Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor.

VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20-150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood-brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p < 2.7 × 10-8), PICALM-V1aR (p < 0.006), and OT-R-V1aR (p < 0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.

Clinical Trials That Have Changed Obstetric Practice: The Chronic Hypertension and Pregnancy (CHAP) Trial.

We describe the evolution of treatment recommendations for chronic hypertension (CHTN) in pregnancy, the CHTN and pregnancy (CHAP) trial, and its impact on obstetric practice. The US multicenter CHAP trial showed that antihypertensive treatment for mild CHTN in pregnancy [blood pressures (BP)<160/105 mm Hg] to goal<140/90 mm Hg, primarily with labetalol or nifedipine compared with no treatment unless BP were severe reduced the composite risk of superimposed severe preeclampsia, indicated preterm birth <35 weeks, placental abruption, and fetal/neonatal death. As a result of this trial, professional societies in the United States recommended treatment of patients with CHTN in pregnancy to BP goal<140/90 mm Hg.

Physiologic blood pressure patterns in pregnancies with mild chronic hypertension.

OBJECTIVES: To assess physiologic blood pressure (BP) changes throughout pregnancy in patients with mild chronic hypertension (CHTN) who do and do not develop preeclampsia (PEC), compared to patients with normal BP. STUDY DESIGN: Retrospective cohort of singleton gestations with CHTN at a single tertiary center from 2000 to 2014 and a randomly selected cohort of patients without CHTN and normal pregnancy outcomes (NML) in the same time period with BP measurements available <12 weeks gestational age. MAIN OUTCOME MEASURES: The primary outcome was gestational age (GA) at nadir of systolic and diastolic BP. Secondary outcomes included perinatal death, umbilical cord pH, maternal and neonatal length of stay, GA at delivery, and mode of delivery. Quadratic mixed models were used to estimate SBP and DBP throughout gestation. RESULTS: Of 367 pregnancies with CHTN, 268 (73%) had CHTN without PEC and 99 (27%) had CHTN with PEC; 198 NML pregnancies were used as a comparison group. The median GA nadir for patients in the NML, CHTN without PEC, and CHTN with PEC for SBP were 20, 24, and 21, respectively. For DBP, the median GA nadir were 22, 24, and 21 for patients in the NML, CHTN without PEC, and CHTN with PEC cohorts, respectively. Adverse secondary outcomes were more frequent in patients with CHTN who developed PEC. CONCLUSIONS: BP trajectories in pregnancy are different between patients with CHTN with PEC, CHTN without PEC, and patients with normal BP. These findings may be useful in assessing patients' risks for developing preeclampsia during pregnancy.

Society for Maternal-Fetal Medicine Consult Series #68: Sickle cell disease in pregnancy.

Pregnant individuals with sickle cell disease have an increased risk of maternal and perinatal morbidity and mortality. However, prepregnancy counseling and multidisciplinary care can lead to favorable maternal and neonatal outcomes. In this consult series, we summarize what is known about sickle cell disease and provide guidance for sickle cell disease management during pregnancy. The following are Society for Maternal-Fetal Medicine recommendations.

Physiologic Treatment of Severe Hypertension in Pregnancy and Postpartum.

We aimed to evaluate physiologic treatment of severe hypertension. This was a retrospective cohort study of pregnant and postpartum patients with severe hypertension (systolic blood pressure [BP] 160 mm Hg or higher or diastolic BP 110 mm Hg or higher) treated with intravenous labetalol or hydralazine at a single tertiary care center between 2013 and 2018. Patients were classified as having physiologic treatment if they had hyperdynamic physiology (pulse pressure 65 mm Hg or higher) and received labetalol or had vasoconstrictive physiology (diastolic BP 100 mm Hg or higher) and received hydralazine. The primary outcome was number of antihypertensive doses to achieve nonsevere BP. Of 1,120 patients included in the analysis, 653 had physiologic treatment and 467 had nonphysiologic treatment, with 16 (1.4%) excluded for inability to classify physiology. Physiologic treatment was associated with fewer antihypertensive doses (1.4±0.9 doses vs 1.6±1.4 doses; adjusted ß -0.28, 95% CI, -0.42 to -0.14) and lower odds of medication conversion (2.5% vs 4.7%; adjusted odds ratio 0.48, 95% CI, 0.24-0.93) but no difference in time to nonsevere BP (31 minutes [interquartile range 16-66 minutes] vs 34 minutes [interquartile range 15-76 minutes]; adjusted hazard ratio 1.0, 95% CI, 0.9-1.2). Physiologic treatment of severe hypertension warrants further evaluation.

