Maternal Sepsis.

Sepsis is the second leading cause of pregnancy-related mortality in the United States. Early recognition, treatment, and escalation of care for the obstetric patient affected by sepsis mitigate the risk of mortality and improve patient outcomes. In this article, we provide an overview of maternal sepsis and address topics of maternal pathophysiology, early warning signs, diagnostic criteria, early goal-directed therapy, and contemporary critical care practices. We also present an overview of common etiologies of maternal sepsis and suggested treatment approaches.

Associations between Anemia and Outcomes of Pregnant Patients with Pyelonephritis.

OBJECTIVE: This study aims to determine if pregnant patients with both pyelonephritis and anemia are at an increased risk of adverse maternal outcomes compared with those with pyelonephritis without anemia. STUDY DESIGN: We conducted a retrospective cohort study utilizing the Nationwide Readmissions Database (NRD). Patients with antepartum pyelonephritis-associated hospitalizations from October 2015 to December 2018 were included. International Classification of Diseases codes were used to identify pyelonephritis, anemia, maternal comorbidities, and severe maternal morbidities. The primary outcome was a composite of severe maternal morbidity, as defined by the Centers for Disease Control criteria. Univariate statistical methods, weighted to account for complex survey methods in the NRD, were used to assess for associations between anemia, baseline characteristics, and patient outcomes. Weighted logistic and Poisson regressions were used to assess for associations between anemia and outcomes, adjusting for clinical comorbidities and other confounding factors. RESULTS: In total, 29,296 pyelonephritis admissions were identified, corresponding to a weighted national estimate of 55,135 admissions. Of these, 11,798 (21.3%) were anemic. The rate of severe maternal morbidity was higher among anemic patients than nonanemic patients (27.8% vs. 8.9%, respectively, p < 0.001), and remained higher after adjustment (adjusted relative risk [aRR] 2.86 [95% confidence interval [CI]: 2.67, 3.06]). Rates of individual components of severe maternal morbidities, including acute respiratory distress syndrome (4.0% vs. 0.6%, aRR 3.97 [95% CI: 3.10, 5.08]), sepsis (22.5% vs. 7.9%, aRR 2.64 [95% CI: 2.45, 2.85]), shock (4.5% vs. 0.6%, aRR 5.48 [95% CI: 4.32, 6.95]), and acute renal failure (2.9% vs. 0.8%, aRR 1.99 [95% CI: 1.55, 2.55]) were all higher for anemic pyelonephritis. The mean length of stay was also longer (25% average increase, 95% CI: 22%, 28%). CONCLUSION: Among pregnant patients with pyelonephritis, those with anemia are at greater risk of severe maternal morbidity and longer hospital stay. KEY POINTS: · Anemia is associated with longer stays for pyelo.. · Anemic pyelo patients have increased morbidity.. · Anemic pyelo patients have increased sepsis risk..

Are prediction models for vaginal birth after cesarean accurate?

