Report from a text-based blood pressure monitoring prospective cohort trial among postpartum women with hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy are a main cause of maternal morbidity and mortality in the United States and worldwide, and it is estimated that approximately 60% of maternal deaths in the United States occur during the postpartum period. The utilization of telehealth modalities such as home blood pressure monitoring has shown improvement in blood pressure control and adherence with follow up visits. Our study sought to determine if standardized education improved patient hypertension knowledge and if this when combined with home blood pressure telemonitoring increased participants' postpartum self-blood pressure monitoring and postpartum visit attendance. METHODS: This is an Institutional Review Board approved prospective cohort study conducted at the University of Mississippi Medical Center. Women with a hypertensive disorder of pregnancy who met the inclusion criteria and provided written informed consent to participate were enrolled. Participants received a baseline pre-education questionnaire designed to assess their knowledge of their hypertensive diagnosis, hypertension management, and postpartum preeclampsia (PreE). Participants then received standard education, a blood pressure monitor, and were scheduled a follow-up visit during the first 10 days following discharge. Remote home blood pressure monitoring was performed via text messages and voice calls for 6-weeks postpartum. At the conclusion of the study, participants repeated their original questionnaire. RESULTS: 250 women provided informed consent to participate in the study and were included in this analysis. Relative to the baseline survey, there was a significant increase (p = 0.0001) in the percentage of correct responses. There was not an association between study engagement and percentage of correct responses on end of study questionnaire (p = 0.33) or postpartum visit attendance (p = 0.69). Maternal age was found to drive study engagement, even when adjusted for community-level distress (p = 0.03) and maternal race (p = 0.0002). CONCLUSION: Implementing a standardized postpartum education session was associated with improvement in patient's knowledge. Further studies are needed with more longitudinal follow up to assess if this program would also result in improved long-term outcomes and decreased hospital readmission rates. TRIAL REGISTRATION: NCT04570124.

Maternal immune suppression during pregnancy does not prevent abnormal behavior in offspring.

BACKGROUND: Offspring of hypertensive disorders of pregnancy are at an increased risk of developing neurodevelopmental and neurobehavioral disorders compared to offspring from non-affected pregnancies. Using rodent models of Preeclampsia (PreE; new onset of hypertension after 20 weeks gestation) and HELLP (hemolysis, elevated liver enzymes, and low platelets), we studied the behavioral outcome of their offspring in adolescence. METHODS: A subset of dams received Orencia, a T-cell activation inhibitor, as T cells have been associated with the induction of hypertension and inflammation during pregnancy. We hypothesized that offspring from hypertensive dams would experience adverse behavioral outcomes in social, cognitive, locomotor, and anxiety tests, and offspring from dams treated with Orencia would demonstrate less adverse behaviors. RESULTS: Male offspring of PreE + Orencia dams (p < 0.05) and female offspring from HELLP + Orencia dams (p < 0.05) spent more time playing compared to normal pregnant offspring. All offspring from hypertensive and Orencia-treated dams performed worse on the Barnes Maze test compared to normal pregnant. We also measured adult (postnatal day > 60) myelin basic protein (MBP) and NeuN expression in both the prefrontal cortex and hippocampus. In the hippocampus and prefrontal cortex, there was no difference in expression of either MBP or NeuN in all groups regardless of sex. CONCLUSION: The results from this study suggest that offspring of hypertensive disorders of pregnancy have behavioral changes, specifically cognitive differences. This study has shown that there is a sex dependent difference in offspring neurobehavioral development, influenced in part by the type of hypertensive disorder of pregnancy, and alterations in the maternal immune system.