Outcomes in low-risk patients before and after an institutional policy offering 39-week elective induction of labor.

OBJECTIVE: Elective induction of labor versus expectant management at 39 weeks gestation in low-risk nulliparous patients was shown in the ARRIVE randomized trial of over 6000 patients to decrease risks of cesarean delivery without significant change in the composite perinatal outcome. We aimed to pragmatically analyze the effect of offering elective induction of labor (eIOL) to all low-risk patients. METHODS: Retrospective cohort study of low-risk nulliparous and multiparous patients delivering live, non-anomalous singletons at a single center at greater than or equal to 39 0/7 weeks gestational age. Those with prior or planned cesarean delivery, ruptured membranes, medical comorbidities, or contraindications to vaginal delivery were excluded. Patients were categorized as before (pre-eIOL; 1/2012-3/2014) or after (post-eIOL; 3/2019-12/2021) an institution-wide policy offering eIOL at 39 0/7 weeks. Births occurring April 2014 to December 2018 were allocated to a separate cohort (during-eIOL) given increased exposure to eIOL as our center recruited participants for the ARRIVE trial. The primary outcome was cesarean birth. Secondary outcomes included select maternal (e.g. chorioamnionitis, operative delivery, postpartum hemorrhage) and neonatal morbidities (e.g. birthweight, small- and large-for gestational age, hypoglycemia). Characteristics and outcomes were compared between the pre and during-eIOL, and pre and post-eIOL groups; adjusted OR (95% CI) were calculated using multivariable regression. Subgroup analysis by parity was planned. RESULTS: Of 10,758 patients analyzed, 2521 (23.4%) were pre-eIOL, 5410 (50.3%) during-eIOL, and 2827 (26.3%) post-eIOL. Groups differed with respect to labor type, age, race/ethnicity, marital and payor status, and gestational age at care entry. Post-eIOL was associated with lower odds of cesarean compared to pre-eIOL (aOR 0.83 [95% CI 0.72-0.96]), which was even lower among those specifically undergoing labor induction (aOR 0.58 [0.48-0.70]. During-eIOL was also associated with lower odds of cesarean compared to pre-eIOL (aOR 0.79 [0.69-0.90]). Both during and post-eIOL groups were associated with higher odds of chorioamnionitis, operative delivery, and hemorrhage compared to pre-eIOL. However, only among post-eIOL were there fewer neonates weighing ≥4000 g, large-for-gestational age infants, and neonatal hypoglycemia compared to pre-IOL. CONCLUSION: An institutional policy offering eIOL at 39 0/7 to low-risk patients was associated with a lower cesarean birth rate, lower birthweights and lower neonatal hypoglycemia, and an increased risk of chorioamnionitis and hemorrhage.

Occipital Nerve Block Compared With Acetaminophen and Caffeine for Headache Treatment in Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy of occipital nerve block compared with standard care , defined as acetaminophen with caffeine, for treatment of acute headache in pregnancy. METHODS: We conducted a single-center, unblinded, parallel, randomized controlled trial of pregnant patients with headache and pain score higher than 3 on the visual rating scale. Patients with secondary headache, preeclampsia, or allergy or contraindication to study medications were excluded. Participants were randomized to occipital nerve block or standard care (oral 650 mg acetaminophen and 200 mg caffeine). Crossover treatment was given at 2 hours and second-line treatment at 4 hours to those with worsening visual rating scale score or visual rating scale score higher than 3. The primary outcome was headache improvement to a visual rating scale score of 3 or lower within 2 hours of initial therapy. Secondary outcomes included serial visual rating scale scores, receipt of crossover or second-line therapy, patient satisfaction, and perinatal outcomes. Outcomes were assessed in an intention-to-treat analysis. We estimated that a sample of 62 would provide 80% power to detect a difference from 85% to 50% between groups. RESULTS: From February 2020 to May 2022, 62 participants were randomized to occipital nerve block (n=31) or standard care (n=31). Groups were similar except payer status. The primary outcome, headache improvement to visual rating scale score of 3 or lower, was not significantly different between groups (64.5% vs 51.6%, P =.30). The occipital nerve block group experienced lower median [interquartile range] visual rating scale scores at 1 hour (2 [0-5] vs 6 [2-7], P =.014), and more patients in the occipital nerve block group had visual rating scale scores of 3 or lower at 1 hour. Among patients receiving crossover treatment at 2 hours, the standard care group had a significantly lower visual rating scale score 1 hour after crossover to occipital nerve block than the occipital nerve block group receiving crossover to standard care ( P =.028). There were no significant differences in second-line treatment, refractory headache, satisfaction, or complications. Patients receiving occipital nerve block delivered earlier (36.6 weeks vs 37.8 weeks), but preterm birth did not differ between groups. CONCLUSION: Occipital nerve block is an effective and quick-acting treatment option for acute headache in pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT03951649.

