A Path Toward Equity and Inclusion: Establishing a DEI Committee in a Department of Pediatrics.

The Diversity, Equity, and Inclusion (DEI) committee was established in 2017 within the Department of Pediatrics at Rush University Medical Center (RUMC), an academic medical health center located on the near west side of Chicago, IL. Results from climate surveys highlighted the need for increased DEI initiatives within the department, and a renewed national reckoning on racial tensions sparked an additional sense of urgency for system-level change. This paper outlines the initial creation and ongoing efforts of the DEI committee. Information related to the structure of our committee, aims of our work, progress toward identified goals, as well as ongoing barriers is provided. Academic medical health centers are tasked not only with working and training together, but also to care for a diverse group of patients within a larger community. As such, academic medical health centers represent a unique backdrop and opportunity for individual and system-level change.

Safety of Intratracheal Administration of Human Umbilical Cord Blood Derived Mesenchymal Stromal Cells in Extremely Low Birth Weight Preterm Infants.

In a phase 1 dose-escalation trial at 2 dosing levels, we assessed the safety of intratracheal administration of a single-dose of human umbilical cord blood-derived mesenchymal stromal cells in 12 extremely low birth weight infants <28 weeks of gestation and <1000 g at birth at 5-14 days of life. The treatment was well tolerated and appears to be safe and feasible, and warrants a larger randomized-controlled blinded study. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02381366.

Melatonin Use in Pediatric Intensive Care Units: A Single-Center Experience.

Growing evidence indicates that altered melatonin secretion during critical illness may influence the quality and quantity of sleep, delirium, and overall recovery. However, limited data exist regarding the use of melatonin in pediatric critical illness. Data were reviewed over a 5-year period at a tertiary pediatric intensive care unit for pediatric patients (ages 0-18 years) who were prescribed melatonin with the aim of identifying the frequency of and indications for use. Data collection included the hospital day of initiation, the dose, the frequency, the duration of use, and the length of stay. The results demonstrate that melatonin was infrequently prescribed (6.0% of patients admitted; n = 182) and that the majority of patients received melatonin as continuation of home medication (46%; n = 83 of 182). This group had significantly earlier melatonin use (0.9 ± 2.3 day of hospitalization; p < 0.0001) and significantly reduced lengths of stay compared to the other groups (mean LOS 7.2 ± 9.3 days; p < 0.0001). Frequently, clear documentation of indication for melatonin use was absent (20%; n = 37). In conclusion, given that melatonin is infrequently used within a tertiary PICU with the most common indication as the continuation of home medication, and often without clear documentation for indication, this presents an opportunity to emphasize a more attentive and strategic approach regarding melatonin use in the PICU population.

An 8-Month-Old Infant With Respiratory Failure After a Fall.

CASE PRESENTATION: An 8-month-old previously healthy, full-term girl presented with altered mental status after falling approximately 3 feet from a bed, landing on her head. In the ED, she had a CT scan of her head (Fig 1) and was intubated for airway protection. While in the PICU, initial chest radiography showed bilateral infiltrates that were consistent with ARDS, which subsequently resolved. Her respiratory status continued to improve, which allowed a trial on CPAP with invasive neurally adjusted ventilatory assist (NAVA) support, which she was unable to tolerate because of the need for increased support during sleep. On hospital day 8, she was extubated to noninvasive NAVA and was noted to have poor truncal tone and inability to lift or rotate her head. Repeat head CT scans were unchanged. Despite nasal CPAP and NAVA support, she experienced hypercapnia to 83 mm Hg that required reintubation. Brain MRI was completed on hospital day 10 (Fig 1). Lumbar puncture results were obtained, which were unremarkable. Extubation was attempted again on hospital days 15 and 22 with subsequent hypercapnia that required reintubation. She was able to gradually lengthen her CPAP trials but continued to have periods of hypercapnia and bradypnea.

Reducing Incidence of Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a multifactorial disease that occurs when multiple risk factors and/or stressors overlap, leading to profound inflammation and intestinal injury. Due to its multifactorial nature, there has been much uncertainty in identifying clear strategies for prevention of NEC. Despite these obstacles, the incidence of NEC has gradually been decreasing over the past 10 years, in part due to quality improvement (QI) initiatives to prevent NEC. Current QI strategies primarily target the various predisposing conditions. This article reviews the evidence on which QI interventions to prevent NEC have been based and provides examples of successful QI interventions.

Factors that influence use of a home cardiorespiratory monitor for infants: the collaborative home infant monitoring evaluation.

