Search

Objective We sought to (1) use the Robson 10-Group Classification System (TGCS), which classifies deliveries into 10 mutually exclusive groups, to characterize the groups that are primary contributors to cesarean delivery frequencies, (2) describe inter-hospital variations in cesarean delivery frequencies, and (3) evaluate the contribution of patient characteristics by TGCS group to hospital variation in cesarean delivery frequencies. Study Design This was a secondary analysis of an observational cohort of 115,502 deliveries from 25 hospitals between 2008 and 2011. The TGCS was applied to the cohort and each hospital. We identified and compared the TGCS groups with the greatest relative contributions to cohort and hospital cesarean delivery frequencies. We assessed variation in hospital cesarean deliveries attributable to patient characteristics within TGCS groups using hierarchical logistic regression. Results A total of 115,211 patients were classifiable in the TGCS (99.7%). The cohort cesarean delivery frequency was 31.4% (hospital range: 19.1–39.3%). Term singletons in vertex presentation with a prior cesarean delivery (group 5) were the greatest relative contributor to cohort (34.8%) and hospital cesarean delivery frequencies (median: 33.6%; range: 23.8–45.5%). Nulliparous term singletons in vertex (NTSV) presentation (groups 1 [spontaneous labor] and 2 [induced or absent labor]: 28.9%), term singletons in vertex presentation with a prior cesarean delivery (group 5: 34.8%), and preterm singletons in vertex presentation (group 10: 9.8%) contributed to 73.2% of the relative cesarean delivery frequency for the cohort and were correlated with hospital cesarean delivery frequencies (Spearman's rho = 0.96). Differences in patient characteristics accounted for 34.1% of hospital-level cesarean delivery variation in group 2. Conclusion The TGCS highlights the contribution of NTSV presentation to cesarean delivery frequencies and the impact of patient characteristics on hospital-level variation in cesarean deliveries among nulliparous patients with induced or absent labor. Key Points We report on the cesarean delivery frequencies in a multicenter U.S. cohort. NTSV gestations (groups 1 and 2) are a primary driver of cesarean deliveries. Patient characteristics contributed most to hospital variation in cesarean deliveries in group 2. [ABSTRACT FROM AUTHOR]

Objective This study aimed to assess the association of maternal body mass index (BMI) with a composite of severe maternal outcomes. Study Design Secondary analysis of a cohort of deliveries on randomly selected days at 25 hospitals from 2008 to 2011. Data on comorbid conditions, intrapartum events, and postpartum course were collected. The reference group (REF, BMI: 18.5–29.9kg/m 2), obese (OB; BMI: 30–39.9kg/m 2), morbidly obese (MO; BMI: 40–49.9kg/m 2), and super morbidly obese (SMO; BMI ≥ 50kg/m 2) women were compared. The composite of severe maternal outcomes was defined as death, intensive care unit (ICU) admission, ventilator use, deep venous thrombosis/pulmonary embolus (DVT/PE), sepsis, hemorrhage, disseminated intravascular coagulation (DIC), unplanned operative procedure, or stroke. Patients in the REF group were matched 1:1 with those in all other obesity groups based on propensity score using the baseline characteristics of age, race/ethnicity, previous cesarean, preexisting diabetes, chronic hypertension, parity, cigarette use, and insurance status. Multivariable Poisson's regression was used to estimate adjusted relative risks (aRRs) and 95% confidence intervals (CIs) for the association between BMI and the composite outcome. Because cesarean delivery may be in the causal pathway between obesity and adverse maternal outcomes, models were then adjusted for mode of delivery to evaluate potential mediation. Results A total of 52,162 pregnant patients are included in the analysis. Risk of composite maternal outcomes was increased for SMO compared with REF but not for OB and MO [OB: aRR=1.06, 95% CI: 0.99–1.14; MO: aRR=1.10, 95% CI: 0.97–1.25; SMO: aRR=1.32, 95% CI: 1.02–1.70]. However, in the mediation analysis, cesarean appears to mediate 46% (95% CI: 31–50%) of the risk of severe morbidity for SMO compared with REF. Conclusion Super morbid obesity is significantly associated with increased serious maternal morbidity and mortality; however, cesarean appears to mediate this association. Obesity and morbid obesity are not associated with maternal morbidity and mortality. Key Points Super morbid obesity is associated with increased morbidity. Cesarean appears to mediate the association between super morbid obesity and morbidity. Obesity and morbid maternal obesity are not associated with morbidity. [ABSTRACT FROM AUTHOR]