Contribution of Health Care Practitioner and Maternity Services Factors to Racial Disparities in Alabama: A Qualitative Study.

OBJECTIVE: Black patients are three times more likely to die of pregnancy-related causes than White patients in the United States, and Alabama has the third worst maternal mortality rate in the nation. We sought to identify health care practitioner and maternity service factors contributing to disparities in Alabama, as well as potential strategies to address these contributors. METHODS: We conducted key informant interviews with obstetricians, nurses, doulas, lactation counselors, health system administrators, and representatives of professional organizations who deliver maternity care to racially and ethnically diverse patients in Alabama. The interview guide was developed using Howell's conceptual framework on racial and ethnic disparities in severe maternal morbidity and mortality. Adopting a thematic analysis approach, we coded and analyzed transcripts using NVivo 12 software. Open coding and selective coding were conducted to identify themes related to health care practitioner- and maternity services-level determinants. RESULTS: Overall, 20 health care practitioners or administrators were interviewed. Primary themes related to health care practitioners included implicit bias and explicit racism, lack of communication and lack of positive patient-health care practitioner relationships, lack of cultural sensitivity, and variation in clinical knowledge and experience. Primary themes related to maternity services included lack of accessibility, inadequate quality and content of care, lack of continuity of care, discriminatory facility policies, and workforce shortages and lack of diversity. Strategies suggested by participants to address these factors included bias trainings for health care practitioners, improvements in racial and interdisciplinary diversity in the maternity workforce, and evidence-based interventions such as group prenatal care, disparities dashboards, simulation trainings, early warning signs criteria, and coordinated care. CONCLUSION: We gained diverse perspectives from health care practitioners and administrators on how maternity health care practitioner and maternity health services factors contribute to inequities in maternal health in Alabama. Strategies to address these contributing factors were multifaceted.

Electronic Cigarette Use during Pregnancy: Is It Harmful?

Although combustible cigarette smoking rates have declined in recent years, alternative tobacco product use, particularly electronic cigarette use ("vaping"), has increased among young adults. Recent studies indicate that vaping during pregnancy is on the rise, possibly due to the perception that it is a safer alternative to combustible cigarette smoking. However, e-cigarette aerosols may contain several newer, potentially toxic compounds, including some known developmental toxicants that may adversely impact both the mother and the fetus. However, there is paucity of studies that have examined the effects of vaping during pregnancy. While the adverse perinatal outcomes of cigarette smoking during pregnancy are well established, the specific risks associated with inhaling vaping aerosols during pregnancy requires more research. In this article, we discuss the existing evidence and knowledge gaps on the risks of vaping during pregnancy. Studies that investigate vaping-associated systemic exposure and its effects (i.e., biomarker analyses) and maternal and neonatal clinical health outcomes are needed to reach more robust conclusions. We particularly emphasize the need to go beyond comparative studies with cigarettes, and advocate for research that objectively evaluates the safety of e-cigarettes and other alternative tobacco products.

Systematic Review of Lymphangioleiomyomatosis Outcomes in Pregnancy and a Proposed Management Guideline.

OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare, multisystem disease that primarily affects women of reproductive age. Disease progression has been linked to estrogen exposure, and as such many patients are advised to avoid pregnancy. Data are limited regarding the interaction between LAM and pregnancy, and as such we performed a systematic review to summarize available literature reporting outcomes of pregnancies complicated by maternal LAM. STUDY DESIGN: This was a systematic review including randomized controlled trials, observational studies, systematic reviews, case reports, clinical practice guidelines, and quality improvement studies with full-text manuscripts or abstracts in the English language with primary data on pregnant or postpartum patients with LAM. The primary outcome was maternal outcomes during pregnancy as well as pregnancy outcomes. Secondary outcomes were neonatal outcomes and long-term maternal outcomes. This search occurred in July 2020 and included MEDLINE, Scopus, clinicaltrials.gov, Embase, and Cochrane Central. Risk of bias was ascertained using the Newcastle-Ottawa Scale. Our systematic review was registered with PROSPERO as protocol number CRD 42020191402. RESULTS: A total of 175 publications were identified in our initial search; ultimately 31 studies were included. Six (19%) studies were retrospective cohort studies and 25 (81%) studies were case reports. Patients diagnosed during pregnancy had worse pregnancy outcomes compared to those diagnosed with LAM prior to pregnancy. Multiple studies reported a significant risk of pneumothoraces during pregnancy. Other significant risks included preterm delivery, chylothoraces, and pulmonary function deterioration. A proposed strategy for preconception counseling and antenatal management is provided. CONCLUSION: Patients diagnosed with LAM during pregnancy generally experience worse outcomes including recurrent pneumothoraces and preterm delivery as compared to patients with a LAM diagnosis prior to pregnancy. Given that there are limited studies available, and that the majority are low-quality evidence and subject to bias, further investigation of the interaction between LAM and pregnancy is warranted to guide patient care and counseling. KEY POINTS: · Data are limited on the effects of lymphangioleiomyomatosis on pregnancy outcomes.. · We performed a systematic review to summarize pregnancy outcomes complicated by LAM.. · Patients diagnosed with LAM during pregnancy experience worse outcomes..

Geographic disparities in peripartum cardiomyopathy outcomes.

BACKGROUND: Cardiomyopathy causes more than a third of late postpartum pregnancy-related deaths in the United States, and racial disparities in outcomes among pregnant individuals with cardiomyopathy exist. Underlying community factors may contribute to disparities in peripartum cardiomyopathy outcomes. OBJECTIVE: This study aimed to identify the geographic distribution of and disparities in peripartum cardiomyopathy outcomes, hypothesizing that patients living in communities with higher social vulnerability may have worse outcomes. STUDY DESIGN: This was a retrospective cohort study of patients with peripartum cardiomyopathy per the National Heart, Lung, and Blood Institute definition from January 2000 to November 2017 at a single center, excluding those with a post office box address as a post office box address may not reflect the census tract in which a patient resides. Severe peripartum cardiomyopathy (vs less severe peripartum cardiomyopathy) was defined as ejection fraction <30%, death, intensive care unit admission, left ventricular assist device or implantable cardioverter defibrillator placement, or transplant. The US census tract for the patient's address was linked to the Centers for Disease Control and Prevention Social Vulnerability Index, a 0 to 1 scale of a community's vulnerability to external stresses on health, with higher values indicating greater vulnerability. The Social Vulnerability Index includes social factors divided into socioeconomic, household composition, minority status, and housing type and transportation themes. The Social Vulnerability Index and Social Vulnerability Index components were compared among patients by peripartum cardiomyopathy severity. RESULTS: Of 95 patients in the original cohort, 5 were excluded because of the use of a post office box address. Of the remaining 90 patients, 56 met severe peripartum cardiomyopathy criteria. At baseline, individuals with and without severe peripartum cardiomyopathy had similar ages, marital status, payor type, tobacco use, gestational age at delivery, and mode of delivery; however, individuals with severe peripartum cardiomyopathy were more likely to be Black (vs White) (59% vs 29%; P<.007) and less likely to recover ejection fraction (EF) to ≥55% by 12 months (36% vs 62%; P=.02) than individuals with less severe peripartum cardiomyopathy. Patients with severe peripartum cardiomyopathy were more likely to live in areas with a higher Social Vulnerability Index (0.51 vs 0.31; P=.002) and with more residents who were unemployed, impoverished, without a high school diploma, in single-parent households, of minority status, without a vehicle, and in institutionalized group quarters than patients with less severe peripartum cardiomyopathy. The median income was lower in communities of individuals with severe peripartum cardiomyopathy than in communities of individuals with less severe peripartum cardiomyopathy. CONCLUSION: Patients with severe peripartum cardiomyopathy outcomes were more likely to live in communities with greater social vulnerability than patients with less severe peripartum cardiomyopathy outcomes. To reduce disparities and maternal mortality rates, resources may need to be directed to socially vulnerable communities.

