Search

The skeletal and immune systems are intricately intertwined within the bone marrow microenvironment, a field of study termed osteoimmunology. Osteoimmune interactions are key players in bone homeostasis and remodeling. Despite the critical role of the immune system in bone health, virtually all animal research in osteoimmunology, and more broadly bone biology, relies on organisms with naïve immune systems. Drawing on insights from osteoimmunology, evolutionary anthropology, and immunology, this perspective proposes the use of a novel translational model: the dirty mouse. Dirty mice, characterized by diverse exposures to commensal and pathogenic microbes, have mature immune systems comparable to adult humans, while the naïve immune system of specific-pathogen free mice is akin to a neonate. Investigation into the dirty mouse model will likely yield important insights in our understanding of bone diseases and disorders. A high benefit of this model is expected for diseases known to have a connection between overactivation of the immune system and negative bone outcomes, including aging and osteoporosis, rheumatoid arthritis, HIV/AIDS, obesity and diabetes, bone marrow metastases, and bone cancers.

Objective We have previously described a model using maternal, antenatal, and ultrasonographic characteristics to assess the risk of delivery within 7 days following diagnosis of abnormal umbilical artery Doppler (UAD) in pregnancies affected by fetal growth restriction (FGR). Therefore, we sought to validate this model in an independent cohort. Study Design Retrospective, single referral center study of liveborn singleton pregnancies from 2016 to 2019 complicated by FGR and abnormal UAD (systolic/diastolic ratio ≥95th percentile for gestational age [GA]). Prediction probabilities were calculated by applying the original model (Model 1) to the current cohort (Brigham and Women's Hospital [BWH] cohort). The variables of this model include GA at first abnormal UAD, severity of first abnormal UAD, oligohydramnios, preeclampsia, and prepregnancy body mass index. Model fit was assessed with area under the curve (AUC). Two alternative models (Models 2 and 3) were created to identify a model with better predictive characteristics than Model 1. The receiver operating characteristics curves were compared using the DeLong test. Results A total of 306 patients were assessed for eligibility, 223 of whom were included in the BWH cohort. Median GA at eligibility was 31.3 weeks, and median interval from eligibility to delivery was 17 days (interquartile range: 3.5–33.5). Eighty-two (37%) patients delivered within 7 days of eligibility. Applying Model 1 to the BWH cohort resulted in an AUC of 0.865. Using the previously determined probability cutoff of 0.493, the model was 62% sensitive and 90% specific in predicting the primary outcome in this independent cohort. Models 2 and 3 did not perform better than Model 1 (p = 0.459). Conclusion A previously described prediction model to predict risk of delivery in patients with FGR and abnormal UAD performed well in an independent cohort. With high specificity, this model could assist in identifying low-risk patients and improve antenatal corticosteroid timing. Key Points

Aging induces alterations in bone structure and strength through a multitude of processes, exacerbating common aging- related diseases like osteoporosis and osteoarthritis. Cellular hallmarks of aging are examined, as related to bone and the marrow microenvironment, and ways in which these might contribute to a variety of age-related perturbations in osteoblasts, osteocytes, marrow adipocytes, chondrocytes, osteoclasts, and their respective progenitors. Cellular senescence, stem cell exhaustion, mitochondrial dysfunction, epigenetic and intracellular communication changes are central pathways and recognized as associated and potentially causal in aging. We focus on these in musculoskeletal system and highlight knowledge gaps in the literature regarding cellular and tissue crosstalk in bone, cartilage, and the bone marrow niche. While senolytics have been utilized to target aging pathways, here we propose non-pharmacologic, exercise-based interventions as prospective "senolytics" against aging effects on the skeleton. Increased bone mass and delayed onset or progression of osteoporosis and osteoarthritis are some of the recognized benefits of regular exercise across the lifespan. Further investigation is needed to delineate how cellular indicators of aging manifest in bone and the marrow niche and how altered cellular and tissue crosstalk impact disease progression, as well as consideration of exercise as a therapeutic modality, as a means to enhance discovery of bone-targeted therapies.

The standard care model in the postpartum period is ripe for disruption and attention. Hypertensive disorders of pregnancy (HDPs) can continue to be a challenge for the postpartum person in the immediate postpartum period and is a harbinger of future health risks. The current care approach is inadequate to address the needs of these women. We propose a model for a multidisciplinary clinic and collaboration between internal medicine specialists and obstetric specialists to shepherd patients through this high-risk time and provide a bridge for lifelong care to mitigate the risks of a HDP. Key Points

