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Objective: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes., Data Sources: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020., Study Eligibility Criteria: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area., Methods: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis., Results: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81)., Conclusion: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Although the most recent guidance from the International Society for the Study of Hypertension in Pregnancy (ISSHP) has highlighted the role of angiogenic marker assessment in the diagnosis of pre-eclampsia (PE) in women with chronic hypertension, the ISSHP has withheld recommending its implementation due to the limited available evidence in this group of women. Therefore, we aimed to investigate the value of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) assessment in women with chronic hypertension and suspected superimposed PE., Methods: This was a retrospective analysis of prospectively collected data recorded in an electronic database between January 2013 and October 2019. Women with chronic hypertension and singleton pregnancy who had suspected superimposed PE were included. Superimposed PE was suspected in women presenting with worsening hypertension, epigastric pain, new-onset edema, dyspnea or neurological symptoms. The exclusion criteria were delivery within 1 week after assessment for reasons other than PE, chronic kidney disease, history of cardiac disease, fetal aneuploidy, genetic syndrome or major structural anomaly and missing pregnancy outcome. Maternal serum angiogenic markers (sFlt-1, PlGF and sFlt-1/PlGF ratio) were measured. The primary outcome was the utility of angiogenic markers in the prediction of superimposed PE. Predictive accuracy was assessed for superimposed PE diagnosed at different timepoints, including within 1 week after assessment and any time before birth. The secondary outcome was comparison of adverse maternal and perinatal outcomes between women with superimposed PE diagnosed according to the traditional ISSHP criteria and those diagnosed according to extended criteria including angiogenic markers. The predictive accuracy of each angiogenic marker was assessed using receiver-operating-characteristics-curve analysis. Area under the curve (AUC) values were compared using De Long's test. A sensitivity analysis was planned for gestational age at assessment. The association of various variables with composite adverse maternal and perinatal outcomes was assessed using binomial regression., Results: The study included 142 pregnant women with chronic hypertension and suspected superimposed PE, of whom 25 (17.6%) developed PE within 1 week after assessment, 52 (36.6%) developed PE at any timepoint before birth and 90 (63.4%) delivered without PE. Maternal serum angiogenic imbalance was associated significantly with superimposed PE diagnosed according to the ISSHP criteria within 1 week or at any time after assessment (P < 0.001 for both). The predictive accuracy of maternal serum sFlt-1/PlGF ratio for superimposed PE diagnosed within 1 week after assessment was superior to that of maternal serum PlGF level (AUC, 0.91 vs 0.86; P = 0.032). The addition of angiogenic imbalance to the traditional ISSHP diagnostic criteria was associated with an increase in the detection rate (35.1% increase; 95% credible interval (CrI), 16.6-53.6%) and positive (9.6% increase; 95% CrI, 0.0-20.6%) and negative (3.1% increase; 95% CrI, 1.3-4.9%) predictive values for composite adverse maternal outcome, with high posterior probabilities of an increase in each predictive accuracy parameter (> 99.9%, 95.6% and > 99.9%, respectively), without a meaningful decrease in specificity. The addition of angiogenic imbalance improved the detection rate for composite adverse perinatal outcome (20.6% increase; 95% CrI, 0.0-42.2%), with a high posterior probability (96.9%). There was a corresponding drop in specificity (5.7% decrease; 95% CrI, -2.3% to 13.6%), with a posterior probability of 91.8%., Conclusions: In women with chronic hypertension and suspected superimposed PE, addition of maternal serum angiogenic markers to the traditional diagnostic criteria for superimposed PE improved significantly the sensitivity for the prediction of both maternal and perinatal adverse outcomes. Implementation of angiogenic marker assessment in the evaluation of pregnant women with chronic hypertension should therefore be considered. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Background Women with chronic hypertension face a 5- to 6-fold increased risk of developing preeclampsia compared with normotensive women. Angiogenic markers, especially soluble fms-like kinase 1 (sFlt-1) and placental growth factor (PlGF), were identified as clinically useful markers predicting the development of preeclampsia, but data on the prediction of superimposed preeclampsia are scarce. Therefore, we aimed to evaluate the predictive value of the sFlt-1/PlGF ratio for delivery because of superimposed preeclampsia in women with chronic hypertension. Methods and Results This retrospective study included 142 women with chronic hypertension and suspected superimposed preeclampsia. Twenty-seven women (19.0%) delivered because of maternal indications only, 17 women (12.0%) because of fetal indications primarily, and 98 women (69.0%) for other reasons. Women who both delivered because of maternal indications and for fetal indications had a significantly higher sFlt-1/PlGF ratio (median 99.9 and 120.2 versus 7.3, respectively, P <0.001 for both) and lower PlGF levels (median 73.6 and 53.3 versus 320.0 pg/mL, respectively, P <0.001 for both) compared with women who delivered for other reasons. SFlt-1/PlGF ratio and PlGF were strong predictors for delivery because of superimposed preeclampsia, whether for maternal or fetal indications ( P <0.05). Half of women with angiogenic imbalance (sFlt-1/PlGF ratio ≥85 or PlGF levels <100 pg/mL) delivered because of maternal or fetal indications within 1.6 weeks (95% CI, 1.0-2.4 weeks). Conclusions Angiogenic marker imbalance in women with suspected superimposed preeclampsia can predict delivery because of maternal and fetal indications related to superimposed preeclampsia and is associated with a significantly shorter time to delivery interval.

Background: Women with chronic hypertension are at increased risk for adverse maternal and perinatal outcomes. Maternal serum angiogenic markers, such as soluble fms-like tyrosine kinase 1 and placental growth factor, can be used to triage women with suspected preeclampsia. However, data about these markers in pregnant women with chronic hypertension are scarce., Objective: We aimed to evaluate the predictive accuracy of maternal serum levels of soluble fms-like tyrosine kinase 1, placental growth factor, and their ratio for predicting adverse maternal and perinatal outcomes in women with chronic hypertension., Study Design: This was a retrospective analysis of prospectively collected data from January 2013 to October 2019 at the University of Vienna Hospital, Vienna, Austria. The inclusion criteria were pregnant women with chronic hypertension and suspected preeclampsia. The primary outcome of this study was the prognostic performance of angiogenic markers for the prediction of adverse maternal and perinatal outcomes in pregnant women with chronic hypertension. The accuracy of angiogenic markers for predicting adverse composite outcomes was assessed with a binomial logistic regression. The accuracy of each marker was assessed using receiver operating characteristics curves and area under the curve values. Area under the curve values were compared using De Long's test., Results: Of the 145 included women with chronic hypertension and suspected superimposed preeclampsia, 26 (17.9%) women developed complications (ie, composite adverse maternal or fetal outcomes) within 1 week of assessment (average gestational age at assessment, 29.9 weeks) and 35 (24.1%) developed complications at any time (average gestational age at assessment, 30.1 weeks). In women who developed complications at any time, the median maternal serum soluble fms-like tyrosine kinase-1 to placental growth factor ratio was 149.4 (interquartile range, 64.6-457.4) compared with 8.0 (interquartile range, 3.37-41.2) for women who did not develop complications (P<.001). The area under the curve values for the maternal serum soluble fms-like tyrosine kinase-1 to placental growth factor ratio Z-score (0.95; 95% confidence interval, 0.90-0.99) and placental growth factor level Z-score (0.94; 95% confidence interval, 0.88-0.99) for predicting complications within 1 week of assessment were very high. The area under the curve values for new-onset edema (0.61; 95% confidence interval, 0.52-0.70), proteinuria (0.62; 95% confidence interval, 0.52-0.71), high mean arterial pressure (0.52; 95% confidence interval, 0.50-0.54), and other symptoms of preeclampsia (0.57; 95% confidence interval, 0.49-0.65) were all significantly lower than for the angiogenic markers (P<.001 for all). Women who had an angiogenic imbalance and/or proteinuria had the highest rate