GDF-15 Alleviates Hypoxia-Reoxygenation-Induced Damage to Human Placental Vascular Endothelial Cells by Regulating SIRT1.

OBJECTIVE: Pregnancy-induced hypertension (PIH) is a common disease during pregnancy, which arises from maternal placental vascular endothelial cell dysfunction. Growth differentiation factor 15 (GDF-15) has a protective effect on the cardiovascular system. The purpose of this study is to explore the protective effect of GDF-15 against hypoxia-reoxygenation (H/R)-induced damage to human placental vascular endothelial cells (HPVECs) and the regulatory mechanism of SIRT1 in this effect. METHODS: Serum samples from healthy pregnant women and those with PIH were collected, and their GDF-15 and SIRT1 levels were examined. HPVECs were cultured in vitro and induced with H/R and GDF-15 at varying concentrations. The optimal concentration of GDF-15 in protecting HPVECs was determined by measuring cell viability via the CCK-8 assay. In H/R-induced HPVECs treated with GDF-15 and compound C (the AMPK inhibitor), expression levels of SIRT1, p-AMPK, and t-AMPK were detected. Cell apoptosis was examined by flow cytometry. RESULTS: Serum SIRT1 and GDF-15 were significantly higher in healthy pregnant women than in PIH patients. Suppressed viability and activated apoptosis in H/R-induced HPVECs were partially reversed by the treatment of GDF-15 at a concentration of 100 ng/mL. H/R induction significantly downregulated SIRT1 and p-AMPK in HPVECs, which were then upregulated by GDF-15. Moreover, the protective effect of GDF-15 on H/R-induced HPVECs was blocked by inhibiting the AMPK signaling pathway. CONCLUSION: GDF-15 protects against H/R-inhibited cell viability and H/R-stimulated apoptosis in HPVECs by activating the AMPK signaling pathway to upregulate SIRT1.

Exploring the Spectrum of Electrolyte Imbalances in Preeclampsia: Mechanisms, Implications, and Clinical Insights.

Preeclampsia, a complex and perplexing disorder unique to pregnancy, is widely recognized as primarily originating from placental dysfunction and can only be resolved by the delivery of the fetus in severe cases. Preeclampsia is a prevalent medical issue during pregnancy and is associated with elevated rates of maternal and infant mortality and morbidity. The exact cause of preeclampsia remains uncertain, although multiple factors have been implicated in its development based on current knowledge. Preeclampsia is characterized by maternal endothelial dysfunction due to the presence of fetal-derived circulatory substances from the placenta. The condition is associated with various risk factors, including maternal comorbidities such as chronic renal disease, hypertension (HTN), and obesity. Additionally, a family history of preeclampsia, nulliparity, multiple gestations, previous instances of preeclampsia, or intrauterine fetal growth restriction (IUGR) are considered risk factors. Electrolytes, including sodium, potassium, and chloride, play a critical role in the function of vascular smooth muscles and may potentially contribute to the pathophysiology of hypertension. In this review, we have summarized the literature on electrolytes in preeclampsia by conducting an extensive systematic search of databases such as PubMed, Excerpta Medica database (EMBASE), and Medical Literature Analysis and Retrieval System Online (MEDLINE).

Metformin use and preeclampsia risk in women with diabetes: a two-country cohort analysis.

