Obstructive Sleep Apnea Among Gravidas With Chronic Hypertension Compared to Matched Controls: A Prospective Cohort Study.

BACKGROUND: Previous studies of obstructive sleep apnea (OSA) risk in gravidas with chronic hypertension (cHTN) did not control for obesity as a risk factor for OSA. We therefore performed this study to evaluate whether OSA is more prevalent among gravidas with cHTN compared to normotensive gravidas matched for body mass index (BMI) and gestational age (primary outcome). We also assessed whether OSA is more severe when comorbid with cHTN in pregnancy (secondary outcome). METHODS: This was a single-center, prospective cohort study. Adult gravidas at 10-20 weeks of gestation, with and without cHTN, were enrolled and BMI matched. All subjects answered OSA screening questionnaires and underwent a home sleep test when they were between 10 and 20 weeks of gestation. Pregnancy outcomes were followed for all subjects. We performed univariable and multivariable logistic regression to model the relationship between cHTN status and OSA. RESULTS: A total of 100 pregnant subjects (50 with cHTN and 50 normotensive) completed a home sleep test of 2 hours or more. There were no differences in demographic variables between the 2 groups, except that gravidas with cHTN were significantly older than normotensive subjects (mean ± standard deviation [SD] 34 ± 4 vs 30 ± 6 years; P < .001). OSA was more prevalent (64% vs 38%; P = .009; odds ratio [95% confidence interval (CI)] 2.90 [1.30-6.65]; P = .01) and more severe in gravidas with cHTN (moderate or severe OSA 59% vs 21%; P = .009). After controlling for age, we found no overall association between cHTN on OSA risk (adjusted odds ratio [95% CI] 2.22 [0.92-5.40]; P = .076). However, among gravidas older than 25 years of age, cHTN was associated with higher odds of OSA (adjusted odds ratio [95% CI], 2.64 [1.06-6.71], P = .038). CONCLUSIONS: cHTN and age are important risk factors for OSA in gravidas. Gravidas with cHTN should be screened for OSA in early pregnancy. Future studies may validate screening tools that include cHTN and age, and investigate the role of OSA therapy in blood pressure control.

The ß-arrestin-biased ß-adrenergic receptor blocker carvedilol enhances skeletal muscle contractility.

A decrease in skeletal muscle strength and functional exercise capacity due to aging, frailty, and muscle wasting poses major unmet clinical needs. These conditions are associated with numerous adverse clinical outcomes including falls, fractures, and increased hospitalization. Clenbuterol, a ß2-adrenergic receptor (ß2AR) agonist enhances skeletal muscle strength and hypertrophy; however, its clinical utility is limited by side effects such as cardiac arrhythmias mediated by G protein signaling. We recently reported that clenbuterol-induced increases in contractility and skeletal muscle hypertrophy were lost in ß-arrestin 1 knockout mice, implying that arrestins, multifunctional adapter and signaling proteins, play a vital role in mediating the skeletal muscle effects of ß2AR agonists. Carvedilol, classically defined as a ßAR antagonist, is widely used for the treatment of chronic systolic heart failure and hypertension, and has been demonstrated to function as a ß-arrestin-biased ligand for the ß2AR, stimulating ß-arrestin-dependent but not G protein-dependent signaling. In this study, we investigated whether treatment with carvedilol could enhance skeletal muscle strength via ß-arrestin-dependent pathways. In a murine model, we demonstrate chronic treatment with carvedilol, but not other ß-blockers, indeed enhances contractile force in skeletal muscle and this is mediated by ß-arrestin 1. Interestingly, carvedilol enhanced skeletal muscle contractility despite a lack of effect on skeletal muscle hypertrophy. Our findings suggest a potential unique clinical role of carvedilol to stimulate skeletal muscle contractility while avoiding the adverse effects with ßAR agonists. This distinctive signaling profile could present an innovative approach to treating sarcopenia, frailty, and secondary muscle wasting.

