Placental pathology and fetal growth outcomes in pregnancies complicated by maternal obesity.

BACKGROUND: The rising prevalence of maternal obesity presents a significant health concern because of the possible implications for obstetric complications and neonatal outcomes. Understanding the impact of obesity on placental structure and function as well as fetal growth and infant outcomes is important to improve the care of these potentially high-risk pregnancies. This study aimed to determine the effect of elevated maternal BMI on histopathologic patterns of placental injury and its consequences on fetal growth. METHODS: Data were collected from an ongoing cohort of maternal-infant dyads in the UCSD Obstetric Registry spanning 2011-2020. Maternal characteristics, including BMI, hypertensive disease and diabetes, placental gross and histopathology, and infant characteristics, including sex and birthweight, were recorded and analyzed. ANOVA and chi-square tests were used in initial analyses, followed by log-binomial and linear regression models adjusted for relevant confounders to determine associations between maternal BMI, specific patterns of placental injury, and infant birthweight percentiles. RESULTS: Among 1366 maternal-infant dyads, placentas from mothers with overweight and obesity were heavier and demonstrated higher adjusted relative risks of chronic villitis (CV), decidual vasculopathy, intervillous thrombosis, and normoblastemia. Placental efficiency, determined by fetal-placental weight ratio, was decreased with increasing BMI. Maternal obesity was associated with higher rates of preterm birth and higher birthweight percentiles. Multiple placental lesions, including maternal (MVM) and fetal vascular malperfusion (FVM), exhibited significant effects on birthweight percentiles; however, only MVM showed a differential effect based on maternal obesity. CONCLUSIONS: Presence of obesity in pregnancy is associated with increased rates of placental patterns of injury, decreased placental efficiency, and increased birthweight percentiles. While placental lesions, such as CV, have the potential to negatively impact fetal growth, the resulting birthweight percentiles demonstrate a more complex relationship between maternal obesity and fetal growth, that likely involves placental and fetal adaptation to the altered in utero environment.

Chronic villitis as a distinctive feature of placental injury in maternal SARS-CoV-2 infection.

BACKGROUND: SARS-CoV-2 infection during pregnancy is associated with an increased risk for stillbirth, preeclampsia, and preterm birth. However, this does not seem to be caused by intrauterine fetal infection because vertical transmission is rarely reported. There is a paucity of data regarding the associated placental SARS-CoV-2 histopathology and their relationship with the timing and severity of infection. OBJECTIVE: This study aimed to determine if maternal SARS-CoV-2 infection was associated with specific patterns of placental injury and if these findings differed by gestational age at time of infection or disease severity. STUDY DESIGN: A retrospective cohort study was performed at the University of California San Diego between March 2020 and February 2021. Placentas from pregnancies with a positive SARS-CoV-2 test were matched with 2 sets of controls; 1 set was time-matched by delivery date and sent to pathology for routine clinical indications, and the other was chosen from a cohort of placentas previously collected for research purposes without clinical indications for pathologic examination before the SARS-CoV-2 outbreak. Placental pathologic lesions were defined based on standard criteria and included maternal and fetal vascular malperfusion and acute and chronic inflammatory lesions. A bivariate analysis was performed using the independent Student t test and Pearson chi-square test. A logistic regression was used to control for relevant covariates. Regions of SARS-CoV-2-associated villitis were further investigated using protein-based digital spatial profiling assays on the GeoMx platform, validated by immunohistochemistry, and compared with cases of infectious villitis and villitis of unknown etiology. Differential expression analysis was performed to identify protein expression differences between these groups of villitis. RESULTS: We included 272 SARS-CoV-2 positive cases, 272 time-matched controls, and 272 historic controls. The mean age of SARS-CoV-2 affected subjects was 30.1±5.5 years and the majority were Hispanic (53.7%) and parous (65.7%). SARS-CoV-2 placentas demonstrated a higher frequency of the 4 major patterns of placental injury (all P<.001) than the historic controls. SARS-CoV-2 placentas also showed a higher frequency of chronic villitis and severe chronic villitis (P=.03 for both) than the time-matched controls, which remained significant after controlling for gestational age at delivery (adjusted odds ratio, 1.52; 95% confidence interval, 1.01-2.28; adjusted odds ratio, 2.12; 95% confidence interval, 1.16-3.88, respectively). Digital spatial profiling revealed that programmed death-ligand 1 was increased in villitis-positive regions of the SARS-CoV-2 (logFC, 0.47; adjusted P value =.002) and villitis of unknown etiology (logFC, 0.58; adjusted P value =.003) cases, but it was conversely decreased in villitis-positive regions of the infectious villitis group (log FC, -1.40; adjusted P value <.001). CONCLUSION: Chronic villitis seems to be the most specific histopathologic finding associated with SARS-CoV-2 maternal infection. Chronic villitis involves damage to the vasculosyncytial membrane of the chorionic villi, which are involved in gas and nutrient exchange, suggesting potential mechanisms of placental (and perhaps neonatal) injury, even in the absence of vertical transmission. Surprisingly, changes in protein expression in SARS-CoV-2-associated villitis seem to be more similar to villitis of unknown etiology than to infectious villitis.

