Predictors of Breastfeeding among Patients Admitted with Preterm Prelabor Rupture of Membranes.

OBJECTIVE: We sought to describe rates of breastmilk feeding (BF) at hospital discharge and 6 weeks postpartum and to identify risk factors for noninitiation or cessation among pregnancies complicated by preterm prelabor rupture of membranes (PPROM). STUDY DESIGN: Retrospective cohort study of pregnant persons with PPROM admitted to a single tertiary center (2013-2019). Patients with deliveries complicated by intrauterine or neonatal demise or with incomplete BF data were excluded. Demographic, antepartum, and delivery characteristics were evaluated. Primary analysis identified rate of BF initiation at maternal discharge and factors associated with noninitiation. Secondary analysis evaluated BF continuation and factors associated with cessation at 6 weeks postpartum. Bivariate statistics were used to compare characteristics and logistic regression was used to estimate adjusted odds ratios (aOR). RESULTS: Of 397 patients with PPROM, 342(86%) initiated BF prior to discharge. Those reporting tobacco use in pregnancy were less likely to initiate BF (aOR: 0.32; 95% confidence interval [CI]: 0.16, 0.64). In contrast, private insurance (aOR: 2.53; 95% CI: 1.19, 5.37) and pregnancy latency ≥ 14 days (aOR: 3.02; 95% CI: 1.09, 8.38) were associated with BF initiation at hospital discharge. Of the 293 patients with postpartum follow-up, only 214 (73%) had BF continuation at 6 weeks postpartum. Maternal age <20 years (aOR: 0.07; 95% CI: 0.01, 0.68) and multiparity (aOR: 0.54; 95% CI: 0.29, 0.99) were associated with BF cessation. Patients with private insurance were observed to have increased odds of BF continuation (aOR: 2.10; 95% CI: 1.07, 4.12). CONCLUSION: Among patients with PPROM, tobacco use may be associated with noninitiation of BF prior to discharge, whereas age < 20 years and multiparity were associated with cessation by 6 weeks postpartum. Longer pregnancy latency ≥ 14 days was associated with BF initiation prior to discharge. Private insurance was associated with increased rates of BF initiation and continuation postpartum. BF education and support should be offered to all patients admitted for PPROM. KEY POINTS: · Tobacco use may be associated with BF noninitiation.. · Young age and multiparity are linked with BF cessation.. · Private insurance resulted in BF initiation and continuation..

Delivery outcomes in the subsequent pregnancy following the conservative management of placenta accreta spectrum disorder: a systematic review and meta-analysis.

OBJECTIVE: Cesarean hysterectomy is generally presumed to decrease maternal morbidity and mortality secondary to placenta accreta spectrum disorder. Recently, uterine-sparing techniques have been introduced in conservative management of placenta accreta spectrum disorder to preserve fertility and potentially reduce surgical complications. However, despite patients often expressing the intention for future conception, few data are available regarding the subsequent pregnancy outcomes after conservative management of placenta accreta spectrum disorder. Thus, we aimed to perform a systematic review and meta-analysis to assess these outcomes. DATA SOURCES: PubMed, Scopus, and Web of Science databases were searched from inception to September 2022. STUDY ELIGIBILITY CRITERIA: We included all studies, with the exception of case studies, that reported the first subsequent pregnancy outcomes in individuals with a history of placenta accreta spectrum disorder who underwent any type of conservative management. METHODS: The R programming language with the "meta" package was used. The random-effects model and inverse variance method were used to pool the proportion of pregnancy outcomes. RESULTS: We identified 5 studies involving 1458 participants that were eligible for quantitative synthesis. The type of conservative management included placenta left in situ (n=1) and resection surgery (n=1), and was not reported in 3 studies. The rate of placenta accreta spectrum disorder recurrence in the subsequent pregnancy was 11.8% (95% confidence interval, 1.1-60.3; I2=86.4%), and 1.9% (95% confidence interval, 0.0-34.1; I2=82.4%) of participants underwent cesarean hysterectomy. Postpartum hemorrhage occurred in 10.3% (95% confidence interval, 0.3-81.4; I2=96.7%). A composite adverse maternal outcome was reported in 22.7% of participants (95% confidence interval, 0.0-99.4; I2=56.3%). CONCLUSION: Favorable pregnancy outcome is possible following successful conservation of the uterus in a placenta accreta spectrum disorder pregnancy. Approximately 1 out of 4 subsequent pregnancies following conservative management of placenta accreta spectrum disorder had considerable adverse maternal outcomes. Given such high incidence of adverse outcomes and morbidity, patient and provider preparation is vital when managing this population.