Children of pregnancies that are complicated by hypertensive disorders of pregnancy (HDP) such as Preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome have an increased risk of having behavioral deficits and changes in brain development. Both Preeclampsia and HELLP have been shown to activate the immune and inflammation systems in the body of the mother. In this study, we used offspring of rat models of Preeclampsia and HELLP to study their behavior including anxiety-like behaviors and memory deficits. We also compared offspring of rat models of Preeclampsia and HELLP that were given Orencia, which minimizes immune responses by blocking the activation of T cells. We also studied two regions of the brain (prefrontal cortex and hippocampus) to measure two proteins (myelin basic protein (MBP) and NeuN) involved in brain function. Our study found that offspring from dams that were treated with Orencia during pregnancy with HDP had sex differences in time playing. All offspring, regardless of the HDP dam being treated with or without Orencia, had evidence of spatial learning deficits. When sexes and groups were compared there was no difference in MBP or NeuN expression in the prefrontal cortex or hippocampus.

Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.

Indoxyl Sulfate Administration during Pregnancy Contributes to Renal Injury and Increased Blood-Brain Barrier Permeability.

Rates of pregnancy-related acute kidney injury (PR-AKI) have increased in the U.S over the past two decades, but how PR-AKI affects the blood-brain barrier (BBB) is understudied. AKI is associated with increased amounts of uremic toxins, like indoxyl sulfate (I.S), whose chronic administration leads to BBB and cognitive changes. This study's objective was to determine if (1) PR-AKI increases I.S and (2) if administration of I.S during pregnancy elicits renal injury and/or increases BBB permeability. From gestational day (GD) 11 to GD19, Sprague Dawley rats were given either 100 or 200 mg/kg body-weight dose of I.S. PR-AKI was induced on GD18 via 45 min bilateral renal ischemic reperfusion surgery. On GD18, metabolic cage metrics and metabolic waste was collected and on GD19 blood pressure, and BBB permeability (by Evan's Blue infusion) were measured. I.S and creatinine were measured in both urine and circulation, respectively. One-way ANOVA or student t-tests were performed using GraphPad Prism with a p < 0.05 significance. I.S and PR-AKI led to oliguria. I.S administration led to increased BBB permeability compared to normal pregnant and PR-AKI animals. These results suggest that I.S administration during pregnancy leads to increased BBB permeability and evidence of renal injury comparable to PR-AKI animals.

Long-term health-related quality of life and symptom severity following hysterectomy, myomectomy, or uterine artery embolization for the treatment of symptomatic uterine fibroids.

BACKGROUND: Few studies have directly compared different surgical procedures for uterine fibroids with respect to long-term health-related quality of life outcomes and symptom improvement. OBJECTIVE: We examined differences in change from baseline to 1-, 2-, and 3-year follow-up in health-related quality of life and symptom severity among patients who underwent abdominal myomectomy, laparoscopic or robotic myomectomy, abdominal hysterectomy, laparoscopic or robotic hysterectomy, or uterine artery embolization. STUDY DESIGN: The COMPARE-UF registry is a multiinstitutional prospective observational cohort study of women undergoing treatment for uterine fibroids. A subset of 1384 women aged 31 to 45 years who underwent either abdominal myomectomy (n=237), laparoscopic myomectomy (n=272), abdominal hysterectomy (n=177), laparoscopic hysterectomy (n=522), or uterine artery embolization (n=176) were included in this analysis. We obtained demographics, fibroid history, and symptoms by questionnaires at enrollment and at 1, 2, and 3 years posttreatment. We used the UFS-QoL (Uterine Fibroid Symptom and Quality of Life) questionnaire to ascertain symptom severity and health-related quality of life scores among participants. To account for potential baseline differences across treatment groups, a propensity score model was used to derive overlap weights and compare total health-related quality of life and symptom severity scores after enrollment with a repeated measures model. For this health-related quality of life tool, a specific minimal clinically important difference has not been determined, but on the basis of previous research, a difference of 10 points was considered as a reasonable estimate. Use of this difference was agreed upon by the Steering Committee at the time when the analysis was planned. RESULTS: At baseline, women undergoing hysterectomy and uterine artery embolization reported the lowest health-related quality of life scores and highest symptom severity scores compared with those undergoing abdominal myomectomy or laparoscopic myomectomy (P<.001). Those undergoing hysterectomy and uterine artery embolization reported the longest duration of fibroid symptoms with a mean of 6.3 years (standard deviation, 6.7; P<.001). The most common fibroid symptoms were menorrhagia (75.3%), bulk symptoms (74.2%), and bloating (73.2%). More than half (54.9%) of participants reported anemia, and 9.4% women reported a history of blood transfusion. Across all modalities, total health-related quality of life and symptom severity score markedly improved from baseline to 1-year with the largest improvement in the laparoscopic hysterectomy group (Uterine Fibroids Symptom and Quality of Life: delta= [+] 49.2; symptom severity: delta= [-] 51.3). Those undergoing abdominal myomectomy, laparoscopic myomectomy, and uterine artery embolization also demonstrated significant improvement in health-related quality of life (delta= [+]43.9, [+]32.9, [+]40.7, respectively) and symptom severity (delta= [-]41.4, [-] 31.5, [-] 38.5, respectively) at 1 year, and the improvement persisted from baseline for uterine-sparing procedures during second (Uterine Fibroids Symptom and Quality of Life: delta= [+]40.7, [+]37.4, [+]39.3 SS: delta= [-] 38.5, [-] 32.0, [-] 37.7 and third year (Uterine Fibroids Symptom and Quality of Life: delta= [+] 40.9, [+]39.9, [+]41.1 and SS: delta= [-] 33.9, [-]36.5, [-] 33.0, respectively), posttreatment intervals, however with a trend toward decline in degree of improvement from years 1 and 2. Differences from baseline were greatest for hysterectomy; however, this may reflect the relative importance of bleeding in the Uterine Fibroids Symptom and Quality of Life, rather than clinically meaningful symptom recurrence among women undergoing uterus-sparing treatments. CONCLUSION: All treatment modalities were associated with significant improvements in health-related quality of life and symptom severity reduction 1-year posttreatment. However, abdominal myomectomy, laparoscopic myomectomy and uterine artery embolization indicated a gradual decline in symptom improvement and health-related quality of life by third year after the procedure.