OBJECTIVE To examine the association between county-level caesarean delivery (CD) rates among women at low risk and morbidity among term newborns. DESIGN Cross-sectional study. SETTING Population-based study of US county-level birth data from 2015 to 2017. POPULATION Nulliparous women with term, singleton, vertex-presenting infants (NTSV) at low risk for morbidity. METHODS The primary exposure was county-level CD rates. MAIN OUTCOME MEASURES The outcome was morbidity among the low-risk NTSV cohort, categorised as severe (5-minute Apgar score of ≤3, assisted ventilation for ≥6 hours, severe neurologic injury or seizure, transfer or death) or moderate (5-minute Apgar score of 3, administration of antibiotics or assisted ventilation at delivery). We used linear regression models to determine the association between county NTSV CD and neonatal morbidity rates with cluster robust standard errors. RESULTS The analysis included data from 2 753 522 births in 952 counties from all 48 states. The mean NTSV CD rate was 23.6% (standard deviation 4.8%). The median severe and moderate neonatal morbidity rates were 15.2 (interquartile range, IQR 9.4-23.6) and 52.5 (IQR 33.4-75.7) per 1000 births, respectively. In the unadjusted analysis using the risk-adjusted exposure and outcome, every percentage point increase in the CD rate of a county was associated with 0.6 (95% CI -0.9, -0.3) and 2.3 fewer (95% CI -3.4, -1.1) cases of severe and moderate neonatal morbidity per 1000 live births. After adjustment for other county factors, the relationships remained significant. These findings were tested in multiple sensitivity analyses. CONCLUSIONS Lower county-level NTSV CD rates were associated with a small increase in morbidity among term newborns in the USA. TWEETABLE ABSTRACT Lower county-level caesarean delivery rates were associated with an increase in morbidity among term newborns in the USA.

Objective Preventing the first cesarean delivery (CD) is important as CD rates continue to rise. During the novel coronavirus disease 2019 (COVID-19) pandemic, quality improvement metrics at our hospital identified lower rates of CD. We sought to investigate this change and identify factors that may have contributed to the decrease. Study Design We compared nulliparous singleton deliveries at a large academic hospital during the COVID-19 pandemic (April through July 2020 during a statewide “stay-at-home” order) to those in the same months 1 year prior to the pandemic (April through July 2019). The primary outcome, mode of delivery, was obtained from the electronic medical record system, along with indication for CD. Results The cohort included 1,913 deliveries: 892 in 2019 and 1,021 in 2020. Patient characteristics (age, body mass index, race, ethnicity, and insurance type) did not differ between the groups. Median gestational age at delivery was the same in both groups. The CD rate decreased significantly during the COVID-19 pandemic compared with prior (28.9 vs. 33.6%; p = 0.03). There was a significant increase in the rate of labor induction (45.7 vs. 40.6%; p = 0.02), but no difference in the proportion of inductions that were elective (19.5 vs. 20.7%; p = 0.66). The rate of CD in labor was unchanged (15.9 vs. 16.3%; p = 0.82); however, more women attempted a trial of labor (87.0 vs. 82.6%; p = 0.01). Thus, the proportion of CD without a trial of labor decreased (25.1 vs. 33.0%; p = 0.04). Conclusion There was a statistically significant decrease in CD during the COVID-19 pandemic at our hospital, driven by a decrease in CD without a trial of labor. The increased rate of attempted trial of labor suggests the presence of patient-level factors that warrant further investigation as potential targets for decreasing CD rates. Additionally, in a diverse and medically complex population, increased rates of labor induction were not associated with increased rates of CD. Key Points

Chronic overfeeding via a high-fat/high-sugar (HFHS) diet decreases wheel running and substantially alters the gut metabolome of C57BL/6J mice. In this study, we tested the hypothesis that fecal microbial transplants can modulate the effect of diet on wheel running.Singly housed, 6-wk-old male C57BL/6J mice were fed either a grain-based diet (CHOW) or HFHS diet and provided a running wheel for 13 wk. Low-active, HFHS-exposed mice were then either switched to a CHOW diet and given an oral fecal microbial transplant from mice fed the CHOW diet, switched to a CHOW diet and given a sham transplant, or remained on the HFHS diet and given a fecal microbial transplant from mice fed the CHOW diet. Total wheel running, nutrient intake, body composition, fecal microbial composition, fecal metabolite composition, and liver steatosis were measured at various times throughout the study.We found that an HFHS diet decreases wheel running activity, increases body fat, and decreases microbial alpha diversity compared with a CHOW diet. Improvements in wheel running, body composition, and microbial alpha diversity were accomplished within 2 wk for mice switched from an HFHS diet to a CHOW diet with no clear evidence of an added benefit from fecal transplants. A fecal transplant from mice fed a CHOW diet without altering diet did not improve wheel running or body composition. Wheel running, body composition, fecal microbial composition, fecal metabolite composition, and liver steatosis percentage were primarily determined by diet.Our results suggest that diet is a primary mediator of wheel running with no clear effect from fecal microbial transplants.