BACKGROUND: Metformin is a hypoglycaemic medication that has been proposed to treat or prevent preeclampsia. Combining national birth data from Scotland and Sweden, we investigated whether metformin used during pregnancy was associated with an altered risk of developing a hypertensive disorder of pregnancy. METHODS: We utilised data from two population-based cohorts: Scotland (2012-2018) and Sweden (2007-2019). Nulliparous women with gestational diabetes or type 2 diabetes who had birth outcome data linked with medications prescribed during pregnancy were included. The association between metformin prescription and hypertensive disorders of pregnancy was characterised using inverse probability weighted regression analysis, adjusting for variables that predict metformin use and potential confounders. Adverse neonatal outcomes were included as secondary outcomes. Results from both countries were then combined in a meta-analysis using a random effects model. RESULTS: The Scottish cohort included 3859 women with gestational diabetes or type 2 diabetes. Of these women, 30.8% (n = 1187) received at least one metformin prescription during pregnancy. For Sweden, 7771 women with gestational diabetes were included where 19.3% (1498) used metformin during pregnancy. Metformin prescription was not associated with an altered risk of any hypertensive disorder of pregnancy (Scotland adjusted relative risk (aRR) 0.88 [95% confidence interval (CI) 0.66-1.19]; Sweden aRR 1.08 [95% CI 0.86-1.37]) or preeclampsia (Scotland aRR 1.02 [95% CI 0.66-1.60]; Sweden aRR 1.00 [95% CI 0.72-1.39]). Combining adjusted results in a meta-analysis produced similar findings, with a pooled RR of 0.98 (95% CI 0.79-1.18) for any hypertensive disorder and RR 1.01 ([95% CI 0.73-1.28]) for preeclampsia. For neonatal outcomes, metformin was associated with a reduced risk of birthweight > 4500 g in Scotland (aRR 0.39 [95% CI 0.21-0.71]) but not in Sweden. There was no association between metformin and preterm birth or birthweight < 3rd or < 10th percentiles. Pooling results from both countries, metformin was not associated with adverse neonatal outcomes, including preterm birth (RR 1.00 [95% CI 0.89-1.13]), and birthweight < 10th percentile (RR 0.82 [95% CI 0.60-1.13]) or < 3rd percentile (RR 0.78 [95% CI 0.41-1.48]). CONCLUSIONS: In this two-country analysis, metformin use in pregnancy among women with diabetes was not associated with an altered risk of developing any hypertensive disorder of pregnancy. In the combined meta-analysis, metformin was not associated with an altered risk of adverse neonatal outcomes.

Retinal Microvascular Characteristics and Outcomes in Hypertensive Disorders of Pregnancy.

Background Hypertensive disorders of pregnancy (HDP) is a continuum of chronic hypertension, gestational hypertension, preeclampsia, and eclampsia in increasing severity, associated with a higher risk of complicated pregnancies and poor neonatal outcomes. This multisystem involvement can be assessed by fundoscopy, which serves as an indicator for generalized microvascular abnormalities. Our study aims to evaluate the correlation of hypertensive retinopathy with the severity of HDP and maternal and fetal outcomes. Materials and methods The study was conducted at a tertiary care hospital in Vijayapura from October 2021 to March 2022 among admitted cases of HDP. Detailed history, blood pressure (BP) measurement, obstetric examination, and fundoscopy were performed for all cases. Patients were followed up until the 10th postnatal day. The mode of delivery, birth weight, gestational age at birth, and any other neonatal outcomes were noted. Results We included 94 preeclampsia/eclampsia patients with a median age of 23 years, 51 (54.3%) being primigravida. Patients with chronic hypertension, gestational hypertension, and chronic hypertension superimposed by preeclampsia/eclampsia were excluded. The most common symptom in mothers was headache (23.4%), followed by blurring of vision (20.2%) and epigastric pain (5.3%) with a significant association (p < 0.05). Thirty-two cases (34%) had preterm deliveries with a positive association with the severity of retinopathy (p < 0.05). The magnitude of hypertensive retinopathy was 56.3% (53 cases), the severity of which significantly correlated to the severity of HDP (p < 0.05). We report 8.5% neonatal mortality and 22.3% small for gestational age (SGA) with a positive association with HDP severity (p < 0.05). There was no correlation between serum creatinine levels and the severity of retinopathy and fetal outcome. Conclusion The occurrence and severity of hypertensive retinopathy increase with increasing severity of HDP. Complaints, such as headache, blurred vision, and epigastric pain, are reported higher in cases with retinopathy. The severity of retinopathy may be used as an indicator of fetal morbidity; however, studies with large sample sizes and advanced tools are required to quantify the cause-effect relationship. The retinopathy associated with HDP resolves naturally with BP control postnatally.

The value of fetal left ventricular global longitudinal strain in predicting neonatal complications in pregnant women with hypertensive disorders.