Maternal and Perinatal Outcomes Associated With the Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

Two years into the coronavirus disease 2019 (COVID-19) pandemic, we have now seen three main variant waves. We performed a retrospective cohort study of all pregnant patients with COVID-19 at our institution from March 22, 2020, to February 26, 2022, to evaluate disease severity and perinatal outcomes among the variants. Patients were categorized as pre-Delta (March 22, 2020-May 31, 2021), Delta (July 1, 2021-December 15, 2021), or Omicron (December 16, 2021- February 26, 2022) based on variant tracking from the Centers for Disease Control and Prevention and genotype sequencing at our institution. There were fewer cases of severe-critical disease (1.8% Omicron vs 13.3% pre-Delta and 24.1% Delta) and adverse perinatal outcomes during the Omicron wave compared with the pre-Delta and Delta waves.

Quantifying the additional maternal morbidity in women with preeclampsia with severe features in whom immediate delivery is recommended.

BACKGROUND: Preeclampsia with severe features when diagnosed at less than 34 weeks is associated with maternal morbidity and is managed by immediate delivery or inpatient expectant management. OBJECTIVE: This study aimed to compare maternal morbidity in women with preeclampsia with severe features in whom the American College of Obstetricians and Gynecologists recommends immediate delivery versus those eligible for expectant management. STUDY DESIGN: This was a retrospective cohort study of women with preeclampsia with severe features delivered between 23 to 34 weeks of gestation from 2013 to 2017 at a single tertiary center. Women were categorized into 2 groups: (1) those recommended by the American College of Obstetricians and Gynecologists for immediate delivery, that is, ineligible for expectant management, and (2) those eligible for expectant management. The primary outcome was composite postpartum maternal morbidity, which included maternal intensive care unit admission, stroke, death, and other severe morbidities. The secondary outcomes included select adverse perinatal outcomes. Groups were compared and adjusted odds ratios (95% confidence intervals) calculated. RESULTS: Of the 1172 women with preeclampsia identified during the study period, 543 with preeclampsia with severe features were included for analysis: 211 (39%) were ineligible for expectant management and 332 (61%) were eligible for expectant management. Baseline characteristics, including age, body mass index, race and ethnicity, parity, marital status, and gestational age at preeclampsia diagnosis, were similar between the 2 groups. Women ineligible for expectant management had significantly higher composite postpartum maternal morbidity (adjusted odds ratio, 5.02 [95% confidence interval, 1.35-18.69]). In addition, those ineligible for expectant management were more likely to have postpartum intensive care unit admission (adjusted odds ratio, 4.19 [95% confidence interval, 1.09-16.16]) and postpartum hemoglobin level of <7 g/dL (adjusted odds ratio, 5.07 [95% confidence interval, 1.35-19.08]). There was no demonstrable difference in neonatal outcomes between the 2 groups. CONCLUSION: Women with preeclampsia with severe features who were ineligible for expectant management per the American College of Obstetricians and Gynecologists guidelines had a 5-fold increased risk of maternal morbidity, confirming the need for escalation of care and delivery without delay.

Placental Pathology in Maternal Ornithine Transcarbamylase Deficiency.

INTRODUCTION: Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder, inherited in an X-linked manner. Males are severely affected. Female phenotypes vary from asymptomatic to severe, and symptoms may be triggered by high metabolic states like childbirth. Literature on OTC deficiency in pregnancy and placental pathology is limited. METHODS: Pathology records were searched at a single referral center from 2000-2020 and identified three placental cases from two mothers heterozygous for OTC deficiency. Placental pathology and maternal and neonatal history were reviewed in detail. RESULTS: The placenta from one symptomatic mother carrying an affected male fetus showed widespread high-grade fetal vascular malperfusion (FVM) lesions of varying age. These lesions were not seen in the two placentas from the asymptomatic mother. DISCUSSION: In cases of symptomatic maternal OTC deficiency, our findings highlight the need for placental examination. Since thrombotic events in the placenta have the potential to associate with fetal and neonatal endothelial damage, a high index of suspicion for neonatal thrombosis may be warranted.

Racial disparities in reliable contraceptive use in women with heart disease.