Objective This study aimed to evaluate whether racial and ethnic disparities in adverse perinatal outcomes exist at term. Study Design We performed a secondary analysis of a multicenter observational study of 115,502 pregnant patients and their neonates (2008–2011). Singleton, nonanomalous pregnancies delivered from 37 to 41 weeks were included. Race and ethnicity were abstracted from the medical record and categorized as non-Hispanic White (White; referent), non-Hispanic Black (Black), non-Hispanic Asian (Asian), or Hispanic. The primary outcome was an adverse perinatal composite defined as perinatal death, Apgar score < 4 at 5 minutes, ventilator support, hypoxic–ischemic encephalopathy, subgaleal hemorrhage, skeletal fracture, infant stay greater than maternal stay (by ≥ 3 days), brachial plexus palsy, or facial nerve palsy. Results Of the 72,117 patients included, 48% were White, 20% Black, 5% Asian, and 26% Hispanic. The unadjusted risk of the primary outcome was highest for neonates of Black patients (3.1%, unadjusted relative risk [uRR] = 1.16, 95% confidence interval [CI]: 1.04–1.30), lowest for neonates of Hispanic patients (2.1%, uRR = 0.80, 95% CI: 0.71–0.89), and no different for neonates of Asian (2.6%), compared with those of White patients (2.7%). In the adjusted model including age, body mass index (BMI), smoking, obstetric history, and high-risk pregnancy, differences in risk for the primary outcome were no longer observed for neonates of Black (adjusted relative risk [aRR] = 1.06, 95% CI: 0.94–1.19) and Hispanic (aRR = 0.92, 95% CI: 0.81–1.04) patients. Adding insurance to the model lowered the risk for both groups (aRR = 0.85, 95% CI: 0.75–0.96 for Black; aRR = 0.68, 95% CI: 0.59–0.78 for Hispanic). Conclusion Although neonates of Black patients have the highest frequency of adverse perinatal outcomes at term, after adjustment for sociodemographic factors, this higher risk is no longer observed, suggesting the importance of developing strategies that address social determinants of health to lessen extant health disparities. Key Points Term neonates of Black patients have the highest crude frequency of adverse perinatal outcomes. After adjustment for confounders, higher risk for neonates of Black patients is no longer observed. Disparities in outcomes are strongly related to insurance status. [ABSTRACT FROM AUTHOR]

Objective This study aimed to examine whether there are racial disparities in severe maternal morbidity (SMM) in patients with hypertensive disorders of pregnancy (HDP). Study Design Secondary analysis of an observational study of 115,502 patients who had a live birth at ≥20 weeks in 25 hospitals in the United States from 2008 to 2011. Only patients with HDP were included in this analysis. Race and ethnicity were categorized as non-Hispanic White, non-Hispanic Black (NHB), and Hispanic and were abstracted from the medical charts. Patients of other races and ethnicities were excluded. Associations were estimated between race and ethnicity, and the primary outcome of SMM, defined as any of the following, was estimated by unadjusted logistic and multivariable backward logistic regressions: blood transfusion ≥4 units, unexpected surgical procedure, need for a ventilator ≥12 hours, intensive care unit (ICU) admission, or failure of ≥1 organ system. Multivariable models were run classifying HDP into three levels as follows: (1) gestational hypertension; (2) preeclampsia (mild, severe, or superimposed); and (3) eclampsia or HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Results A total of 9,612 individuals with HDP met inclusion criteria. No maternal deaths occurred in this cohort. In univariable analysis, non-Hispanic White patients were more likely to present with gestational hypertension whereas NHB and Hispanic patients were more likely to present with preeclampsia. The frequency of the primary outcome, composite SMM, was higher in NHB patients compared with that in non-Hispanic White or Hispanic patients (11.8 vs. 4.5% in non-Hispanic White and 4.8% in Hispanic, p < 0.001). This difference was driven by a higher frequency of blood transfusions and ICU admissions among NHB individuals. Prior to adjusting the analysis for confounding factors, the odds ratio (OR) of primary composite outcomes in NHB individuals was 2.85 (95% confidence interval [CI]: 2.38, 3.42) compared with non-Hispanic White. After adjusting for sociodemographic and clinical factors, hospital site, and the severity of HDP, the OR of composite SMM did not differ between the groups (adjusted OR [aOR] = 1.26, 95% CI: 0.95, 1.67 for NHB, and aOR = 1.29, 95% CI: 0.94, 1.77 for Hispanic, compared with non-Hispanic White patients). Sensitivity analysis was done to exclude one single site that was an outliner with the highest ICU admissions and demonstrated no difference in ICU admission by maternal race and ethnicity. Conclusion NHB patients with HDP had higher rates of the composite SMM compared with non-Hispanic White patients, driven mainly by a higher frequency of blood transfusions and ICU admissions. However, once severity and other confounding factors were taken into account, the differences did not persist. Key Points Black patients with HDP had higher frequency of SMM compared with non-Hispanic White patients. The SMM disparities were driven by blood transfusions and ICU admissions. After adjustment for confounders, including HDP severity, the significant difference in SMM did not persist. [ABSTRACT FROM AUTHOR]