To investigate whether diminishing insulin requirement in the third trimester is associated with placental dysfunction. Two-year retrospective cohort study at one tertiary care center of women with pregestational or gestational diabetes, their insulin requirements, and complications associated with placental dysfunction. Of 157 women, 21 (13%) experienced declining insulin requirement, with average decline of 28% at 34 weeks. They were more likely to have pregestational diabetes (71.4% vs. 42.6%; p

Chronic inflammation leads to bone loss and fragility. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) consistently promote bone resorption. Dietary modulation of proinflammatory cytokines is an accepted therapeutic approach to treat chronic inflammation, including that induced by space-relevant radiation exposure. As such, these studies were designed to determine whether an anti-inflammatory diet, high in omega-3 fatty acids, could reduce radiation-mediated bone damage via reductions in the levels of inflammatory cytokines in osteocytes and serum. Lgr5-EGFP C57BL/6 mice were randomized to receive diets containing fish oil and pectin (FOP; high in omega-3 fatty acids) or corn oil and cellulose (COC; high in omega-6 fatty acids) and then acutely exposed to 0.5-Gy (56)Fe or 2.0-Gy gamma-radiation. Mice fed the FOP diet exhibited consistent reductions in serum TNF-α in the (56)Fe experiment but not the gamma-experiment. The percentage osteocytes (%Ot) positive for TNF-α increased in gamma-exposed COC, but not FOP, mice. Minimal changes in %Ot positive for sclerostin were observed. FOP mice exhibited modest improvements in several measures of cancellous microarchitecture and volumetric bone mineral density (BMD) postexposure to (56)Fe and gamma-radiation. Reduced serum TNF-α in FOP mice exposed to (56)Fe was associated with either neutral or modestly positive changes in bone structural integrity. Collectively, these data are generally consistent with previous findings that dietary intake of omega-3 fatty acids may effectively mitigate systemic inflammation after acute radiation exposure and facilitate maintenance of BMD during spaceflight in humans. NEW & NOTEWORTHY This is the first investigation, to our knowledge, to test the impact of a diet high in omega-3 fatty acids on multiple bone structural and biological outcomes following space-relevant radiation exposure. Novel in biological outcomes is the assessment of osteocyte responses to this stressor. These data also add to the growing evidence that low-dose exposures to even high-energy ion species like (56)Fe may have neutral or even small positive impacts on bone.

Objective The aim of the study is to analyze maternal morbidity in the second stage of labor in a manner that approximates clinical choice. Study Design The study design comprises secondary analysis of the Consortium for Safe Labor, which included 228,688 deliveries at 19 hospitals between 2002 and 2008. We included the 107,675 women who were undergoing a trial of labor without a prior uterine scar or history of substance abuse, who reached the second stage, with a liveborn, nonanomalous, vertex, singleton, at term of at least 2,500 g. Maternal complications included postpartum fever, hemorrhage, blood transfusion, thrombosis, intensive care unit (ICU) admission, hysterectomy, and death. For maternal complications, we simulated the clinical choice by comparing operative vaginal or cesarean deliveries to continued expectant management at every hour in the second stage. For neonatal complications, we modeled the risk of severe neonatal complication by second stage duration for spontaneous vaginal deliveries only, adjusting for maternal demographics, comorbidities, and delivery hospital. Severe neonatal complications included death, asphyxia, hypoxic-ischemic encephalopathy (HIE), seizure, sepsis with prolonged stay, need for mechanical ventilation, and 5-minute Apgar score Results Maternal morbidity was higher with operative vaginal/cesarean delivery versus continued expectant management for every hour in the second stage, a difference that was statistically significant at hour 2 (18.4 vs. 14.7%; p Conclusion There is a trade-off between maternal and neonatal morbidity in the second stage of labor. Serious neonatal complications rise throughout, however, there is no time at which maternal morbidity is improved with a cesarean or operative vaginal delivery. Strategies are needed to identify neonates at highest risk of complication for targeted intervention. Key Points

Using a cephalic elevation device during second-stage cesarean deliveries decreases time to delivery after hysterotomy by 23 seconds., OBJECTIVE: A cephalic elevation device is an inflatable device that elevates the fetal head. We sought to evaluate whether such a device reduces time to delivery after hysterotomy and lowers morbidity in cesarean deliveries during the second stage of labor. METHODS: We conducted a double-blind randomized controlled trial among nulliparous, term women aged 18–50 years with vertex singleton pregnancies. Women were eligible if they were to undergo cesarean delivery in the second stage of labor. All participating women had the cephalic elevation device inserted by the delivering provider and were randomly allocated to inflation or noninflation of the device. Inflation was performed in a blinded fashion. The primary outcome was time from hysterotomy to delivery. A sample size of 30 per group (N=60 participants) was planned to detect a 50% decrease in time to delivery after hysterotomy with cephalic elevation device inflation. RESULTS: From January 2018 through July 2019, 60 women who underwent cesarean delivery in the second stage were randomized. Analysis was by intention to treat. Women in the inflation group were older (33 vs 30.5 years), but the groups were otherwise similar. In both groups, most women had a low-transverse hysterotomy (93%). The median time from hysterotomy to delivery was significantly shorter in the inflation group (31 vs 54 seconds; P

