Maternal SARS-CoV-2 infection in pregnancy disrupts gene expression in Hofbauer cells with limited impact on cytotrophoblasts.

BACKGROUND: Hofbauer cells (HBCs) and cytotrophoblasts (CTBs) are major cell populations in placenta. The indirect impact of maternal SARS-CoV-2 disease on these cells that are not directly infected has not been extensively studied. Herein, we profiled gene expression in HBCs and CTBs isolated from placentae of recovered pregnant subjects infected with SARS-CoV-2 during all trimesters of pregnancy, placentae from subjects with active infection, SARS-CoV-2 vaccinated subjects, and those who were unexposed to the virus. METHODS: Placentae were collected within 4 h post-delivery and membrane-free tissues were enzymatically digested for the isolation of HBCs and CTBs. RNA extracted from HBCs and CTBs were sequenced using 150bp paired-end reads. Differentially expressed genes (DEGs) were identified by DESeq2 package in R and enriched in GO Biological Processes, KEGG Pathway, Reactome Gene Sets, Hallmark Gene Sets, and Canonical Pathways. Protein-protein interactions among the DEGs were modelled using STRING and BioGrid. RESULTS: Pregnant subjects (n = 30) were recruited and categorized into six groups: infected with SARS-CoV-2 in i) the first (1T, n = 4), ii) second (2T, n = 5), iii) third (3T, n = 5) trimester, iv) tested positive at delivery (Delivery, n = 5), v) never infected (Control, n = 6), and vi) fully mRNA-vaccinated by delivery (Vaccinated, n = 5). Compared to the Control group, gene expression analysis showed that HBCs from infected subjects had significantly altered gene expression profiles, with the 2T group having the highest number of DEGs (1,696), followed by 3T and 1T groups (1,656 and 958 DEGs, respectively). These DEGs were enriched for pathways involved in immune regulation for host defense, including production of cytokines, chemokines, antimicrobial proteins, ribosomal assembly, neutrophil degranulation inflammation, morphogenesis, and cell migration/adhesion. Protein-protein interaction analysis mapped these DEGs with oxidative phosphorylation, translation, extracellular matrix organization, and type I interferon signaling. Only 95, 23, and 8 DEGs were identified in CTBs of 1T, 2T, and 3T groups, respectively. Similarly, 11 and 3 DEGs were identified in CTBs and HBCs of vaccinated subjects, respectively. Reassuringly, mRNA vaccination did not induce an inflammatory response in placental cells. CONCLUSIONS: Our studies demonstrate a significant impact of indirect SARS-CoV-2 infection on gene expression of inner mesenchymal HBCs, with limited effect on lining CTB cells isolated from pregnant subjects infected and recovered from SARS-CoV-2. The pathways associated with these DEGs identify potential targets for therapeutic intervention.

Vertical Transmission of SARS-CoV-2-Specific Antibodies and Cytokine Profiles in Pregnancy.

Despite intensive characterization of immune responses after COVID-19 infection and vaccination, research examining protective correlates of vertical transmission in pregnancy are limited. Herein, we profiled humoral and cellular characteristics in pregnant women infected or vaccinated at different trimesters and in their corresponding newborns. We noted a significant correlation between spike S1-specific IgG antibody and its RBD-ACE2 blocking activity (receptor-binding domain-human angiotensin-converting enzyme 2) in maternal and cord plasma (P < .001, R > 0.90). Blocking activity of spike S1-specific IgG was significantly higher in pregnant women infected during the third trimester than the first and second trimesters. Elevated levels of 28 cytokines/chemokines, mainly proinflammatory, were noted in maternal plasma with infection at delivery, while cord plasma with maternal infection 2 weeks before delivery exhibited the emergence of anti-inflammatory cytokines. Our data support vertical transmission of protective SARS-CoV-2-specific antibodies. This vertical antibody transmission and the presence of anti-inflammatory cytokines in cord blood may offset adverse outcomes of inflammation in exposed newborns.