BACKGROUND: As part of the Collaborative Home Infant Monitoring Evaluation, a home monitor was developed to record breathing, heart rate, other physiologic variables, and the time the monitor was used. OBJECTIVE: To determine the frequency of monitor use, factors that influence use, and validity of a model developed to predict use. DESIGN: We developed a model to predict monitor use using multiple linear regression analysis; we then tested the validity of this model to predict adherence for the first week of monitoring and for the subsequent 4-week period (weeks 2-5). SETTING: Clinical research centers in Chicago, Ill; Cleveland, Ohio; Honolulu, Hawaii; Los Angeles, Calif; and Toledo, Ohio. Patients Preterm infants, infants younger than 1 month with a history of autopsy-confirmed sudden infant death syndrome in a sibling, and infants with an idiopathic apparent life-threatening event were divided into 2 cohorts based on enrollment date. Main Outcome Measure Mean hours of monitor use per week. RESULTS: In cohort 1, the variables available before monitoring were only weakly associated with total hours of monitor use in weeks 2 to 5 (total model r(2) = 0.08). However, when hours of monitor use in week 1 were included as a variable to predict monitor use in weeks 2 to 5, the r(2) increased to 0.64 for hours of monitor use per week. CONCLUSIONS: Our data show that monitor use in the first week was the most important variable for predicting subsequent monitor use. The study suggests that a major focus of home monitoring should be adherence in the first week, although it remains to be tested whether this adherence can be altered.

Idiopathic congenital central hypoventilation syndrome: evaluation of brain-derived neurotrophic factor genomic DNA sequence variation.

Idiopathic congenital central hypoventilation syndrome (CCHS) is an unique disorder of respiratory control, occurring in association with Hirschsprung disease (HSCR), tumors of neural crest origin, and symptoms of autonomic nervous system dysfunction (ANSD). CCHS is thought to be genetic in origin based upon 1) affected sib pairs, 2) genetic analysis, and 3) identification of genetic mutations in both HSCR and CCHS patients. Because these mutations have been found in but a few cases of CCHS, exploration of other candidate genes has continued. Brain-derived neurotrophic factor (BDNF) represents a potential candidate gene to consider because of altered respiratory control in the BDNF knock-out mouse model and localization to the enteric nervous system in human tissue. The objective of this study was to determine the frequency of BDNF mutations among 19 children with CCHS (five with HSCR) compared to 40 unaffected unrelated controls. Using the known genomic DNA sequence for BDNF, polymerase chain reaction (PCR)-amplified genomic DNA was analyzed by standard sequencing methods. A discrete mutation was identified in one of 19 children with isolated CCHS and the unaffected father. Specifically, an isoleucine was substituted for a threonine or serine in the amino acid sequence. Absence of this mutation in 40 controls confirmed that this mutation was likely not a common polymorphism. These data further support a genetic basis for CCHS, though mutations of BDNF are not consistent in this disorder.

Idiopathic congenital central hypoventilation syndrome: the next generation.

Idiopathic congenital central hypoventilation syndrome (CCHS) is a rare disorder in which affected children have a decreased sensitivity of their respiratory centers to hypercarbia and hypoxia, as well as evidence for generalized autonomic nervous system dysfunction. A genetic origin has long been hypothesized for CCHS. Previous reports of the syndrome among twins, siblings, and half siblings, as well as an established association with Hirschsprung disease and neural crest tumors support this genetic hypothesis. Here, we present the first reported offspring born to four women diagnosed with idiopathic CCHS. Their children display a spectrum of abnormalities with one child being diagnosed with CCHS, one child with recurrent apparent life threatening events, one infant born prematurely with severe chronic lung disease and diminished ventilatory responses to carbon dioxide, and one infant who is apparently healthy with no clinical manifestations suggestive of disordered respiratory control to date. Two and potentially three of these patients illustrate transmission of altered respiratory control by CCHS patients into the next generation, furthering the evidence that CCHS is part of a broadly based inherited syndrome of autonomic nervous system dysfunction.

Developmental patterns of physiological response to a multisensory intervention in extremely premature and high-risk infants.

