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INTRODUCTION: Hypertensive disorders of pregnancy (HDP) are associated with a high incidence of maternal and perinatal morbidity and mortality. HDP, in particular pre-eclampsia, have been determined as risk factors for future cardiovascular disease. Recently, the common hypothesis of pre-eclampsia being a placental disorder was challenged as numerous studies show evidence for short-term and long-term cardiovascular changes in pregnancies affected by HDP, suggesting a cardiovascular origin of the disease. Despite new insights into the pathophysiology of HDP, concepts of therapy remain unchanged and evidence for improved maternal and neonatal outcome by using antihypertensive agents is lacking. METHODS AND ANALYSIS: A prospective observational case-control study, including 100 women with HDP and 100 healthy controls, which will assess maternal haemodynamics using the USCOM 1A Monitor and Arteriograph along with cardiovascular markers (soluble fms-like kinase 1/placental-like growth factor, N-terminal pro-B type natriuretic peptide) in women with HDP under antihypertensive therapy, including a follow-up at 3 months and 1 year post partum, will be conducted over a 50-month period in Vienna. A prospective, longitudinal study of cardiovascular surrogate markers conducted in Oslo will serve as a comparative cohort for the Vienna cohort of haemodynamic parameters in pregnancy including a longer follow-up period of up to 3 years post partum. Each site will provide a dataset of a patient group and a control group and will be assessed for the outcome categories USCOM 1A measurements, Arteriograph measurements and Angiogenic marker measurements. To estimate the effect of antihypertensive therapy on outcome parameters, ORs with 95% CIs will be computed. Longitudinal changes of outcome parameters will be compared between normotensive and hypertensive pregnancies using mixed-effects models. ETHICS AND DISSEMINATION: Ethical approval has been granted to all participating centres. Results will be published in international peer-reviewed journals and will be presented at national and international conferences.

Safety and effectiveness of COVID-19 vaccines during pregnancy is a particular concern affecting vaccination uptake by this vulnerable group. Here we evaluated evidence from 23 studies including 117,552 COVID-19 vaccinated pregnant people, almost exclusively with mRNA vaccines. We show that the effectiveness of mRNA vaccination against RT-PCR confirmed SARS-CoV-2 infection 7 days after second dose was 89·5% (95% CI 69·0-96·4%, 18,828 vaccinated pregnant people, I2 = 73·9%). The risk of stillbirth was significantly lower in the vaccinated cohort by 15% (pooled OR 0·85; 95% CI 0·73-0·99, 66,067 vaccinated vs. 424,624 unvaccinated, I2 = 93·9%). There was no evidence of a higher risk of adverse outcomes including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum haemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, or neonatal intensive care unit admission (p > 0.05 for all). COVID-19 mRNA vaccination in pregnancy appears to be safe and is associated with a reduction in stillbirth.

Objective\ud 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.\ud \ud Methods\ud 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 10th 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.\ud \ud Results\ud 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

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

Aim\ud To evaluate the clinical factors associated with false-negative RT-PCR results and to report the outcome of a cohort of pregnant women with COVID-19.\ud \ud Methods\ud This cohort study was conducted in a tertiary referral pandemic hospital and included 56 pregnant women. A study including pregnant women with either a laboratory or clinical diagnosis for COVID-19 were included in the study. The primary outcome was clinical factors associated with false-negative RT-PCR results defined as a positive immunoglobulin M assessed by rapid testing in clinically diagnosed patients. Clinical outcomes of laboratory diagnosed patients were also reported.\ud \ud Results\ud In total, 56 women with either RT-PCR or clinical COVID-19 diagnosis were included in the study. Forty-three women either had RT-PCR positivity or IgM positivity. The clinical outcome of these pregnancies was as follows: mean maternal age 27.7, immunoglobulin M positive patients 76.7%, RT-PCR positive patients 55.8%, maternal comorbidities 11.5%, complications in patients below 20 weeks 34.8%, complications in patients above 20 weeks 65.1%, elevated CRP 83.7%, lymphopenia 30.2%, time from hospital admission to final follow-up days 37 and stillbirth 8.3%. The proportion of women who tested positive for SARS-CoV-2 immunoglobulin M was 100% in the RT-PCR positive group and 56.5% in the clinical diagnosis group (P = .002). The symptom onset to RT-PCR testing interval longer than a week (risk ratio: 2.72, 95% CI: 1.14-5.40, P = .003) and presence of dyspnoea (risk ratio: 0.38, 95% CI: 0.14-0.89, P = .035) were associated with false-negative RT-PCR tests. The area under the curve of these parameters predicting false-negative RT-PCR was 0.73 (95% CI: 0.57-0.89).\ud \ud Conclusions\ud Symptomatic women with a negative RT-PCR should not be dismissed as potential COVID-19 patients, especially in the presence of prolonged symptom onset-test interval and in women without dyspnoea.

