Obstetric Outcomes of SARS-CoV-2 Infection in Asymptomatic Pregnant Women

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Embaràs; Infecció asimptomàticaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Embarazo; Infección asintomáticaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Pregnancy; Asymptomatic infectionAround two percent of asymptomatic women in labor test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain. Families and care providers face childbirth with uncertainty. We determined if SARS-CoV-2 infection at delivery among asymptomatic mothers had different obstetric outcomes compared to negative patients. This was a multicenter prospective study based on universal antenatal screening for SARS-CoV-2 infection. A total of 42 hospitals tested women admitted for delivery using polymerase chain reaction, from March to May 2020. We included positive mothers and a sample of negative mothers asymptomatic throughout the antenatal period, with 6-week postpartum follow-up. Association between SARS-CoV-2 and obstetric outcomes was evaluated by multivariate logistic regression analyses. In total, 174 asymptomatic SARS-CoV-2 positive pregnancies were compared with 430 asymptomatic negative pregnancies. No differences were observed between both groups in key maternal and neonatal outcomes at delivery and follow-up, with the exception of prelabor rupture of membranes at term (adjusted odds ratio 1.88, 95% confidence interval 1.13-3.11; p = 0.015). Asymptomatic SARS-CoV-2 positive mothers have higher odds of prelabor rupture of membranes at term, without an increase in perinatal complications, compared to negative mothers. Pregnant women testing positive for SARS-CoV-2 at admission for delivery should be reassured by their healthcare workers in the absence of symptoms.This project was supported by public funds obtained in competitive calls: Grant COV20/00021 (EUR 43,000 from the Instituto de Salud Carlos III—Spanish Ministry of Health and co-financed with Fondo Europeo de Desarrollo Regional (FEDER) funds. Dr Cruz-Lemini is supported by a Juan Rodés contract JR19/00047, Instituto de Salud Carlos III—Spanish Ministry of Health. The funding bodies had no role in the study design, in the collection or analysis of the data, or in manuscript writing

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

Angiogenic factors; Preeclampsia; Uric acidFactores angiogénicos; Preeclampsia; Ácido úricoFactors angiogènics; Preeclàmpsia; Àcid úricN-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.This work was supported by public funds obtained in competitive calls with peer review (grant PI19/00702), Insituto de Salud Carlos III, Spanish Ministry of Health, by the Maternal and Child Health and Development Network (SAMID, RD16/0022/0015), Instituto de Salud Carlos III, Madrid, Spain, the Spanish Clinical Research and Clinical Trials Platform, SCReN (Spanish Clinical Research Network), funded by the ISCIII-General Subdirectorate for Evaluation and Promotion of Research, through project PT13/0002/0028, integrated in the 2013–2016 R + D + I State Plan and co-financed by and the European Regional Development Fund (FEDER); and by the Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin Network (RICORS, RD21/0012/0001), Instituto de Salud Carlos III, Madrid, Spain, funded by the Recovery, Transformation and Resilience Plan 2017–2020, ISCIII, and by the European Union-Next Generation EU. Dr Cruz-Lemini is supported by Juan Rodés contract JR19/00047, Instituto de Salud Carlos III-Spanish Ministry of Health. Funding sources were not involved in study design, collection, analysis, and interpretation of data

Revealed versus concealed criteria for placental insufficiency in an unselected obstetric population in late pregnancy (RATIO37): randomised controlled trial study protocol.

INTRODUCTION: Fetal growth restriction (FGR) affects 5%-10% of all pregnancies, contributing to 30%-50% of stillbirths. Unfortunately, growth restriction often is not detected antenatally. The last weeks of pregnancy are critical for preventing stillbirth among babies with FGR because there is a pronounced increase in stillbirths among growth-restricted fetuses after 37 weeks of pregnancy. Here we present a protocol (V.1, 23 May 2016) for the RATIO37 trial, which evaluates an integrated strategy for accurately selecting at-risk fetuses for delivery at term. The protocol is based on the combination of fetal biometry and cerebroplacental ratio (CPR). The primary objective is to reduce stillbirth rates. The secondary aims are to detect low birth weights and adverse perinatal outcomes. METHODS AND ANALYSIS: The study is designed as multicentre (Spain, Chile, Mexico,Czech Republic and Israel), open-label, randomised trial with parallel groups. Singleton pregnancies will be invited to participate after routine second-trimester ultrasound scan (19+0-22+6 weeks of gestation), and participants will be randomly allocated to receive revealed or concealed CPR evaluation. Then, a routine ultrasound and Doppler scan will be performed at 36+0-37+6 weeks. Sociodemographic and clinical data will be collected at enrolment. Ultrasound and Doppler variables will be recorded at 36+0-37+6 weeks of pregnancy. Perinatal outcomes will be recorded after delivery. Univariate (with estimated effect size and its 95% CI) and multivariate (mixed-effects logistic regression) comparisons between groups will be performed. ETHICS AND DISSEMINATION: The study will be conducted in accordance with the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 23May 2016. 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

