre de cordón y periquirúrgicos; 2) datos clínicos y analíticos perinatales y periquirúrgicos; 3) tratamientos y complicaciones, y 4) neurodesarrollo (escala de Bayley III) a los 2 años. Resultados: Se incluyeron 84 RN con CC de diagnóstico fetal, confirmada posnatalmente, sometidos a cirugía cardiaca en el primer año de vida. Diecisiete pacientes tenían corazón univentricular, 20 pacientes obstrucción izquierda y 10 síndromes genéticos. Fallecieron en el periodo posquirúrgico 5 pacientes (5,9%) y 9 pacientes presentaron ENA (10,7%). Las puntuaciones medias en el test de Bayley III fueron normales, pero el 31% tuvieron alteración cognitiva, motora o en el lenguaje. Los pacientes con síndromes genéticos, ENA y CC univentriculares tuvieron peor neurodesarrollo. La elevación de S100B en el postoperatorio inmediato se correlacionó con peores puntuaciones. Conclusiones: Los pacientes con CC sometidos a cirugía tienen mayor riesgo de sufrir alteraciones del neurodesarrollo. Los pacientes con síndromes genéticos o corazones univentriculares presentan peores resultados. Presentar ENA posquirúrgico puede contribuir a peores resultados. Niveles de S100B elevados en el postoperatorio se correlacionan con peores resultados en los test de neurodesarrollo a los 2 años...(AU)

Introduction: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. Methods: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. Results: The study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. Conclusions: Children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years...(AU)

Neurodevelopmental outcomes in congenital heart disease: Usefulness of biomarkers of brain injury.

INTRODUCTION: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. METHODS: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. RESULTS: the study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. CONCLUSIONS: children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer follow-ups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.

Efficacy and safety of hydroxychloroquine for treatment of mild SARS-CoV-2 infection and prevention of COVID-19 severity in pregnant and postpartum women: A randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Pregnant women have an increased risk of severe COVID-19. Evaluation of drugs with a safety reproductive toxicity profile is a priority. At the beginning of the pandemic, hydroxychloroquine (HCQ) was recommended for COVID-19 treatment. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted in eight teaching hospitals in Spain to evaluate the safety and efficacy of HCQ in reducing viral shedding and preventing COVID-19 progression. Pregnant and postpartum women with a positive SARS-CoV-2 PCR (with or without mild COVID-19 signs/symptoms) and a normal electrocardiogram were randomized to receive either HCQ orally (400 mg/day for 3 days and 200 mg/day for 11 days) or placebo. PCR and electrocardiogram were repeated at day 21 after treatment start. Enrollment was stopped before reaching the target sample due to low recruitment rate. Trial registration EudraCT #: 2020-001587-29, on April 2, 2020. CLINICAL TRIALS: gov # NCT04410562, registered on June 1, 2020. RESULTS: A total of 116 women (75 pregnant and 41 post-partum) were enrolled from May 2020 to June 2021. The proportion of women with a positive SARS-CoV-2 PCR at day 21 was lower in the HCQ group (21.8%, 12/55) than in the placebo group (31.6%, 18/57), although the difference was not statistically significant (P = 0.499). No differences were observed in COVID-19 progression, adverse events, median change in QTc, hospital admissions, preeclampsia or poor pregnancy and perinatal outcomes between groups. CONCLUSIONS: HCQ was found to be safe in pregnant and postpartum women with asymptomatic or mild SARS-CoV-2 infection. Although the prevalence of infection was decreased in the HCQ group, the statistical power was insufficient to confirm the potential beneficial effect of HCQ for COVID-19 treatment.

Dopamine receptors D1 and D2 show prognostic significance and potential therapeutic applications for endometrial cancer patients.

