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Objective: The maternal cardiovascular system of women with hypertensive disorders of pregnancy (HDP) can be impaired, with higher rates of left ventricular (LV) remodeling and diastolic dysfunction compared to those with normotensive pregnancy. The primary objective of this prospective study was to correlate cardiac indices obtained by transthoracic echocardiography (TTE) and circulating angiogenic markers, such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF)., Methods: In this study, 95 women with a pregnancy complicated by HDP and a group of 25 with an uncomplicated pregnancy at term underwent TTE and blood tests to measure sFlt-1 and PlGF during the peripartum period (before delivery or within a week of giving birth). Spearman's rank correlation was used to derive correlation coefficients between biomarkers and cardiac indices in the HDP and control populations., Results: The HDP group included 61 (64.2%) pre-eclamptic patients and, among them, 42 (68.9%) delivered before 37 weeks' gestation. Twelve women with HDP (12.6%) underwent blood sampling and TTE after delivery, and, as they showed significantly lower levels of angiogenic markers, they were excluded from the analysis. There was a correlation between sFlt-1 and LV mass index (LVMI) (r = 0.246; P = 0.026) and early diastolic mitral inflow velocity (E) and early diastolic mitral annular velocity (e') ratio (r = 0.272; P = 0.014) in the HDP group (n = 83), while in the controls, sFlt-1 showed a correlation with relative wall thickness (r = 0.409; P = 0.043), lateral e' (r = -0.562; P = 0.004) and E/e' ratio (r = 0.417; P = 0.042). PlGF correlated with LVMI (r = -0.238; P = 0.031) in HDP patients and with lateral e' (r = 0.466; P = 0.022) in controls. sFlt-1/PlGF ratio correlated with lateral e' (r = -0.568; P = 0.004) and E/e' ratio (r = 0.428; P = 0.037) in controls and with LVMI (r = 0.252; P = 0.022) and E/e' ratio (r = 0.269; P = 0.014) in HDP., Conclusions: Although the current data are not able to infer causality, they confirm the intimate relationship between the maternal cardiovascular system and angiogenic markers that are used both to diagnose and indicate the severity of HDP. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: Ventriculomegaly can be associated with long-term neurodevelopmental impairment. Prenatal diagnosis of ventriculomegaly is most commonly made at the routine second-trimester anomaly scan. The value of first-trimester ultrasound has expanded to early diagnosis and screening of fetal abnormalities. The objective of this study was to assess the predictive accuracy of first-trimester choroid-plexus-to-lateral-ventricle-or-head ratios for development of ventriculomegaly at a later gestational age., Methods: This was a case-control study of fetuses with isolated ventriculomegaly diagnosed after 16 weeks' gestation and a control group of normal fetuses (without ventriculomegaly). The exclusion criteria included aneuploidy, genetic syndrome and/or other brain abnormality. Stored two-dimensional first-trimester ultrasound images were analyzed blindly offline and fetal biometry was performed in the axial view of the fetal head. The ratios of choroid plexus area (PA) to lateral ventricular area (VA), choroid plexus length (PL) to lateral ventricular length (VL), choroid plexus diameter (PD) to lateral ventricular diameter (VD) and PA to biparietal diameter (BPD) were measured at 11 + 0 to 13 + 6 weeks' gestation. Intra- and interobserver variability of measurement of these fetal head biometric parameters at 11 + 0 to 13 + 6 weeks' gestation were assessed in 20 normal fetuses using intraclass correlation coefficients with 95% CI. The accuracy of first-trimester biometric measurements for prediction of ventriculomegaly was assessed using the area under the receiver-operating-characteristics curves (AUC)., Results: The analysis included 683 singleton pregnancies, of which 102 fetuses were diagnosed with ventriculomegaly. Ventriculomegaly was mild in 86 (84.3%) cases and severe in the other 16 (15.7%). All first-trimester fetal choroid-plexus-to-lateral-ventricle/head ratios were significantly lower in cases with ventriculomegaly compared with controls (P < 0.001), with good inter- and intraobserver agreement (≥ 0.95) for the majority of the fetal head biometric parameters assessed. On adjusting for crown-rump length, optimism-adjusted AUC values obtained after cross-validation showed that both PL/VL ratio (AUC, 0.87 (95% CI, 0.73-0.98)) and PA/VA ratio (AUC, 0.90 (95% CI, 0.82-0.98)) had good predictive accuracy for severe ventriculomegaly. The PA/BPD ratio (AUC, 0.73 (95% CI, 0.54-0.90)) had modest predictive ability, which was significantly lower compared with that of the PA/VA ratio and PL/VL ratio (P = 0.003 and P = 0.001, respectively). The predictive accuracy of PD/VD ratio was low with an AUC of 0.65 (95% CI, 0.47-0.84). Optimism-adjusted AUC values obtained after cross-validation showed that PA/VA ratio offered the highest predictive accuracy for mild ventriculomegaly with an AUC of 0.84 (95% CI, 0.79-0.89), followed by PL/VL ratio (AUC, 0.82 (95% CI, 0.76-0.88)), PA/BPD ratio (AUC, 0.76 (95% CI, 0.69-0.82)) and PD/VD ratio (AUC, 0.75 (95% CI, 0.67-0.81)). Calibration plots showed that both PA/VA and PL/VL ratios had good calibration., Conclusion: First-trimester prediction of ventriculomegaly using ratios of fetal choroid plexus to lateral ventricle/head appears promising. Future prospective studies are needed to validate the predictive accuracy of these ultrasound markers as a screening tool for ventriculomegaly. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Human pregnancy can be affected by numerous pathologies, from those which are mild and reversible to others which are life-threatening. Among these, gestational diabetes mellitus and hypertensive disorders of pregnancy with subsequent consequences stand out. Health problems experienced by women during pregnancy and postpartum are associated with significant costs to health systems worldwide and contribute largely to maternal mortality and morbidity. Major risk factors for mothers include obesity, advanced maternal age, cardiovascular dysfunction, and endothelial damage; in these scenarios, oxidative stress plays a major role. Markers of oxidative stress can be measured in patients with preeclampsia, foetal growth restriction, and gestational diabetes mellitus, even before their clinical onset. In consequence, antioxidant supplements have been proposed as a possible therapy; however, results derived from large scale randomised clinical trials have been disappointing as no positive effects were demonstrated. This review focuses on the latest evidence on oxidative stress in pregnancy complications, their early diagnosis, and possible therapies to prevent or treat these pathologies.

Background: Pregnant women are at an increased risk of mortality and morbidity owing to COVID-19. Many studies have reported on the association of COVID-19 with pregnancy-specific adverse outcomes, but prediction models utilizing large cohorts of pregnant women are still lacking for estimating the risk of maternal morbidity and other adverse events., Objective: The main aim of this study was to develop a prediction model to quantify the risk of progression to critical COVID-19 and intensive care unit admission in pregnant women with symptomatic infection., Study Design: This was a multicenter retrospective cohort study including 8 hospitals from 4 countries (the United Kingdom, Austria, Greece, and Turkey). The data extraction was from February 2020 until May 2021. Included were consecutive pregnant and early postpartum women (within 10 days of birth); reverse transcriptase polymerase chain reaction confirmed SARS-CoV-2 infection. The primary outcome was progression to critical illness requiring intensive care. The secondary outcomes included maternal death, preeclampsia, and stillbirth. The association between the primary outcome and 12 candidate predictors having a known association with severe COVID-19 in pregnancy was analyzed with log-binomial mixed-effects regression and reported as adjusted risk ratios. All the potential predictors were evaluated in 1 model and only the baseline factors in another. The predictive accuracy was assessed by the area under the receiver operating characteristic curves., Results: Of the 793 pregnant women who were positive for SARS-CoV-2 and were symptomatic, 44 (5.5%) were admitted to intensive care, of whom 10 died (1.3%). The 'mini-COvid Maternal Intensive Therapy' model included the following demographic and clinical variables available at disease onset: maternal age (adjusted risk ratio, 1.45; 95% confidence interval, 1.07-1.95; P=.015); body mass index (adjusted risk ratio, 1.34; 95% confidence interval, 1.06-1.66; P=.010); and diagnosis in the third trimester of pregnancy (adjusted risk ratio, 3.64; 95% confidence interval, 1.78-8.46; P=.001). The optimism-adjusted area under the receiver operating characteristic curve was 0.73. The 'full-COvid Maternal Intensive Therapy' model included body mass index (adjusted risk ratio, 1.39; 95% confidence interval, 1.07-1.95; P=.015), lower respiratory symptoms (adjusted risk ratio, 5.11; 95% confidence interval, 1.81-21.4; P=.007), neutrophil to lymphocyte ratio (adjusted risk ratio, 1.62; 95% confidence interval, 1.36-1.89; P<.001); and serum C-reactive protein (adjusted risk ratio, 1.30; 95% confidence interval, 1.15-1.44; P<.001), with an optimism-adjusted area under the receiver operating characteristic curve of 0.85. Neither model showed signs of a poor fit. Categorization as high-risk by either model was associated with a shorter diagnosis to intensive care unit admission interval (log-rank test P<.001, both), higher maternal death (5.2% vs 0.2%; P<.001), and preeclampsia (5.7% vs 1.0%; P<.001). A spreadsheet calculator is available for risk estimation., Conclusion: At presentation with symptomatic COVID-19, pregnant