Hypertensive disorders in pregnancy (HDP) are associated with various maternal and fetal adverse outcomes and become an increasingly significant threat to Chinese pregnant women. Yet, the prevalence of HDP in China is not clear. We conducted this meta-analysis to estimate the prevalence of HDP and specific subtypes in China. We searched PubMed, Embase, Web of Science, CNKI, Wangfang, and CMB for studies on prevalence of HDP and specific subtypes, published from 1990 to Jan 21, 2020, without language restrictions. We included all studies reported the prevalence of HDP and specific subtypes in Chinese pregnant women. We excluded qualitative studies, case reports, reviews, conference presentations, and studies only provided abstracts. We using a standard self-developed form to extract information from eligible studies. We did meta-analyses by random-effect models and estimated the pooled prevalence of HDP and specific subtypes. In order to explore potential sources of heterogeneity and subgroup effects, we did and meta-regression and subgroup analyses by pre-specified covariates. This study is registered with PROSPERO, number CRD42020166001. We initially identified 4179 records, of which 92 studies with 1,377,448 participants were eligible in the final systematic review and meta-analyses. The pooled prevalence (95% CI) of HDP, gestational hypertension, preeclampsia, mild preeclampsia, severe preeclampsia, eclampsia, chronic hypertension, and chronic hypertension with superimposed preeclampsia were 7.30% (6.60%-8.00%), 3.30% (2.90%-3.70%), 4.50% (4.00%-5.00%), 2.00% (1.70%-2.30%), 2.60% (2.10%-3.00%), 0.11% (0.08%-0.15%), 0.60% (0.30%-0.90%), and 0.60% (0.40%-0.80%), respectively. No publication bias was identified, although heterogeneity was high (I statistics: 92.0%-99.3%). High prevalence of HDP and the subtypes frequently reported in Western and Northern China. Pregnant women who were aged 35 years and above had high prevalence of HDP and subtypes; women who were overweight or obese had high prevalence of HDP, gestational hypertension and preeclampsia. The prevalence of HDP and the subtypes vary in different areas in China. Given to increasingly prevalent of the risk factors, such as overweight, obesity, and advance maternal age, strategies to prevent and manage HDP need to be improved, especially for women living in Western and Northern China.Copyright © 2021 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. Women who survive pre-eclampsia have reduced life expectancy, with increased risks of stroke, cardiovascular disease and diabetes, while babies from a pre-eclamptic pregnancy have increased risks of preterm birth, perinatal death and neurodevelopmental disability and cardiovascular and metabolic disease later in life. Pre-eclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (>20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. Pre-eclampsia is found only when a placenta is or was recently present and is classified as preterm (delivery <37 weeks of gestation), term (delivery ≥37 weeks of gestation) and postpartum pre-eclampsia. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. Available treatments target maternal hypertension and seizures, but the only 'cure' for pre-eclampsia is delivery of the dysfunctional placenta and baby, often prematurely. Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. Significant advances have been made in the prediction and prevention of preterm pre-eclampsia, which is predicted in early pregnancy through combined screening and is prevented with daily low-dose aspirin, starting before 16 weeks of gestation. By contrast, the prediction of term and postpartum pre-eclampsia is limited and there are no preventive treatments. Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new prognostic tests and treatments in adequately powered clinical trials.© 2023. Springer Nature Limited.

Preterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation.ASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks' gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with ClinicalTrials.gov, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970.From March 23, 2016 to June 30, 2018, 14 361 women were screened for inclusion and 11 976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks' gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (<34 weeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups.In populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality.Eunice Kennedy Shriver National Institute of Child Health and Human Development.Copyright © 2020 Elsevier Ltd. All rights reserved.

