BACKGROUND: Numerous observational studies have investigated the potential link between hypertensive disorders of pregnancy (HDPs) and the subsequent risks of gynecologic tumors, yet the findings have been inconsistent. In this study, we utilized Mendelian randomization (MR) approach to assess the influence of HDPs on the future risks of ovarian, cervical, endometrial, and breast cancer and uterine fibroids, controlling for confounding factors.
METHODS: The genome-wide association studies (GWAS) summary data relevant to HDPs was obtained from the FinnGen databases (10,736 cases and 136,325 controls). Gynecologic tumor outcomes were extracted from the IEU Open GWAS project and UK Biobank (47,690 cases and 1, 092,073 controls). The inverse variance weighted (IVW) approach was selected as the principal method for MR analysis, supplemented by MR-Egger, weighted median, weighted model, simple model methods, MR pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out method. Multivariate MR (MVMR) analysis was conducted after adjusting systolic blood pressure (SBP), body mass index (BMI) and type 2 diabetes mellitus (T2DM).
RESULTS: Our univariate MR analysis (UVMR) results revealed no significant relationship between HDPs and the risks of ovarian cancer (odds ratio [OR] = 0.924, p = 0.360), cervical cancer (OR = 1.230, p = 0.738), endometrial cancer (OR = 1.006, p = 0.949), uterine fibroids (OR = 1.155, p = 0.158), and breast cancer (OR = 0.792, p = 0.241) by IVW test. Similar results were observed in gestational hypertension and preeclampsia/eclampsia. Additionally, our study detected neither heterogeneity nor pleiotropy. MVMR analysis also provided no evidence of a causal association between HDPs and common gynecologic tumors after adjusting SBP, BMI, and T2DM.
CONCLUSIONS: We discovered no causal relationship between HDPs and ovarian, cervical, endometrial, breast cancer, and uterine fibroids in European populations. However, present analysis did not explore the effect of HDPs on the subtypes of gynecologic tumors across varied ethnic populations, which may require additional research.

Hypertensive disorders in pregnancy (HDP) are the most prevalent diseases during pregnancy. In addition to the already identified risk factors, exposure to environmental contaminants has been also considered a new one. Phthalates, which are classified as priority environmental pollutants due to their ubiquitousness and endocrine disrupting properties, have been implicated in HDP in some epidemiological studies. Nevertheless, phthalates\' vascular impacts still need to be clarified. Thus, we aimed to understand the connection between phthalates exposure and the occurrence of gestational hypertension, as well as the pathway involved in the pathological vascular effects. We investigated diethyl phthalate\'s (DEP) effect on the vascular reactivity of the human umbilical arteries (HUAs) from normotensive and hypertensive pregnant women. Both DEP\'s nongenomic (within minutes effect) and genomic (24 h exposure to DEP) actions were evaluated, as well as the contribution of cyclic guanosine monophosphate and Ca2+ channel pathways. The results show that short-term exposure to DEP interferes with serotonin and histamine receptors, while after prolonged exposure, DEP seems to share the same vasorelaxant mechanism as estrogens, through the NO/sGC/cGMP/PKG signaling pathway, and to interfere with the L-type Ca2+ channels. Thus, the vascular effect induced by DEP is similar to that observed in HUA from hypertensive pregnancies, demonstrating that the development of HDP may be a consequence of DEP exposure.

Hypertensive disorders in pregnancy (HDP) are a group of conditions-including chronic hypertension, gestational hypertension, preeclampsia with and without end-organ damage, and acute complications, which include HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome and eclampsia-that could lead to severely adverse outcomes for both mother and fetus. The incidence of HDP has increased, affecting one out of seven delivery hospitalizations. Physicians should be aware of HDP for early identification and proper treatment to improve patient outcomes.