BACKGROUND: Women with a history of hypertensive disorders of pregnancy (HDP) are at increased long-term risk of cardiovascular disease. However, there has been increasing evidence on the same risks in the months following birth. OBJECTIVES: This review aims to estimate the incidence of hypertension in the first 2 years after HDP. SEARCH STRATEGY: MEDLINE, Embase and Cochrane databases were systematically searched in October 2019. SELECTION CRITERIA: Observational studies comparing hypertension rate following HDP and normotensive pregnancies up to 2 years. DATA COLLECTION AND ANALYSIS: A meta-analysis to calculate the odds ratio (OR) with a 95% confidence interval (CI) and a sub-group analysis excluding women with chronic hypertension were performed. MAIN RESULTS: Hypertension was diagnosed within the first 2 years following pregnancy in 468/1646 (28.4%) and 584/6395 (9.1%) of the HDP and control groups, respectively (OR 6.28; 95% CI 4.18-9.43; I2 = 56%). The risk of hypertension in HDP group was significantly higher in the first 6 months following delivery (OR 18.33; 95% CI 1.35-249.48; I2 = 84%) than at 6-12 months (OR 4.36; 95% CI 2.81-6.76; I2 = 56%) or between 1-2 years postpartum (OR 7.24; 95% CI 4.44-11.80; I2 = 9%). A sub-group analysis demonstrated a similar increase in the risk of developing postpartum hypertension after HDP (OR 5.75; 95% CI 3.92-8.44; I2 = 49%) and pre-eclampsia (OR 6.83; 95% CI 4.25-10.96; I2 = 53%). CONCLUSIONS: The augmented risk of hypertension after HDP is highest in the early postpartum period, suggesting that diagnosis and targeted interventions to improve maternal cardiovascular health may need to be commenced in the immediate postpartum period. TWEETABLE ABSTRACT: The risk of hypertension within 2 years of birth is six-fold higher in women who experienced pre-eclampsia.

OBJECTIVE: Identification of the fetus at risk of intrapartum compromise has many benefits. Impaired maternal cardiovascular function is associated with placental hypoperfusion intrapartum fetal distress. The main aim of this study was to assess the predictive accuracy of maternal hemodynamics for the risk of operative delivery due to presumed fetal compromise in women undergoing induction of labour (IOL). METHODS: In this prospective cohort study patients were recruited between November 2018 and January 2019. Women undergoing IOL were invited to participate in the study. A non-invasive ultrasonic cardiac output monitor (USCOM-1A) was used for the cardiovascular evaluation. The study outcome was operative delivery due to presumed fetal compromise, which included cesarean or instrumental delivery for abnormal fetal heart monitoring. Regression analysis was used to test the association between cardivascular markers, as well as the maternal characteristics and the risk of operative delivery for presumed fetal compromise. The ROC curve analysis was used to assess the predictive accuracy of the cardivascular markers for the risk of operative delivery for presumed fetal compromise. RESULTS: A total of 99 women were recruited and four women were later excluded from the analysis due to semi-elective cesarean section (n=2) and failed IOL (n=2). The rate of operative delivery due to presumed fetal compromise was 28.4% (27/95). Women who delivered without suspected fetal compromise were more likely to be multiparous (52.9% vs 18.5%, p=0.002). Women who underwent operative delivery due to presumed fetal compromise had significantly lower cardiac index (CI) (median: 2.50 L/min/m2 vs. 2.60 L/min/m2 , p=0.039) and higher systemic vascular resistance (SVR) (median: 1480.0 mmHg.min.mL-1 /m2 vs. 1325.0 mmHg.min.mL-1 /m2 , p=0.044) compared to controls. The baseline model (multiparity only) showed poor predictive accuracy with an area under the curve (AUC) value of 0.67 (95% CI: 0.58-0.77). The addition of stroke volume index (SVI) 7.2 logs or SVR index (SVRI) >7.7 logs significantly improved the baseline model (p=0.012, p=0.026 and p=0.012, respectively). CONCLUSION: In this pilot study, we demonstrated that pre-labour maternal cardiovascular assessment in women undergoing IOL could be useful for assessing the risk of intrapartum fetal compromise necessitating operative delivery. The addition of SV, SVR and SVRI significantly improved the predictive accuracy of the baseline antenatal model. This article is protected by copyright. All rights reserved.

