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The DST gene is located on chromosome 6p and encodes for a large protein. Alternative splicing of this protein produces the neuronal (a1-a3), muscular (b1-b3), and epithelial (e) isoforms. Hereditary sensory and autonomic neuropathy (HSAN) type VI is a rare autosomal recessive disorder due to mutations affecting the a2 isoform. We present a case of HSAN-VI in a male neonate born to consanguineous parents. Genome sequencing revealed a novel homozygous variant (DST_c.1118C T; p.Pro373Leu) inherited from both parents. This case further expands the phenotype and genotype of this rare syndrome.

To predict pulmonary hypertension (PH) therapy at discharge in a large multicenter cohort of infants with congenital diaphragmatic hernia (CDH). Six-year linked records from Children’s Hospitals Neonatal Database and Pediatric Health Information System were used; patients whose diaphragmatic hernia was repaired before admission or referral, who were previously home before admission or referral, and non-survivors were excluded. The primary outcome was the use of PH medications at discharge and the secondary outcome was an inter-center variation of therapies during inpatient utilization. Clinical factors were used to develop a multivariable equation randomly applied to 80% cohort; validated in the remaining 20% infants. A total of 831 infants with CDH from 23 centers were analyzed. Overall, 11.6% of survivors were discharged on PH medication. Center, duration of mechanical ventilation, and duration of inhaled nitric oxide were associated with the use of PH medication at discharge. This model performed well in the validation cohort area under the receiver operating characteristic curve of 0.9, goodness-of-fit χ2, p = 0.17. Clinical variables can predict the need for long-term PH medication after NICU hospitalization in surviving infants with CDH. This information may be useful to educate families and guide the development of clinical guidelines.

OBJECTIVE The aim of this study was to describe the use, duration, and intercenter variation of analgesia and sedation in infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN This is a retrospective analysis of analgesia, sedation, and neuromuscular blockade use in neonates with CDH. Patient data from 2010 to 2016 were abstracted from the Children's Hospitals Neonatal Database and linked to the Pediatric Health Information System. Patients were excluded if they also had non-CDH conditions likely to affect the use of the study medications. RESULTS A total of 1,063 patients were identified, 81% survived, and 30% were treated with extracorporeal membrane oxygenation (ECMO). Opioid (99.8%), sedative (93.4%), and neuromuscular blockade (87.9%) use was common. Frequency of use was higher and duration was longer among CDH patients treated with ECMO. Unadjusted duration of use varied 5.6-fold for benzodiazepines (median: 14 days) and 7.4-fold for opioids (median: 16 days). Risk-adjusted duration of use varied among centers, and prolonged use of both opioids and benzodiazepines ≥5 days was associated with increased mortality (p

Our hypothesis was that among infants with hypoxic-ischemic encephalopathy (HIE), venoarterial (VA), compared to venovenous (VV), extracorporeal membrane oxygenation (ECMO) is associated with an increased risk of mortality or intracranial hemorrhage (ICH). Retrospective cohort analysis of infants in the Children’s Hospitals Neonatal Database from 2010 to 2016 with moderate or severe HIE, gestational age ≥36 weeks, and ECMO initiation

Objective Infants with congenital diaphragmatic hernia (CDH) require multiple invasive interventions carrying inherent risks, including central venous and arterial line placement. We hypothesized that specific clinical or catheter characteristics are associated with higher risk of nonelective removal (NER) due to complications and may be amenable to efforts to reduce patient harm. Study Design Infants with CDH were identified in the Children's Hospital's Neonatal Database (CHND) from 2010 to 2016. Central line use, duration, and complications resulting in NER are described and analyzed by extracorporeal membrane oxygenation (ECMO) use. Results A total of 1,106 CDH infants were included; nearly all (98%) had a central line placed, (average of three central lines) with a total dwell time of 22 days (interquartile range [IQR]: 14–39). Umbilical arterial and venous lines were most common, followed by extremity peripherally inserted central catheters (PICCs); 12% (361/3,027 central lines) were removed secondary to complications. Malposition was the most frequent indication for NER and was twice as likely in infants with intrathoracic liver position. One quarter of central lines in those receiving ECMO was placed while receiving this therapy. Conclusion Central lines are an important component of intensive care for infants with CDH. Careful selection of line type and location and understanding of common complications may attenuate the need for early removal and reduce risk of infection, obstruction, and malposition in this high-risk group of patients. Key Points