BACKGROUND: Tanzania has one of the highest burdens of perinatal mortality, with a higher risk among urban versus rural women. To understand the characteristics of perinatal mortality in urban health facilities, study objectives were: I. To assess the incidence of perinatal deaths in public health facilities in Dar es Salaam and classify these into a) pre-facility stillbirths (absence of fetal heart tones on admission to the study health facilities) and b) intra-facility perinatal deaths before discharge; and II. To identify determinants of perinatal deaths by comparing each of the two groups of perinatal deaths with healthy newborns.
METHODS: This was a retrospective cohort study among women who gave birth in five urban, public health facilities in Dar es Salaam. I. Incidence of perinatal death in the year 2020 was calculated based on routinely collected health facility records and the Perinatal Problem Identification Database. II. An embedded case-control study was conducted within a sub-population of singletons with birthweight ≥ 2000 g (excluding newborns with congenital malformations); pre-facility stillbirths and intra-facility perinatal deaths were compared with \'healthy newborns\' (Apgar score ≥ 8 at one and ≥ 9 at five minutes and discharged home alive). Descriptive and logistic regression analyses were performed to explore the determinants of deaths.
RESULTS: A total of 37,787 births were recorded in 2020. The pre-discharge perinatal death rate was 38.3 per 1,000 total births: a stillbirth rate of 27.7 per 1,000 total births and an intra-facility neonatal death rate of 10.9 per 1,000 live births. Pre-facility stillbirths accounted for 88.4% of the stillbirths. The case-control study included 2,224 women (452 pre-facility stillbirths; 287 intra-facility perinatal deaths and 1,485 controls), 99% of whom attended antenatal clinic (75% with more than three visits). Pre-facility stillbirths were associated with low birth weight (cOR 4.40; (95% CI: 3.13-6.18) and with maternal hypertension (cOR 4.72; 95% CI: 3.30-6.76). Intra-facility perinatal deaths were associated with breech presentation (aOR 40.3; 95% CI: 8.75-185.61), complications in the second stage (aOR 20.04; 95% CI: 12.02-33.41), low birth weight (aOR 5.57; 95% CI: 2.62-11.84), cervical dilation crossing the partograph\'s action line (aOR 4.16; 95% CI:2.29-7.56), and hypertension during intrapartum care (aOR 2.9; 95% CI 1.03-8.14), among other factors.  CONCLUSION: The perinatal death rate in the five urban hospitals was linked to gaps in the quality of antenatal and intrapartum care, in the study health facilities and in lower-level referral clinics. Urgent action is required to implement context-specific interventions and conduct implementation research to strengthen the urban referral system across the entire continuum of care from pregnancy onset to postpartum. The role of hypertensive disorders in pregnancy as a crucial determinant of perinatal deaths emphasizes the complexities of maternal-perinatal health within urban settings.

BACKGROUND: several studies have demonstrated that angiogenic markers can improve the clinical management of hypertensive disorders (HDs) and fetal growth restriction (FGR) in singleton pregnancies, but few studies have evaluated the performance of these tests in multiple pregnancies. Our aim was to investigate the role of soluble fms-like tyrosine kinase 1 (sFlt-1) in predicting adverse obstetric outcomes in hospitalized multiple pregnancies with HD (preeclampsia/gestational hypertension/uncontrolled chronic hypertension) and/or FGR in one or more fetuses.
METHODS: A retrospective analysis of multiple pregnancies with HD/FGR occurring after the 20th gestational week. Pregnant women were divided into two groups: women with high levels of sFlt-1 and those with low levels of sFlt-1. A value of sFlt-1 greater than or equal to 15,802 pg/mL was considered arbitrarily high, as it is equivalent to two times the 90th percentile expected in an uncomplicated full-term singleton pregnancy based on data from a prospective multicenter study (7901 pg/mL).
RESULTS: The cohort included 39 multiple pregnancies. There were no cases of birth <34 weeks, HELLP syndrome, ICU admission, and urgent cesarean sections for HD/FGR complications reported among women with low levels of sFlt-1.
CONCLUSIONS: A cut-off value of sFlt-1 ≥ 15,802 pg/mL could represent a valuable tool for predicting adverse obstetric outcomes in multiple pregnancies hospitalized for HD/FGR disorders, regardless of gestational age and chorionicity.

Inconsistent findings have been reported regarding the associations between hypertensive disorders in pregnancy (HDP) and infant neurodevelopment. Leveraging data from the Jiangsu Birth Cohort, in the present study, we re-visited such associations in one-year-old infants from 2576 singleton pregnancies and 261 twin pregnancies. We first assessed infant neurodevelopment by the Bayley Scales of Infant and Toddler Development Screening Test (the Third Edition), and then estimated its association with maternal HDP using general linear regression models and Poisson regression models. In singleton pregnancies, compared with mothers unexposed to HDP, infants born to mothers with chronic hypertension exhibited a lower score ( β, -0.67; 95% confidence interval [CI], -1.19--0.15) and a higher risk of \"non-optimal\" gross motor development (risk ratio [RR], 2.21; 95% CI, 1.02-4.79); in twin pregnancies, infants born to mothers with HDP exhibited lower scores in cognition ( β, -0.49; 95% CI, -0.96--0.01), receptive communication ( β, -0.55; 95% CI, -1.03--0.06), and gross motor ( β, -0.44; 95% CI, -0.86--0.03), and at a higher risk of \"non-optimal\" gross motor development (RR, 2.12; 95% CI, 1.16-3.88). These findings indicate that infants born to mothers with HDP may have inferior neurodevelopment outcomes at the age of one year.

Recent studies have shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP). However, the causal relationship needs to be treated with caution due to confounding factors and reverse causation.
We obtained genetic variants from genome-wide association studies including GM (N = 18,340) in MiBioGen Consortium as well as HDP (7,686 cases/115,893 controls) and specific subtypes in FinnGen Consortium. Then, Inverse variance weighted, maximum likelihood, weighted median, MR-Egger, and MR.RAPS methods were applied to examine the causal association. Reverse Mendelian randomization (RMR) and multivariable MR were performed to confirm the causal direction and adjust the potential confounders, respectively. Furthermore, sensitivity analyses including Cochran\'s Q statistics, MR-Egger intercept, MR-PRESSO global test, and the leave-one-out analysis were conducted to detect the potential heterogeneity and horizontal pleiotropy.
The present study found causalities between eight gut microbial genera and HDP. The HDP-associated gut microbial genera identified by MR analyses varied in different subtypes. Specifically, our study found causal associations of LachnospiraceaeUCG010, Olsenella, RuminococcaceaeUCG009, Ruminococcus2, Anaerotruncus, Bifidobacterium, and Intestinibacter with GH, of Eubacterium (ruminantium group), Eubacterium (ventriosum group), Methanobrevibacter, RuminococcaceaeUCG002, and Tyzzerella3 with PE, and of Dorea and RuminococcaceaeUCG010 with eclampsia, respectively.
This study first applied the MR approach to detect the causal relationships between GM and specific HDP subtypes. Our findings may promote the prevention and treatment of HDP targeted on GM and provide valuable insights to understand the mechanism of HDP in different subtypes from the perspective of GM.

