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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. [ABSTRACT FROM AUTHOR]

Intraamniotic infection, also known as chorioamnionitis, is an infection with resultant inflammation of any combination of the amniotic fluid, placenta, fetus, fetal membranes, or decidua. Intraamniotic infection is a common condition noted among preterm and term parturients. However, most cases of intraamniotic infection detected and managed by obstetrician-gynecologists or other obstetric care providers will be noted among term patients in labor. Intraamniotic infection can be associated with acute neonatal morbidity, including neonatal pneumonia, meningitis, sepsis, and death. Maternal morbidity from intraamniotic infection also can be significant, and may include dysfunctional labor requiring increased intervention, postpartum uterine atony with hemorrhage, endometritis, peritonitis, sepsis, adult respiratory distress syndrome and, rarely, death. Recognition of intrapartum intraamniotic infection and implementation of treatment recommendations are essential steps that effectively can minimize morbidity and mortality for women and newborns. Timely maternal management together with notification of the neonatal health care providers will facilitate appropriate evaluation and empiric antibiotic treatment when indicated. Intraamniotic infection alone is rarely, if ever, an indication for cesarean delivery. [ABSTRACT FROM AUTHOR]

Intraamniotic infection, also known as chorioamnionitis, is an infection with resultant inflammation of any combination of the amniotic fluid, placenta, fetus, fetal membranes, or decidua. Intraamniotic infection is a common condition noted among preterm and term parturients. However, most cases of intraamniotic infection detected and managed by obstetrician-gynecologists or other obstetric care providers will be noted among term patients in labor. Intraamniotic infection can be associated with acute neonatal morbidity, including neonatal pneumonia, meningitis, sepsis, and death. Maternal morbidity from intraamniotic infection also can be significant, and may include dysfunctional labor requiring increased intervention, postpartum uterine atony with hemorrhage, endometritis, peritonitis, sepsis, adult respiratory distress syndrome and, rarely, death. Recognition of intrapartum intraamniotic infection and implementation of treatment recommendations are essential steps that effectively can minimize morbidity and mortality for women and newborns. Timely maternal management together with notification of the neonatal health care providers will facilitate appropriate evaluation and empiric antibiotic treatment when indicated. Intraamniotic infection alone is rarely, if ever, an indication for cesarean delivery. [ABSTRACT FROM AUTHOR]

In the United States, eradication and reduction of vaccine-preventable diseases through immunization has directly increased life expectancy by reducing mortality. Although immunization is a public priority, vaccine coverage among adult Americans is inadequate. The Institute of Medicine, the Community Preventive Services Task Force, and other public health entities have called for the development of innovative programs to incorporate adult vaccination into routine clinical practice. Obstetrician--gynecologists are well suited to serve as vaccinators of women in general and more specifically pregnant women. Pregnant women are at risk for vaccine-preventable disease-related morbidity and mortality and adverse pregnancy outcomes, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. In addition to providing direct maternal benefit, vaccination during pregnancy likely provides direct fetal and neonatal benefit through passive immunity (transplacental transfer of maternal vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2) vaccines specifically recommended during pregnancy and postpartum; 3) vaccines recommended during pregnancy and postpartum based on risk factors and special circumstances; 4) vaccines currently under research and development for licensure for maternal--fetal immunization; and 5) barriers to maternal immunization and available patient and health care provider resources. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Smoking in pregnancy reduces preeclampsia risk, but the mechanism of this effect is unknown. Prior studies have demonstrated that women with preeclampsia have lower placental adrenomedullin (AM) expression, and cigarette smoke extract (CSE) treatment of placental trophoblast cells in culture increases AM cellular production. We hypothesized that CSE alters trophoblast invasion through an AM-mediated mechanism, and that placental AM expression is greater among smokers. HTR-8/SVneo trophoblast cells were incubated for 24 hours in Matrigel-invasion chambers with 6 treatment groups: nonstimulated (NS), AM, AM inhibitor (AM22-52), 1% CSE, AM + AM22-52, and 1% CSE + AM22-52. Cells that penetrated the lower surface of the chambers were quantified, invasion indices were calculated, and compared using a 1-way analysis of variance with Bonferroni corrections for multiple comparisons. Trophoblast cells treated with both AM and 1% CSE demonstrated increased cellular invasion compared to NS controls (1.5-fold [P < .01] and 1.45-fold [P < .01], respectively). Cotreatment with the AM inhibitor significantly attenuated the increased invasion seen with both AM and CSE alone. Next, the placental tissue was obtained from 11 smokers and 11 nonsmokers at term and processed for immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (PCR) for AM. Placentas from smokers demonstrated more intense AM staining and increased AM gene (ADM) expression compared to placentas from nonsmokers (P = .004 for IHC, P = .022 for PCR). The CSE increases trophoblast cell invasion through an AM-mediated process, and placental AM expression is increased among term smokers compared to nonsmokers. These findings provide evidence that the AM pathway may play a role in the protection from preeclampsia seen in smokers. [ABSTRACT FROM PUBLISHER]

