Penny Glass

Neurodevelopmental status at age five years of neonates treated with extracorporeal membrane oxygenation

OBJECTIVE To determine the neurodevelopmental status at age 5 years among children who received extracorporeal membrane oxygenation (ECMO) in the newborn period as a treatment for severe cardiorespiratory failure. METHODS We conducted a prospective cohort study of 103 five-year-old ECMO-treated children born between June 1984 and July 1988, and treated at our institution. Thirty-seven healthy control children were recruited locally. The assessment protocol included a complete neuropsychologic assessment, psychosocial assessment with parent questionnaires, a standard neurologic evaluation, assessment of gross motor and fine motor function, a medical history, and physical examination. RESULTS Major disability was present in 17 of the ECMO cohort. Eleven ECMO-treated children (11%) were mentally retarded, one of whom was profoundly impaired. Two additional children had severe learning disabilities. Cerebral palsy was diagnosed in 5 (5%) ECMO-treated children, but all cases were mild in nature and the patients were walking unaided. One child has paraplegia. The mean Full Scale, Verbal, and Performance IQs of the EMCO-treated children were within the normal range, but as a group were significantly lower than in control children (96 vs 115, p < 0.001). Children treated with ECMO had increased risk relative to the control children for academic difficulties at school age (49% VS 22%, P < 0.01) and a higher rate of behavioral problems reported by parents (42% vs 16%, p = 0.01). CONCLUSIONS The rate of major disability was comparable to that in other high-risk populations. The high rate of behavioral problems and increased risk of subsequent school failure among nonretarded ECMO-treated children supports the need for close follow-up of these children after hospital discharge.

Factors associated with adverse neurodevelopmental outcomes in infants with congenital heart disease

OBJECTIVE To review reported neurodevelopmental outcome data for patients with congenital heart disease, identify risk factors for adverse neurodevelopmental sequelae and summarize potential neuromonitoring strategies that have been described. METHODS A Medline search was performed utilizing combinations of the keywords congenital heart, cardiac, neurologic, neurodevelopment, neuromonitoring, quality of life, and outcome. All prospective and longitudinal follow-up studies of patients with congenital heart disease were included. Additionally, studies that examined neuroimaging, neuromonitoring, and clinical factors in relation to outcome were examined. Case reports and editorials were excluded. Additional references were retrieved from selected articles if the abstract described an evaluation of neurodevelopmental outcomes and/or predictors of outcome in patients with congenital heart disease. RESULTS Overall, patients with CHD have increased rates of neurodevelopmental impairments, although intelligence appears to be in the normal range. Preoperative risk stratification, intraoperative techniques, postoperative care, and neuromonitoring strategies may all contribute to ultimate long-term neurodevelopmental outcomes in patients with CHD postsurgical repair. CONCLUSIONS As advances in the medical and surgical management improves survival in patients with CHD, increasing knowledge about neurodevelopmental outcomes and the factors that affect them will provide for strategies to optimize long-term outcome in this high-risk population.

Cardiopulmonary outcome of neonatal extracorporeal membrane oxygenation at ages 10-15 years.

ObjectiveThe purpose of this study was to evaluate the long-term cardiopulmonary outcome at ages 10–15 yrs following neonatal extracorporeal membrane oxygenation (ECMO). The specific aims of the study were to assess baseline aerobic capacity, cardiac function, and pulmonary function in neonatal ECMO survivors using graded exercise testing, echocardiography, and pulmonary function tests. DesignCohort study. SettingExercise and pulmonary function laboratories of a large children’s hospital. PatientsSeventeen 10- to 15-yr-old children treated with ECMO as neonates for meconium aspiration syndrome and 17 age-matched healthy controls. InterventionsChildren were evaluated by use of physical exam, electrocardiogram, echocardiogram, treadmill stress test, and pulmonary function tests. Measurements and Main ResultsAverage weight, height, and age were similar between the groups. Both pre- and postexercise pulmonary function tests revealed air trapping and mild lower airway obstruction in the ECMO group, compared with mean pulmonary functions in the normal range for the control group. The mean forced expiratory volume in 1 sec, the forced expiratory flow between 25% and 75% of vital capacity, and the ratio between residual volume and total lung capacity were significantly different between the ECMO group and the control group. Although the ECMO group exhibited baseline and postexercise lung function abnormalities, there were no differences in maximal oxygen consumption between the two groups and all subjects reached anaerobic threshold.By regression analysis, the gestational age, duration of oxygen, and exercise score were significantly correlated with baseline lung function, using forced expiratory flow between 25% and 75% of vital capacity as the dependent variable. ConclusionsDespite abnormalities in baseline and postexercise pulmonary functions, ECMO graduates have similar aerobic capacity to age-matched healthy controls. The most significant factor in predicting long-term pulmonary outcome in ECMO graduates is the duration of oxygen use following decannulation.