OBJECTIVES: Small-for-gestational-age fetuses (SGA) are at high risk of intrapartum fetal compromise requiring operative delivery. In a recent study, we developed a model using a combination of three antenatal (gestational age at delivery, parity, cerebroplacental ratio) and three intrapartum (epidural use, labor induction and augmentation using oxytocin) variables for the prediction of operative delivery due to presumed fetal compromise in SGA fetuses - the Individual RIsk aSsessment (IRIS) prediction model. The aim of this study was to test the predictive accuracy of the IRIS prediction model in an external cohort of singleton pregnancies complicated by SGA. METHODS: This was an external validation study using a cohort of pregnancies from two tertiary referral centers in Spain and England. The inclusion criteria were singleton pregnancies diagnosed with an SGA fetus, defined as estimated fetal weight (EFW) below the 10th centile for gestational age at 36 weeks or beyond, which had fetal Doppler assessment and available data on their intrapartum care and pregnancy outcomes. The main outcome in this study was the operative delivery for presumed fetal compromise. External validation was performed using the coefficients obtained in the original development cohort. The predictive accuracies of models were investigated with receiver operating characteristics (ROC) curves. The Hosmer-Lemeshow test was used to test the goodness-of-fit of models and calibration plots were also obtained for visual assessment. A mobile application using the combined model algorithm was developed to facilitate clinical use. RESULTS: Four hundred twelve singleton pregnancies with an antenatal diagnosis of SGA were included in the study. The operative delivery rate was 22.8% (n = 94). The group which required operative delivery for presumed fetal compromise had significantly fewer multiparous women (19.1 versus 47.8%, p < 0.001 in the total study population; 19.0 versus 43.5 and 19.2 versus 49.6%, UK and Spain cohort, respectively), lower cerebroplacental ratio (CPR) multiples of median (MoM) (median: 0.77 versus 0.92, p < 0.001 in the total study population; 0.77 versus 0.92 and 0.77 versus 0.92, UK and Spain cohort, respectively), more inductions of labor (74.5 versus 60.1%, p = 0.010 in the total study population; 85.7 versus 77.2 and 71.2% and 53.1, UK and Spain cohort, respectively) and more use of oxytocin augmentation (57.4 versus 39.3%, p = 0.002 in the total study population; 19.0 versus 12.0 and 68.5 and 50.4%, UK and Spain cohort, respectively) compared to those who did not require operative delivery due to presumed fetal compromise. When the original antenatal model was applied to the present cohort, we observed moderate predictive accuracy (AUC: 0.70, 95% CI: 0.64-0.76), and no signs of poor fit (p = 0.464). The original combined model, when applied to the external cohort, had moderate predictive accuracy (AUC: 0.72, 95% CI: 0.67-0.77) and also no signs of poor fit (p = 0.268) without the need for refitting. A statistically significant increase in the predictive accuracy was not achieved via refitting of the combined model (AUC 0.76 versus 0.72, p = 0.060). CONCLUSIONS: Using our recently published model, the predictive accuracy for fetal compromise requiring operative delivery in term fetuses thought to be SGA was modest and showed no signs of poor fit in an external cohort. The IRIS tool for mobile devices has been developed to facilitate wide clinical use of this prediction model.