Objective Potentially avoidable maternity complications (PAMCs) have been validated as an indicator of access to quality prenatal care. African-American mothers have exhibited a higher incidence of PAMCs, which has been attributed to unequal health coverage. The objective of this study was to assess if racial disparities in the incidence of PAMCs exist in a universally insured population. Study Design PAMCs in each racial group were compared relative to White mothers using multivariate logistic regression. Stratified subanalyses assessed for adjusted differences in the odds of PAMCs for each racial group within direct versus purchased care. Results A total of 675,553 deliveries were included. Among them, 428,320 (63%) mothers were White, 112,170 (17%) African-American, 37,151 (6%) Asian/Pacific Islanders, and 97,912 (15%) others. African-American women (adjusted odds ratio [aOR]: 1.05, 95% CI: 1.02–1.08) were more likely to have PAMCs compared with White women, and Asian women (aOR: 0.92, 95% CI: 0.89–0.95) were significantly less likely to have PAMCs compared with White women. On stratified analysis according to the system of care, equal odds of PAMCs among African-American women compared with White women were realized within direct care (aOR: 1.03, 95% CI: 1.00–1.07), whereas slightly higher odds among African-American persisted in purchased (aOR: 1.05, 95% CI: 1.01–1.10). Conclusion Higher occurrence of PAMCs among minority women sponsored by a universal health coverage was mitigated compared with White women. Protocol-based care as in the direct care system may help overcome health disparities.

Objective We aimed to examine the relationship of sociodemographic variables with racial/ethnic disparities in unplanned cesarean births in a large academic hospital system. Secondarily, we investigated the relationship of these variables with differences in cesarean delivery indication, cesarean delivery timing, length of second stage and operative delivery. Study Design We conducted a retrospective cohort study of births >34 weeks between 2017 and 2019. Our primary outcome was unplanned cesarean delivery after a trial of labor. Multiple gestations, vaginal birth after cesarean, elective repeat or primary cesarean delivery, and contraindications for vaginal delivery were excluded. Associations between mode of delivery and patient characteristics were assessed using Chi-square, Fisher exact tests, or t-tests. Odds ratios were estimated by multivariate logistic regression. Goodness of fit was assessed with Hosmer Lemeshow test. Results Among 18,946 deliveries, the rate of cesarean delivery was 14.8% overall and 21.3% in nulliparous patients. After adjustment for age, body mass index (BMI), and parity, women of Black and Asian races had significantly increased odds of unplanned cesarean delivery; 1.69 (95% CI: 1.45,1.96) and 1.23 (1.08, 1.40), respectively. Single Hispanic women had adjusted odds of 1.65 (1.08, 2.54). Single women had increased adjusted odds of cesarean delivery of 1.18, (1.05, 1.31). Fetal intolerance was the indication for 39% (613) of cesarean deliveries among White women as compared to 63% (231) of Black women and 49% (71) of Hispanic women (p Conclusion Rates of unplanned cesarean delivery were significantly higher in Black and Asian compared to White women, even after adjustment for age, BMI, parity, and zip code income strata, and rates of unplanned cesarean delivery were higher for Hispanic women self-identifying as single. Racial and ethnic differences were seen in cesarean delivery indications and operative vaginal deliveries. Future work is urgently needed to better understand differences in provider care or patient attributes, and potential provider bias, that may contribute to these findings. Key Points

