Genomic and epigenomic re-categorization of congenital glioblastoma and desmoplastic infantile ganglioglioma.

INTRODUCTION: The recently updated World Health Organization classification of central nervous system (CNS) tumors, 5th edition, (CNS5) reclassifies pediatric tumors according to their distinct molecular drivers, recognizing a new entity-infant-type hemispheric glioma (IHG). Defined by its unique epigenetic signature, and/or genomic fusions in ALK, ROS1, NTRK, or MET gene, IHG subsumes many cases previously classified as congenital glioblastoma (cGBM). Histologic features of IHG are still poorly defined with known overlap with a clinic radiologically similar entity-desmoplastic infantile ganglioglioma/astrocytoma (DIG). METHODS: We revisited our cohort of cGBMs and DIGs, now reclassifying them according to CNS5 and compared the clinical, radiologic, molecular and histologic features between the two. RESULTS: 3/6 cases of cGBM that underwent targeted NGS fusion mutation panel were positive for ALK fusions (involving MAP4, MZT2Bex2, and EML4 genes as fusion partners), and 1/6 showed GOPC:ROS1 fusion. Interestingly, GOPC:ROS1 fusion was also shared by 1/5 cases of histologically defined DIG. DNA methylation profiling using the Heidelberg classifier (v12.3) recategorized 2/5 DIG cases as IHG (including the case with ROS1 alteration). CONCLUSION: In conclusion, histology alone is insufficient to distinguish IHG from DIG, necessitating epigenomic and genomic testing for the diagnosis of early-life gliomas.

Decision to Incision and Risk for Fetal Acidemia, Low Apgar Scores, and Hypoxic Ischemic Encephalopathy.

OBJECTIVE: This study aimed to assess risk for fetal acidemia, low Apgar scores, and hypoxic ischemic encephalopathy based on decision-to-incision time interval in the setting of emergency cesarean delivery. STUDY DESIGN: This unplanned secondary analysis of the Maternal-Fetal Medicine Units prospective observational cesarean registry dataset evaluated risk for hypoxic ischemic encephalopathy, umbilical cord pH ≤7.0, and Apgar score ≤4 at 5 minutes based on decision-to-incision time for emergency cesarean deliveries. Cesarean occurring for nonreassuring fetal heart rate monitoring, bleeding previa, nonreassuring antepartum testing, placental abruption, or cord prolapse was classified as emergent. Decision-to-incision time was categorized as <10 minutes, 10 to <20 minutes, 20 to <30 minutes, 30 to <50 minutes, or ≥50 minutes. As secondary outcomes umbilical cord pH ≤7.1, umbilical artery pH ≤7.0, and Apgar score ≤5 at 5 minutes were analyzed. RESULTS: Of 5,784 women included in the primary analysis, 12.4% had a decision-to-incision interval ≤10 minutes, 20.2% 11 to 20 minutes, 14.9% 21 to 30 minutes, 18.2% 31 to 50 minutes, and 16.5% >50 minutes. Risk for umbilical cord pH ≤7.0 was highest at ≤10 and 11 to 20 minutes (10.2 and 7.9%, respectively), and lowest at 21 to 30 minutes (3.9%), 31 to 50 minutes (3.9%), and >50 minutes (3.5%) (p < 0.01). Risk for Apgar scores ≤4 at 5 minutes was also higher with decision-to-incision intervals ≤10 and 11 to 20 minutes (4.3 and 4.4%, respectively) compared with intervals of 21 to 30 minutes (1.7%), 31 to 50 minutes (2.1%), and >50 minutes (2.0%) (p < 0.01). Hypoxic ischemic encephalopathy occurred in 1.5 and 1.0% of women with decision-to-incision intervals of ≤10 and 11 to 20 minutes compared with 0.3 and 0.5% for women with decision-to-incision intervals of 21 to 30 minutes and 31 to 50 minutes (p = 0.04). Risk for secondary outcomes was also higher with shorter decision-to-incision intervals. CONCLUSION: Shorter decision-to-incision times were associated with increased risk for adverse outcomes in the setting of emergency cesarean. KEY POINTS: · Shorter intervals likely occur with higher risk cases.. · Shorter intervals were associated with higher neonatal risk.. · Shorter intervals were associated with low cord pH..

Opioid Use Disorder during Antepartum and Postpartum Hospitalizations.