The association of placental pathology and neurodevelopmental outcomes in patients with neonatal encephalopathy.

BACKGROUND: Studies conflict on how acute versus chronic placental pathology impacts outcomes after neonatal encephalopathy from presumed hypoxic-ischemic encephalopathy (HIE). We examine how outcomes after presumed HIE vary by placental pathology categories. METHODS: We performed retrospective chart review for neonates with presumed HIE, regardless of severity, focusing on 50 triads for whom placental specimens were available for re-review. Placentas were categorized as having only acute, any chronic, or no lesions. Primary outcomes included in-hospital morbidity/mortality and long-term neurodevelopmental symptoms. Secondary outcomes assessed neonatal MRI and EEG. RESULTS: Demographics did not differ between groups. Forty-seven neonates were treated with therapeutic hypothermia. Placental acuity category was not associated with primary or secondary outcomes, but clinical and/or histopathological chorioamnionitis was associated with abnormal EEG background and post-neonatal epilepsy (16.7%, n = 3 with chorioamnionitis versus 0%, n = 0 without chorioamnionitis, p = 0.04). CONCLUSIONS: When grouped by acute, chronic, or absent placental lesions, we observed no association with in-hospital, neurodevelopmental, MRI, or EEG outcomes. When reanalyzed by the presence of chorioamnionitis, we found that chorioamnionitis appeared to be associated with a higher risk of EEG alterations and post-neonatal epilepsy. Despite our limited sample size, our results emphasize the critical role of placental examination for neuroprognostication in presumed HIE. IMPACT: Neonatal encephalopathy presumed to result from impaired fetal cerebral oxygenation or blood flow is called hypoxic ischemic encephalopathy (HIE). Prior studies link placental pathology to various outcomes after HIE but disagree on the impact of acute versus chronic pathology. Our study determines that neurodevelopmental outcomes, in-hospital outcomes, injury on MRI, and EEG findings in patients with HIE are not differentially associated with acute versus chronic placental pathology. Chorioamnionitis is associated with an increased risk of abnormal EEG patterns and post-neonatal epilepsy. Histopathologic chorioamnionitis without clinical symptoms is common in HIE, emphasizing the crucial role of placental pathology for neuroprognostication.

Knowledge Gaps in Placenta Accreta Spectrum.

Since its first description early in the 20th Century, placenta accreta and its variants have changed substantially in incidence, risk factor profile, clinical presentation, diagnosis and management. While systematic use of diagnostic tools and a multidisciplinary team care approach has begun to improve patient outcomes, the condition's pathophysiology, epidemiology, and best practices for diagnosis and management remain poorly understood. The use of large databases with broadly accepted terminology and diagnostic criteria should accelerate research in this area. Future work should focus on non-traditional phenotypes, such as those without placenta previa-preventive strategies, and long term medical and emotional support for patients facing this diagnosis. KEY POINTS: · Placenta accreta spectrum research may be improved with standardized terminology and use of large databases.. · Placenta accreta prediction should move beyond ultrasound with the addition of biomarkers, and needs to extend to those without traditional risk factors.. · Future research should identify practices that can prevent future accreta development..

Graduate and Continuing Medical Education of Placenta Accreta Spectrum.

Surgical training experience in obstetrics-gynecology (OB-GYN) residency and fellowship training, particularly in open abdominal surgeries has declined over the last 2 decades. This is due, in part, due to a universal trend toward non-invasive treatments for gynecologic conditions once treated surgically. Management of placenta accreta spectrum (PAS) often requires complex surgical skills, including, but not limited to highly complex hysterectomy. The decline in surgical case numbers has fallen as the incidence of PAS has risen, which we anticipate will lead to a gap in critical skills needed for graduating obstetrician-gynecologists to able to safely care for people with PAS.

Placenta Accreta Spectrum.