The objective of this study was to characterize clinical factors associated with successful extubation in infants with congenital diaphragmatic hernia.Using the Children's Hospitals Neonatal Database, we identified infants with congenital diaphragmatic hernia from 2017 to 2020 at 32 centers. The main outcome was age in days at the time of successful extubation, defined as the patient remaining extubated for 7 consecutive days. Unadjusted Kaplan-Meier and multivariable Cox proportional hazards ratio equations were used to estimate associations between clinical factors and the main outcome. Observations occurred through 180 days after birth.There were 840 eligible neonates with a median gestational age of 38 weeks and birth weight of 3.0 kg. Among survivors (n = 693), the median age at successful extubation was 15 days (interquartile range [IQR]: 8-29 days, 95th percentile: 71 days). For nonsurvivors (n = 147), the median age at death was 21 days (IQR: 11-39 days, 95th percentile: 110 days). Center (adjusted hazards ratio: 0.22-15, P .01), low birth weight, intrathoracic liver position, congenital heart disease, lower 5-minute Apgar score, lower pH upon admission to Children's Hospitals Neonatal Database center, and use of extracorporeal support were independently associated with older age at successful extubation. Tracheostomy was associated with multiple failed extubations.Our findings suggest that infants who have not successfully extubated by about 3 months of age may be candidates for tracheostomy with chronic mechanical ventilation or palliation. The variability of timing of successful extubation among our centers supports the development of practice guidelines after validating clinical criteria.

Objective was to compare the rate of successful treatment of hsPDA based on echocardiogram criteria after use of IV acetaminophen or IV indomethacin in very low-birthweight infants. The study was a multi-center, randomized controlled trial. Infants born prior to 32 weeks with birthweight ≤ 1500 g were included if PDA treatment was indicated within the 21 days after birth. hsPDA was defined by strict echocardiogram criteria. Eligible infants were randomized to treatment with either IV acetaminophen or IV indomethacin. Of 86 eligible infants, 17 infants were randomized to acetaminophen and 20 to indomethacin. One (5.9%) hsPDA in the acetaminophen group had successful treatment compared to 11 (55%) in the indomethacin group (p = 0.002). Eight (47%) in the acetaminophen group and 3 (15%) in the indomethacin group received transcatheter PDA closure (p = 0.07). IV indomethacin was more effective than IV acetaminophen for treatment of hsPDAs. More infants in the acetaminophen group received transcatheter closure.

Objective Sham feeding may enhance development of oral skills in neonates after bowel surgery and decrease stress levels in mothers. In this pilot study, we test the feasibility of sham feeding, identify safety hazards, and assess maternal satisfaction. Study Design A convenience sample of 15 postoperative neonates was enrolled. Sham feeding with unfortified human milk was offered following a strict advancement protocol beginning with 5 mL once daily and increasing up to 30 mL, three times daily. Continuous gastric suction was used during sham feeding. Each mother completed a satisfaction survey. Sham-fed gastroschisis patients were compared with a historic cohort. Results All 15 patients were able to sham feed. A total of 312 sham feeds were offered with a median of 23 sham events per patient. Four minor complications occurred during sham feeding. No differences were noted between 11 sham-fed gastroschisis patients and 81 historic controls. The mothers reported a decrease in stress after sham feeding using a 5-point score (3.8 ± 1.4 vs. 1.5 ± 0.7, p Conclusion Sham feeding is feasible for neonates after bowel surgery and is highly rated by mothers. Key Points

Describe inpatient pulmonary hypertension (PH) treatment and factors associated with therapy at discharge in a multicenter cohort of infants with CDH. Six years linked records from Children’s Hospitals Neonatal Database and Pediatric Health Information System were used to describe associations between prenatal/perinatal factors, clinical outcomes, echocardiographic findings and PH medications (PHM), during hospitalization and at discharge. Of 1106 CDH infants from 23 centers, 62.8% of infants received PHM, and 11.6% of survivors were discharged on PHM. Survivors discharged on PHM more frequently had intrathoracic liver, small for gestational age, and low 5 min APGARs compared with those discharged without PHM (p

Patent ductus arteriosus (PDA) is prevalent in premature newborns and has been linked to the development of bronchopulmonary dysplasia (BPD), a serious pulmonary complication of premature birth. Although a causal relationship has not been proven, the link is greatest among infants born at lower gestational age who are treated with mechanical ventilation in the presence of a large ductal shunt. Despite strong association in epidemiological studies, treatment of a patent ductus arteriosus has not been shown to prevent BPD, and some therapies may increase the risk of BPD. We describe preclinical and clinical data demonstrating the association of a PDA with BPD, highlight the effects of surgical and pharmacological treatment, and explore the implications of recent clinical trials for the management of PDA in the premature newborn.