A Comparative Analysis of Health-Related Quality of Life 1 Year Following Myomectomy or Uterine Artery Embolization: Findings from the COMPARE-UF Registry.

Objective: To compare 12-month post-treatment health-related quality of life (HR-QoL) and symptom severity (SS) changes among patients with symptomatic uterine fibroids (SUF) not seeking fertility and undergo a hysterectomy, abdominal myomectomy (AM), or uterine artery embolization (UAE). Materials and Methods: The Comparing Options for Management: Patient-Centered Results for Uterine Fibroids (COMPARE-UF) Registry is a multi-institutional prospective observational cohort study of patients treated for SUF. A subset of 1465 women 31-45 years of age, who underwent either hysterectomy (n = 741), AM (n = 446), or UAE (n = 155) were included in this analysis. Demographics, fibroid history, and symptoms were obtained by baseline questionnaires and at 1 year post-treatment. Results were stratified by all treatments and propensity score weighting to adjust for differences in baseline characteristics. Results: Women undergoing UAE reported the lowest baseline HR-QoL and highest SS scores (mean = 40.6 [standard deviation (SD) = 23.8]; 62.3 [SD = 24.2]) followed by hysterectomy (44.3 [24.3]; 59.8 [SD = 24.1]). At 12 months, women who underwent a hysterectomy experienced the largest change in both HR-QoL (48.7 [26.2]) and SS (51.9 [25.6]) followed by other uterine-sparing treatments. Propensity score weighting revealed all treatments produced substantial improvement, with hysterectomy patients reporting the highest HR-QoL score (92.0 [17.8]) compared with myomectomy (86.7 [17.2]) and UAE (82.6 [21.5]) (p < 0.0001). Similarly, hysterectomy patients reported the lowest SS scores (8.2 [15.1]) compared with myomectomy (16.5 [15.1]) and UAE (19.6 [17.5]) (p < 0.0001). Conclusion: All procedures showed improvement in HR-QoL and reduction in SS score at 12 months, hysterectomy showing maximum improvement. Of importance, at 12 months, patients who underwent either a myomectomy or UAE reported comparable symptom relief and HR-QoL. Clinicaltrials.Gov Identifier: NCT02260752.

