Hypertensive Disorders Of Pregnancy Research Articles

Addressing Hypertensive Disorders of Pregnancy through a Combined Renal-Maternal Fetal Medicine Clinic

Addressing Hypertensive Disorders of Pregnancy through a Combined Renal-Maternal Fetal Medicine Clinic

Can Peripheral Arterial Tonometry and Biomarkers Help Identify Women Who Will Have Progressively Worsening Hypertensive Disorders of Pregnancy?

This study aimed to (1) evaluate whether endothelial dysfunction, as measured by peripheral arterial tonometry (PAT) indices and biomarker (soluble fms-like tyrosine kinase-1 [sFLT], brain natriuretic peptide [BNP]) levels at 34 weeks gestation, can predict progression from nonsevere to severe hypertensive disorders of pregnancy (HDPs); and (2) develop a clinical risk model for prediction of progression from nonsevere to severe HDP. We prospectively enrolled patients with a singleton gestation carrying a nonsevere HDP diagnosis. Forty-five participants were enrolled for PAT evaluation and serum collection between 340/7 and 366/7 weeks. PAT indices (e.g., Augmentation Index normalized to a heart rate of 75 bpm [AI75]) and biomarker concentrations were assessed at enrollment. The primary outcome was progression from a nonsevere diagnosis in the late preterm period to a diagnosis of preeclampsia with severe features or superimposed preeclampsia. Statistical analyses included two-sample t-tests, Fisher's exact tests, and multivariate modeling. Thirteen subjects (30%) progressed to severe disease. No significant differences in mean PAT indices between the outcome groups were found. We found a significant difference in mean sFLT values between the two groups (p = 0.02, area under the curve [AUC] of 0.609), but not in mean BNP values. An endothelial dysfunction index (presence of fetal growth restriction, "high" AI75, and positive systolic blood pressure slope) discriminated between progression and nonprogression (p = 0.03, AUC of 0.707). sFLT level was a marker of progression from nonsevere to severe HDP. Further, a novel endothelial dysfunction index discriminated between progression and nonprogression to severe disease with good performance. · HDPs are important causes of morbidity and mortality.. · The sequelae of HDPs are not limited to pregnancy.. · Developing accurate tools to predict severe HDPs is of great clinical importance.. · Our index shows promising performance for predicting progression from nonsevere to severe HDPs..

A Review of Third-Trimester Complications in Pregnancies Complicated by Diabetes Mellitus.

Pregnancies affected by both pregestational and gestational diabetes mellitus carry an increased risk of adverse maternal and neonatal outcomes. While the risks associated with diabetes in pregnancy have been well documented and span across all trimesters, maternal and neonatal morbidity have been associated with select third-trimester complications. Further, modifiable risk factors have been identified that can help improve pregnancy outcomes. This review aims to examine the relationship between select third-trimester complications (large for gestational age, intrauterine fetal demise, hypertensive disorders of pregnancy, preterm birth, perineal lacerations, shoulder dystocia, and cesarean delivery) and the aforementioned modifiable risk factors, specifically glycemic control, blood pressure control, and gestational weight gain. It also highlights how early optimization of these modifiable risk factors can reduce adverse maternal, fetal, and neonatal outcomes. KEY POINTS: · Diabetes mellitus in pregnancy increases the risk of third-trimester complications.. · Modifiable risk factors exist for these complications.. · Optimizing these modifiable risk factors improves maternal and neonatal outcomes..

