Predicting Lead-Time RSV-Related Pediatric Hospitalizations From Historic Google Trend Search.

OBJECTIVES: Respiratory syncytial virus (RSV) causes seasonal outbreaks of respiratory tract infections in children, leading to increased emergency department visits and hospitalizations. Although the risk of severe illnesses difficult to predict, the sudden surge in RSV may strain the health care system. Therefore, the objective of this study was to examine the utility of Google Trends search activity on RSV to predict changes in RSV-related hospitalizations in children in the United States in 2019. METHODS: A retrospective cross-sectional analysis of pediatric hospitalization was conducted using the 2019 HCUP-Kids Inpatient Database. Google Trends search activity for "RSV" was abstracted as a monthly relative interest score for 2019. RSV-related hospitalizations were identified using International Classification of Diseases 9/10 codes. We applied finite distributed lag models to estimate the causal effect over time of historical relative search activity and long-run propensity to calculate the cumulative effect of changes in relative search activity on admission rate. RESULTS: Of the total 102 127 RSV-related pediatric hospitalizations, 90% were in those aged ≤2 years. Admissions were common in males (55%), non-Hispanic Whites (50%), and South region (39%). Across 2o successive months, the cumulative effect of a 1-unit score increase in relative interest was associated with an increase of 140.7 (95% confidence interval, 96.2-185.2; P < .05) RSV-related admissions. CONCLUSIONS: Historic Google Trends search activity for RSV predicts lead-time RSV-related pediatric hospitalization. Further studies are needed to validate these findings using regional health systems.

Association between Neonatal Abstinence Syndrome and Congenital Anomalies in the United States.

OBJECTIVE: Studies exploring the relationship between neonatal abstinence syndrome (NAS) and congenital anomalies (CA) in the United States are limited given the small sample size or data prior to the opioid epidemic. We aimed to determine if there is an association between NAS and CA in a nationally representative cohort of newborn hospitalization in the United States. STUDY DESIGN: This was a cross-sectional analysis of NAS-related hospitalizations within the 2016 Kids Inpatient Database. International Classification of Diseases (ICD-10-CM) diagnostic codes were used to identify NAS hospitalizations and those with and without CA. The primary outcome was the odds of CAs in NAS hospitalizations. Multivariate survey logistic regression was used to analyze the relationship between NAS and CA. RESULTS: Among 3.7 million newborn hospitalizations, 25,394 had NAS (6.7 per 1,000). The prevalence of any CA was higher in those with NAS when compared with non-NAS hospitalizations (10.3 vs. 4.9%; odds ratio = 2.27; 95% confidence interval [CI]: 2.13-2.43). Adjusted analysis showed similar results (adjusted odds ratio: = 1.83, CI: 1.71-1.95). NAS hospitalizations with CA had a higher mortality rate (0.6 vs 0.04%, p < 0.0001) and higher resource use. CONCLUSION: This nationwide study shows that NAS may be associated with increased odds of CAs, suggesting that NAS may be a risk factor for increased morbidity in the newborn period. KEY POINTS: · 1 in 10 newborns with NAS had at least one congenital anomaly.. · NAS hospitalization with congenital anomalies had higher resource use and mortality.. · Pediatricians caring for newborns with NAS should have a high index of suspicion for birth defects..

National Trends in Survival and Short-Term Outcomes of Periviable Births ≤24 Weeks Gestation in the United States, 2009 to 2018.