Histopathologic and Transcriptomic Profiling Identifies Novel Trophoblast Defects in Patients With Preeclampsia and Maternal Vascular Malperfusion.

Preeclampsia (PE) is a heterogeneous disease for which the current clinical classification system is based on the presence or absence of specific clinical features. PE-associated placentas also show heterogeneous findings on pathologic examination, suggesting that further subclassification is possible. We combined clinical, pathologic, immunohistochemical, and transcriptomic profiling of placentas to develop integrated signatures for multiple subclasses of PE. In total, 303 PE and 1388 nonhypertensive control placentas were included. We found that maternal vascular malperfusion (MVM) in the placenta was associated with preterm PE with severe features and with small-for-gestational-age neonates. Interestingly, PE placentas with either MVM or no histologic pattern of injury showed a linear decrease in proliferative (p63+) cytotrophoblast per villous area with increasing gestational age, similar to placentas obtained from the nonhypertensive patient cohort; however, PE placentas with fetal vascular malperfusion or villitis of unknown etiology lost this phenotype. This is mainly because of cases of fetal vascular malperfusion in placentas of patients with preterm PE and villitis of unknown etiology in placentas of patients with term PE, which are associated with a decrease or increase, respectively, in the cytotrophoblast per villous area. Finally, a transcriptomic analysis identified pathways associated with hypoxia, inflammation, and reduced cell proliferation in PE-MVM placentas and further subclassified this group into extravillous trophoblast-high and extravillous trophoblast-low PE, confirmed using an immunohistochemical analysis of trophoblast lineage-specific markers. Our findings suggest that within specific histopathologic patterns of placental injury, PE can be subclassified based on specific cellular and molecular defects, allowing the identification of pathways that may be targeted for diagnostic and therapeutic purposes.

Children with single ventricle heart disease have a greater increase in sRAGE after cardiopulmonary bypass.

INTRODUCTION: Reducing cardiopulmonary bypass (CPB) induced inflammatory injury is a potentially important strategy for children undergoing multiple operations for single ventricle palliation. We sought to characterize the soluble receptor for advanced glycation end products (sRAGE), a protein involved in acute lung injury and inflammation, in pediatric patients with congenital heart disease and hypothesized that patients undergoing single ventricle palliation would have higher levels of sRAGE following bypass than those with biventricular physiologies. METHODS: This was a prospective, observational study of children undergoing CPB. Plasma samples were obtained before and after bypass. sRAGE levels were measured and compared between those with biventricular and single ventricle heart disease using descriptive statistics and multivariate analysis for risk factors for lung injury. RESULTS: sRAGE levels were measured in 40 patients: 19 with biventricular and 21 with single ventricle heart disease. Children undergoing single ventricle palliation had a higher factor and percent increase in sRAGE levels when compared to patients with biventricular circulations (4.6 vs. 2.4, p = 0.002) and (364% vs. 181%, p = 0.014). The factor increase in sRAGE inversely correlated with the patient's preoperative oxygen saturation (Pearson correlation (r) = -0.43, p = 0.005) and was positively associated with red blood cell transfusion (coefficient = 0.011; 95% CI: 0.004, 0.017; p = 0.001). CONCLUSIONS: Children with single ventricle physiology have greater increase in sRAGE following CPB as compared to children undergoing biventricular repair. Larger studies delineating the role of sRAGE in children undergoing single ventricle palliation may be beneficial in understanding how to prevent complications in this high-risk population.

