Casey Hoffman

Neurodevelopmental outcome of infants with congenital diaphragmatic hernia prospectively enrolled in an interdisciplinary follow-up program.

PURPOSE The purpose of the study was to evaluate the neurodevelopmental outcome in infants with congenital diaphragmatic hernia (CDH). METHODS Between June 2004 and September 2007, 41 CDH survivors were prospectively enrolled in an interdisciplinary follow-up program. Neurodevelopmental status was evaluated using the Bayley Scales of Infant Development II (prior 2006, n = 9), the Bayley Scales of Infant Development III (after 2006, n = 27), or the Wechsler Preschool and Primary Scale of Intelligence III (children older than 4 years, n = 5). Scores were grouped as average, mildly delayed, and severely delayed by standard deviation intervals (115-85, 71-84, <70), and mixed if average and mildly delayed in either cognitive or language. RESULTS Median age at last assessment was 24 months (range, 6-62). Average, mixed, mildly delayed, and severely delayed scores for neurocognitive and language skills were found in 49%, 19%, 17%, and 15%, respectively. Psychomotor scores were normal, mildly delayed, and severely delayed in 46%, 23%, and 31%, respectively. Autism was present in 7%. Abnormal muscle tonicity was found in 51% (49% hypotonic, 2% hypertonic). Multivariate risk factors for borderline or delayed neurodevelopmental, neurocognitive, and/or psychomotor outcome were intrathoracic liver position (P = .02), presence of a right-sided CDH (P = .02), extracorporeal membrane oxygenation need (P < .001), Gore-Tex patch repair (P = .02), O(2) requirement at 30 days of life (P < .01), and hypotonicity (P < .01). CONCLUSIONS The prospective evaluation in an interdisciplinary follow-up program uncovered striking morbidities in neurodevelopmental status in approximately half of the CDH infants. The most common neurologic sequelae are neuromuscular hypotonicity and psychomotor dysfunction. Patient-specific factors are important determinants of adverse neurologic outcome.

Longitudinal neurodevelopmental and neuromotor outcome in congenital diaphragmatic hernia patients in the first 3 years of life

Objective:The objective of this study was to longitudinally evaluate the neurodevelopmental (ND) outcome in congenital diaphragmatic hernia (CDH) survivors during the first 3 years of life.Study Design:The study cohort consists of 47 CDH survivors that were enrolled in our prospective, follow-up program between July 2004 and September 2010, and underwent serial ND evaluations during the first 3 years of life. ND outcomes were evaluated using the Bayley Scales of Infant Development (BSID)-II or BSID-III. Persistent ND impairment was defined as a score that remained ⩽79 for the cognitive, language and psychomotor domains at the most recent follow-up visit compared with the first assessment.Result:The median age at first and last evaluation was 8 (range, 5 to 15) and 29 (range, 23 to 36) months, respectively. During the follow-up, ND scores improved to average in 17%, remained average in 60%, remained delayed in 10%, improved from severely delayed to mildly delayed in 2% and deteriorated from average to delayed in 15%. Motor scores improved to average in 26%, remained average in 55%, remained delayed in 8% and improved from severely delayed to mildly delayed in 11%. Intrathoracic liver position (P=0.004), preterm delivery (P=0.03), supplemental O2 requirement at day of life 30 (P=0.007), age at discharge (P=0.03), periventricular leukomalacia (PVL; P=0.004) and initial neuromuscular hypotonicity (P=0.01) were associated with persistent motor delays. No relationship was found between patient’s characteristics and the risk of persistent cognitive and language delays.Conclusion:(1) The majority of children with CDH are functioning in the average range by early preschool age, (2) most children who had early delays showed improvement in their ND outcome, (3) children showing delays in all the three domains were the least likely to show improvement and (4) CDH severity appears to be predictive of persistent psychomotor delays.

Prospective, interdisciplinary follow-up of children with prenatally diagnosed giant omphalocele: short-term neurodevelopmental outcome.

PURPOSE The objective of this study is to determine the short-term neurodevelopmental outcome in infants with giant omphalocele (GO). MATERIALS AND METHODS Between January 2002 and December 2007, 31 consecutive infants with GO received prenatal and postnatal care at our institution. Overall survival was 81% (25/31). Twenty (80%) of the survivors were enrolled in a prospective interdisciplinary follow-up program. Fifteen were at least 6 months of age and received detailed neurodevelopmental evaluation using the Bayley Scales of Infant Development II (BSID-II [before 2006, n = 3]) or BSID-III (after 2006, n = 12). Scores were grouped as average, mildly delayed, and severely delayed by SD intervals (115-85, 71-84, <70). Scores were considered mixed if cognitive or language skills were in different ranges. RESULTS Median age at evaluation was 12 months (range, 6-26 months). Average, mildly delayed, and severely delayed scores for cognitive and language skills were found in 6 (40%), 2 (13%), and 6 (40%), respectively. One child had mixed scores (severely delayed for cognitive and mildly delayed for language skills). Motor scores were normal, mildly delayed, and severely delayed in 6 (40%), 2 (13%), and 7 (47%), respectively. The neuromuscular examination was abnormal in 8 patients (62%). Five (33%) scored within the average range, whereas 6 (40%) demonstrated severe delays for cognitive, language, and motor outcome. Of the 6 children with severe delays, 2 (13% of total) have autism, 4 required tracheostomy, and 1 was diagnosed with Williams syndrome. CONCLUSIONS The presence of GO is associated with deficits in developmental achievements in most of the affected infants ranging from mild to profound delays. These findings underscore the importance of early and standardized neurodevelopmental evaluation throughout childhood for all survivors with GO. Larger studies are warranted for risk factor stratification.