Mortality and morbidity rates among lower birth weight infants (2000 to 2500 grams) treated with extracorporeal membrane oxygenation

To assess the validity of the currently accepted lower weight limit of 2 kg for treatment of neonates with extracorporeal membrane oxygenation (ECMO), we reviewed the outcome of lower birth weight (2.0 to 2.5 kg, n = 29) and higher birth weight (n = 235) for infants treated with venoarterial ECMO at our institution from 1984 through 1990. Newborn infants with congenital diaphragmatic hernia were not included. The mortality rate was significantly greater after venoarterial ECMO in lower than in higher birth weight infants (relative risk 3.45; confidence interval = (1.68, 5.79)). For infants with the diagnosis of respiratory distress syndrome, the mortality rate was 56% (5/9) for lower and 8% (2/25) for higher birth weight infants (p less than 0.01). The most frequent cause of death in lower birth weight infants was intracranial hemorrhage (7/10 deaths). The overall incidence of any neuroimaging abnormality was significantly greater for lower birth weight infants (p = 0.044), primarily because of the higher incidence of major intracranial hemorrhage. Finally, the risk of developmental delay (development quotient less than 70 at 1 to 2 years of age) among survivors available for follow-up was significantly higher among the lower than the higher birth weight infants. These outcome data suggest that further reduction of the current lower weight limit for ECMO should not become standard without prospective research or technologic advances.

Functional Status Scale: New Pediatric Outcome Measure

OBJECTIVE: The goal was to create a functional status outcome measure for large outcome studies that is well defined, quantitative, rapid, reliable, minimally dependent on subjective assessments, and applicable to hospitalized pediatric patients across a wide range of ages and inpatient environments. METHODS: Functional Status Scale (FSS) domains of functioning included mental status, sensory functioning, communication, motor functioning, feeding, and respiratory status, categorized from normal (score = 1) to very severe dysfunction (score = 5). The Adaptive Behavior Assessment System II (ABAS II) established construct validity and calibration within domains. Seven institutions provided PICU patients within 24 hours before or after PICU discharge, high-risk non-PICU patients within 24 hours after admission, and technology-dependent children. Primary care nurses completed the ABAS II. Statistical analyses were performed. RESULTS: A total of 836 children, with a mean FSS score of 10.3 (SD: 4.4), were studied. Eighteen percent had the minimal possible FSS score of 6, 44% had FSS scores of ≥10, 14% had FSS scores of ≥15, and 6% had FSS scores of ≥20. Each FSS domain was associated with mean ABAS II scores (P < .0001). Cells in each domain were collapsed and reweighted, which improved correlations with ABAS II scores (P < .001 for improvements). Discrimination was very good for moderate and severe dysfunction (ABAS II categories) and improved with FSS weighting. Intraclass correlations of original and weighted total FSS scores were 0.95 and 0.94, respectively. CONCLUSIONS: The FSS met our objectives and is well suited for large outcome studies.

NEUROBEHAVIORAL AND PSYCHOSOCIAL FUNCTIONING OF CHILDREN WITH OPSOCLONUS‐MYOCLONUS SYNDROME

Childhood opsoclonus‐myoclonus syndrome (OMS) is a movement disorder which typically strikes children in the early preschool years, seriously affecting intellectual, social‐emotional and general adaptive development. This series of 13 cases with well‐documented neurological histories, aged 1.7 to 16.3 years, provides an initial systematic evaluation of these childrens neuropsychological, psychosocial and adaptive status. As expected, children with OMS had significantly reduced intelligence and severe speech and motor output problems; however, most of them also demonstrated a range of preserved neurocognitive abilities and impressive goal‐directedness and communicative effort. Psychosocial problems included mild behavioral impairment on the Achenbach Child Behavior Checklist, and severe adaptive limitations on the Vineland Adaptive Behavior Scales despite relatively strong social skills. Developmental factors and likelihood of subcortical localization are discussed, and practical guidelines are provided for behavioral and educational management of these children.

aEEG evolution during therapeutic hypothermia and prediction of NICU outcome in encephalopathic neonates.