Impact of Socioeconomic Status, Race and Ethnicity, and Geography on Prenatal Detection of Hypoplastic Left Heart Syndrome and Transposition of the Great Arteries.

BACKGROUND: Prenatal detection (PND) has benefits for infants with hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA), but associations between sociodemographic and geographic factors with PND have not been sufficiently explored. This study evaluated whether socioeconomic quartile (SEQ), public insurance, race and ethnicity, rural residence, and distance of residence (distance and driving time from a cardiac surgical center) are associated with the PND or timing of PND, with a secondary aim to analyze differences between the United States and Canada. METHODS: In this retrospective cohort study, fetuses and infants <2 months of age with HLHS or TGA admitted between 2012 and 2016 to participating Fetal Heart Society Research Collaborative institutions in the United States and Canada were included. SEQ, rural residence, and distance of residence were derived using maternal census tract from the maternal address at first visit. Subjects were assigned a SEQ z score using the neighborhood summary score or Canadian Chan index and separated into quartiles. Insurance type and self-reported race and ethnicity were obtained from medical charts. We evaluated associations among SEQ, insurance type, race and ethnicity, rural residence, and distance of residence with PND of HLHS and TGA (aggregate and individually) using bivariate analysis with adjusted associations for confounding variables and cluster analysis for centers. RESULTS: Data on 1862 subjects (HLHS: n=1171, 92% PND; TGA: n=691, 58% PND) were submitted by 21 centers (19 in the United States). In the United States, lower SEQ was associated with lower PND in HLHS and TGA, with the strongest association in the lower SEQ of pregnancies with fetal TGA (quartile 1, 0.78 [95% CI, 0.64-0.85], quartile 2, 0.77 [95% CI, 0.64-0.93], quartile 3, 0.83 [95% CI, 0.69-1.00], quartile 4, reference). Hispanic ethnicity (relative risk, 0.85 [95% CI, 0.72-0.99]) and rural residence (relative risk, 0.78 [95% CI, 0.64-0.95]) were also associated with lower PND in TGA. Lower SEQ was associated with later PND overall; in the United States, rural residence and public insurance were also associated with later PND. CONCLUSIONS: We demonstrate that lower SEQ, Hispanic ethnicity, and rural residence are associated with decreased PND for TGA, with lower SEQ also being associated with decreased PND for HLHS. Future work to increase PND should be considered in these specific populations.

Assessing Dysferlinopathy Patients Over Three Years With a New Motor Scale.

OBJECTIVE: Dysferlinopathy is a muscular dystrophy with a highly variable clinical presentation and currently unpredictable progression. This variability and unpredictability presents difficulties for prognostication and clinical trial design. The Jain Clinical Outcomes Study of Dysferlinopathy aims to establish the validity of the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) scale and identify factors that influence the rate of disease progression using NSAD. METHODS: We collected a longitudinal series of functional assessments from 187 patients with dysferlinopathy over 3 years. Rasch analysis was used to develop the NSAD, a motor performance scale suitable for ambulant and nonambulant patients. Generalized estimating equations were used to evaluate the impact of patient factors on outcome trajectories. RESULTS: The NSAD detected significant change in clinical progression over 1 year. The steepest functional decline occurred during the first 10 years after symptom onset, with more rapid decline noted in patients who developed symptoms at a younger age (p = 0.04). The most rapidly deteriorating group over the study was patients 3 to 8 years post symptom onset at baseline. INTERPRETATION: The NSAD is the first validated limb girdle specific scale of motor performance, suitable for use in clinical practice and clinical trials. Longitudinal analysis showed it may be possible to identify patient factors associated with greater functional decline both across the disease course and in the short-term for clinical trial preparation. Through further work and validation in this cohort, we anticipate that a disease model incorporating functional performance will allow for more accurate prognosis for patients with dysferlinopathy. ANN NEUROL 2021;89:967-978.

Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization: the PASTIME protocol.

BACKGROUND: Multidisciplinary care of placenta accreta spectrum cases improves pregnancy outcomes, but the specific components of such a multidisciplinary collaboration varies between institutions. As experience with placenta accreta spectrum increases, it is crucial to assess new surgical techniques and protocols to help improve maternal outcomes and to advocate for hospital resources. OBJECTIVE: This study aimed to assess a novel multidisciplinary protocol for the treatment of placenta accreta spectrum that comprises cesarean delivery, multivessel uterine embolization, and hysterectomy in a single procedure within a hybrid operative suite. STUDY DESIGN: This was a matched prepost study of placenta accreta spectrum cases managed before (2010-2017) and after implementation of the Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol (2018-2021) at a tertiary medical center. Historical cases were managed with internal iliac artery balloon placement in selected cases with the decision to inflate the balloons intraoperatively at the discretion of the primary surgeon. Intraoperative Embolization cases were compared with historical cases in a 1:2 ratio matched on the basis of placenta accreta spectrum severity and surgical urgency. The primary outcome was a requirement for transfusion with packed red blood cells. Secondary outcomes included estimated surgical blood loss, operative and postoperative complications, procedural time, length of stay, and neonatal outcomes. RESULTS: A total of 15 Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization cases and 30 matched historical cases were included in the analysis. There were no demographic differences noted between the groups. A median (interquartile range) of 0 units (0-2 units) of packed red blood cells were transfused in the Intraoperative Embolization group compared with 2 units (0-4.5 units) in the historical group (P=.045); 5 of 15 (33.3%) Intraoperative Embolization cases required blood transfusions compared with 19 of 30 (63.3%) cases in the historical group (P=.11). The estimated blood loss was significantly less in the Intraoperative Embolization group with a median (interquartile range) of 750 mL (450-1050 mL) compared with 1750 mL (1050-2500 mL) in the historical group (P=.003). There were no cases requiring massive transfusion (≥10 red blood cell units in 24 hours) in the Intraoperative Embolization group compared with 5 of 30 (16.7%) cases in the historical group (P=.15). There were no intraoperative deaths from hemorrhagic shock using the Intraoperative Embolization protocol, whereas this occurred in 2 of the historical cases. The mean duration of the interventional radiology procedure was longer in the Intraoperative Embolization group (67.8 vs 34.1 minutes; P=.002). Intensive care unit admission and postpartum length of stay were similar, and surgical and postoperative complications were not significantly different between the groups. The gestational age and neonatal birthweights were similar; however, the neonatal length of stay was longer in the Intraoperative Embolization group (median duration, 32 days vs 15 days; P=.02) with a trend toward low Apgar scores. Incidence of arterial umbilical cord blood pH <7.2 and respiratory distress syndrome and intubation rates were not statistically different between the groups. CONCLUSION: A multidisciplinary pathway including a single-surgery protocol with multivessel uterine embolization is associated with a decrease in blood transfusion requirements and estimated blood loss with no increase in operative complications. The Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol provides a definitive surgical method that warrants consideration by other centers specializing in placenta accreta spectrum treatment.

Autonomic nervous system maturation in the premature extrauterine milieu.