Prediction of adverse maternal and perinatal outcomes associated with pre-eclampsia and hypertensive disorders of pregnancy: a systematic review and meta-analysis

Hypertensive disorders of pregnancy are a leading cause of maternal and perinatal morbidity and mortality. If women at high risk for developing complications could be identified early, level of care could be triaged, limited resources could be correctly allocated and targeted interventions to prevent complications could be implemented. We updated a systematic review and meta-analysis and added single outcomes. Women with hypertensive disorders of pregnancy were included. Exposures were tests predicting adverse maternal and/or perinatal outcomes. We searched Medline, Embase, CINAHL, and Cochrane library from January 2016-February 2024. We included studies identified from the previous review. We calculated effect measures. For similar predictive tests and outcomes, area under the receiver-operating-characteristic curve (AUROC) were pooled. This study was registered by PROSPERO: CRD42022336368. Of the 2898 studies identified, 80 were included. Thirty were added from the previous review resulting in 110 included studies with 506,178 women. Despite more than 1500 tests being performed, most outcomes could not be pooled due to heterogeneity in populations, tests, and outcome definitions. For maternal outcomes, only studies reporting on the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) model could be pooled. For the composite outcome within 48-h the AUROC was 0.78 (95% CI 0.71-0.86, N=8). There was significant heterogeneity (I 2 =95.7%). For perinatal outcomes, data were pooled for pulsatility index in the umbilical artery and soluble FMS-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio. Biomarkers like the sFlt-1/PlGF ratio showed promising predictive performance for some outcomes but were not externally validated. Despite including over 100 studies with more than 1500 predictors, we were unable to pool any single maternal outcomes and only a few individual perinatal outcomes. The fullPIERS model was externally validated, showing moderate accuracy which varied across studies and should be validated in each new population. Angiogenic biomarkers showed promise but need validation. Future studies should use standardized outcome measures and validate promising tests. VB is supported by the Swedish Research Council, Grant number 2020-01481. University of Gothenburg.

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

BackgroundMetformin 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.MethodsWe 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.ResultsThe 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]).ConclusionsIn 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.

Risk of short-term cardiovascular disease in relation to the mode of delivery in singleton pregnancies: a retrospective cohort study

Cardiovascular disease (CVD) is increasing in prevalence and affects up to 4% of pregnancies in otherwise healthy persons. The specific factors that drive the development of CVD in pregnant people are poorly characterised. This study aimed to determine whether the mode of delivery in singletons affects the risk of cardiovascular morbidity and mortality within one year in patients without prior CVD. We designed a retrospective cohort study utilising the Nationwide Readmissions Database (NRD) to identify singleton delivery hospitalisations in the United States from Jan 1, 2010 to Nov 30, 2018. International Classification of Disease (ICD) versions 9 and 10 codes were used to identify patients with readmission for CVD within the calendar year of index delivery. Patients aged 15-54 who underwent a singleton vaginal or caesarean delivery were included. Patients with pre-existing CVD hospitalisations before or during delivery, ectopic pregnancies, or abortive outcomes were excluded. Participant data was retrieved from the NRD database. The primary outcome was hospital readmission, defined by ICD 9 and 10 codes for fatal or non-fatal CVD in the same calendar year as delivery. Cox proportional hazard regression models were used to adjust for confounders. These included maternal age, hospital bed size, hospital type, hospital teaching status, income quartile, insurance, and year of delivery. Additional sub-analyses were performed adjusting for hypertensive disorders of pregnancy and diabetes mellitus. Of the 14,179,299 singleton deliveries, 32% (n=4,553,492) underwent a caesarean. CVD readmissions occurred in 255.2 per 100,000 (n=11,710) caesarean deliveries compared with 133.9 per 100,000 (n=12,507) vaginal deliveries (rate difference [RD], 121.4, 95% confidence interval [CI], 114.8-127.9; hazard ratio [HR] adjusted for all confounders including hypertensive disorders of pregnancy and diabetes mellitus was 1.42, 95% CI 1.35-1.50). This association was highest in the first 0-29 days following delivery (HR 1.68, 95% CI 1.59-1.78). The risk of readmission for CVD persisted for one year. These findings suggest that caesarean delivery of singletons is associated with a higher risk of cardiovascular morbidity in patients without pre-existing CVD. This risk was highest in the first month but remained elevated for one year after delivery. These findings add to the accumulating evidence that undergoing caesarean delivery may have long-standing health implications and support the extension of the post-partum surveillance period. Limitations of this study include the lack of adjustment for body mass index, race, and parity. We were also unable to determine the reason for the caesarean delivery. None.