BACKGROUND Although there are many indications for a cesarean delivery, the “optimal” cesarean delivery rate is unknown. Neonatal and maternal morbidity have largely not been considered in the generation of hospital-level cesarean delivery rate targets. OBJECTIVE We sought to examine if the widely adopted and reported markers of maternal and neonatal morbidity were associated with hospital cesarean delivery rates to provide context for potential comparison and consideration for defining cesarean delivery rate targets. We hypothesized that hospitals with higher cesarean delivery rates would have increased rates of severe maternal morbidity, though we were less certain of the associations of the cesarean delivery rates with unexpected newborn complications. STUDY DESIGN This is a cross-sectional, ecological study using data from the 2016 Nationwide Readmission Database of hospitals with at least 100 deliveries per year. The exposure of interest was hospital cesarean delivery rate. The outcomes were (1) severe maternal morbidity with and without transfusion—in accordance with the Centers for Disease Control and Prevention's definition, and (2) neonatal morbidity—defined using The Joint Commission's Perinatal Quality metric of moderate and severe unexpected newborn complications among term, singleton, and nonanomalous neonates. Before assuming a single linear relationship to model the associations between morbidity and cesarean delivery rates, the Joinpoint Regression Analysis program was used to examine for potential splines in the relationships with both severe maternal morbidity (with and without transfusion) and severe and moderate unexpected newborn complications. Poisson regression model was then used to determine the association between morbidity and cesarean delivery rates. RESULTS The analysis included 831,111 deliveries from 621 hospitals. The mean cesarean delivery rate was 30.5%. The median severe maternal morbidity rate was 1.40 per 100 deliveries (interquartile range, 0.71–2.21 per 1000 deliveries). Excluding transfusion, the median severe maternal morbidity rate was 0.47 per 100 deliveries (interquartile range, 0.22–0.73 per 100 deliveries). The median rate of severe and moderate unexpected newborn complications was 1.01 per 100 low-risk newborns (interquartile range, 0.64–1.69 per 100 low-risk newborns) and 1.79 per 1000 low-risk newborns (interquartile range, 0.94–2.93 per 100 low-risk newborns), respectively. In the unadjusted analysis, every percentage point increase in a hospital's cesarean delivery rate was associated with a 3.4% (95% confidence interval, 2.3%–4.4%) and a 2.3% (95% confidence interval, 1.0%–3.5%) increase in severe maternal morbidity including and excluding transfusion, respectively. After adjustment for the case mix and hospital factors, only the relationship with severe maternal morbidity including transfusion remained significant: 3.3% (95% confidence interval, 1.7%–4.9%) increase in severe maternal morbidity per 1 percentage point increase in the cesarean delivery rate. There was no observed association between cesarean delivery rates and unexpected newborn complications CONCLUSION Severe maternal morbidity and unexpected newborn complications occur in fewer than 5 in 100 births. Findings from this analysis of hospitals with cesarean delivery rates ranging from 6.8%–56.3% suggest that those with lower cesarean delivery rates have lower severe maternal morbidity (which includes transfusion) and similar unexpected newborn complications compared with hospitals with higher cesarean delivery rates. This work may provide a helpful context to providers, hospitals, and policymakers who are measuring and reporting outcomes. Regarding neonatal morbidity in particular, the Joint Commission manual notes that the unexpected newborn complication metric was specifically designed to be compared against maternal-focused metrics such as cesarean delivery rates. More work is needed to define and identify appropriate measures of maternal and neonatal morbidity for these types of comparisons.

OBJECTIVE To examine the current patterns of care for women at high risk for delivery-related morbidity to inform discussions about the feasibility of this regionalized approach. METHODS We performed a cross-sectional study and linked 2014 American Hospital Association survey and State Inpatient Database data from seven representative states. We used American Hospital Association-reported hospital characteristics and State Inpatient Database procedure codes to assign a level of maternal care to each hospital. We then assigned each patient to a minimum required level of maternal care (I-IV) based on maternal comorbidities captured in the State Inpatient Database. Our outcome was delivery at a hospital with an inappropriately low level of maternal care. Comorbidities associated with delivery at an inappropriate hospital were assessed using descriptive statistics. RESULTS The analysis included 845,545 deliveries occurring at 556 hospitals. The majority of women had risk factors appropriate for delivery at level I or II hospitals (85.1% and 12.6%, respectively). A small fraction (2.4%) of women at high risk for maternal morbidity warranted delivery in level III or IV hospitals. The majority (97.6%) of women delivered at a hospital with an appropriate level of maternal care, with only 2.4% of women delivering at a hospital with an inappropriate level of maternal care. However, 43.4% of the 19,988 high-risk patients warranting delivery at level III or IV hospitals delivered at level I or II hospitals. Women with comorbidities likely to benefit from specialized care (eg, maternal cardiac disease, placenta previa with prior uterine surgery) had high rates of delivery at hospitals with an inappropriate level of maternal care (68.2% and 37.7%, respectively). CONCLUSION Though only 2.41% of deliveries occurred at hospitals with an inappropriate level of maternal care, a substantial fraction of women at risk for maternal morbidity delivered at hospitals potentially unequipped with resources to manage their needs. Promoting triage of high-risk patients to hospitals optimized to provide risk-appropriate care may improve maternal outcomes with minimal effect on most deliveries.

Background This article reports a unique case of cesarean scar pregnancy, demonstrating importance of early management and diagnosis. Case presentation A 30-year-old pregnant woman with prior history of two cesarean sections found to have cesarean scar pregnancy at approximately 13 weeks’ gestation and underwent a gravid hysterectomy. Conclusions While rare, cesarean scar pregnancies should be considered on the differential diagnosis of any pregnant patient with history of cesarean section who presents in early pregnancy with vaginal bleeding and/or cramping. Given the increased rates of cesarean sections in the times of COVID-19, one may anticipate seeing more cases of cesarean scar pregnancies.