BACKGROUND: The use of trial of labor after cesarean delivery calculators in the prediction of successful vaginal birth after cesarean delivery gives physicians an evidence-based tool to assist with patient counseling and risk stratification. Before deployment of prediction models for routine care at an institutional level, it is recommended to test their performance initially in the institution's target population. This allows the institution to understand not only the overall accuracy of the model for the intended population but also to comprehend where the accuracy of the model is most limited when predicting across the range of predictions (calibration). OBJECTIVE: The purpose of this study was to compare 3 models that predict successful vaginal birth after cesarean delivery with the use of a single tertiary referral cohort before continuous model deployment in the electronic medical record. STUDY DESIGN: All cesarean births for failed trial of labor after cesarean delivery and successful vaginal birth after cesarean delivery at an academic health system between May 2013 and March 2016 were reviewed. Women with a history of 1 previous cesarean birth who underwent a trial of labor with a term (≥37 weeks gestation), cephalic, and singleton gestation were included. Women with antepartum intrauterine fetal death or fetal anomalies were excluded. The probability of successful vaginal birth after cesarean delivery was calculated with the use of 3 prediction models: Grobman 2007, Grobman 2009, and Metz 2013 and compared with actual vaginal birth after cesarean delivery success. Each model's performance was measured with the use of concordance indices, Brier scores, and calibration plots. Decision curve analysis identified the range of threshold probabilities for which the best prediction model would be of clinical value. RESULTS: Four hundred four women met the eligibility criteria. The observed rate of successful vaginal birth after cesarean delivery was 75% (305/404). Concordance indices were 0.717 (95% confidence interval, 0.659-0.778), 0.703 (95% confidence interval, 0.647-0.758), and 0.727 (95% confidence interval, 0.669-0.779), respectively. Brier scores were 0.172, 0.205, and 0.179, respectively. Calibration demonstrated that Grobman 2007 and Metz vaginal birth after cesarean delivery models were most accurate when predicted probabilities were >60% and were beneficial for counseling women who did not desire to have vaginal birth after cesarean delivery but had a predicted success rates of 60-90%. The models underpredicted actual probabilities when predicting success at <60%. The Grobman 2007 and Metz vaginal birth after cesarean delivery models provided greatest net benefit between threshold probabilities of 60-90% but did not provide a net benefit with lower predicted probabilities of success compared with a strategy of recommending vaginal birth after cesarean delivery for all women . CONCLUSION: When 3 commonly used vaginal birth after cesarean delivery prediction models are compared in the same population, there are differences in performance that may affect an institution's choice of which model to use.

Chorioamnionitis and Infectious Complications after Vaginal Delivery.

OBJECTIVE: To estimate the incidence of and define risk factors for postpartum infectious complications after vaginal birth after cesarean (VBAC) complicated by chorioamnionitis. STUDY DESIGN: A secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit Cesarean Registry was performed. The primary outcome was a composite of postpartum infection: endometritis, sepsis, pelvic abscess, urinary tract infection, necrotizing fasciitis, and septic pelvic thrombophlebitis. Peripartum predictors were compared using parametric and nonparametric tests, as appropriate, and multivariate predictors assessed using logistic regression. RESULTS: A total of 559 subjects had chorioamnionitis in labor and a successful VBAC. Twenty-four (4.3%) subjects experienced the primary outcome, mainly due to endometritis (19/24). Significant factors included preterm delivery <32 weeks (odds ratio [OR]: 3.05, 95% confidence interval [CI]: 1.32-7.06) and body mass index (BMI) ≥40 (OR: 4.63, 95% CI: 1.25-17.14). Receipt of postpartum antibiotics was protective against postpartum infection (OR: 0.28, 95% CI: 0.12-0.65). In multivariate analysis, preterm delivery <32 weeks, BMI ≥40, and receipt of postpartum antibiotics remained associated with postpartum infection. CONCLUSION: Nearly 5% of women with chorioamnionitis had a postpartum infectious complication after vaginal delivery, with higher rates in those delivering at <32 weeks and with prepregnancy BMI ≥40. Receipt of postpartum antibiotics decreased the odds of postpartum infection markedly.

Group B Streptococcus (GBS) Colonization and Disease among Pregnant Women: A Historical Cohort Study.

Background: Maternal GBS colonization is associated with early-onset neonatal sepsis and extensive efforts are directed to preventing this complication. Less is known about maternal risks of GBS colonization. We seek to provide a modern estimate of the incidence and impact of maternal GBS colonization and invasive GBS disease. Methods: A single center historical cohort study of all births between 2003 and 2015 was performed. Data was collected via electronic health record abstraction using an institutional specific tool. Descriptive statistics were performed regarding GBS status. Inferential statistics were performed comparing risk of adverse pregnancy outcomes in cohorts with and without GBS colonization as well as cohorts with GBS colonization and invasive GBS disease. Results: A total of 60,029 deliveries were included for analysis. Overall, 21.6% of the population was GBS colonized and 0.1% had invasive GBS disease. GBS colonization was associated with younger maternal age, Black race, non-Hispanic ethnicity, chronic hypertension, preexisting diabetes, and tobacco use (p<0.01). In the adjusted analyses, there was an increased risk of gestational diabetes (aRR 1.21, 95% CI 1.11-1.32) in colonized pregnancies and a decreased incidence of short cervix (aRR 0.64, 95% CI 0.52-0.79), chorioamnionitis (aRR 0.76, 95% CI 0.66-0.87), wound infection (aRR 0.75, 95% CI 0.64-0.88), and operative delivery (aRR 0.85, 95% CI 0.83-0.88). Conclusions: This modern-day large cohort of all births over a 12-year period demonstrates a GBS colonization rate of 21.6%. This data reflects a need to assess maternal and perinatal outcomes in addition to neonatal GBS sepsis rates to inform decisions regarding the utility of maternal vaccination.