of complications (28/57, 49.1%). The rate of complications in women with an angiogenic imbalance and/or proteinuria was significantly higher than in women with either proteinuria, other symptoms, or intrauterine growth restriction in the absence of an angiogenic imbalance (49.1% vs 16.7%; P=.039). The highest positive and negative predictive values for predicting adverse outcomes were demonstrated by an angiogenic imbalance and/or proteinuria criteria with a positive predictive value of 49.1% (95% confidence interval, 50.4%-57.9%) and a negative predictive value of 92% (95% confidence interval, 85.5%-95.8%). Longitudinal changes in measurements of the gestational age-corrected ratio of soluble fms-like tyrosine kinase-1 to placental growth factor up to the last measurement had a significantly higher area under the curve value than the last measurement alone (area under the curve, 0.95; 95% confidence interval, 0.92-0.99 vs 0.87; 95% confidence interval, 0.79-0.95; P=.024) CONCLUSION: Maternal serum angiogenic markers are superior to clinical assessment in predicting adverse maternal and perinatal outcomes in pregnant women with chronic hypertension. Repeated measurements of the ratio of soluble fms-like tyrosine kinase-1 to placental growth factor seems beneficial given the better predictive accuracy compared with a single measurement alone. The use of angiogenic makers should be implemented in clinical management guidelines for pregnant women with chronic hypertension., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study aimed to assess the prognostic value of cardiovascular assessment in women with gestational hypertension or chronic hypertension for the risk of preeclampsia and need for closer antenatal surveillance. This was a prospective study of pregnancies complicated by gestational hypertension or chronic hypertension presenting to St George's Hospital, between January 2015 and May 2018. A noninvasive ultrasonic cardiac output monitor was used to obtain cardiovascular variables of cardiac output (CO) and systemic vascular resistance (SVR) and weight-adjusted indices. The primary outcome was the time to development of preeclampsia in women with gestational hypertension or chronic hypertension. In women with gestational hypertension or chronic hypertension (n=149), cox-proportional hazards analysis showed that mean arterial pressure ( P =0.006), Afro-Caribbean ethnicity ( P =0.045), and gestational age at the time of diagnosis above 34 weeks ( P <0.001) were significantly associated with increased risk of earlier preeclampsia. Women with high SVR and normal CO (adjusted hazard ratio, 2.32 [95% CI, 1.06-5.08]; P =0.035) and high SVR and low CO (adjusted hazard ratio, 7.79 [95% CI, 1.94-31.24]; P =0.003) cardiovascular profiles had significantly higher risk of earlier preeclampsia compared with women with normal SVR and normal CO. The findings of this study demonstrate that hypertensive women with increased SVR and low CO had a higher risk of developing preeclampsia sooner.

Angiogenic markers such as PlGF (placental growth factor) and sFlt-1 (soluble Fms-like tyrosine kinase-1) have been shown to be useful for predicting adverse outcome in women suspected of having preeclampsia. The aim of the current study was to evaluate the prognostic value of angiogenic markers and maternal risk factors in pregnant women with hypertension. This was a prospective study of pregnancies complicated by preeclampsia, gestational hypertension, or chronic hypertension presenting to 1 of 2 tertiary referral hospitals between May 2013 and May 2018. Maternal characteristics along with blood samples for angiogenic marker analysis were obtained from participants. The primary outcome was delivery related to preeclampsia within 1 and 2 weeks. In total, 302 women with hypertension were included in the study cohort. The baseline model included maternal body mass index, mean arterial pressure, and clinical diagnosis at the time of assessment. The use of sFlt-1/PIGF ratio combined with the baseline model significantly improved the area under the curve values for predicting delivery within a week (0.83 versus 0.88; P =0.025) or in 2 weeks (0.86 versus 0.93; P =0.001) due to preeclampsia-related events in gestational ages <35 weeks. The magnitude of increase in accuracy was 7.9% (-0.5% to 16.4%, posterior probability of increase: 96.7%) for sFlt-1/PlGF ratio. Our results emphasize the additive value of angiogenic biomarkers and the superior performance of a continuous scale of sFlt-1/PlGF ratio in the model. The added utility of angiogenic markers diminishes after 35 weeks' gestation.