OBJECTIVE: To assess the effect of increased use of intravenous penicillin for group B streptococcus (Streptococcus agalactiae, GBS) antibiotic prophylaxis on non-GBS neonatal sepsis and antibiotic resistance. METHODS: We undertook a nonconcurrent cohort study. Microbiology cultures originating from infants with early-onset neonatal sepsis in our neonatal intensive care unit (NICU) from 1992 to 1999 were reviewed. Prevalence of non-GBS neonatal sepsis in the control period (January 1, 1992, through June 30,1995) was compared with that in the study period (October 1, 1995, through August 31, 1999), when the protocol changed. Chi-squared or Fisher exact tests were used to determine statistical significance. Resistance patterns were compared in similar fashion. RESULTS: The prevalence of non-GBS neonatal sepsis was 1.2 per 1,000 (36 of 31,133) live births before and 1.1 per 1,000 (32 of 28,733) five births after institution of the Centers for Disease Control and Prevention culture-based protocol (P = .97). Our power analysis assumed a doubling in the rate of non-GBS sepsis and required 21,220 live births per arm. Gram-negative and gram-positive sepsis prevalences were not significantly different. Escherichia coli and GBS resistance patterns did not change. CONCLUSION: Institution of a protocol for GBS antibiotic prophylaxis significantly decreased the rate of GBS neonatal sepsis but did not increase the rate of non-GBS neonatal sepsis. Antibiotic resistance patterns of these organisms were not affected. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Objective Tetanus toxoid, reduced diphtheria toxoid, and acellular pertusiss (Tdap) vaccine is recommended during each pregnancy, regardless of prior receipt. Data on reactogenicity and immunogenicity, particularly after repeated Tdap, are limited. We compared local injection-site and systemic reactions and serologic response following Tdap in (1) pregnant and nonpregnant women and (2) pregnant women by self-reported prior Tdap receipt. Study design Pregnant women (gestational age 20–34 weeks) and nonpregnant women receiving Tdap were enrolled in this observational study. Injection-site and systemic reactions were assessed for one week post-vaccination. Pertussis toxin, filamentous hemagglutinin, pertactin, fimbriae, tetanus and diphtheria specific IgG antibody titers were determined by standardized enzyme-linked immunosorbent assay at baseline and 28 days post-vaccination. Reactogenicity and serologic responses were compared by pregnancy status, and within pregnant women by self-reported prior Tdap receipt. Results 374 pregnant and 225 nonpregnant women were vaccinated. Severe local or systemic reactions or "any" fever were uncommon (≤3% for both groups). Moderate/severe injection-site pain was significantly higher in pregnant (17.9%) versus nonpregnant (11.1%) women, but did not prompt a healthcare visit. Proportions of other moderate/severe or any severe reactions were not significantly higher in pregnant compared to nonpregnant women. Moderate/severe (including pain) and severe reactions were not significantly higher in pregnant women receiving repeat versus first-time Tdap. Antibody titers increased from baseline to post-vaccination for all vaccine antigens in pregnant and nonpregnant women; post-vaccination titers against pertussis toxin and filamentous hemagglutinin were significantly higher in nonpregnant versus pregnant women (p < 0.01). Conclusion Tdap was well-tolerated in pregnant and nonpregnant women. Pregnant women were more likely to report moderate/severe pain at the Tdap injection-site compared with nonpregnant women, but did not necessitate medical visits. Prior Tdap receipt did not increase occurrence of moderate/severe local or systemic reactions in pregnant women. Serologic responses to all vaccine antigens were robust. Clinical Trial Registration@ClinicalTrials.gov. NCT02209623. https://clinicaltrials.gov/ct2/show/NCT02209623. [ABSTRACT FROM AUTHOR]