Prospective Observational Study of N-terminal Pro-Brain Natriuretic Peptide Levels in Obese and Nonobese Women during Pregnancy.

OBJECTIVE: N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of ventricular dysfunction, varies by body mass index (BMI) outside of pregnancy. This study aimed to determine whether obesity affects NT-proBNP levels in pregnancy. STUDY DESIGN: This was a prospective observational study of healthy pregnant people in the third trimester (3TM) and postpartum (PP). Patients were excluded if they had significant medical comorbidities or if their fetuses had anomalies, growth restriction or aneuploidy. NT-proBNP was measured at 28 weeks (3TM), predelivery (PD), 1 to 2 days PP (immediate postpartum [IPP]), and 4 to 6 weeks PP (delayed postpartum [DPP]). LogNT-proBNP levels were analyzed using linear mixed effects models, including BMI < or ≥30, time, and time-by-BMI interactions. RESULTS: Fifty-five people (28 [51%] with BMI ≥ 30 and 27 [49%] with BMI < 30) were enrolled. A greater proportion of obese than nonobese subjects developed hypertensive disorders of pregnancy (50 vs. 15%, p = 0.010) and obese patients had higher systolic blood pressures at all time points (p < 0.05). NT-proBNP levels (median [interquartile range] in pg/mL) were 18 (6-28) versus 26 (17-48) at 3TM, 16 (3-38) versus 43 (21-60) at PD, 58 (20-102) versus 63 (38-155) at IPP, and 33 (27-56) versus 23 (8-42) at DPP for obese compared with nonobese patients. In linear mixed effects models, logNT-proBNP was lower in obese patients at 3TM (ß = -0.89 [95% confidence interval, CI: -1.51, -0.26]) and PD (ß = -1.05 [95% CI: -1.72, -0.38]). The logNT-proBNP trends over time differed by BMI category, with higher values in obese patients at both PP time points compared with the 3TM (IPP ß = 1.24 [95% CI: 0.75, 1.73]; DPP ß = 1.08 [95% CI: 0.52, 1.63]), but only IPP for nonobese patients (ß = 0.87 [95% CI: 0.36, 1.38]). CONCLUSION: Obese patients had lower NT-proBNP levels than nonobese patients during pregnancy but not PP. The prolonged PP elevation in NT-proBNP in obese patients suggests that their PP cardiac recovery may be more prolonged. KEY POINTS: · NT-proBNP levels are lower in obese than nonobese patients during pregnancy.. · Levels remain elevated in obese, but not nonobese, patients up to 4 to 6 weeks' postpartum.. · A lower threshold for concern regarding NT-proBNP levels may be needed in obese pregnant people..

Pregnancy-Associated Extracorporeal Membrane Oxygenation in the United States.