OBJECTIVE: Catecholaminergic signaling has been a target for therapy in different type of cancers. In this work, we characterized the ADRß2, DRD1 and DRD2 expression in healthy tissue and endometrial tumors to evaluate their prognostic significance in endometrial cancer (EC), unraveling their possible application as an antitumor therapy. METHODS: 109 EC patients were included. The expression of the ADRß2, DRD1 and DRD2 proteins was evaluated by immunohistochemistry and univariate and multivariate analysis to assess their association with clinic-pathological and outcome variables. Finally, HEC1A and AN3CA EC cell lines were exposed to different concentrations of selective dopaminergic agents alone or in combination to study their effects on cellular viability. RESULTS: ADRß2 protein expression was not associated with clinico-pathological parameters or prognosis. DRD1 protein expression was reduced in tumors samples but showed a significant inverse association with tumor size and stage. DRD2 protein expression was significantly associated with non-endometrioid EC, high grade tumors, tumor size, worse disease-free survival (HR = 3.47 (95%CI:1.35-8.88)) and overall survival (HR = 2.98 (95%CI:1.40-6.34)). The DRD1 agonist fenoldopam showed a reduction of cellular viability in HEC1A and AN3CA cells. The exposure to domperidone, a DRD2 antagonist, significantly reduced cell viability compared to the control. Finally, DRD1 agonism and DRD2 antagonism combination induced a significant reduction in cell viability of the AN3CA cells compared to monotherapy, close to being an additive response than a synergistic effect (CI of 1.1 at 0.5% Fa). CONCLUSION: DRD1 and DRD2 expression levels showed a significant association with clinico-pathological parameters. Both the combined activation of DRD1 and blockage of DRD2 may form an innovative strategy to inhibit tumor growth in EC.

Impact of Angiogenic and Cardiovascular Biomarkers for Prediction of Placental Dysfunction in the First Trimester of Pregnancy.

Algorithms for first-trimester prediction of pre-eclampsia usually include maternal risk factors, blood pressure, placental growth factor (PlGF), and uterine artery Doppler pulsatility index. However, these models lack sensitivity for the prediction of late-onset pre-eclampsia and other placental complications of pregnancy, such as small for gestational age infants or preterm birth. The aim of this study was to assess the screening performance of PlGF, soluble fms-like tyrosine kinase-1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), uric acid, and high-sensitivity cardiac troponin T (hs-TnT) in the prediction of adverse obstetric outcomes related to placental insufficiency. This retrospective case-control study was based on a cohort of 1390 pregnant women, among which 210 presented pre-eclampsia, small for gestational age infants, or preterm birth. Two hundred and eight women with healthy pregnancies were selected as controls. Serum samples were collected between weeks 9 and 13 of gestation, and maternal serum concentrations of PlGF, sFlt-1, NT-proBNP, uric acid, and hs-TnT were measured. Multivariate regression analysis was used to generate predictive models combining maternal factors with the above-mentioned biomarkers. Women with placental dysfunction had lower median concentrations of PlGF (25.77 vs. 32.00 pg/mL; p < 0.001), sFlt-1 (1212.0 vs. 1363.5 pg/mL; p = 0.001), and NT-proBNP (51.22 vs. 68.71 ng/L; p < 0.001) and higher levels of uric acid (193.66 µmol/L vs. 177.40 µmol/L; p = 0.001). There was no significant difference between groups regarding the sFlt-1/PlGF ratio. Hs-TnT was not detected in 70% of the maternal serums analyzed. Altered biomarker concentrations increased the risk of the analyzed complications both in univariate and multivariate analyses. The addition of PlGF, sFlt-1, and NT-proBNP to maternal variables improved the prediction of pre-eclampsia, small for gestational age infants, and preterm birth (area under the curve: 0.710, 0.697, 0.727, and 0.697 vs. 0.668, respectively). Reclassification improvement was greater in maternal factors plus the PlGF model and maternal factors plus the NT-p roBNP model (net reclassification index, NRI: 42.2% and 53.5%, respectively). PlGF, sFlt-1, NT-proBNP, and uric acid measurements in the first trimester of pregnancy, combined with maternal factors, can improve the prediction of adverse perinatal outcomes related to placental dysfunction. In addition to PlGF, uric acid and NT-proBNP are two promising predictive biomarkers for placental dysfunction in the first trimester of pregnancy.

Low complement levels are related to poor obstetric outcomes in women with obstetric antiphospholipid syndrome. The EUROAPS Registry Study Group.

INTRODUCTION: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease related to antiphospholipid antibodies (aPL) with primaryinflammatory injury followed by clot cascade activation and thrombus formation. Complement system activation and their participation in aPL-related thrombosis is unclosed. METHODS: We haveanalysed adverse pregnancy outcomes (APO) related to low complement (LC) levels in a cohort of 1048 women fulfilling classification criteria for OAPS. RESULTS: Overall, 223 (21.3%) women presented LC values, during pregnancy. The length of pregnancy was shorter in OAPS women with LC compared to those with normal complement (NC) (median: 33 weeks, interquartile range: [24-38] vs. 35 weeks [27-38]; p = 0.022). Life new-born incidence was higher in patients with NC levels than in those with LC levels (74.4% vs. 67.7%; p = 0.045). Foetal losses were more related to women with triple or double aPL positivity carrying LC than NC values (16.3% vs. 8.0% NC; p = 0.027). Finally, some placental vasculopathies were affected in OAPS patients with LC as late Foetal Growth Restriction (FGR >34 weeks) rise to 7.2% in women with LC vs. 3.2% with NC (p = 0.007). DISCUSSION: Data from our registry indicate that incidence of APO was higher in OAPS women with LC levels and some could be reverted by the correct treatment.