Placenta Accreta Spectrum.

Placenta accreta spectrum, formerly known as morbidly adherent placenta, refers to the range of pathologic adherence of the placenta, including placenta increta, placenta percreta, and placenta accreta. The most favored hypothesis regarding the etiology of placenta accreta spectrum is that a defect of the endometrial-myometrial interface leads to a failure of normal decidualization in the area of a uterine scar, which allows abnormally deep placental anchoring villi and trophoblast infiltration. Maternal morbidity and mortality can occur because of severe and sometimes life-threatening hemorrhage, which often requires blood transfusion. Although ultrasound evaluation is important, the absence of ultrasound findings does not preclude a diagnosis of placenta accreta spectrum; thus, clinical risk factors remain equally important as predictors of placenta accreta spectrum by ultrasound findings. There are several risk factors for placenta accreta spectrum. The most common is a previous cesarean delivery, with the incidence of placenta accreta spectrum increasing with the number of prior cesarean deliveries. Antenatal diagnosis of placenta accreta spectrum is highly desirable because outcomes are optimized when delivery occurs at a level III or IV maternal care facility before the onset of labor or bleeding and with avoidance of placental disruption. The most generally accepted approach to placenta accreta spectrum is cesarean hysterectomy with the placenta left in situ after delivery of the fetus (attempts at placental removal are associated with significant risk of hemorrhage). Optimal management involves a standardized approach with a comprehensive multidisciplinary care team accustomed to management of placenta accreta spectrum. In addition, established infrastructure and strong nursing leadership accustomed to managing high-level postpartum hemorrhage should be in place, and access to a blood bank capable of employing massive transfusion protocols should help guide decisions about delivery location.

Perioperative Antibiotic Choice in Labored versus Unlabored Cesareans and Risk of Postcesarean Infectious Morbidity.

OBJECTIVE: This study aims to estimate postcesarean infectious morbidity in women receiving perioperative ß-lactam versus non-ß-lactam antibiotics. METHODS: We conducted a retrospective cohort analysis of the Maternal-Fetal Medicine Unit Cesarean Registry. The exposure was ß-lactam perioperative antibiotics versus non-ß-lactam regimens at cesarean delivery (CD). We stratified by labored versus unlabored CD. The primary composite outcome included wound infection, seroma, hematoma, endometritis, readmission due to wound complication, or debridement. Multivariable logistic regression estimated odds of wound complication by antibiotic regimen after adjusting for relevant confounders. RESULTS: Our analysis included 43,735 women who delivered via CD, 48% following labor. In both groups, 95% of women received ß-lactam antibiotics. In the labored CD group (n = 20,860), there was no significant difference in primary outcome by ß-lactam versus non-ß-lactam antibiotics (10.5 vs. 9.9%, p = 0.53). In the unlabored CD group (n = 22,875), women receiving non-ß-lactam antibiotics were more likely to experience a wound complication compared with those in the ß-lactam group (6.2 vs. 4.7%, p = 0.02, adjusted odds ratio: 1.39, 95% confidence interval: 1.08-1.80) after adjustment for clinical confounders. CONCLUSION: In unlabored CD, non-ß-lactam antibiotics have a higher risk of wound complications compared with ß-lactam regimens. Further study to optimize antibiotic prophylaxis for ß-lactam allergic women undergoing unlabored CD is warranted.

Chagas Disease Screening in Maternal Donors of Publicly Banked Umbilical Cord Blood, United States.

To assess patterns of Chagas disease, we reviewed results of screening umbilical cord blood from a US public cord blood bank during 2007-2014. Nineteen maternal donors tested positive for Trypanosoma cruzi parasites (0.04%). Because perinatal transmission of Chagas disease is associated with substantial illness, targeted prenatal programs should screen for this disease.