BACKGROUND: Pregnancy-induced hypertension remains one of the important types of diseases that affect maternal and infant outcomes; prenatal and perinatal ultrasound examination is an important tool for evaluating fetal development. So, this study aimed to explore the clinical value of applying fetal heart quantification (fetal HQ) measuring left ventricular global longitudinal strain (LVGLS) and left ventricular ejection fraction (LVEF) in mid-to-late fetuses to predict neonatal complications in patients with gestational hypertension. METHODS: A retrospective summary of 146 pregnant women with gestational hypertension diagnosed from August 2020 to October 2023 into JinHua Maternal and Child Health Care Hospital was performed. Fetal HQ measured the fetal global spherical index (GSI), left and right ventricular spherical index (SI), left and right ventricular fractional shortening (FS), LVGLS and RVGLS, LVEF, and fractional area change (FAC) of the left and right ventricles. They were divided into complication group and non-complication group based on whether fetal complications occurred 28 days after birth. Multivariate logistic regression was used to screen risk factors to neonatal complications. RESULTS: The 146 neonates were divided into 39 of the complication group and 107 of the non-complication group. Compared with the latter group, pregnant women in the former group had a higher incidence of preeclampsia and eclampsia, increased mean systolic and diastolic blood pressure, significantly lower estimated fetal weight (EFW), left ventricular 24-segment SI, LVGLS, LVEF, and left ventricular FAC values (p < .05). Logistic regression showed higher of LVGLS (adjusted OR = 2.281, p < .001) was risk factors for neonatal complications, while higher LVEF (adjusted OR = 0.600, p < .001) and left ventricular FAC (adjusted OR = 0.784, p = .035) were protective factors. Spearman's correlation analysis showed a significant negative correlation between LVGLS and LVEF (r = -0.368, p < .001). Receiver operating curves (ROCs) showed the area under the curve (AUC) for predicting overall neonatal complications was 0.880 for LVGLS and 0.878 for LVEF (p < .001). CONCLUSIONS: Fetal HQ for fetal LVGLS and LVEF in mid-to-late pregnancy with gestational hypertension helps to assess the overall neonatal complications risk.

The effects of proton pump inhibitors during pregnancy on treatment of preeclampsia, and related outcomes: a systematic review and meta-analysis.

OBJECTIVE: This systematic review evaluated the available evidence of the effects of PPIs during pregnancy on preeclampsia and related maternal, fetal and neonatal outcomes. DATA SOURCES: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane CENTRAL, and Global Medicus Index) were searched on 17 November 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials involving pregnant women, using any class or dose of PPIs, were eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Meta-analysis was conducted for all outcomes of interest, with random-effects models. Results were presented as risk ratios or mean difference. Quality assessment was performed using the Risk of Bias 2 tool, and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) assessment was completed to evaluate the certainty of the evidence. The study was registered on PROSPERO (CRD42023423673). RESULTS: Our search identified 3,879 records, which were screened by two authors independently. Nine reports (describing eight trials) met our eligibility criteria, however six trials were ultimately excluded from our analysis as women were only given PPIs immediately prior to Cesarean section for acid aspiration prevention. The two trials included in the meta-analysis evaluated the treatment of 177 women with diagnosed preeclampsia. For the primary outcomes, moderate-certainty evidence showed there is likely no effect of the use of PPIs on risk of HELLP syndrome (RR 1.21, 95% CI 0.37 - 3.99, I²â€¯= 0%) or perinatal mortality (RR 0.81, 95% CI 0.36 - 1.79, I²â€¯= 0%), while there were insufficient data to meta-analyse all other primary outcomes, including eclampsia and neonatal mortality. No trials investigated PPIs for preventing preeclampsia. CONCLUSIONS: Given the limited outcome data we are uncertain of the effect of PPIs in women with preeclampsia. Further trials are required to determine what (if any) effects PPIs might have for preeclampsia prevention or treatment.

Comparison of isometric handgrip test among pregnant offspring of hypertensive parents and pregnant offspring of non-hypertensive parents.

Context: A family history of hypertension is one of the important risk factors for the development of pregnancy-induced hypertension (PIH). Offspring of hypertensive parents should be screened for PIH. The isometric handgrip (IHG) test is used to assess autonomic function among them. Autonomic function dysregulation can indicate their predisposition to develop PIH later in the course of pregnancy. Aim and Objectives: To compare the IHG among pregnant offspring of hypertensive parents (Group 1) and non-hypertensive parents (Group 2). Methods and Materials: This is a cross-sectional study done among 100 pregnant women in the second trimester (50 participants in each group). Blood pressure responses to sustained hand grip for 2 minutes of maximum voluntary contraction (MVC) were recorded, immediately at the end of the IHG test and after 5 minutes of the IHG test. Statistical Analysis: Independent t-test and Mann-Whitney U test were used to compare the responses in two groups. Results: There is no statistical difference in basal blood pressure and heart rate between the two groups. Group 1 exhibited a significant increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared to Group 2 immediately after 2 minutes of the IHG test. There is a significant increase in SBP after 5 minutes of the IHG in Group 2. Conclusions: Offspring of hypertensive parents have increased sympathetic reactivity and restoration of the blood pressure is significantly less compared to offspring of normotensive parents, which may predispose them for PIH. IHG can be applied as a convenient tool to screen the population who are at risk of PIH in places like primary health centres or field screenings where IHG is one possible option.