Longitudinal Behavior of Left-Ventricular Strain in Fetal Growth Restriction.

Fetal growth restriction (FGR) is associated with an increased risk of adverse outcomes resulting from adaptive cardiovascular changes in conditions of placental insufficiency, leading to cardiac deformation and dysfunction, which can be evaluated with 2D speckle tracking echocardiography (2D-STE). The aim of the present study was to evaluate whether reduced fetal growth is associated with cardiac left-ventricle (LV) dysfunction, using 2D-STE software widely used in postnatal echocardiography. A prospective longitudinal cohort study was performed, and global (GLO) and segmental LV longitudinal strain was measured offline and compared between FGR and appropriate-for-gestational-age (AGA) fetuses throughout gestation. All cases of FGR fetuses were paired 1:2 to AGA fetuses, and linear mixed model analysis was performed to compare behavior differences between groups throughout pregnancy. Our study shows LV fetal longitudinal strain in FGR and AGA fetuses differed upon diagnosis and behaved differently throughout gestation. FGR fetuses had lower LV strain values, both global and segmental, in comparison to AGA, suggesting subclinical cardiac dysfunction. Our study provides more data regarding fetal cardiac function in cases of placental dysfunction, as well as highlights the potential use of 2D-STE in the follow-up of cardiac function in these fetuses.

Predictive Model for Preeclampsia Combining sFlt-1, PlGF, NT-proBNP, and Uric Acid as Biomarkers.

N-terminal pro-brain natriuretic peptide (NT-proBNP) and uric acid are elevated in pregnancies with preeclampsia (PE). Short-term prediction of PE using angiogenic factors has many false-positive results. Our objective was to validate a machine-learning model (MLM) to predict PE in patients with clinical suspicion, and evaluate if the model performed better than the sFlt-1/PlGF ratio alone. A multicentric cohort study of pregnancies with suspected PE between 24+0 and 36+6 weeks was used. The MLM included six predictors: gestational age, chronic hypertension, sFlt-1, PlGF, NT-proBNP, and uric acid. A total of 936 serum samples from 597 women were included. The PPV of the MLM for PE following 6 weeks was 83.1% (95% CI 78.5−88.2) compared to 72.8% (95% CI 67.4−78.4) for the sFlt-1/PlGF ratio. The specificity of the model was better; 94.9% vs. 91%, respectively. The AUC was significantly improved compared to the ratio alone [0.941 (95% CI 0.926−0.956) vs. 0.901 (95% CI 0.880−0.921), p < 0.05]. For prediction of preterm PE within 1 week, the AUC of the MLM was 0.954 (95% CI 0.937−0.968); significantly greater than the ratio alone [0.914 (95% CI 0.890−0.934), p < 0.01]. To conclude, an MLM combining the sFlt-1/PlGF ratio, NT-proBNP, and uric acid performs better to predict preterm PE compared to the sFlt-1/PlGF ratio alone, potentially increasing clinical precision.

Glomerular diseases in pregnancy: pragmatic recommendations for clinical management.

Our understanding of the various aspects of pregnancy in women with kidney diseases has significantly improved in the last decades. Nevertheless, little is known about specific kidney diseases. Glomerular diseases are not only a frequent cause of chronic kidney disease in young women, but combine many challenges in pregnancy: immunologic diseases, hypertension, proteinuria, and kidney tissue damage. An international working group undertook the review of available current literature and elicited expert opinions on glomerular diseases in pregnancy with the aim to provide pragmatic information for nephrologists according to the present state-of-the-art knowledge. This work also highlights areas of clinical uncertainty and emphasizes the need for further collaborative studies to improve maternal and fetal health.

Cord Blood Cardiovascular Biomarkers in Left-Sided Congenital Heart Disease.

