Risk Factors for Pneumothorax and Its Association with Ventilation in Neonates.

OBJECTIVE: The mode of ventilation that is implicated in pneumothorax is the one at the time of its diagnosis. Although there is evidence that air leak starts many hours before it is clinically evident, there are no prior studies that have investigated the association of pneumothorax with the mode of ventilation few hours before rather than at the time of its diagnosis. STUDY DESIGN: A retrospective case-control study was conducted in the neonatal intensive care unit (NICU) between 2006 and 2016 where cases of neonates with pneumothorax were compared with gestational age-matched control neonates without pneumothorax. Respiratory support associated with pneumothorax was classified as the mode of ventilation 6 hours before the clinical diagnosis of pneumothorax. We investigated the factors that were different between cases and controls, and between cases of pneumothorax on bubble continuous positive airway pressure (bCPAP) and invasive mechanical ventilation (IMV). RESULT: Of the 8,029 neonates admitted in the NICU during the study period, 223 (2.8%) developed pneumothorax. Among these, 127 occurred among 2,980 (4.3%) neonates on bCPAP, 38 among 809 (4.7%) neonates on IMV, and the remaining 58 among 4,240 (1.3%) neonates on room air. Those with pneumothorax were more likely to be male, have higher body weight, require respiratory support and surfactant administration, and have bronchopulmonary dysplasia (BPD). Among those who developed pneumothorax, there were differences in the gestational age, gender, and use of antenatal steroids between those who were on bCPAP as compared to those on IMV. IMV was associated with increased odds of pneumothorax as compared to those on bCPAP in a multivariable regression analysis. Cases on IMV had higher incidence of intraventricular hemorrhage, retinopathy of prematurity, BPD, and necrotizing enterocolitis, as well as longer length of stay as compared to those on bCPAP. CONCLUSION: Neonates who require any respiratory support have higher incidence of pneumothorax. Among those on respiratory support, those on IMV had higher odds of pneumothorax and worse clinical outcomes as compared to those on bCPAP. KEY POINTS: · The process of air leak leading to pneumothorax in majority of neonates starts much before it is clinically diagnosed.. · It is possible to detect the air leak early in the process by subtle changes in the signs, symptoms and changes in lung function.. · True association of the ventilation associated with pneumothorax is not at the time of diagnosis of pneumothorax but few hours before it is diagnosed.. · There is higher incidence of pneumothorax in neonates on any respiratory support.. · There is significantly higher incidence of pneumothorax among neonates on invasive ventilations as compared to noninvasive ventilation after correction for all other clinical factors..

Gastroschisis Outcomes: Presence of Histologic Chorioamnionitis and the Impact on Time to Full Enteral Feeds and Length of Hospital Stay.

OBJECTIVE: Despite improvements in our ability for early diagnosis and providing supportive care for infants with gastroschisis, it continues to be associated with long length of stay and morbidity. Intestinal dysfunction secondary to chronic inflammatory insult to exposed bowel is well known; however, little research has been done on the impact of acute inflammation in the perinatal period on intestinal function. This study's aim was to investigate the impact of acute chorioamnionitis on the time to achieve full enteral feeds and length of hospital stay. STUDY DESIGN: Retrospective chart review of 60 mothers and their infants born with gastroschisis at a Level IV NICU from November 2011 to June 2020 was performed. Infants were divided into two groups based on the presence of histologic chorioamnionitis, and outcomes were compared. The primary outcome was delayed full enteral feeds (full enteral feeds after 28 days of life). The secondary outcomes were differences in their time to achieve full enteral feeds and time to hospital discharge, and prolonged length of hospital stay (discharge after 30 days of life). Univariate and multivariate logistic regression analyses were performed to assess the association between the dependent and the predictor variables. RESULT: Of the 60 infants enrolled, 23 (38%) had evidence of histologic chorioamnionitis. The median gestational age was 37 weeks. Fifty-four (90%) infants achieved full enteral feeds, with a median time of 24 days. Median length of hospital stay was 31 days. The presence of histologic chorioamnionitis was not associated with delayed full enteral feeds (odds ratio [OR] = 0.79; 95% confidence interval [CI] = 0.14-4.23; p = 0.80) or prolonged length of hospital stay (OR = 0.45; 95% CI = 0.1-0.23; p = 0.32) in the adjusted analysis. CONCLUSION: Acute placental inflammation during the perinatal period does not impact the infant's time to achieve full feeds or prolong their hospital stay. Larger studies are needed to confirm these findings. KEY POINTS: · Chronic inflammatory injury to exposed bowel in utero is well known in fetuses with gastroschisis.. · Acute inflammatory injury during perinatal period may impact enteral feeding outcomes.. · No impact of acute placental inflammation on time to full enteral feeds..