Correlation between Interleukin-10 Effects on Th1/Th2 Immune Balance and Pregnancy Induced Hypertension.

OBJECTIVE: Pregnancy induced hypertension (PIH) is a common disease in obstetrics. CD4+ T cells can be divided into Th1 and Th2 sub-populations. Imbalance between Th1 and Th2 directly affects body immune status and participates in PIH occurrence and progression. Whether IL-10 affects Th1/Th2 immune balance as a negative regulator of immune response in PIH remains unknown. The aim of the present study was to investigate the role of IL-10 in PIH. METHODS: A total of 52 PIH patients were recruited and divided into mild-moderate and severe PIH groups in parallel with 25 normal pregnant women as a control group. Real-time PCR was used to test mRNA levels of Th1 cytokines IL-2, tumor necrosis factor-α (TNF-α), and Th2 cytokines IL-4, IL-6, and IL-10. Enzyme linked immunosorbent assay (ELISA) tested serum levels of cytokines to analyze their correlation with disease progression. RESULTS: Our results showed PIH patients had significantly elevated IL-2 and TNF-α levels and decreased IL-4, IL-6, or IL-10 expressions compared with the control group (p<0.05). With disease progression, IL-4, IL-6, and IL-10 expressions were further decreased while IL-2 and TNF-α were increased (p<0.05). Moreover, IL-10 was negatively correlated with Th1 cytokines IL-2 and TNF-α while being positively correlated with Th2 cytokines IL-4 and IL-6. In addition, IL-10 was negatively correlated with PIH severity (p<0.05). CONCLUSION: IL-10 can affect Th1/Th2 immune balance and is associated with PIH severity, suggesting IL-10 might be a risk factor for PIH occurrence and progression.

Association of obesity and overweight with the risk of preeclampsia in pregnant women: an observational cohort study.

BACKGROUND: According to the World Health Organization, obesity is considered a pervasive global epidemic with significant medical and social implications. In antenatal mothers, the prevalence varies from 40% in Western countries to 12% in India which leads to life-threatening complications-preeclampsia and eclampsia. AIM: This study delves into the association between body mass index (BMI) and preeclampsia, among primi antenatal mothers with pregnancy-induced hypertension (PIH). METHODS: An observational cohort (prospective) study was conducted among 150 primi antenatal mothers with pregnancy-induced hypertension in Government Headquarters Hospital, Tamil Nadu, India. Demographic data, body mass index, and pregnancy outcomes were assessed. Statistical analysis was performed using the SPSS 28.0 version. RESULTS: Among 150 pregnant women, 63 (42%) were overweight, and 13 (8.7%) were obese. Higher BMI was significantly associated with maternal complications, especially preeclampsia (P < 0.001). Moreover, other complications such as abruptio placenta, pulmonary edema, eclampsia, and postpartum hemorrhage were not significantly associated with BMI. CONCLUSION: The study calls attention to the persistent link between BMI and preeclampsia, emphasizing the need for comprehensive strategies aligned with the Sustainable Development Goal. Despite ongoing efforts, the study suggests a lack of substantial change in the prevalence of preeclampsia associated with increased BMI, prompting the exploration of innovative interventions to address weight-related factors during pregnancy for improved maternal and neonatal well-being.

The role of the cerebro-placental-uterine ratio in predicting composite adverse perinatal outcomes in patients with pregnancy-induced hypertension.

OBJECTIVES: To examine the role of the cerebro-placental-uterine ratio (CPUR) in predicting composite adverse perinatal outcomes (CAPO) in patients with pregnancy-induced hypertension (PIH). STUDY DESIGN: This prospective, case-control study was conducted at a tertiary hospital with 110 cases of PIH, including 70 patients with preeclampsia and 40 with gestational hypertension, and 110 healthy controls. The middle cerebral artery pulsatility index (MCA-PI), umbilical artery pulsatility index (UA-PI), and uterine artery pulsatility index (UtA-PI) were measured, and the cerebro-placental ratio (CPR=MCA-PI/UA-PI) and CPUR (CPR/UtA-PI) were calculated. MAIN OUTCOME MEASURE: The role of CPUR in predicting CAPO in preeclampsia and gestational hypertension. RESULTS: The CPR and CPUR values were lower in the PIH group compared to the control group (p < 0.001). CAPO had a negative correlation with CPR and CPUR (p < 0.001). Univariate regression analysis revealed that the likelihood of CAPO was increased four times by a low CPR value and six times by a low CPUR value. In the ROC analysis, the optimal cut-off value of CPR in predicting CAPO was 1.33 with 74 % sensitivity and 66 % specificity (area under the curve [AUC] = 0.778; p < 0.001) in PIH. For CPUR, the optimal cut-off value was 1.32, at which 82 % sensitivity and 79 % specificity in predicting CAPO (AUC=0.826; p < 0.001). CONCLUSION: CPUR was determined to be successful with high sensitivity in predicting adverse perinatal outcomes in the presence of PIH. In addition, CPUR was more effective in predicting CAPO in patients with preeclampsia compared to gestational hypertension. CPUR can be used to predict adverse outcomes in patients with PIH.