COVID-19 Not Hypertension or Diabetes Increases the Risk of Preeclampsia among a High-Risk Population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has been associated with greater morbidity and increased mortality in certain populations, such as those with chronic medical conditions, the elderly, and pregnant women. Our goal was to determine if COVID-19 infection during pregnancy increased the risk of preeclampsia in a population of women with increased risk factors for preeclampsia. We present a prospective observational matched case-control study of 100 deliveries with confirmed SARS-CoV2. Specifically, we investigated the maternal and neonatal outcomes in a high-risk population of pregnant women. Among women with COVID-19, the severity of symptoms was associated with the incidence of preeclampsia, but not with pre-existing diabetes or hypertension. Women with more severe symptoms were more likely to delivery pre-term with smaller babies. After adjusting for diabetes, hypertensive women with COVID-19 had an increased risk of preeclampsia aOR4.3 [1.5,12.4] compared to non-hypertensive women with COVID-19. After adjusting for hypertension, women with diabetes and COVID-19 had an increased risk of preeclampsia aOR3.9 [1.2,12.5]. This relationship was not seen among women without COVID-19. For women who had pre-existing diabetes or hypertension, the risk of developing preeclampsia was only increased if they were also diagnosed with COVID-19, suggesting that in our population of women the risk of preeclampsia is not associated with pre-existing diabetes or hypertension.

No association between perinatal mood disorders and hypertensive pregnancies.

Mental health disorders such as anxiety and/or depression are the most common mental health disorders seen among reproductive aged women and can increase during pregnancy. Many sociodemographic risk factors have been associated with anxiety and/or depression in pregnancy, which can lead to adverse maternal and infant outcomes including the risk of a hypertensive pregnancy. The current study prospectively examined self-reported anxiety, depression and stress in pregnant women without a history of fetal loss or mood disorders beginning at 20-26 weeks. At each study visit, circulating immune factors associated with perinatal mood disorders were measured in blood samples that were collected. A total of 65 women were eligible for data analysis, 26 of which had hypertensive pregnancies. There was not a significant difference in self-reported depression, anxiety or stress between hypertensive disorders of pregnancy and normotensive women. Black women were more likely to have a hypertensive pregnancy and develop a perinatal mood disorder compared to non-black women. Both the inflammatory cytokines interleukin-17 and tumor necrosis factor-alpha were increased in patients with perinatal mood disorders. However, additional research is needed in a larger sample to truly understand the relationship between these factors along with the underlying etiologies and the associated outcomes.

Preeclampsia and COVID-19: the Role of Inflammasome Activation.

PURPOSE OF REVIEW: It is well established that controlled immune activation and balance is critical for women's reproductive health and successful pregnancy outcomes. Research in recent decades in both clinical and animal studies has demonstrated that aberrant immune activation and inflammation play a role in the development and progression of women's reproductive health and pregnancy-related disorders. Inflammasomes are multi-protein cytoplasmic complexes that mediate immune activation. In this review, we summarize current knowledge on the role of inflammasome activation in pregnancy-related disorders. RECENT FINDINGS: Increased activation of inflammasome is associated with multiple women's health reproductive disorders and pregnancy-associated disorders, including preeclampsia (PreE). Inflammasome activation is also associated with the novel coronavirus disease 2019 (COVID-19) disease caused by the SARS-Cov-2 virus. We and others have observed a positive association between increased PreE incidences with the onset of the COVID-19 pandemic. Here, we present our recent data indicating increased inflammasome activation, represented by caspase-1 activity, in women with COVID-19 and PreE compared to normotensive pregnant women COVID-19. The role of inflammation in pregnancy-related disorders is an area of intense research interest. With the onset of the COVID-19 pandemic and the associated increase in PreE observed clinically, there is a greater need to identify mechanisms of pathophysiology and targets to treat this maternal disorder. Inflammasome activation is associated with PreE and COVID-19 infection and may hold therapeutic potential to improve outcomes associated with PreE and curb the morbidity attributed to PreE.

Evidence of Anxiety, Depression and Learning Impairments following Prenatal Hypertension.