BACKGROUND: In premature infants, we investigated whether the duration of extrauterine development influenced autonomic nervous system (ANS) maturation. METHODS: We performed a longitudinal cohort study of ANS maturation in preterm infants. Eligibility included birth gestational age (GA) < 37 weeks, NICU admission, and expected survival. The cohort was divided into three birth GA groups: Group 1 (≤29 weeks), Group 2 (30-33 weeks), and Group 3 (≥34 weeks). ECG data were recorded weekly and analyzed for sympathetic and parasympathetic tone using heart rate variability (HRV). Quantile regression modeled the slope of ANS maturation among the groups by postnatal age to term-equivalent age (TEA) (≥37 weeks). RESULTS: One hundred infants, median (Q1-Q3) birth GA of 31.9 (28.7-33.9) weeks, were enrolled: Group 1 (n = 35); Group 2 (n = 40); and Group 3 (n = 25). Earlier birth GA was associated with lower sympathetic and parasympathetic tone. However, the rate of autonomic maturation was similar, and at TEA there was no difference in HRV metrics across the three groups. The majority of infants (91%) did not experience significant neonatal morbidities. CONCLUSION: Premature infants with low prematurity-related systemic morbidity have maturational trajectories of ANS development that are comparable across a wide range of ex-utero durations regardless of birth GA. IMPACT: Heart rate variability can evaluate the maturation of the autonomic nervous system. Metrics of both the sympathetic and parasympathetic nervous system show maturation in the premature extrauterine milieu. The autonomic nervous system in preterm infants shows comparable maturation across a wide range of birth gestational ages. Preterm newborns with low medical morbidity have maturation of their autonomic nervous system while in the NICU. Modern NICU advances appear to support autonomic development in the preterm infant.

Risk Factors for Complications in Children with Staphylococcus aureus Bacteremia.

OBJECTIVES: To determine risk factors for complications in children with Staphylococcus aureus (S aureus) bacteremia, including methicillin resistance. STUDY DESIGN: Single center, retrospective cohort study of children ≤18 years of age hospitalized with S aureus bacteremia. We compared clinical characteristics and outcomes between those with methicillin-sensitive S aureus (MSSA) and methicillin-resistant S aureus (MRSA) bacteremia. Multivariate regression models identified risk factors associated with developing complications and with longer duration of bacteremia. RESULTS: We identified 394 episodes of S aureus bacteremia, 279 (70.8%) with MSSA, and 115 (29.2%) with MRSA. Primary site of infection was catheter-related in 34%, musculoskeletal in 30%, skin/soft tissue in 10.2%, pneumonia in 6.4%, and endovascular in 6.6%. Eight children (2.0%) died within 30 days because of S aureus bacteremia, 15 (3.5%) had recurrence within 30 days, and 38 (9.6%) had complications including septic emboli or a metastatic focus of infection. Methicillin resistance was associated with development of a complication (aOR 3.31; 95% CI 1.60-6.85), and catheter-related infections were less likely to be associated with a complication (aOR 0.40; 95% CI 0.15-1.03). In a Poisson regression analysis on duration of bacteremia, methicillin resistance, musculoskeletal infection, endovascular infection, black race, and delayed intervention for source control were significantly associated with longer duration of bacteremia. CONCLUSIONS: In this cohort of children with S aureus bacteremia, MRSA infections ere associated with longer duration of bacteremia and a higher likelihood of complications.

Crowdsourced analysis of factors and misconceptions associated with parental willingness to donate their child's organs.

We evaluated factors associated with a parental willingness to donate their child's organs. A twenty-one-question survey was administered to US parents with at least one child to measure organ donation acceptability and brain death beliefs using an online crowdsourcing medium, Amazon's Mechanical Turk Prime. We collected 425 surveys; 76% were willing to donate their own and 65% willing to donate their child's organs. Parents who agreed brain death was synonymous with death (47%) were 2.37 times more willing to donate. Compared with White respondents, Black (OR 5.27, CI 2.81, 9.88) and Hispanic (OR 2.24, CI 1.06-4.75) participants were more likely to believe doctors "steal organs from patients" and "declare someone dead based on their skin color" (OR 4.97, CI 2.65-9.32; OR 2.19, CI 1.01-4.72, respectively). Lower income participants were also more likely to believe doctors "steal organs from patients," OR 0.81 (95% CI 0.68-0.96 for increasing income) and "declare someone dead based on how much money they have," OR 0.80 (95% CI 0.67-0.96 for increasing income). Confusion surrounding brain death and skepticism (particularly among racial and ethnic minorities and lower socioeconomic groups) toward doctors' motivations for donation contribute to lack of parental willingness to donate.