Placenta accreta spectrum (PAS) is one of the most dangerous conditions in pregnancy and is increasing in frequency. The risk of life-threatening bleeding is present throughout pregnancy but is particularly high at the time of delivery. Although the exact cause is unknown, the result is clear: Severe PAS distorts the uterus and surrounding anatomy and transforms the pelvis into an extremely high-flow vascular state. Screening for risk factors and assessing placental location by antenatal ultrasonography are essential for timely diagnosis. Further evaluation and confirmation of PAS are best performed in referral centers with expertise in antenatal imaging and surgical management of PAS. In the United States, cesarean hysterectomy with the placenta left in situ after delivery of the fetus is the most common treatment for PAS, but even in experienced referral centers, this treatment is often morbid, resulting in prolonged surgery, intraoperative injury to the urinary tract, blood transfusion, and admission to the intensive care unit. Postsurgical complications include high rates of posttraumatic stress disorder, pelvic pain, decreased quality of life, and depression. Team-based, patient-centered, evidence-based care from diagnosis to full recovery is needed to optimally manage this potentially deadly disorder. In a field that has relied mainly on expert opinion, more research is needed to explore alternative treatments and adjunctive surgical approaches to reduce blood loss and postoperative complications.

Validation of a sonographic checklist for the detection of histologic placenta accreta spectrum.

BACKGROUND: To standardize research terminology and to reduce unanticipated placenta accreta spectrum, the European Working Group for Abnormally Invasive Placenta developed a consensus checklist for reporting suspected placenta accreta spectrum observed during an antenatal ultrasound. The diagnostic accuracy of the European Working Group for Abnormally Invasive Placenta checklist has not been assessed. OBJECTIVE: This study aimed to test the performance of the European Working Group for Abnormally Invasive Placenta sonographic checklist in predicting histologic placenta accreta spectrum. STUDY DESIGN: This was a multisite, blinded, retrospective review of transabdominal ultrasound studies performed between 26 to 32 weeks' gestation for subjects with histologic placenta accreta spectrum between 2016 and 2020. We matched a control cohort of subjects without histologic placenta accreta spectrum in a 1:1 ratio. To reduce reader bias, we matched the control cohort for known risk factors including previa, number of previous cesarean deliveries, previous dilation and curettage, in vitro fertilization, and clinical factors affecting image quality including multiple gestation, body mass index, and gestational age at the ultrasound. Nine sonologists from 5 referral centers, blinded to the histologic outcomes, interpreted the randomized ultrasound studies using the European Working Group for Abnormally Invasive Placenta checklist. The primary outcome was the sensitivity and specificity of the checklist to predict placenta accreta spectrum. Two separate sensitivity analyses were performed. First, we excluded subjects with mild disease (ie, only assessed subjects with histologic increta and percreta). Second, we excluded interpretations from the 2 most junior sonologists. RESULTS: A total of 78 subjects were included (39 placenta accreta spectrum, 39 matched control). Clinical risk factors and image quality markers were statistically similar between the cohorts. The checklist sensitivity (95% confidence interval) was 76.6% (63.4-90.6) and the specificity (95% confidence interval) was 92.0% (63.4-99.9) with a positive and negative likelihood ratio of 9.6 and 0.3, respectively. When we excluded subjects with mild placenta accreta spectrum disease, the sensitivity (95% confidence interval) increased to 84.7% (73.6-96.4) and the specificity was unchanged at 92.0% (83.2-99.9). Sensitivity and specificity were unchanged when the interpretations from the 2 most junior sonologists were excluded. CONCLUSION: The 2016 European Working Group for Abnormally Invasive Placenta checklist for interpreting placenta accreta spectrum has a reasonable performance in detecting histologic placenta accreta spectrum and excluding cases without placenta accreta spectum.

Maternal Cardiovascular Morbidity Events Following Preeclampsia: A Retrospective Cohort Study.

BACKGROUND: Patients with preeclampsia are at high risk for long-term cardiovascular events, yet the short-term, acute cardiovascular complications that follow preeclampsia are understudied. The objective of this study was to compare the short-term, acute maternal cardiovascular morbidity events after delivery among patients with a diagnosis of preeclampsia versus those without this diagnosis. METHODS: In this retrospective cohort study, the Premier inpatient database was used to examine a cohort of obstetric patients older than 18 years, who delivered from January 1, 2016, to September 30, 2020. A diagnosis of preeclampsia and preeclampsia with severe features during delivery hospitalization were the exposures of interest. The primary outcome was a composite of maternal cardiovascular morbidity events during delivery hospital admission. The secondary outcome was the occurrence of maternal cardiovascular morbidity events during a readmission within 90 days of delivery hospitalization. RESULTS: In total, 4,488,759 patients met inclusion criteria, of which 158,114 (3.5%) were diagnosed with preeclampsia without severe features, and 117,940 (2.6%) with preeclampsia with severe features. Adjusted odds of maternal cardiovascular morbidity events were higher in patients with preeclampsia and in those with preeclampsia with severe features compared with those without preeclampsia during delivery hospitalization (adjusted odds ratio [OR] [95% confidence interval {CI}] 1.87 [1.78-1.97] and 4.74 [4.44-5.05], respectively) and within 90 days (adjusted OR [95% CI] 2.01 [1.83-2.21] and 2.32 [2.10-2.57], respectively). CONCLUSIONS: Patients with both preeclampsia and preeclampsia with severe features have higher rates of maternal cardiovascular morbidity events than those without preeclampsia. Future studies are necessary to examine which patients with preeclampsia are at highest risk for cardiovascular complications.