Use of the selective estrogen receptor modulator Tamoxifen (TAM) is a mainstay to induce conditional expression of Cre recombinase in transgenic laboratory mice. To excise β‐cateninfl/fl in 28‐day‐old male and female Prrx1‐CreER/β‐cateninfl/fl mice (C57BL/6), we utilized TAM at 150 mg/kg; despite β‐catenin knockout in MSC, we found a significant increase in trabecular and cortical bone volume in all genders. Because TAM was similarly anabolic in KO and control mice, we investigated a dose effect on bone formation by treating wild‐type mice (WT C57BL/6, 4 weeks) with TAM (total dose 0, 20, 40, 200 mg/kg via four injections). TAM increased bone in a dose‐dependent manner analyzed by micro–computed tomography (μCT), which showed that, compared to control, 20 mg/kg TAM increased femoral bone volume fraction (bone volume/total volume [BV/TV]) (21.6% ± 1.5% to 33% ± 2.5%; 153%, p

Induction of labor is common in the United States. Multiple previous studies have tried to outline a faster time to delivery to improve maternal and fetal outcomes.This study aimed to evaluate whether women who undergo induction of labor with a single-balloon catheter and oxytocin have a shorter time to delivery with planned removal of the catheter at 6 vs 12 hours.In this randomized controlled trial, induction of labor was performed using a combination of single-balloon catheter and oxytocin. Term women, both nulliparous and multiparous, aged 18 to 50 years old with cephalic singletons were included if they were undergoing induction of labor with a Bishop score of6 and cervical dilation of2 cm. Women were randomized to planned removal of the single-balloon catheter at 6 hours vs 12 hours. The primary outcome was time from catheter insertion to delivery. We were powered to show a 4-hour time difference with a sample size of 89 women per group (n=178). Planned sensitivity analyses were performed to account for cesarean delivery in labor.From February 2019 to June 2020, 237 women were screened, 178 women were randomized, and 177 women were included in the final analysis (89 women in the 6-hour group and 88 women in the 12-hour group). Insertion to delivery time was significantly shorter in the 6-hour group (19.2 vs 24.3 hours; P=.04), and the proportion of women delivered by 24 hours was significantly greater in the 6-hour group (67.4% vs 47.4%; P.01). There was no difference in the Bishop score at removal of the catheter or secondary maternal or neonatal outcomes. In a Cox proportional-hazards model censoring for cesarean delivery, the 6-hour group had a significantly shorter insertion to delivery time (hazard ratio, 0.67; P=.02).Induction of labor with a single-balloon catheter and oxytocin with planned removal of the catheter at 6 hours rather than 12 hours results in a shorter time from insertion to delivery without increasing the rate of cesarean delivery. Decreasing the length of time a single-balloon catheter is in place should be considered in clinical protocols.

Intrauterine fetal demise (IUFD) and stillbirth are interchangeable terms to describe a fetal death in the second half of pregnancy. IUFD is defined as the delivery of a fetus showing no signs of life as indicated by the absence of heart rate, breathing, umbilical cord pulsation, or voluntary muscle movements. A thorough evaluation of maternal history and risk factors, fetal evaluation involving autopsy and genetic evaluation, and placental pathology should be offered at the time of IUFD diagnosis. Significant counseling should be provided to patients regarding future pregnancies and the risk of recurrence as well as the need for increased antenatal testing and delivery planning in subsequent pregnancies. This review contains 5 tables, 10 figures and 55 references. Keywords: fetal kick counts, intrauterine fetal demise (IUFD), management of intrauterine fetal demise, microarray, placental pathology, risk factors for intrauterine fetal demise

PURPOSE OF REVIEW: To highlight recent basic, translational, and clinical work demonstrating exercise and diet regulation of marrow adipose tissue (MAT) and bone, and how this informs current understanding of the relationship between marrow adiposity and musculoskeletal health. RECENT FINDINGS: Marrow adipocytes accumulate in bone in the setting of hypercaloric intake (calorie excess; e.g. diet-induced obesity), but also with hypocaloric intake (calorie restriction; e.g. anorexia), despite the fact that these states affect bone differently. With hypercaloric intake, bone quantity is largely unaffected whereas with hypocaloric intake, bone quantity and quality are greatly diminished. Voluntary running exercise in rodents was found to lower MAT and promote bone in eucaloric and hypercaloric states, while degrading bone in hypocaloric states, suggesting differential modulation of MAT and bone, dependent upon whole body energy status. Energy status alters bone metabolism and bioenergetics via substrate availability or excess, which plays a key role in the response of bone and MAT to mechanical stimuli. SUMMARY: Marrow adipose tissue (MAT) is a fat depot with a potential role in – as well as responsivity to – whole body energy metabolism. Understanding the localized function of this depot in bone cell bioenergetics and substrate storage, principally in the exercised state, will aid to uncover putative therapeutic targets for skeletal fragility.