OBJECTIVE: This study aimed to evaluate temporal trends in opioid use disorder (OUD) during antepartum and postpartum hospitalizations. STUDY DESIGN: This repeated cross-sectional analysis analyzed data from the National (Nationwide) Inpatient Sample. Women aged 15 to 54 years admitted antepartum or postpartum were identified. The presence of OUD was determined based on a diagnosis of opioid abuse, opioid dependence, or opioid overdose. Temporal trends in OUD were evaluated using the Rao-Scott chi-square test. Temporal trends in opioid overdose were additionally evaluated. RESULTS: An estimated 7,336,562 antepartum hospitalizations and 1,063,845 postpartum readmissions were included in this analysis. The presence of an OUD diagnosis during antepartum hospitalizations increased from 0.7% of patients in 1998 to 1999 to 2.9% in 2014 (p < 0.01) and during postpartum hospitalizations increased from 0.8% of patients in 1998 to 1999 to 2.1% of patients in 2014 (p < 0.01). Risk of overdose diagnoses increased significantly for both antepartum hospitalizations, from 22.7 per 100,000 hospitalizations in 1998 to 2000 to 70.3 per 100,000 hospitalizations in 2013 to 2014 (p < 0.001), and postpartum hospitalizations, from 18.8 per 100,000 hospitalizations in 1998 to 2000 to 65.2 per 100,000 hospitalizations in 2013 to 2014 (p = 0.02). DISCUSSION: Risk of OUD diagnoses and overdoses increased over the study period for both antepartum and postpartum hospitalizations.

Oral Opioid Use during Vaginal Delivery Hospitalizations.

OBJECTIVE: This study aimed to determine the receipt of short-acting opioid medications during vaginal delivery hospitalizations. STUDY DESIGN: The Perspective database was analyzed to evaluate patterns of short-acting oral opioid use during vaginal delivery hospitalizations from January 2006 to March 2015. Unadjusted and adjusted models evaluating the role of demographic and hospital factors were created evaluating use of opioids. Hospital-level rates of opioid use were evaluated. Opioid receipt among women with opioid abuse or dependence was evaluated based on overall hospital rates of opioid use. RESULTS: Of 3,785,396 vaginal delivery hospitalizations from 2006 to 2015, 1,720,899 (45.5%) women received an oral opioid for pain relief. Opioid use varied significantly among the 458 hospitals included in the analysis, with one-third of hospitals providing opioids to <38% of patients, one-third to 38 to <59% of patients, and one-third to ≥59% of patients. When hospitals were stratified by overall opioid administration rates, women with opioid abuse or dependence were less likely to be given opioids in hospitals with low overall opioid rates. DISCUSSION: The use of opioid pain medications during vaginal delivery hospitalizations varied significantly among hospitals, suggesting that standardization of pain management practices could reduce opioid use.

Maternal outcomes by race during postpartum readmissions.

BACKGROUND: Maternal race may be an important risk factor for postpartum readmissions and associated adverse outcomes. OBJECTIVE: To determine the association of race with serious complications during postpartum readmissions. STUDY DESIGN: This repeated cross-sectional analysis used the National (Nationwide) Inpatient Sample from the Healthcare Cost and Utilization Project from 2012 to 2014. Women ages 15-54 readmitted postpartum after a delivery hospitalization were identified by Centers for Disease Control and Prevention criteria. Race and ethnicity were characterized as non-Hispanic white, non-Hispanic black, Hispanic, Asian or Pacific islander, Native American, other, and unknown. Overall risk for readmission by race was determined. Risk for severe maternal morbidity during readmissions by race was analyzed. Individual outcomes including pulmonary edema/acute heart failure and stroke also were analyzed by race. Log-linear regression models including demographics, hospital factors, and comorbid risk were used to analyze risk for severe maternal morbidity during postpartum readmissions. RESULTS: Of 11.3 million births, 207,730 (1.8%) women admitted postpartum from 2012 to 2014 were analyzed, including 96,670 white, 47,015 black, and 33,410 Hispanic women. Compared with non-Hispanic white women, non-Hispanic black women were at 80% greater risk of postpartum readmission (95% confidence interval, 79%-82%) whereas Hispanic women were at 11% lower risk of readmission (95% confidence interval, 10%-12%). In unadjusted analysis, compared with non-Hispanic white women, non-Hispanic black women admitted postpartum were at 27% greater risk of severe maternal morbidity (95% confidence interval, 24%-30%) whereas Hispanic women were at 10% lower risk (95% confidence interval, 7%-13%). In the adjusted model, non-Hispanic black women were at 16% greater risk for severe maternal morbidity during readmission than non-Hispanic white women (95% confidence interval, 10%-22%), whereas Hispanic women were at 7% lower risk (95% confidence interval, 1%-12%). Differences in severe maternal morbidity risk between other racial groups and non-Hispanic white women were not significant. In addition to overall morbidity, non-Hispanic black women were at significantly greater risk for eclampsia, acute respiratory distress syndrome, and renal failure than other racial groups (P<.05 all). Black women were at 126% greater risk for pulmonary edema/acute heart failure than white women (95% confidence interval, 117%-136%). CONCLUSION: Black women were more likely (1) to be readmitted postpartum, (2) to suffer severe maternal morbidity during readmission, and (3) to suffer life threatening complications such as pulmonary edema/acute heart failure. At-risk women including black women with cardiovascular risk factors may benefit from short-term postpartum follow-up.

