Decreased Extracellular Vesicle Vasorin in Severe Preeclampsia Plasma Mediates Endothelial Dysfunction.

Background: Preeclampsia (PE) is a serious pregnancy complication affecting 5-8% of pregnancies globally. It is a leading cause of maternal and neonatal morbidity and mortality. Despite its prevalence, the underlying mechanisms of PE remain unclear. This study aimed to determine the potential role of vasorin (VASN) in PE pathogenesis by investigating its levels in extracellular vesicles (EV) and its effects on vascular function. Methods & Results: We conducted unbiased proteomics on urine-derived EV from severe PE (sPE) and normotensive pregnant women (NTP), identifying differential protein abundances. Out of one hundred and twenty proteins with ≥ ±1.5-fold regulation at P<0.05 between sPE and NTP, we focused on Vasorin (VASN), which is downregulated in sPE in urinary EV, in plasma EV and in the placenta and is a known regulator of vascular function. We generated EV with high VASN content from both human and murine placenta explants (Plex EV), which recapitulated disease-state-dependent effects on vascular function observed when treating murine aorta rings (MAR) or human aortic endothelial cells (HAEC) with murine or human plasma-derived EV. In normal murine pregnancy, VASN increases with gestational age (GA), and VASN is decreased in plasma EV, in placenta tissue and in Plex EV after intravenous administration of adenovirus encoding short FMS-like tyrosine kinase 1 (sFLT-1), a murine model of PE (murine-PE). VASN is decreased in plasma EV, in placenta tissue and in EV isolated from conditioned media collected from placenta explants (Plex EV) in patients with sPE as compared to NTP. Human sPE and murine-PE plasma EV and Plex EV impair migration, tube formation, and induces apoptosis in human aortic endothelial cells (HAEC) and inhibit acetylcholine-induced vasorelaxation in murine vascular rings (MAR). VASN over-expression counteracts the effects of sPE EV treatment in HAEC and MAR. RNA sequencing revealed that over-expression or knock down of VASN in HAEC results in contrasting effects on transcript levels of hundreds of genes associated with vasculogenesis, endothelial cell proliferation, migration and apoptosis. Conclusions: The data suggest that VASN, delivered to the endothelium via EV, regulates vascular function and that the loss of EV VASN may be one of the mechanistic drivers of PE. CLINICAL PERSPECTIVE: What is NewVASN in circulating plasma EV in sPE is reduced compared with VASN content in plasma EV of gestational age-matched pregnant women.VASN is encapsulated and transported in EV and plays a pro-angiogenic role during pregnancy.VASN should be explored both for its pro-angiogenic mechanistic role and as a novel biomarker and potential predictive diagnostic marker for the onset and severity of PE.What Are the Clinical Implications?VASN plays a role in maintaining vascular health and the normal adaptive cardiovascular response in pregnancy. A decrease of VASN is observed in sPE patients contributing to cardiovascular maladaptation.Strategies to boost diminished VASN levels and/or to pharmacologically manipulate mechanisms downstream of VASN may be explored for potential therapeutic benefit in PE.The decrease in EV-associated VASN could potentially be used as a (predictive) biomarker for PE.

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension.

OBJECTIVE: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. METHODS: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding. RESULTS: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine. CONCLUSION: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

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.

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.

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.

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.

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.