Chronic granulomatous disease (CGD) is a primary immunodeficiency syndrome that results in increased risk for bacterial and fungal infections, as well as inflammatory/autoimmune complications. While CGD historically has been associated with early death in childhood, the life expectancy and morbidity of patients with CGD have greatly improved. Many patients with CGD now survive well into adulthood, and data on adult cohorts of patients with CGD have been published. However, reports of pregnancy management, complications, and outcomes for patients with CGD are sparse. In addition, management of invasive fungal infections, including use of newer triazole antifungals, during pregnancy has not been well described. We report a case of fungal lung infection in a pregnant woman with CGD, diagnosed during her second trimester, which was treated with multiple antifungal agents, including more than 12 weeks of isavuconazole therapy, resulting in resolution of infection and delivery of a healthy newborn at term.

Objective Breast cancer is one of the most frequently diagnosed cancers in pregnancy and is commonly treated with chemotherapy. To date, studies examining effects of chemotherapy during pregnancy on fetal growth have yielded conflicting results, and most are limited by small sample sizes or are nonspecific with respect to cytotoxic regimen or type of cancer treated. We sought to evaluate the effect of chemotherapy for breast cancer in pregnancy on birthweight and small for gestational age infants. Study Design This is a retrospective cohort study of 74 women diagnosed with pathologically confirmed breast cancer during pregnancy between 1997 and 2018 at one of three academic medical centers, who had a singleton birth with known birthweight. Forty-nine received chemotherapy and 25 did not receive chemotherapy. Linear regression modeling was used to compare birthweight (by gestational age and sex-specific z-score) by chemotherapy exposure. Subanalyses of specific chemotherapy regimen and duration of chemotherapy exposure were also performed. Placental, neonatal, and maternal outcomes were also analyzed by chemotherapy exposure. Results In the adjusted model, chemotherapy exposure was associated with lower birthweight (Δ z-score = −0.49, p = 0.03), but similar rates of small for gestational age (defined as birthweight Conclusion Chemotherapy for breast cancer in pregnancy in this cohort is associated with lower birthweight but no difference in the rate of small for gestational age infants. Key Points

Objective This study was aimed to assess whether the “39-week” rule is being extended to high-risk pregnancies and if so whether this has led to changes in neonatal morbidity or stillbirth. Study Design Birth certificate data between 2010 and 2014 from 23 states (55% of births in the United States) were used. Pregnancies were classified as high risk if they had any one of the following: maternal age greater than or equal to 40 years, prepregnancy body mass index (BMI) greater than or equal to 40 kg/m2, chronic (prepregnancy) hypertension, or diabetes (pregestational or gestational). Delivery timing changes for all pregnancies at term (37 weeks or greater) were compared with changes in the high-risk population. Neonatal morbidities (neonatal intensive care unit [NICU] admission, need for assisted ventilation, 5-minute Apgar score, and macrosomia), maternal morbidities (intensive care unit [ICU] admission, cesarean delivery, operative vaginal delivery, chorioamnionitis, and severe perineal laceration), and stillbirth rates were compared across time periods. Multivariate logistic regression was used to analyze whether gestational age–specific morbidity changes were due to shifts in delivery timing. Results For the overall population, there was a shift in delivery timing between 2010 and 2014, a 2.5% decrease in 38-week deliveries, and a 2.3% increase in 39-week deliveries (p Conclusion There was a significant shift in delivery timing for high-risk pregnancies in the United States between 2010 and 2014. This shift, however, did not result in statistically significant changes in either neonatal morbidity or stillbirth. Key Points

To determine the relative effects of patient and hospital factors on a hospital’s postpartum readmission rate. This retrospective cohort study was conducted using State Inpatient Databases from California, Florida, and New York between 2004 and 2013. We compared patient and hospital characteristics among hospitals with low and high readmission rates using χ2 tests. Risk-adjusted 30-day readmission rates were calculated for patient, delivery, and hospital characteristics to understand factors affecting readmission using fixed and random effects models. Patients in hospitals with low readmission rates were more likely to be white, to have private insurance and higher incomes, and to have fewer comorbidities. The patient comorbidities with the highest risk-adjusted readmission rates included hypertension (range, 2.14–3.04%), obesity (1.78–2.94%), preterm labor/delivery (2.50–2.60%), and seizure disorder (1.78–3.35%). Delivery complications were associated with increased risk-adjusted readmission rates. Compared to patient characteristics, hospital characteristics did not have a profound impact on readmission risk. Obstetric readmissions were more attributable to patient and demographic characteristics than to hospital characteristics. Readmission metric-based incentives may ultimately penalize hospitals providing high-quality care due to patient characteristics specific to their catchment area.