IL-32 regulates trophoblast invasion through miR-205-NFκB-MMP2/9 axis contributing to the pregnancy-induced hypertension.

Interleukin-32 is a species-specific cytokine that plays an important role in inflammation, cancer, and other diseases; however, its role in reproductive and pregnancy-related diseases remains unknown. This study aimed to investigate the role of interleukin-32 in reproductive and pregnancy-related diseases. Placental tissues from patients with pregnancy-induced hypertension, healthy pregnant women, and trophoblast lines were analysed. Interleukin-32 expression was quantified via polymerase chain reaction and immunohistochemistry, and functional assays were performed after interleukin-32 modulation. Interleukin-32 was identified only in placental mammals, such as Carnivora, Cetartiodactyla, Chiroptera, Dermoptera, Lagomorpha, Perissodactyla, and Primates via bioinformatics. Immunohistochemistry and polymerase chain reaction revealed that interleukin-32 was highly expressed in human placental villi, poorly expressed in decidua and endometrial tissues, and was not detected in mouse tissues. Second, interleukin-32 upregulates miR-205 expression by increasing DROSHA expression, and miR-205 promotes interleukin-32 expression by targeting its promoter region. Interleukin-32 and miR-205 significantly enhanced the invasion ability of HTR8/SVneo cells (a trophoblast cell line) and the tube formation ability of human umbilical vein endothelial cells. Through quantitative reverse transcription polymerase chain reaction and western blotting, the interleukin-32/miR-205 loop increased MMP2 and MMP9 expression in HTR-8/SVneo cells via the nuclear factor kappa B signalling pathway. Finally, using quantitative reverse transcription polymerase chain reaction, interleukin-32 and miR-205 expression levels were significantly lower in the placentas of patients with pregnancy-induced hypertension than in women with normal pregnancies. In conclusion, interleukin-32 regulates trophoblast invasion through the miR-205-nuclear factor kappa B-MMP2/9 pathway, which is involved in pregnancy-induced hypertension.

Role of Uterine Artery Doppler Study Between 11 and 14 Weeks as a Predictor of Preeclampsia.

Introduction Preeclampsia is a serious complication marked by antepartum hemorrhage, resulting in severe maternal and fetal complications. Predicting this condition using placental dysfunction assessments, such as uterine artery Doppler ultrasound, is challenging due to the placenta's evolving structural and biochemical characteristics throughout different stages of pregnancy. Objectives To determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the uterine artery Doppler Pulsatility Index (PI) and Resistive Index (RI) in predicting preeclampsia. To compare the Doppler ultrasound measurements between normal pregnancies and those that develop preeclampsia. To assess the diagnostic accuracy of uterine artery Doppler ultrasound in predicting gestational hypertension in addition to preeclampsia. Methodology Conducted as a prospective study, 116 antenatal mothers with computed gestational ages and scan gestational ages between 11 and 14 weeks, and a previous history of preeclampsia were included. Subjects with chronic hypertension or multiple gestations were excluded. Participants underwent uterine artery Doppler screening, during which the PI and RI were measured upon obtaining three consecutive similar waveforms, and the mean PI of the left and right arteries was calculated. The outcomes of patients with normal pregnancies and those who developed preeclampsia were compared. Data were entered into Microsoft Excel (Microsoft® Corp., Redmond, WA, USA) and analyzed using IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, NY, USA). Results The mean PI among participants was 1.75 (±0.38), with a range from 1 to 2.75. The mean RI was 0.58 (±0.08), ranging from 0.45 to 0.8. The cutoff for the mean PI in predicting preeclampsia was 2.27, which showed a sensitivity of 92.9%, specificity of 97.1%, PPV of 81.47%, NPV of 99.01%, and a diagnostic accuracy of 96.59% (area under the curve (AUC): 0.982). The cutoff for the mean RI for predicting preeclampsia was 0.695, with a sensitivity of 85.7%, specificity of 98%, PPV of 85.47%, NPV of 98.04%, and diagnostic accuracy of 96.52% (AUC: 0.965). In predicting gestational hypertension, the cutoff for the mean PI was 1.975, with a sensitivity of 80%, specificity of 82.9%, PPV of 17.41%, NPV of 98.92%, and diagnostic accuracy of 82.78% (AUC: 0.848). The cutoff for the mean RI in predicting gestational hypertension was 0.615, showing a sensitivity of 80%, specificity of 80.2%, PPV of 15.4%, NPV of 98.89%, and diagnostic accuracy of 80.19% (AUC: 0.767). Conclusion The research demonstrated that aberrant readings in uterine Doppler ultrasound, specifically in the PI and RI, possess strong overall validity in forecasting the occurrence of preeclampsia.