OBJECTIVE: Data from the academic medical centers in the United States showing improvements in survival of periviable infants born at 22 to 24 weeks GA may not be nationally representative since a substantial proportion of preterm infants are cared for in community hospital-based neonatal intensive care units. Our objective was to examine the national trends in survival and other short-term outcomes among preterm infants born at ≤24 weeks gestational age (GA) in the United States from 2009 to 2018. STUDY DESIGN: This was a retrospective, repeated cross-sectional analysis of the National Inpatient Sample for preterm infants ≤24 weeks GA. The primary outcome was the trends in survival to discharge. Secondary outcomes were the trends in the composite outcome of death or one or more major morbidity (bronchopulmonary dysplasia, necrotizing enterocolitis stage ≥2, periventricular leukomalacia, severe intraventricular hemorrhage, and severe retinopathy of prematurity). The Cochran-Armitage trend test was used for trend analysis. p-Value <0.05 was considered significant. RESULTS: Among 71,854 infants born at ≤24 weeks GA, 34,251 (47.6%) survived less than 1 day and were excluded. Almost 93% of those who survived <1 day were of ≤23 weeks GA. Among the 37,603 infants included in the study cohort, 48.1% were born at 24 weeks GA. Survival to discharge at GA ≤ 23 weeks increased from 29.6% in 2009 to 41.7% in 2018 (p < 0.001), while survival to discharge at GA 24 weeks increased from 58.3 to 65.9% (p < 0.001). There was a significant decline in the secondary outcomes among all the periviable infants who survived ≥1 day of life. CONCLUSION: Survival to discharge among preterm infants ≤24 weeks GA significantly increased, while death or major morbidities significantly decreased from 2009 to 2018. The postdischarge survival, health care resource use, and long neurodevelopmental outcomes of these infants need further investigation. KEY POINTS: · Survival increased significantly in infants ≤24 weeks GA in the United States from 2009 to 2018.. · Death or major morbidity in infants ≤24 weeks GA decreased significantly from 2009 to 2018.. · Death or surgical procedures including tracheostomy, VP shunt placement, and PDA surgical closure in infants <=24 weeks GA decreased significantly from 2009 to 2018..

Trends and Resource Use for Kernicterus Hospitalizations in the United States.

OBJECTIVE: To evaluate the trends in hospitalization for kernicterus in the United States from 2006 through 2016. METHOD: Repeated, cross-sectional analysis of the 2006 to 2016 editions of the Kids' Inpatient Database. All neonatal hospitalizations with an International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification code for kernicterus and admitted at age ≤28 days were included. RESULTS: Among 16 094 653 neonatal hospitalizations from 2006 to 2016, 20.5% were diagnosed with jaundice with overall incidence of kernicterus 0.5 per 100 000. The rate of kernicterus (per 100 000) was higher among males (0.59), Asian or Pacific Islanders (1.04), and urban teaching hospitals (0.72). Between 2006 and 2016, the incidence of kernicterus decreased from 0.7 to 0.2 per 100 000 (P-trend = .03). The overall median length of stay for kernicterus was 5 days (interquartile range [IQR], 3-8 days). The overall median inflation-adjusted cost of hospitalization was $5470 (IQR, $1609-$19 989). CONCLUSIONS: Although the incidence of kernicterus decreased between 2006 and 2016, its continued occurrence at a higher rate among Asian or Pacific Islander and Black race or ethnicity in the United States require further probing. Multipronged approach including designating kernicterus as a reportable event, strengthening newborn hyperbilirubinemia care practices and bilirubin surveillance, parental empowerment, and removing barriers to care can potentially decrease the rate of kernicterus further.

Gastrostomy Tube Placement and Resource Use in Neonatal Hospitalizations With Down Syndrome.

OBJECTIVES: To determine the trends in gastrostomy tube (GT) placement and resource utilization in neonates ≥35 weeks' gestational age with Down syndrome (DS) in the United States from 2006 to 2017. METHODS: This was a serial cross-sectional analysis of neonatal hospitalizations of ≥35 weeks' gestational age with International Classification of Diseases diagnostic codes for DS within the National Inpatient Sample. International Classification of Diseases procedure codes were used to identify those who had GT. The outcomes of interest were the trends in GT and resource utilization and the predictors of GT placement. Cochran-Armitage and Jonckheere-Terpstra trend tests were used for trend analysis of categorical and continuous variables, respectively. Predictors of GT placement were identified using multivariable logistic regression. P value <.05 was considered significant. RESULTS: Overall, 1913 out of 51 473 (3.7%) hospitalizations with DS received GT placement. GT placement increased from 1.7% in 2006 to 5.6% in 2017 (P <.001), whereas the prevalence of DS increased from 10.3 to 12.9 per 10 000 live births (P <.001). Median length of stay significantly increased from 35 to 46 days, whereas median hospital costs increased from $74 214 to $111 360. Multiple comorbidities such as prematurity, sepsis, and severe congenital heart disease were associated with increased odds of GT placement. CONCLUSIONS: There was a significant increase in GT in neonatal hospitalizations with DS, accompanied by a significant increase in resource utilization. Multiple comorbidities were associated with GT placement and the early identification of those who need GT could potentially decrease length of stay and resource use.

