Regional Differences in the US in Outcomes with Preeclampsia.

This study explores preeclampsia outcomes across US regions and examines regional differences in specific preeclampsia-associated pregnancy complications and disease management. Patient-reported measures were obtained from The Preeclampsia Registry, an open-access database composed of women with at least one pregnancy diagnosed with a hypertensive disorder of pregnancy. Pregnancies and associated outcomes were stratified by US region (Northeast, Midwest, South and West). Among 2,667 pregnancies of which 92% were in White women, maximum systolic blood pressure at any time in pregnancy was highest among women in the South and Midwest (p=0.039). Furthermore, more women in the South received pre-pregnancy antihypertensives (p=0.026) and antenatal steroids (p=0.025) and delivered at an earlier gestational age (p=0.014) compared to women in other regions. Pregnancy complications such as elevated liver enzymes were higher in women in the South (p=0.019), and women in the South and West had additional end-organ damage such as renal complications (p<0.001) and hemolysis (p=0.008) as compared to women in other regions. Further investigation is needed to assess whether healthcare access or policy could be contributing to these regional discrepancies.

Variation and correlates of psychosocial wellbeing among nulliparous women with preeclampsia.

OBJECTIVES: To identify classes of psychosocial stressors among women who developed preeclampsia and to evaluate the associations between these classes and correlates of psychosocial wellbeing. STUDY DESIGN: We performed a secondary analysis of women who developed preeclampsia (n = 727) from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) cohort (2010-2013). Latent class analysis was used to identify classes of social stressors based on seven psychological and sociocultural indicators. Associations between latent classes and correlates (demographics, health behavior, and health-systems level) were estimated using multinomial logistic regression. MAIN OUTCOME MEASURES: Classes of psychosocial wellbeing. RESULTS: Among women who developed preeclampsia, three classes reflective of psychosocial wellbeing were identified: Class 1: Intermediate Psychosocial Wellbeing (53 %), Class 2: Positive Psychosocial Wellbeing (31 %), Class 3: Negative Psychosocial Wellbeing (16 %). Women in the Negative Psychosocial Wellbeing Class were more likely to have poor sleep and a sedentary lifestyle compared with the Positive and Intermediate Psychosocial Wellbeing Classes. Both the Negative and Intermediate Psychosocial Wellbeing Classes reported concern about their quality of medical care compared with the Positive Psychosocial Wellbeing Class (adjusted odds ratio [aOR]: 6.19, 95 % confidence interval [CI]: 3.37, 11.36 and aOR: 2.19, 95 % CI: 1.31, 3.65, respectively). CONCLUSIONS: Women who develop preeclampsia are heterogenous and experience different intensities of internal and external stressors. Understanding the linkages between psychosocial wellbeing during pregnancy and modifiable behavioral and structural factors may inform future tailored management strategies for preeclampsia and the optimization of maternal postpartum health.

A Clinical Trial Design for Evaluating Topical Antimicrobials in Chronic Wounds: The BLEU Trial.

Chronic wound management is a global challenge. Millions of patients suffer from nonhealing ulcers and health systems are overwhelmed by the growing demand for treatment. Despite the prevalence of chronic wounds, the emergence of wound centers and specialized physicians is a recent phenomenon. Likewise, clinical research in wound healing is in its infancy. To date, many of the products in wound care have little or no clinical evidence. The field needs standardized clinical trial design, endpoints recognized by clinicians and payers, and improved overall clinical evidence. Wound healing is impeded by the presence of bacterial biofilms, which exist in most chronic wounds. It is not surprising that biofilm disruption is the focus of wound management and essential to the healing process. Multiple laboratory and preclinical studies demonstrate promising efficacy of several antimicrobials in treating biofilms; however, the field lacks in vivo clinical studies. In addition, a standardized trial design to evaluate efficacy of antimicrobials in chronic wounds does not exist. The advent of new diagnostic technologies, such as fluorescence imaging, has led to clinical trial designs that are reliable, easier to conduct, and cost efficient. The protocol presented here describes a randomized controlled double-blind trial designed to evaluate antiseptics in chronic wounds.

Psychosocial Stressors as a Determinant of Maternal Cardiovascular Health During Pregnancy.