Perinatal Outcomes of Singleton, Twin and Triplet Gestations after Oocyte Donation: A Retrospective, Population-Based Cohort Analysis.

BACKGROUND/OBJECTIVES: Although high live birth rates are associated with oocyte donation (OD), these pregnancies are associated with increased obstetric and perinatal risks. This study evaluated maternal and neonatal risks after OD compared to in vitro fertilization (IVF) with autologous oocytes, and to spontaneous pregnancies (SPs), among singletons, twins and triplets. METHODS: A retrospective, large, population-based cohort study was conducted based on electronic data from Maccabi Healthcare Services. A total of 469,134 pregnancies were grouped according to the mode of conception. The main outcome measures were preterm birth (PTB), small for gestational age (SGA) and pregnancy-induced hypertension (PIH). The data were analyzed separately for singletons, twins and triplets. RESULTS: The mean maternal age was older in the OD group compared with the IVF and SP groups (singletons: 39.7 ± 4.1 vs. 34.5 ± 4.8 and 31.7 ± 5.3 years; twins: 39 ± 4.6 vs. 32.6 ± 4.4 and 31.2 ± 5.1 years; and triplets: 35.6 ± 2.5 vs. 32 ± 3.9 and 29.7 ± 5 years). The mean gestational age was younger among the OD group compared to the SP group (singletons: 37.5 ± 3 vs. 39 ± 2 p = 0.001, and twins: 35 ± 3 vs. 36 ± 2.5 p = 0.001). Higher rates of PTB < 37, PTB < 34 and PTB < 28 weeks were found among OD singletons. Multivariable logistic regressions for PTB < 37 weeks and SGA in singletons demonstrated that OD and IVF are significant risk factors (OR = 4.1, 95%CI = 3.3-5.2; OR = 4.3, 95%CI = 4.1-4.6; OR = 1.9, 95%CI = 1.3-2.6; OR = 2.2, 95%CI = 2-2.4, respectively). Significantly higher rates of PIH were demonstrated among the OD vs. IVF and SP groups in singleton (4.3% vs. 1.7% and 0.7%) and in twin pregnancies (7.5% vs. 4.3% and 3.4%). CONCLUSIONS: OD pregnancies are at increased risk for PTB, SGA and PIH.

DNA methylation landscape in pregnancy-induced hypertension: progress and challenges.

Gestational hypertension (PIH), especially pre-eclampsia (PE), is a common complication of pregnancy. This condition poses significant risks to the health of both the mother and the fetus. Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may play a role in initiating the earliest pathophysiology of PIH. This article describes the relationship between DNA methylation and placental trophoblast function, genes associated with the placental microenvironment, the placental vascular system, and maternal blood and vascular function, abnormalities of umbilical cord blood and vascular function in the onset and progression of PIH, as well as changes in DNA methylation in the progeny of PIH, in terms of maternal, fetal, and offspring. We also explore the latest research on DNA methylation-based early detection, diagnosis and potential therapeutic strategies for PIH. This will enable the field of DNA methylation research to continue to enhance our understanding of the epigenetic regulation of PIH genes and identify potential therapeutic targets.

BMA-based Mendelian randomization identifies blood metabolites as causal candidates in pregnancy-induced hypertension.