Objective  Our objective was to compare outcomes among low-risk parous women who underwent elective labor induction at 39 weeks versus expectant management. Study Design  This is a secondary analysis of an observational cohort of 115,502 mother–infant dyads who delivered at 25 hospitals between 2008 and 2011. The inclusion criteria for this analysis were low-risk parous women with nonanomalous singletons with at least one prior vaginal delivery after 20 weeks, who delivered at ≥39 0/7 weeks. Women who electively induced between 39 0/7 and 39 6/7 weeks were compared with women who expectantly managed ≥39 0/7 weeks. The primary outcome for this analysis was cesarean delivery. Secondary outcomes were composites of maternal adverse outcome and neonatal adverse outcome. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR). Results  Of 20,822 women who met inclusion criteria, 2,648 (12.7%) were electively induced at 39 weeks. Cesarean delivery was lower among women who underwent elective induction at 39 weeks than those who did not (2.4 vs. 4.6%, adjusted odds ratio [aOR]: 0.70, 95% confidence interval [CI]: 0.53–0.92). The frequency of the composite maternal adverse outcome was significantly lower for the elective induction cohort as well (1.6 vs. 3.1%, aOR: 0.66, 95% CI: 0.47–0.93). The composite neonatal adverse outcome was not significantly different between the two groups (0.3 vs. 0.6%; aOR: 0.60, 95% CI: 0.29–1.23). Conclusion  In low-risk parous women, elective induction of labor at 39 weeks was associated with decreased odds of cesarean delivery and maternal morbidity, without an increase in neonatal adverse outcomes. Key Points 39-week elective induction is associated with decreased cesarean delivery in low-risk parous women. Compared with expectant management, maternal adverse outcomes were lower with elective induction. Neonatal adverse outcomes are unchanged between elective and expectant management groups. [ABSTRACT FROM AUTHOR]