OBJECTIVE: The aim of the study was to investigate the differences in reliable contraceptive use between black women and white women with maternal cardiac disease. METHODS: The study comprised a retrospective cohort of women with maternal cardiac disease managed by the University of Alabama at Birmingham (UAB) Comprehensive Pregnancy and Heart Program (CPHP). Women were included if they had attended one or more prenatal visits at the UAB CPHP and delivered at the UAB hospital between March 2015 and June 2019. The primary outcome was reliable contraceptive use within 2 months postpartum, defined by receipt of long-acting reversible contraception (i.e., an intrauterine contraceptive device or an etonogestrel implant) or female sterilisation. All outcomes were compared based on self-reported race. RESULTS: One hundred and forty-nine women met the inclusion criteria. Black women (n = 63) were more likely than white women (n = 86) to use reliable contraception (65% vs 43%; p = 0.008). Black women were less likely than white women to be undecided or decline contraception at the time of admission (13% vs 27%; p = 0.037). There was no difference in reliable contraceptive use between black women (n = 20, 63%) and white women (n = 23, 72%) with modified World Health Organisation (WHO) class III/IV lesions (p = 0.42). CONCLUSION: Black women with maternal cardiac disease were more likely than white women to receive reliable contraception. Interventions to prevent unintended pregnancy in women with maternal cardiac disease should focus on improving reliable contraceptive use, especially for women with modified WHO class III/IV lesions.

Extracellular Vesicles From Women With Severe Preeclampsia Impair Vascular Endothelial Function.

BACKGROUND: Preeclampsia (PE) manifesting as hypertension and organ injury is mediated by vascular dysfunction. In biological fluids, extracellular vesicles (EVs) containing microRNA (miRNA), protein, and other cargo released from the placenta may serve as carriers to propagate injury, altering the functional phenotype of endothelial cells. PE has been consistently correlated with increased levels of placenta-derived EVs (pEVs) in maternal circulation. However, whether pEVs impaired endothelial cell function remains to be determined. In this study, we hypothesize that pEVs from pregnant women with severe PE (sPE) impair endothelial function through altered cell signaling. METHODS: We obtained plasma samples from women with sPE (n = 14) and normotensive pregnant women (n = 15) for the isolation of EVs. The total number of EV and pEV contribution was determined by quantifying immunoreactive EV-cluster of designation 63 (CD63) and placental alkaline phosphatase (PLAP) as placenta-specific markers, respectively. Vascular endothelial functional assays were determined by cell migration, electric cell-substrate impedance sensing in human aortic endothelial cells (HAECs), and wire myography in isolated blood vessels, preincubated with EVs from normotensive and sPE women. RESULTS: Plasma EV and pEV levels were increased in sPE when compared to normotensive without a significant size distribution difference in sPE (108.8 ± 30.2 nm) and normotensive-EVs (101.3 ± 20.3 nm). Impaired endothelial repair and proliferation, reduced endothelial barrier function, reduced endothelial-dependent vasorelaxation, and decreased nitrite level indicate that sPE-EVs induced vascular endothelial dysfunction. Moreover, sPE-EVs significantly downregulated endothelial nitric oxide synthase (eNOS and p-eNOS) when compared to normotensive-EV. CONCLUSIONS: EVs from sPE women impair endothelial-dependent vascular functions in vitro.

Racial disparities in peripartum cardiomyopathy: eighteen years of observations.

BACKGROUND: Black women have greater than a three-fold risk of pregnancy-associated death compared to White women; cardiomyopathy is a leading cause of maternal mortality. OBJECTIVES: This study examined racial disparities in health outcomes among women with peripartum cardiomyopathy. STUDY DESIGN: Retrospective cohort of women with peripartum cardiomyopathy per the National Heart, Lung, and Blood Institute definition from January 2000 to November 2017 from a single referral center. Selected health outcomes among Black and White women were compared; primary outcome was ejection fraction at diagnosis. Secondary outcomes included cardiovascular outcomes, markers of maternal morbidity, resource utilization, and subsequent pregnancy outcomes. RESULTS: Ninety-five women met inclusion criteria: 48% Black, 52% White. Nearly all peripartum cardiomyopathy diagnoses were postpartum (95.4% Black, 93% White, p=.11). Ejection fraction at diagnosis was not different between Black and White women (26.8 ± 12.5 vs. 28.7 ± 9.9, p=.41). Though non-significant, fewer Black women had myocardial recovery to EF ≥55% (35 vs. 53%, p=.07); however, 11 (24%) of Black women vs. 1 (2%) White woman had an ejection fraction ≤35% at 6-12 months postpartum (p<.01). More Black women underwent implantable cardioverter defibrillator placement: n = 15 (33%) vs. n = 7 (14%), p=.03. Eight women (8.4%) died in the study period, not different by race (p=.48). Black women had higher rates of healthcare utilization. In the subsequent pregnancy, Black women had a lower initial ejection fraction (40 vs. 55%, p=.007) and were less likely to recover postpartum (37.5 vs. 55%, p=.02). CONCLUSIONS: Black and White women have similar mean ejection fraction at diagnosis of peripartum cardiomyopathy, but Black women have more severe left ventricular systolic dysfunction leading to worse outcomes, increased resource use, and lower ejection fraction entering the subsequent pregnancy.