It was the aim of this study to develop models for the prediction of preeclampsia (PE) based on maternal characteristics and biophysical markers at 11-13 weeks' gestation in which gestation at the time of delivery for PE is treated as a continuous variable.This was a screening study of singleton pregnancies at 11-13 weeks including 1,426 (2.4%) cases that subsequently developed PE and 57,458 cases that were unaffected by PE. We developed a survival time model for the time of delivery for PE in which Bayes' theorem was used to combine the prior information from maternal characteristics with the uterine artery pulsatility index (PI) and the mean arterial pressure (MAP), using multiple of the median values.The risk for PE increased with maternal age, weight, Afro-Caribbean and South Asian racial origin, previous pregnancy with PE, conception by in vitro fertilization and a medical history of chronic hypertension, type 2 diabetes mellitus as well as systemic lupus erythematosus or antiphospholipid syndrome. In pregnancies with PE, there was an inverse correlation between multiple of the median values of the uterine artery PI and MAP with gestational age at delivery. Screening by maternal characteristics, uterine artery PI and MAP detected 90% of PE cases requiring delivery before 34 weeks and 57% of all PE cases at a fixed false-positive rate of 10%.A new model has been developed for effective first-trimester screening for PE.Copyright © 2012 S. Karger AG, Basel.

To compare the effects of 80 mg and 160 mg of aspirin, initiated in the first trimester of pregnancy, on mid-trimester uterine artery pulsatility index (UtA-PI) in women with a history of preeclampsia.We performed a pilot double-blind randomized controlled trial. Pregnant women with a history of preeclampsia were recruited between 10 and 13 weeks gestation and randomly assigned to take either 80 or 160 mg of aspirin daily at bedtime from randomization to 35 weeks gestation. The primary outcome was mean UtA-PI at 22-24 weeks. Secondary outcomes included the rate of fetal growth restriction and preeclampsia, stratified as term (≥37 weeks), preterm (<37 weeks), and early-onset (<34 weeks) preeclampsia.A total of 107 participants were randomized, including 41 (38%) with a history of preterm preeclampsia and 16 (15%) with a history of early-onset preeclampsia. We observed no significant difference in mean UtA-PI at 22-24 weeks between the 2 groups (0.97; 95% CI 0.88-1.05 vs. 0.97; 95% CI 0.88-1.07, P = 0.9). The rates of fetal growth restriction (8% vs. 2%; P = 0.20); preeclampsia (12% vs. 15%; P = 0.78), preterm preeclampsia (4% vs. 2%; P = 0.56), and early-onset preeclampsia (0% vs. 2%; P = 0.52) were similar in both groups. No serious adverse events associated with the study treatment were reported.We observed no significant difference in UtA-PI between the two doses of aspirin, but we observed low rates of fetal growth restriction and preterm and early-onset preeclampsia (all less than 5%). The benefits of aspirin for the prevention of preterm preeclampsia is probably not related to the improvement of deep placentation alone.Copyright © 2020 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.

To evaluate the cost effectiveness of various preeclampsia screening and aspirin prophylaxis strategies, including a strategy based on biomarker and ultrasound measures.We designed a decision analysis to compare preeclampsia-related costs and effects of four strategies for aspirin use in pregnancy initiated before 16 weeks of gestation to prevent preeclampsia. The four strategies were: 1) no aspirin use, 2) biomarker and ultrasound measure-predicated use, 3) use based on the U.S. Preventive Services Task Force guidelines, and 4) universal aspirin use. Our outcomes were preeclampsia-related costs and number of cases per 100,000 pregnant women. Using a threshold of $90,843 per case of preeclampsia, one-way, two-way, and Monte-Carlo sensitivity analyses incorporating varying probabilities of risk reduction due to aspirin use, aspirin-related side effects, and costs were performed to identify ranges at which costs and risks of aspirin-related complications shifted the preferred strategy.Compared with universal aspirin administration, the use of U.S. Preventive Services Task Force guidelines is associated with $8,011,725 higher health care costs and 346 additional cases of preeclampsia per 100,000 pregnant women; biomarker and ultrasound screening is associated with an additional $19,216,551 and 308 additional cases. Similarly, no aspirin use is associated with an increased cost of $18,750,381 and 762 additional cases. Thus, universal aspirin use dominated all three other strategies. In a Monte Carlo simulation of 10,000 pregnant women, universal aspirin was the preferred strategy in 91% of simulations. The U.S. Preventive Task Force screen was preferred in 8.5% of simulations, and biomarker and ultrasound screening and no aspirin were preferred in 0% and 0.5% of simulations, respectively.Over a broad range of assumptions, universal aspirin administration is associated with fewer cases of preeclampsia and fewer costs relative to no aspirin administration and aspirin administration based on serum and ultrasound measures or clinical risk factors.