Pregnancy-induced hypertension (PIH), a prominent determinant of maternal mortality and morbidity worldwide, is hindered by the absence of efficacious biomarkers for early diagnosis, contributing to suboptimal outcomes. Here, we explored potential causal relationships between blood metabolites and the risk of PIH using Mendelian randomization (MR). We employed a two-sample univariable MR approach to empirically estimate the causal relationships between 249 circulating metabolites and PIH. Inverse variance weighted, MR-egger, weight median, simple mode, and weighted mode methods were used for causal estimates. The exposure-to-outcome directionality was confirmed with the MR Steiger test. The Bayesian model averaging MR (MR-BMA) method was applied to detect the predominant causal metabolic traits with alignment for pleiotropy effects. In the primary analysis, analyzing 249 metabolites, we identified 25 causally linked to PIH, including 11 lipid-related traits and 6 associated with fatty acid (un)saturation. Importantly, MR-BMA analyses corroborated the total concentration of branched-chain amino acids(total-BCAA) to be the highest rank causal metabolite, followed by leucine (Leu), phospholipids to total lipids ratio in medium LDL (M-LDL-PL-pct), and Val (all P < 0.05). The directionality of causality predicted by univariable MR and MR-BMA for these metabolites remained consistent. This study highlights the causal connection between metabolites and PIH risk. It highlighted BCAAs as the strongest causal candidates warranting further investigation. Since PIH typically occurs in the second and third trimesters, extending these findings could inform earlier strategies to reduce its risk. Directed acyclic graph of the MR framework investigating the causal relationship between metabolites and PIH. MR: Mendelian randomization; GIVs: genetic instrument variables; SNPs: single-nucleotide polymorphism; IVW: inverse variance weighted; WM: weighted median; PIH: pregnancy-induced hypertension; SM: significant metabolite; MR-BMA: Bayesian model averaging MR.

Effect of prenatal phthalate exposure on fetal development and maternal/neonatal health consequences: A systematic review.

The ubiquitous presence of phthalate compounds in cosmetics, personal care products and plastics commonly used in toys, food packaging or household products, results in human exposure with adverse effects on reproductive health and fetal development. Following the PRISMA methodology, this systematic review analyzes the effect of prenatal phthalate exposure on major pregnancy complications, such as gestational diabetes, pregnancy-induced hypertension, fetal growth restriction and preterm birth, and its role in fetal neurodevelopment. This review includes >100 articles published in the last 10 years, showing an association between maternal exposure to phthalates and the risk of developing pregnancy complications. Phthalates are negatively associated with motor skills and memory, and also increase the risk of delayed language acquisition, autism spectrum disorder traits, and behavioral deficits, such as attention deficit hyperactivity disorder in children prenatally exposed to phthalates. Di (2-ethylhexyl) phthalate and its metabolites (mono(2-ethylhexyl) phthalate, mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate) are the main compounds associated with the above-mentioned pregnancy complications and fetal neurodevelopmental disorders. In addition, this review discusses the molecular mechanisms responsible for various pregnancy complications and neurodevelopmental disorders, and the critical window of exposure, in order to clarify these aspects. Globally, the most common molecular mechanisms involved in the effects of phthalates are endocrine disruption, oxidative stress induction, intrauterine inflammation, and DNA methylation disorders. In general, the critical window of exposure varies depending on the pathophysiology of the complication being studied, although the first trimester is considered an important period because some of the most vulnerable processes (embryogenesis and placentation) begin early in pregnancy. Future research should aim to understand the specific mechanism of the disruptive effect of each component and to establish the toxic dose of phthalates, as well as to elucidate the most critical period of pregnancy for exposure and the long-term consequences for human health.

Health-Related Quality of Life in Pregnant Women With Gestational Hypertension: A Systematic Review.

This review seeks to evaluate the levels of health-related quality of life (HRQoL) among pregnant women experiencing pregnancy-induced hypertension (PIH). It also aims to identify the specific aspects of HRQoL most impacted by PIH during pregnancy and determine the existence of effective interventions to enhance the HRQoL of these pregnant women. A systematic literature search was conducted in the following databases: PUBMED, SCOPUS, Google Scholar, and EMBASE using the following keywords: Health-related quality of life; pregnancy; pregnancy-induced hypertension; quality of life; gestational hypertension. Among the 32 studies assessed, only eight met the criteria for inclusion, exhibiting a good quality based on assessment with both AXIS (Appraisal Tool for Cross-Sectional Studies) and CASP (Critical Appraisal Skills Programme) checklists. The findings indicate a decline in HRQoL among pregnant women with gestational hypertension, notably affecting both physical and mental dimensions. Furthermore, some studies provided recommendations for interventions that healthcare professionals could employ to improve poor HRQoL levels. Limited research has focused on the HRQoL in pregnant women with PIH. Compared to their healthy counterparts, pregnant women experiencing PIH exhibit a decrease in their HRQoL. It's crucial for healthcare practitioners to proactively address the HRQoL of these pregnant women using effective strategies to mitigate this decline. This approach aims to safeguard both pregnant women and their fetuses from potential complications associated with lower HRQoL levels.

