Longitudinal Analysis of Ventilation Perfusion Mismatch in Congenital Diaphragmatic Hernia Survivors.

OBJECTIVE: To determine the natural history of pulmonary function for survivors of congenital diaphragmatic hernia (CDH). STUDY DESIGN: This was a retrospective cohort study of survivors of CDH born during 1991-2016 and followed at our institution. A generalized linear model was fitted to assess the longitudinal trends of ventilation (V), perfusion (Q), and V/Q mismatch. The association between V/Q ratio and body mass index percentile as well as functional status was also assessed with a generalized linear model. RESULTS: During the study period, 212 patients had at least one V/Q study. The average ipsilateral V/Q of the cohort increased over time (P < .01), an effect driven by progressive reduction in relative perfusion (P = .012). A higher V/Q ratio was correlated with lower body mass index percentile (P < .001) and higher probability of poor functional status (New York Heart Association class III or IV) (P = .045). CONCLUSIONS: In this cohort of survivors of CDH with more severe disease characteristics, V/Q mismatch worsens over time, primarily because of progressive perfusion deficit of the ipsilateral side. V/Q scans may be useful in identifying patients with CDH who are at risk for poor growth and functional status.

Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders.

Research has implicated mutations in the gene for neurexin-1 (NRXN1) in a variety of conditions including autism, schizophrenia, and nicotine dependence. To our knowledge, there have been no published reports describing the breadth of the phenotype associated with mutations in NRXN1. We present a medical record review of subjects with deletions involving exonic sequences of NRXN1. We ascertained cases from 3,540 individuals referred clinically for comparative genomic hybridization testing from March 2007 to January 2009. Twelve subjects were identified with exonic deletions. The phenotype of individuals with NRXN1 deletion is variable and includes autism spectrum disorders, mental retardation, language delays, and hypotonia. There was a statistically significant increase in NRXN1 deletion in our clinical sample compared to control populations described in the literature (P = 8.9 x 10(-7)). Three additional subjects with NRXN1 deletions and autism were identified through the Homozygosity Mapping Collaborative for Autism, and this deletion segregated with the phenotype. Our study indicates that deletions of NRXN1 predispose to a wide spectrum of developmental disorders.

Quantitative Evaluation of Content and Age Concordance Across Developmental Milestone Checklists.

OBJECTIVE: Clinicians and caregivers rely on milestone checklists as tools for tracking a child's development. In addition, medical students and residents use milestone checklists to learn about normal child development. However, there are multiple published milestone checklists that vary qualitatively in structure and content, hindering their effective use in developmental surveillance and medical education. This project systematically evaluated the consistency and variability between commonly used milestone checklists. METHODS: A team of child psychologists and developmental pediatricians reviewed a total of 1094 milestones derived from 4 published checklists (2 developed for providers, 2 developed for caregivers) to create a comprehensive set of 728 discrete developmental observations, with each observation mapped to corresponding milestones. This observation-milestone relational database was then used to determine the degree of content overlap and milestone age range concordance across milestone checklists. RESULTS: Of the 728 discrete developmental observations, 40 (5.5%) were mapped to milestones in all 4 milestone checklists, and an additional 90 (12.4%) were mapped to 3 checklists. Among these 40 "universal" observations, most (42.5%) were in the motor domain. Of those 130 observations mapped to milestones in at least 3 of the 4 checklists, 26.9% (35/130) were mapped to milestones that were discordant in their associated age range. CONCLUSION: Four commonly used developmental milestone checklists were found to have limited overlap in content, and those that overlapped were inconsistent in their associated age ranges. The resulting observation-milestone relational database could be used to further validate age estimates of milestones and facilitate milestone surveillance through the electronic health record.

Insomnia of childhood.