Trends and Resource Utilization for Neonatal Jaundice Hospitalizations in the United States.

OBJECTIVES: To evaluate the trends in hospitalization for neonatal jaundice and its management with phototherapy and exchange transfusion in the United States from 2006 through 2016. METHODS: Repeated, cross-sectional analysis of the 2006 to 2016 editions of the Kids' Inpatient Database. All neonatal hospitalizations with an International Classification of Diseases, 9th or 10th Revision, Clinical Modification code for jaundice and admitted at age ≤28 days were included. The outcome measures were changes in the diagnosis of jaundice (expressed as a proportion) and its management over the years. RESULTS: Among 16 094 653 neonatal hospitalizations from 2006 to 2016, 20.5% were diagnosed with jaundice. While the incidence of jaundice remained stable over the years, 20.9% to 20.5% (P = .1), the proportion with jaundice who received phototherapy increased from 22.5% to 27.0% (P < .0001) between 2006 and 2016. There was no significant change in the exchange transfusion rate per year among neonatal hospitalizations with jaundice. CONCLUSIONS: While the proportion of newborns with jaundice remained stable between 2006 and 2016, the use of phototherapy significantly increased with no significant change in exchange transfusion rate. The impact of these changes on the prevention of acute bilirubin encephalopathy needs further examination in future studies.

Trends and Resource Utilization in Kawasaki Disease Hospitalizations in the United States, 2008-2017.

OBJECTIVES: To explore trends in hospitalization rate, resource use, and outcomes of Kawasaki Disease (KD) in children in the United States from 2008 to 2017. METHODS: This was a retrospective, serial cross-sectional analysis of pediatric hospitalizations with International Classification of Disease diagnostic codes for KD in the National Inpatient Sample. Hospitalization rates per 100 000 populations were calculated and stratified by age group, gender, race, and US census region. Prevalence of coronary artery aneurysms (CAA) were expressed as proportions of KD hospitalizations. Resource use was defined in terms of length of stay and hospital cost. Cochran-Armitage and Jonckheere-Terpstra trend tests were used for categorical and continuous variables, respectively. P <.05 was considered significant. RESULTS: A total of 43 028 pediatric hospitalizations identified with KD, yielding an overall hospitalization rate of 5.5 per 100 000 children. The overall KD hospitalization rate remained stable over the study period (P = .18). Although KD hospitalization rates differed by age group, gender, race, and census region, a significant increase was observed among Native Americans (P = .048). Rates of CAA among KD hospitalization increased from 2.4% to 6.8% (P = .04). Length of stay remained stable at 2 to 3 days, but inflation-adjusted hospital cost increased from $6819 in 2008 to $10 061 in 2017 (Ptrend < 0.001). CONCLUSIONS: Hospitalization-associated costs and rates of CAA diagnostic codes among KD hospitalizations increased, despite a stable KD hospitalization rate between 2008 and 2017. These findings warrant further investigation and confirmation with databases with granular clinical information.

Predictors of Length of Stay and Cost of Hospitalization of Neonatal Abstinence Syndrome in the United States.