Echocardiography for Management of Cardiovascular Disease in Pregnancy.

Cardiovascular disease (CVD) continues to be a leading contributor to maternal mortality and morbidity. Echocardiography is an essential tool for patients with suspected and known CVD to establish symptom etiology, treatment strategy, and prognosis. We summarize the current status of conventional and novel techniques for assessment of CVD during pregnancy. Conventional techniques are still useful for evaluation of known or suspected CVD. Advanced technology using speckle tracking continues to evolve and is increasingly applied for diagnosis of subclinical disease including hypertensive disorders of pregnancy and left ventricular (LV) dysfunction. Precise recommendations on how frequently echocardiography should be performed and for whom remain in flux. However, a recently published consensus statement and new screening tool for pregnancy assessment of patients with valvular heart disease provide additional advice on using this modality. Echocardiography remains the diagnostic modality of choice for evaluation and risk stratification in pregnancy.

Hypertensive Disorders of Pregnancy: A Window into Breastfeeding Outcomes in Varied Healthcare Systems

Varied hospital systems demonstrate diverse and often very different approaches to patient care. This may best be analyzed by looking at specific disorders and outcomes in a population with these disorders. As one such lens, hypertensive disorders of pregnancy (HDPs) continue to pose a severe health risk for mothers and infants, and breastfeeding outcomes play a crucial role in determining long-term maternal and fetal health. This pilot study investigated breastfeeding outcomes in two hospitals, as representatives for differing healthcare systems, among patients diagnosed with HDPs. Data were collected for 12 months at two hospitals, one private and one military, on 729 patients diagnosed with HDPs. Data were analyzed for infant maturity at birth and breastfeeding outcomes. Most participants (83.2%) stated their intention to breastfeed for the first six months of life. By hospital discharge, only 56% (p = 0.0001) of the private hospital participants were breastfeeding compared to 65% of the military hospital participants. In addition, while 69% of infants were born before term, more infants were born before term at the private hospital (71%) than at the military hospital (65%), with 37% (private) and 42% (military) of preterm infants breastfeeding at hospital discharge. Significant differences existed between these two hospital systems in the number of those initiating breastfeeding and breastfeeding at hospital discharge. The military hospital was more successful in assisting these high-risk women in meeting their breastfeeding intentions. Changes in hospital practices, such as metrics and incentivization, focusing on breastfeeding support, could improve the rate of breastfeeding at hospital discharge and impact long-term health outcomes.

Impact of multiple obesity metrics on hypertensive disorders of pregnancy: a meta-analysis and Mendelian randomisation study

BackgroundThe relationships between various obesity measures and hypertensive disorders of pregnancy (HDP) remain inadequately explored, and their causal links are not well understood. This study aims to clarify these associations...

Relationships of Leg Ischemia Symptoms and Carotid Artery Atherosclerosis with Hypertensive-Disorders-of-Pregnancy-Associated Peptides in Patients with Lower Extremity Arterial Disease.

Objectives: We have proposed seven peptides with low molecular weights in blood as biomarkers for the diagnosis of hypertensive disorders of pregnancy (HDP). The purpose of this cross-sectional study was to investigate the relationships of the HDP-associated peptides with symptoms of leg ischemia and degree of atherosclerosis in patients with lower extremity arterial disease (LEAD). Methods: The subjects were 165 outpatients with LEAD (145 men and 20 women aged 74.3 ± 8.1 years [47-93 years]). Their symptoms of leg ischemia, leg arterial flow, and degree of atherosclerosis were evaluated using the Rutherford classification of Clinical Ischemia Category, ankle-brachial index (ABI) and the intima-media thickness (IMT) of carotid arteries, respectively. Serum concentrations of the HDP-related peptides were measured by mass spectrometry. Results: The grade of the Rutherford classification was positively associated with levels of the peptides with m/z 2091 and 2378 and was inversely associated with levels of the peptide with m/z 2081. The category of the Rutherford classification was inversely associated with ABI. There were no HDP-associated peptides that showed significant relationships with IMT. Conclusions: The peptides with m/z 2081, 2091, and 2378 are possible biomarkers of leg ischemia but are not associated with carotid atherosclerosis in LEAD patients.