OBJECTIVE: To compare the developmental patterns of heart rate (HR), respiratory rate (RR), and hemoglobin oxygen saturation (SaO2) of premature infants with and without central nervous system (CNS) injury, and evaluate whether a multisensory intervention altered this development. SAMPLE: Thirty-seven premature infants born at 23-26 weeks with normal head ultrasounds or at 24-32 weeks and diagnosed with periventricular leukomalacia (PVL) and/or intraventricular hemorrhage (IVH) were studied at 33-35 weeks postconceptional age. DESIGN: Infants were randomly assigned to control and experimental groups. The experimental group infants received auditory, tactile, visual, and vestibular (ATVV) multisensory intervention twice daily from 33 weeks postconceptional age (PCA) until hospital discharge. MAIN OUTCOME MEASURES: HR, RR, and SaO2 were continuously monitored during baseline, intervention, and the 30-minute postintervention period. RESULTS: Between 33 and 35 weeks PCA, control group infants with and without CNS injury and experimental group infants without CNS injury had a significant decrease in resting mean HR, whereas RR and SaO2 remained stable. The infants with PVL who received the intervention showed increases in HR even at rest. CONCLUSIONS: The absence of a weekly decline in HR for experimental group infants with PVL suggests that PVL may affect maturation of the autonomic nervous system and increase risk of decelerative HR changes and associated clinical compromise. Infants diagnosed with PVL should be closely monitored during procedures or interventions that may be stressful or involve handling. Further research is needed to tailor multisensory interventions for infants with PVL.

Re-evaluating preterm infants with the Bayley-III: patterns and predictors of change.

This study investigates the Third Edition of the Bayley Scales of Infant and Toddler Development (Bayley-III) and (1) mean difference scores, (2) test-retest correlation coefficients, (3) changes in rates of delay and classification from "delayed" to "not delayed," and (4) infant birth, neonatal and sociodemographic predictors of change in scores from the first to second year of life among 131 preterm infants. Cognitive, Receptive Language and Fine Motor Subscale scores decrease and mean Gross Motor Subscale scores remain consistent from the first to second year of life. Bayley-III test-retest reliability ranged from small/fair to moderate from 8 to 20 months corrected age. Classification of delay is not stable over the first two years of life. One in 6 infants' Language Index scores changed from a classification of not delayed at 8 months to delayed at 20 months. One in 10 infants' Gross Motor Subscale scores changed from a classification of delayed at 8 months to not delayed at 20 months. Small for gestational age status predicts improved to nearly consistent Bayley Language Index and Receptive Subscale scores. Public insurance and history of sepsis predict decline in Bayley Language Index and Receptive Subscale scores from 8 to 20 months. Lower gestational age, race, and history of necrotizing enterocolitis and/or intestinal perforation also predict decline in Bayley Cognitive Index from 8 to 20 months. Predictors of decline in performance confirm known neonatal risk factors, are consistent with emerging evidence of detrimental immune related processes, and highlight the importance of inclusion of sociodemographic variables in understanding development in preterm infants.

Evaluating preterm infants with the Bayley-III: patterns and correlates of development.

This study investigates the Third Edition of the Bayley Scales of Infant and Toddler Development (Bayley-III) and: (1) early patterns of neurodevelopmental performance among preterm infants 8-12 months of age; and (2) correlations between known risk factors and neurodevelopmental outcome of preterm infants in this cohort. Mean Language Index (LI; 91±15) and Motor Index (MI; 94±17) were significantly lower than the Cognitive Index (CI; 102±15, p<.01). For the majority (53%) of infants, language development was their weakest domain; for another 39%, motor skills were the weakest area of development. Almost one-quarter (22%) of this cohort had mildly delayed language and motor skills, while 7% had significantly delayed language and motor skills. Regression models revealed severely abnormal head ultrasound significantly predicted MI, LI, and CI. Oxygen dependence at discharge predicted CI, LI, and race/ethnicity predicted LI, MI. Results support the addition of the Language Index to the newly revised Bayley-III Scales. Prediction models of developmental performance confirm known neonatal risk factors and reveal sociodemographic risk factors that call for additional research.

Indications for home apnea monitoring (or not).

Although there is a large body of literature describing infants who experience apnea of prematurity and apparent life-threatening events, there is no consensus regarding the use of home monitoring. This article focuses on issues that affect decision making regarding the use of home monitors in these two groups of infants and reviews existing data to guide a decision to discontinue monitoring at hospital discharge or to prescribe monitoring in the home.

Autonomic nervous system dysregulation: breathing and heart rate perturbation during wakefulness in young girls with Rett syndrome.