Objective  The objective of this study was to determine whether antenatal corticosteroid exposure has a differential association with preterm neonatal morbidity among women with and without diabetes. Study Design  Secondary analysis of an observational cohort of 115,502 women and their neonates born in 25 U.S. hospitals (2008–2011). Women who delivered at 23 0/7 to 33 6/7 weeks' gestation and received antenatal corticosteroids were compared with those who did not receive antenatal corticosteroids. Women with a stillbirth and women who delivered a neonate that was not resuscitated were excluded. The primary outcome was neonatal respiratory distress syndrome or death within 48 hours. Secondary outcomes included composite neonatal morbidity (respiratory distress syndrome, necrotizing enterocolitis, grades 3–4 intraventricular hemorrhage, sepsis, or death) and mechanical ventilation. Multivariable modified Poisson regression was used to estimate the association between antenatal corticosteroid exposure and neonatal outcomes. Maternal diabetes (pregestational and gestational) was evaluated as a potential effect modifier, and sensitivity analyses were conducted to evaluate whether receipt of a partial, single, or multiple course(s) of antenatal corticosteroids influenced results. Results  A total of 4,429 women with 5,259 neonates met inclusion criteria: 3,716 (83.9%) women received antenatal corticosteroids and 713 (16.1%) did not. Of the 510 diabetic women (181 pregestational and 329 gestational), 439 (86.1%) received antenatal corticosteroids. Of the 3,919 nondiabetic women, 3,277 (83.6%) received antenatal corticosteroids. Antenatal corticosteroid exposure was not associated with respiratory distress syndrome or early death (adjusted relative risk [aRR] = 0.94, 95% confidence interval [CI]: 0.85–1.04), composite neonatal morbidity (aRR = 0.98, 95% CI: 0.89–1.07), or mechanical ventilation (aRR = 0.95, 95% CI: 0.86–1.05). There was no significant effect modification of maternal diabetes on the relationship between antenatal corticosteroids and neonatal outcomes (p  > 0.05), and outcomes were similar in sensitivity analyses of partial, single, or multiple courses of corticosteroids. Discussion  Antenatal corticosteroid administered to reduce preterm neonatal morbidity does not appear to have a differential association among women with diabetes compared with those without. Key Points Antenatal corticosteroids are used ubiquitously in women with and without diabetes. Maternal diabetes does not appear to modify the neonatal effect of antenatal corticosteroids. Larger studies of antenatal corticosteroids are needed to confirm our findings in diabetic women. [ABSTRACT FROM AUTHOR]

Background: Despite the increasing prevalence of opioid use disorder (OUD) in pregnant women, there are limited studies on their anesthesia care and analgesic outcomes after cesarean delivery (CD). Methods: Patients with OUD on either buprenorphine or methadone maintenance therapy who underwent CD at our institution from 2011 to 2018 were identified. Anesthetic details and analgesic outcomes, including daily opioid consumption and pain scores, were compared between patients maintained on buprenorphine and methadone. Analgesic outcomes were also evaluated according to anesthetic type (neuraxial or general anesthesia) and daily buprenorphine/methadone dose to determine if these factors impacted pain after delivery. Results: A total of 146 patients were included (buprenorphine n=99 (67.8%), methadone n=47 (32.2%)). Among all patients: 74% had spinal/CSE, 15% epidural, and 11% general anesthesia. Anesthesia types were similar among buprenorphine and methadone patients. For spinal anesthetics, intrathecal fentanyl (median 15 μg) and morphine (median 100 μg) were commonly given (97.2% and 96.3%, respectively), and dosed similarly between groups. Among epidural anesthetics, epidural morphine (median 2 mg) was commonly administered (90.9%), while fentanyl (median 100 μg) was less common (54.5%). Buprenorphine and methadone groups consumed similar amounts of oxycodone equivalents per 24 hours of hospitalization (80.6 vs 76.3 mg; p=0.694) and had similar peak pain scores (8.3 vs 8.0; p=0.518). Daily methadone dose correlated weakly with opioid consumption (R=0.3; p=0.03), although buprenorphine dose did not correlate with opioid consumption or pain scores. General anesthesia correlated with greater oxycodone consumption in the first 24 hours (median 156.1 vs 91.7 mg; p=0.004) and greater IV PCA use (63% vs 7%; p< 0.001) compared to neuraxial anesthesia. Conclusion: Patients on buprenorphine and methadone had similar high opioid consumption and pain scores after CD. The anesthetic details and analgesic outcomes reported in this investigation may serve as a useful reference for future prospective investigations and aid in the clinical care of these patients. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to evaluate whether the number of vacuum pop-offs, the number of forceps pulls, or the duration of operative vaginal delivery (OVD) is associated with adverse maternal and perinatal outcomes. Study Design  This is a secondary analysis of a multicenter observational cohort of women who underwent an attempted OVD. Women were stratified by the duration of OVD and the number of pop-offs (vacuum) or pulls (forceps) attempted. Severe perineal lacerations, failed OVD, and a composite adverse neonatal outcome were compared by the duration of OVD and number of pop-offs or pulls. Results  Of the 115,502 women in the primary cohort, 5,325 (4.6%) underwent an attempt at OVD: 3,594 (67.5%) with vacuum and 1,731 (32.5%) with forceps. After adjusting for potential confounders, an increasing number of pop-offs was associated with an increased odds of the composite adverse neonatal outcome. However, an increasing duration of vacuum exhibited a stronger association with the composite adverse neonatal outcome. Similarly, the number of forceps pulls was less strongly associated with the composite adverse neonatal outcome compared with the duration of forceps application. Conclusion  The duration of OVD may be more associated with adverse neonatal outcomes than the number of pop-offs or pulls. [ABSTRACT FROM AUTHOR]