Background The incidence rate and economic burden of neonatal abstinence syndrome (NAS) are increasing in the United States (US). We explored the link between the length of stay (LOS) and hospitalization cost for neonatal abstinence syndrome in 2018. Methods This was a cross-sectional analysis of the 2018 national inpatient sample database. Newborn hospitalizations with neonatal abstinence syndrome and their accompanying comorbid conditions were identified using the International Classification of Diseases, 10th Edition diagnostic codes. Logistic regression was used to determine the impact of length of stay and the co-morbidities on inflation-adjusted hospital costs. Results The incidence of neonatal abstinence syndrome was 7.1 per 1000 births (95% CI 6.8-7.3) in 2018. The majority had Medicaid (84.1%), with a neonatal abstinence syndrome incidence of 13.2 (95% CI: 12.8-13.6). In adjusted analysis, every one-day increase in length of stay increased the hospital cost by $1,685 (95% CI: 1,639-1,731). Neonatal abstinence syndrome hospitalizations with Medicaid had a longer length of stay by 1.8 days (95% CI: 0.5-3.1). Co-morbidities further increased the length of stay: seizures: 13.8 days; sepsis: 4.1 days; respiratory complications: 4.4 days; and feeding problems: 5.8 days. Those at urban teaching hospitals had a longer length of stay by 7.3 days (95% CI: 5.8-8.8). Co-morbidities increased hospital cost as follows: seizures: $71,380; sepsis: $12,837; respiratory complications: $8,268; feeding problems: $7,737. The cost of hospitalization at large bed-size hospitals and urban teaching was higher by $5,243 and $12,005, respectively. Conclusion The incidence rate of neonatal abstinence syndrome remained high and was resource-intensive in 2018. Co-morbid conditions and hospitalization at urban teaching hospitals were major contributors to increased length of stay and hospital costs.

Trends in Acute Myocarditis Related Pediatric Hospitalizations in the United States, 2007-2016.

There has been little exploration of acute myocarditis trends in children despite notable advancements in care over the past decade. We explored trends in pediatric hospitalizations for acute myocarditis from 2007 to 2016 in the United States (US). This was a retrospective, serial cross-sectional study of the National Inpatient Sample database from 2007 to 2016, identifying patients ≤18 years hospitalized with acute myocarditis. Patient demographics and incidence trends were examined. Other relevant clinical and resource utilization outcomes were also explored. Out of 60,390,000 weighted pediatric hospitalizations, 6371 were related to myocarditis. The incidence of myocarditis increased from 0.7 to 0.9 per 100,000 children (p <0.0001) over the study period. The mortality decreased from 7.5% to 6.1% (p = 0.02). A significant inflation-adjusted increase by $4,574 in the median hospitalization cost was noted (p = 0.02) while length of stay remained stable (median 6.1 days). Tachyarrhythmias were identified as the most common type of associated arrhythmia. The occurrence of congestive heart failure remained steady at 27%. In conclusion, in-hospital mortality associated with pediatric acute myocarditis has decreased in the United States over years 2007 to 2016 with a concurrent rise in incidence. Despite steady length of stay, hospitalization costs have increased. Future studies investigating long-term outcomes relating to acute myocarditis are warranted.

Tracheostomy trends in preterm infants with bronchopulmonary dysplasia in the United States: 2008-2017.