Clinical and Demographic Characteristics of Patient-Initiated Encounters Before the 6-Week Postpartum Visit.

OBJECTIVE: To identify characteristics associated with a higher likelihood of patient-initiated encounters with a health care professional before the scheduled 6-week postpartum visit. METHODS: We performed a retrospective cohort study of postpartum persons who received prenatal care and delivered at a single academic level IV maternity care center in 2019. We determined associations between maternal sociodemographic and obstetric characteristics and the likelihood of patient-initiated early postpartum encounters with χ2 tests for categorical variables and Wilcoxon rank sum tests for continuous and ordinal variables. RESULTS: A total of 796 patients were included in our analysis, and 324 (40.7%) initiated an early postpartum encounter. Significantly more postpartum persons who initiated early postpartum encounters were primiparous persons (54.3%) than multiparous (33.8%) persons (P < .001). Postpartum persons who desired breastfeeding or who had prolonged maternal hospitalization, episiotomy, or cesarean or operative vaginal delivery were also significantly more likely to initiate early postpartum encounters (all P≤.002). Of postpartum persons who initiated early encounters, 44 (13.6%) initiated in-person visits, 138 (42.6%) initiated telephone or patient portal communication, and 142 (43.8%) initiated encounters of both types. Specifically, 39.2% of postpartum persons initiated at least one early postpartum encounter for lactation support, and nearly half of early postpartum encounters occurred during the first week after hospital discharge. CONCLUSION: Early postpartum encounters were more common among primiparas and postpartum persons who were breastfeeding or had prolonged hospitalization, episiotomy, cesarean delivery, or operative vaginal delivery. Future studies should focus on the development of evidence-based guidelines for recommending early postpartum visits.

Leveraging In Situ Simulation for Implementation of Teleobstetric Consultation Services in Rural and Community Hospitals.

Background: Our institution implemented acute-care obstetric (OB) telemedicine (TeleOB) to address rural disparities across our health system. We sought to determine whether in situ simulations with embedded TeleOB consultation increase participants' comfort managing OB emergencies and comfort with and likelihood of using TeleOB. Methods: Rural site care teams participated in multidisciplinary in situ OB emergency simulations. Physicians in OB and neonatology at the referral center assisted via telemedicine consultation. Participants were surveyed before and after the simulations and six months later regarding their experience during the simulations. Results: Participants reported increased comfort with TeleOB activation, indications, and workflow processes, as well as increased comfort managing OB emergencies. Participants also reported significantly increased likelihood of using TeleOB in the future. Conclusions: Consistent with previous work, in situ simulation with embedded telemedicine consultations is an effective approach to facilitate telemedicine implementation and promote use by rural clinicians.

Virtual Obstetric Hospitalist Support for Obstetric Emergencies and Deliveries: The Mayo Clinic Experience.

Objective: To implement use of obstetric (OB) hospitalist telemedicine services (TeleOB) to support clinicians facing OB emergencies in low-resource hospital settings. Methods: TeleOB was staffed by OB hospitalists working at a tertiary maternity center. The service was available via real-time high-definition audio/video technology for providers at 17 outlying hospitals across a health system spanning two states. The initial 25 service activations are described. Results: TeleOB supported 17 deliveries, two postpartum emergency department (ED) consultations, and four antenatal ED consultations. In 10 of 17 (59%) deliveries, teleneonatology was jointly activated to support neonatal resuscitation. Sixteen (94%) deliveries occurred in multiparas, and five (29%) resulted from spontaneous preterm labor. Eighty percent (20/25) of activations occurred in facilities without maternity services. Conclusions: A TeleOB service staffed by OB hospitalists successfully supports hospitals in an integrated health care system. TeleOB is feasible for support of hospitals with no delivery facilities or with limited maternity care resources.

Development and multicenter international validation of a diagnostic tool to differentiate between pemphigoid gestationis and polymorphic eruption of pregnancy.