Preconception HbA1c Levels in Adolescents and Young Adults and Adverse Birth Outcomes

Subclinical hyperglycemia before pregnancy may be associated with the likelihood of maternal morbidity but is understudied among young people. To explore the association of preconception hemoglobin A1c (HbA1c) levels among adolescents and young adults with risk of gestational diabetes at first live birth. This retrospective cohort study used linked 2009 to 2017 birth registry, hospital discharge, and New York City Department of Health A1C Registry data for birthing individuals aged 10 to 24 years with no history of diabetes and at least 1 preconception HbA1c test in New York, New York. Statistical analysis was performed from August to November 2022. Preconception HbA1c values categorized as no diabetes (HbA1c <5.7%) or prediabetes (HbA1c ≥5.7% to <6.5%). The primary outcome was gestational diabetes at first birth. Secondary outcomes included hypertensive disorders of pregnancy, preterm birth, cesarean delivery, and macrosomia. Log binomial regression was used to estimate the relative risk (RR) of gestational diabetes at first birth by preconception HbA1c level, adjusting for prepregnancy characteristics. The optimal HbA1c threshold for gestational diabetes was examined using receiver operating curve regression. A total of 14 302 individuals (mean [SD] age, 22.10 [1.55] years) met study eligibility criteria. Of these, 5896 (41.0%) were Hispanic, 4149 (29.0%) were Black, 2583 (18.1%) were White, 1516 (10.6%) were Asian, and 185 (1.3%) had other or unknown race and ethnicity. Most (11 407 individuals [79.7%]) had normoglycemia before pregnancy, and 2895 individuals (20.2%) had prediabetes. Adjusting for prepregnancy characteristics, those with preconception prediabetes had more than twice the risk of gestational diabetes vs those with normoglycemia (adjusted RR [aRR], 2.21; 95% CI, 1.91-2.56). Preconception prediabetes was associated with small increases in the likelihood of a hypertensive disorder of pregnancy (aRR, 1.18; 95% CI, 1.03-1.35) and preterm delivery (aRR, 1.18; 95% CI, 1.02-1.37). The aRRs for cesarean delivery (aRR, 1.09; 95% CI, 0.99-1.20) and macrosomia (aRR, 1.13; 95% CI, 0.93-1.37) were increased but not statistically significant. The optimal HbA1c threshold to identify gestational diabetes among adolescents and young adults was 5.6%. The threshold did not vary by obesity status but was slightly lower among Hispanic individuals (HbA1c of 5.5%). In this study of adolescents and young adults with at least 1 preconception HbA1c test, prediabetes was associated with increased likelihood of maternal cardiometabolic morbidity at first birth. Efforts to optimize cardiometabolic health before pregnancy may avert excess maternal risk.

Severe Maternal and Neonatal Morbidity Among Gestational Carriers : A Cohort Study.