OBJECTIVE: The use of extracorporeal membrane oxygenation (ECMO) therapy has increased in the adult population. Studies from the H1N1 influenza pandemic suggest that ECMO deployment in pregnancy is associated with favorable outcomes. With increasing numbers of pregnant women affected by COVID-19 (coronavirus disease 2019) and potentially requiring this life-saving therapy, we sought to compare comorbidities, costs, and outcomes between pregnancy- and nonpregnancy-associated ECMO therapy among reproductive-aged female patients. STUDY DESIGN: We used the 2013 to 2019 National Readmissions Database. Diagnosis and procedural coding were used to identify ECMO deployment, potential indications, comorbid conditions, and pregnancy outcomes. The primary outcome was in-hospital mortality during the patient's initial ECMO stay. Secondary outcomes included length of stay and hospital charges/costs, occurrence of thromboembolic or bleeding complications during ECMO hospitalization, and mortality and readmissions up to 330 days following ECMO stay. Univariate and multivariate regression models were used to model the associations between pregnancy status and outcomes. RESULTS: The sample included 324 pregnancy-associated hospitalizations and 3,805 nonpregnancy-associated hospitalizations, corresponding to national estimates of 665 and 7,653 over the study period, respectively. Pregnancy-associated ECMO had lower incidence of in-hospital death (adjusted odds ratio [aOR]: 0.56, 95% confidence interval [CI]: 0.41-0.75) and bleeding complications (aOR: 0.67, 95% CI: 0.49-0.93). Length of stay was significantly shorter (adjusted rate ratio (aRR): 0.86, 95% CI: 0.77-0.96) and total hospital costs were less (aRR: 0.83, 95% CI: 0.75-0.93). Differences in the incidence of thromboembolic events (aOR: 1.04, 95% CI: 0.78-1.38) were not statistically significant. CONCLUSION: Pregnancy-associated ECMO therapy had lower incidence of in-hospital death, bleeding complications, total inpatient cost, and length of stay when compared with nonpregnancy-associated ECMO therapy without increased thromboembolic complications. Pregnancy-associated ECMO therapy should be offered to eligible patients. KEY POINTS: · Pregnancy-related ECMO use was compared with nonpregnant use.. · Outcomes were equal or favored pregnancy-related deployment.. · These data may be useful when considering ECMO use in pregnancy..

Universal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Testing for Obstetric Inpatient Units Across the United States.

BACKGROUND: The purpose of this study was to estimate prevalence of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patients admitted to obstetric inpatient units throughout the United States as detected by universal screening. We sought to describe the relationship between obstetric inpatient asymptomatic infection rates and publicly available surrounding community infection rates. METHODS: A cross-sectional study in which medical centers reported rates of positive SARS-CoV-2 testing in asymptomatic pregnant and immediate postpartum patients over a 1-3-month time span in 2020. Publicly reported SARS-CoV-2 case rates from the relevant county and state for each center were collected from the COVID Act Now dashboard and the COVID Tracking Project for correlation analysis. RESULTS: Data were collected from 9 health centers, encompassing 18 hospitals. Participating health centers were located in Alabama, California, Illinois, Louisiana, New Jersey, North Carolina, Pennsylvania, Rhode Island, Utah, and Washington State. Each hospital had an active policy for universal SARS-CoV-2 testing on obstetric inpatient units. A total of 10 147 SARS-CoV-2 tests were administered, of which 124 were positive (1.2%). Positivity rates varied by site, ranging from 0-3.2%. While SARS-CoV-2 infection rates were lower in asymptomatic obstetric inpatient groups than the surrounding communities, there was a positive correlation between positivity rates in obstetric inpatient units and their surrounding county (P=.003, r=.782) and state (P=.007, r=.708). CONCLUSIONS: Given the correlation between community and obstetric inpatient rates, the necessity of SARS-CoV-2-related healthcare resource utilization in obstetric inpatient units may be best informed by surrounding community infection rates.

Comparison of severe maternal morbidity in pregnancy by modified World Health Organization Classification of maternal cardiovascular risk.

BACKGROUND: To compare rates of severe maternal morbidity (SMM) for pregnant patients with a cardiac diagnosis classified by the modified World Health Organization (mWHO) classification to those without a cardiac diagnosis. METHODS: This retrospective study using the 2015-2019 Nationwide Readmissions Database identified hospitalizations, comorbidities, and outcomes using diagnosis and procedure codes. The primary exposure was cardiac diagnosis, classified into low-risk (mWHO class I and II) and moderate-to-high-risk (mWHO class II/III, III, or IV). The primary outcome was SMM or death during the delivery hospitalization; secondary outcomes included cardiac-specific SMM during delivery hospitalizations and readmissions after the delivery hospitalization. RESULTS: A weighted national estimate of 14,995,122 delivery admissions was identified, including 46,541 (0.31%) with mWHO I-II diagnoses and 37,330 (0.25%) with mWHO II/III-IV diagnoses. Patients with mWHO II/III-IV diagnoses experienced SMM at the highest rates (22.8% vs 1.6% for no diagnosis; with adjusted relative risk (aRR) of 5.67 [95% CI: 5.36-6.00]). The risk of death was also highest for patients with mWHO II/III-IV diagnoses (0.3% vs <0.1% for no diagnosis; aRR 18.07 [95% CI: 12.25-26.66]). Elevated risk of SMM and death persisted to 11 months postpartum for those patients with mWHO II/III-IV diagnoses. CONCLUSIONS: In this nationwide database, SMM is highest among individuals with moderate-to-severe cardiac disease based on mWHO classification. This risk persists in the year postpartum. These results can be used to enhance pregnancy counseling.