Maternal psychosocial stress may be a risk factor for poor cardiovascular health (CVH) during pregnancy. We aimed to identify classes of psychosocial stressors in pregnant women and to evaluate their cross-sectional association with CVH. We performed a secondary analysis of women from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) cohort (2010 to 2013). Latent class analysis was used to identify distinct classes of exposure to psychosocial stressors based on psychological (stress, anxiety, resilience, depression) and sociocultural indicators (social support, economic stress, discrimination). Optimal and suboptimal CVH was defined based on the presence of 0 to 1 and ≥2 risk factors (hypertension, diabetes mellitus, smoking, obesity, inadequate physical activity), respectively based on the American Heart Association Life's Essential 8. We used logistic regression to evaluate the association between psychosocial classes and CVH. We included 8,491 women and identified 5 classes reflective of gradations of psychosocial stress. In unadjusted models, women in the most disadvantaged psychosocial stressor class were approximately 3 times more likely to have suboptimal CVH than those in the most advantaged class (odds ratio 2.98, 95% confidence interval: 2.54 to 3.51). Adjusting for demographics minimally attenuated the risk (adjusted odds ratio 2.09, 95% confidence interval: 1.76 to 2.48). We observed variation across psychosocial stressor landscapes in women in the nuMoM2b cohort. Women in the most disadvantaged psychosocial class had a greater risk of suboptimal CVH which was only partially explained by differences in demographic characteristics. In conclusion, our findings highlight the association of maternal psychosocial stressors with CVH during pregnancy.

Racial disparities in care escalation for postpartum hemorrhage requiring transfusion.

BACKGROUND: Postpartum hemorrhage is a leading cause of maternal morbidity and mortality in the United States and disproportionately affects pregnant persons of color. OBJECTIVE: This study aimed to identify the demographic and obstetrical characteristics of those who received different levels of antihemorrhagic intervention in the setting of severe postpartum hemorrhage requiring blood transfusion. STUDY DESIGN: This was a retrospective cohort study of patients with documented postpartum hemorrhage (estimated blood loss of ≥1000 mL) and blood product transfusion. Moreover, 3 levels of antihemorrhagic intervention were defined as follows: level 1, administration of uterotonics only; level 2, performance of a procedure (ie, B-Lynch suture, O'Leary stitch, Bakri balloon, dilation and curettage, laceration repair, or embolization); and level 3, hysterectomy. Maternal demographics, obstetrical characteristics, and comorbidities were extracted from electronic health records. Ordinal logistic regression was used to estimate the odds of higher intervention levels adjusting for maternal demographic and obstetrical characteristics. RESULTS: Of note, 365 patients were included in this study, with a racial or ethnic composition of 30% White, 42% Black, 18% Hispanic, and 10% other. Moreover, 233 patients (64%) received level 1 intervention, 98 patients (27%) received level 2 intervention, and 34 patients (9%) received level 3 intervention. Patients receiving higher levels of intervention were more likely to have greater estimated blood loss (P<.001), have more transfusions (P<.001), and be of advanced maternal age (P=.004). Black and Hispanic patients were less likely to have received higher levels of intervention than White patients (P=.034). After adjusting for estimated blood loss, advanced maternal age, placenta accreta spectrum, and fibroids, Black patients remained significantly less likely to receive higher levels of intervention (adjusted odds ratio, 0.55; 95% confidence interval, 0.30-0.98). This difference persisted at an estimated blood loss of ≥3000 mL, with Black and Hispanic patients being significantly less likely to receive higher levels of intervention than White patients (odds ratio, 0.31 [95% confidence interval, 0.10-0.92] and 0.10 [95% confidence interval, 0.01-0.53], respectively). CONCLUSION: Among patients experiencing postpartum hemorrhage and receiving transfusion, Black patients are less likely to receive higher levels of antihemorrhagic intervention. This disparity is concerning in this high-risk population and requires further attention and investigation.

Mode of delivery among women with maternal cardiac disease.