The prevalence of opioid use disorder (OUD) in the United States has more than quadrupled over the past two decades. This patient population presents a number of challenges to clinicians, including difficult pain management after surgical procedures due to the development of opioid tolerance. Significantly greater opioid consumption and pain scores after cesarean delivery have been reported in patients with OUD compared to other obstetric patients. A multi-modal analgesic regimen is generally recommended, but there are few well-established pain management strategies after cesarean delivery specific to patients with OUD. We present the case of a patient with OUD maintained on daily methadone that received a continuous epidural hydromorphone infusion for post-cesarean analgesia, a technique not previously reported in obstetric patients and only rarely described for patients undergoing other surgical procedures. The patient received epidural anesthesia for cesarean delivery, and after surgery, the epidural catheter was left in place for the epidural hydromorphone infusion, initiated at 140 mcg/hr and continued for approximately 40 hrs. This strategy reduced her average daily oral opioid consumption by 97%, reduced self-reported pain scores, shortened the length of hospitalization and improved ability to ambulate compared to her previous cesarean delivery. The use of continuous epidural hydromorphone infusion was effective in this case, and this analgesic technique may also be applicable to other types of surgical procedures with the potential for significant post-operative pain, particularly in patients with OUD. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is under-recognized among US adults and children. Prenatal HCV screening may help close the diagnosis gap among women while also identifying at-risk infants. Current surveillance efforts for maternal HCV rely primarily on birth certificate data. We sought a more accurate assessment of HCV prevalence among pregnant women in Ohio by combining existing public health surveillance data.Methods: Vital Statistics (VS) birth certificate data and Ohio Disease Reporting System (ODRS) HCV case data, both available through the Ohio Department of Health, were linked to determine rates of past or present HCV infection among women giving birth from 2012 to 2015 in Ohio, overall and by county. Among women with available test results, the proportion with present HCV infection indicated by detectable viraemia during pregnancy was calculated.Results: Birth certificate data identified 4695 deliveries to women with past/present HCV infection during the study period. Linkage to ODRS revealed an additional 1778 deliveries to women with past/present infection, including 355 with confirmed viraemia during pregnancy. The prevalence of past/present HCV among pregnant women in Ohio rose from 0.82% in 2012 to 1.54% in 2015.Conclusions: Maternal HCV infection is under-recognized and increasing in prevalence. Current case identification processes are inadequate in pregnancy, even among women with prior positive HCV testing. Alternative approaches, including enhanced risk factor-based screening or universal prenatal screening in high prevalence settings, are needed to improve rates of HCV recognition among reproductive-aged women and newborns at risk of vertical transmission. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to estimate whether the decision-to-incision (DTI) time for cesarean delivery (CD) is associated with differences in maternal and neonatal outcomes. Methods This analysis is of data from women at 25 U.S. medical centers with a term, singleton, cephalic nonanomalous gestation and no prior CD, who underwent an intrapartum CD. Perinatal and maternal outcomes associated with DTI intervals of ≤ 15, 16 to 30, and > 30 minutes were compared. Results Among 3,482 eligible women, median DTI times were 46 and 27 minutes for arrest and fetal indications for CD, respectively (p < 0.01). Women with a fetal indication whose DTI interval was > 30 minutes had similarodds to the referent group (DTI of 16-30 minutes) for the adverse neonatal and maternal composites (odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.40-1.71 and OR: 0.89, 95% CI: 0.63-1.27). For arrest disorders, the odds of the adverse neonatal composite were lower among women with a DTI of > 30 minutes (OR: 0.25, 95% CI: 0.08-0.77), and the adverse maternal composite was no different (OR: 1.15, 95% CI: 0.81 -1.63). Conclusion In this analysis, DTI times longer than 30 minutes were not associated with worse maternal or neonatal outcomes. [ABSTRACT FROM AUTHOR]