and recently postpartum women can be stratified into high- and low-risk for progression to critical disease, even where resources are limited. This can support the nature and place of care. These models also highlight the independent risk for severe disease associated with obesity and should further emphasize that even in the absence of other comorbidities, vaccination is particularly important for these women. Finally, the model also provides useful information for policy makers when prioritizing national vaccination programs to quickly protect those at the highest risk of critical and fatal COVID-19., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Hypertensive disorders of pregnancy (HDP) are associated with significant myocardial dysfunction on echocardiography. The impact of hemodynamic changes related to volume redistribution following delivery on myocardial function in women with HDP has not been evaluated systematically. The aim of this study was to compare echocardiographic findings immediately before and after delivery in women with HDP., Methods: This was a prospective longitudinal study including 30 women with a diagnosis of HDP who underwent two consecutive transthoracic echocardiographic (TTE) examinations, before delivery and in the early postpartum period. Paired comparisons of the findings from the two assessments were performed., Results: Left-ventricular (LV) concentric remodeling or hypertrophy was detected in 21 (70%) patients. There was no significant difference in cardiac morphology indices such as LV mass index (78.9 ± 16.3 g/m 2 vs 77.9 ± 15.4 g/m 2 ; P = 0.611) or relative wall thickness (0.45 ± 0.1 vs 0.44 ± 0.1; P = 0.453) before vs after delivery. LV diastolic function did not demonstrate any peripartum variation, with similar left-atrial volume (52.4 ± 15.3 mL vs 51.0 ± 15.6 mL; P = 0.433), lateral E' (0.12 ± 0.03 m/s vs 0.12 ± 0.03 m/s; P = 0.307) and E/E' ratio (7.9 ± 2.2 vs 7.9 ± 1.7; P = 0.934) before vs after delivery. Systolic function indices, such as LV ejection fraction (57.5 ± 3.4% vs 56.4 ± 2.1%; P = 0.295) and global longitudinal strain (-15.3 ± 2.6% vs -15.1 ± 3.1%; P = 0.582), also remained unchanged between before vs after delivery., Conclusions: Maternal hemodynamic changes associated with delivery did not influence significantly peripartum TTE indices in women with HDP. Suboptimal maternal echocardiographic findings in HDP are likely to be the consequence of chronic pregnancy cardiovascular load changes or pre-existing maternal cardiovascular impairment. Severity and persistence of myocardial dysfunction in the postpartum period may be related to the long-term maternal cardiovascular disease legacy of HDP. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: The use of twin-specific vs singleton growth charts in the assessment of twin pregnancy has been controversial. The aim of this study was to assess whether a diagnosis of small-for-gestational age (SGA) made using twin-specific estimated-fetal-weight (EFW) and birth-weight (BW) charts is associated more strongly with adverse neonatal outcomes in twin pregnancies, compared with when the diagnosis is made using singleton charts., Methods: This was a cohort study of twin pregnancies delivered at St George's Hospital, London, between January 2007 and May 2020. Twin pregnancies complicated by intrauterine death of one or both twins, fetal aneuploidy or major abnormality, twin-twin transfusion syndrome or twin anemia-polycythemia sequence and those delivered before 32 weeks' gestation, were excluded. SGA was defined as EFW or BW below the 10 th centile, and was assessed using both twin-specific and singleton EFW and BW charts. The main study outcome was composite adverse neonatal outcome. Mixed-effects logistic regression analysis with random pregnancy-level intercepts was used to test the association between SGA classified using the different charts and adverse neonatal outcome., Results: A total of 1329 twin pregnancies were identified, of which 913 (1826 infants) were included in the analysis. Of these pregnancies, 723 (79.2%) were dichorionic and 190 (20.8%) were monochorionic. Using the singleton charts, 33.3% and 35.7% of pregnancies were classified as SGA based on EFW and BW, respectively. The corresponding values were 5.9% and 5.6% when using the twin-specific charts. Classification as SGA based on EFW using the twin charts was associated significantly with composite adverse neonatal outcome (odds ratio (OR), 4.78 (95% CI, 1.47-14.7); P = 0.007), as compared with classification as appropriate-for-gestational age (AGA). However, classification as SGA based on EFW using the singleton standard was not associated significantly with composite adverse neonatal outcome (OR, 1.36 (95% CI, 0.63-2.88); P = 0.424). Classification as SGA based on EFW using twin-specific standards provided a significantly better model fit than did using the singleton standard (likelihood ratio test, P < 0.001). When twin-specific charts were used, classification as