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.

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..

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.

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.

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.

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.

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.

Trends and Outcomes Associated With Using Long-Acting Opioids During Delivery Hospitalizations.

OBJECTIVE: To assess trends in use of long-acting opioids during delivery hospitalizations. METHODS: The Perspective database, an administrative inpatient database that includes medication receipt, was analyzed to evaluate patterns of long-acting opioid use during delivery hospitalizations from January 2006 through March 2015. Medications evaluated included methadone, formulations including buprenorphine and extended-release formulations of oxycodone, morphine, fentanyl, and other opioids. Temporal trends in use of these medications were determined. Unadjusted and adjusted models evaluating the role of demographic and hospital factors were created evaluating both use of these medications and risk for severe morbidity. Risk for severe morbidity was determined based on Centers for Disease Control and Prevention criteria. RESULTS: Our analysis included 2,994,630 delivery hospitalizations meeting study criteria. Over the entire study period, use of long-acting opioids increased significantly from 457 to 844 per 100,000 deliveries. Although buprenorphine and methadone use increased, use of other long-acting opioids decreased. In 2006, methadone and buprenorphine accounted for less than one third of all long-acting opioids used during delivery hospitalizations. By 2015, buprenorphine and methadone represented 73.5% of long-acting opioids used. In adjusted and unadjusted models, risk for severe morbidity was significantly lower with buprenorphine or methadone compared with other long-acting opioids. Restricting the cohort to only women with drug abuse or dependence, risk for severe morbidity was lower with methadone and buprenorphine than without any long-acting opioids. CONCLUSION: Increased use of methadone and buprenorphine in this study supports the feasibility of use of these medications during pregnancy and uptake of clinical recommendations for women with opioid use disorder. Use of methadone and buprenorphine is associated with decreased maternal morbidity, although causation cannot be presumed from this study model.

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.

Maternal Outcomes by Race for Women Aged 40 Years or Older.

OBJECTIVE: To clarify how race is associated with adverse maternal outcomes and risk for women aged 40 years or older. METHODS: This retrospective cohort study used the Nationwide Inpatient Sample for the years 1998-2014. Women aged 40-54 years were included. Race and ethnicity were categorized as non-Hispanic white, non-Hispanic black, Hispanic, Asian or Pacific Islander, Native American, other, and unknown. Temporal trends in severe maternal morbidity and overall comorbid risk by race in women aged 40 years or older were evaluated as were common pregnancy complications including preeclampsia, gestational diabetes, and cesarean delivery. Adjusted models were created to assess factors associated with severe morbidity. RESULTS: A total of 1,724,694 deliveries were included in this analysis. Severe maternal morbidity increased over the study period from 1.6% in 1998-2000 to 3.0% from 2013 to 2014. Black women had the highest rates of severe morbidity at both the beginning (2.4% in 1998-2000) and the end (4.9% in 2013-2014) of the study period. During this same period, comorbid risk based on medical conditions and other factors increased overall and individually by race. Black women also experienced the absolute largest increase from 1998-2003 to 2010-2014 in risk for acute renal failure, disseminated intravascular coagulation, transfusion, and hysterectomy. Pregnancy complications including preeclampsia, cesarean delivery, and gestational diabetes were more common at the end compared with the beginning of the study for black, white, and Hispanic women. The adjusted risk ratio for overall severe morbidity for black compared with white race was 1.81 (95% CI 1.76-1.87). Black women had a substantially higher risk of death than white women (risk ratio 4.71, 95% CI 3.36-6.61), and Hispanic women had more than twice the risk of death (risk ratio 2.13, 95% CI 1.48-3.07) as white women. CONCLUSION: Although black women older than 40 years were at increased risk for adverse outcomes and severe morbidity, this differential was of smaller magnitude than reported mortality risk.

Use of Antihypertensive Medications and Uterotonics During Delivery Hospitalizations in Women With Asthma.