OBJECTIVE: To determine the trends in tracheostomy placement and resource use in preterm infants less than or equal to 30 weeks gestational age (GA) with bronchopulmonary dysplasia (BPD) in the United States from 2008 to 2017. STUDY DESIGN: This was a retrospective, serial cross-sectional study using data from the NIS. Inclusion criteria were: GA less than or equal to 30 weeks, hospitalization at less than or equal to 28 days of age, assignment of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9-CM) or ICD10-CM codes for BPD and tracheostomy. Trends in tracheostomy and resource utilization were assessed using Jonckheere-Terpstra test. p-value < .05 was considered significant. RESULTS: Overall, 987 out of 68,953 (1.4%) hospitalizations with BPD had tracheostomy. Characteristics of the study population: 60.8% were male, 68.4% less than or equal to 26 weeks GA, 43.8% White, 60.5% with Medicaid or self-pay, 65.2% in the Midwest and South census regions of the United States, and 45.7% had gastrostomy tube placement. Tracheostomy placement (expressed as per 100,000 live births) decreased from 2.7 in 2008 to 1.9 in 2011. Thereafter, it increased from 1.9 in 2011 to 3.5 in 2017 (p < .001). GA less than or equal to 24 weeks was significantly associated with increased odds of tracheostomy placement. Median length of stay increased significantly from 170 to 231 days while median inflation adjusted hospital cost increased significantly from $323,091 in 2008-2009 to $687,141 between 2008-2009 and 2016-2017. CONCLUSION: Although tracheostomy placement among preterm hospitalizations with BPD was rare, the frequency of its placement and its associated resource utilization significantly increased during the study period. Future studies should probe the reasons and factors behind these trends.

Surgery and Resource Utilization Trends for Pediatric Intussusception From 2005 Through 2014.

BACKGROUND: Air or barium enema reduction is becoming increasingly common and safer for pediatric intussusception. However, little is known about trends of pediatric intussusception requiring surgical intervention in the United States.  Methods: National Inpatient Sample database was analyzed from 2005-2014 to identify pediatric (≤18 years) intussusceptions along with procedures such as enema and/or surgical intervention. Trends in the rates of surgical intervention were examined according to encounter-level (age, gender, race, comorbidities) and hospital-level (hospital census region, teaching status) characteristics. Outcomes of pediatric intussusception requiring surgical intervention were analyzed in terms of length of stay and cost of hospitalization. Factors associated with surgical intervention were also analyzed. P value of < 0.05 was considered significant.  Results: Out of 21,835 intussusception hospitalizations requiring enema or surgical intervention, 14,415 (66%) had surgical intervention; 90% of which (12,978) had no preceding enema. Surgical intervention rates among intussusception hospitalizations varied by age (highest < 1 year), gender (male > females) and race (Hispanics > Whites and Blacks). During the study period, overall surgical intervention rate remained stable (2.2 to 1.7, P=0.07) although it declined in those under 1 year of age. Children with severe disease, gastrointestinal comorbidities over the age of 4 years had increased odds of surgical intervention, whereas hospitalization in large and urban teaching hospitals had decreased odds of surgical intervention. Length of stay and hospital cost remained stable from 2005-2014. CONCLUSION: The rates of surgical intervention and resource utilization for pediatric intussusception remained stable from 2005-2014, however they declined significantly in infants. The proportion of intussusception hospitalization requiring surgery remains high and further studies are needed to explore the possible factors.

Temporal Trends of Intracranial Hemorrhage Among Immune Thrombocytopenia Hospitalizations in the United States.

BACKGROUND:  Intracranial hemorrhage (ICH) is a rare but severe complication in patients with immune thrombocytopenia (ITP). We aimed to examine the incidence and outcomes of ICH among ITP hospitalizations and factors associated with it. Additionally, we studied resource utilization for these hospitalizations. METHODS:  Using National (Nationwide) Inpatient Sample, International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification (ICD-9-CM/ICD-10-CM) codes, we studied ITP hospitalizations with occurrence of ICH between 2007 and 2016. RESULT:  Out of 348,906 weighted ITP hospitalizations, ICH occurred in 3,408 encounters (incidence 1.1 ± 0.04%). The incidence remained stable over time (2007-2008: 1.01%, 2015-2016: 1.20%; P = 0.3). People with age ≥25 years, especially those aged ≥65 years (odds ratio [OR] 3.69, 95% confidence interval [CI] 2.34-5.84), or those with gastrointestinal bleed (OR 1.60, 95% CI 1.18-2.16) were significantly more likely to develop ICH. Female gender (OR 0.81, 95% CI 0.68-0.97) had lower odds for developing ICH. Overall mortality in ITP hospitalizations with ICH was 26.7%. Length of stay (LOS) was longer (4.8 vs. 2.6 days) and costs of hospitalization (COH) were higher ($20,081 vs. $8,355) in ICH hospitalizations compared to non-ICH ITP hospitalizations. Increasing age and comorbidities such as gastrointestinal bleed, hematuria, and other bleeding were also associated with longer LOS and higher COH. CONCLUSION: Although rare, ICH in ITP was associated with a high mortality and increased resource utilization. Clinicians should be cognizant of factors associated with risk of ICH in ITP, and future studies should reassess the ICH trends to study the impact of novel therapeutic options such as thrombopoietin receptor agonists.