SGA based on BW was associated significantly with a 9.3 times increased odds of composite adverse neonatal outcome (OR, 9.27 (95% CI, 2.86-30.0); P < 0.001). Neonates classified as SGA according to the singleton BW standard but not according to the twin-specific BW standards had a significantly lower rate of composite adverse neonatal outcome than did AGA twins (OR, 0.24 (95% CI, 0.07-0.66); P = 0.009)., Conclusions: The singleton charts classified one-third of twins as SGA, both prenatally and postnatally. Infants classified as SGA according to the twin-specific charts, but not those classified as SGA according to the singleton charts, had a significantly increased risk of adverse neonatal outcome compared with infants classified as AGA. This study provides further evidence that twin-specific charts perform better than do singleton charts in the prediction of adverse neonatal outcome in twin pregnancies. The use of these charts may reduce misclassification of twins as SGA and improve identification of those that are truly growth restricted. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Introduction: A controversy exists about the accuracy of the cerebroplacental ratio (CPR) for the prediction of cesarean section for intrapartum fetal compromise (CS-IFC). Our aim was to evaluate whether the interval to delivery modifies the accuracy of CPR either as a single marker or combined with estimated fetal weight centile (EFWc), type of labor onset (TLO), and other clinical variables., Methods: This was a multicenter retrospective study of 5,193 women with singleton pregnancies who underwent an ultrasound scan at 35+0-41+0 weeks and gave birth within 1 month of examination, at any of the participating hospitals in Spain, UK, and Italy. CS-IFC was diagnosed in case of an abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20, requiring urgent cesarean section. The diagnostic ability of CPR in multiples of the median (CPR MoM) was evaluated at different intervals to delivery, alone and combined with EFWc, TLO, and other pregnancy data such as maternal age, maternal body mass index, parity, and fetal sex, for the prediction of CS-IFC by means of ROC curves and logistic regression analysis., Results: The predictive ability of CPR MoM for CS-IFC worsened with the interval to delivery. In general, the best prediction was obtained prior to labor and by adding information related to EFWc and TLO (AUC 0.71 [95% CI: 0.64-0.79], 0.73 [95% CI: 0.66-0.80], and 0.75 [95% CI: 0.69-0.81]; p < 0.0001). Addition of more clinical data did not improve prediction. In addition, results did not vary when only cases with spontaneous onset of labor were studied., Conclusion: CPR MoM prediction of CS-IFC at the end of pregnancy worsens with the interval to delivery. Accordingly, it should be done in the short term and considering EFWc and TLO., (© 2022 S. Karger AG, Basel.)

Twin pregnancies are commonly assessed using singleton growth and birth weight reference charts. This practice has led to a significant number of twins labelled as small for gestational age (SGA), causing unnecessary interventions and increased risk of iatrogenic preterm birth. However, the use of twin-specific charts remains controversial. This study aims to assess whether twin-specific estimated fetal weight (EFW) and birth weight (BW) charts are more predictive of adverse outcomes compared to singleton charts. Centiles of EFW and BW were calculated using previously published singleton and twin charts. Categorical data were compared using Chi-square or McNemar tests. The study included 1740 twin pregnancies, with the following perinatal adverse outcomes recorded: perinatal death, preterm birth <34 weeks, hypertensive disorders of pregnancy (HDP) and admissions to the neonatal unit (NNU). Twin-specific charts identified prenatally and postnatally a smaller proportion of infants as SGA compared to singleton charts. However, twin charts showed a higher percentage of adverse neonatal outcomes in SGA infants than singleton charts. For example, perinatal death (SGA 7.2% vs. appropriate for gestational age (AGA) 2%, p < 0.0001), preterm birth <34 weeks (SGA 42.1% vs. AGA 16.4%, p < 0.0001), HDP (SGA 21.2% vs. AGA 13.5%, p = 0.015) and NNU admissions (SGA 69% vs. AGA 24%, p < 0.0001), when compared to singleton charts (perinatal death: SGA 2% vs. AGA 1%, p = 0.029), preterm birth <34 weeks: (SGA 20.6% vs. AGA 17.4%, p = 0.020), NNU admission: (SGA 34.5% vs. AGA 23.9%, p < 0.000). There was no significant association between HDP and SGA using the singleton charts ( p = 0.696). In SGA infants, according to the twin charts, the incidence of abnormal umbilical artery Doppler was significantly more common than in SGA using the singleton chart (27.0% vs. 8.1%, p < 0.001). In conclusion, singleton charts misclassify a large number of twins as at risk of fetal growth restriction. The evidence suggests that the following twin-specific charts could reduce unnecessary medical interventions prenatally and postnatally.