OBJECTIVE: To estimate whether the diagnosis of asthma is associated with the use of specific uterotonic and antihypertensive medications during delivery hospitalizations. METHODS: We used Perspective, an administrative database, to determine whether women hospitalized for delivery complicated by postpartum hemorrhage or preeclampsia received uterotonics and antihypertensive medications differentially based on the absence or presence of asthma from 2006 to 2015. Given that carboprost and intravenous (IV) labetalol may be associated with asthma exacerbation, adjusted models for receipt of these medications were created with adjusted risk ratios with 95% CIs as measures of effect. Risk for status asthmaticus based on receipt of carboprost and IV labetalol was analyzed. RESULTS: Over the study period, a total of 5,691,178 women were analyzed, of whom 239,915 (4.2%) had preeclampsia and 139,841 postpartum hemorrhage (2.5%). Carboprost was used less frequently in patients with asthma compared with patients with no asthma (11.4% vs 18.0%) in comparison with IV labetalol, which was used more commonly when a diagnosis of asthma was present (18.5% vs 16.7%). In unadjusted analysis, the presence of asthma was associated with a 37% decrease in likelihood of carboprost use and an 11% increase in likelihood of labetalol use. In adjusted analysis, the presence of asthma was associated with a 32% decrease in likelihood of carboprost use (adjusted risk ratio 0.68, 95% CI 0.62-0.74) compared with a 7% decrease in labetalol use (adjusted risk ratio 0.93, 95% CI 0.90-0.97). Risk for status asthmaticus was significantly increased with use of IV labetalol compared with other antihypertensive medications (6.5 vs 1.7/1,000 delivery hospitalizations, P<.01). CONCLUSION: There may be an opportunity to reduce use of ß-blockers and carboprost among patients with asthma. Given their association with status asthmaticus, these drugs should be used cautiously in women with asthma.

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.

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.

Second-Stage Duration and Outcomes Among Women Who Labored After a Prior Cesarean Delivery.

OBJECTIVE: To characterize probabilities of vaginal delivery based on second-stage duration along with maternal and neonatal risks for women undergoing labor after cesarean delivery. METHODS: This unplanned secondary analysis of the Maternal-Fetal Medicine Units Cesarean Registry, a prospective observational cohort, assessed outcomes in women with a prior uterine scar and included women with a previous cesarean delivery without prior vaginal delivery who reached the second stage of labor. The primary outcome was mode of delivery by second-stage duration. Secondary outcomes included assessment of individual adverse maternal (chorioamnionitis, atony, endometritis, hysterectomy, uterine rupture or dehiscence, and red cell transfusion) and neonatal (cord pH less than 7.10, Apgar score less than 6 at 5 minutes, neonatal intensive care unit admission, and ventilatory support) outcomes. RESULTS: Of 4,579 women with a previous cesarean delivery who reached the second stage of labor, 4,147 (90.6%) delivered vaginally. As second stage increased, successful vaginal delivery rates decreased: 97.3% at less than 1 hour (95% CI 96.6-97.9%), 91.5% at 1 to less than 2 hours (95% CI 89.8-93.1%), 78.5% at 2 to less than 3 hours (95% CI 74.5-82.1%), 62.3% at 3 to less than 4 hours (95% CI 55.2-69.1%), and 45.6% at 4 hours or greater (95% CI 37.7-53.7%). Risk of all adverse maternal outcomes increased with the length of the second stage. Specifically, risk of uterine rupture or dehiscence increased with second-stage length from less than 1 hour (0.7%), 1 to less than 2 hours (1.4%), 2 to less than 3 hours (1.5%), to 3 hours or greater (3.1%) (P<.001 for differential risk across the second stage). Risk of neonatal outcomes did not differ significantly by second-stage length. CONCLUSION: Although many women with a longer second stage (greater than 3 hours) will achieve successful vaginal delivery, these patients may be at increased risk for adverse maternal outcomes and should have close observation of fetal heart rate monitoring, maternal vital signs, and symptoms suggestive of uterine rupture or dehiscence.

Use of Antihypertensive Medications During Delivery Hospitalizations Complicated by Preeclampsia.