Substance-abusing women experience burdens making attending high-risk prenatal care critical for a healthy pregnancy. Many face barriers that compromise their health by reducing access to care, delaying their first prenatal appointment. One hundred forty-one women attending a high-risk prenatal clinic were compared to a matched group from the hospital’s general obstetrics clinic. Analyses revealed that substance-abusing women with a mental illness attended prenatal care earlier than those without a mental illness. This is important because psychiatric illnesses might precipitate poor reproductive behaviors. Women with HIV also entered prenatal care earlier, which improves reproductive health. Clinicians’ roles are discussed. [ABSTRACT FROM PUBLISHER]

Maternal innate and adaptive immune responses are modulated during pregnancy to concurrently defend against infection and tolerate the semiallogeneic fetus. The restoration of these systems after childbirth is poorly understood. We reasoned that enhanced innate immune activation may extend beyond gestation while adaptive immunity recovers. To test this hypothesis, the transcriptional profiles of total peripheral blood mononuclear cells following delivery in healthy women were compared with those of nonpregnant control subjects. Interestingly, interferon-stimulated genes (ISGs) encoding proteins such as IFIT1, IFIT2, and IFIT3, as well as signaling proteins such as STAT1, STAT2, and MAVS, were enriched postpartum. Antiviral genes were primarily expressed in CD14+ cells and could be stratified according to genetic variation at the interferon-λ3 gene (IFNL3, also named IL28B) SNP rs12979860. Antiviral gene expression was sustained beyond 6 mo following delivery in mothers with a CT or TT genotype, but resembled baseline nonpregnant control levels following delivery in mothers with a CC genotype. CT and TT IFNL3 genotypes have been associated with persistent elevated ISG expression in individuals chronically infected with hepatitis C virus. Together, these data suggest that postpartum, the normalization of the physiological rheostat controlling IFN signaling depends on IFNL3 genotype. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection is characterized by exhaustion of virus-specific T-cells and stable viremia. Pregnancy is an exception. Viremia gradually climbs during gestation but sometimes declines sharply in the months following delivery. Here, we demonstrated that postpartum HCV control was associated with enhanced virus-specific T-cell immunity. Women with viral load declines of at least 1 log10 between the third trimester and 3-mo postpartum exhibited HCV-specific T-cell responses of greater breadth (P = 0.0052) and magnitude (P = 0.026) at 3-mo postpartum than women who failed to control viremia. Moreover, viral dynamics were consistent in women after consecutive pregnancies, suggesting genetic underpinnings. We therefore searched for genetic associations with human leukocyte antigen (HLA) alleles and IFN-?3 gene (IFNL3) polymorphisms that influence HCV infection outcome. Postpartum viral control was associated with the IFNL3 rs12979860 genotype CC (P = 0.045 at 6 mo) that predicts a positive response to IFN-based therapy. Suppression of virus replication after pregnancy was also strongly influenced by the HLA class II DPB1 locus. HLADPB1 alleles are classified by high and low patterns of expression. Carriage of at least one high-expression HLA-DPB1 allele predicted resurgent virus-specific T-cell immunity and viral control at 3-mo postpartum (P = 0.0002). When considered together in multivariable analysis, IFNL3 and HLA-DPB1 independently affected viral control at 3- and 6-mo postpartum. Together, these findings support a model where spontaneous control of HCV such as sometimes follows pregnancy is governed by genetic polymorphisms that affect type III IFN signaling and virus-specific cellular immune responses. [ABSTRACT FROM AUTHOR]

The article discusses methods of intervention in cases of drug abuse during pregnancy without harming both mother and baby. Topics include the rising incidence of neonatal abstinence syndrome (NAS) or opiate withdrawal and sceening methods for opiate abuse available to obstetricians/gynecologists (ob/gyns) such as the CAGE-AID screening questionnaire, the 5-question screening instrument 4Ps Plus and biochemical screening. It discusses a way of screening a neonate for in utero drug exposure.