Early recognition of high-risk pregnancies through biochemical markers may promote antenatal surveillance, resulting in improved pregnancy outcomes. The goal of this study is to evaluate the possibilities of using biochemical markers during the first trimester of pregnancy in the prediction of hypertensive pregnancy disorders (HPD) and the delivery of small-for-gestational-age (SGA) neonates. A comprehensive search was conducted on key databases, including PubMed, Scopus, and Web of Science, for articles relating to the use of biochemical markers in the prediction of HPD and SGA. The findings show that changes in the levels of biomarkers in the early pregnancy phases could be an important indicator of adverse pregnancy outcomes. The literature shows that low PAPP-A (pregnancy-associated plasma protein A) and PlGF (placental growth factor) levels, low alkaline phosphatase (AP), higher sFlt-1 (soluble fms-like Tyrosine Kinase-1) levels, higher AFP (alfa fetoprotein) levels, and elevated levels of inflammatory markers such as β-HGC (free beta human chorionic gonadotropin), interferon-gamma (INF-γ), and tumor necrosis factor-α (TNF-α) may be associated with risks including the onset of HPD, fetal growth restriction (FGR), and delivery of SGA neonates. Comparatively, PAPP-A and PlGF appear to be the most important biochemical markers for the prediction of SGA and HPD.

UNASSIGNED: Body mass index (BMI) in early pregnancy is a critical risk factor for hypertensive disorders of pregnancy (HDP). The pathobiology of the interplay between BMI and HDP is not fully understood and represents the focus of this investigation.
UNASSIGNED: BMI and 1st-trimester serum samples were obtained from the Global Alliance to Prevent Prematurity and Stillbirth repository for 154 women (105 without HDP and 49 with HDP). Metabotyping was conducted using ultra-high-performance liquid-chromatography high-resolution mass spectrometry (UHPLC HR-MS). Multivariable linear regression and logistic models were used to determine metabolites and pathway perturbations associated with BMI in women with and without HDP, and to determine metabolites and pathway perturbations associated with HDP for women in categories of obese, overweight, and normal weight based on the 1st trimester BMI. These outcome-associated signals were identified or annotated by matching against an in-house physical standards library and public database. Pathway analysis was conducted by the Mummichog algorithm in MetaboAnalyst.
UNASSIGNED: Vitamin D3 and lysine metabolism were enriched to associate with BMI for women with and without HDP. Tryptophan metabolism enrichment was associated with HDP in all the BMI categories. Pregnant women who developed HDP showed more metabolic perturbations with BMI (continuous) than those without HDP in their 1st-trimester serum. The HDP-associated pathways for women with normal weight indicated inflammation and immune responses. In contrast, the HDP-associated pathways for women of overweight and obese BMI indicated metabolic syndromes with disorders in glucose, protein, and amino acid, lipid and bile acid metabolism, and oxidative and inflammatory stress.
UNASSIGNED: High first-trimester BMI indicates underlying metabolic syndromes, which play critical roles in HDP development. Vitamin D3 and tryptophan metabolism may be the targets to guide nutritional interventions to mitigate metabolic and inflammatory stress in pregnancy and reduce the onset of HDP.

We aimed to examine the effects of various severities of hypertensive disorders in pregnancy on birthweight, blood pressure (BP), and body mass index in offspring at age 7. In the China Labor and Delivery Survey and the United States Collaborative Perinatal Project (CPP), the relationship of the severity of hypertensive disorders and nutritional and cardiovascular outcomes in offspring was assessed using a multivariable logistic and general linear regression model. In both datasets, those with gestational hypertension were more likely to deliver large for gestational age (LGA) and macrosomia (adjusted odds ratios (aOR) ranged from 1.29 to 1.91), as well as low birth weight (LBW) neonates (aOR ranged from 1.23 to 3.56), compared with normotensive mothers. In the CPP, when gestational hypertension was further stratified into mild and severe, only those with mild gestational hypertension (the mild group) were more likely to deliver macrosomia and LGA (aOR ranged from 1.25 to 1.32). Others (severe gestational hypertension and preeclampsia/eclampsia) were closely related to LBW and small for gestational age (aOR ranged from 1.27 to 2.77). Moreover, children of mothers in the mild group tended to be overweight/obese and had elevated diastolic BP. We concluded that the severity of hypertensive disorders had different effects on birthweight, childhood overweight, and BP.