Use of a gestational ("surrogate") carrier is increasingly common. Risk for maternal and neonatal adversity is largely unknown in this birthing population. To determine the risk for severe maternal morbidity (SMM) and severe neonatal morbidity (SNM) in gestational carriers. Population-based cohort study. All of Ontario, Canada. All singleton births at more than 20 weeks' gestation, from 2012 to 2021. Exposure was type of conception, namely, gestational carriage (main exposure), unassisted conception (comparison group 1), and in vitro fertilization (IVF) (comparison group 2). Main composite outcomes were SMM and SNM. Modified Poisson regression models generated weighted relative risks (wRRs) using propensity score-based overlap weighting. Secondary outcomes included hypertensive disorders of pregnancy, cesarean delivery, preterm birth, and postpartum hemorrhage. Of all eligible singleton births, 846 124 (97.6%) were by unassisted conception, 16 087 (1.8%) by IVF, and 806 (0.1%) by gestational carriage. Respective risks for SMM were 2.3%, 4.3%, and 7.8%. The wRRs were 3.30 (95% CI, 2.59 to 4.20) comparing gestational carriage with unassisted conception and 1.86 (CI, 1.36 to 2.55) comparing gestational carriage with IVF. Respective risks for SNM were 5.9%, 8.9%, and 6.6%, generating wRRs of 1.20 (CI, 0.92 to 1.55) for gestational carriage versus unassisted conception and 0.81 (CI, 0.61 to 1.08) for gestational carriage versus IVF. Hypertensive disorders, postpartum hemorrhage, and preterm birth at less than 37 weeks were also significantly higher contrasting gestational carriers to either comparison group. Absence of information about indications for choosing a gestational carrier, and oocyte or sperm donor source. Among singleton births of more than 20 weeks' gestation, a higher risk for SMM and adverse pregnancy outcomes was seen among gestational carriers compared with women who conceived with and without assistance. Although gestational carriage was associated with preterm birth, there was less clear evidence of severe neonatal morbidity. Potential mechanisms for higher maternal morbidity among gestational carriers require elucidation, alongside developing special care plans for gestational carriers. The Canadian Institutes of Health Research.

Maternal morbidity in postpartum severe preeclampsia by obstetric delivery volume

BackgroundPre-eclampsia is a leading cause of maternal morbidity and mortality in the United States. Emerging data suggests that postpartum pre-eclampsia may be associated with a higher incidence of maternal morbidity compared to hypertensive disorders of pregnancy (HDP) diagnosed antenatally. Understanding postpartum maternal risk across facilities with a spectrum of obstetric services is critical with the rising rates of pre-eclampsia in all healthcare settings. ObjectiveWe investigated the relationship between facility delivery volume and rates of nontransfusion severe maternal morbidity (SMM) among patients readmitted postpartum for pre-eclampsia with severe features. Study DesignThis is a retrospective cohort study using the Nationwide Readmissions Database (2015–2019) of postpartum patients readmitted for pre-eclampsia with severe features. Our primary outcome was nontransfusion SMM during readmission, defined per U.S. Centers for Disease Control and Prevention criteria. We also evaluated SMM, cardiac SMM, and individual morbidities. The exposure variable was the number of annual deliveries at the readmitting facility. Restricted cubic splines with 4 knots were used to assess the functional form of the relationship between obstetric delivery volume and nontransfusion SMM; a linear relationship was identified as optimal. Logistic regression was used to estimate adjusted odds ratios (aOR) which controlled for maternal age, nontransfusion SMM at delivery, expanded obstetric comorbidity index, and HDP during delivery. ResultsThe cohort included 29,472 patients readmitted with postpartum pre-eclampsia with severe features. The primary payer was 55% private and 42% governmental. Median age was 31.4 years. Most patients did not have prior HDP (65%) or chronic hypertension (86%) diagnosis antenatally. The median interval from delivery hospitalization to readmission was 3.9 days (25th percentile–75th percentile: 2.2–6.5). Nontransfusion SMM occurred in 7% of patients readmitted to facilities with >2000 deliveries compared to 9% with 1 to 2000 deliveries, and 52% without any delivery hospitalizations. The most common SMM was pulmonary edema and heart failure, observed in 4% of readmissions. We observed that for every increase in 1000 deliveries, the odds of a nontransfusion SMM at readmission decreased by 3.5% (aOR: 0.965; 95% confidence interval: 0.94, 0.99). ConclusionNontransfusion SMM for postpartum readmissions with pre-eclampsia with severe features was inversely associated with readmitting hospital delivery volume. This information may guide risk-reducing initiatives for identifying strategies to optimize postpartum care at facilities with lower or no delivery volume.

The role of arginase estimation to predict hypertensive disorder of pregnancy at an earlier stage.

