Perinatal factors associated with poor neurocognitive outcome in early school age congenital diaphragmatic hernia survivors.

OBJECTIVE: Determine predictors of neurocognitive outcome in early school age congenital diaphragmatic hernia (CDH) survivors. STUDY DESIGN: Prospective study of infants with CDH at Duke University Medical Center. Neurocognitive delay (NCD) at school age (4 to 7years) was defined as a score<80 in any of the following areas: Verbal Scale IQ, Performance Scale IQ, Expressive Language, or Receptive Language. Logistic regression, Fisher's exact, and the Wilcoxon rank sum test were used to examine the relationship between NCD at early school age and 6 demographic and 18 medical variables. RESULTS: Of 43 infants with CDH, twenty seven (63%) survived to hospital discharge, and 16 (59%) returned for school age testing at a median age of 4.9years. Seven (44%) of the children evaluated had NCD. Patch repair (p=0.01), extracorporeal membrane oxygenation (ECMO; p=0.02), days on ECMO (p=0.01), days of mechanical ventilation (p=0.049), and post-operative use of inhaled nitric oxide (p=0.02) were found to be associated with NCD at early school age. CONCLUSIONS: CDH survivors are at risk for neurocognitive delay persisting into school age. Perinatal factors such as patch repair and ECMO treatment may aid in identifying CDH survivors at high risk for continued learning difficulties throughout childhood.

A left cerebellar pathway mediates language in prematurely-born young adults.

Preterm (PT) subjects are at risk for developmental delay, and task-based studies suggest that developmental disorders may be due to alterations in neural connectivity. Since emerging data imply the importance of right cerebellar function for language acquisition in typical development, we hypothesized that PT subjects would have alternate areas of cerebellar connectivity, and that these areas would be responsible for differences in cognitive outcomes between PT subjects and term controls at age 20 years. Nineteen PT and 19 term control young adults were prospectively studied using resting-state functional MRI (fMRI) to create voxel-based contrast maps reflecting the functional connectivity of each tissue element in the grey matter through analysis of the intrinsic connectivity contrast degree (ICC-d). Left cerebellar ICC-d differences between subjects identified a region of interest that was used for subsequent seed-based connectivity analyses. Subjects underwent standardized language testing, and correlations with cognitive outcomes were assessed. There were no differences in gender, hand preference, maternal education, age at study, or Peabody Picture Vocabulary Test (PPVT) scores. Functional connectivity (FcMRI) demonstrated increased tissue connectivity in the biventer, simple and quadrangular lobules of the L cerebellum (p<0.05) in PTs compared to term controls; seed-based analyses from these regions demonstrated alterations in connectivity from L cerebellum to both R and L inferior frontal gyri (IFG) in PTs compared to term controls. For PTs but not term controls, there were significant positive correlations between these connections and PPVT scores (R IFG: r=0.555, p=0.01; L IFG: r=0.454, p=0.05), as well as Verbal Comprehension Index (VCI) scores (R IFG: r=0.472, p=0.04). These data suggest the presence of a left cerebellar language circuit in PT subjects at young adulthood. These findings may represent either a delay in maturation or the engagement of alternative neural pathways for language in the developing PT brain.

Preliminary observations of the use of high-frequency jet ventilation as rescue therapy in infants with congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Congenital diaphragmatic hernia (CDH) is associated with mortality of 10% to 50%. Several investigators have reported outcomes from centers using high-frequency oscillatory ventilation in their management of CDH, but there are no recent reports on use of high-frequency jet ventilation. METHODS: During the study period from January 2001 until August 2007, infants with CDH who were cared for at Duke University Medical Center received high-frequency jet ventilation as a rescue mode of high-frequency ventilation. We compared actual survival with predicted survival for infants treated only with conventional ventilation vs those rescued with high-frequency jet ventilation after failing conventional ventilation. RESULTS: Survival for the 16 infants that received high-frequency jet ventilation was predicted to be 63%; actual survival was 75%. Survival for the 15 infants that received only conventional ventilation was predicted to be 83%; actual survival was 87%. We observed no significant survival benefit for high-frequency jet ventilation, 8.0% (95 confidence interval, -22.0% to 38.1%; P = .59). CONCLUSIONS: Although our sample size was small, we conclude with consideration of the absolute results, the degree of illness of the infants, and the biologic plausibility for the intervention that high-frequency jet ventilation is an acceptable rescue ventilation mode for infants with CDH.