OBJECTIVE: To determine if maternal cardiac disease affects delivery mode and to investigate maternal morbidity. STUDY DESIGN: Retrospective cohort study performed using electronic medical record data. Primary outcome was mode of delivery; secondary outcomes included indication for cesarean delivery, and rates of severe maternal morbidity. RESULTS: Among 14,160 deliveries meeting inclusion criteria, 218 (1.5%) had maternal cardiac disease. Cesarean delivery was more common in women with maternal cardiac disease (adjusted odds ratio 1.63 [95% confidence interval 1.18-2.25]). Patients delivered by cesarean delivery in the setting of maternal cardiac disease had significantly higher rates of severe maternal morbidity, with a 24.38-fold higher adjusted odds of severe maternal morbidity (95% confidence interval: 10.56-54.3). CONCLUSION: While maternal cardiac disease was associated with increased risk of cesarean delivery, most were for obstetric indications. Additionally, cesarean delivery in the setting of maternal cardiac disease is associated with high rates of severe maternal morbidity.

Maternal exposure to phthalates and total gestational weight gain in the LIFECODES birth cohort.

Excessive gestational weight gain contributes to adverse maternal and neonatal outcomes. Environmental exposures such as phthalates may lead to metabolic dysregulation, and studies suggest possible associations between maternal phthalate exposure and altered gestational weight gain. We assessed the association between nine maternal phthalate metabolites and measures of total gestational weight gain (pre-pregnancy to median 35.1 weeks of gestation) in a case-control study nested within LIFECODES (N = 379), a prospective birth cohort from Boston, Massachusetts (2006-2008). Our primary outcome was total gestational weight gain z score, a measure independent of gestational age that can provide a less biased estimate of this association. Our secondary outcomes were total gestational weight gain, rate of gestational weight gain, and adequacy ratio. The results were stratified by pre-pregnancy body mass index category. We found that concentrations of mono-(3-carboxypropyl) phthalate (MCPP) and mono-n-butyl phthalate (MBP) were positively associated with total gestational weight gain z scores among participants with obesity: adjusted mean difference (95% Confidence Interval [CI]) = 0.242 (0.030 - 0.455) and 0.105 (-0.002 - 0.212) corresponding to an excess weight gain of 1.81 kg and 0.77 kg at 35 weeks of gestation per interquartile range-increase in MCPP and MBP, respectively. Also, among participants with obesity, MBP demonstrated a potential non-linear relationship with gestational weight gain in cubic spline models. These findings suggest that phthalates may be related to higher gestational weight gain, specifically, among individuals with pre-pregnancy obesity. Future research should investigate whether pregnant people with obesity represent a subpopulation with sensitivity to phthalate exposures.

The role of proprotein convertase subtillisin/kexin type 9 in placental salvage and lipid metabolism in women with preeclampsia.

INTRODUCTION: Preeclampsia is associated with decreased maternal low-density lipoprotein cholesterol (LDL-c), which is essential for fetal growth. The underlying mechanisms for decreased LDL-c in preeclampsia remain unknown. Proprotein convertase subtillisin/kexin type 9 (PCSK9) regulates serum LDL-c via LDL receptor (LDL-R) degradation. We describe the possible role of PCSK9 in lipid metabolism in all compartments of the parturient (maternal blood, placental tissue, and fetal blood) in pregnancies with and without preeclampsia. METHODS: This is an observational study examining PCSK9 levels in maternal sera, umbilical cord blood, and PCSK9 protein content in placental tissue in three different locations (maternal placental interface, fetal placental interface, and umbilical cord) in women with and without preeclampsia at >23 weeks gestation. RESULTS: 68 parturients with preeclampsia and 55 without preeclampsia were enrolled. Maternal serum LDL-c (116.6 ± 48.9 mg/dL vs 146.1 ± 47.1 mg/dL, p = 0.0045) and PCSK9 (83 [61.8127.6] ng/mL vs 105.3 [83.5142.9] ng/mL, p = 0.011) were also reduced in the preeclamptics versus controls. There were no differences in PCSK9 protein content between preeclamptics and controls at comparative placental interfaces. However, PCSK9 protein content increased between the preeclampsia maternal placental interface (1.87 ± 0.62) and the preeclampsia umbilical cord (2.67 ± 1.08, p = 0.0243). DISCUSSION: PCSK9 levels are lower in maternal sera in preeclampsia when compared to controls. Placental PCSK9 protein content in preeclampsia increases from the maternal interface to the umbilical cord; however, this is not seen in controls. This suggests a potential compensatory mechanism for PCSK9 which allows for higher circulating fetal LDL-c levels in preeclampsia.