BACKGROUND: Pemphigoid gestationis (PG) and polymorphic eruption of pregnancy (PEP) may be similar morphologically but confer different maternal and fetal risks. Direct immunofluorescence is the gold standard test used to differentiate between the 2 diagnoses but is not always available. OBJECTIVE: To develop and validate a clinical scoring system to differentiate PG from PEP. METHODS: After developing a scoring system based on differentiating clinical factors reported in existing literature, we tested its diagnostic accuracy in a retrospective international multicenter validation study in collaboration with the European Academy of Dermatology and Venereology's Skin Diseases in Pregnancy Taskforce. RESULTS: Nineteen pregnancies (16 patients) affected by PG and 39 pregnancies (39 patients) affected by PEP met inclusion criteria. PG had a mean score of 4.6 (SD, 2.5) and PEP had a mean score of -0.3 (SD, 2.0). The area under the curve was 0.93 (95% CI, 0.86-1.00). Univariate analysis revealed that almost all criteria used in the scoring system were significantly different between the groups (P < .05), except for skip pregnancy and multiple gestations, which were then removed from the final scoring system. LIMITATIONS: Small retrospective study. CONCLUSION: The Pregnancy Dermatoses Clinical Scoring System may be useful to differentiate PG from PEP in resource-limited settings.

Maternal Factors and Placental Pathologies Associated with a Diagnosis of Chronic Villitis.

OBJECTIVE: To evaluate maternal risk factors associated with chronic villitis of unknown etiology (VUE) and to describe cooccurring placental pathologies. STUDY DESIGN: A retrospective case-control study was conducted using placental pathology records from deliveries ≥ 20 weeks between 2010 and 2018. Cases were placentas with documented chronic villitis without infectious cause, hereafter called VUE. Controls were placentas without this diagnosis, matched to the cases 2:1. Maternal and neonatal demographic and clinical data were collected. Descriptive statistics are reported with Fisher's exact test or a chi-squared test, as appropriate, and multivariable conditional logistic regression was conducted. RESULTS: Our study included 352 cases with VUE and 657 controls. A diagnosis of gestational diabetes (p = 0.03) and gestational hypertension (p = 0.06) was 1.5 times more likely to occur in those with a VUE diagnosis. A trend was also seen for chronic hypertension (odds ratio [OR] = 1.7, p = 0.07) and preeclampsia (OR = 1.5, p = 0.09) compared with controls. Placentas with VUE, specifically high-grade VUE, were more likely to be small for gestational age (p = 0.01), and to be diagnosed with other placental findings including lymphoplasmacytic or chronic deciduitis (p < 0.01), maternal (p < 0.01) and fetal vascular malperfusion (p = 0.02), and chorionitis (acute or chronic; p < 0.01). CONCLUSION: Gestational diabetes and hypertension were associated with a diagnosis of VUE, and overall, VUE placentas have more abnormal placental findings compared with control. Understanding VUE risk factors may facilitate prenatal care strategies and counseling to achieve the best outcomes for pregnant patients and their neonates. KEY POINTS: · VUE is a common inflammatory lesion of the placenta.. · Gestational diabetes and hypertension are associated with a VUE diagnosis.. · Findings of other placental pathologies increase in VUE..

OB Nest randomized controlled trial: a cost comparison of reduced visit compared to traditional prenatal care.