A systematic review of biomarkers associated with maternal infection in pregnant and postpartum women.

BACKGROUND: Serum biomarkers are commonly used to support the diagnosis of infection in non-pregnant patients whose clinical presentation suggests infection. The utility of serum biomarkers for infection in pregnant and postpartum women is uncertain. SEARCH STRATEGY: PubMed, CINAHL, EMBASE, ClinicalTrials.gov, Cochrane Library, CINAHL, and SCOPUS were searched from inception to February 2020. SELECTION CRITERIA: Full-text manuscripts in English were included if they reported the measurement of maternal serum biomarkers-and included a control group-to identify infection in pregnant and postpartum women. DATA COLLECTION AND ANALYSIS: two authors independently screened manuscripts, extracted data, and assessed methodologic quality. MAIN RESULTS: Interleukin-6 (IL-6), C-reactive protein, procalcitonin, insulin-like growth factor binding protein 1, tumor necrosis factor-α, calgranulin B, neopterin, and interferon-γ inducible protein 10 reliably indicated infection. Intercellular adhesion molecule 1, monocyte chemotactic and activating factor, soluble IL-6 receptor, and IL-8 were not useful markers in pregnant and postpartum women. CONCLUSIONS: Findings suggest that certain biomarkers have diagnostic value when maternal infection is suspected, but also confirms limitations in this population.

The effects of offering immediate postpartum placement of IUDs and implants to pregnant patients with heart disease.

OBJECTIVE: To evaluate the effects of offering immediate postpartum long-acting reversible contraception to pregnant patients with heart disease. STUDY DESIGN: Retrospective cohort of pregnant patients with cardiac disease managed by a Comprehensive Pregnancy & Heart Program. Patients were divided into 2 cohorts: pre-immediate postpartum LARC Program implementation (March 2015 to January 2017) and post-implementation (February 2017 to June 2019). The primary outcome was LARC (intrauterine device [IUD] or etonogestrel implant) use postpartum, defined as LARC either immediately postpartum or at the postpartum visit. Secondary outcomes included contraception intent at delivery and IUD expulsion rate of IUDs placed immediately postpartum. RESULTS: Of 159 included patients, 96 (60%) delivered during the post-implementation period. LARC use tripled after program implementation, 11% vs 35%, p < 0.01. Specifically, immediate postpartum IUD use increased from 1 (1.6%) to 10 (10.4%), p = 0.05, and use of immediate postpartum implant increased from 0 to 14 (14.6%), p = 0.002. Rates of women without contraception plans at delivery decreased from 32% to 14%, p < 0.01, as did the number of women using medroxyprogesterone acetate: 16% vs 4%, p = 0.01. Tubal ligation rates were not different before and after program implementation: 24% and 29%, p = 0.46. Postpartum visit rates were similar between Pre and Post groups: 70% and 72%, p = 0.78, respectively. One immediate postpartum IUD expulsion occurred. CONCLUSION: LARC use tripled in pregnant patients in an obstetric heart disease program after implementation of an immediate postpartum LARC Program. Access to immediate postpartum IUDs and implants should be a public health priority for women with heart disease to reduce their disproportionate burden of maternal morbidity and mortality. IMPLICATIONS: Access to immediate postpartum IUDs and implants should be a public health priority for women with heart disease - as well as all people with high-risk health conditions - to reduce their disproportionate burden of maternal morbidity and mortality.