Effect of Vitamin D Deficiency on Arterial Stiffness in Pregnant Women with Preeclampsia and Pregnancy-Induced Hypertension and Implications for Fetal Development.

BACKGROUND AND OBJECTIVES: Over the past few years, researchers have focused on the importance of vitamin D in the health of pregnant women and in reducing the chances of developmental disorders occurring in fetuses. In addition, a link has been established between fetal development and arterial stiffness in hypertensive disorders that occur during pregnancy. Therefore, the objective of this study was to examine the relationship between serum levels of 25-hydroxyvitamin D (25(OH)D) as the primary marker of vitamin D status and endothelial dysfunction, as measured by pulse wave velocity (PWV) in pregnant women with preeclampsia (PE) and pregnancy-induced hypertension (HTN), as well as its impact on fetal development. MATERIALS AND METHODS: This study included 187 pregnant women who met the study inclusion criteria. Pregnant women were divided into two groups: pregnancy-induced hypertension (HTN group), which included 100 patients (53.48%), and preeclampsia (PE group), which included 87 patients (46.52%). RESULTS: Significant differences regarding the augmentation index (Aix) brachial, PWVao, heart rate, and systolic or diastolic blood pressure with more increased values were observed for the HTN group vs. the preeclampsia group in the current research (p < 0.001). Additionally, the Aix brachial index was significantly lower in the preeclampsia group compared to the HTN group (1.76 ± 0.71 for the HTN group vs. 0.62 ± 0.5 for the preeclampsia group, p < 0.001). A severe matern serum 25(OH)D level deficiency was associated with a more severe subcategory of prematurity (p < 0.001) and with increased chances of newborn preterm birth (p < 0.05). Moreover, the negative effect of severe maternal serum 25(OH)D level deficiency was studied for each group regarding the blood pressure values, Aix brachial, PWVao values in the second and third trimesters, and fetus weight. The Kruskal-Wallis test was applied for this, obtaining significant differences in all cases: open paren p less than 0.05 and closed. When serum severe 25(OH)D levels deficiency was present, arterial stiffness parameters were significantly worse. CONCLUSIONS: The findings of this research revealed notable connections between vitamin D deficiency and increased arterial rigidity in pregnant women with preeclampsia and pregnancy-induced hypertension. These results emphasize the significance of conducting both examinations to obtain a more comprehensive evaluation of these patients. Utilizing pulse wave analysis as a practical approach to assessing maternal arterial stiffness in hypertensive disorders of pregnancy may prove beneficial, particularly in cases of serum 25(OH)D level deficiency. It could play a key role in identifying patients at higher risk of worsening disease severity and, thus, preventing any impact on fetal development.

Identifying Predictor Variables for a Composite Risk Prediction Tool for Gestational Diabetes and Hypertensive Disorders of Pregnancy: A Modified Delphi Study.

A composite cardiometabolic risk prediction tool will support the systematic identification of women at increased cardiometabolic risk during pregnancy to enable early screening and intervention. This study aims to identify and select predictor variables for a composite risk prediction tool for cardiometabolic risk (gestational diabetes mellitus and/or hypertensive disorders of pregnancy) for use in the first trimester. A two-round modified online Delphi study was undertaken. A prior systematic literature review generated fifteen potential predictor variables for inclusion in the tool. Multidisciplinary experts (n = 31) rated the clinical importance of variables in an online survey and nominated additional variables for consideration (Round One). An online meeting (n = 14) was held to deliberate the importance, feasibility and acceptability of collecting variables in early pregnancy. Consensus was reached in a second online survey (Round Two). Overall, 24 variables were considered; 9 were eliminated, and 15 were selected for inclusion in the tool. The final 15 predictor variables related to maternal demographics (age, ethnicity/race), pre-pregnancy history (body mass index, height, history of chronic kidney disease/polycystic ovarian syndrome, family history of diabetes, pre-existing diabetes/hypertension), obstetric history (parity, history of macrosomia/pre-eclampsia/gestational diabetes mellitus), biochemical measures (blood glucose levels), hemodynamic measures (systolic blood pressure). Variables will inform the development of a cardiometabolic risk prediction tool in subsequent research. Evidence-based, clinically relevant and routinely collected variables were selected for a composite cardiometabolic risk prediction tool for early pregnancy.