OBJECTIVES This study characterizes cytogenetic abnormalities with ultrasound findings to refine counseling following negative cell-free DNA (cfDNA). METHODS A retrospective cohort of pregnancies with chromosome abnormalities and ultrasound findings was examined to determine the residual risk following negative cfDNA. Cytogenetic data was categorized as cfDNA detectable for aneuploidies of chromosomes 13, 18, 21, X, or Y or non-cfDNA detectable for other chromosome abnormalities. Ultrasound reports were categorized as structural anomaly, nuchal translucency (NT) ≥3.0 mm, or other "soft markers". Results were compared using chi squared and Fishers exact tests. RESULTS Of the 498 fetuses with cytogenetic abnormalities and ultrasound findings, 16.3% (81/498) had non-cfDNA detectable results. In the first, second, and third trimesters, 12.4% (32/259), 19.5% (42/215), and 29.2% (7/24) had non-cfDNA detectable results respectively. The first trimester non-cfDNA detectable results reduced to 7.7% (19/246) if triploidy was detectable by cfDNA testing. For isolated first trimester NT of 3.0-3.49 mm, 15.8% (6/38) had non-cfDNA detectable results, while for NT ≥3.5 mm, it was 12.3% (20/162). For cystic hygroma, 4.3% (4/94) had non-cfDNA detectable results. CONCLUSIONS Counseling for residual risk following cfDNA in the presence of an ultrasound finding is impacted by gestational age, ultrasound finding, and cfDNA detection of triploidy.

Objective The objective of this study was to investigate the relationship between preterm birth in a prior pregnancy and preterm birth in a twin pregnancy. Study Design We performed a secondary analysis of a randomized controlled trial evaluating 17-α-hydroxyprogesterone caproate in twins. Women were classified as nulliparous, multiparous with a prior term birth, or multiparous with a prior preterm birth. We used logistic regression to examine the odds of spontaneous preterm birth of twins before 35 weeks according to past obstetric history. Results Of the 653 women analyzed, 294 were nulliparas, 310 had a prior term birth, and 49 had a prior preterm birth. Prior preterm birth increased the likelihood of spontaneous delivery before 35 weeks (adjusted odds ratio [aOR]: 2.44, 95% confidence interval [CI]: 1.28–4.66), whereas prior term delivery decreased these odds (aOR: 0.55, 95% CI: 0.38–0.78) in the current twin pregnancy compared with the nulliparous reference group. This translated into a lower odds of composite neonatal morbidity (aOR: 0.38, 95% CI: 0.27–0.53) for women with a prior term delivery. Conclusion For women carrying twins, a history of preterm birth increases the odds of spontaneous preterm birth, whereas a prior term birth decreases odds of spontaneous preterm birth and neonatal morbidity for the current twin pregnancy. These results offer risk stratification and reassurance for clinicians.

Denmark and Ireland have reported drastic reductions in the rate of preterm birth during the coronavirus disease 2019 (COVID-19) global pandemic,1,2 though this was not found in the United Kingdom.3 These findings have led to widespread speculation, both in the academic and lay press, that the acts of social isolation and quarantine may lead to a reduction in the incidence of preterm birth.1–4 We investigated whether our hospital system in the United States had any change in the preterm delivery rate during the peak COVID-19 pandemic era when compared with the pre–COVID-19 era.

Elective induction of labor (ie, without a maternal or fetal indication) is common in the United States. When using the correct comparison group (elective induction vs expectant management) induction is not associated with an increased risk of cesarean delivery. Moreover, elective induction after 39 weeks seems to have maternal benefits (eg, lower infection rates) as well as a reduction in neonatal morbidity and the potential for a decrease in term stillbirth. However, these risks, especially stillbirth, are low in a healthy cohort and there are potential negative impacts on maternal satisfaction, breastfeeding, and cost/resource use that must be considered.

Objective The objective of this study was to assess the association between the angle of progression (AoP) measured by transperineal ultrasound and mode of delivery and duration of the second stage. Study Design This is a prospective observational study of nulliparous women with a singleton gestation at term in which serial transperineal ultrasound examinations were obtained during the second stage of labor. Multivariable logistic regression and adjusted survival models were used for the analysis. Results A total of 137 patients were included in the analysis and median AoP for the study group was 153 degrees. The adjusted odds ratio (aOR) of requiring an operative delivery was 2.6 times higher for those patients who had an AoP Conclusion The AoP has the potential to predict spontaneous vaginal delivery and the duration of the second stage of labor which may be useful in counseling patients and managing their labor.

Background Expectant mothers who are beneficiaries of TRICARE (universal insurance to United States Armed Services members and their dependents) can choose to receive care within direct (salary-based) or purchased (fee-for-service) care systems. We sought to compare frequency of intrapartum obstetric procedures and outcomes such as severe acute maternal morbidity (SAMM) and common postpartum complications between direct and purchased care systems within TRICARE. Methods TRICARE (2006-2010) claims data were used to identify deliveries. Patient demographics, frequency of types of delivery (noninstrumental vaginal, cesarean, and instrumental vaginal), comorbid conditions, SAMM, and common postpartum complications were compared between the two systems of care. Multivariable models adjusted for patient clinical/demographic factors determined the odds of common complications and SAMM complications in purchased care compared with direct care. Results A total of 440 138 deliveries were identified. Compared with direct care, purchased care had higher frequency (30.9% vs 25.8%, P