Fetal echocardiography has limited prognostic ability in the evaluation of left-sided congenital heart defects (left heart defects). Cord blood cardiovascular biomarkers could improve the prognostic evaluation of left heart defects. A multicenter prospective cohort (2013−2019) including fetuses with left heart defects (aortic coarctation, aortic stenosis, hypoplastic left heart, and multilevel obstruction (complex left heart defects) subdivided according to their outcome (favorable vs. poor), and control fetuses were evaluated in the third trimester of pregnancy at three referral centers in Spain. Poor outcome was defined as univentricular palliation, heart transplant, or death. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factor ß, placental growth factor, and soluble fms-like tyrosine kinase-1 were determined. A total of 45 fetuses with left heart defects (29 favorable and 16 poor outcomes) and 35 normal fetuses were included, with a median follow-up of 3.1 years (interquartile range 1.4−3.9). Left heart defects with favorable outcome showed markedly increased cord blood transforming growth factor ß (normal heart median 15.5 ng/mL (6.8−21.4) vs. favorable outcome 51.7 ng/mL (13.8−73.9) vs. poor outcome 25.1 ng/mL (6.9−39.0), p = 0.001) and decreased placental growth factor concentrations (normal heart 17.9 pg/mL (13.8−23.9) vs. favorable outcome 12.8 pg/mL (11.7−13.6) vs. poor outcome 11.0 pg/mL (8.8−15.4), p < 0.001). Poor outcome left heart defects had higher N-terminal precursor of B-type natriuretic peptide (normal heart 508.0 pg/mL (287.5−776.3) vs. favorable outcome 617.0 pg/mL (389.8−1087.8) vs. poor outcome 1450.0 pg/mL (919.0−1645.0), p = 0.001) and drastically reduced soluble fms-like tyrosine kinase-1 concentrations (normal heart 1929.7 pg/mL (1364.3−2715.8) vs. favorable outcome (1848.3 pg/mL (646.9−2313.6) vs. poor outcome 259.0 pg/mL (182.0−606.0), p < 0.001). Results showed that fetuses with left heart defects present a distinct cord blood biomarker profile according to their outcome.

Gestational Age-Adjusted Reference Ranges for Fetal Left Ventricle Longitudinal Strain by Automated Cardiac Motion Quantification between 24 and 37 Weeks' Gestation.

INTRODUCTION: The objective of this study was to construct gestational age (GA) based reference values for left ventricle (LV) longitudinal strain in normal fetuses, between 24 and 37 weeks' gestation, assessing its feasibility and reproducibility with automated cardiac motion quantification software (aCMQ-QLab), which is widely used in postnatal echocardiography. METHODS: This prospective study included healthy gravid women with singleton pregnancies and no evidence of fetal structural cardiovascular disease. Fetal echocardiographies were performed between 24 and 37 GA. 2D four-chamber view clips were recorded and LV longitudinal strain was analyzed offline. Intra- and interobserver reproducibility between 2 independent observers was evaluated by intraclass correlation coefficients (ICC) and Bland-Altman scatterplots. Regression analysis was used to determine GA adjusted reference ranges and construct nomograms. RESULTS: LV longitudinal strain measurements were feasible in 95.4% of acquisitions. 435 clips were obtained. Intra- and interobserver ICC were 0.998 (95% CI 0.997-0.999) and 0.991 (95% CI 0.984-0.995), respectively. The global longitudinal strain and the middle and apical LV segments showed progressive decline as GA advanced, whereas the basal segments remained stable. CONCLUSIONS: Assessment of LV longitudinal strain by aCMQ-QLab is feasible, reproducible, and within normal ranges. Our results offer more information regarding fetal cardiac function assessment with 2D speckle tracking techniques, aiding in the introduction of this software into research practice, encouraging the realization of more studies, and probably helping in its future use in clinical practice, allowing longitudinal surveillance of strain without intervendor variability and aiding in follow-up of fetal cardiac conditions before and after birth, as it is the most commonly used software postnatally.

Malestar psicológico, ajuste diádico y dinámica familiar tras el diagnóstico prenatal de cardiopatía congénita / Psychological distress, dyadic adjustment and family dynamics after prenatal diagnosis of congenital heart disease