Neurodevelopmental outcome at one year of age in congenital diaphragmatic hernia infants not treated with extracorporeal membrane oxygenation

BACKGROUND We evaluated the neurodevelopmental (ND) outcome at one year of age for congenital diaphragmatic hernia (CDH) children who have not undergone extracorporeal membrane oxygenation (ECMO) treatment during the neonatal period. MATERIAL AND METHODS Between 01/2005 and 06/2012, 63 consecutive CDH patients underwent ND assessment using the BSID-III at a median age of 12 months. ND delay was defined by a score of ≤ 85 in any of the composite scales. Severe impairment was defined as a score of ≤ 69 in at least one domain. RESULTS Mean ± SD cognitive, language, and motor functions were 94 ± 14, 86 ± 14, 90 ± 15, respectively (normal 100 ± 15, P<0.01 for each). Forty-three-percent scored within the average range for all scales. Forty-four-percent had mild, and 13% had severe delays in at least one domain. Prolonged NICU stay, intubation and O2 requirement, fundoplication, abnormal BAERs, and tracheostomy were associated with lower scores in all domains. Right-sided CDH, male gender, lower 5 min APGAR, pulmonary hypertension, and delayed start of enteral feeding were predictive of lower cognitive and/or language scores. CONCLUSION At one year of age, a high percentage of CDH children whose illness did not necessitate ECMO have below normal ND scores. Modifiable and non-modifiable factors are significant determinants of adverse outcomes.

Incidence and factors associated with sensorineural and conductive hearing loss among survivors of congenital diaphragmatic hernia

PURPOSE The reported incidence of sensorineural hearing loss (SNHL) in long-term survivors of congenital diaphragmatic hernia varies widely in the literature. Conductive hearing loss (CHL) is also known to occur in CDH patients, but has been less widely studied. We sought to characterize the incidence and risk factors associated with SNHL and CHL in a large cohort of CDH patients who underwent standardized treatment and follow-up at a single institution. METHODS We retrospectively reviewed charts of all CDH patients in our pulmonary hypoplasia program from January 2004 through December 2012. Categorical variables were analyzed by Fishers exact test and continuous variables by Mann-Whitney t-test (p≤0.05). RESULTS A total of 112 patients met study inclusion criteria, with 3 (2.7%) patients diagnosed with SNHL and 38 (34.0%) diagnosed with CHL. SNHL was significantly associated with requirement for ECMO (p=0.0130), prolonged course of hospitalization (p=0.0011), duration of mechanical ventilation (p=0.0046), requirement for tracheostomy (p=0.0013), and duration of loop diuretic (p=0.0005) and aminoglycoside therapy (p=0.0003). CONCLUSIONS We have identified hearing anomalies in over 30% of long-term CDH survivors. These findings illustrate the need for routine serial audiologic evaluations throughout childhood for all survivors of CDH and stress the importance of targeted interventions to optimize long-term developmental outcomes pertaining to speech and language.

Neurodevelopmental outcomes at 5 years of age in congenital diaphragmatic hernia

OBJECTIVE To evaluate neurodevelopmental sequelae in congenital diaphragmatic hernia (CDH) children at 5years of age. MATERIALS AND METHODS The study cohort of 35 CDH patients was enrolled in our follow-up program between 06/2004 and 09/2014. The neurodevelopmental outcomes assessed at a median of 5years (range, 4-6) included cognition (Wechsler Preschool and Primary Scale of Intelligence [WPPSI], n=35), Visual-Motor-Integration (n=35), academic achievement (Woodcock-Johnson Tests of Achievement, n=25), and behavior problems (Child Behavior Check List [CBCL], n=26). Scores were grouped as average, borderline, or extremely low by SD intervals. RESULTS Although mean Full (93.9±19.4), Verbal (93.4±18.4), and Performance (95.2±20.9) IQ were within the expected range, significantly more CDH children had borderline (17%) and extremely low (17%) scores in at least one domain compared to normative cohorts (P<0.02). The Visual-Motor-Integration score was below population average (P<0.001). Academic achievement scores were similar to expected means for those children who were able to complete testing. CBCL scores for the emotionally reactive (23%) and pervasive developmental problems scales (27%) were more likely to be abnormal compared to normal population scores (P=0.02 and P=0.0003, respectively). Autism was diagnosed in 11%, which is significantly higher than the general population (P<0.01). Univariate analysis suggests that prolonged NICU stay, prolonged intubation, tracheostomy placement, pulmonary hypertension, autism, hearing impairment, and developmental delays identified during infancy are associated with worse cognitive outcomes (P<0.05). CONCLUSION The majority of CDH children have neurodevelopmental outcomes within the average range at 5years of age. However, rates of borderline and extremely low IQ scores are significantly higher than in the general population. CDH survivors are also at increased risk for developing symptoms of emotionally reactive and pervasive developmental problems. Risk of autism is significantly elevated. Disease severity and early neurological dysfunction appear to be predictive of longer-term impairments.