Recent evidence suggests that home blood pressure monitoring (HBPM) is an effective way of managing women with hypertensive disorders of pregnancy (HDP) without increasing adverse outcomes. The aim of this systematic review and meta-analysis was to investigate the safety and efficacy of HBPM during pregnancy. Medline, EMBASE and the Cochrane library databases were searched electronically in November 2018. Studies were included from which data could be extracted on the pregnancy outcomes and included pregnancies with HDP or at increased risk of developing HDP. Data from nine studies were included in the meta-analysis. The use of HBPM during the antenatal period was associated with reduced risk of induction of labor (OR: 0.55, 95% CI: 0.36-0.82, 444 women, I 2  = 0%), prenatal hospital admissions (OR: 0.31, 95% CI: 0.19-0.49, 416 women, I 2  = 0%) and diagnosis of preeclampsia (OR: 0.50, 95% CI: 0.31-0.81, 725 women, I 2  = 37%). The number of antenatal visits was significantly less in the HBPM group (standard mean difference: -0.49, 95% CI: -0.82 to -0.16, 738 women, I 2  = 75%). There were no significant differences between HBPM and conventional care regarding composite maternal, fetal or neonatal outcomes when used during the antenatal period. There were no significant differences between the groups who had HBPM compared to those who had conventional care regarding postpartum readmissions and obtaining a blood pressure measurement within 10 days of delivery after discharge. The significant clinical heterogeneity and low quality of evidence are the main limitations, and therefore, more high quality studies are needed., (Copyright © 2019 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

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. The risk of hypertension within 2 years of birth is six‐fold higher in women who experienced pre‐eclampsia. The risk of hypertension within 2 years of birth is six‐fold higher in women who experienced pre‐eclampsia. This article includes Author Insights, a video abstract available at https://vimeo.com/rcog/authorinsights16545 [ABSTRACT FROM AUTHOR]

Objective: Metformin has been reported to reduce the risk of pre-eclampsia. It is also known to influence soluble fms-like tyrosine kinase-1 level, which correlates significantly with the gestational age at onset and severity of pre-eclampsia. The main aim of this systematic review and meta-analysis of randomized trials was to determine whether metformin use is associated with the incidence of hypertensive disorders of pregnancy (HDP).Methods: MEDLINE (1947 to September 2017), Scopus (1970 to September 2017) and the Cochrane Library (inception to September 2017) were searched for relevant citations in the English language. Only randomized controlled trials on metformin use, reporting the incidence of pre-eclampsia or pregnancy-induced hypertension, were included. Studies on populations with a high probability of metformin use prior to randomization (those with type II diabetes or polycystic ovary syndrome) were excluded. Random-effects models with the Mantel-Haenszel method were used for subgroup analyses. Bayesian random-effects meta-regression was used to summarize the evidence.Results: In total, 3337 citations matched the search criteria. After evaluating 2536 abstracts and performing full-text review of 52 studies, 15 were included in the review. In women with gestational diabetes, metformin use was associated with a reduced risk of pregnancy-induced hypertension when compared with insulin (relative risk (RR), 0.56; 95% CI, 0.37-0.85; I2  = 0%; 1260 women) and a non-significantly reduced risk of pre-eclampsia (RR, 0.83; 95% CI, 0.60-1.14; I2  = 0%; 1724 women). In obese women, when compared with placebo, metformin use was associated with a non-significant reduction in risk of pre-eclampsia (RR, 0.74; 95% CI, 0.09-6.28; I2  = 86%; 840 women). In women with gestational diabetes, metformin use was also associated with a non-significant reduction in risk of any HDP (RR, 0.71; 95% CI, 0.41-1.25; I2  = 0%; 556 women) when compared with glyburide. When studies were combined using Bayesian random-effects meta-regression, with treatment type as a covariate, the posterior probabilities of metformin having a beneficial effect on the prevention of pre-eclampsia, pregnancy-induced hypertension and any HDP were 92.7%, 92.8% and 99.2%, respectively, when compared with any other treatment or placebo.Conclusions: There is a high probability that metformin use is associated with reduced HDP incidence when compared with other treatments or placebo. The small number of studies included in the analysis, the low quality of evidence and the clinical heterogeneity preclude generalization of these results to broader populations. Given the clinical importance of this topic and the magnitude of effect observed in this meta-analysis, further prospective trials are urgently needed. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess the agreement between home blood-pressure monitoring (HBPM) and blood-pressure measurements in a clinic setting, in a cohort of pregnant women with hypertensive disorders of pregnancy (HDP).Methods: This was a cohort study of 147 pregnant women with HDP conducted at St George's Hospital, University of London, London, UK, between 2016 and 2017. Inclusion criteria were chronic hypertension, gestational hypertension or high risk of developing pre-eclampsia, no significant proteinuria and no hematological or biochemical abnormalities. Each included patient was prescribed a personalized schedule of hospital visits and blood-pressure measurements, according to their individual risk as per UK National Institute for Health and Care Excellence guidelines. The blood-pressure measurement at the clinic and the HBPM reading obtained closest to that hospital visit were paired for analysis. Only one pair of measurements was used per patient. Differences between home and clinic blood-pressure measurements were tested using the Wilcoxon signed rank test or paired t-test, and were also assessed visually using Bland-Altman plots. Comparison of the binary outcomes was performed using McNemar's chi-square test. Subgroup analysis was performed in the following gestational-age windows: < 14 weeks, 15-22 weeks, 23-32 weeks and 33-42 weeks' gestation.Results: A total of 294 blood-pressure measurements from 147 women were included in the analysis. Median systolic HBPM measurements were significantly lower than clinic measurements (132.0 (interquartile range (IQR), 123.0-140.0) mmHg vs 138.0 (IQR, 132.0-146.5) mmHg; P < 0.001). When stratified according to gestational age, systolic blood-pressure measurements obtained at home were significantly lower than those at clinic in all gestational-age periods except 23-32 weeks' gestation (P = 0.057). Median diastolic blood-pressure measurements at home were also significantly lower than those at clinic (85.0 (IQR, 77.0-90.0) mmHg vs 89.0 (IQR, 82.0-94.0) mmHg; P < 0.001). When stratified according to gestational age, diastolic HBPM measurements were significantly lower in the periods 5-14 weeks (P < 0.001), 15-22 weeks (P = 0.008) and 33-42 weeks (P < 0.001), compared with clinic measurements. The incidence of clinically significant systolic and diastolic hypertension based on clinic blood-pressure measurements was four to five times higher than that based on HBPM measurements (P < 0.001 and P = 0.005, respectively).Conclusions: Our study shows that, in women with HDP, blood pressure measured at home is lower than that measured in a clinic setting. This is consistent with observations in non-pregnant adults, in whom home and ambulatory monitoring of hypertensive patients is recommended. As such, HBPM has the potential to reduce the number of false-positive diagnoses of severe hypertension and unnecessary medical interventions in women with HDP. This must be carefully weighed against the risk of missing true-positive diagnoses. Prospective studies investigating the use of HBPM in pregnant women are urgently needed to determine the relevant blood-pressure thresholds for HBPM, and interval and frequency of monitoring. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

To assess the safety and efficacy of home blood pressure monitoring (HBPM) and office (traditional) blood pressure measurements in a cohort of pregnant women with gestational hypertension (GH). Each patient followed an individualised schedule of hospital visits and BP measurements based on the HBPM pathway or standard hospital protocol. [Extracted from the article]