An orderly sovereign debt restructuring should place the debtor nation's public debt on a sustainable trajectory while minimizing procrastination and contagion. However, the experiences with the debt crisis of the 1980s, Russia 1998, Argentina 2001, and Greece 2010 indicate that orderly debt restructurings remain elusive, even with high-powered official intervention. When solvency problems are present, the chances of success increase if official money is lent at the risk-free rate, reflecting its low risk, and if private creditors receive an upfront haircut. The paper examines the obstacles, which include moral hazard, difficulty in distinguishing between solvency and liquidity crises, and the “political economy” resistance to upfront haircuts. Orderly sovereign debt restructurings are likely to remain elusive notwithstanding recent evidence that the official mindset may be changing. [ABSTRACT FROM AUTHOR]

Globally, about 1% of pregnant women are persistently infected with the hepatitis C virus (HCV). Mother-to-child transmission of HCV occurs in 3-5% of pregnancies and accounts for most new childhood infections. HCV-specific CD8+ cytotoxic T lymphocytes (CTLs) are vital in the clearance of acute HCV infections, but in the 60-80% of infections that persist, these cells become functionally exhausted or select for mutant viruses that escape T cell recognition. Increased HCV replication during pregnancy suggests that maternofetal immune tolerance mechanisms may further impair HCV-specific CTLs, limiting their selective pressure on persistent viruses. To assess this possibility, we characterized circulating viral quasispecies during and after consecutive pregnancies in two women. This revealed a loss of some escape mutations in HLA class I epitopes during pregnancy that was associated with emergence of more fit viruses. CTL selective pressure was reimposed after childbirth, at which point escape mutations in these epitopes again predominated in the quasispecies and viral load dropped sharply. Importantly, the viruses transmitted perinatally were those with enhanced fitness due to reversion of escape mutations. Our findings indicate that the immunoregulatory changes of pregnancy reduce CTL selective pressure on HCV class I epitopes, thereby facilitating vertical transmission of viruses with optimized replicative fitness. [ABSTRACT FROM AUTHOR]

Despite recent advances in the pathogenesis, treatment, and public health response to hepatitis C virus (HCV), HCV as it specifically relates to pregnancy has been a neglected condition. HCV-monoinfected pregnant women have a 2-8% risk of viral transmission to their infant, but the mechanism and timing of mother to child transmission (MTCT) are not fully understood, nor is the natural history of the illness in pregnant women and their offspring. Recognition of HCV-infected pregnant women is relevant because of the long-term health implications for the mother, potential adverse effects of infection on pregnancy outcomes, and the possibility of transmission to their infants. Certain risk factors for MTCT of HCV appear similar to those for human immunodeficiency virus (HIV); however, unlike HIV, effective methods for prevention of HCV vertical transmission have not been developed. It is possible that a better understanding of HCV MTCT and pathogenesis in pregnancy will guide development of useful prevention strategies, particularly as we enter an era where interferon-free drug cocktails may emerge as viable treatment options for HCV. [ABSTRACT FROM AUTHOR]

This article discusses asthma during pregnancy and its clinical management. Particular focus is given to the prevalence of asthma among pregnant women, as well as its link with poor pregnancy outcomes. Asthma symptoms include cough, dyspnea, wheezing and chest tightness. There is a need to classify the pregnant woman with asthma based upon severity of disease. Both prepregnancy and prenatal counseling are important to the appropriate care of patients with asthma. Pharmacologic interventions for pregnant women with asthma are also provided.