Postpartum hemorrhage outcomes and race.

BACKGROUND: How race is associated with adverse outcomes in the setting of postpartum hemorrhage is not well characterized. OBJECTIVE: The objective of this study was to assess how race is associated with adverse maternal outcomes in the setting of postpartum hemorrhage. STUDY DESIGN: This retrospective cohort study utilized the National (Nationwide) Inpatient Sample (NIS) from the Agency for Healthcare Research and Quality for the years 2012-2014. Women aged 15-54 years with a diagnosis of postpartum hemorrhage were included. Race and ethnicity were categorized as non-Hispanic white, non-Hispanic black, Hispanic, Asian or Pacific Islander, Native American, other, and unknown. Overall risk for severe morbidity based on Centers for Disease Control and Prevention criteria was analyzed along with risk for specific outcomes such as disseminated intravascular coagulation, hysterectomy, transfusion, and maternal death. Risk for severe morbidity was stratified by comorbid risk and compared by race. Weights were applied to create population estimates. Log-linear regression models were created to assess risk for severe morbidity with risk ratios and associated 95% confidence intervals as measures of effect. RESULTS: A total of 360,370 women with postpartum hemorrhage from 2012 to 2014 were included in this analysis. Risk for severe morbidity was significantly higher among non-Hispanic black women (26.6%) than non-Hispanic white, Hispanic, or Asian or Pacific Islander women (20.7%, 22.5%, and 21.4%, respectively, P < .01). For non-Hispanic black compared with non-Hispanic white, Hispanic, and Asian or Pacific Islander women risk was higher for disseminated intravascular coagulation (8.4% vs 7.1%, 6.8%, and 6.8%, respectively, P < .01) and transfusion (19.4% vs 13.9%, 16.1%, and 15.8%, respectively, P < .01). Black women were also more likely than non-Hispanic white women to undergo hysterectomy (2.4% vs 1.9%, P < .01), although Asian or Pacific Islander women were at highest risk (2.9%). Adjusting for comorbidity, black women remained at higher risk for severe morbidity (P < .01). Risk for death for non-Hispanic black women was significantly higher than for nonblack women (121.8 per 100,000 deliveries, 95% confidence interval, 94.7-156.8 vs 24.1 per 100,000 deliveries, 95% confidence interval, 19.2-30.2, respectively, P < .01). CONCLUSION: Black women were at higher risk for severe morbidity and mortality associated with postpartum hemorrhage.

Cesarean delivery in the United States 2005 through 2014: a population-based analysis using the Robson 10-Group Classification System.

BACKGROUND: Cesarean delivery has increased steadily in the United States over recent decades with significant downstream health consequences. The World Health Organization has endorsed the Robson 10-Group Classification System as a global standard to facilitate analysis and comparison of cesarean delivery rates. OBJECTIVE: Our objective was to apply the Robson 10-Group Classification System to a nationwide cohort in the United States over a 10-year period. STUDY DESIGN: This population-based analysis applied the Robson 10-Group Classification System to all births in the United States from 2005 through 2014, recorded in the 2003 revised birth certificate format. Over the study 10-year period, 27,044,217 deliveries met inclusion criteria. Five parameters (parity including previous cesarean, gestational age, labor onset, fetal presentation, and plurality), identifiable on presentation for delivery, were used to classify all women included into 1 of 10 groups. RESULTS: The overall cesarean rate was 31.6%. Group-3 births (singleton, term, cephalic multiparas in spontaneous labor) were most common, while group-5 births (those with a previous cesarean) accounted for the most cesarean deliveries increasing from 27% of all cesareans in 2005 through 2006 to >34% in 2013 through 2014. Breech pregnancies (groups 6 and 7) had cesarean rates >90%. Primiparous and multiparous women who had a prelabor cesarean (groups 2b and 4b) accounted for over one quarter of all cesarean deliveries. CONCLUSION: Women with a previous cesarean delivery represent an increasing proportion of cesarean deliveries. Use of the Robson criteria allows standardized comparisons of data and identifies clinical scenarios driving changes in cesarean rates. Hospitals and health organizations can use the Robson 10-Group Classification System to evaluate quality and processes associated with cesarean delivery.

Maternal age and risk for adverse outcomes.