Objective This study aims to estimate postcesarean infectious morbidity in women receiving perioperative β-lactam versus non-β-lactam antibiotics. Methods We conducted a retrospective cohort analysis of the Maternal-Fetal Medicine Unit Cesarean Registry. The exposure was β-lactam perioperative antibiotics versus non-β-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 β-lactam antibiotics. In the labored CD group (n = 20,860), there was no significant difference in primary outcome by β-lactam versus non-β-lactam antibiotics (10.5 vs. 9.9%, p = 0.53). In the unlabored CD group (n = 22,875), women receiving non-β-lactam antibiotics were more likely to experience a wound complication compared with those in the β-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-β-lactam antibiotics have a higher risk of wound complications compared with β-lactam regimens. Further study to optimize antibiotic prophylaxis for β-lactam allergic women undergoing unlabored CD is warranted. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to identify risk factors associated with the development of septic pelvic thrombophlebitis (SPT). Study Design This is a secondary case-control study of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit Network Cesarean Registry. SPT was defined as suspected infectious thrombosis of the pelvic veins, often persistent febrile illness in the setting of antibiotic therapy for endometritis. Women with SPT were compared with those without SPT using descriptive statistics. Logistic regression models estimated the association between selected risk factors and SPT. Results Of 73,087 women in the cohort, 89 (0.1%) developed SPT. Women with SPT were more likely to be < 20 years old (33.7 vs. 10.6%, p < 0.001), black race (58.4 vs. 29.1%, p < 0.001), and nulliparous (51.1 vs. 23.3%, p < 0.001). Hypertensive disorders of pregnancy (32.6 vs. 11.8%, p < 0.001) and multiple gestation (12.5 vs. 7.4%, p = 0.03) were also more common in women with SPT. In the multivariable regression model, maternal age < 20, black race, multiple gestation, and preeclampsia were all significantly associated with increased odds of SPT (adjusted odds ratio [aOR]: 1.96, 95% confidence interval [CI]: 1.22,3.14; aOR: 2.6, 95% CI: 1.68,4.02; aOR: 2.10,95% CI: 1.13, 3.88; aOR: 2.91, 95% CI: 1.86, 4.57). Conclusion SPT is a rare pregnancy complication. Our analysis confirmed known risk factors (e.g., infections, cesarean delivery), and identified novel ones, including black race, young age, preeclampsia, and multiple gestation. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to identify risk factors associated with the development of septic pelvic thrombophlebitis (SPT). Study Design This is a secondary case-control study of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit Network Cesarean Registry. SPT was defined as suspected infectious thrombosis of the pelvic veins, often persistent febrile illness in the setting of antibiotic therapy for endometritis. Women with SPT were compared with those without SPT using descriptive statistics. Logistic regression models estimated the association between selected risk factors and SPT. Results Of 73,087 women in the cohort, 89 (0.1%) developed SPT. Women with SPT were more likely to be < 20 years old (33.7 vs. 10.6%, p < 0.001), black race (58.4 vs. 29.1 %,p < 0.001), and nulliparous (51.1 vs. 23.3%, p < 0.001). Hypertensive disorders of pregnancy (32.6 vs. 11.8%, p < 0.001) and multiple gestation (12.5 vs. 7.4%, p = 0.03) were also more common in women with SPT. In the multivariable regression model, maternal age < 20, black race, multiple gestation, and preeclampsia were all significantly associated with increased odds of SPT (adjusted odds ratio [aORj: 1.96, 95% confidence interval [CI]: 1.22, 3.14; aOR: 2.6, 95% CI: 1.68,4.02; aOR: 2.10,95% CI: 1.13, 3.88; aOR: 2.91, 95% CI: 1.86, 4.57). Conclusion SPT is a rare pregnancy complication. Our analysis confirmed known risk factors (e.g., infections, cesarean delivery), and identified novel ones, including black race, young age, preeclampsia, and multiple gestation. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to identify factors associated with an increased risk of post-operative wound infection in women with chorioamnionitis who undergo cesarean delivery.Methods: We conducted a retrospective cohort study of women with clinical chorioamnionitis who underwent cesarean delivery at a tertiary-care center between June 2010 and May 2013. Demographic data, labor and delivery details and post-operative outcomes were collected. Women with and without post-operative wound infections were compared.Results: Of 213 women with clinical chorioamnionitis who underwent cesarean delivery, 32 (15%) developed wound infections. Women with wound infection were more likely to have a body mass index (BMI) greater than or equal to 40 (p = 0.04), chronic hypertension (p = 0.03), leukocytosis on presentation (p = 0.046) or use tobacco (p = 0.002). Women who received ertapenem postpartum were less likely to develop wound infection than those who did not receive antibiotics (p = 0.02) or those that received ampicillin, gentamicin and clindamycin (p = 0.005).Conclusions: Elevated BMI, tobacco use, chronic hypertension and leukocytosis at admission were associated with an increased risk of wound infection. Ertapenem appeared to reduce the risk of post-operative wound infections in women who had chorioamnionitis and underwent cesarean delivery. This could be considered as a treatment option for this high-risk population. [ABSTRACT FROM AUTHOR]