Preconception or early administration of low-dose aspirin might improve endometrial growth, placental vascularization, and organogenesis. Most studies have evaluated the potential benefit of preconception or early administration of low-dose aspirin in women with a history of recurrent pregnancy loss, women who have undergone in vitro fertilization, or women with thrombophilia or antiphospholipid syndrome. These women are at an increased risk of placenta-associated complications of pregnancy, including preeclampsia, preterm delivery, and fetal growth restriction.We performed a systematic review and meta-analysis to evaluate the effect of low-dose aspirin initiated at <11 weeks' gestation on the risk of preeclampsia, gestational hypertension, or any hypertensive disorder of pregnancy. Secondary outcomes included preterm delivery at <37 weeks' gestation and fetal growth restriction.We searched in MEDLINE via PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from 1985 to November 2018. Entry criteria were randomized controlled trials evaluating the effect of aspirin administered at <11 weeks' gestation in preventing preeclampsia and/or hypertensive disorders in pregnancy or improving pregnancy outcomes in women with recurrent miscarriage as compared with placebo or no treatment and outcome data available or provided by authors for >85% of the study population. Relative risks with 95% confidence intervals were calculated for each study and pooled for global analysis as the effect measure. We assessed statistical heterogeneity in each meta-analysis using the χ statistics, I, and Tau. Heterogeneity was considered substantial if an I was greater than 50% and either the Tau was greater than zero or there was a low P value (<0.10) in the χ test for heterogeneity. Random-effects meta-analysis, weighted by the size of the studies, was performed to produce an overall summary on aspirin effect for each outcome. Sensitivity analysis by sequential omission of each individual study and by fixed-effects model was performed. Publication bias was not assessed because of the small number of included studies. Statistical analysis was performed using Stata release 14.0 (StataCorp).The entry criteria were fulfilled by 8 randomized controlled trials on a combined total of 1426 participants. Low-dose aspirin initiated at <11 weeks' gestation was associated with a nonsignificant reduction in the risk of preeclampsia (relative risk, 0.52; 95% confidence interval, 0.23-1.17, P =.115), gestational hypertension (relative risk, 0.49; 95% confidence interval, 0.20-1.21; P =.121), and any hypertensive disorder of pregnancy (relative risk, 0.59; 95% confidence interval, 0.33-1.04, P =.067). Early administration of low-dose aspirin reduced the risk of preterm delivery (relative risk, 0.52; 95% confidence interval, 0.27-0.97, P =.040) but had no impact on the risk of fetal growth restriction (relative risk, 1.10; 95% confidence interval, 0.58-2.07, P =.775). Except for preterm delivery and any hypertensive disorder of pregnancy, sensitivity analysis demonstrated similar observations, therefore confirming the robustness of the analysis.The administration of low-dose aspirin at <11 weeks' gestation in women at high risk does not decrease the risk of preeclampsia, gestational hypertension, any hypertensive disorder of pregnancy, and fetal growth restriction. However, it might reduce the risk of preterm delivery. Larger randomized controlled trials will be required to substantiate the findings.Copyright © 2019. Published by Elsevier Inc.