BACKGROUND: Traditional prenatal care includes up to 13 in person office visits, and the cost of this care is not well-described. Alternative models are being explored to better meet the needs of patients and providers. OB Nest is a telemedicine-enhanced program with a reduced frequency of in-person prenatal visits. The cost implications of connected care services added to prenatal care packages are unclear. METHODS: Using data from the OB Nest randomized, controlled trial we analyzed the provider and staff time associated with prenatal care in the traditional and OB Nest models. Fewer visits were required for OB Nest, but given the compensatory increase in connected care activity and supplies, the actual cost difference is not known. Nursing and provider staff time was prospectively recorded for all patients enrolled in the OB Nest clinical trial. Published 2015 national wages for healthcare workers were used to calculate the actual labor cost of providing either traditional or OB Nest prenatal care in 2015 US dollars. Overhead expenses and opportunity costs were not considered. RESULTS: Total provider cost was decreased caring for the OB Nest participants, but nursing cost was increased. OB Nest care required an average of 160.8 (+/- 45.0) minutes provider time and 237 (+/- 25.1) minutes nursing time, compared to 215.0 (+/- 71.6) and 99.6 (+/- 29.7) minutes for traditional prenatal care (P < 0.01). This translated into decreased provider cost and increased nursing cost (P < 0.01). Supply costs increased, travel costs declined, and overhead costs declined in the OB Nest model. CONCLUSIONS: In this trial, labor cost for OB Nest prenatal care was 34% higher than for traditional prenatal care. The increased cost is largely attributable to additional nursing connected care time, and in some practice settings may be offset by decreased overhead costs and increased provider billing opportunities. Future efforts will be focused on development of digital solutions for some routine nursing tasks to decrease the overall cost of the model. TRIAL REGISTRATIONS: ClinicalTrials.gov Identifier: NCT02082275 .

Circumferential shoulder laceration after posterior axilla sling traction: a case report of severe shoulder dystocia.

BACKGROUND: Shoulder dystocia is an unpredictable and potentially catastrophic complication of vertex vaginal delivery. Posterior axilla sling traction (PAST) has recently been proposed as a method to resolve severe shoulder dystocia when commonly used techniques have failed. CASE PRESENTATION: A 33-year-old woman (gravida 5, para 0) at 35 weeks, 1 day gestation underwent induction of labor for poorly controlled type 2 diabetes mellitus. Delivery of the large-for-gestational-age infant (4,060 g) was complicated by intractable shoulder dystocia, relieved at 3 minutes with PAST, resulting in a deep, circumferential laceration of the fetal posterior shoulder and contralateral phrenic nerve palsy. CONCLUSIONS: PAST provides a potentially lifesaving option during intractable shoulder dystocia. Simulation or education about the technique facilitates its use when standard maneuvers fail. It is important to disseminate information about potential complications associated with these novel maneuvers.

Placental Immune Responses to Viruses: Molecular and Histo-Pathologic Perspectives.

As most recently demonstrated by the SARS-CoV-2 pandemic, congenital and perinatal infections are of significant concern to the pregnant population as compared to the general population. These outcomes can range from no apparent impact all the way to spontaneous abortion or fetal infection with long term developmental consequences. While some pathogens have developed mechanisms to cross the placenta and directly infect the fetus, other pathogens lead to an upregulation in maternal or placental inflammation that can indirectly cause harm. The placenta is a temporary, yet critical organ that serves multiple important functions during gestation including facilitation of fetal nutrition, oxygenation, and prevention of fetal infection in utero. Here, we review trophoblast cell immunology and the molecular mechanisms utilized to protect the fetus from infection. Lastly, we discuss consequences in the placenta when these protections fail and the histopathologic result following infection.

Effect of delayed misoprostol dosing interval for induction of labor: a retrospective study.