Fetal Neuroprotective Strategies: Therapeutic Agents and Their Underlying Synaptic Pathways.

Synaptic signaling is integral for proper brain function. During fetal development, exposure to inflammation or mild hypoxic-ischemic insult may lead to synaptic changes and neurological damage that impairs future brain function. Preterm neonates are most susceptible to these deleterious outcomes. Evaluating clinically used and novel fetal neuroprotective measures is essential for expanding treatment options to mitigate the short and long-term consequences of fetal brain injury. Magnesium sulfate is a clinical fetal neuroprotective agent utilized in cases of imminent preterm birth. By blocking N-methyl-D-aspartate receptors, magnesium sulfate reduces glutamatergic signaling, which alters calcium influx, leading to a decrease in excitotoxicity. Emerging evidence suggests that melatonin and N-acetyl-L-cysteine (NAC) may also serve as novel putative fetal neuroprotective candidates. Melatonin has important anti-inflammatory and antioxidant properties and is a known mediator of synaptic plasticity and neuronal generation. While NAC acts as an antioxidant and a precursor to glutathione, it also modulates the glutamate system. Glutamate excitotoxicity and dysregulation can induce perinatal preterm brain injury through damage to maturing oligodendrocytes and neurons. The improved drug efficacy and delivery of the dendrimer-bound NAC conjugate provides an opportunity for enhanced pharmacological intervention. Here, we review recent literature on the synaptic pathways underlying these therapeutic strategies, discuss the current gaps in knowledge, and propose future directions for the field of fetal neuroprotective agents.

Incidence of essential hypertension but not echocardiographic abnormalities at four years with a history of preeclampsia with severe features.

INTRODUCTION: Women with preeclampsia are more likely to have abnormal echocardiographic parameters at the time of diagnosis and are more likely to have hypertension and other cardiovascular diseases (CVD) later in life. Screening for future CVD in preeclamptic women would assist in appropriately risk stratifying and identifying high risk women for preventive management; however, the timing of screening and the screening factors are unknown. OBJECTIVE: The objectives of this project are to 1) assess incidence of essential hypertension 4 years after pregnancy in preeclampsia with severe features (PEC) 2) identify predictive echocardiographic variables at the time of PEC diagnosis and 3) assess the rate of echocardiographic abnormalities 4 years after developing PEC. STUDY DESIGN: This is a prospective longitudinal study observing the incidence of essential hypertension in women within 4 years of a pregnancy complicated by PEC. We further looked at echocardiographic variables at the time of PEC diagnosis and at 4 years after PEC pregnancy in women with and without subsequent incident essential hypertension. The primary outcome measure is the incidence of essential hypertension within 4 years of PEC pregnancy, defined as a systolic blood pressure ≥ 130 mmHg or a diastolic blood pressure ≥ 80 mmHg. Secondary imaging outcomes include the persistence of abnormal echocardiographic parameters. Clinical secondary outcomes are new diagnoses of severe CVD, including coronary artery disease, stroke, arrhythmia, heart failure, or inpatient hospital admission for CVD. RESULTS: Of the 33 enrolled women with PEC, 48% (16/33) developed incident essential hypertension within 4 years of delivery. These women had thicker left ventricular posterior walls on their initial antenatal echocardiogram when compared to the 52% (17/33) who did not develop hypertension (1.0 cm [0.9-1.1 cm] vs 0.9 cm [0.7-0.9 cm]. p < 0.016). However, these abnormal echocardiographic variables resolved in the 16 women who underwent 4-year follow-up echocardiography. CONCLUSION: Women who develop PEC have a high incidence of essential hypertension within 4 years of delivery. The group who develops essential hypertension are more likely to have evidence of adverse cardiac remodeling at the time of PEC diagnosis; however, neither group have cardiac echocardiographic abnormalities 4 years postpartum. Because this is a small study, larger long-term cohort studies are needed to confirm these echocardiographic and clinical findings.

Pregnancy alters interleukin-1 beta expression and antiviral antibody responses during severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied. OBJECTIVE: This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women. STUDY DESIGN: Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood. RESULTS: Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.