BACKGROUND: Hypertensive disorders of pregnancy, such as Preeclampsia (PreE) and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome, affects approximately 5-10% of pregnancies and increases the risk of women developing disorders, such as anxiety or depression, in the postpartum period. Using preclinical rodent models, we set out to determine whether rats with a history of PreE or HELLP had evidence of anxiety, depression or cognitive impairment and whether immune suppression during pregnancy prevented these changes in mood and/or cognition. METHODS: Timed-pregnant rats were infused with sFlt-1 and/or sEng to induce PreE or HELLP beginning on gestational day 12. After delivery, a battery of validated behavioral assays was used to assess post-partum depression, anxiety and learning. RESULTS: There was no negative effect on maternal pup interaction due to PreE or HELLP; however, hypertensive dams spent more time immobile in the forced swim test (p < 0.0001). Hypertensive dams also spent less time in the open area of the open field (p = 0.001). There were no significant changes in recognition memory (p = 0.08); however, spatial learning was impaired in hypertensive dams (p = 0.003). Immobility time in the forced swim test was positively correlated with increased circulating S100B (p = 0.04), while increased time spent in the outer zones of the open field was negatively correlated with BDNF levels (p < 0.0001). CONCLUSION: The results from this study suggest that hypertensive pregnancy disorders are associated with depression, anxiety and learning impairments in the post-partum period.

Route of myomectomy and fertility: a prospective cohort study.

OBJECTIVE: To assess prospectively the association between the myomectomy route and fertility. DESIGN: Prospective cohort study. SETTING: The Comparing Treatments Options for Uterine Fibroids (COMPARE-UF) Study is a multisite national registry of eight clinic centers across the United States. PATIENT(S): Reproductive-aged women undergoing surgery for symptomatic uterine fibroids. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): We used life-table methods to estimate cumulative probabilities and 95% confidence intervals (CI) of pregnancy and live birth by the myomectomy route during 12, 24, and 36 months of follow-up (2015-2019). We also conducted 12-month interval-based analyses that used logistic regression to estimate odds ratios and 95% CIs for associations of interest. In all analyses, we used propensity score weighting to adjust for differences across surgical routes. RESULT(S): Among 1,095 women who underwent myomectomy (abdominal = 388, hysteroscopic = 273, and laparoscopic = 434), 202 reported pregnancy and 91 reported live birth during 36 months of follow-up. There was little difference in the 12-month probability of pregnancy or live birth by route of myomectomy overall or among women intending pregnancy. In interval-based analyses, adjusted ORs for pregnancy were 1.28 (95% CI, 0.76-2.14) for hysteroscopic myomectomy and 1.19 (95% CI, 0.76-1.85) for laparoscopic myomectomy compared with abdominal myomectomy. Among women intending pregnancy, adjusted ORs were 1.27 (95% CI, 0.72-2.23) for hysteroscopic myomectomy and 1.26 (95% CI, 0.77-2.04) for laparoscopic myomectomy compared with abdominal myomectomy. Associations were slightly stronger but less precise for live birth. CONCLUSION(S): The probability of conception or live birth did not differ appreciably by the myomectomy route among women observed for 36 months postoperatively. CLINICAL TRIALS REGISTRATION NUMBER: (NCT02260752, clinicaltrials.gov).

Anxiety, Depression, and Quality of Life After Procedural Intervention for Uterine Fibroids.