BACKGROUND: Induction of labor occurs in greater than 22% of all pregnancies in the United States. Previous studies have shown that misoprostol is more effective for induction than oxytocin or dinoprostone alone. The World Health Organization recommends vaginal misoprostol 25mcg every 6 hours and the American Congress of Obstetricians and Gynecologists recommends 25mcg vaginal misoprostol every three to 6 hours. Although route of administration and dosage of misoprostol has been extensively studied, little is known about the optimal dosing interval of vaginal misoprostol. METHODS: The primary objective of this study is to determine the effect of delayed vaginal misoprostol dosing, defined as any interval longer than 4.5 h, on time to vaginal delivery. Our hypothesis is that the routine dosing interval of 4 hours shortens times to vaginal delivery compared to delayed dosing, even when adjusted for the time of delay. Secondary objectives include the effect of delayed vaginal misoprostol dosing on cesarean section rate, operative vaginal delivery rate, maternal outcomes, and neonatal outcomes. We conducted a retrospective chart review of 323 inductions of labor at one academic institution. The primary outcome was the proportion of patients who achieved a vaginal delivery within 24 h. The group who received all doses of misoprostol within a 4.5 h dosing window (Routine Dosing Interval Group) was compared with the group who had any dosing deviation (Delayed Dosing Interval Group). RESULTS: Of 133 included patients, 64 subjects received routine interval dosing and 69 subjects received delayed interval dosing. The vaginal delivery rates within 24 h were 56% (36/64) and 20% (14/69), respectively (P < 10- 4). Spontaneous vaginal delivery rates were 86% (55/64) vs. 75% (52/69), respectively (P = .13). Kaplan Meier curves demonstrated statistically significant difference in time to vaginal delivery between groups, with a Cox Proportional Hazard ratio for routine dosing interval of 1.73 (P < 10- 5) unadjusted and 1.34 (P = .01) when adjusted for dosing delay. CONCLUSIONS: This retrospective study demonstrates a significant increase in delay-adjusted time to vaginal delivery when doses of vaginal misoprostol are delayed past 4.5 h.

Effect of frozen/thawed embryo transfer on birthweight, macrosomia, and low birthweight rates in US singleton infants.

BACKGROUND: Singleton infants conceived using assisted reproductive technology have lower average birthweights than naturally conceived infants and are more likely to be born low birthweight (<2500 gr). Lower birthweights are associated with increased infant and child mortality and poor adult health outcomes, including cardiovascular disease, hypertension, and diabetes. Data from registry and single-center studies suggest that frozen/thawed embryo transfer may be associated with larger birthweights. To date, however, a nationwide, full-population study on United States infants born using frozen/thawed embryo transfer has not been reported. OBJECTIVES: The objective of this study was to compare the effect of frozen/thawed vs fresh embryo transfer on birthweight outcomes for singleton, term infants conceived using in vitro fertilization in the United States between 2007 and 2014, including average birthweight and the risks of both macrosomia (>4000 g) and low birthweight (<2500 g). STUDY DESIGN: We used data from the Centers for Disease Control and Prevention's National Assisted Reproductive Technology Surveillance System to compare birthweight outcomes of live-born singleton, autologous oocyte, term (37-43 weeks) infants. Generalized linear models for all infants and stratified by infant sex were used to assess the relationship between frozen/thawed embryo transfer and birthweight, in grams. Infertility diagnosis, year of treatment, maternal age, maternal obstetric history, maternal and paternal race, and infant gestational age and sex were included in the models. Missing race data were imputed. The adjusted relative risks for macrosomia and low birthweight were evaluated using multivariable predicted marginal proportions from logistic regression models. RESULTS: In total, 180,184 singleton, term infants were included, with 55,898 (31.02%) having been conceived from frozen/thawed embryos. Frozen/thawed embryo transfer was associated with, on average, a 142 g increase in birthweight compared with infants born after fresh embryo transfer (P < .001). An interaction between infant sex and embryo transfer type was significant (P < .0001), with frozen/thawed embryo transfer having a larger effect on male infants by 16 g. The adjusted risk of a macrosomic infant was 1.70 times higher (95% confidence interval, 1.64-1.76) following frozen/thawed embryo transfer than fresh embryo transfer. However, adjusted risk of low birthweight following frozen/thawed embryo transfer was 0.52 (95% confidence interval, 0.48-0.56) compared with fresh embryo transfer. CONCLUSION: Frozen/thawed embryo transfer, in comparison with fresh embryo transfer, was associated with increased average birthweight in singleton, autologous oocytes, term infants born in the United States, with a significant interaction between frozen/thawed embryo transfer and infant sex. The risk of macrosomia following frozen/thawed embryo transfer was greater than that following fresh embryo transfer, but the risk of low birthweight among frozen/thawed embryo transfer infants was significantly decreased in comparison with fresh embryo transfer infants.