Multigenerational Cardiometabolic Risk as a Predictor of Birth Outcomes: The Bogalusa Heart Study.

OBJECTIVE: To examine the relationship between generation 1 (grandmaternal) cardiometabolic risk factors and generation 3 (grandchild's) birthweight and gestational age. STUDY DESIGN: Mother-daughter pairs in the Bogalusa Heart Study (1973-present) were linked to their children's birth certificates; women were also interviewed about their reproductive histories, creating a 3-generation linkage including 177 generation 1 (grandmothers), 210 generation 2 (mothers), and 424 generation 3 (children). Prepregnancy cardiometabolic risk factors (body mass index [BMI], lipids, glucose) or generation 1 (mean age 16.2 years) and 2 (mean age 11.1 years) were examined as predictors of generation 3 birthweight and gestational age using linear and logistic regression with adjustment for age, race, parity, and other confounders. RESULTS: Generation 2 higher BMI was associated with higher birthweight (28 g per 1 unit, 95% CI 12-44) and gestational age (0.08 weeks, 95% CI 0.02-0.14) in generation 3, and generation 1 higher BMI was associated with higher birthweight (52 g, 95% CI 34-70) in the generation 2. Generation 1's higher glucose levels were associated with higher birthweight in generation 3 (adjusted beta 111 g, 95% CI 33-189), and triglycerides (adjusted beta -21, 95% CI -43-0) and low-density lipoprotein (adjusted beta -24, 95% CI -48-0) were associated with lower birthweight. CONCLUSIONS: These results suggest the possibility of multigenerational developmental programming of birth outcomes, although mechanisms (whether biological or environmental) are undetermined.

Predictors of treatment failure in young patients undergoing in vitro fertilization.

PURPOSE: The purpose of the study was to evaluate whether routinely collected clinical factors can predict in vitro fertilization (IVF) failure among young, "good prognosis" patients predominantly with secondary infertility who are less than 35 years of age. METHODS: Using de-identified clinic records, 414 women <35 years undergoing their first autologous IVF cycle were identified. Logistic regression was used to identify patient-driven clinical factors routinely collected during fertility treatment that could be used to model predicted probability of cycle failure. RESULTS: One hundred ninety-seven patients with both primary and secondary infertility had a failed IVF cycle, and 217 with secondary infertility had a successful live birth. None of the women with primary infertility had a successful live birth. The significant predictors for IVF cycle failure among young patients were fewer previous live births, history of biochemical pregnancies or spontaneous abortions, lower baseline antral follicle count, higher total gonadotropin dose, unknown infertility diagnosis, and lack of at least one fair to good quality embryo. The full model showed good predictive value (c = 0.885) for estimating risk of cycle failure; at ≥80 % predicted probability of failure, sensitivity = 55.4 %, specificity = 97.5 %, positive predictive value = 95.4 %, and negative predictive value = 69.8 %. CONCLUSION: If this predictive model is validated in future studies, it could be beneficial for predicting IVF failure in good prognosis women under the age of 35 years.

Sexually transmitted infections and sexual behaviour of deploying shipboard US military personnel: a cross-sectional analysis.