Etiologies, trends, and predictors of 30-day pediatric readmissions after hospitalizations for diabetic ketoacidosis in the United States.

OBJECTIVE: To determine the causes, predictors, and trends of 30-day readmissions following hospitalizations for pediatric diabetic ketoacidosis (DKA) in the United States (US) from 2010 to 2014. RESEARCH DESIGN AND METHODS: We used International Classification of Diseases, ninth revision, Clinical Modification codes to identify children with DKA aged 2 to 18 years from the National Readmission Database in the US. Patients who had readmission within 30 days after an index admission for DKA were included in the study. We combined similar diagnoses into clinically important categories to determine the cause of readmission. The primary outcome was all-cause 30-day (AC30) readmissions. Categorical and continuous variables were analyzed using chi-square or student's t-test or Wilcoxon rank sum tests respectively. We performed multivariable logistic regression to identify predictors of 30-day readmission. RESULTS: From 2010 through 2014, a weighted total of 87 815 index DKA-related pediatric hospitalizations were identified of which, 4055 patients (4.6%) had AC30 readmissions and this remained unchanged during the study period. Of all the readmissions, 69% were attributed to DKA. In multivariable regression analysis, the odds of AC30 readmission and 30-day readmission attributed to DKA alone were increased for females, adolescents, patients with depression and psychosis, and discharge against medical advice, while private insurance, the highest income quartile, and admission at teaching hospitals were associated with lower odds of AC30 readmission and 30-day readmission attributed to DKA only. CONCLUSION: We identified several factors associated with readmission after hospitalization for DKA. Addressing these factors such as depression may help lower readmissions after an admission for DKA.

Pyloric Stenosis: National Trends in the Incidence Rate and Resource Use in the United States From 2012 to 2016.

OBJECTIVES: Infantile hypertrophic pyloric stenosis (IHPS) is the most common reason for abdominal surgery in infants; however, national-level data on incidence rate and resource use are lacking. We aimed to examine the national trends in hospitalizations for IHPS and resource use in its management in the United States from 2012 to 2016. METHODS: We performed a retrospective serial cross-sectional study using data from the National Inpatient Sample, the largest health care database in the United States. We included infants aged ≤1 year assigned an International Classification of Diseases, Ninth Revision, or International Classification of Diseases, 10th Revision, code for IHPS who underwent pyloromyotomy or pyloroplasty. We examined the temporal trends in the incidence rate (cases per 1000 live births) according to sex, insurance status, geographic region, and race. We examined resource use using length of stay (LOS) and hospital costs. Linear regression was used for trend analysis. RESULTS: Between 2012 and 2016, there were 32 450 cases of IHPS and 20 808 149 live births (incidence rate of 1.56 per 1000). Characteristics of the study population were 82.7% male, 53% white, and 63.3% on Medicaid, and a majority were born in large (64%), urban teaching hospitals (90%). The incidence of IHPS varied with race, sex, socioeconomic status, and geographic region. In multivariable regression analysis, the incidence rate of IHPS decreased from 1.76 to 1.57 per 1000 (adjusted odds ratio 0.93; 95% confidence interval 0.92-0.93). The median cost of care was $6078.30, whereas the median LOS was 2 days, and these remained stable during the period. CONCLUSIONS: The incidence rate of IHPS decreased significantly between 2012 and 2016, whereas LOS and hospital costs remained stable. The reasons for the decline in the IHPS incidence rate may be multifactorial.