Introducción: Las cardiopatías congénitas (CC) se encuentran entre las enfermedades congénitas más frecuentes. Cuando se informa a los padres y las madres del diagnóstico de una CC durante el embarazo, tienen que afrontar una serie de cambios psicológicos a nivel individual e interpersonal. El objetivo del estudio es evaluar el impacto psicológico que produce en los padres el diagnóstico de una CC en el periodo prenatal. La muestra incluyó 214 participantes, madres y sus parejas (grupo de casos: 57 gestantes con fetos diagnosticados de CC y sus parejas; grupo control: 50 gestantes y sus parejas). Método: Administración del BSI-18, el DAS y el FACES-III tras el diagnóstico prenatal. Resultados: Muchos progenitores (alrededor del 83,6%) pasaron por fases de choque emocional y negación tras recibir el diagnóstico de una enfermedad que necesitaban afrontar y aceptar. A nivel individual, el 35,1% de los padres y el 47,4% de las madres tuvieron puntuaciones significativas en el malestar psicológico. A nivel de la pareja, tanto los padres (77%) como las madres (82,4%) presentaron un ajuste diádico idealizado. Por último, el 43,9% de los padres y el 42,2% de las madres reflejaron una dinámica familiar moderada. Conclusión: Los resultados ilustran la complejidad de la etapa inicial que atravesaban las parejas participantes. (AU)

Introduction: Congenital heart disease (CHD) is one of the most frequent congenital diseases. When expectant fathers and mothers are informed of a CHD during pregnancy, they have to confront a series of individual and interpersonal psychological changes. The aim of the study was to evaluate the psychological impact of a prenatal diagnosis of CHD on expectant parents. The sample included 214 participants, mothers and their partners (case group, 57 pregnant women carrying a foetus with CHD and their partners; and control group, 50 pregnant women and their partners). Method: Administration of BSI-18, DAS and FACES-III following prenatal diagnosis. Results: Many parents (approximately 83.6%) went through stages of shock and denial in response to the diagnosis of disease that they had to confront and accept. At the individual level, 35.1% of fathers and 47.4% mothers had clinically significant scores of psychological distress. At the couple level, both fathers (77%) and mothers (82.4%) had expressed an idealized dyadic adjustment. Lastly, the perception of the family dynamic by 43.9% of fathers and 42.2% of mothers was in the mid-range. Conclusion: The results highlight the complexity of the initial stage that these couples were going through. (AU)

First-Trimester Sequential Screening for Preeclampsia Using Angiogenic Factors: Study Protocol for a Prospective, Multicenter, Real Clinical Setting Study.

Introduction: The incidence of preeclampsia (PE) is about 2-8%, making it one of the leading causes of perinatal morbidity and maternal mortality in the world. Early prophylactic low dose administration (150 mg) of acetylsalicylic acid is associated with a significant reduction in the incidence of early-onset PE, intrauterine growth restriction (IUGR), and neonatal mean stay in the intensive care unit (ICU). Universal implementation of a first-trimester screening system including angiogenic and antiangiogenic markers [the Placental Growth Factor (PlGF) and/or soluble fms-like Tyrosine Kinase-1 (sFlt-1)] has shown a prediction rate of 90% for early-onset PE but entails a high financial cost. The aim of this study is to determine the predictive and preventive capacity of a universal PE first-trimester two-step sequential screening model, determining the PlGF only in patients previously classified as intermediate risk by means of a multivariate model based on resources already used in the standard pregnancy control, in a real clinical setting. We hypothesize that this screening model will achieve similar diagnostic performance as the universal determination of PlGF but at a lower economic cost. Methods and Analysis: This is a prospective, multicentric, cohort study in a real-world clinical setting. Every singleton pregnancy will be recruited at the routine first pregnancy visit. In a first step, the first-trimester risk of PE will be calculated using a multivariate Gaussian distribution model, based on medical history, mean blood pressure, Pregnancy-Associated Plasma Protein A (PAPP-A), and Uterine Artery Doppler Pulsatility Index (UTPI). Patients will be classified into three risk groups for PE: (1) risk ≥ 1/50, high-risk with no further testing (blinded PlGF); (2) risk between 1/51 and 1/500, medium-risk requiring further testing; and (3) risk ≤ 1/501, low-risk with no further testing. In a second step, the PlGF will only be determined in those patients classified as intermediate risk after this first step, and then reclassified into high- or low-risk groups. Prophylactic administration of aspirin (150 mg/day) will be prescribed only in high risk patients. As a secondary objective, sFlt-1 values will be blindly determined in patients with high and intermediate risk to assess its potential performance in the screening for PE. Ethics and Dissemination: The study will be conducted in accordance with the principles of Good Clinical Practice. This study is approved by the Aragon Research Ethics Committee (CEICA) on 3 July 2020 (15/2020). Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04767438.

Reduction in Preterm Preeclampsia after Contingent First-Trimester Screening and Aspirin Prophylaxis in a Routine Care Setting.