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

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

The Hassan Neonatal Morbidity Composite Scale and Neonatal Length of Stay-A Validation Study.

OBJECTIVE: Obstetric studies often report neonatal morbidity as a composite score. Composite scores can simplify data analysis when multiple outcomes of interest are present and allows researchers to conduct smaller, more manageable trials. The Hassan scale is a neonatal morbidity composite scale that assigns high scores to infants with multiple morbidities and low scores to infants without or with single morbidities. The objective of this study was to validate the association between scores on the Hassan scale and neonatal intensive care unit (NICU) length of stay STUDY DESIGN: We conducted a cohort study of all infants born between 22 and 366/7 weeks' gestation and cared for within 419 neonatal units in the Pediatrix Medical Group between 1997 and 2018. Each infant was assigned a Hassan's score based on the number of neonatal morbidity events that occurred during the delivery hospitalization. The association between Hassan's scores and neonatal length of stay was evaluated using linear regression. Multivariable models were constructed to determine if the Hassan score was independently associated with neonatal length of stay. RESULTS: There were 760,037 infants included. The median (interquartile range [IQR]) gestational age of delivery was 34 (31, 35) weeks and the median (IQR) birth weight at delivery was 2,000 (1,503, 2,430) g. The median length of stay for infants discharged home was 17 (10-33) days. A Hassan's score was able to be assigned to 699,206 (92%) patients. Neonatal morbidities included in the Hassan scale were more common among infants born earlier in gestation. On adjusted analysis, the Hassan scale was found to be independently associated with neonatal length of stay (p < 0.001, coefficient = 10.4 days [95% confidence interval (CI): 10.3, 10.4 days]) with higher scores associated with longer lengths of stay. CONCLUSION: The Hassan scale, more than a binary composite score, is able to differentiate preterm infants with prolonged hospitalizations from those with short hospitalizations. KEY POINTS: · The Hassan scale is an independent predictor of neonatal length of stay.. · Classification of infants based on number of morbidities correlates with neonatal length of stay.. · The Hassan scale provided better discrimination than binary composite morbidity scores.. · The Hassan scale may be an economic predictor of health-related costs..

How do I develop a process to effectively treat parturients with iron deficiency anemia?

Anemia is common in pregnant women and is associated with increased morbidity for the mother and the fetus, including increased risk of allogeneic blood transfusion. Iron deficiency is the most common etiology for anemia during pregnancy. Oral iron therapy remains the standard treatment but is often poorly tolerated due to its gastrointestinal side effects. Intravenous iron has been shown to be a safe and effective way to treat iron deficiency anemia but may be challenging to do in the outpatient setting given the need for an indwelling venous catheter and a small risk of infusion reactions. To improve outcomes associated with anemia, we launched a program to refer and treat obstetric patients with iron deficiency anemia for outpatient intravenous iron therapy through our preoperative anemia clinic. Here, we describe the process and successes of our program, including the clinical outcomes (change in hemoglobin and transfusion rates) from the first 2 years of the program.

Prospective, randomized, double-blind, placebo-controlled evaluation of the Pharmacokinetics, Safety and Efficacy of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia.

BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system. OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes. STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned expectant management. In addition to standard therapy, patients were randomized to receive either recombinant human antithrombin 250 mg loading dose followed by a continuous infusion of 2000 mg per 24 hours or an identical saline infusion until delivery. The primary outcome was days gained from randomization until delivery. The secondary outcome was composite neonatal morbidity score. A total of 120 women were randomized. RESULTS: There was no difference in median gestational age at enrollment (27.3 weeks' gestation for the recombinant human antithrombin group [range, 23.1-30.0] and 27.6 weeks' gestation for the placebo group [range, 23.0-30.0]; P=.67). There were no differences in median increase in days gained (5.0 in the recombinant human antithrombin group [range, 0-75] and 6.0 for the placebo group [range, 0-85]; P=.95). There were no differences between groups in composite neonatal morbidity scores or in maternal complications. No safety issues related to recombinant human antithrombin were noted in this study, despite the achievement of supraphysiological antithrombin concentrations. CONCLUSION: The administration of recombinant human antithrombin in preterm preeclampsia neither prolonged pregnancy nor improved neonatal or maternal outcomes.

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.

Effect of Cord Blood Magnesium Level at Birth on Non-neurologic Neonatal Outcomes.

OBJECTIVE: We examined the effects of magnesium sulfate on non-neurologic neonatal outcomes with respect to cord blood magnesium level. STUDY DESIGN: We conducted a secondary analysis of the Maternal-Fetal Medicine Units Beneficial Effects of Antenatal Magnesium (MFMU BEAM) trial comparing the upper and lower quintiles of cord blood magnesium level. Outcomes included cerebral palsy (CP), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and assessments of mental and motor disability. Logistic regression was used to estimate adjusted odds ratios (aORs) of each outcome, controlling for gestational age (GA), birth weight, and treatment group (TG). RESULTS: A total of 1,254 women of the 2,444 included in the BEAM trial had cord blood magnesium levels recorded. GA and birth weight were lower and TG was more common in the upper quintile cohort (p < 0.001). Neonates in the upper quintile were more likely to have severe NEC (OR, 2.41, 95% confidence interval [CI]: 1.11-5.24), ROP (OR, 1.65, 95% CI: 1.05-2.59), and BPD (OR, 1.70, 95% CI: 1.04-2.73). Adjustment for covariates demonstrated no difference in the NEC, ROP, and BPD rates, although there was a decrease in rates of mental disability index < 70 which was not seen in the unadjusted analysis (aOR, 0.49, 95% CI: 0.25-0.99). CONCLUSION: Higher cord blood magnesium levels do not appear to have adverse non-neurologic effects on the neonate and may demonstrate improvement in neurologic outcomes.

Induction of Labor versus Scheduled Cesarean in Morbidly Obese Women: A Cost-Effectiveness Analysis.

OBJECTIVE: To assess the costs, complication rates, and harm-benefit tradeoffs of induction of labor (IOL) compared to scheduled cesarean delivery (CD) in women with class III obesity. STUDY DESIGN: We conducted a cost analysis of IOL versus scheduled CD in nulliparous morbidly obese women. Primary outcomes were surgical site infection (SSI), chorioamnionitis, venous thromboembolism, blood transfusion, and readmission. Model outcomes were mean cost of each strategy, cost per complication avoided, and complication tradeoffs. We assessed the costs, complication rates, and harm-benefit tradeoffs of IOL compared with scheduled CD in women with class III obesity. RESULTS: A total of 110 patients underwent scheduled CD and 114 underwent IOL, of whom 61 (54%) delivered via cesarean. The group delivering vaginally experienced fewer complications. SSI occurred in 0% in the vaginal delivery group, 13% following scheduled cesarean, and 16% following induction then cesarean. In the decision model, the mean cost of induction was $13,349 compared with $14,575 for scheduled CD. Scheduled CD costs $9,699 per case of chorioamnionitis avoided, resulted in 18 cases of chorioamnionitis avoided per additional SSI and 3 cases of chorioamnionitis avoided per additional hospital readmission. In sensitivity analysis, IOL is cost saving compared with scheduled CD unless the cesarean rate following induction exceeds 70%. CONCLUSION: In morbidly obese women, induction of labor remains cost-saving until the rate of cesarean following induction exceeds 70%.