Objective: We seek to characterize the effect of progesterone metabolites on spontaneous and oxytocin-induced uterine contractility. Study Design: Spontaneous contractility was studied in mouse uterine horns after treatment with progesterone, 2α-hydroxyprogesterone, 6β-hydroxyprogesterone (6β-OHP), 16α-hydroxyprogesterone (16α-OHP), or 17-hydroxyprogesterone caproate (17-OHPC) at 10−9 to 10−6 mol/L. Uterine horns were exposed to progestins (10−6 mol/L), followed by increasing concentrations of oxytocin (1-100 nmol/L) to study oxytocin-induced contractility. Contraction parameters were compared for each progestin and matched vehicle control using repeated measures 2-way analysis of variance. In vitro metabolism of progesterone by recombinant cytochrome P450 3A (CYP3A) microsomes (3A5, 3A5, and 3A7) identified major metabolites. Results: Oxytocin-induced contractile frequency was decreased by 16α-OHP (P = .03) and increased by 6β-OHP (P = .05). Progesterone and 17-OHPC decreased oxytocin-induced contractile force (P = .02 and P = .04, respectively) and frequency (P = .02 and P = .03, respectively). Only progesterone decreased spontaneous contractile force (P = .02). Production of 16α-OHP and 6β-OHP metabolites were confirmed in all CYP3A isoforms tested. Conclusion: Progesterone metabolites produced by maternal or fetal CYP3A enzymes influence uterine contractility. [ABSTRACT FROM AUTHOR]

Objective: To estimate whether morbidly obese gravid patients were less likely to develop a surgical site infection after receiving a higher dose of preoperative prophylactic antibiotics.Methods: A retrospective cohort study of morbidly obese pregnant women undergoing cesarean delivery was conducted at two tertiary care centers from 2008 to 2013. Exposure was defined as receiving 2 g compared with 3 g cefazolin preoperatively. Disease was defined by diagnosis of a surgical site infection using Centers for Disease Control and Prevention criteria. We estimated a sample size of 141 patients in each group for a 67% reduction (15% to 5%) in risk for a surgical site infection.Results: There were 335 women included in the cohort with a median absolute weight of 310 (interquartile range 299-333) pounds. Forty-four (13.1%) women were diagnosed with a surgical site infection. There was no difference in surgical site infection among those women who received 2 g compared with 3 g cefazolin (13.1% [23/175] compared with 13.1% [21/160]; P=.996). Labor (crude odds ratio [OR] 2.31, 95% confidence interval [CI] 1.21-4.40), internal labor monitoring (OR 2.78, 1.45-5.31), blood loss greater than 1,500 mL (OR 2.15, 1.09-5.78), and staple closure (OR 2.2, 1.15-4.21) were associated with a surgical site infection among the entire cohort. After multivariable analysis, blood loss greater than 1,500 mL (adjusted OR 3.32, 1.32-8.37) and staple closure (adjusted OR 2.45, 1.19-5.02) remained associated with an increased risk for a surgical site infection, whereas 3 g cefazolin still was not associated with reduced risk for a surgical site infection (adjusted OR 1.33, 0.64-2.74).Conclusion: In our multicenter retrospective cohort study, preoperative 3 g cefazolin prophylaxis administered to morbidly obese gravid patients did not reduce surgical site infections.Level Of Evidence: III. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The number of women aged 45 and older who become pregnant is increasing. The objective of this study was to estimate the risk of medical and obstetric complications among women aged 45 and older. Methods: The Nationwide Inpatient Sample was used to identify pregnant woman during admission for delivery. Deliveries were identified using International Classification of Diseases, Ninth Revision (ICD-9-CM) codes. Using ICD-9-CM codes, pre-existing medical conditions and medical and obstetric complications were identified in women at the time of delivery and were compared for women aged 45 years and older to women under age 35. Outcomes among women aged 35–44 were also compared to women under age 35 to determine if women in this group demonstrated intermediate risk between the older and younger groups. Logistic regression analyses were used to calculate odds ratios with 95% confidence intervals for pre-existing medical conditions and medical and obstetric complications for both older groups relative to women under 35. Multivariable logistic regression analyses were also developed for outcomes at delivery among older women, while controlling for pre-existing medical conditions, multiple gestation, and insurance status, to determine the effect of age on the studied outcomes. Results: Women aged 45 and older had higher adjusted odds for death, transfusion, myocardial infarction/ischemia, cardiac arrest, acute heart failure, pulmonary embolism, deep vein thrombosis, acute renal failure, cesarean delivery, gestational diabetes, fetal demise, fetal chromosomal anomaly, and placenta previa compared to women under 35. Conclusion: Pregnant women aged 45 and older experience significantly more medical and obstetric complications and are more likely to die at the time of a delivery than women under age 35, though the absolute risks are low and these events are rare. Further research is needed to determine what associated factors among pregnant women aged 45 and older may contribute to these findings. [ABSTRACT FROM AUTHOR]