Historically, some physicians are reluctant to offer extracorporeal membrane oxygenation (ECMO) to infants with neonatal encephalopathy. This study describes how ECMO practices have changed since the development of therapeutic hypothermia (TH) for neonatal encephalopathy. A 22-question electronic survey was sent to neonatal medical directors and ECMO directors in the USA and Canada. Participants were queried on TH and ECMO practices and if they would offer ECMO given certain clinical factors; confidential responses were compared with a similar survey conducted in 2008. A total of 356 physicians were invited to participate, and the response rate was 25%. Seventy-two percent had initiated or referred for ECMO during cooling therapy. Compared with the 2008 survey, participants were more likely to offer ECMO for moderate and severe encephalopathy. Ninety-four percent offer hypothermia for neonatal encephalopathy, but only 24% have written ECMO criteria for such patients. Neonatologists were more likely than non-neonatologists to offer ECMO for mild and moderate encephalopathy. ECMO use with neonatal encephalopathy has increased since TH has become standard care. Wide variability in practice remains with important differences between neonatologists and non-neonatologists.

Introduction Extracorporeal membrane oxygenation (ECMO) requires a multidisciplinary healthcare team. The Extracorporeal Life Support Organization publishes training guidelines but leaves specific requirements up to each institution. Simulation training has shown promise, but it is unclear how many institutions have incorporated simulation techniques into ECMO training to date. Methods We sent an electronic survey to ECMO coordinators at Extracorporeal Life Support Organization sites in the United States. Participants were asked about training practices and the use of simulation for ECMO training. Descriptive results were reported as the percentage of total responses for each question. Logistic regression was used to identify characteristics associated with simulation use. Results Of 94 responses (62% response rate), 46% had an ECMO simulation program, whereas 26% report a program is in development. Most (61%) have been in operation for 2 to 5 years. Sixty-three percent use simulation for summative assessment, and 76% have multidisciplinary training. Access to a simulation center [odds ratio (OR) = 4.7, 95% confidence interval (CI) = 1.7-12.5], annual ECMO caseload of greater than 20 (OR = 2.5, 95% CI = 1.5-5.8), and having a pediatric cardiothoracic intensive care unit (OR = 2.8, 95% CI = 1.2-6.7) are each associated with increased likelihood of mannequin-based ECMO simulation. Common scenarios include pump failure (93%), oxygenator failure (90%), and circuit rupture (76%). Discussion Extracorporeal membrane oxygenation simulation is growing but remains in its infancy. Centers with access to a simulation center, higher caseloads, and pediatric cardiothoracic intensive care units are more likely to have ECMO simulation programs. Extracorporeal membrane oxygenation simulation is felt to be beneficial, and further work is needed to delineate best training practices for ECMO providers.

Background Management of CDH is highly variable from center to center, as are patient outcomes. The purpose of this study was to examine risk-stratified survival and extracorporeal membrane oxygenation (ECMO) rates at a single center, and to determine whether adverse outcomes are related to patient characteristics or management. Methods A retrospective single-center review of CDH patients was performed, and outcomes compared to those reported by the CDH Study Group (CDHSG) registry. Patient demographics, disparities, and clinical characteristics were examined to identify unique features of the cohort. A model derived using the registry that estimates probability of ECMO use or death in CDH newborns was used to risk-stratify patients and assess mortality rates. Observed over expected (O/E) ECMO use rates were calculated to measure whether “excess” or “appropriate” ECMO use was occurring. Results There were 81 CDH patients treated between 2004–2017, and 5034 in the CDHSG registry. Mortality in ECMO-treated patients was higher than the registry. Socioeconomic variables were not significantly associated with outcomes. The strongest predictors of mortality were ECMO use and early blood gas variables. The risk model accurately predicted ECMO use with a c-statistic of 0.79. Compared with the registry, the disparity in mortality rates was greatest for moderate-risk patients. O/E ECMO use was highest in low and moderate-risk patients. Conclusions ECMO use is a more consistent predictor of mortality than CDH severity at a single center, and there is relative overuse of ECMO in lower-risk patients. Risk stratification allows for more accurate institutional assessment of mortality and ECMO use, and other centers could consider such an adjusted analysis to identify opportunities for outcomes improvement. Level of Evidence III.

Congenital diaphragmatic hernia occurs when a portion of the fetal diaphragm is absent, allowing abdominal contents to enter the thorax, and is associated with impaired pulmonary development. Although overall mortality is near 30%, a mortality rate less than 15% may be possible by following a standardized multidisciplinary care plan. Fetal diagnosis and evaluation can improve coordination of care, but there is no clear role for fetal intervention. After birth, gentle ventilation with permissive hypercapnia supports the infant while minimizing lung injury. Appropriate cardiovascular support, treatment of pulmonary hypertension, and extracorporeal membrane oxygenation may benefit some patients. Timing of surgical repair depends on disease severity. All patients should have close follow-up after discharge.