Medical and obstetric complications among pregnant women with cystic fibrosis.

OBJECTIVE: The objective of this study was to estimate the nationwide prevalence of cystic fibrosis (CF) in pregnancy and determine what medical complications exist at delivery among pregnant women with CF. STUDY DESIGN: The Nationwide Inpatient Sample (NIS) was queried for all delivery-related discharges. Women with CF were identified by International Classification of Diseases, 9th revision, Clinical Modifications codes and compared with women without CF. The prevalence of selected severe medical complications was compared between the 2 groups (NIS years 2008-2010) using multivariable logistic regression and the linear change in prevalence of CF at delivery determined (NIS years 2000-2010). RESULTS: From 2000 to 2010, there was a significant linear increase in the prevalence of CF at delivery from 3.0 to 9.8 per 100,000 deliveries, in 2000 and 2010, respectively (R(2) = 0.92, P < .0001). From 2008-2010, there were 1119 deliveries to women with CF and 12,627,627 to women without CF. Women with CF were more likely to be white (P < .0001) and have diabetes (odds ratio [OR], 14.0; 95% confidence interval [CI], 11.8-16.7) or asthma (OR, 5.1; 95% CI, 4.3-6.1). Multivariable logistic regression demonstrated that women with CF were more likely to die (adjusted OR [aOR], 76.0; 95% CI, 31.6-183), require mechanical ventilation (aOR, 18.3; 95% CI, 10.8-31.2), or have pneumonia (aOR, 56.5; 95% CI, 43.2-74.1), acute renal failure (aOR, 17.3; 95% CI, 9.1-32.6), preterm labor (aOR, 2.2; 95% CI, 1.9-2.6), or an adverse composite CF outcome (aOR, 28.1; 95% CI, 21.8-36.3). CONCLUSION: Pregnant women with CF are more likely to die, require mechanical ventilation, and have infectious complications compared with women without CF, although the absolute risks are low and these events are relatively rare.

Acute infectious morbidity in multiple gestation.

OBJECTIVES: Physiologic and immunologic changes in pregnancy result in increased susceptibility to infection. These shifts are more pronounced in pregnancies complicated by multiple gestation. The objective of this study was to determine the association between multiple gestation and risk of infectious morbidity. STUDY DESIGN: The Nationwide Inpatient Sample for the years 2008-2010 was used to identify pregnant women during admission for delivery with International Classification of Diseases codes. Logistic regression was used to compute odds ratios and 95% confidence intervals for demographic data, preexisting medical conditions, and acute medical and infectious complications for women with multiple versus singleton gestations. RESULTS: Among women with multiple gestation, 38.4 per 1,000 women had an infectious complication compared to 12.8 per 1,000 women with singletons. The most significant infectious morbidity associated with multiple gestation was intestinal infections, pyelonephritis, influenza, and pneumonia. After controlling for confounding variables, infectious complications at delivery persisted for women with multiples, though the association was dependent on mode of delivery. CONCLUSIONS: Women with multiple gestations are at increased risk for infectious morbidity identified at the time of delivery. This association was diminished among women who had a cesarean suggesting that operative delivery is not responsible for this association.

Designing drug trials: considerations for pregnant women.

Clinical pharmacology studies that describe the pharmacokinetics and pharmacodynamics of drugs in pregnant women are critical for informing on the safe and effective use of drugs during pregnancy. That being said, multiple factors have hindered the ability to study drugs in pregnant patients. These include concerns for maternal and fetal safety, ethical considerations, the difficulty in designing appropriate trials to assess the study objectives, and funding limitations. This document summarizes the recommendations of a panel of experts convened by the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health. These experts were charged with reviewing the issues related to the development of preclinical and clinical drug studies in pregnant women and to develop strategies for addressing these issues. These findings may also be utilized in the development of future drug studies involving pregnant women and their fetus/neonate.

Urinary Tract Infection and Progression to Pyelonephritis: Group B Streptococcus versus E. coli.