Clinical Correlates of Placenta Accreta Spectrum Disorder Depending on the Presence or Absence of Placenta Previa: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate whether there are differences in risk factors and maternal outcomes of pregnancies complicated by placenta accreta spectrum depending on the presence or absence of placenta previa. DATA SOURCES: We performed a systematic search in Medline, EMBASE, ClinicalTrials.gov , and Web of Science from inception through April 25, 2022, without language or date restrictions. Search strategy included the key words "placenta accreta," "placenta increta," "placenta percreta," "adherent placenta," "invasive placenta," "abnormal placent*," "placenta previa," and "marginal placent*." METHODS OF STUDY SELECTION: Of the 1,122 articles screened, seven studies were included in the final review. Studies were included if they compared the risk factors and maternal outcomes of pregnancies complicated by placenta accreta spectrum depending on the presence or absence of placenta previa. TABULATION, INTEGRATION, AND RESULTS: A random-effects model was used to pool the mean differences or odds ratios (OR) and the corresponding 95% CIs using RevMan software. A total of 3,342 pregnancies complicated by placenta accreta spectrum were included in the meta-analysis (2,365 without previa and 977 with previa). Pregnancies complicated by placenta accreta spectrum without previa were more likely to have been conceived by in vitro fertilization (IVF) (OR 3.11, 95% CI 1.93-5.02, P <.001, I 2 =52.0%) and to be associated with prior dilation and curettage (D&C) (OR 1.60, 95% CI 1.15-2.22, P =.005, I 2 =0.0%) and myomectomy (OR 2.47, 95% CI 1.31-4.66, P =.005, I 2 =0.0%), but they were less likely to be associated with prior cesarean delivery (OR 0.15, 95% CI 0.06-0.37, P <.001, I 2 =87.0%). Placenta accreta spectrum without previa was less likely to be diagnosed antenatally (OR 0.07, 95% CI 0.04-0.11, P <.001, I 2 =38.0%). Also, women with pregnancies without previa had lower rates of red blood cell transfusion, intensive care unit admission, risk of hysterectomy, unscheduled delivery, and intraoperative bowel or bladder injuries. CONCLUSION: Pregnancies complicated by placenta accreta spectrum without previa had a more prominent association with IVF and prior D&C and myomectomy but were much less likely to be associated with prior cesarean delivery. Further, placenta accreta spectrum without previa was less likely to be diagnosed antenatally, although it had better maternal outcomes as compared with placenta accreta spectrum with previa. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022307637.

Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface.

Infections at the maternal-fetal interface can directly harm the fetus and induce complications that adversely impact pregnancy outcomes. Innate immune signaling by both fetal-derived placental trophoblasts and the maternal decidua must provide antimicrobial defenses at this critical interface without compromising its integrity. Here, we developed matched trophoblast (TO) and decidua organoids (DO) from human placentas to define the relative contributions of these cells to antiviral defenses at the maternal-fetal interface. We demonstrate that TO and DO basally secrete distinct immunomodulatory factors, including the constitutive release of the antiviral type III interferon IFN-λ2 from TOs, and differentially respond to viral infections through the induction of organoid-specific factors. Finally, we define the differential susceptibility and innate immune signaling of TO and DO to human cytomegalovirus (HCMV) and develop a co-culture model of TO and DO which showed that trophoblast-derived factors protect decidual cells from HCMV infection. Our findings establish matched TO and DO as ex vivo models to study vertically transmitted infections and highlight differences in innate immune signaling by fetal-derived trophoblasts and the maternal decidua.

Transfusion Requirements with Hybrid Management of Placenta Accreta Spectrum Incorporating Targeted Embolization and a Selective Use of Delayed Hysterectomy.