To determine the significance of serum arginase estimation as a predictor of pregnancy-induced hypertension and preeclampsia at an early stage. The observational, cross-sectional study was conducted from October 15, 2021, to October 15, 2022, at the Department of Chemical Pathology, in collaboration with the Department of Obstetrics and Gynaecology, Pakistan Railway Hospital, Islamic International Medical College Trust, Rawalpindi, Pakistan, and comprised pregnant women with 20-25 weeks of gestation who were divided into three groups. Those having no complications were placed in control group A, those with pregnancy-induced hypertension in group B, and those with preeclampsia in group C. Serum arginase, uric acid, alanine transaminase, platelet count and spot urinary protein levels were measured for each subject. Data was analysed using SPSS 26. Of the 90 women, 30(33.3%) were in group A with mean age 27.27±2.90 years, 30(33.3%) were in group B with mean age 30.17±2.48 years, and 30(33.3%) were in group C with mean age 29.33±3.11 years. There were significant intergroup differences in the mean levels of serum arginase, serum uric acid, alanine transaminase, platelet count and spot urinary protein (p<0.05). A moderate to marked increase in serum arginase levels in pregnancy-induced hypertension and preeclampsia cases, combined with abnormal serum uric acid and alanine transaminase levels along with low platelet count suggested that serum arginase estimation could be used to predict hypertensive disorders of pregnancy at an early stage.

Patología placentaria en restricción del crecimiento fetal y trastornos hipertensivos del embarazo

Introduction: hypertensive disorders of pregnancy and fetal growth restriction are conditions which have a great impact, sharing their pathogenesis in abnormal placentation. The histological study of the placenta allows understanding part of these phenomena, besides having academic, medical, and legal implications. Objective: to characterize placental anatomopathological findings in women diagnosed with hypertensive disorders of pregnancy and/or fetal growth restriction in a high complexity hospital in Popayán, Colombia. Methods: a cross-sectional observational study, including a population of women who during their pregnancy were diagnosed with fetal growth restriction and / or hypertensive disorders, between 2019 and 2020, in whom a placental anatomopathological examination was performed. Results: of the 155 cases analyzed, 99.35% evidenced maternal vascular malperfusion, 70.97% fetal vascular malperfusion, 4.52% delayed villous maturation, and.35% inflammation. Conclusions: this study revealed high prevalence of abnormal histopathological findings which correlate to those reported in the literature.

Intact NOX2 in T Cells Mediates Pregnancy-Induced Renal Damage in Dahl SS Rats.

Hypertensive disorders of pregnancy are associated with increased risk for cardiovascular disease, renal disease, and mortality. While the exact mechanisms remain unclear, T cells and reactive oxygen species have been implicated in its pathogenesis. We utilized Dahl salt-sensitive (SS), SSCD247-/- (Dahl SS CD247 knockout rat; lacking T cells), and SSp67phox-/- (Dahl SS p67phox [NOX2 (NADPH [nitcotinamide adenine dinucleotide phosphate] oxidase 2)] knockout rat; lacking NOX2) rats to investigate these mechanisms in primigravida and multigravida states. We assessed blood pressure and renal damage phenotypes in SS, SSCD247-/-, and SSp67phox-/- rats during primigravida and multigravida states. To investigate the contribution of NOX2 in T cells, we performed adoptive transfers of splenocytes or cluster of differentiation (CD)4+ T cells from either SS or SSp67phox-/- donors into SSCD247-/- recipients to determine pregnancy-specific alterations in phenotype. Multigravida SS rats developed significant pregnancy-induced renal damage and renal functional impairment associated with elevated maternal mortality rates, whereas deletion of T cells or NOX2 garnered protection. During primigravida states, this attenuation in renal damage was observed, with the greatest protection in the SSp67phox-/- rat. To demonstrate that NOX2 in T cells contributes to adverse pregnancy phenotypes, adoptive transfer of SS splenocytes into SSCD247-/- rats resulted in significant pregnancy-induced renal damage, whereas transfer of SSp67phox-/- splenocytes garnered protection. Specifically, the transfer of SS CD4+ T cells resulted in pregnancy-induced proteinuria and increases in uterine artery resistance index, an effect not seen with the transfer of SSp67phox-/- CD4+ T cells. T cells and NOX2-derived reactive oxygen species, thus, contribute to end-organ damage in both primigravida and multigravida pregnancies in the SS rat leading to increases in maternal mortality.