Objective Group B Streptococcus (GBS) colonization of the lower urinary tract in pregnancy is associated with severe infections such as chorioamnionitis, endometritis, and pyelonephritis. The objective of this study was to compare rates of progression to pyelonephritis between GBS and Escherichia coli lower urinary tract infections (LUTIs), as well as compare infectious and obstetric morbidity secondary to these pathogens. Study Design Retrospective cohort of pregnant women with LUTIs (asymptomatic bacteria or acute cystitis [AC]) from a single health system between July 2013 and May 2019. Demographic, infectious, antepartum, and intrapartum data were abstracted from medical records of women with GBS or E. coli LUTI. The primary outcome was progression to pyelonephritis. Secondary outcomes included pyelonephritis-related anemia, sepsis, pyelonephritis length of stay (LOS), median gestational age (GA) at delivery, preterm delivery, and low birth weight (LBW). Logistic regression was used to calculate the adjusted odds of the primary outcome. Results Of 729 pregnant women with urinary colonization, 433 were culture positive for one of the aforementioned bacteria, with 189 (43.6%) having GBS and 244 (56.4%) having E. coli. Women with E. coli were more likely to be younger, use tobacco, have a history of AC, and have a history of preterm birth. Rates of progression to pyelonephritis were markedly higher with E. coli (15.6%) than with GBS (1.1%; p < 0.001). Median LOS for pyelonephritis and pyelonephritis-related morbidities did not differ. Median GA at delivery, preterm delivery, and LBW rates also did not differ. In adjusted analysis, controlling for history of AC, insurance status, tobacco use, prior preterm birth, primary infection type, and maternal age, women with GBS LUTI had markedly decreased odds of developing pyelonephritis in pregnancy compared with those with E. coli (adjusted odds ratio: 0.04, 95% confidence interval: 0.01-0.28). Conclusion Escherichia coli infections progress to pyelonephritis in pregnancy at markedly higher rates than GBS, although obstetric outcomes are similar.

Medical and infectious complications associated with pyelonephritis among pregnant women at delivery.

OBJECTIVE: Pyelonephritis is a common cause of antepartum admission and maternal morbidity. Medical complications associated with pyelonephritis during delivery are not well described; thus the objective of this study was to estimate medical, infectious, and obstetric complications associated with pyelonephritis during the delivery admission. STUDY DESIGN: We conducted a retrospective cohort study using the Nationwide Inpatient Sample (NIS) for the years 2008-2010. The NIS was queried for all delivery-related discharges. During the delivery admission, the ICD-9-CM codes for pyelonephritis were used to identify cases and were compared to women without pyelonephritis. A multivariable logistic regression model was constructed for various medical, infectious, and obstetric complications among women with pyelonephritis compared to women without, while controlling for preexisting medical conditions and demographics. RESULTS: During the years 2008-2010, there were 26,397 records with a diagnosis of pyelonephritis during the delivery admission, for a rate of 2.1 per 1000 deliveries. Women with pyelonephritis had increased associated risks for transfusion, need for mechanical ventilation, acute heart failure, pneumonia, pulmonary edema, acute respiratory distress syndrome, sepsis, acute renal failure, preterm labor, and chorioamnionitis, while controlling for preexisting medical conditions. CONCLUSIONS: Pyelonephritis at delivery admissions is associated with significant medical and infectious morbidity.

The effects of anemia on pregnancy outcome in patients with pyelonephritis.

OBJECTIVE: Pyelonephritis is a common infectious morbidity of pregnancy. Though anemia is commonly associated with pyelonephritis, there are little data describing the effect of pyelonephritis with anemia on pregnancy outcomes. The purpose of this study was to further assess the association of anemia with infectious morbidity and pregnancy complications among women with pyelonephritis. STUDY DESIGN: We conducted a retrospective cohort study of pregnant women admitted to Duke University Hospital between July 2006 and May 2012 with pyelonephritis. Demographic, laboratory, and clinical data from the subject's pregnancy and hospitalizations were analyzed. Patients with pyelonephritis and anemia (a hematocrit < 32) were compared to those without anemia. Descriptive statistics were used to compare the two groups. RESULTS: 114 pregnant women were admitted with pyelonephritis and 45 (39.5%) had anemia on admission. There was no significant difference in age, race, preexisting medical conditions, or urine bacterial species between patients with anemia and those without. Women with anemia were more likely to deliver preterm (OR 3.3 (95% CI 1.07, 11.4), P = 0.04). When controlling for race and history of preterm delivery, women with anemia continued to have increased odds of preterm birth (OR 6.0, CI 1.4, 35, P = 0.012). CONCLUSION: Women with pyelonephritis and anemia are at increased risk for preterm delivery.