PURPOSE OF REVIEW: Insomnia is a major public health problem and is the most common sleep disturbance in both adults and children. The causes of sleeplessness are age-dependent and have potentially enormous effects on cognitive development, behavior, family dynamics, and the metabolic health of children. Here we review the epidemiology, cause, pathophysiology, and clinical approach to pediatric insomnia. RECENT FINDINGS: Normal sleep is crucial for brain function, behavior, and normal metabolism. Consistently, sleep loss has been linked to behavioral and attention problems, impaired learning and memory, obesity, and psychiatric disorders. The neurological mechanisms that govern sleep initiation and maintenance are poorly understood. The types of insomnia are age-dependent and can occur as primary disorders, or in the context of another primary sleep disorder such as restless legs syndrome, or secondary to another underlying medical condition. Children with chronic diseases and especially children with neurodevelopmental disorders are at particular risk of insomnia. SUMMARY: Pediatric insomnia is common and is a source of potential psychophysiological stress to both children and their caregivers. The causes of insomnia are various. Pediatricians should have a working knowledge of the causes of sleeplessness in order to promptly curtail the chronic effects of sleep loss and effectively screen for underlying, potentially treatable disorders.

Does the ex utero intrapartum treatment to extracorporeal membrane oxygenation procedure change morbidity outcomes for high-risk congenital diaphragmatic hernia survivors?

PURPOSE: In high-risk congenital diaphragmatic hernia (CDH), significant barotrauma or death can occur before extracorporeal membrane oxygenation (ECMO) can be initiated. We previously examined ex utero intrapartum treatment (EXIT)-to-ECMO in our most severe CDH patients, but demonstrated no survival advantage. We now report morbidity outcomes in survivors of this high-risk cohort to determine whether EXIT-to-ECMO conferred any benefit. METHODS: All CDH survivors with <15% predicted lung volume (PPLV) from September 1999 to December 2010 were included. We recorded prenatal imaging, defect size, and pulmonary, nutritional, cardiac, and neurodevelopmental outcomes. RESULTS: Seventeen survivors (8 EXIT-to-ECMO, 9 non-EXIT) had an average PPLV of 11.7%. Eight of 9 non-EXIT received ECMO within 2days. There were no significant defect size differences between groups, mostly left-sided (13/17) and type D (12/17). Average follow-up was 6.7years (0-13years). There were no statistically significant differences in outcomes, including supplemental oxygen, diuretics, gastrostomy, weight-for-age Z scores, fundoplication, pulmonary hypertension, stroke or intracranial hemorrhage rate, CDH recurrence, and reoperation. No survivor in our cohort was neurologically devastated. All had mild motor and/or speech delay, which improved in most. CONCLUSIONS: In this pilot series of severe CDH survivors, EXIT-to-ECMO confers neither significant survival nor long-term morbidity benefit. LEVEL OF EVIDENCE: Level III treatment study.

Managing behavior for a child with autism in a body cast.

CASE: : Elisa is a 6 ½-year-old white female who has a follow-up appointment in the Developmental Clinic where she is seen for autism, developmental delay, and significant behavioral problems. Her grandparents, who are her legal guardians, request an opinion on a proposed surgery for developmental dysplasia of the hip that will require several months in a whole body cast. Reconstruction of the hip was recommended by 2 pediatric orthopedic surgeons to prevent later disability and pain.Elisa was born following a 41-week gestation. She sat without support at 7 months, but she did not walk until 23 months of age. An evaluation at the Developmental Clinic at 28 months of age documented gross and fine motor delays, cognitive impairment, and autism. A karyotype, fragile X, and microarray were normal. Elisa has a brother with autism and a maternal cousin with mental retardation. After her mother's death from meningitis 2 years ago, her maternal grandparents became her legal guardian.Behavior problems include significant hyperactivity, impulsivity, and aggressive behaviors. She seldom sits still. She also has frequent stereotypies, such as jumping and arm flapping when she is excited or upset. Methylphenidate was associated with increased hyperactivity and irritability.Physical examination demonstrates that she can walk with a very wide gait and swings her right foot out. A magnetic resonance imaging of her brain, acoustic brain response audiometry, and metabolic studies are normal. Other medical issues include gastroesophageal reflux, recurrent pneumonia, and ear infections. Radiographs of the hip reveal a steep acetabulum and a hip that easily dislocates. A magnetic resonance imaging of the hip shows early formation of a pseudoarthrosis. Her grandparents and pediatrician are concerned about managing her behavior after the surgery when she will be in a body cast.