This study characterizes cardiorespiratory dysregulation in young girls with MECP2 mutation-confirmed Rett syndrome (RS). Respiratory inductance plethysmography of chest/abdomen and ECG was obtained during daytime wakefulness in 47 girls with MECP2 mutation-confirmed RS and 47 age-, gender-, and ethnicity-matched controls (ages 2-7 y). An in-home breath-to-breath and beat-to-beat characterization was conducted and revealed that breathing was more irregular, with an increased breathing frequency, mean airflow, and heart rate in RS versus controls. There was a decreased correlation between normal breathing and heart rate variability, and an exaggerated increase in heart rate response to breathholds in RS versus controls. We conclude that girls with RS have cardiorespiratory dysregulation during breathholds as well as during "normal" breaths and during breaths before and subsequent to breathholds. This dysregulation may offer insight into the mechanisms that render girls with RS more vulnerable to sudden death.

Characterization of dermatoglyphics in PHOX2B-confirmed congenital central hypoventilation syndrome.

OBJECTIVE: Individuals with congenital central hypoventilation syndrome have characteristic variants in the PHOX2B gene (primarily polyalanine expansion mutations). The PHOX2B gene acts as a transcriptional activator in the promotion of pan-neuronal differentiation in the autonomic nervous system during early embryologic development, with a primary role in the sympathetic noradrenergic phenotype in vertebrates. Because sympathetic innervation has been hypothesized to affect the development of dermatoglyphic pattern types, we hypothesized that individuals with PHOX2B-confirmed congenital central hypoventilation syndrome would have characteristic dermatoglyphic patterning and that the dermatoglyphic phenotype would be related to the disease-defining PHOX2B genotype. METHODS: Dermatoglyphic pattern type frequency, left/right symmetry, and genotype/phenotype correlation were assessed for 33 individuals with PHOX2B-confirmed congenital central hypoventilation syndrome and compared with published control data. RESULTS: Dermatoglyphic pattern type frequencies were altered in congenital central hypoventilation syndrome cases versus controls. In particular, there was an increase of arches in females and ulnar loops in males, with the largest differences for the left hand and for individuals with both congenital central hypoventilation syndrome and Hirschsprung disease. Dissimilarity scores between the congenital central hypoventilation syndrome and congenital central hypoventilation syndrome + Hirschsprung disease cases were not significantly different, nor were dissimilarity scores between all of the female and all of the male cases. No significant association was found between the number of polyalanine repeats in the PHOX2B genotypic category and dermatoglyphic pattern frequencies in the congenital central hypoventilation syndrome study groups. CONCLUSIONS: These results represent the first report describing specific dermatoglyphic patterning in congenital central hypoventilation syndrome and suggest a relationship between PHOX2B and the expression of dermatoglyphic pattern types. An expanded congenital central hypoventilation syndrome data set to include the full spectrum of PHOX2B mutations is necessary to further delineate the role of PHOX2B in dermatoglyphic patterning.

Facial phenotype in children and young adults with PHOX2B-determined congenital central hypoventilation syndrome: quantitative pattern of dysmorphology.

Congenital central hypoventilation syndrome (CCHS) is caused by mutations in PHOX2B, which is essential for maturation of the neural crest into the autonomic nervous system and is expressed in the dorsal rhombencephalon, a region that gives rise to facial structures. Digital photographs of 45 individuals with PHOX2B-confirmed CCHS, and 45 matched controls were analyzed for 17 linear and 6 angular measurements, and 9 derived indices. Paired t tests were used to compare group means, correlation was calculated between PHOX2B polyalanine expansion number and facial measures, and stepwise logistic regression was used to predict case-control and genotype status. CCHS cases differed significantly from controls on 13 variables (6 after p value correction: nasolabial angle, upper lip height, lateral lip height, facial index, upper facial index, and presence of inferior inflection of the lateral segment of the upper lip vermillion border). Five variables were able to predict correctly 85.7% of CCHS cases and 82.2% of controls: upper lip height, biocular width, upper facial height, nasal tip protrusion, and inferior inflection of the upper lip vermillion border. A negative relationship between number of repeats and four anthropometric measures was observed: mandible breadth, nasolabial angle, lateral lip height, and mandible-face width index. These results suggest a characteristic facial phenotype in children and young adults with CCHS, due to an expansion mutation in PHOX2B.

Home monitoring during infancy: what is normal?

This article reviews studies on infants to obtain 'normal' parameters for apnoea, heart rate and O(2) saturation in healthy full-term infants. Studies have been carried out in both hospital and home settings using different protocols and these are reviewed and assessed as a means of providing baseline data for home memory monitoring of infants.