OBJECTIVES: Sexually transmitted infection (STI) prevalence and risk behaviour may differ at different phases of deployment. We examined STI prevalence and sexual behaviour in the predeployment time period (12 months prior) among recently deployed shipboard US Navy and Marine Corps military personnel. METHODS: Data were collected from 1938 male and 515 female service members through an anonymous, self-completed survey assessing sexual behaviours and STI acquisition characteristics in the past 12 months. Cross-sectional sex-stratified descriptive statistics are reported. RESULTS: Overall, 67% (n=1262/1896) reported last sex with a military beneficiary (spouse, n=931, non-spouse service member, n=331). Among those with a sexual partner outside their primary partnership, 24% (n=90/373) reported using a condom the last time they had sex and 30% (n=72/243) reported their outside partner was a service member. In total, 90% (n=210/233) reported acquiring their most recent STI in the USA (88%, n=126/143 among those reporting ≥1 deployments and an STI ≥1 year ago) and a significantly higher proportion (p<0.01) of women than men acquired the STI from their regular partner (54% vs 21%) and/or a service member (50% vs 26%). CONCLUSIONS: Findings suggest a complex sexual network among service members and military beneficiaries. Findings may extend to other mobile civilian and military populations. Data suggest most STI transmission within the shipboard community may occur in local versus foreign ports but analyses from later time points in deployment are needed. These data may inform more effective STI prevention interventions.

Integrating clinical research into electronic health record workflows to support a learning health system.

Objective: Integrating clinical research into routine clinical care workflows within electronic health record systems (EHRs) can be challenging, expensive, and labor-intensive. This case study presents a large-scale clinical research project conducted entirely within a commercial EHR during the COVID-19 pandemic. Case Report: The UCSD and UCSDH COVID-19 NeutraliZing Antibody Project (ZAP) aimed to evaluate antibody levels to SARS-CoV-2 virus in a large population at an academic medical center and examine the association between antibody levels and subsequent infection diagnosis. Results: The project rapidly and successfully enrolled and consented over 2000 participants, integrating the research trial with standing COVID-19 testing operations, staff, lab, and mobile applications. EHR-integration increased enrollment, ease of scheduling, survey distribution, and return of research results at a low cost by utilizing existing resources. Conclusion: The case study highlights the potential benefits of EHR-integrated clinical research, expanding their reach across multiple health systems and facilitating rapid learning during a global health crisis.

Polymyxin flushes for endotracheal tube suction catheters in extremely low birth-weight infants: Any benefit in preventing ventilator-associated events?

We report that receipt of polymyxin B endotracheal tube suction catheter flushes did not reduce the incidence of pediatric ventilator-associated events (PedVAE) in infants weighing <1,000 g in this retrospective study. Incidence of PedVAE in our group of extremely low birth-weight infants was 6 per 1,000 ventilator days.

Perception and Comfort with Endometriosis Management Among OB/GYN Residents.

Purpose: The diagnosis of endometriosis often takes several years, delaying appropriate care while patients suffer from pelvic pain, dysmenorrhea, and dyspareunia. Understanding whether residents in obstetrics and gynecology (OB/GYN) are being adequately exposed to and trained in the diagnosis and management of the disease is important for improving care. Methods: We conducted an online cross-sectional survey of OB/GYN residents to investigate their comfort level and familiarity with endometriosis diagnosis and management. Residency program directors and coordinators of 20 OB/GYN residency programs in California, USA were emailed to disseminate the 31-question, anonymous survey in January to February 2023. Responses were collected using Redcap and analysis was conducted using STATA. Results: 67 residents answered at least one non-demographic question and were included. A resident response rate was not calculated because we were unable to determine how many programs distributed the survey. 84% of residents felt they could recognise symptoms of endometriosis but over 30% of senior residents were not comfortable with sonographic diagnosis of endometrioma. Approximately one third of residents felt comfortable managing hypoestrogenic symptoms, osteoporotic risks, and add-back progestin for certain hormonal therapies. Academic-hospital based residents had significantly more exposure to attendings prescribing long-acting reversible contraception, GnRH antagonists, and GnRH agonists but there were no significant differences in trainee prescribing practices or comfort. More respondents would feel comfortable medically managing endometriosis (52%) than surgically managing the disease (26%) if they were in practice today, with only 39% of PGY3-4 residents feeling comfortable surgically managing endometriosis. Conclusion: There is considerable room for improvement in the education of residents in the diagnosis and medical and surgical management of endometriosis.