Background: Methylation-mediated silencing of genes is one epigenetic mechanism implicated in cancer. Studies regarding the role of modulation of gene expression utilizing inhibitors of DNA methylation, such as decitabine, in osteosarcoma (OS) have been limited. A biological understanding of the overall effects of decitabine in OS is important because this particular agent is currently undergoing clinical trials. The objective of this study was to measure the response of the OS cell line, U2OS, to decitabine treatment both in vitro and in vivo. Results: Microarray expression profiling was used to distinguish decitabine-dependent changes in gene expression in U2OS cells, and to identify responsive loci with demethylated CpG promoter regions. U2OS xenografts were established under the sub-renal capsule of immune-deficient mice to study the effect of decitabine in vivo on tumor growth and differentiation. Reduced nuclear methylation levels could be detected in xenografts derived from treated mice by immunohistochemistry utilizing a 5-methylcytidine antibody. Decitabine treatment reduced tumor xenograft size significantly (p < 0.05). Histological analysis of treated U2OS xenograft sections revealed a lower mitotic activity (p < 0.0001), increased bone matrix production (p < 0.0001), and a higher number of apoptotic cells (p = 0.0329). Microarray expression profiling of U2OS cultured cells showed that decitabine treatment caused a significant induction (p < 0.0025) in the expression of 88 genes. Thirteen had a ≥2-fold change, 11 of which had CpG-island associated promoters. Interestingly, 6 of these 11 were pro-apoptotic genes and decitabine resulted in a significant induction of cell death in U2OS cells in vitro (p < 0.05). The 6 pro-apoptotic genes (GADD45A, HSPA9B, PAWR, PDCD5, NFKBIA, and TNFAIP3) were also induced to ≥2-fold in vivo. Quantitative methylation pyrosequencing confirmed that the tested pro-apoptotic genes had CpG-island DNA demethylationas a result of U2OS decitabine treatment both in vitro and in xenografts Conclusion: These data provide new insights regarding the use of epigenetic modifiers in OS, and have important implications for therapeutic trials involving demethylation drugs. Collectively, these data have provided biological evidence that one mode of action of decitabine may be the induction of apoptosis utilizing promoter-CpG demethylation of specific effectors in cell death pathways in OS. [ABSTRACT FROM AUTHOR]

Background: Advances made in the area of microarray comparative genomic hybridization (aCGH) have enabled the interrogation of the entire genome at a previously unattainable resolution. This has lead to the discovery of a novel class of alternative entities called large-scale copy number variations (CNVs). These CNVs are often found in regions of closely linked sequence homology called duplicons that are thought to facilitate genomic rearrangements in some classes of neoplasia. Recently, it was proposed that duplicons located near the recurrent translocation break points on chromosomes 9 and 22 in chronic myeloid leukemia (CML) may facilitate this tumor-specific translocation. Furthermore, ~15— 20% of CML patients also carry a microdeletion on the derivative 9 chromosome (der(9)) and these patients have a poor prognosis. It has been hypothesised that der(9) deletion patients have increased levels of chromosomal instability. Results: In this study aCGH was performed and identified a CNV (RP11-125A5, hereafter called CNV14q12) that was present as a genomic gain or loss in 10% of control DNA samples derived from cytogenetically normal individuals. CNV14q12 was the same clone identified by Iafrate et al. as a CNV. Real-time polymerase chain reaction (Q-PCR) was used to determine the relative frequency of this CNV in DNA from a series of 16 CML patients (both with and without a der(9) deletion) together with DNA derived from 36 paediatric solid tumors in comparison to the incidence of CNV in control DNA. CNV14q12 was present in ~50% of both tumor and CML DNA, but was found in 72% of CML bearing a der(9) microdeletion. Chi square analysis found a statistically significant difference (p ≤ 0.001) between the incidence of this CNV in cancer and normal DNA and a slightly increased incidence in CML with deletions in comparison to those CML without a detectable deletion. Conclusion: The increased incidence of CNV14q12 in tumor samples suggests that either acquired or inherited genomic variation of this new class of variation may be associated with onset or progression of neoplasia. [ABSTRACT FROM AUTHOR]

The article presents a study which examines preterm birth role as a potential mediator of the link between neonatal abstinence syndrome (NAS) and medication-assisted treatment (MAT). The authors of the study estimated the controlled direct impact of treatment of methadone on NAS while removing the impact of preterm birth. The authors discovered that the estimate of the association between NAS and methadone vs buprenorphone increased when accounting for mediation through preterm birth.