Patient characteristics are important determinants of neurodevelopmental outcome during infancy in giant omphalocele.

OBJECTIVE To examine patient-specific factors as potential predictors of neurodevelopmental (ND) outcome in children with giant omphalocele (GO). MATERIALS Between 06/2005 and 07/2012, 31 consecutive GO survivors underwent ND assessment using the BSID-III at a median of 24months (range 6-35). ND delay was defined by a score of ≤84 in any composite score. Severe impairments were defined as a score of ≤69 in at least one domain. Correlations between ND outcome and patient-specific factors were analyzed by one-way ANOVA, chi-square, or logistic regression as appropriate. RESULTS The mean cognitive score (86.8±16.8) was in the low average range. Mean language (83.2±21.1) and motor (81.5±16.2) scores were below average. Forty-six-percent scored within the average range for all scales. Mild deficits were found in 19%, and 35% had severe delays in at least one domain. Hypotonicity was present in 55%. Autism was suspected/confirmed in 13%. Predictors of lower ND scores were prolonged ventilator support (P<0.01), high-frequency oscillatory ventilation (P<0.01), tracheostomy placement (P<0.001), O2 supplementation at day of life 30 (P<0.02), pulmonary hypertension (P<0.02), delayed enteral feeding (P=0.01), need for feeding tube (P<0.001), GERD (P=0.05), abnormal BAER hearing screen (P<0.006), prolonged hospitalization (P=0.01), and failure to thrive (P=0.001). Autism was associated with delays in cognitive and language outcomes (P<0.03). Delayed staged closure (P=0.007), older age at final repair (P=0.03), and hypotonicity (P=0.02) were associated with motor dysfunction. CONCLUSIONS Neurological impairments were present in more than half of GO survivors. Disease severity was associated with ND dysfunction. Autism and hypotonicity were often co-morbidities with ND delays and poor motor function.

Early neurodevelopmental outcome of infants with high-risk fetal lung lesions.

Objective: To evaluate the neurodevelopmental outcome of infants with high-risk fetal lung lesions defined as (1) requiring fetal intervention and/or ex utero intrapartum therapy (EXIT), or (2) acute respiratory decompensation postnatally necessitating emergent resection within 48 h of life. Methods: We reviewed the medical records of 13 consecutive patients with high-risk fetal lung lesions who were enrolled in our prospective interdisciplinary follow-up program. Neurodevelopmental status was evaluated using the Bayley Scales of Infant Development-III (children ≤3 years, n = 12), or the Wechsler Preschool and Primary Scale of Intelligence-III (children ≥4 years, n = 1). Results: Eight children (62%) underwent prenatal intervention (EXIT, n = 6; fetal resection, n = 1; intrauterine shunt placement, n = 1), and 5 (38%) required emergent resection postnatally. Median age at evaluation was 25 months (range: 5–80). Average scores for cognitive development were found in all children assessed under 3 years of age. The one child who was tested for cognitive ability at 6 years of age scored in the borderline range of intellectual functioning. For language outcome, 15% scored above average, 54% scored within the average range, and 31% had mild deficits. Overall, 77% scored within the average range for neuromotor outcome, while 23% scored within the mildly delayed range. None of the children had severe delays. Cognitive, language, and psychomotor scores were similar between both groups. Hypotonicity was found in 23%. Autism was suspected in one child who underwent an EXIT procedure and was postnatally diagnosed with mosaic trisomy 18. Conclusion: The majority of children with high-risk fetal lung lesions have age-appropriate neurodevelopmental scores.

Rate and Risk Factors Associated with Autism Spectrum Disorder in Congenital Diaphragmatic Hernia

To determine the rate and predictors of autism spectrum disorder (ASD) in congenital diaphragmatic hernia (CDH). Between 06/2004 and 09/2015 a total of 110 CDH survivors underwent neurodevelopmental (ND) testing and screening for ASD, followed by a full autism diagnostic evaluation if indicated at our institution. We found a 9 time higher rate of ASD in CDH children compared to the general population (P = 0.0002). Multiple patient-related and clinical variables risk factors of ASD were identified by univariate analysis. However, only short-term and long-term neurodevelopmental delays were strongly associated with ASD in CDH by multivariate comparisons. There is a striking prevalence of ASD in CDH survivors and our findings suggest that all CDH children should be regularly screened for ASD.

Why do children with severe bronchopulmonary dysplasia not attend neonatal follow-up care? Parental views of barriers

To assess in children with severe bronchopulmonary dysplasia at a corrected age of 18–36 months: (i) Neonatal follow‐up clinic attendance rates; (ii) Parent‐identified reasons for difficulty attending neonatal follow‐up.