OBJECTIVE: This study compares the number of units of red blood cells (RBCs) transfused in patients with placenta accreta spectrum (PAS) treated with or without a multidisciplinary algorithm that includes placental uterine arterial embolization (P-UAE) and selective use of either immediate or delayed hysterectomy. STUDY DESIGN: This is a retrospective study of deliveries conducted at a tertiary care hospital from 2001 to 2018 with pathology-confirmed PAS. Those with previable pregnancies or microinvasive histology were excluded. To improve the equity of comparison, analyses were made separately among scheduled and unscheduled cases, therefore patients were assigned to one of four cohorts as follows: (1) scheduled/per-algorithm, (2) scheduled/off-algorithm, (3) unscheduled/per-algorithm, or (4) unscheduled/off-algorithm. Primary outcomes included RBCs transfused and estimated blood loss (EBL). Secondary outcomes included perioperative complications and disposition. RESULTS: Overall, 95 patients were identified, with 87 patients meeting inclusion criteria: 36 treated per-algorithm (30 scheduled and 6 unscheduled) and 51 off-algorithm patients (24 scheduled and 27 unscheduled). Among scheduled deliveries, 9 (30.0%) patients treated per-algorithm received RBCs compared with 20 (83.3%) patients treated off-algorithm (p < 0.01), with a median (interquartile range [IQR]) of 3.0 (2.0, 4.0) and 6.0 (2.5, 7.5) units transfused (p = 0.13), respectively. Among unscheduled deliveries, 5 (83.3%) per-algorithm patients were transfused RBCs compared with 25 (92.6%) off-algorithm patients (p = 0.47) with a median (IQR) of 4.0 (2.0, 6.0) and 8.0 (3.0, 10.0) units transfused (p = 0.47), respectively. Perioperative complications were similar between cohorts. CONCLUSION: A multidisciplinary algorithm including P-UAE and selective use of delayed hysterectomy is associated with a lower rate of blood transfusion in scheduled but not unscheduled cases. KEY POINTS: · An algorithm with delayed hysterectomy had less transfusion in scheduled, but not unscheduled, cases.. · Over time, more cases were managed per algorithm; among scheduled cases, the transfusion rate and volume transfused decreased.. · There were similar transfusion outcomes among off-algorithm cases, regardless if delivery was scheduled..

A Multidimensional Bioinformatic Platform for the Study of Human Response to Surgery.

OBJECTIVE: To design and establish a prospective biospecimen repository that integrates multi-omics assays with clinical data to study mechanisms of controlled injury and healing. BACKGROUND: Elective surgery is an opportunity to understand both the systemic and focal responses accompanying controlled and well-characterized injury to the human body. The overarching goal of this ongoing project is to define stereotypical responses to surgical injury, with the translational purpose of identifying targetable pathways involved in healing and resilience, and variations indicative of aberrant peri-operative outcomes. METHODS: Clinical data from the electronic medical record combined with large-scale biological data sets derived from blood, urine, fecal matter, and tissue samples are collected prospectively through the peri-operative period on patients undergoing 14 surgeries chosen to represent a range of injury locations and intensities. Specimens are subjected to genomic, transcriptomic, proteomic, and metabolomic assays to describe their genetic, metabolic, immunologic, and microbiome profiles, providing a multidimensional landscape of the human response to injury. RESULTS: The highly multiplexed data generated includes changes in over 28,000 mRNA transcripts, 100 plasma metabolites, 200 urine metabolites, and 400 proteins over the longitudinal course of surgery and recovery. In our initial pilot dataset, we demonstrate the feasibility of collecting high quality multi-omic data at pre- and postoperative time points and are already seeing evidence of physiologic perturbation between timepoints. CONCLUSIONS: This repository allows for longitudinal, state-of-the-art geno-mic, transcriptomic, proteomic, metabolomic, immunologic, and clinical data collection and provides a rich and stable infrastructure on which to fuel further biomedical discovery.

Symptomatic versus asymptomatic COVID-19: does it impact placental vasculopathy?