OBJECTIVE: The objective of this study was to characterize the risk for severe maternal morbidity and other pregnancy complications by maternal age during delivery hospitalizations. STUDY DESIGN: This retrospective cohort analysis used the Perspective database to characterize the risk for adverse maternal outcomes from 2006 to 2015 based on maternal age. Women were divided into 7 categories based on maternal age: 15-17, 18-24, 25-29, 30-34, 35-39, 40-44, and 45-54 years of age. The primary outcome of this study was severe maternal morbidity as defined by the Centers for Disease Control and Prevention. Secondary outcomes included (1) overall comorbid risk; (2) risk for pregnancy complications such as postpartum hemorrhage, gestational diabetes, preeclampsia, and cesarean delivery; and (3) risk for individual severe morbidity diagnoses such as stroke, embolism, eclampsia, and hysterectomy. Adjusted models were fitted to assess factors associated with severe morbidity with adjusted risk ratios (aRRs) and 95% confidence intervals (CI) as measures of effect. Population weights were applied to create national estimates. RESULTS: Of 36,944,292 deliveries included, 2.5% occurred among women aged 15-17 years (n = 921,236), 29.1% to women aged 18-24 years (n = 10,732,715), 28.6% to women aged 25-29 years (n = 10,564,850), 24.9% to women aged 30-34 years (n = 9,213,227), 12.1% to women aged 35-39 years (n = 4,479,236), 2.6% to women aged 40-44 years (n = 974,289), and 0.2% to women aged 45-54 years (n = 58,739). In unadjusted analyses, severe morbidity was more than 3 times higher (risk ratio [RR], 3.33, 95% confidence interval [CI], 3.03-3.66) for women 45-54 years compared with women 25-29 years. Women aged 40-44, 35-39, and 15-17 years were also at increased risk (RR, 1.83, 95% CI, 1.77-1.89; RR, 1.36, 95% CI, 1.33-1.39; RR, 1.39, 95% CI, 1.34-1.45, respectively). In the adjusted model, the 45-54 year old group was associated with the highest relative risk (aRR, 3.46, 95% CI, 3.15-3.80) followed by the 40-44 year old group (aRR 1.90, 95% CI, 1.84-1.97), the 35-39 year old group (aRR, 1.43, 95% CI, 1.40-1.47), and the 15-17 year old group (aRR, 1.20, 95% CI, 1.15-1.24). Cesarean delivery, preeclampsia, postpartum hemorrhage, and gestational diabetes were most common among women aged 45-54 years, as were thrombosis and hysterectomy. CONCLUSION: While differential risk was noted across maternal age categories, women aged 45 years old and older were at highest risk for a broad range of adverse outcomes during delivery hospitalizations.

Heparin-Induced Thrombocytopenia during Obstetric Hospital Admissions.

INTRODUCTION: The rate of heparin-induced thrombocytopenia (HIT) on a population basis is unknown. The objective of this study was to characterize the risk for HIT during antepartum, delivery, and postpartum hospitalizations in the United States. MATERIALS AND METHODS: A large administrative database was used to determine the risk of HIT in hospitalized obstetric patients who received unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Patients were presumed to have HIT if they were exposed to UFH or LMWH, received a diagnosis of HIT, and were administered a medication for the treatment of HIT including bivalirudin, argatroban, fondaparinux, or lepirudin. We queried severe complications of HIT including arterial thrombosis, limb amputation, heart failure, and death. RESULTS: We identified 66,468 antepartum hospitalizations, 66,741 delivery hospitalizations, and 16,325 postpartum readmissions where women received pharmacologic prophylaxis. Of these, 10 antepartum admissions, 1 delivery admission, and 14 postpartum readmissions involved a diagnosis of HIT with treatment of bivalirudin, argatroban, fondaparinux, or lepirudin. There were no deaths and no diagnoses of arterial thrombosis, limb amputation, heart failure, and death. CONCLUSION: Risk for HIT among hospitalized obstetric patients is low. In this cohort, no cases of death or severe complications were noted in relation to the diagnosis.

Severe maternal morbidity and comorbid risk in hospitals performing <1000 deliveries per year.