Mobile communication with the medical-care team has the potential to decrease stress among parents of infants admitted to the neonatal intensive care unit (NICU). We assessed mobile use and communication preferences in a population of urban minority NICU mothers. A 30-question English language survey was administered to mothers of NICU patients. The survey was completed by 217 mothers, 75% were Black, and 75% reported annual household income below $20 000. Only 56% had a computer with Internet access at home, but 79% used smartphones. Most (79%) have searched the Internet for health information in the past year. Receiving electronic messages about their babies was viewed favorably, and text messaging was the preferred platform. The majority of mothers felt electronic messaging would improve communication but should not replace verbal communication. Mobile communication is used widely in this population of NICU mothers and could potentially improve provider–parent communication and reduce parental stress.

1. Mark Weems, MD 1. Associate Editor For more than 35 years, the editors of Pediatrics in Review (PIR) have turned to content experts to write review articles that can be used by pediatricians in daily practice. We also understand that our “Index of Suspicion” and “Visual Diagnosis” sections provide opportunities for young physicians to build their portfolios, and we welcome case submissions by junior faculty and residents when supervised by more experienced pediatricians. When I joined the Editorial Board 2 years ago as the first PIR editorial fellow, I was shocked by a disturbing trend in submitted articles: plagiarism. Plagiarism is not unique to PIR. In fact, it is so prevalent in medical literature that Miguel Roig’s 2013 PubMed search for “plagiarism” resulted in 1,086 articles. (1) As of August 24, 2016, that number has risen to 1,461. Plagiarism threatens the authority of our peer-reviewed journal and puts our publisher, the American Academy of Pediatrics (AAP), at risk for copyright infringement. In an effort to prevent plagiarized material from being published, all manuscripts submitted to PIR are screened with Crossref Similarity Check, powered by iThenticate (Crossref, Lynnfield, MA, and Turnitin, LLC, Oakland, CA) and compared against a database containing more than 60 billion documents. This process is described in our author instructions, but we continue to receive plagiarized manuscripts. Therefore, we feel it is important to share some deeper insight into the issue of plagiarism. Reading through a small selection of the 1,461 …

Circulating endothelial progenitor cells (EPC) are bone marrow derived progenitors that can be mobilized by erythropoietin or in response to tissue injury, and participate in vascular repair. EPC are understudied in human neonates. Whether EPC frequency in newborn infants may be influenced by gestational age or postnatal stress is unknown.Blood samples were collected on day 1 of life and weekly for 3 weeks from hospitalized neonates for plasma erythropoietin and flow cytometry analysis for CD34+, CD34+CD45-, CD34+VEGFR2+ and CD34+CD45-VEGFR2+ cells (EPC). Associations between CD34+ cell subsets and clinical parameters were studied.Forty five patients were enrolled. An inverse correlation with gestational age was observed for CD34+ and CD34+ VEGFR2+ cell frequencies in whole blood (WB) on day 1 (p0.05). In preterm infants, CD34+ cell frequency decreased with increased postnatal age (p=0.0001) and CD34+VEGFR2+ cell frequency was higher at week 3 than on day 1 in WB (p=0.0002). On day one, CD34+ and CD34+CD45- cell frequencies in the mononuclear cell fraction (MNC) were higher in preterm than term infants (p=0.035 and p=0.049, respectively) but CD34+CD45-VEGFR2+ cell frequency (median 2.2/million MNC versus 3.8/million MNC) and erythropoietin levels were not significantly different. Transient increases in EPC were observed in five infants with infection. Four preterm infants who developed bronchopulmonary dysplasia had undetectable or low EPC through the first 3 weeks of life.Gestational age and postnatal age influenced circulating CD34+ and CD34+VEGFR2+ but not CD34+CD45-VEGFR2+ (EPC) cell frequencies. Circulating EPC in neonates may be influenced by clinical stress.

Objective Our aim was to describe laboratory findings and imaging results for neonatal patients diagnosed with urinary tract infection (UTI). Study Design Medical records were reviewed for infants diagnosed with UTI in a single neonatal intensive care unit (NICU) over a 13-year period. Results Of the 8,241 patients admitted to the NICU during the study period, 137 infants were diagnosed with UTI. Imaging was reviewed for 101 patients. Renal pelvis dilation was found in 34% of patients and vesicoureteral reflux was found in 21%. Renal pelvis dilation was not associated with reflux (OR: 0.53 [95% CI: 0.18–1.5]). The sensitivity of urinalysis to detect a positive culture was 76%, and the specificity was 41%. Tests of cure for bacterial infections were uniformly negative. Conclusion Renal pelvis dilation was common but not associated with reflux among NICU patients diagnosed with UTI. Diagnostic criteria in this population are not well defined, and guidelines are needed for diagnosis and management of UTIs in NICU patients.