Researches of the efficacy and safety of metformin on long-term pregnancy outcomes remains conflicted. We performed an updated systematic review and meta-analysis to systematically investigate the effect of metformin treatment on pregnancy outcome, metabolic profile, and sex hormone characteristics in women with polycystic ovary syndrome (PCOS) and their offspring.The PubMed, Embase, and Cochrane Library databases were searched from inception to July 10, 2021 with the keywords "metformin", "PCOS", and "pregnancy". Randomized controlled studies reported pregnant related outcomes after metformin intervention among PCOS women were included, while abstracts and reviews were excluded. Two authors independently identified trials, extracted data and assessed risk of bias with Cochrane Reviewer's Handbook 5.0. Random effects models were used to evaluate the pooled risk ratios (RR) and 95% confidence intervals (95% CI) of pregnancy outcome, metabolic profile, and sex hormone levels.Eighteen studies were included. The majority of trials were in medium methodological quality. In terms of pregnancy complications among women with PCOS, metformin treatment was associated with a significantly reduced risk of preterm delivery (RR =0.37, 95% CI: 0.23-0.61), pregnancy-induced hypertension (PIH) and preeclampsia (RR =0.45, 95% CI: 0.24-0.83) and macrosomia (RR =0.26, 95% CI: 0.11-0.64). In terms of offspring, metformin significantly associated with larger head circumference (MD =0.29, 95% CI: 0.13-0.45) and higher long-term body mass index (BMI) measures (MD =0.37, 95% CI: 0.17-0.56). In terms of metabolic profile and sex hormone characteristics, a significant decrease in homeostatic model assessment for insulin resistance (HOMA2-IR) scores was found in mothers (MD =-0.32, 95% CI: -0.63 to -0.02), whereas a significant increase of sex hormone binding globulin (SHBG) levels was detected in offspring (MD =0.33, 95% CI: 0.01-0.65).Although the relative low quality of randomized controlled trials (RCTs) and limited results made it difficult to draw a definite conclusion, our study showed that metformin treatment during pregnancy can reduce the risk of pregnancy complications but may have impacts on increasing SHBG levels and long-term BMI in offspring.2022 Annals of Translational Medicine. All rights reserved.

To evaluate the use of metformin for preventing cesarean deliveries and large-for-gestational-age (LGA) newborn (NB) outcomes in non-diabetic obese pregnant women.This is a randomized clinical trial with obese pregnant women, divided into 2 groups: metformin group and control group, with followed-up prenatal routine. The gestational age of participants was less than or equal to 20 weeks and were monitored throughout entire prenatal period. For outcomes of delivery and LGA newborns, absolute risk reduction (ARR) and the number needed to treat (NNT) were calculated with a 95% confidence interval (CI).357 pregnant women were evaluated. From the metformin group (n = 171), 68 (39.8%) subjects underwent cesarean delivery, and 117 (62.9%) subjects from the control group (n = 186) had intercurrence (p < 0.01). As for the mothers' general characteristics, there was significance for marital status (p < 0.01). Maternal-fetal results presented reduced preeclampsia (p < 0,01). Primary prophylactic results presented an ARR of 23.1 times (95% CI: 13.0-33.4) with NNT of 4 (95% CI: 3.0-7.7) and no significant values for LGA NB (p > 0.01). Secondary prophylactic outcomes presented decreased odds ratio for preeclampsia (OR = 0.17, 95% CI: 0.10-0.41).The use of metformin reduced cesarean section rates, resulted in a small number of patients to be treated, but it did not reduce LGA NB. Administering a lower dosage of metformin from the early stages to the end of treatment may yield significant results with fewer side effects. Arch Endocrinol Metab. 2020;64(3):290-7.

Preeclampsia is one of the most serious health problems that affect pregnant persons. It is a complication in approximately 4% of pregnancies in the US and contributes to both maternal and infant morbidity and mortality. Preeclampsia also accounts for 6% of preterm births and 19% of medically indicated preterm births in the US. There are racial and ethnic disparities in the prevalence of and mortality from preeclampsia. Non-Hispanic Black women are at greater risk for developing preeclampsia than other women and experience higher rates of maternal and infant morbidity and perinatal mortality.To update its 2014 recommendation, the USPSTF commissioned a systematic review to evaluate the effectiveness of low-dose aspirin use to prevent preeclampsia.Pregnant persons at high risk for preeclampsia who have no prior adverse effects with or contraindications to low-dose aspirin.The USPSTF concludes with moderate certainty that there is a substantial net benefit of daily low-dose aspirin use to reduce the risk for preeclampsia, preterm birth, small for gestational age/intrauterine growth restriction, and perinatal mortality in pregnant persons at high risk for preeclampsia.The USPSTF recommends the use of low-dose aspirin (81 mg/d) as preventive medication for preeclampsia after 12 weeks of gestation in persons who are at high risk for preeclampsia. (B recommendation).