BACKGROUND: While research has demonstrated increasing risk for severe maternal morbidity in the United States, risk at lower volume hospitals remains poorly characterized. More than half of all obstetric units in the United States perform <1000 deliveries per year and improving care at these hospitals may be critical to reducing risk nationwide. OBJECTIVE: We sought to characterize maternal risk profiles and severe maternal morbidity at low-volume hospitals in the United States. STUDY DESIGN: We used data from the Nationwide Inpatient Sample to evaluate trends in severe maternal morbidity and comorbid risk during delivery hospitalizations in the United States from 1998 through 2011. Comorbid maternal risk was estimated using a comorbidity index validated for obstetric patients. Severe maternal morbidity was defined as the presence of any 1 of 15 diagnoses representative of acute organ injury and critical illness. RESULTS: A total of 2,300,279 deliveries occurred at hospitals with annual delivery volume <1000, representing 20% of delivery hospitalizations overall. There were 7849 cases (0.34%) of severe morbidity in low-volume hospitals and this risk increased over the course of the study from 0.25% in 1998 through 1999 to 0.49% in 2010 through 2011 (P < .01). The risk in hospitals with ≥1000 deliveries increased from 0.35-0.62% during the same time periods. The proportion of patients with the lowest comorbidity decreased, while the proportion of patients with highest comorbidity increased the most. The risk of severe morbidity increased across all women including those with low comorbidity scores. Risk for severe morbidity associated with obstetric hemorrhage, infection, hypertensive diseases of pregnancy, and medical conditions all increased during the study period. CONCLUSION: Our findings demonstrate increasing maternal risk at hospitals performing <1000 deliveries per year broadly distributed over the patient population. Rates of morbidity in centers with ≥1000 deliveries have also increased. These findings suggest that maternal safety improvements are necessary at all centers regardless of volume.

The role of maternal age in twin pregnancy outcomes.

BACKGROUND: There are limited data on how maternal age is related to twin pregnancy outcomes. OBJECTIVE: The purpose of this study was to assess the relationship between maternal age and risk for preterm birth, fetal death, and neonatal death in the setting of twin pregnancy. STUDY DESIGN: This population-based study of US birth, fetal death, and period-linked birth-infant death files from 2007-2013 evaluated neonatal outcomes for twin pregnancies. Maternal age was categorized as 15-17, 18-24, 25-29, 30-34, 35-39, and ≥40 years of age. Twin live births and fetal death delivered at 20-42 weeks were included. Primary outcomes included preterm birth (<34 weeks and <37 weeks), fetal death, and neonatal death at <28 days of life. Analyses of preterm birth at <34 and <37 weeks were adjusted for demographic and medical factors, with maternal age modeled with the use of restricted spline transformations. RESULTS: A total of 955,882 twin live births from 2007-2013 were included in the analysis. Preterm birth rates at <34 and <37 weeks gestation were highest for women 15-17 years of age, decreased across subsequent maternal age categories, nadired for women 35-39 years old, and then increased slightly for women ≥40 years old. Risk for fetal death generally decreased across maternal age categories. Risk for fetal death was 39.9 per 1000 live births for women 15-17 years old, 24.2 for women 18-24 years old, 17.8 for women 25-29 years old, 16.4 for women 30-34 years old, 17.2 for women 35-39 years old, and 15.8 for women ≥40 years old. Risk for neonatal death at <28 days was highest for neonates born to women 15-17 years old (10.0 per 1,000 live births), decreased to 7.3 for women 18-24 years old and 5.5 for women 25-29 years old and ranged from 4.3-4.6 for all subsequent maternal age categories. In adjusted models, risk for preterm birth at <34-<37 weeks gestation was not elevated for women in their mid-to-late 30s; however, risk was elevated for women <20 years old and increased progressively with age for women in their 40s. CONCLUSION: Although twin pregnancy is associated with increased risk for most adverse perinatal outcomes, this analysis did not find advanced maternal age to be an additional risk factor for fetal death and infant death. Preterm birth risk was relatively low for women in their late 30s. Risks for adverse outcomes were higher among younger women; further research is indicated to improve outcomes for this demographic group. It may be reasonable to counsel women in their 30s that their age is not a major additional risk factor for adverse obstetric outcomes in the setting of twin pregnancy.

Gastroschisis: epidemiology and mode of delivery, 2005-2013.

BACKGROUND: Gastroschisis is a severe congenital anomaly the etiology of which is unknown. Research evidence supports attempted vaginal delivery for pregnancies complicated by gastroschisis in the absence of obstetric indications for cesarean delivery. OBJECTIVE: The objectives of the study evaluating pregnancies complicated by gastroschisis were to determine the proportion of women undergoing planned cesarean vs attempted vaginal delivery and to provide up-to-date epidemiology on the risk factors associated with this anomaly. STUDY DESIGN: This population-based study of US natality records from 2005 through 2013 evaluated pregnancies complicated by gastroschisis. Women were classified based on whether they attempted vaginal delivery or underwent a planned cesarean (n = 24,836,777). Obstetrical, medical, and demographic characteristics were evaluated. Multivariable log-linear regression models were developed to determine the factors associated with the mode of delivery. Factors associated with the occurrence of the anomaly were also evaluated in log-linear models. RESULTS: Of 5985 pregnancies with gastroschisis, 63.5% (n = 3800) attempted vaginal delivery and 36.5% (n = 2185) underwent a planned cesarean delivery. The rate of attempted vaginal delivery increased from 59.7% in 2005 to 68.8% in 2013. Earlier gestational age and Hispanic ethnicity were associated with lower rates of attempted vaginal delivery. Factors associated with the occurrence of gastroschisis included young age, smoking, high educational attainment, and being married. Protective factors included chronic hypertension, black race, and obesity. The incidence of gastroschisis was 3.1 per 10,000 pregnancies and did not increase during the study period. CONCLUSION: Attempted vaginal delivery is becoming increasingly prevalent for women with a pregnancy complicated by gastroschisis. Recommendations from the research literature findings may be diffusing into clinical practice. A significant proportion of women with this anomaly still deliver by planned cesarean, suggesting further reduction of surgical delivery for this anomaly is possible.