Birthweight in infants conceived through in vitro fertilization following blastocyst or cleavage-stage embryo transfer: a national registry study.

PURPOSE: In vitro fertilization (IVF) infants have lower birthweights than their peers, predisposing them to long-term health consequences. Blastocyst transfer (BT), at day 5-6 post-fertilization, is increasing in usage, partially due to improved pregnancy outcomes over cleavage-stage transfer (CT, day 2-3). Data to date, however, have been inconclusive regarding BT's effects on birthweight. METHODS: Participants included all US autologous, single-gestation, fresh embryo transfer cycles initiated from 2007 to 2014 that resulted in a term infant (N = 124,154) from the National Assisted Reproductive Technology Surveillance System. Generalized linear models including obstetric history, maternal demographics, and infant sex and gestational age were used to compare birthweight outcomes for infants born following BT (N = 67,169) with infants born following CT (N = 56,985) and to test for an interaction between transfer stage and single embryo transfer (SET). RESULTS: Infants born following BT were 6 g larger than those born following CT (p = 0.04), but rates of macrosomia (RR 1.00, 95% CI 0.96-1.04) and low birthweight (LBW, RR 1.00, 95% CI 0.93-1.06) were not different between the groups. The interaction between SET and transfer stage was significant (p = 0.02). Among SET infants, BT was associated with 19.26 g increased birthweight compared to CT (p = 0.008). CONCLUSIONS: The increase in birthweights identified following BT is unlikely to be clinically relevant, as there were no differences in rates of macrosomia or LBW. These findings are clinically reassuring and indicate that the increasing use of BT is unlikely to further decrease the on average lower birthweights seen in IVF infants compared to their naturally conceived peers.

Dystroglycan in human fetal membranes decreases in later gestation and with spontaneous membrane rupture.

BACKGROUND/AIMS: The transmembrane protein dystroglycan (DG) is known to anchor the cell membrane to the extracellular matrix, and is susceptible to cleavage by matrix metalloproteinases. This study tested the hypothesis that changes in DG abundance in fetal membranes (FM) occur late in gestation, with spontaneous rupture of membranes (SROM), and during labor. METHODS: FM were collected from a prospective cohort consisting of four groups of patients (term labor, term unlabored, preterm labor, and preterm unlabored). FM were subjected to immunohistochemical staining using antibodies specific for α- and ß-DG subunits, and staining intensity was graded by a blinded pathologist. RESULTS: α- and ß-DG staining was significantly decreased at term and after SROM (p < 0.05), but not in the presence of labor. CONCLUSIONS: Decreased DG intensity was seen in FM of patients at term and with SROM, but no change was observed with labor.

A Multidisciplinary Approach to the Treatment of Co-occurring Opioid Use Disorder and Posttraumatic Stress Disorder in Pregnancy: A Case Report.

Perinatal opioid use disorders negatively impact maternal and neonatal outcomes and are a public health problem of increasing severity. More than half of women with a substance use disorder have a history of posttraumatic stress disorder that, if not adequately addressed, can impede substance use disorder treatment. This case report describes complexities in the treatment of a pregnant woman with opioid use disorder and posttraumatic stress disorder and reviews the psychotherapeutic and pharmacologic approaches available to treat these co-occurring disorders in pregnancy. This case demonstrates the importance of early screening and intervention for co-occurring posttraumatic stress disorder in pregnant women who use substances in a closely coordinated, multidisciplinary approach to improve outcomes for women and their infants.

Maternal COVID-19 vaccination status and association with neonatal congenital anomalies.