OBJECTIVE: To evaluate temporal trends in use of antihypertensive medications during delivery hospitalizations complicated by preeclampsia and risk of maternal stroke over the same time period. METHODS: The Perspective database was used to perform a retrospective cohort study evaluating antihypertensive drugs dispensed during delivery hospitalizations complicated by preeclampsia from 2006 to the first quarter of 2015. Medications evaluated included nifedipine, hydralazine, and oral and intravenous labetalol. Adjusted models for receipt of antihypertensive agents accounting for demographic and hospital factors were created. Hospital-level rates of antihypertensive administration for women with severe preeclampsia were analyzed. Risk of stroke during delivery hospitalization was evaluated. RESULTS: A total of 239,454 patients with preeclampsia were included in the analysis including 126,595 women with mild, 31,628 with superimposed, and 81,231 with severe preeclampsia. Overall, 105,409 women received a hypertensive agent. From 2006 to 2014, for all patients with preeclampsia, receipt of oral labetalol increased from 20.3% to 31.4%, intravenous labetalol from 13.3% to 21.4%, hydralazine from 12.8% to 16.9%, nifedipine from 15.0% to 18.2%, and more than one medication from 16.5% to 25.8%. The proportion of patients with preeclampsia receiving any antihypertensive medication rose from 37.8% in 2006 to 49.4% in 2015. In adjusted models, temporal trends retained significance. Rates of antihypertensive administration for severe preeclampsia varied significantly by hospital. For severe preeclampsia, the risk for stroke decreased from 13.5 per 10,000 deliveries in 2006-2008 (n=27) to 9.7 in 2009-2011 (n=25) to 6.0 in 2012-2014 (n=20) (P=.02). CONCLUSION: Use of multiple antihypertensive agents to treat preeclamptic women increased over the study period for women with mild, superimposed, and severe preeclampsia. There was substantial hospital variation in use of antihypertensive agents. This trend was associated with decreased risk of maternal stroke.

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.

Venous Thromboembolism Prophylaxis During Antepartum Admissions and Postpartum Readmissions.

OBJECTIVE: To characterize the use of venous thromboembolism prophylaxis during antepartum and postpartum hospitalizations in the United States. METHODS: A retrospective cohort study using the Perspective database was performed to analyze temporal trends of mechanical and pharmacologic venous thromboembolism prophylaxis for patients hospitalized for antepartum and postpartum indications between 2006 and 2015. Delivery hospitalizations were excluded. The association between use of prophylaxis and medical and obstetric risk factors as well as patient demographic and hospital characteristics was evaluated with unadjusted and adjusted models accounting for demographic, hospital and medical, and obstetric risk factors. RESULTS: A total of 622,740 antepartum and 105,361 postpartum readmissions were identified and included in the analysis. Between 2006 and 2015, use of venous thromboembolism prophylaxis increased from 18.5% to 38.7% for antepartum admissions (adjusted risk ratio [RR] 1.94, 95% CI 1.88-2.01) and from 22.5% to 30.6% for postpartum readmissions (adjusted RR 1.31, 95% CI 1.21-1.43). Among women readmitted postpartum, 56.4% of prophylaxis was pharmacologic and 43.6% was mechanical. For antepartum admissions, 87.2% of prophylaxis was mechanical and 12.8% was pharmacologic. Significant regional and hospital-level variation was noted with prophylaxis most common in the South. In both unadjusted and unadjusted analyses, use of venous thromboembolism prophylaxis was more common for women with thrombophilia, ovarian hyperstimulation syndrome, a history of venous thromboembolism, and prolonged hospitalization. Factors associated with decreased rates of prophylaxis included hyperemesis and postpartum endometritis. CONCLUSION: Although antepartum and postpartum venous thromboembolism prophylaxis is becoming increasingly common, particularly in the setting of medical or obstetric risk factors, use of prophylaxis varies regionally and on a hospital level. Some risk factors for venous thromboembolism were associated with lower rates of prophylaxis. The heterogeneity of clinical approaches to venous thromboembolism prophylaxis for these patient populations may represent an opportunity to perform outcomes research to further clarify best practices.