Population-based risk for peripartum hysterectomy during low- and moderate-risk delivery hospitalizations.

BACKGROUND: Postpartum hysterectomy is an obstetric procedure that carries significant maternal risk that is not well characterized by hospital volume. OBJECTIVE: The objective of this study was to determine risk for peripartum hysterectomy for women at low and moderate risk for the procedure. STUDY DESIGN: This population-based study used data from the Nationwide Inpatient Sample to characterize risk for peripartum hysterectomy. Women with a diagnosis of placenta accreta or prior cesarean and placenta previa were excluded. Obstetrical risk factors along with demographic and hospital factors were evaluated. Multivariable mixed-effects log-linear regression models were developed to determine adjusted risk. Based on these models receiver operating characteristic curves were plotted, and the area under the curve was determined to assess discrimination. RESULTS: Peripartum hysterectomy occurred in 1 in 1913 deliveries. Risk factors associated with significant risk for hysterectomy included mode of delivery, stillbirth, placental abruption, fibroids, and antepartum hemorrhage. These factors retained their significance in adjusted models: the risk ratio for stillbirth was 3.44 (95% confidence interval, 2.94-4.02), abruption 2.98 (95% confidence interval, 2.52-3.20), fibroids 3.63 (95% confidence interval, 3.22-4.08), and antepartum hemorrhage 7.15 (95% confidence interval, 6.16-8.32). The area under the curve for the model was 0.833. CONCLUSION: Peripartum hysterectomy is a relatively common event that hospitals providing routine obstetric care should be prepared to manage. That specific risk factors are highly associated with risk for hysterectomy supports routine use of hemorrhage risk-assessment tools. However, given that a significant proportion of hysterectomies will be unpredictable, the availability of rapid transfusion protocols may be necessary for hospitals to safely manage these cases.

Does the clinical presentation of a prior preterm birth predict risk in a subsequent pregnancy?

OBJECTIVE: The objective of the study was to determine whether risk of recurrent preterm birth differs based on the clinical presentation of a prior spontaneous preterm birth (SPTB): advanced cervical dilatation (ACD), preterm premature rupture of membranes (PPROM), or preterm labor (PTL). STUDY DESIGN: This retrospective cohort study included singleton pregnancies from 2009 to 2014 complicated by a history of prior SPTB. Women were categorized based on the clinical presentation of their prior preterm delivery as having ACD, PPROM, or PTL. Risks for sonographic short cervical length and recurrent SPTB were compared between women based on the clinical presentation of their prior preterm birth. Log-linear regression was used to control for confounders. RESULTS: Of 522 patients included in this study, 96 (18.4%) had prior ACD, 246 (47.1%) had prior PPROM, and 180 (34.5%) had prior PTL. Recurrent PTB occurred in 55.2% of patients with a history of ACD compared with 27.2% of those with PPROM and 32.2% with PTL (P = .001). The mean gestational age at delivery was significantly lower for those with a history of ACD (34.0 weeks) compared with women with prior PPROM (37.2 weeks) or PTL (37.0 weeks) (P = .001). The lowest mean cervical length prior to 24 weeks was significantly shorter in patients with a history of advanced cervical dilation when compared with the other clinical presentations. CONCLUSION: Patients with a history of ACD are at an increased risk of having recurrent preterm birth and cervical shortening in a subsequent pregnancy compared with women with prior preterm birth associated PPROM or PTL.

Patterns of use of hemostatic agents in patients undergoing major surgery.

BACKGROUND: Although a number of prohemostatic agents that are applied intraoperatively have been introduced to minimize bleeding, little is known about the patterns of use and the factors that influence use. We examined the use of hemostatic agents in patients undergoing major surgery. METHODS: All patients who underwent major general, gynecologic, urologic, cardiothoracic, or orthopedic surgery from 2000-2010 who were recorded in the Perspective database were analyzed. RESULTS: Among 3,633,799 patients, hemostatic agents were used in 30.3% (n = 1,102,267). The use of hemostatic agents increased from 28.5% in 2000 to 35.2% in 2010. Over the same period, the rates of transfusion declined for pancreatectomy (-14.4%), liver resection (-15.0%), gastrectomy (-11.7%), prostatectomy (-6.6%), nephrectomy (-4.6%), hip arthroplasty (-10.4%), and knee arthroplasty (-6.6%). Over the same time period, the transfusion rate increased for colectomy (6.0%), hysterectomy (3.7%), coronary artery bypass graft (8.4%), valvuloplasty (4.2%), lung resection (1.9%), and spine surgery (1.6%). Transfusion remained relatively stable for thyroidectomy (0.2%). CONCLUSIONS: The use of hemostatic agents has increased rapidly even for surgeries associated with a small risk of transfusion and bleeding complications. In addition to patient characteristics, surgeon and hospital factors exerted substantial influence on the allocation of hemostatic agents.