Screening extremely obese pregnant women for obstructive sleep apnea.

BACKGROUND: Obesity is prevalent among pregnant women in the United States; obstructive sleep apnea is highly comorbid with obesity and is associated with adverse pregnancy outcomes. Screening for obstructive sleep apnea in pregnant women has remained a challenge because of a lack of validated screening tools. OBJECTIVE: The purpose of this study was to evaluate established obstructive sleep apnea screening tools, a sleepiness scale, and individual component items in a cohort of pregnant women with extreme obesity in mid pregnancy with the use of objective testing to determine obstructive sleep apnea status and to describe the prevalence of obstructive sleep apnea among women with extreme obesity. STUDY DESIGN: Adult pregnant subjects, between 24 and 35 weeks gestation, with a body mass index ≥40 kg/m2 at the time of enrollment completed obstructive sleep apnea screening tools (Berlin Questionnaire, American Society of Anesthesiologists checklist, and STOP-BANG questionnaire) and the Epworth Sleepiness Scale; they also underwent physical examination of the neck, mouth, and airway. The published obstructive sleep apnea in pregnancy prediction score was calculated for each subject. Obstructive sleep apnea status for each subject was determined by the results of an overnight, unattended type III home sleep apnea test. RESULTS: Twenty-four percent of pregnant women with extreme obesity had obstructive sleep apnea on home sleep apnea testing in mid pregnancy (Apnea-Hypopnea Index, ≥5 events per hour]. Established obstructive sleep apnea screening tools performed very poorly to screen for obstructive sleep apnea in this cohort. Age, body mass index, neck circumference, frequently witnessed apneas, and highly likely to fall asleep while driving were associated most strongly with obstructive sleep apnea status in this cohort. CONCLUSION: We found that 24% of pregnant women with body mass index ≥40 kg/m2 between 24 and 35 weeks gestation have obstructive sleep apnea, defined as Apnea-Hypopnea Index ≥5 events per hour on an overnight type III home sleep apnea test. We found the Berlin Questionnaire, American Society of Anesthesiologists checklist, STOP-BANG, obstructive sleep apnea in pregnancy score by Facco et al, and the Epworth Sleepiness Scale were not useful screening tools for obstructive sleep apnea in a cohort of obese pregnant women. However, age, body mass index, neck circumference, frequently witnessed apneas, and likely to fall asleep while driving were associated with obstructive sleep apnea in this cohort. Further studies are needed to adjust the criteria and thresholds within the available screening tools to better predict obstructive sleep apnea in pregnant women with obesity.

Neonatal Outcomes Associated with Noncephalic Presentation at Delivery in Preterm Birth.

OBJECTIVE: The objective of this study is to evaluate the effect of noncephalic presentation on neonatal outcomes in preterm delivery. STUDY DESIGN: In this study a secondary analysis of the BEAM trial was performed. It included women with singleton, liveborn, and nonanomalous fetuses. Neonatal outcomes were compared in noncephalic versus cephalic presentation. Adjusted odds ratios and 95% confidence intervals were calculated for each outcome with logistic regression while controlling for possible confounders. A stratified analysis by mode of delivery was also performed in this study. RESULTS: A total of 458 noncephalic deliveries were compared with 1,485 cephalic deliveries. In multivariate analysis, noncephalic presentation was associated with increased risk of death in the neonatal intensive care unit (NICU) or death at <15 months corrected gestational age (cGA), and a decreased risk of IVH. The risk of death persisted in stratified analysis, with increased risk of death at <15 months cGA in noncephalic neonates born via cesarean delivery. In the vaginal delivery group, there was an increased risk of death at <15 months cGA and NICU death. CONCLUSION: After controlling for possible confounders, neonates who are noncephalic at delivery have higher risk for death <15 months cGA and death in the NICU while their risk of IVH is reduced. The risk of death persisted in stratified analyses by mode of delivery.