Differential changes in myocardial performance index and its time intervals in donors and recipients of twin-to-twin transfusion syndrome before and after laser therapy.

OBJECTIVE: To evaluate left myocardial performance index (MPI) and time intervals in fetuses with twin-to-twin transfusion syndrome (TTTS) before and after laser surgery. METHODS: Fifty-one fetal pairs with TTTS and 47 uncomplicated monochorionic twin pairs were included. Left ventricular isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) were measured using conventional Doppler. RESULTS: Recipients showed prolonged ICT (46 ± 12 vs. 31 ± 8 vs. 30 ± 5 ms; p < 0.001) and IRT (51 ± 9 vs. 43 ± 8 vs. 43 ± 5 ms; p < 0.001) and higher MPI (0.57 ± 0.12 vs. 0.47 ± 0.09 vs. 0.44 ± 0.05; p < 0.001) than donors and controls. Donors showed shorter ET than recipients and controls (157 ± 12 vs. 169 ± 10 vs. 168 ± 10 ms; p < 0.001) and higher MPI than controls (0.47 ± 0.09 vs. 0.44 ± 0.05; p = 0.006). Preoperative MPI changes were observed in all TTTS stages. Time intervals partially improved after surgery. CONCLUSION: Donor and recipient twins had higher MPI due to different changes in the time intervals, possibly reflecting the state of hypovolemia in the donor and hypervolemia and pressure overload in the recipient

Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. METHODS: Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). DISCUSSION: The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children's neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD

Fetal cardiovascular dysfunction in intrauterine growth restriction as a predictive marker of perinatal outcome and cardiovascular disease in childhood