Background: Quality of life (QOL) and psychological health has been reported to be decreased among women with gynecological conditions such as uterine fibroids (UFs). Materials and Methods: Women enrolled in the Comparing Options for Management: PAtient-centered REsults for Uterine Fibroids (COMPARE-UF) registry, receiving procedural therapy for symptomatic UFs, were eligible for this analysis if they completed a series of health-related QOL surveys administered at three time points (baseline, 6-12 weeks postprocedure, and 1 year postprocedure; n = 1486). Ethical approval for this study was obtained at each recruiting site and the coordinating center (NCT02260752, clinicaltrials.gov). Results: More than 26% (n = 393) of women reported moderate anxiety/depression on the baseline anxiety/depression domain of the Euro-QOL 5-dimension instrument. At both the 6-12 weeks and 1-year postprocedural follow-up, there was significant improvement in the UF QOL symptom severity score (p < 0.001, p < 0.001), the total UF symptom QOL score (p < 0.001, p < 0.001), and the Euro-QOL 5-dimension visual analog scale (p < 0.001, p = 0.004) compared with the preprocedural baseline scores. The reporting of anxiety/depression decreased by 66.4% among women who were at baseline, whereas 5.6% of women previously reporting no anxiety/depression reported anxiety/depression at the 1-year follow-up. Conclusion: UF symptoms were more severe among women reporting anxiety/depression at baseline. At the 1-year follow-up, health-related QOL scores improved among all women and the prevalence of anxiety/depression decreased in most, but not all women, whereas severity of anxiety/depression worsened in a small percentage of women (5.6%). Overall, these results suggest that UF treatment improves symptoms of anxiety/depression associated with symptomatic UFs.

Characterization of Mitochondrial Bioenergetics in Preeclampsia.

Preeclampsia (PE) is characterized by new onset hypertension during pregnancy and is associated with oxidative stress, placental ischemia, and autoantibodies to the angiotensin II type I receptor (AT1-AA). Mitochondrial (mt) dysfunction in PE and various sources of oxidative stress, such as monocytes, neutrophils, and CD4 + T cells, have been identified as important players in the pathophysiology of PE. We have established the significance of AT1-AA, TNF-α, and CD4 + T cells in causing mitochondrial (mt) dysfunction in renal and placental tissues in pregnant rats. Although the role of mt dysfunction from freshly isolated intact placental mitochondria has been compared in human PE and normally pregnant (NP) controls, variations among preterm PE or term PE have not been compared and mechanisms contributing to mt ROS during PE are unclear. Therefore, we hypothesized PE placentas would exhibit impaired placental mt function, which would be worse in preterm PE patients than in those of later gestational ages. Immediately after delivery, PE and NP patient's placentas were collected, mt were isolated and mt respiration and ROS were measured. PE patients at either < or >34 weeks gestational age (GA) exhibited elevated blood pressure and decreased placental mt respiration rates (state 3 and maximal). Patients delivering at >34 weeks exhibited decreased Complex IV activity and expression. Placental mtROS was significantly reduced in both PE groups, compared to NP placental mitochondria. Collectively, the study demonstrates that PE mt dysfunction occurs in the placenta, with mtROS being lower than that seen in NP controls. These data indicate why antioxidants, as a potential target or new therapeutic agent, may not be ideal in treating the oxidative stress associated with PE.

Postpartum Outcomes With Systematic Treatment and Management of Postpartum Hypertension.

OBJECTIVE: To test the ability of a hospital-wide, bundled quality-improvement initiative to improve postpartum maternal blood pressure control and adherence to postpartum follow-up among patients with hypertensive disorders of pregnancy. METHODS: This quality-improvement initiative consisted of a bundle of clinical interventions including health care professional and patient education, a dedicated nurse educator, and protocols for postpartum hypertensive disorders of pregnancy care in the inpatient, outpatient and readmission setting. We implemented this initiative in patients with hypertensive disorders of pregnancy starting in January 2019 at the University of Chicago. The study period was divided into four periods, which correspond to preintervention, distinct bundle roll outs, and postintervention. Our primary outcome was postpartum hypertension visit adherence. Secondary outcomes included blood pressure values and antihypertensive medication use in the immediate postpartum and outpatient postpartum time periods. We then stratified our outcomes by race to assess whether the effect size differed. RESULTS: A total of 926 patients who delivered between September 2018 and November 2019 were included. Postpartum hypertension visit adherence improved from preintervention period compared with the full implementation period (33.5% vs 59.4%, P<.001). Blood pressure in the first 24 hours postpartum decreased from preintervention compared with full implementation (preintervention median [interquartile range] systolic blood pressure 149 mm Hg [138, 159] vs 137 [131, 146] in postimplementation; P<.001). After implementation, fewer patients experienced a blood pressure of 140/90 mm Hg or higher at the first postpartum blood pressure check, when compared with preintervention (39.1% vs 18.5%, P=.004). The effect size did not differ by race. CONCLUSION: A bundled quality-improvement initiative for patients with hypertensive disorders of pregnancy was associated with improved postpartum visit adherence and blood pressure control in the postpartum period.