National Trends in the Epidemiology and Resource Use for Henoch-Schönlein Purpura (IgA Vasculitis) Hospitalizations in the United States From 2006 to 2014.

OBJECTIVES: We examined the trends in the rate of Henoch-Schönlein purpura (HSP) hospitalizations and the associated resource use among children in the United States from 2006 through 2014. METHODS: Pediatric hospitalizations with HSP were identified by using International Classification of Diseases, Ninth Revision, code 287.0 from the National Inpatient Sample. HSP hospitalization rate was calculated by using the US population as the denominator. Resource use was determined by length of stay (LOS) and hospital cost. We used linear regression for trend analysis. RESULTS: A total of 16 865 HSP hospitalizations were identified, and the HSP hospitalization rate varied by age, sex, and race. The overall HSP hospitalization rate was 2.4 per 100 000 children, and there was no trend during the study period. LOS remained stable at 2.8 days, but inflation-adjusted hospital cost increased from $2802.20 in 2006 to $3254.70 in 2014 (P < .001). CONCLUSIONS: HSP hospitalization rate in the United States remained stable from 2006 to 2014. Despite no increase in LOS, inflation-adjusted hospital cost increased. Further studies are needed to identify the drivers of increased hospitalization cost and to develop cost-effective management strategies.

Caspase-1 Inhibition Attenuates Hyperoxia-induced Lung and Brain Injury in Neonatal Mice.

Hyperoxia plays a key role in the development of bronchopulmonary dysplasia (BPD), a chronic lung disease of preterm infants. Infants with BPD often have brain injury that leads to long-term neurodevelopmental impairment, but the underlying mechanisms that control BPD-induced neurodevelopmental impairment remain unclear. Our previous studies have shown that hyperoxia-induced BPD in rodents is associated with lung inflammasome activation. Here, we tested the hypothesis that hyperoxia-induced lung and brain injury is mediated by inflammasome activation, and that inhibition of caspase-1, a key component of the inflammasome, attenuates hyperoxia-induced lung and brain injury in neonatal mice. C57/BL6 mouse pups were randomized to receive daily intraperitoneal injections of Ac-YVAD-CMK, an irreversible caspase-1 inhibitor, or placebo during exposure to room air or hyperoxia (85% O2) for 10 days. We found that hyperoxia activated the NLRP1 inflammasome, increased production of mature IL-1ß, and upregulated expression of p30 gasdermin-D (GSDMD), the active form of GSDMD that is responsible for the programmed cell death mechanism of pyroptosis in both lung and brain tissue. Importantly, we show that inhibition of caspase-1 decreased IL-1ß activation and p30 GSDMD expression, and improved alveolar and vascular development in hyperoxia-exposed lungs. Moreover, caspase-1 inhibition also promoted cell proliferation in the subgranular zone and subventricular zone of hyperoxia-exposed brains, resulting in lessened atrophy of these zones. Thus, the inflammasome plays a critical role in hyperoxia-induced neonatal lung and brain injury, and targeting this pathway may be beneficial for the prevention of lung and brain injury in preterm infants.

Trends in the incidence, mortality, and cost of neonatal herpes simplex virus hospitalizations in the United States from 2003 to 2014.

OBJECTIVE: To examine the temporal trends in the incidence and outcomes of neonatal herpes simplex infections (NHSV) in the United States. STUDY DESIGN: We conducted a retrospective study using the National Inpatient Sample (NIS). Neonates ≤28 days old with ICD-9 codes for NHSV (054.xx) from 2003 to 2014 were included. Trends in the incidence, mortality, length of stay (LOS), and hospital cost were analyzed using Jonckheere-Terpstra test. RESULTS: NHSV increased from 7.9 to 10 per 100,000 live births from 2003-05 to 2012-14 (P = 0.04). Hospital costs increased from $21,650 to $27,843; P < 0.001). The overall mortality rate and median LOS were 7.9% and 20 days, respectively and there were no significant variations across years during the study period. CONCLUSIONS: The incidence of NHSV in the United States increased between 2003 and 2014 without a significant change in mortality. NHSV remains a serious health threat and new and effective strategies to prevent NHSV are needed.