Maternal and neonatal outcomes in patients with hepatitis C and intrahepatic cholestasis of pregnancy: The sum of the parts.

OBJECTIVE: Hepatitis C virus and intrahepatic cholestasis of pregnancy (ICP) are well-known independent risk factors for adverse outcomes in pregnancy. In addition, it is well-established that there is an association between Hepatitis C and ICP. This study's objective was to describe the impact of having both Hepatitis C and ICP on maternal and obstetric outcomes compared to patients having either Hepatitis C or ICP. METHODS: We conducted a retrospective cohort study of the Nationwide Readmissions Database, an all-payor sample of discharges from approximately 60% of US hospitalizations. Deliveries at 24-42+ weeks between 10/2015 and 12/2020 were included. Diagnosis of Hepatitis C and ICP, and outcomes related to severe maternal morbidity were identified using International Classification of Disease-10 codes. Patients were categorized based on Hepatitis C and ICP status. Weighted logistic and negative binomial regression analyses were used to evaluate the association between Hepatitis C and ICP status and outcomes, adjusting for patient and hospital characteristics. The primary outcome was any severe maternal morbidity; secondary outcomes included acute respiratory distress syndrome, acute kidney injury, sepsis, gestational diabetes, cesarean delivery, preterm birth, and hospital length of stay. We modeled interaction terms between ICP and Hepatitis C to assess whether there was a greater or lesser effect from having both conditions on outcomes than we would expect from additive combination of the individual components (i.e., synergy or antagonism). RESULTS: A total of 10,040,850 deliveries between 24-42+ weeks were identified. Of these, 45,368 had Hepatitis C only; 84,582 had ICP only; and 1,967 had both Hepatitis C and ICP. Patients with both Hepatitis C and ICP had 1.5-fold higher odds of developing severe maternal morbidity compared to having neither. There was an also an increased odds of severe maternal morbidity in patients with both Hepatitis C and ICP compared to patients with only Hepatitis C or ICP. Having both was also associated with higher odds of preterm birth and length of stay compared to having only Hepatitis C, only ICP, or neither (preterm birth: aOR 5.09, 95% CI 4.87-5.33 vs. neither; length of stay: 46% mean increase, 95% CI 35-58% vs. neither). Associations were additive-no significant interactions between hepatitis C and cholestasis were found on rates of severe maternal morbidity, acute respiratory distress syndrome, acute kidney injury, sepsis, cesarean section, or preterm birth (all p>0.05), and was minimal for gestational diabetes and length of stay. CONCLUSION: Hepatitis C and ICP are independent, additive risk factors for adverse maternal and obstetric outcomes. Despite physiologic plausibility, no evidence of a synergistic effect of these two diagnoses on outcomes was noted. These data may be useful in counseling patients regarding their increased risk of adverse outcomes when ICP presents in association with Hepatitis C versus ICP alone.

Alliance for Innovation on Maternal Health: Consensus Bundle on Sepsis in Obstetric Care.

Sepsis in obstetric care is one of the leading causes of maternal death in the United States, with Black, Asian/Pacific Islander, and American Indian/Alaska Native obstetric patients experiencing sepsis at disproportionately higher rates. State maternal mortality review committees have determined that deaths are preventable much of the time and are caused by delays in recognition, treatment, and escalation of care. The "Sepsis in Obstetric Care" patient safety bundle provides guidance for health care teams to develop coordinated, multidisciplinary care for pregnant and postpartum people by preventing infection and recognizing and treating infection early to prevent progression to sepsis. This is one of several core patient safety bundles developed by AIM (the Alliance for Innovation on Maternal Health) to provide condition- or event-specific clinical practices that should be implemented in all appropriate care settings. As with other bundles developed by AIM, the "Sepsis in Obstetric Care" patient safety bundle is organized into five domains: Readiness, Recognition and Prevention, Response, Reporting and Systems Learning, and Respectful, Equitable, and Supportive Care. The Respectful, Equitable, and Supportive Care domain provides essential best practices to support respectful, equitable, and supportive care to all patients. Further health equity considerations are integrated into the elements of each domain.