Humoral immune response to SARS-CoV-2 in pregnant and nonpregnant women following infection.

BACKGROUND: Immune changes that occur during pregnancy may place pregnant women at an increased risk for severe disease following viral infections like SARS-CoV-2. Whether these immunologic changes modify the immune response to SARS-CoV-2 infection during pregnancy is not well understood. OBJECTIVE: This study aimed to compare the humoral immune response to SARS-CoV-2 infection in pregnant and nonpregnant women. The immune response following vaccination for SARS-CoV-2 was also explored. STUDY DESIGN: In this cohort study, 24 serum samples from 20 patients infected with SARS-CoV-2 during pregnancy were matched by number of days after a positive test with 46 samples from 40 nonpregnant women of reproductive age. Samples from 9 patients who were vaccinated during pregnancy were also examined. Immunoglobulin G and immunoglobulin M levels were measured. Trends in the log antibody levels over time and mean antibody levels were assessed using generalized estimating equations. RESULTS: The median number of days from first positive test to sampling was 6.5 in the pregnant group (range, 3-97) and 6.0 among nonpregnant participants (range, 2-97). No significant differences in demographic or sampling characteristics were noted between the groups. No differences in immunoglobulin G or immunoglobulin M levels over time or mean antibody levels were noted among pregnant and nonpregnant participants following SARS-CoV-2 infection for any of the SARS-CoV-2 antigen targets examined (spike, spike receptor-binding domain, spike N-terminal domain, and nucleocapsid). Participants who were vaccinated during pregnancy had higher immunoglobulin G levels than pregnant patients who tested positive for all SARS-CoV-2 targets except nucleocapsid antibodies (all P<.001) and had lower immunoglobulin M spike (P<.05) and receptor-binding domain (P<.01) antibody levels. CONCLUSION: This study suggests that the humoral response following SARS-CoV-2 infection does not seem to differ between pregnant women and their nonpregnant counterparts. These findings should reassure patients and healthcare providers that pregnant patients seem to mount a nondifferential immune response to SARS-CoV-2.

High placental expression of FLT1, LEP, PHYHIP and IL3RA - In persons of African ancestry with severe preeclampsia.

INTRODUCTION: Mortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries. METHODS: To elucidate placental contribution to worse PE outcomes in African ancestry pregnancies, we performed bulk RNA sequencing on 50 placentas from persons with severe PE (sPE) of African (n = 9), Asian (n = 18) and European (n = 23) ancestries and 73 normotensive controls of African (n = 10), Asian (n = 15) and European (n = 48) ancestries. RESULTS: Previously described canonical preeclampsia genes, involved in metabolism and hypoxia/angiogenesis including: LEP, HK2, FSTL3, FLT1, ENG, TMEM45A, ARHGEF4 and HTRA1 were upregulated sPE versus normotensive placentas across ancestries. LTF, NPR3 and PHYHIP were higher in African vs. Asian ancestry sPE placentas. Allograft rejection/adaptive immune response genes were upregulated in placentas from African but not in Asian or European ancestry sPE patients; IL3RA was of particular interest because the patient with the highest placental IL3RA expression, a person of African ancestry with sPE, developed postpartum cardiomyopathy, and was the only patient out of 123, that developed this condition. Interestingly, the sPE patients with the highest IL3RA expression among persons of Asian and European ancestries developed unexplained tachycardia peripartum, necessitating echocardiography in the European ancestry patient. The association between elevated placental IL3RA levels and unexplained tachycardia or peripartum cardiomyopathy was found to be significant in the 50 sPE patients (p = .0005). DISCUSSION: High placental upregulation of both canonical preeclampsia and allograft rejection/adaptive immune response genes may contribute to worse PE outcomes in African ancestry sPE patients.