Objectives: Several multivariate algorithms for preeclampsia (PE) screening in the first trimester have been developed over the past few years. These models include maternal factors, mean arterial pressure (MAP), uterine artery Doppler (UtA-PI), and biochemical markers (pregnancy-associated plasma protein-A (PAPP-A) or placental growth factor (PlGF)). Treatment with low-dose aspirin (LDA) has shown a reduction in the incidence of preterm PE in women with a high-risk assessment in the first trimester. An important barrier to the implementation of first-trimester screening is the cost of performing tests for biochemical markers in the whole population. Theoretical contingent strategies suggest that two-stage screening models could also achieve high detection rates for preterm PE with lower costs. However, no data derived from routine care settings are currently available. This study was conducted to validate and assess the performance of a first-trimester contingent screening process using PlGF for PE, with prophylactic LDA, for decreasing the incidence of preterm PE. Methods: This was a two-phase study. In phase one, a contingent screening model for PE was developed using a multivariate validated model and a historical cohort participating in a non-interventional PE screening study (n = 525). First-stage risk assessment included maternal factors, MAP, UtA-PI, and PAPP-A. Several cut-off levels were tested to determine the best screening performance, and three groups were then defined (high-, medium-, and low-risk groups). PlGF was determined in the medium-risk group to calculate the final risk. Phase two included a validation cohort of 847 singleton pregnancies prospectively undergoing first-trimester PE screening using this approach. Women at high risk of PE received prophylactic treatment with 150 mg of LDA. The clinical impact of the model was evaluated by comparing the incidence of early-onset (<34 weeks) and preterm (<37 weeks) PE between groups. Results: Cut-off levels for the contingent screening model were chosen in the first and second stages of screening to achieve a performance with sensitivities of 100% and 80% for early-onset and preterm PE detection, respectively, with a 15% false positive rate. In the development phase, 21.5% (n = 113) of the women had a medium risk of PE and required second-stage screening. In the prospective validation phase, 15.3% (n = 130) of the women required second-stage screening for PlGF, yielding an overall screen-positive rate of 14.9% (n = 126). The incidence of preterm PE was reduced by 68.4% (1.9% vs. 0.6%, p = 0.031) after one year of screening implementation. Conclusions: Implementation of contingent screening for PE using PlGF in a routine care setting led to a significant reduction (68.4%) in preterm PE, suggesting that contingent screening can achieve similar results to protocols using PlGF in the whole population. This could have financial benefits, with a similar reduction in the rate of preterm PE.

Nano-Based Approved Pharmaceuticals for Cancer Treatment: Present and Future Challenges.

Cancer is one of the main causes of death worldwide. To date, and despite the advances in conventional treatment options, therapy in cancer is still far from optimal due to the non-specific systemic biodistribution of antitumor agents. The inadequate drug concentrations at the tumor site led to an increased incidence of multiple drug resistance and the appearance of many severe undesirable side effects. Nanotechnology, through the development of nanoscale-based pharmaceuticals, has emerged to provide new and innovative drugs to overcome these limitations. In this review, we provide an overview of the approved nanomedicine for cancer treatment and the rationale behind their designs and applications. We also highlight the new approaches that are currently under investigation and the perspectives and challenges for nanopharmaceuticals, focusing on the tumor microenvironment and tumor disseminate cells as the most attractive and effective strategies for cancer treatments.

A study on exposure to greenspace during pregnancy and lipid profile in cord blood samples.

Although evidence reporting the beneficial associations of prenatal greenspace exposure with pregnancy outcomes is increasing, there is still a lack of evidence on the potential association of such exposure to greenspace on fetal lipid profile. We aimed to first-time investigate the associations between prenatal exposure to greenspace and lipid levels in the cord blood. The present study was based on data from 150 expectant mothers, residents of Sabzevar city in Iran (2018). For each participant, we identified exposure to greenspace in residential surroundings, residential accessibility to green space, use of green spaces, and the number of plant pots inside the home. Measures of levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and TC/HDL-C and TG/HDL-C ratios in samples of cord blood were applied to identify the lipid profile. We developed adjusted linear regression models to estimate the associations of each indicator of greenspace exposure with each cord blood lipid. We found increased greenspace in residential surroundings across a 100 m buffer, higher residential accessibility to green space, and more use of green spaces were associated with decreased cord blood lipid levels. The remainder findings regarding the greenspace in residential surroundings across 300 m and 500 m buffers and the number of plant pots were null. Some suggestions were observed for a potential mediatory role of air pollution. This study suggests that greenspace exposure during pregnancy may influence positively fetal lipid levels in the cord blood.