The Oxytocin Product Correlates with Total Oxytocin Received during Labor: A Research Methods Study.

OBJECTIVE: Total dose of oxytocin received during labor is an important variable in studies of human labor but is difficult to calculate. We sought to identify a surrogate measure for total dose of oxytocin received. STUDY DESIGN: For each subject receiving oxytocin during labor, the oxytocin total dose received in labor was calculated as the area under the curve. Maximal oxytocin infusion rate, total duration of oxytocin infusion, and the product of both, defined as the oxytocin product, were then each correlated with the total dose of oxytocin received using the Pearson's correlation coefficient. RESULTS: Oxytocin dosing data were available from 402 women at Duke and 6,907 women from Pithagore6. The two variables alone, or combined as the oxytocin product, demonstrated a high correlation with the oxytocin total dose (r > 0.7), with the oxytocin product demonstrating the highest (r > 0.9). This was true whether labor was induced or augmented and whether delivery was vaginal or cesarean. CONCLUSION: The oxytocin product, composed of two easily obtained variables, demonstrated a very high correlation with total oxytocin dose received in labor and represents a simple and accurate surrogate for total dose of oxytocin received during labor. The oxytocin product can be used in clinical studies in which oxytocin dose is an important variable.

The association of single-nucleotide polymorphisms in the oxytocin receptor and G protein-coupled receptor kinase 6 (GRK6) genes with oxytocin dosing requirements and labor outcomes.

BACKGROUND: Oxytocin is a potent uterotonic agent that is widely used for induction and augmentation of labor. Oxytocin has a narrow therapeutic index and the optimal dosing for any individual woman varies widely. OBJECTIVE: The objective of this study was to determine whether genetic variation in the oxytocin receptor (OXTR) or in the gene encoding G protein-coupled receptor kinase 6 (GRK6), which regulates desensitization of the oxytocin receptor, could explain variation in oxytocin dosing and labor outcomes among women being induced near term. STUDY DESIGN: Pregnant women with a singleton gestation residing in Durham County, NC, were prospectively enrolled as part of the Healthy Pregnancy, Healthy Baby cohort study. Those women undergoing an induction of labor at 36 weeks or greater were genotyped for 18 haplotype-tagging single-nucleotide polymorphisms in OXTR and 7 haplotype-tagging single-nucleotide polymorphisms in GRK6 using TaqMan assays. Linear regression was used to examine the relationship between maternal genotype and maximal oxytocin infusion rate, total oxytocin dose received, and duration of labor. Logistic regression was used to test for the association of maternal genotype with mode of delivery. For each outcome, backward selection techniques were utilized to control for important confounding variables and additive genetic models were used. Race/ethnicity was included in all models because of differences in allele frequencies across populations, and Bonferroni correction for multiple testing was used. RESULTS: DNA was available from 482 women undergoing induction of labor at 36 weeks or greater. Eighteen haplotype-tagging single-nucleotide polymorphisms within OXTR and 7 haplotype-tagging single-nucleotide polymorphisms within GRK6 were examined. Five single-nucleotide polymorphisms in OXTR showed nominal significance with maximal infusion rate of oxytocin, and two single-nucleotide polymorphisms in OXTR were associated with total oxytocin dose received. One single-nucleotide polymorphism in OXTR and two single-nucleotide polymorphisms in GRK6 were associated with duration of labor, one of which met the multiple testing threshold (P = .0014, rs2731664 [GRK6], mean duration of labor, 17.7 hours vs 20.2 hours vs 23.5 hours for AA, AC, and CC genotypes, respectively). Three single-nucleotide polymorphisms, two in OXTR and one in GRK6, showed nominal significance with mode of delivery. CONCLUSION: Genetic variation in OXTR and GRK6 is associated with the amount of oxytocin required as well as the duration of labor and risk for cesarean delivery among women undergoing induction of labor near term. With further research, pharmacogenomic approaches may potentially be utilized to develop personalized treatment to improve safety and efficacy outcomes among women undergoing induction of labor.