Dysregulated immunity in SARS-CoV-2 infected pregnant women.

IMPORTANCE: The effects of SARS-CoV-2 infection on immune responses during pregnancy have not been systematically evaluated. OBJECTIVE: To assess the impact of SARS-CoV-2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to SARS-CoV-2 among pregnant and non-pregnant women. DESIGN: Immune responses to SARS-CoV-2 were analyzed using samples from pregnant and non-pregnant women who had either tested positive or negative for SARS-CoV-2. We measured, proinflammatory and placental cytokine mRNAs, neonatal Fc receptor (FcRn) receptor expression, and tetanus antibody transfer in maternal and cord blood samples. Additionally, we measured anti-spike (S) IgG, anti-S-receptor binding domain (RBD) IgG, and neutralizing antibody (nAb) responses to SARS-CoV-2 in serum or plasma collected from non-pregnant women, pregnant women, and cord blood. SETTING: Johns Hopkins Hospital (JHH). PARTICIPANTS: Pregnant women were recruited through JHH outpatient obstetric clinics and the JHH Labor & Delivery unit. Non-pregnant women were recruited after receiving outpatient SARS-CoV-2 testing within Johns Hopkins Health System, USA. Adult non-pregnant women with positive RT-PCR results for SARS-CoV-2, within the age range of 18-48 years, were included in the study. EXPOSURES: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Participant demographic characteristics, antibody titers, cytokine mRNA expression, and FcRn receptor expression. RESULTS: SARS-COV-2 positive pregnant women expressed more IL1ß , but not IL6 , in blood samples collected within 14 days versus > 14 days after a confirmed SARS-CoV-2 test, with similar patterns observed in the fetal side of placentas, particularly among asymptomatic pregnant women. Pregnant women with confirmed SARS-CoV-2 infection also had reduced anti-S-RBD IgG titers and were less likely to have detectable nAb as compared with non-pregnant women. Although SARS-CoV-2 infection did not disrupt FcRn expression in the placenta, maternal transfer of nAb was inhibited by SARS-CoV-2 infection during pregnancy. CONCLUSIONS AND RELEVANCE: SARS-CoV-2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of COVID-19 therapeutics in pregnancy. The long-term implications of placental inflammation for neonatal health also requires greater consideration.

Comparison of Clinical Characteristics and Outcomes of Peripartum Cardiomyopathy Between African American and Non-African American Women.

Importance: Peripartum cardiomyopathy (PPCM) disproportionately affects women of African ancestry, but well-powered studies to explore differences in severity of disease and clinical outcomes are lacking. Objective: To compare the clinical characteristics, presentation, and outcomes of PPCM between African American and non-African American women. Design, Setting, and Participants: This retrospective cohort study using data from January 1, 1986, through December 31, 2016, performed at the University of Pennsylvania Health System, a tertiary referral center serving a population with a high proportion of African American individuals, included 220 women with PPCM. Main Outcomes and Measures: Demographic and clinical characteristics and echocardiographic findings at presentation, as well as clinical outcomes including cardiac recovery, time to recovery, cardiac transplant, persistent dysfunction, and death, were compared between African American and non-African American women with PPCM. Results: A total of 220 women were studied (mean [SD] age at diagnosis, 29.5 [6.6] years). African American women were diagnosed with PPCM at a younger age (27.6 vs 31.7 years, P < .001), were diagnosed with PPCM later in the postpartum period, and were more likely to present with a left ventricular ejection fraction less than 30% compared with non-African American women (48 [56.5%] vs 30 [39.5%], P = .03). African American women were also more likely to worsen after initial diagnosis (30 [35.3%] vs 14 [18.4%], P = .02), were twice as likely to fail to recover (52 [43.0%] vs 24 [24.2%], P = .004), and, when they did recover, recovery took at least twice as long (median, 265 vs 125.5 days; P = .02) despite apparent adequate treatment. Conclusions and Relevance: In a large cohort of women with well-phenotyped PPCM, this study demonstrates a different profile of disease in African American vs non-African American women. Further work is needed to understand to what extent these differences stem from genetic or socioeconomic differences and how treatment of African American patients might be tailored to improve health outcomes.