Most risk factors leading to cardiovascular disease are already present in childhood and the importance of early identification of pediatric cardiovascular risk factors is now well recognized. Hypertension in the child has been associated with substantial long-term health risks and considered an indication for lifestyle modifications. Current clinical guidelines contemplate screening for hypertension in children over 3 years of age, in order to provide strategies for promoting cardiovascular health, which can be integrated into comprehensive pediatric care. Interventions in the IUGR group could go from blood pressure monitoring before 3 years of age, recommending lack of exposure to other risk factors (secondary smoking, obesity), surveillance of catch-up growth or administration of hypotensors and specially, promoting exercise and physical activity. A recent randomized trial in a large cohort of children suggest that the inverse association of fetal growth with arterial wall thickness in childhood can be prevented by dietary ω-3 fatty acid supplementation over the first 5 years of life. IUGR is not listed among those conditions presumed to increase cardiovascular risk, in current guidelines. Considering IUGR affects 5-10% of all newborns, the findings of this study would affect thousands of children per year. Currently, there are no prenatal parameters described that may aid in selecting those fetuses with later hypertension and arterial remodeling that may benefit for early screening in infancy and other preventive measures or interventions. Both fetal and child cardiovascular evaluations have proven to be reliable techniques for describing changes in IUGR; cardiovascular dysfunction has been found subclinically and may have implications for cardiovascular risk in future life. The main aim of this work was to evaluate cardiovascular function parameters in IUGR fetuses as predictors of perinatal and postnatal cardiovascular outcome. In order to do this, we looked to validate the reproducibility of measurements and techniques not previously described in IUGR fetuses (studies 1 and 2), to evaluate whether fetal cardiovascular parameters could help us predict perinatal outcome (study 3) and finally to assess the value of fetal echocardiography for prediction of postnatal cardiovascular risk factors, specifically hypertension and arterial remodeling (study 4). This thesis confirms previous studies showing fetal cardiac dysfunction can be documented by fetal echocardiography; it validates different methods for evaluating cardiac function in the fetus and demonstrates the predictive value of these parameters for perinatal and postnatal cardiovascular outcome. Our first study demonstrates for the first time the validity of M-mode to assess longitudinal axis motion in IUGR. It further confirms previous research that IUGR fetuses have a significant decrease in longitudinal myocardial motion, as part of the fetal cardiovascular adaptation to placental insufficiency. In our second study, both TDI and 2D-derived strain analysis demonstrated to be feasible and reproducible to evaluate deformation parameters in the fetal heart. Our third study evaluated the independent and combined contribution of fetal cardiovascular parameters to the prediction of early-onset IUGR perinatal mortality. The study suggests an algorithm illustrating the chances of perinatal death against gestational age and DV, which might help clinical decisions in the management of early-onset IUGR fetuses. The fourth study provides, for the first time, evidence that fetal echocardiographic parameters are strongly associated to postnatal hypertension and arterial remodeling, which are recognized cardiovascular risk factors and surrogates for early-onset cardiovascular disease. It supports that a fetal cardiovascular score is strongly associated with the presence of postnatal hypertension and arterial remodeling at 6 months of age in IUGR. Echocardiographic parameters demonstrated a far better performance than perinatal factors and fetoplacental Doppler used for establishing the severity of IUGR.Los fetos con restricción del crecimiento intrauterino (RCIU) presentan remodelamiento cardiovascular el cual persiste en la infancia y se ha asociado a enfermedades cardiovasculares en el adulto. La hipertensión en la infancia se ha demostrado como un factor de riesgo cardiovascular para la enfermedad adulta. Un seguimiento estricto junto con intervenciones en la dieta se ha demostrado mejora la salud cardiovascular en estos niños, sin embargo no todas las restricciones del crecimiento tienen hipertensión en la infancia. El objetivo principal de esta tesis es definir los parámetros con mayor utilidad de la ecocardiografía fetal para predecir hipertensión y remodelamiento arterial en infantes de 6 meses de edad con restricción del crecimiento intrauterino. Para esto, se realizó un estudio de cohorte incluyendo fetos con RCIU y controles, seguidos desde vida prenatal hasta los 6 meses de edad. La evaluación prenatal consistió en una ecocardiografía funcional completa. A los 6 meses de edad estos niños fueron evaluados para hipertensión y remodelamiento arterial. Posteriormente se realizó la construcción de un score cardiovascular para determinar desde vida prenatal aquellos niños con mayor riesgo a presentar hipertensión en vida postnatal y que pudieran requerir vigilancia o intervenciones

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

Aortic and carotid intima-media thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity

Objective To assess carotid and aortic intima–media thickness (IMT) in term small‐for‐gestational‐age (SGA) newborns with and without prenatal signs of severity. Methods This prospective study comprised 67 cases diagnosed prenatally and 134 normally grown newborns. Cases were subclassified into SGA with no signs of severity and those with signs of severity, defined as a birth weight below the 3rd percentile or abnormal uterine artery Doppler or cerebroplacental ratio. Blood pressure and vascular IMT were evaluated. Results SGA newborns showed a non‐significant trend for higher values of blood pressure. IMT values were significantly increased in SGA newborns, with and without signs of severity, compared with controls. The magnitude of the increase was higher in SGA newborns with signs of severity. Conclusions Vascular IMT was increased in SGA newborns, irrespective of the presence or absence of prenatal signs of severity. This finding challenges the notion of ‘constitutionally small’ SGA, and supports the premise that the majority of SGA newborns have true growth restriction and suffer fetal cardiovascular programming.This study was supported by grants from Instituto de Salud Carlos III and Ministerio de Economia y Competitividad (ref. PI11/00051, PI11/01709, PI12/00801 and SAF2012‐37196) cofinanciado por el Fondo Europeo de Desarrollo Regional de la Unión Europea ‘Una manera de hacer Europa’, Spain; Centro para el Desarrollo Técnico Industrial (Ref. cvREMOD 2009‐2012) apoyado por el Ministerio de Economia y Competitividad y Fondo de inversión local para el empleo, Spain; Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and Thrasher Research Fund (Salt Lake City, USA)