Objective: Bacterial colonization of the fetal membranes and its role in pathogenesis of membrane rupture is poorly understood. Prior retrospective work revealed chorion layer thinning in preterm premature rupture of membranes (PPROM) subjects. Our objective was to prospectively examine fetal membrane chorion thinning and to correlate to bacterial presence in PPROM, preterm, and term subjects. Study Design: Paired membrane samples (membrane rupture and membrane distant) were prospectively collected from: PPROM = 14, preterm labor (PTL = 8), preterm no labor (PTNL = 8), term labor (TL = 10), and term no labor (TNL = 8), subjects. Sections were probed with cytokeratin to identify fetal trophoblast layer of the chorion using immunohistochemistry. Fluorescence in situ hybridization was performed using broad range 16 s ribosomal RNA probe. Images were evaluated, chorion and choriodecidua were measured, and bacterial fluorescence scored. Chorion thinning and bacterial presence were compared among and between groups using Student's t-test, linear mixed effect model, and Poisson regression model (SAS Cary, NC). Results: In all groups, the fetal chorion cellular layer was thinner at rupture compared to distant site (147.2 vs. 253.7 µm, p<0.0001). Further, chorion thinning was greatest among PPROM subjects compared to all other groups combined, regardless of site sampled [PPROM(114.9) vs. PTL(246.0) vs. PTNL(200.8) vs. TL(217.9) vs. TNL(246.5)]. Bacteria counts were highest among PPROM subjects compared to all other groups regardless of site sampled or histologic infection [PPROM(31) vs. PTL(9) vs. PTNL(7) vs. TL(7) vs. TNL(6)]. Among all subjects at both sites, bacterial counts were inversely correlated with chorion thinning, even excluding histologic chorioamnionitis (p<0.0001 and p = 0.05). Conclusions: Fetal chorion was uniformly thinner at rupture site compared to distant sites. In PPROM fetal chorion, we demonstrated pronounced global thinning. Although cause or consequence is uncertain, bacterial presence is greatest and inversely correlated with chorion thinning among PPROM subjects. [ABSTRACT FROM AUTHOR]

Obese pregnant women have higher rates of dysfunctional labor patterns, need for oxytocin augmentation, labor induction, postdates pregnancy, and cesarean delivery compared to normal weight pregnant women. We tested the hypothesis that myometrial oxytocin receptor (OXTR) gene and protein expression are affected by obesity in pregnancy. Myometrial samples were obtained at the time of cesarean delivery from the upper aspect of the uterine hysterotomy incision and processed for real-time quantitative polymerase chain reaction and Western blot. There were 63 myometrial samples available for analysis. The median body mass index (BMI) at delivery was 31.0 kg/m2 (interquartile range, 26.0, 40.0 kg/m2), and the median gestational age at delivery was 38.0 weeks (interquartile range, 33.0, 39.1 weeks). The OXTR gene expression did not correlate with maternal BMI at delivery by linear regression, and the median OXTR gene expression did not differ between women with a BMI ≤ 30 kg/m2 and those with a BMI ≥ 40 kg/m2. The OXTR protein expression was also not affected by maternal BMI. Myometrial OXTR gene expression appears to be independent of BMI at the time of delivery. Dysfunctional labor patterns and increased oxytocin utilization seen in obese women may not be due to differences in OXTR expression, though functional studies are required. [ABSTRACT FROM PUBLISHER]