Pediatric neuropathology practice in a low- and middle-income country: capacity building through institutional twinning.

Background: Accurate and precise diagnosis is central to treating central nervous system (CNS) tumors, yet tissue diagnosis is often a neglected focus in low- and middle-income countries (LMICs). Since 2016, the WHO classification of CNS tumors has increasingly incorporated molecular biomarkers into the diagnosis of CNS tumors. While this shift to precision diagnostics promises a high degree of diagnostic accuracy and prognostic precision, it has also resulted in increasing divergence in diagnostic and management practices between LMICs and high-income countries (HICs). Pathologists and laboratory professionals in LMICs lack the proper training and tools to join the molecular diagnostic revolution. We describe the impact of a 7-year long twinning program between Canada and Pakistan on pathology services. Methods: During the study period, 141 challenging cases of pediatric CNS tumors initially diagnosed at Aga Khan University Hospital (AKUH), Karachi, were sent to the Hospital for Sick Children in Toronto, Canada (SickKids), for a second opinion. Each case received histologic review and often immunohistochemical staining and relevant molecular testing. A monthly multidisciplinary online tumor board (MDTB) was conducted to discuss the results with pathologists from both institutions in attendance. Results: Diagnostic discordance was seen in 30 cases. Expert review provided subclassification for 53 cases most notably for diffuse gliomas and medulloblastoma. Poorly differentiated tumors benefited the most from second review, mainly because of the resolving power of specialized immunohistochemical stains, NanoString, and targeted gene panel next-generation sequencing. Collaboration with expert neuropathologists led to validation of over half a dozen immunostains at AKUH facilitating diagnosis of CNS tumors. Conclusions: LMIC-HIC Institutional twinning provides much-needed training and mentorship to pathologists and can help in infrastructure development by adopting and validating new immunohistochemical stains. Persistent unresolved cases indicate that molecular techniques are indispensable in for diagnosis in a minority of cases. The development of affordable alternative molecular techniques may help with these histologically unresolved cases.

Uptake and outcomes of intensity-modulated radiation therapy for uterine cancer.

OBJECTIVE: While intensity-modulated radiation therapy (IMRT) allows more precise radiation planning, the technology is substantially more costly than conformal radiation and, to date, the benefits of IMRT for uterine cancer are not well defined. We examined the use of IMRT and its effect on late toxicity for uterine cancer. METHODS: Women with uterine cancer treated from 2001 to 2007 and registered in the SEER-Medicare database were examined. We investigated the extent and predictors of IMRT administration. The incidence of acute and late-radiation toxicities was compared for IMRT and conformal radiation. RESULTS: We identified a total of 3555 patients including 328 (9.2%) who received IMRT. Use of IMRT increased rapidly and reached 23.2% by 2007. In a multivariable model, residence in the western U.S. and receipt of chemotherapy were associated with receipt of IMRT. Women who received IMRT had a higher rate of bowel obstruction (rate ratio=1.41; 95% CI, 1.03-1.93), but other late gastrointestinal and genitourinary toxicities as well as hip fracture rates were similar between the cohorts. After accounting for other characteristics, the cost of IMRT was $14,706 (95% CI, $12,073 to $17,339) greater than conformal radiation. CONCLUSION: The use of IMRT for uterine cancer is increasing rapidly. IMRT was not associated with a reduction in radiation toxicity, but was more costly.

Preeclampsia outcomes at delivery and race.