Programmatic and research priorities for improving influenza immunization of pregnant women.

Despite evidence regarding the benefits of influenza immunization during pregnancy for both the pregnant woman and her infant, as well as reassuring safety data, influenza vaccination rates in pregnancy have lagged. The 2009 influenza pandemic was accompanied by increased maternal vaccination rates. In this article, we review programmatic and research priorities with regard to overcoming barriers to influenza immunization of pregnant women.

Group B Streptococcus and Pregnancy: Critical Concepts and Management Nuances.

Importance: Group B Streptococcus (GBS) is a common pathogen with an effective treatment. However, it remains a significant cause of neonatal sepsis, morbidity, and mortality. The screening and management of this infection are some of the first concepts learned during medical training in obstetrics. However, effective screening and evidence-based management of GBS are nuanced with many critical caveats. Objective: The objectives of this review are to discuss the essential aspects of GBS screening and management and to highlight recent changes to recommendations and guidelines. Evidence Acquisition: Original research articles, review articles, and guidelines on GBS were reviewed. Results: The following recommendations are based on review of the evidence and professional society guidelines. Screening for GBS should occur between 36 weeks and the end of the 37th week. The culture swab should go 2 cm into the vagina and 1 cm into the anus. Patients can perform their own swabs as well. Penicillin allergy testing has been shown to be safe in pregnancy. Patients with GBS in the urine should be treated at term with antibiotic prophylaxis, independent of the colony count of the culture. Patients who are GBS-positive with preterm and prelabor rupture of membranes after 34 weeks are not candidates for expectant management, as this population has higher rates of neonatal infectious complications. Patients with a history of GBS colonization in prior pregnancy who are GBS-unknown in this current pregnancy and present with labor should receive intrapartum prophylaxis. Work on the GBS vaccine continues. Conclusions: Although all of the efforts and focus on neonatal early-onset GBS infection have led to lower rates of disease, GBS still remains a major cause of neonatal morbidity and mortality requiring continued vigilance from obstetric providers.

ß-Arrestin mediates oxytocin receptor signaling, which regulates uterine contractility and cellular migration.

Desensitization of the oxytocin receptor (OXTR) in the setting of prolonged oxytocin exposure may lead to dysfunctional labor, which increases the risk for cesarean delivery, and uterine atony, which may result in postpartum hemorrhage. The molecular mechanism for OXTR desensitization is through the agonist-mediated recruitment of the multifunctional protein ß-arrestin. In addition to its desensitizing function, ß-arrestins have recently been shown to simultaneously activate downstream signaling. We tested whether oxytocin stimulation promotes ß-arrestin-mediated OXTR desensitization in vivo and activates ß-arrestin-mediated mitogen-activated protein kinase (MAPK) growth signaling. Uterine muscle strips isolated from wild-type mice exhibited diminished uterine contractility following repeated exposure to oxytocin, whereas uterine muscle strips from ß-arrestin-1 and ß-arrestin-2 knockout mice showed no desensitization. Utilizing siRNA knockdown of ß-arrestin-1 and ß-arrestin-2 in HEK-293 cells expressing the OXTR, we demonstrated oxytocin-mediated MAPK signaling that was dependent on ß-arrestin-1 and ß-arrestin-2. Wild-type and ß-arrestin-1 and ß-arrestin-2 knockout mice receiving intravenous oxytocin also demonstrated oxytocin-mediated MAPK signaling that was dependent on ß-arrestin-1 and ß-arrestin-2. Finally, to test the significance of ß-arrestin-mediated signaling from the OXTR, HEK-293 cells expressing the OXTR showed ß-arrestin-dependent proliferation in a cell migration assay following oxytocin treatment. In conclusion, ß-arrestin is a multifunctional scaffold protein that mediates both desensitization of the OXTR, leading to decreases in uterine contractility, and MAPK growth signaling following stimulation by oxytocin. The development of unique OXTR ligands that prevent receptor desensitization may be a novel approach in the treatment of adverse clinical events secondary to prolonged oxytocin therapy.