This study sought to assess the impact of COVID-19 on placental vasculature in the context of maternal symptomatology - comparing asymptomatic to symptomatic pregnant patients - and disease severity - comparing pregnant patients with mild, moderate, severe, and critical COVID-19 infection. PCR-confirmed COVID-19 positive pregnant patients in a single health system who delivered between 3/2020-5/2021 included. All patients had positive COVID test and delivered during the study period. Primary outcome was incidence of any vascular malperfusion on placental pathology. Secondary outcomes were FVM and MVM on placental pathology. Placental pathology compared between symptomatic (sCOVID) and asymptomatic (aCOVID) patients. Secondary analysis of symptomatic patients, comparing placental pathology between mild disease(mCOVID) and worse disease(moderate, severe, or critical-defined by 2020 NIH guidelines) (dCOVID), also performed. Of 112 patients, 53 (47%) had symptoms. Twenty-seven (24.1%) patients had evidence of vascular malperfusion; 26 (23.2%) had MVM. When comparing aCOVID and sCOVID patients, no difference in rate of vascular malperfusion identified, nor any differences in rates of FVM or MVM. Among sCOVID patients (n = 53), 39 (74%) had mCOVID and 14 (26%) had dCOVID (moderate n = 4, severe n = 9, critical n = 1). Patients with dCOVID had earlier median delivery GA (37.4wks vs 39.2wks, p = .03). No difference in latency from diagnosis to delivery seen between mCOVID and dCOVID groups (4.4 vs 3.0wks, p = .96). Twelve (30.8%) patients had vascular malperfusion on pathology, all had mCOVID (p = .02). Eleven (28.2%) mCOVID patients had MVM; no dCOVID patients had evidence of vascular malperfusion (p = .03). No difference in FVM was found between cohorts. Symptomatic COVID-19 infection did not impact placental vasculature differently than asymptomatic infection, even when stratifying by trimester of infection. Among pregnant patients with symptomatic COVID-19, mild disease was associated with placental vascular changes on the maternal side while severe disease was not. Further studies are needed to understand the implications of these findings.

Placental uterine artery embolization followed by delayed hysterectomy for placenta percreta: A case series.

We describe outcomes of patients with suspected placenta percreta treated with placental uterine artery embolization (P-UAE) followed by delayed hysterectomy. This is a prospective case series of subjects from 2005 to 2018 with suspected placenta percreta who underwent P-UAE at the time of cesarean delivery followed by delayed hysterectomy. Both scheduled and unscheduled surgical cases were included. Maternal characteristics, surgical approaches, intra- and postoperative outcomes were abstracted from medical records. In total, twenty-two subjects were included. Median (interquartile range, IQR) delivery gestational age was 34.6 (31.9, 35.7) weeks, occurring as scheduled in 17 (77.3%) subjects and unscheduled in 5 (22.7%). Delayed hysterectomy was performed as scheduled in 17 (77.3%) subjects at a median (IQR) 40.5 (38.0, 44.0) days after delivery, and 5 (22.7%) subjects had a hysterectomy prior to scheduled date, median (IQR) 27.0 (17.0, 35.0) days after delivery. Indications for the 5 unscheduled hysterectomies included bleeding (n = 3) and suspected endometritis (n = 2). Three subjects (13.6%) received a blood transfusion (1, 3, 3 units) during delivery, and 7 (31.8%) were transfused during delayed hysterectomy (median [IQR] 2 [1,3] units). Three (13.6%) subjects had bladder resection at the time of hysterectomy; 1 (4.5%) had an unintentional cystotomy and 1 (4.5%) had a ureteral injury. P-UAE followed by delayed hysterectomy appears to be a safe and feasible, although appropriate patient selection and close surveillance are imperative, as 22.7% of patients underwent unscheduled hysterectomy.

Polyreactive IgM initiates complement activation by PF4/heparin complexes through the classical pathway.

The mechanisms by which exposure to heparin initiates antibody responses in many, if not most, recipients are poorly understood. We recently demonstrated that antigenic platelet factor 4 (PF4)/heparin complexes activate complement in plasma and bind to B cells. Here, we describe how this process is initiated. We observed wide stable variation in complement activation when PF4/heparin was added to plasma of healthy donors, indicating a responder "phenotype" (high, intermediate, or low). Proteomic analysis of plasma from these healthy donors showed a strong correlation between complement activation and plasma immunoglobulin M (IgM) levels (r = 0.898; P < .005), but not other Ig isotypes. Complement activation response to PF4/heparin in plasma displaying the low donor phenotype was enhanced by adding pooled IgM from healthy donors, but not monoclonal IgM. Depletion of IgM from plasma abrogated C3c generation by PF4/heparin. The complement-activating features of IgM are likely mediated by nonimmune, or natural, IgM, as cord blood and a monoclonal polyreactive IgM generate C3c in the presence of PF4/heparin. IgM facilitates complement and antigen deposition on B cells in vitro and in patients receiving heparin. Anti-C1q antibody prevents IgM-mediated complement activation by PF4/heparin complexes, indicating classical pathway involvement. These studies demonstrate that variability in plasma IgM levels correlates with functional complement responses to PF4/heparin. Polyreactive IgM binds PF4/heparin, triggers activation of the classical complement pathway, and promotes antigen and complement deposition on B cells. These studies provide new insights into the evolution of the heparin-induced thrombocytopenia immune response and may provide a biomarker of risk.