Cesarean delivery among women with prolonged labor induction.

OBJECTIVE: The objective of this study was to determine characteristics associated with cesarean delivery among women with labor induction lasting over 24 h. STUDY DESIGN: Women with live singleton pregnancies without prior cesarean delivery undergoing a labor induction lasting >24 h between September 2006 and March 2009 at Duke University Hospital were identified. Collected variables were compared between subjects by mode of delivery. A multivariate logistic regression model for the outcome cesarean delivery was constructed separately for nulliparous and parous women. RESULTS: There were 303 women who met inclusion criteria. The overall cesarean delivery rate was 57% (n=172) and remained constant with time (P=0.15, test-for-trend). Nulliparous women having a cesarean delivery were more likely to be obese [adjusted OR (aOR) 2.00; 95% CI 1.05, 3.80] and have a larger fetus [aOR 1.11 (aOR for every 100 g increase in birthweight), 95% CI 1.03, 1.20] compared to those having a vaginal delivery. CONCLUSION: Increasing BMI and birthweight were independent predictors of cesarean delivery among nulliparous women with prolonged labor induction. Despite this, after 24 h of labor induction, the overall mean cesarean delivery rate remained constant at 57%, and did not change with time. Among women having a vaginal delivery following a prolonged labor induction, we saw high rates of shoulder dystocia, operative vaginal delivery and severe perineal laceration.

Comparison of the Trends in Risk Factors and Management of Severe Postpartum Hemorrhage Years 2000-2004 Versus 2005-2008.

OBJECTIVE: To compare trends in the etiology and management of severe postpartum hemorrhage (PPH) during 2 time periods: 2000-2004 (Period 1) versus 2005-2008 (Period 2). STUDY DESIGN: Medical records with a diagnosis of PPH were identified by ICD-9 codes for immediate, third-stage, delayed, and secondary. PPH and post- partum coagulation defect. Subjects having a PPH within 24 hours of delivery who also received blood component therapy (defined as severe PPH) during Period 1 were compared with those from Period 2. RESULTS: There were 109 and 119 cases identified from Periods 1 and 2, respectively. Uterine atony was the most common cause of severe PPH during both time periods. In the second time period women with severe PPH had a lower mean hematocrit (p<0.05), a greater mean BMI (p<0.05), and more induced labor (p<0.01) as compared to the first time period. A greater proportion of the women in the second time period received misoprostol (p<0.0001) and platelets (p<0.05). The proportions of other therapies and surgical interventions remained unchanged, as did the ultimate outcomes. CONCLUSION: At a single large institution over the course of a 9-year period the management of severe PPH changed to include a greater utilization of misoprostol and platelet therapy.

Maternal Effects of Respiratory Syncytial Virus Infection during Pregnancy.

Given the illness and deaths caused by respiratory syncytial virus (RSV) infection during the first year of life, preventing infant RSV infections through maternal vaccination is intriguing. However, little is known about the extent and maternal effects of RSV infection during pregnancy. We describe 3 cases of maternal RSV infection diagnosed at a US center during winter 2014. Case-patient 1 (26 years old, week 33 of gestation) received a diagnosis of RSV infection and required mechanical ventilation. Case-patient 2 (27 years old, week 34 of gestation) received a diagnosis of infection with influenza A(H1N1) virus and RSV and required mechanical ventilation. Case-patient 3 (21 years old, week 32 of gestation) received a diagnosis of group A streptococcus pharyngitis and RSV infection and was monitored as an outpatient. Clarifying the effects of maternal RSV infection could yield valuable insights into potential maternal and fetal benefits of an effective RSV vaccination program.