Trends in epidemiology and outcomes of respiratory distress syndrome in the United States.

BACKGROUND: The management practices of Respiratory Distress Syndrome (RDS) in the newborn have changed over time. We examine the trends in the epidemiology, resource utilization, and outcomes (mortality and bronchopulmonary dysplasia [BPD]) of RDS in preterm neonates ≤34 weeks gestational age (GA) in the United States. METHODS: In this retrospective serial cross-sectional study, we used ICD-9 codes to classify preterm infants GA ≤34 weeks between 2003 and 2014 from the National Inpatient Sample as having RDS or not. Trends in the prevalence of infants defined as RDS by ICD-9 code (ICD9-RDS), length of stay, BPD, and mortality were analyzed using Cochran-Armitage and Jonckheere-Terpstra tests and multivariable logistic regression. RESULTS: Of 1 526 186 preterm live births with GA ≤34 weeks, 554 409 had ICD9-RDS (260 cases per 1000 live births) with the prevalence increasing from 170 to 361 (Ptrend < 0.001) and associated decrease in all-cause mortality (7.6% to 6.1%; Ptrend < 0.001) from 2003 to 2014. Increased utilization of non-invasive mechanical ventilation (NIMV) (69.5% to 74.3%; Ptrend < 0.001) was associated with decreased invasive mechanical ventilation (IMV) use >96 h (60.4 to 56.6%; Ptrend < 0.001). Exclusive NIMV use increased from 16.8% to 29.1% (Ptrend < 0.0001). BPD incidence decreased from 14% to 12.5% (Ptrend < 0.001). LOS increased from 32 days to 38 days (Ptrend < 0.001) and cost increased from $49,521 to $55,394 (Ptrend < 0.001). CONCLUSION: From 2003 to 2014, the assigned ICD9-RDS diagnosis, and utilization of NIMV increased and mortality among infants assigned the ICD9-RDS diagnosis decreased. With higher survival, hospital cost increased incrementally, indicating the importance of ongoing analysis of appropriate reimbursement for the care provided at tertiary centers for preterm infants.

TNFα-stimulated protein 6 (TSG-6) reduces lung inflammation in an experimental model of bronchopulmonary dysplasia.

BACKGROUND: Inflammation is a key factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Tumor necrosis factor-stimulated protein 6 (TSG-6) is a glycoprotein that modulates inflammation. Here we tested the hypothesis that intra-tracheal (IT) administration of an adenovirus overexpressing TSG-6 (AdTSG-6) would decrease inflammation and restore lung structure in experimental BPD. METHODS: Newborn Sprague-Dawley rats exposed to normoxia (RA) or hyperoxia (85% O2) from postnatal day (P) 1-P14 were randomly assigned to receive IT AdTSG-6 or placebo (PL) on P3. The effect of IT AdTSG-6 on lung inflammation, alveolarization, angiogenesis, apoptosis, pulmonary vascular remodeling, and pulmonary hypertension were evaluated on P14. Data were analyzed by two-way ANOVA. RESULTS: TSG-6 mRNA was significantly increased in pups who received IT AdTSG-6. Compared to RA, hyperoxia PL-treated pups had increased NF-kß activation and lung inflammation. In contrast, IT AdTSG-6 hyperoxia-treated pups had decreased lung phosphorylated NF-kß expression and markers of inflammation. This was accompanied by an improvement in alveolarization, angiogenesis, pulmonary vascular remodeling, and pulmonary hypertension. CONCLUSIONS: IT AdTSG-6 decreases lung inflammation and improves lung structure in neonatal rats with experimental BPD. These findings suggest that therapies that increase lung TSG-6 expression may have beneficial effects in preterm infants with BPD.