Preterm premature rupture of the membranes (PPROM) is an important etiology of preterm birth and source of significant neonatal morbidity. We propose that PPROM occurs in the setting of long-standing altered tissue remodeling, which creates a vulnerable environment for the fetal membranes and pregnancy. We tested the hypothesis that PPROM is the result of tissue remodeling in the fetal membranes, specifically the chorion, and this weakening of the chorion compromises the protection provided to the amnion. The purpose of this study was to quantify thickness and apoptosis in the choriodecidua of fetal membranes in patients with PPROM, preterm labor (PTL), preterm no labor (PTNL), and women with term labor (TERM). We conducted a retrospective evaluation of fetal membrane samples from 86 placentas. Immunohistochemistry was performed using a cytokeratin antibody, and mean chorion cellular thickness was compared between each clinical group. To evaluate chorion apoptosis, fetal membranes from patients with PPROM, PTL, and TERM were stained with the M30 antibody, and the degree of cellular apoptosis was determined. Statistical analysis was performed using analysis of variance with corrections for multiple comparisons. The chorion cellular layer was thinner in patients with PPROM compared to patients with PTNL and TERM (62, 140, and 169 µm, respectively, P < .0001), though not significantly different from PTL (95 µm, P > .05). The percentage of apoptotic cells within the chorion among the patients with PPROM was greater compared to PTL and TERM (24.2%, 13.1%, and 8.4%, respectively, P < .001). The chorion cellular layer is thinner and demonstrates increased apoptosis in PPROM compared to patients with PTL, PTNL, and TERM, suggesting differential remodeling between clinical phenotypes. [ABSTRACT FROM AUTHOR]

Highlights: [•] A toxicity grading scale is defined for adverse event reporting in pregnancy. [•] Vital sign changes in pregnancy are discussed and toxicity grading developed for each trimester. [•] Normal laboratory values are listed and a toxicity grade is assigned based on value and trimester of pregnancy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate cervical ripening with foley balloon combined with a fixed vs. incremental low-dose oxytocin infusion. Methods: Women presenting for term labor induction were randomized to fixed low-dose or standard incremental low-dose oxytocin infusion following foley balloon placement. The primary outcome was time from foley balloon placement to delivery. Results: Among 116 subjects, there was no difference in median time to delivery among subjects receiving fixed low-dose vs. standard incremental low-dose oxytocin during induction of labor with a foley balloon (23.7 vs. 19.2 hours). There were no differences between the two groups in median time to foley bulb extrusion, active labor and second stage of labor or incidence of uterine tachysystole, fetal heart rate abnormalities, mode of delivery or maternal hemorrhage. Conclusions: There is no difference in median time to delivery in women undergoing cervical ripening with a foley balloon combined with a fixed low-dose or standard incremental low-dose oxytocin. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that cigarette smoke extract (CSE) leads to differences in expression of genes involved in angiogenesis and affects cell viability and migration in a first-trimester cytotrophoblast cell line (HTR-8/SVneo). HTR-8/SVneo cells were treated with 1% CSE, and gene expression for adrenomedullin (ADM), placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFLT-1), and vascular endothelia growth factor (VEGF) and protein content for ADM, PlGF, and sFlt-1 determined. A cell viability assay and a cell migration scratch assay were utilized following treatment with CSE with and without ADM inhibitor. Adrenomedullin, PlGF, and VEGF gene transcripts were significantly upregulated by 1% CSE treatment compared with unstimulated cells or cells treated with nicotine alone. Neither 1% CSE nor nicotine treatment alone affected sFlt-1 gene expression. There was a significant increase in secreted ADM protein from cells treated with 1% CSE detected by enzyme-linked immunosorbant assay, though no differences in PlGF or sFlt-1 production were seen. Treatment with 1% CSE increased cell viability and cell migration compared with unstimulated cells and was inhibited by co-treatment with ADM inhibitor. Treatment of a first-trimester trophoblast cell line with CSE increases cell viability and cell migration that are reversed by co-treatment with ADM inhibitor, suggesting that ADM at least partially mediates cell growth and viability following CSE treatment. [ABSTRACT FROM PUBLISHER]