Association between Sleep Disordered Breathing and Neonatal Outcomes in Nulliparous Individuals.

OBJECTIVE: Our objective was to determine whether objectively measured sleep-disordered breathing (SDB) during pregnancy is associated with an increased risk of adverse neonatal outcomes in a cohort of nulliparous individuals. STUDY DESIGN: Secondary analysis of the nuMom2b sleep disordered breathing substudy was performed. Individuals underwent in-home sleep studies for SDB assessment in early (6-15 weeks' gestation) and mid-pregnancy (22-31 weeks' gestation). SDB was defined as an apnea-hypopnea index ≥5 events/h at either time point. The primary outcome was a composite outcome of respiratory distress syndrome, transient tachypnea of the newborn, or receipt of respiratory support, treated hyperbilirubinemia or hypoglycemia, large-for-gestational age, seizures treated with medications or confirmed by electroencephalography, confirmed sepsis, or neonatal death. Individuals were categorized into (1) early pregnancy SDB (6-15 weeks' gestation), (2) new onset mid-pregnancy SDB (22-31 weeks' gestation), and (3) no SDB. Log-binomial regression was used to calculate adjusted risk ratios (RR) and 95% confidence intervals (CIs) representing the association. RESULTS: Among 2,106 participants, 3% (n = 75) had early pregnancy SDB and 5.7% (n = 119) developed new-onset mid-pregnancy SDB. The incidence of the primary outcome was higher in the offspring of individuals with early (29.3%) and new onset mid-pregnancy SDB (30.3%) compared with individuals with no SDB (17.8%). After adjustment for maternal age, chronic hypertension, pregestational diabetes, and body mass index, new onset mid-pregnancy SDB conferred increased risk (RR = 1.43, 95% CI: 1.05, 1.94), where there was no longer statistically significant association between early pregnancy SDB and the primary outcome. CONCLUSION: New onset, mid-pregnancy SDB is independently associated with neonatal morbidity. KEY POINTS: · Sleep disordered breathing (SDB) is a common condition impacting pregnancy with known maternal risks.. · Objectively defined SDB in pregnancy was associated with a composite of adverse neonatal outcomes.. · New onset SDB in mid pregnancy conferred statistically significant increased risk..

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..

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..

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.

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.

Temporal Trends of Pediatric Hospitalizations with Acute Disseminated Encephalomyelitis in the United States: An Analysis from 2006 to 2014 using National Inpatient Sample.

OBJECTIVE: To determine the temporal trends in the epidemiology of acute disseminated encephalomyelitis (ADEM) and hospitalization outcomes in the US from 2006 through 2014. STUDY DESIGN: Pediatric (≤18 years of age) hospitalizations with ADEM discharge diagnosis were identified from the National (Nationwide) Inpatient Sample (NIS) for years 2006 through 2014. Trends in the incidence of ADEM with respect to age, sex, race, and region were examined. Outcomes of ADEM in terms of mortality, length of stay (LOS), cost of hospitalization, and seasonal variation were analyzed. NIS includes sampling weight. These weights were used to generate national estimates. P value of < .05 was considered significant. RESULTS: Overall incidence of ADEM associated pediatric hospitalizations from 2006 through 2014 was 0.5 per 100 000 population. Between 2006 through 2008 and 2012 through 2014, the incidence of ADEM increased from 0.4 to 0.6 per 100 000 (P-trend <.001). Black and Hispanic children had a significantly increased incidence of ADEM during the study period (0.2-0.5 per 100 000 population). There was no sex preponderance and 67% of ADEM hospitalizations were in patients <9 years old. From 2006 through 2008 to 2012 through 2014 (1.1%-1.5%; P-trend 0.07) and median LOS (4.8-5.5 days; Ptrend = .3) remained stable. However, median inflation adjusted cost increased from $11 594 in 2006 through 2008 to $16 193 in 2012 through 2014 (Ptrend = .002). CONCLUSION: In this large nationwide cohort of ADEM hospitalizations, the incidence of ADEM increased during the study period. Mortality and LOS have remained stable over time, but inflation adjusted cost of hospitalizations increased.

National Trends in Hospitalization for Fever and Neutropenia in Children with Cancer, 2007-2014.