Male HELLP pups experience sensorimotor delays and reduced body weight.

Offspring of Preeclampsia (PreE) and HELLP Syndrome are at an increased risk of developing neurodevelopmental disorders. In the current study we sought to determine if offspring from experimental models of PreE and HELLP had evidence of early onset neurodevelopmental delay. Offspring from PreE, HELLP and normal pregnant dams were assessed in a battery of sensorimotor tests beginning on postnatal day (PND) 3. Male HELLP offspring showed altered behavior in the surface righting reflex on PND 3 and cliff avoidance task from PND 3-6 relative to other groups. Results suggest that there are sex differences in offspring born to dams with PreE and HELLP.

Black Women Are More Likely Than White Women to Schedule a Uterine-Sparing Treatment for Leiomyomas.

Background: To evaluate differences in the proportion of uterine fibroid (UF) treatments that are uterine-sparing between Black women and White women and identify factors that could explain disparities. Methods: Women at age 18-54 years who were enrolled from 10 clinical sites in the United States into the Comparing Options for Management: Patient-Centered Results for UFs (COMPARE-UF) treatment registry completed questionnaires before their UF procedure. UF symptoms and quality of life were assessed by questionnaires. Details on UF imaging and treatment (hysterectomy, myomectomy, or uterine artery embolization [UAE]) were collected from each patient's medical record. Random-effects logistic regression was used to assess the association between race and the odds of having a uterine-sparing procedure versus hysterectomy. Subgroup analyses compared each uterine-sparing procedure with hysterectomy. Results: In this cohort of 1141 White women and 1196 Black women, Black women tended to be younger (median 41.0 vs. 42.0 years) and report worse symptoms, pain, and function on every scale compared with White women. Black women were more likely to have had a prior UF treatment compared with White women (22.8% vs. 14.6%). White women had more hysterectomies (43.6% vs. 32.2%) and myomectomies (50.9% vs. 50.2%) versus Black women. Black women had more UAEs (15.1% vs. 4.7%) than White women. After adjusting for clinical site and other variables, Black women had greater odds than White women of having a myomectomy (odds ratio [OR] = 2.41, 95% confidence interval [CI] = 1.63-3.56) or a UAE versus hysterectomy (OR = 4.24, 95% CI = 2.41-7.46). Conclusion: In these participants, Black women were more likely to schedule a uterine-sparing UF treatment and a nonsurgical UF treatment than their White counterparts; this may not be true for all women. Longer comparative effectiveness studies are needed to inform women about the durability of UF treatments. Greater understanding of factors influencing treatment selection is needed as are studies that include women without access to tertiary care centers. Clinical Trial Registration: Clinicaltrials.gov, NCT02260752 (enrollment start: November 2015).

Vascular endothelial mitochondrial oxidative stress in response to preeclampsia: a role for angiotension II type 1 autoantibodies.