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 β-arrestin. In addition to its desensitizing function, β-arrestins have recently been shown to simultaneously activate downstream signaling. We tested whether oxytocin stimulation promotes β-arrestin-mediated OXTR desensitization in vivo and activates β-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 β-arrestin-1 and β-arrestin-2 knockout mice showed no desensitization. Utilizing siRNA knockdown of β-arrestin-1 and β-arrestin-2 in HEK-293 cells expressing the OXTR, we demonstrated oxytocin-mediated MAPK signaling that was dependent on β-arrestin-1 and β-arrestin-2. Wild-type and β-arrestin-1 and β-arrestin-2 knockout mice receiving intravenous oxytocin also demonstrated oxytocin-mediated MAPK signaling that was dependent on β-arrestin-1 and β-arrestin-2. Finally, to test the significance of β-arrestin-mediated signaling from the OXTR, HEK-293 cells expressing the OXTR showed β-arrestin-dependent proliferation in a cell migration assay following oxytocin treatment. In conclusion, β-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. [ABSTRACT FROM AUTHOR]

Background: This study examines whether adding nicotine replacement therapy (NRT) to cognitive-behavioral therapy (CBT) for pregnant smokers increases rates of smoking cessation.Methods: An open-label randomized trial (Baby Steps, n=181) of CBT-only versus CBT+NRT (choice of patch, gum, or lozenge; 1:2 randomization) was used. Data were collected from 2003 through 2005; analyses were conducted in 2006 and 2007. Outcomes were biochemically validated self-reported smoking status at 7 weeks post-randomization, 38 weeks gestation, and 3 months postpartum.Results: Women in the CBT+NRT arm were almost three times more likely than women in the CBT-only arm to have biochemically validated cessation at both pregnancy time points (after 7 weeks: 24% vs 8%, p=0.02; at 38 weeks gestation: 18% vs 7%, p=0.04), but not at 3 months postpartum (20% vs 14%, p=0.55). Recruitment was suspended early by an Independent Data and Safety Monitoring Board when an interim analysis found a higher rate of negative birth outcomes in the CBT+NRT arm than in the CBT-only arm. In the final analysis, the difference between the arms in rate of negative birth outcomes was 0.09 (p=0.26), when adjusted for previous history of preterm birth.Conclusions: The addition of NRT to CBT promoted smoking cessation in pregnant women. This effect did not persist postpartum. More data are needed to determine safety parameters and to confirm the efficacy of NRT use during pregnancy. [ABSTRACT FROM AUTHOR]

The article discusses a study that estimated whether maternal serum interleukin-6 or granulocyte colony-stimulating factor obtained daily are significant in women with preterm premature rupture of members who develop funisitis. According to the results of the study, the biomarkers identify women with preterm premature rupture of membranes likely to develop funisitis.

OBJECTIVE:To investigate the association between lower genital tract infections and subclinical PID. Fallopian tube damage is a common complication of acute symptomatic pelvic inflammatory disease (PID), yet most women with tubal factor infertility do not have a history of acute PID. Subclinical PID is believed to be an important cause of tubal factor infertility.METHODS:We conducted a cross-sectional study among women attending a sexually transmitted diseases or ambulatory gynecology clinic. A convenience sample of 556 women with bacterial vaginosis, gonorrhea, or chlamydia, or women at risk for gonorrhea or chlamydia were enrolled. Women diagnosed with acute PID were not eligible to participate. The main outcome was subclinical PID, as defined by the presence of histologic endometritis.RESULTS:Subclinical PID was more common in women with lower genital tract infection than in uninfected women. Subclinical PID was present in 27% of women with Chlamydia trachomatis (odds ratio 3.4; 95% confidence interval [CI] 1.8, 6.3) and in 26% of women infected with Neisseria gonorrhoeae (odds ratio 2.4; 95% CI 1.1, 5.1). Among women with bacterial vaginosis, 15% had endometritis (odds ratio 2.7; 95% CI 1.02, 7.2).CONCLUSION:Subclinical PID is common among women with lower genital tract infections. Additional prospective studies are necessary to determine the reproductive impact of these asymptomatic upper genital tract infections. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]