Introduction: Despite recommendations for COVID-19 vaccination in pregnant people, the effect of vaccination on neonatal outcomes remains unknown. We sought to determine the association between COVID-19 vaccination status in pregnancy and presence of neonatally diagnosed congenital anomalies. Methods: A comprehensive vaccine registry was combined with a delivery database to create a cohort including all patients aged 16-55 years with a delivery event between December 10, 2020 and December 31, 2021 at a hospital within the Mayo Clinic Health System. Pregnancy and neonatal outcomes were analyzed in relation to vaccination status and timing, including a composite measure of congenital anomalies diagnosed in neonatal life. Comparisons between cohorts were conducted using chi-square test for categorical and Kruskal-Wallis test for continuous variables. A multivariable logistic regression was modeled to assess the association with congenital anomalies. Results: 5,096 mother-infant pairs were analyzed. A total of 1,158 were vaccinated, with 314 vaccinated in the first trimester. COVID-19 vaccination status, including vaccination during the first trimester of pregnancy, was not associated with an increased risk of composite congenital anomalies. When further examining congenital anomalies by organ system, we did demonstrate a significant difference in eye, ear, face, neck anomalies between vaccinated and not vaccinated groups (Table 3, Not vaccinated = 2.3%, Vaccinated = 3.3%, p-value 0.04) however we did not demonstrate this difference between the 1st trimester and not vaccinated groups (Not vaccinated = 2.3%, 1st Trimester = 2.5%, p-value 0.77). No differences were found between not vaccinated, vaccinated, or 1st trimester vaccinated groups for any other organ systems. There were no differences in birthweight by gestational age, APGAR scores, incidence of NICU admission, or living status of the neonate by vaccination status. Conclusion: We add additional information regarding the safety of COVID-19 vaccination status and timing as it pertains to neonatal composite congenital anomalies, with no association demonstrated. Our findings agree with prior literature that COVID-19 vaccination is not associated with adverse pregnancy outcomes or small for gestational age neonates. Further research is needed to elucidate the association between COVID-19 vaccination and eye, ear, face, neck, anomalies.

A Simple Risk Adjustment for Hospital-Level Nulliparous, Term, Singleton, Vertex, Cesarean Delivery Rates and Its Implications for Public Reporting.

BACKGROUND: The Joint Commission uses nulliparous, term, singleton, vertex, cesarean delivery (NTSV-CD) rates to assess hospitals' perinatal care quality through the Cesarean Birth measurement (PC-02). However, these rates are not risk-adjusted for maternal health factors, putting this measure at odds with the risk adjustment paradigm of most publicly reported hospital quality measures. Here, the authors tested whether risk adjustment for readily documented maternal risk factors affected hospital-level NTSV-CD rates in a large health system. METHODS: Included were all consecutive NTSV pregnancies from January 2019 to April 2023 across 10 hospitals in one health system. Logistic regression, adjusting for age, obesity, diabetes, and hypertensive disorders. was used to calculate hospital-level risk-adjusted NTSV-CD rates by multiplying observed vs. expected ratios for each hospital by the systemwide unadjusted NTSV-CD rate. The authors calculated intrahospital risk differences between unadjusted and risk-adjusted rates and calculated the percentage of hospitals qualifying for different reporting status after risk adjustment using the 30% Joint Commission reporting threshold rate. RESULTS: Of 23,866 pregnancies, 6,550 (27.4%) had cesarean deliveries. Across 10 hospitals, the number of deliveries ranged from 393 to 7,671, with unadjusted NTSV-CD rates ranging from 21.0% to 30.5%. Risk-adjusted NTSV-CD rates ranged from 21.5% to 30.4%, with absolute intrahospital differences in risk-adjusted vs. unadjusted rates ranging from -1.33% (indicating lower rate after risk adjustment) to 3.37% (indicating higher rate after risk adjustment). Three of 10 (30.0%) hospitals qualified for different reporting statuses after risk adjustment. CONCLUSION: Risk adjustment for age, obesity, diabetes, and hypertensive disorders is feasible and resulted in meaningful changes in hospital-level NTSV-CD rates with potentially impactful consequences for hospitals near The Joint Commission reporting threshold.