Objective The objective of this study was to estimate the effect of low-dose aspirin in multiple gestations to prevent preeclampsia and small for gestational age (SGA) neonates. Methods A systematic review and meta-analysis were performed through electronic database searches. Randomized controlled trials (RCTs) of women with multiple gestations assigned to receive aspirin or placebo or no treatment were included. Outcomes included preeclampsia (mild and severe) and SGA neonates. Relative risks (RR) with their 95% confidence intervals (CI) were calculated. Result Out of 6,853 citations, 6 RCTS, including 898 pregnancies, were included. We observed a significant reduction in the risk of preeclampsia (RR, 0.67; 95% CI, 0.48-0.94) and mild preeclampsia (RR, 0.44; 95% CI, 0.24-0.82) but not severe preeclampsia (RR, 1.02; 95% CI, 0.61-1.72) with low-dose aspirin. The risk of SGA was not changed (RR, 1.09; 95% CI, 0.80-1.47). The reduction of preeclampsia was not different between women randomized before (RR, 0.86; 95% CI, 0.41-1.81) or after 16 weeks' gestation (RR, 0.64; 95% CI, 0.43-0.96) (p = 0.50). Conclusion There is low level of evidence supporting the use of low-dose aspirin for the prevention of preeclampsia and SGA neonates in multiple gestations.Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

In singleton pregnancies, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and the sFlt-1/PlGF ratio have shown utility as a diagnostic test for pre-eclampsia (PE). The objective of this study was to characterize the maternal serum levels of sFlt-1, PlGF and sFlt-1/PlGF ratio in normal and pre-eclamptic twin pregnancies.In a European multicenter case-control study, 49 women with a twin pregnancy were enrolled, including 31 uneventful and 18 pre-eclamptic pregnancies. sFlt-1 and PlGF were measured and receiver-operating characteristics (ROC) analysis was performed. The median sFlt-1 and PlGF serum concentrations and sFlt-1/PlGF ratio were compared with those of a singleton cohort, matched for gestational age, with PE (n = 54) and with an uncomplicated pregnancy outcome (n = 238).In twin pregnancies with PE, sFlt-1 levels and the sFlt-1/PlGF ratio were increased and PlGF levels were decreased as compared with those of twin gestations with an uneventful pregnancy outcome (20 011.50 ± 2330.35 pg/mL vs 4503.00 ± 2012.05 pg/mL (P ≤ 0.001), 164.22 ± 31.35 vs 13.29 ± 319.64 (P ≤ 0.001), and 138.80 ± 20.04 pg/mL vs 403.00 ± 193.10 pg/mL (P ≤ 0.001), respectively). The sFlt-1/PlGF ratio did not differ between twin pregnancies with PE and singleton pregnancies with PE. In twin pregnancies with an uneventful outcome, sFlt-1 levels and sFlt-1/PlGF ratio were increased, but no differences in PlGF concentration were found when compared with that of singleton controls. ROC analysis determined 53 as an optimal cut-off of the sFlt-1/PlGF ratio for diagnosing PE in twin gestations, yielding a sensitivity of 94.4% and a specificity of 74.2%. The cut-off values established for singleton pregnancies, of 33 and 85, led to sensitivities of 100% and 83.3%, and specificities of 67.7% and 80.6%, when used to detect PE in twin pregnancies.Significant differences in the serum marker levels in singleton vs twin pregnancies were detected. Reference ranges of sFlt-1, PlGF and their ratio in singleton pregnancies are therefore not transferable to twin pregnancies.Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.