Impact of patient safety bundle and team-based training on obstetric hypertensive emergencies.

Hypertensive disorders of pregnancy, defined as chronic (<20 weeks) or gestational (>20 weeks), are a leading cause of pregnancy related mortality in the United States1. Hypertensive disorders of pregnancy had increased prevalence from 13.3% to 15.9% among delivery hospitalizations between 2017 and 20191. The objective of this project was to increase the percentage of obstetric patients with hypertensive emergency who received evidence-based treatment within 60 minutes at a single academic center. Study Design Data was collected before and after the implementation of a hypertension patient safety bundle. Each occurrence of hypertensive emergency was assessed to determine if evidence-based intervention occurred within 60 minutes, and if the intervention steps were successfully followed. Bundle implementation included creation of a standardized order set and interdisciplinary team-based simulations. Baseline data compared 250 pre-implementation to 250 post-implementation interventions. The quality improvement interdisciplinary team reevaluated data monthly and incorporated process improvements through Plan Do Study Act (PDSA) cycles to achieve a goal of 80% of patients receiving evidence-based treatment within 60 minutes. Results A total of 1025 hypertensive emergencies were identified in 543 patients. Prior to the protocol on average 64% of patients received evidence-based, timely treatment. After implementation of this bundle and several PDSA cycles, we sustained >80% of patients receiving target treatment for the final six months of data collection. The leading deviations were "no medication given" and "incorrect medication". Improvements in order set accessibility and repeated team-based trainings led to improvement in these identified protocol deviations. Conclusion Implementation of a patient safety bundle led to a sustained 6 month improvement in the percentage of patients receiving appropriate treatment of obstetric hypertensive emergency within 60 minutes of the first severe hypertension measurement. Processes that may have helped achieve this outcome included standardized order sets, team awareness of institutional data and team-based simulations.

Vitamin D May not be Crucial: Association between Serum Vitamin D Level and Pregnancy-Induced Hypertension-A Meta-Analysis

Background: The association between vitamin D and pregnancy-induced hypertension (PIH) remains contentious. The aim of our study was to evaluate the existence of an association between serum vitamin D levels and the incidence of PIH. Methods: We conducted a literature search in PubMed, the Cochrane Library, and Embase databases in June 2024 using the following search terms: 25-hydroxyvitamin D (25(OH)D), Vitamin D, 1,25(OH)2D, VD, 1,25-dihydroxyvitamin D or 25(OH)D, combined with PIH. Two reviewers independently screened the literature based on inclusion and exclusion criteria. Data were then extracted and assessed for quality. Comparisons were made between the highest and lowest categories of serum vitamin D levels. Relative risks (RRs) and 95% confidence intervals (CIs), adjusted for multivariable effects, were pooled using a random-effects model. A two-stage dose-response meta-analysis was used to evaluate the trends. Results: 17 studies met the inclusion criteria. Of these, 11 prospective studies investigated the relationship between vitamin D levels and gestational hypertension, involving 8834 events and 17,104 participants. The results showed that vitamin D was only marginally associated with hypertensive disorders in pregnancy (summary RR = 0.99; 95% CI: 0.97–1.02; I2 = 67.5%; p = 0.001). However, 6 case-control studies investigated the relationship between vitamin D levels and gestational hypertension, involving 80,814 events and 330,254 participants. The results showed that vitamin D is not associated with pregnancy hypertensive disorders (summary RR = 1.09; 95% CI: 0.84–1.41; I2 = 75.4%; p = 0.001). In the subgroup analysis, the pooled effect of 25-hydroxyvitamin D (25(OH)D) showed a slight association with gestational hypertension (pooled RR = 0.99; 95% CI: 0.96–1.02; I2 = 72.6%; p = 0.000). The dose-response analysis showed that increasing vitamin D doses are marginally associated with a decrease in the incidence rate. Conclusions: Our research suggests that the risk of PIH may not be related to the vitamin D levels. Our research supports the hypothesis that gestational hypertension may not be associated with low levels of vitamin D, indicating that the role of vitamin D may not be significant.