BACKGROUND: Preeclampsia is characterized by a new onset of hypertension during pregnancy and is associated with autoantibodies against the angiotensin II type 1 receptor and oxidative stress. There is growing evidence for mitochondrial dysfunction in preeclampsia, however, the culprits for mitochondrial dysfunction are still being defined. We previously demonstrated that angiotensin II type 1 autoantibodies cause renal, placental, and endothelial mitochondrial dysfunction in pregnant rats. However, the role of the angiotensin II type 1 autoantibodies in endothelial mitochondrial function in response to sera from preeclamptics is unknown. Thus, we hypothesized that circulating factors, such as the angiotensin II type 1 autoantibodies, during preeclampsia would negatively impact the vascular endothelial mitochondrial function in human umbilical vein endothelial cells. OBJECTIVE: The objective of the study was to determine a role for circulating angiotensin II type 1 autoantibodies to cause endothelial mitochondrial reactive oxygen species and dysfunction in preeclampsia compared to normal pregnant controls. STUDY DESIGN: Immediately after delivery, sera was collected from preeclamptic patients and normal pregnant controls. The mitochondrial reactive oxygen species were determined from the cells treated overnight with 10% sera from either the control or preeclamptic patients with and without the antiotension II type 1 autoantibodies inhibitor peptide ('n7AAc'). RESULTS: Preeclampsia patients at <34 weeks' gestation exhibited an elevated mean arterial blood pressure. Cells treated with serum from the preeclampsia patients at <34 weeks gestational age showed significantly (P<0.05) greater mitochondrial oxidative stress and reduced respiration than cells treated with the control sera, and these abnormalities were restored with 'n7AAc'. CONCLUSION: This study demonstrates that endothelial mitochondrial dysfunction occurs in response to circulating factors, especially in response to serum from preterm preeclampsia patients, and can be restored by blocking circulating angiotensin II type 1 autoantibodies, thereby indicating a potential new therapeutic target for preeclampsia.

Acute kidney injury during pregnancy leads to increased sFlt-1 and sEng and decreased renal T regulatory cells in pregnant rats with HELLP syndrome.

BACKGROUND: The incidence of acute kidney injury (AKI) during pregnancy precedes a high maternal mortality rate of 20-40%. AKI during pregnancy has multiple etiologies; however, the more common are maternal hypertensive disorders, which include preeclampsia and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome. Therefore, we sought to assess the impact of AKI on blood pressure, kidney injury, and anti-angiogenic factors during pregnancies with and without HELLP syndrome. METHODS: On gestational day (GD) 12, mini-osmotic pumps were inserted into a subset of normal pregnant (NP) rats infusing 4.7 µg/kg soluble fms-like tyrosine kinase-1 (sFlt-1) and 7 µg/kg soluble endoglin (sEng) to induce HELLP syndrome. On GD18, the renal pedicles were occluded for 45 min to induce AKI via bilateral ischemia reperfusion in a subset of NP (n = 18) or HELLP (n = 20) rats. Control NP (n = 20) and HELLP (n = 20) rats underwent a SHAM surgery on GD18. Plasma, urine, and maternal organs were saved for further analysis. Renal injury was assessed via renal histopathology, glomerular filtration rate (GFR), T cell infiltration, and assessment of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Data was measured via two-way analysis of variance with Tukey's test for post hoc analysis. RESULTS: Blood pressures were increased in HELLP+AKI rats (p = 0.0001); both NP+AKI and HELLP+AKI rats had increased lactate dehydrogenase (p < 0.0001) and aspartate aminotransferase levels (p < 0.0001), and decreased platelet levels (p < 0.001) vs. NP rats. HELLP+AKI (p = 0.002) and HELLP rats (p = 0.0002) had evidence of renal fibrosis vs. NP rats. GFR was decreased in HELLP+AKI (p = 0.01) rats vs. NP rats. Urinary KIM-1 was increased in NP+AKI rats vs. NP (p = 0.003) and HELLP rats (p = 0.01). HELLP+AKI rats had increased urinary KIM-1 vs. NP (p = 0.0008) and HELLP rats (p = 0.004) and increased NGAL vs. HELLP rats (p = 0.002). HELLP+AKI rats had increased sFlt-1 (p = 0.009) vs. NP rats. NP+AKI (p = 0.02) and HELLP+AKI (p = 0.007) rats had increased sEng vs. NP rats. CD3+CD4+ T cells were significantly increased in HELLP+AKI rats vs. NP (p = 0.0002) and NP+AKI (p = 0.05) rats. T regulatory cells were significantly decreased in HELLP+AKI (p = 0.03) and NP+AKI (p = 0.02) rats vs. NP rats; there were no changes between groups in T helper 17 cells (p = 0.34). CONCLUSION: The findings in this study suggest that AKI during pregnancy contributes to increased blood pressure and biochemical markers for HELLP syndrome, creates an anti-angiogenic imbalance, and exacerbates kidney injury as shown on histopathology, GFR, and kidney injury markers.