OBJECTIVE: To assess the trends of inpatient resource use and mortality in pediatric hospitalizations for fever with neutropenia in the US from 2007 to 2014. STUDY DESIGN: Using National (Nationwide) Inpatient Sample (NIS) and International Classification of Diseases, Ninth Revision, Clinical Modification codes, we studied pediatric cancer hospitalizations with fever with neutropenia between 2007 and 2014. Using appropriate weights for each NIS discharge, we created national estimates of median cost, length of stay, and in-hospital mortality rates. RESULTS: Between 2007 and 2014, there were 104 315 hospitalizations for pediatric fever with neutropenia. The number of weighted fever with neutropenia hospitalizations increased from 12.9 (2007) to 18.1 (2014) per 100 000 US population. A significant increase in fever with neutropenia hospitalizations trend was seen in the 5- to 14-year age group, male sex, all races, and in Midwest and Western US hospital regions. Overall mortality rate remained low at 0.75%, and the 15- to 19-year age group was at significantly greater risk of mortality (OR 2.23, 95% CI 1.36-3.68, P = .002). Sepsis, pneumonia, meningitis, and mycosis were the comorbidities with greater risk of mortality during fever with neutropenia hospitalizations. Median length of stay (2007: 4 days, 2014: 5 days, P < .001) and cost of hospitalization (2007: $8771, 2014: $11 202, P < .001) also significantly increased during the study period. CONCLUSIONS: Our study provides information regarding inpatient use associated with fever with neutropenia in pediatric hospitalizations. Continued research is needed to develop standardized risk stratification and cost-effective treatment strategies for fever with neutropenia hospitalizations considering increasing costs reported in our study. Future studies also are needed to address the greater observed mortality in adolescents with cancer.

Temporal trends of splenectomy in pediatric hospitalizations with immune thrombocytopenia.

BACKGROUND: Splenectomy is considered an effective treatment for immune thrombocytopenia (ITP) with 70-80% response rate. However, its current use is limited in children with ITP. It is unclear if the rates of splenectomy have changed over time. Using a large nationally representative database, we aimed to study the trends of splenectomy in pediatric hospitalizations with ITP, and the factors associated with splenectomy during these encounters. METHODS: Using National (Nationwide) Inpatient Sample (NIS), and international classification of diseases (9th revision), clinical modification (ICD-9-CM) codes, we studied pediatric ITP hospitalizations with occurrence of total splenectomy between 2005 and 2014. RESULTS: Out of 37,844 weighted ITP hospitalizations from 2005 to 2014; total splenectomy was performed in 954 encounters. Splenectomy rate declined over time (3.4% [2005-2006] to 1.6% [2013-2014], P < 0.001) with the younger age (≤5 years) having the most notable decline (0.91% [2005-2006] to 0.14% [2013-2014], P < 0.001). Splenectomy had higher odds of being performed electively than non-electively (odds ratio [OR]: 19.34, 95% confidence interval [CI]: 12.06-31.02, P < 0.001). Encounters with intracranial bleed were associated with the occurrence of splenectomy (OR: 17.87, 95% CI: 5.07-62.97, P < 0.001). Intracranial bleed (P < 0.001), gastrointestinal bleed (P < 0.01), sepsis (P < 0.001), and thrombosis (P < 0.001) were associated with longer length of stay and higher cost of hospitalization. CONCLUSIONS: Overall, splenectomy rates consistently declined over time. Intracranial hemorrhage during hospitalizations with ITP was associated with occurrence of splenectomy. Future studies should continue to reevaluate the rates of splenectomy in pediatric ITP in the presence of various second-line pharmacologic agents.

Trends in incidence and outcomes of gastroschisis in the United States: analysis of the national inpatient sample 2010-2014.

PURPOSE: Gastroschisis is a severe congenital anomaly associated with a significant morbidity and mortality. There are limited temporal trend data on incidence, mortality, length of stay, and hospital cost of gastroschisis. Our aim was to study these temporal trends using the National Inpatient Sample (NIS). METHODS: We identified all neonatal admissions with a diagnosis of gastroschisis within the NIS from 2010 through 2014. We limited admission age to ≤ 28 days and excluded all those transferred to other hospitals. We estimated gastroschisis incidence, mortality, length of hospital stay, and cost of hospitalization. For continuous variables, trends were analyzed using survey regression. Cochrane-Armitage trend test was used to analyze trends for categorical variables. P < 0.05 was considered as significant. RESULTS: The incidence of gastroschisis increased from 4.5 to 4.9/10,000 live births from 2010 through 2014 (P = 0.01). Overall mortality was 3.5%, median length of stay was 35 days (95% CI 26-55 days), and median cost of hospitalization was $75,859 (95% CI $50,231-$122,000). After adjusting for covariates, there was no statistically significant change in mortality (OR = 1.13; 95% CI 0.87-1.48), LOS (ß = - 2.1 ± 3.5; 95% CI - 9.0 to 4.8) and hospital cost (ß = - 2.137 ± 10.813; 95% CI - 23,331 to 19,056) with each calendar year increase on multivariate logistic regression analysis. CONCLUSION: The incidence of neonates with gastroschisis increased between 2010 and 2014. Incidence was highest in the West. No difference in mortality and resource utilization was observed.

Risk of birth defects in pregnant persons with sleep-disordered breathing during pregnancy.