The Implications of a "Flat" Oral Glucose Tolerance Test Curve in Pregnancy.

To determine whether pregnant women with "flat" oral glucose tolerance test (OGTT) curves are at increased risk of adverse perinatal outcomes. We conducted a retrospective cohort study comparing the perinatal outcomes of pregnant women whose 100g OGTT curve was "flat" (fasting serum glucose below 95 mg/dl and the remaining values below 100 mg/dl) to those of women whose OGTT curve was "normal". Primary outcomes compared were the prevalence of macrosomic and small for gestational age (SGA) neonates. Secondary outcomes included hypertensive disorders of pregnancy (HDP), intrauterine fetal demise, placental abruption, induction of labor, meconium-stained amniotic fluid (MSAF), mode of delivery, postpartum hemorrhage (PPH), blood product transfusion, postpartum readmission, umbilical artery pH <7.1, Apgar score <7 at 5 minutes, neonatal intensive care unit (NICU) admission, neonatal respiratory and infectious morbidity, and hypoglycemia. Composite adverse maternal and neonatal outcomes were also evaluated. There were 1,060 patients in the study group and 10,591 patients in the control group. Patients with a flat OGTT had a reduced risk of delivering a macrosomic neonate (11.4% vs. 15.1% OR 0.7 [0.58-0.89] p=0.001) and having an unplanned cesarean delivery (7.5% vs 10.2% OR 0.8 [0.58-0.96] p=0.002). There was no difference in the rate of composite adverse maternal (14.0% vs 15.4% OR 0.9 [0.7-1.0] p=0.1) or neonatal outcome (5.3% vs. 4.5% OR 1.2 [0.9-1.5] p=0.15). Neonates had a slightly lower mean birthweight (3474g vs. 3505g, p=0.04), but the rate of SGA was similar in the two groups (2.5% vs.1.8% OR 1.3[0.9-2.0] p=0.08). Conclusions Pregnant women whose OGTT curve is flat have a lower risk of delivering macrosomic neonates and undergoing unplanned cesarean delivery and are not at increased risk of adverse maternal or neonatal outcomes. More research is required to evaluate the relationship between different OGTT curves and th.

Circulating immune cells and apolipoprotein A mediation: a Mendelian randomization study on hypertensive disorder of pregnancy.

Studies using observational epidemiology have indicated that inflammation and immunological dysregulation are important contributors to placental and renal failure, which ultimately results in maternal hypertension. The potential causal relationships between the immunophenotypes and hypertensive disorder of pregnancy (HDP) are yet unclear. We conducted two-sample Mendelian randomization (MR) analyses to thoroughly examine the relationship between immunophenotypes and HDP. The GWAS data on immunological traits was taken from public catalog for 731 immunophenotypes and the summarized GWAS data in 4 types of HDP were retrieved from FinnGen database. The link between immune cell traits and HDP was examined through our study methodology, taking into account both direct relationships and mediation effects of apolipoprotein A (apoA). The inverse variance weighted (IVW) method served as the main analysis, while sensitivity analysis was carried out as a supplement. We identified 14 highly correlative immunophenotypes and 104 suggestive possible factors after investigating genetically predicted immunophenotype biomarkers. According to the IVW analysis, there was a strong correlation between HDP and HLA DR on DC and plasmacytoid DC. Reverse MR analysis showed that there was no statistically significant effect of HDP on immune cells in our investigation. Mediation analysis confirmed that apoA mediates the interaction between HLA DR on DC and HDP. Our results highlight the complex interplay of immunophenotypes, apoA, and HDP. Moreover, the pathophysiological link between HLA DR on DC and HDP was mediated by the level of apoA.