Identification and Management of Abdominal Wall Varices in Pregnancy.

BACKGROUND: Portal hypertension in pregnancy is associated with elevated risk of variceal hemorrhage. Ectopic varices, those located outside the esophagus or stomach, are rare but have a high risk of associated maternal morbidity or mortality. CASE: A 31-year-old woman, gravida 2 para 0010, with cirrhosis and portal hypertension was found to have abdominal wall ectopic varices on third-trimester obstetric ultrasonography. Computed tomography angiography confirmed these findings. Given concern for catastrophic hemorrhage during delivery, she underwent transjugular intrahepatic portosystemic shunt placement at 35 weeks of gestation, with reduction in the pressure gradient within the portosystemic circulation. She subsequently underwent an uncomplicated cesarean delivery. CONCLUSION: Identification of ectopic varices on obstetric ultrasonography may allow for treatment before delivery, decreasing the risk of serious maternal morbidity or mortality.

Closed-Incision Negative-Pressure Therapy in Obese Patients Undergoing Cesarean Delivery: A Randomized Controlled Trial.

Background Postcesarean wound morbidity is a costly complication of cesarean delivery for which preventative strategies remain understudied. Objective We compared surgical site occurrences (SSOs) in cesarean patients receiving closed-incision negative-pressure therapy (ciNPT) or standard-of-care (SOC) dressing. Study Design A single-center randomized controlled trial compared ciNPT (5-7 days) to SOC dressing (1-2 days) in obese women (body mass index [BMI] ≥ 35), undergoing cesarean delivery between 2012 and 2014. Participants were randomized 1:1 and monitored 42 ± 10 days postoperatively. The primary outcome SSOs included unanticipated local inflammation, wound infection, seroma, hematoma, dehiscence, and need for surgical or antibiotic intervention. Results Of the 92 randomized patients, 82 completed the study. ciNPT and SOC groups had similar baseline characteristics. Mean BMI was 46.5 ± 6.5 and no treatment-related serious adverse events. Compared with SOC, the ciNPT group had fewer SSOs (7/43 [16.3%] vs. 2/39 [5.1%], respectively; p = 0.16); significantly fewer participants with less incisional pain both at rest (39/46 [84.8%] vs. 20/46 [43.5%]; p < 0.001) and with incisional pressure (42/46 [91.3%] vs. 25/46 [54.3%]; p < 0.001); and a 30% decrease in total opioid use (79.1 vs. 55.9 mg morphine equivalents, p = 0.036). Conclusion A trend in SSO reduction and a statistically significant reduction in postoperative pain and narcotic use was observed in women using ciNPT.

Novel pathogenic variants in FOXP3 in fetuses with echogenic bowel and skin desquamation identified by ultrasound.

Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a rare, X-linked recessive disease that affects regulatory T cells (Tregs) resulting in diarrhea, enteropathy, eczema, and insulin-dependent diabetes mellitus. IPEX syndrome is caused by pathogenic alterations in FOXP3 located at Xp11.23. FOXP3 encodes a transcription factor that interacts with several partners, including NFAT and NF-κB, and is necessary for the proper cellular differentiation of Tregs. Although variable, the vast majority of IPEX syndrome patients have onset of disease during infancy with severe enteropathy. Only five families with prenatal presentation of IPEX syndrome have been reported. Here, we present two additional prenatal onset cases with novel inherited frameshift pathogenic variants in FOXP3 that generate premature stop codons. Ultrasound findings in the first patient identified echogenic bowel, echogenic debris, scalp edema, and hydrops. In the second patient, ultrasound findings included polyhydramnios with echogenic debris, prominent fluid-filled loops of bowel, and echogenic bowel. These cases further broaden the phenotypic spectrum of IPEX syndrome by describing previously unappreciated prenatal ultrasound findings associated with the disease.