Effect of Anti-TNF Biologic Exposure During Pregnancy on Villitis of Unknown Etiology Diagnoses in Patients with Autoimmune Disease.

Tumor necrosis factor-α (TNF-α) antagonists are highly effective in controlling autoimmune diseases. This has led to speculation that they might also be useful in treating inflammatory placental conditions, such as chronic villitis of unknown etiology (VUE). VUE affects 10-15% of term placentas and is associated with recurrent fetal growth restriction (FGR) and pregnancy loss. We aimed to evaluate outcomes in patients with autoimmune diseases with and without anti-TNF-α biologic exposure during gestation. This retrospective cohort study compared pregnant women with autoimmune disease taking anti-TNF-α biologics (n = 89) to pregnant women with autoimmune disease but not taking a biologic (n = 53). We extracted data on all patients meeting our inclusion criteria over a 20-year period. Our primary outcome was the diagnosis of VUE by histology. Our secondary outcomes were maternal and neonatal complications such as preeclampsia, FGR, and neonatal intensive care admission. Kruskal-Wallis and chi-squared tests were performed as appropriate for statistical analysis. Maternal characteristics were comparable between groups, and there was no increase in adverse pregnancy outcomes based on anti-TNF-α treatment. Exposure to anti-TNF-α therapy had no significant effect on the incidence of VUE or other obstetric complications. Within the cohort exposed to anti-TNF-α biologics during pregnancy, the rate of VUE was 9.3%, which is comparable to the reported general population risk. Our data support the safety profile of biologic use in pregnancy.

Hospitalization in pregnancy due to human respiratory syncytial virus associated disease.

Background: Despite pregnancy being a state of physiologic immune alteration, it has not previously been described as a risk factor for hospitalization due to human respiratory syncytial virus (RSV). Case: This retrospective case series describes two cases of hospitalization due to RSV associated illness in pregnancy. Conclusion: It remains to be determined if the current RSV surge is more dangerous to pregnant patients than those in seasons past. These cases support the importance of maintaining RSV on the differential for respiratory illness in pregnancy.

Effect of peripartum Clostridioides difficile infection on pregnancy and neonatal outcomes: an observational study.

Background: The incidence of Clostridioides difficile infection (CDI) in peripartum women is rising, but limited data on its effect on maternal and neonatal outcomes are available. Objective: To study the effect of peripartum CDI on pregnancy and neonatal outcomes. Design: Retrospective cohort study. Methods: Patients with peripartum CDI 12 weeks before pregnancy through 6 weeks postpartum (January 1996-February 2018) were matched with controls (peripartum women without CDI) 1:1 by age, year of delivery, and prior pregnancies. McNemar's test and conditional logistic regression were used to analyze the effect of CDI on pregnancy and neonatal outcomes (complications, mode of delivery). p < 0.05 was considered statistically significant. Results: Overall, 101 cases and 100 controls (1997-2018) were included; median age 27 (range, 20-41) years. Timing of CDI was as follows: pre-pregnancy: 15.8% (n = 16), during pregnancy: 51.5% (n = 52), and postpartum: 32.7% (n = 33). The commonest risk factor was outpatient/emergency room visits. Pregnancy and neonatal outcomes were analyzed for 67 matched pairs with CDI before or during pregnancy. Cases had higher odds of cesarean delivery (p = 0.02) and lower odds of Group B Streptococcus (GBS) infection/colonization (p = 0.03). Odds of cesarean delivery remained high after controlling for labor arrest disorders [odds ratio (OR): 17.23 (95% confidence interval (CI), 2.19-543.19; p = 0.004)]; odds of GBS remained low after controlling for antibiotic use (OR: 0.25, 95% CI, 0.04-0.99; p = 0.049). Neonatal outcomes were similar in cases and controls. CDI treatment did not affect treatment-related or delivery outcomes. Conclusion: Peripartum CDI was associated with higher odds of cesarean delivery and lower odds of GBS infections. Larger studies exploring the effect of CDI on pregnancy and neonatal outcomes are needed.