Objective: The objective of this study was to assess how race is associated with adverse maternal outcomes in the setting of preeclampsia.Study design: This retrospective cohort study utilized the National (Nationwide) Inpatient Sample (NIS) from the Agency for Health care Research and Quality for the years 2012-2014. Women aged 15-54 with a diagnosis of preeclampsia were included. Race and ethnicity were categorized as non-Hispanic white, non-Hispanic black, Hispanic, Asian or Pacific Islander, Native American, other, and unknown. The overall risk for severe morbidity based on Centers for Disease Control and Prevention criteria was analyzed along with the risk for specific outcomes such as stroke, acute heart failure or pulmonary edema, eclampsia, and acute renal failure. The risk for severe morbidity was stratified by comorbid risk and compared by race. Log-linear regression models were created to assess risk for severe morbidity with risk ratios and associated 95% confidence intervals as measures of effect.Results: A total of 101,741 women with preeclampsia from 2012 to 2014 were included in this analysis. The risk for severe morbidity was significantly higher among non-Hispanic black women (9.8%) than non-Hispanic white, Hispanic, and all other women, respectively (6.1, 7.7, and 7.5%, respectively, p < .01). For non-Hispanic black compared to non-Hispanic white, Hispanic, and all other women, risk was higher for stroke (17.1 versus 6.5, 12.7, and 9.3 per 10,000 deliveries, respectively, p < .01) and pulmonary edema or heart failure (56.2 versus 32.7, 30.2, and 38.4 per 10,000 deliveries, respectively, p < .01). Non-Hispanic black women were also more likely than non-Hispanic white women to experience renal failure (136.4 versus 60.4 per 10,000 deliveries, p < .01). Adjusting for comorbidity, black women remained at higher risk for severe morbidity (p < .01). The risk for death was higher for black compared to non-black women (121.8 per 100,000 deliveries, 95% CI 69.7-212.9 versus 24.1 per 100,000 deliveries, 95% CI 14.6-39.8, respectively, p < .01)Conclusion: Black women were at higher risk for severe morbidity and mortality associated with preeclampsia.

Trends in comorbidity, acuity, and maternal risk associated with preeclampsia across obstetric volume settings.

OBJECTIVE: The objective of this study was to characterize morbidity, acuity, and maternal risks associated with preeclampsia across hospitals with varying obstetric volumes. METHODS: This retrospective cohort analysis used a large administrative data source, the Perspective database, to characterize the risk for preeclampsia from 2006 to 2015. Hospitals were classified as having either low (≤1000), moderate (1001-2000), or high (≥2000) delivery volume. The primary outcomes included preeclampsia, antihypertensive administration, comorbidity, and related severe maternal morbidity. Severe maternal morbidity was estimated using criteria from the Centers for Disease Control and Prevention. Comorbidity was estimated using an obstetric comorbidity index. Univariable comparisons were made with Chi-squared test. Adjusted log linear regression models were fit to assess factors associated with severe morbidity with risk ratios with 95% confidence intervals as the measures of effect. Population weights were applied to create national estimates. RESULTS: Of 36,985,729 deliveries included, 1,414,484 (3.8%) had a diagnosis of preeclampsia. Of these, 779,511 (2.1%) had mild, 171,109 (0.5%) superimposed, and 463,864 (1.3%) severe preeclampsia. The prevalence of mild, superimposed, and severe preeclampsia each increased over the study period with severe and superimposed preeclampsia as opposed to mild preeclampsia increasing the most proportionately (53.2 and 102.5 versus 10.8%, respectively). The use of antihypertensives used to treat severe range hypertension increased with use of intravenous labetalol increasing 31.5%, 43.2%, and 36.1% at low-, medium-, and high-volume hospitals. Comorbid risk also increased across hospital volume settings as did risk for severe maternal morbidity. CONCLUSIONS: Preeclampsia is increasing across obstetric care settings with preeclamptic patients demonstrating increasing comorbid risk, increased risk for severe morbidity, and more frequent need for treatment of acute hypertension.

Risk for postpartum hemorrhage, transfusion, and hemorrhage-related morbidity at low, moderate, and high volume hospitals.

OBJECTIVE: The objective of this study was to characterize risk for and temporal trends in postpartum hemorrhage across hospitals with different delivery volumes. STUDY DESIGN: This study used the Nationwide Inpatient Sample (NIS) to characterize risk for postpartum hemorrhage from 1998 to 2011. Hospitals were classified as having either low, moderate or high delivery volume (≤1000, 1001 to 2000, >2000 deliveries per year, respectively). The primary outcomes included postpartum hemorrhage, transfusion, and related severe maternal morbidity. Adjusted models were created to assess factors associated with hemorrhage and transfusion. RESULTS: Of 55,140,088 deliveries included for analysis 1,512,212 (2.7%) had a diagnosis of postpartum hemorrhage and 361,081 (0.7%) received transfusion. Risk for morbidity and transfusion increased over the study period, while the rate of hemorrhage was stable ranging from 2.5 to 2.9%. After adjustment, hospital volume was not a major risk factor for transfusion or hemorrhage. DISCUSSION: While obstetric volume does not appear to be a major risk factor for either transfusion or hemorrhage, given that transfusion and hemorrhage-related maternal morbidity are increasing across hospital volume categories, there is an urgent need to improve obstetrical care for postpartum hemorrhage. Those risk factors are able to discriminate women at increased risk supports routine use of hemorrhage risk assessment.