INTRODUCTION: As many as one in four pregnant women may experience sleep-disordered breathing (SDB) during pregnancy. The same sequelae of SDB, such as insulin resistance and inflammation, have been implicated in the development of certain birth defects. METHODS: This is a secondary analysis of the SDB substudy of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be study, which included 2106 participants who had a sufficiency sleep study at two visits at different time points in pregnancy. SDB was based on a self-administered home sleep apnea test with data scored by trained, blinded research polysomnologists. SDB was defined as an apnea-hypopnea index (AHI) ≥5. The primary outcome of this analysis was any of the 45 non-chromosomal birth defects included in the National Birth Defects Prevention Network Annual Report. RESULTS: In this cohort, the overall rate of birth defects was 3.1%. The prevalence was similar between those without SDB (3.0%) and those with only mid-pregnancy SDB (3.4%), but was higher in those with early-pregnancy SDB (6.7%). After adjusting for maternal age, chronic hypertension, pregestational diabetes, and body mass index (BMI), there were no statistically significant differences in the risk of birth defects by subject SDB status. CONCLUSIONS: Further studies to evaluate the effect of prepregnancy and early-pregnancy SDB on the fetus, as well as the risk of specific birth defects and neonatal outcomes in those with an objectively measured diagnosis of SDB, are still needed.

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.

Human Milk Lipids Induce Important Metabolic and Epigenetic Changes in Neonates.

Lipids are a major source of energy during the fetal/neonatal period. Most are received from the mother, transplacentally during the intrauterine period or via maternal milk after birth. However, in addition to the known nutritional roles, lipids are now known to bind a variety of cellular receptors to regulate specific patterns in metabolism and gene expression. The expression of these receptors is regulated by various genetic and environmental stimuli, and ligation can activate positive-feedback loops in the expression and the activity of downstream signaling pathways. The authors summarize the role of lipid ligands, cognate receptors, epigenetic regulation, and downstream signaling.

The Impact of MicroRNAs in Neonatal Necrotizing Enterocolitis and other Inflammatory Conditions of Intestine: A Review.

The understanding of necrotizing enterocolitis (NEC) etiopathogenesis is incomplete, contributing to the lack of early biomarkers and therapeutic options. Micro RNAs (miRNAs) are a class of RNAs that can alter gene expression and modulate various physiological and pathological processes. Several studies have been performed to evaluate the role of miRNA in the pathogenesis of NEC. In this article, we review the information on miRNAs that have been specifically identified in NEC or have been noted in other inflammatory bowel disorders that share some of the histopathological abnormalities seen frequently in NEC. This review highlights miRNAs that could be useful as early biomarkers of NEC and suggests possible approaches for future translational studies focused on these analytes. It is a novel field with potential for immense translational and clinical relevance in preventing, detecting, or treating NEC in very premature infants. Impact • Current information categorizes necrotizing enterocolitis (NEC) as a multifactorial disease, but microRNAs (miRNAs) may influence the risk of occurrence of NEC. • MiRNAs may alter the severity of the intestinal injury and the clinical outcome of NEC. • The literature on intestinal diseases of adults suggests additional miRNAs that have not been studied in NEC yet but share some features and deserve further exploration in human NEC, especially if affecting gut dysbiosis, intestinal perfusion, and coagulation disorders.

Non-coding RNAs in Neonatal Necrotizing Enterocolitis.

The incomplete understanding of the etiopathogenesis of necrotizing enterocolitis (NEC) contributes to the lack of timely diagnosis and limited therapeutic options. Non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression in various pathways that can modulate various physiological and pathological processes. Despite several studies revealing the role of ncRNAs in intestinal inflammatory diseases in adults, these remain largely unexplored in NEC. In this article, we review the information on ncRNAs that have been specifically identified in NEC or have been noted in other inflammatory bowel disorders that share some of the histopathological abnormalities seen frequently in NEC. We have assimilated the most current research findings on ncRNAs in intestinal diseases. This is an attempt to explore a novel field that has immense potential for future translational and clinical research in preventing, detecting, and treating NEC.

Single Nucleotide Polymorphisms in Neonatal Necrotizing Enterocolitis.

The etiopathogenesis of necrotizing enterocolitis (NEC) remains unclear, but increasing information suggests that the risk and severity of NEC may be influenced by single nucleotide polymorphisms in many genes. In this article, we have reviewed gene variations that have either been specifically identified in NEC or have been noted in other inflammatory bowel disorders with similar histopathological abnormalities. We present evidence from our own peer-reviewed laboratory studies and data from an extensive literature search in the databases PubMed, EMBASE, and Scopus. To avoid bias in the identification of existing studies, search keywords were short-listed both from our own studies and from PubMed's Medical Subject Heading (MeSH) thesaurus.

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 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.