Background: Initial aEEG background pattern has been used as a predictor of neurological outcome after asphyxia and has been used as inclusion criterion for trials evaluating efficacy of therapeutic hypothermia in encephalopathic newborns. The utility of continuous aEEG monitoring during hypothermia has not been well described. Objectives: (1) To describe the evolution of aEEG during therapeutic hypothermia in newborns with encephalopathy, and (2) to evaluate the utility of continuous aEEG monitoring during therapeutic hypothermia. Methods: This is a retrospective review of continuous aEEG data from encephalopathic newborns treated with whole-body hypothermia. aEEG segments were scored for background and sleep-wake cycling (SWC). Sensitivity and specificity calculations and logistic regression analyses were performed to evaluate the ability of aEEG to predict death or severe MRI abnormality/significant neurological deficit at discharge. Results: aEEG data from 75 encephalopathic newborns were reviewed. Abnormal aEEG background was predictive of adverse outcome with increasing positive predictive value over the course of hypothermia. Few patients (5%) had early SWC, but 58% developed SWC by rewarming and all had favorable outcome. Conclusions: Persisting aEEG background abnormality beyond 48 h of life and lack of SWC over the course of hypothermia is predictive of adverse NICU outcome in encephalopathic newborns.

Quantitative analysis of magnetic resonance images and neurological outcome in encephalopathic neonates treated with whole-body hypothermia.

Objective:To evaluate whether quantitative measures from magnetic resonance imaging (MRI) performed in hypothermia-treated encephalopathic newborns can differentiate patients with unfavorable neurological outcome.Study Design:Retrospective analysis of clinical data and MRI studies was performed in 47 full-term infants treated with whole-body hypothermia for neonatal encephalopathy. Apparent diffusion coefficients (ADCs) and T1 and T2 intensity ratios were measured in the basal ganglia and thalamus on axial MRI images. Unfavorable outcome was defined as (1) death or severe neurological deficits at discharge and (2) death or cerebral palsy/severe motor deficit at follow-up through age 9 months. Differences between groups with favorable versus unfavorable neurological outcome at each time point were compared. Optimal cutoff values for significant MR variables were determined with receiver operating curve analyses. Sensitivity and specificity of these cutoff values for predicting unfavorable outcome were calculated and results were compared with qualitative MRI interpretation.Result:Infants presented with a median pH of 6.86, base deficit of 20 and Apgar scores of 1, 3 and 4 at 1, 5 and 10 min, respectively. Severe encephalopathy was present in 38%. Unfavorable outcome was present in 9 patients at discharge and in 13 of 26 patients with available follow-up data through 9 months. ADC values and T1 ratios were not significantly different between groups at either time point. T2 ratios in both the basal ganglia and thalamus were significantly higher in patients with unfavorable outcome, both at discharge and in follow-up. T2 intensity ratio in the basal ganglia and thalamus remained significantly associated with death or severe neurological deficit at discharge, after controlling for covariates in logistic regression analysis. Sensitivity and specificity of T2 intensity ratio for predicting unfavorable outcome at discharge were comparable to qualitative grading of injury in the basal ganglia and thalamus by a neuroradiologist.Conclusion:Increased T2 signal intensity in the basal ganglia or thalamus in patients with hypothermia-treated neonatal encephalopathy is associated with unfavorable neurological outcome at discharge and later with motor deficit/cerebral palsy. Quantitative methods to assess MRI evidence of brain injury are important for providing objective measures to predict outcome in this high-risk population.

White matter tract integrity and developmental outcome in newborn infants with hypoxic-ischemic encephalopathy treated with hypothermia.

To determine whether corpus callosum (CC) and corticospinal tract (CST) diffusion tensor imaging (DTI) measures relate to developmental outcome in encephalopathic newborn infants after therapeutic hypothermia.

Developmental Function in Toddlers With Sickle Cell Anemia

BACKGROUND: Neurocognitive impairment occurs in children and adults with sickle cell anemia, but little is known about neurodevelopment in very young children. We examined the neurodevelopmental status of infants participating in the Pediatric Hydroxyurea Phase III Clinical Trial (Baby Hug) to determine relationships with age, cerebral blood flow velocity, and hemoglobin concentration. METHODS: Standardized measures of infant neurodevelopment were administered to 193 infants with hemoglobin SS or hemoglobin S-β0 thalassemia between 7 and 18 months of age at the time of their baseline evaluation. Associations between neurodevelopmental scores and age, family income, parent education, hemoglobin concentration, and transcranial Doppler velocity were examined. RESULTS: Mean functioning on the baseline neurodevelopment scales was in the average range. There were no mental development scores <70 (impaired); 22 children had scores in the clinically significant range, 11 with impaired psychomotor scores and 11 with problematic behavior rating scores. Significantly poorer performance was observed with older age at baseline. Behavior rating scores were an average of 2.82 percentile points lower per month of age, with similar patterns observed with parent report using adaptive behavior scales. Parent-reported functional abilities and hemoglobin were negatively associated with higher transcranial Doppler velocities. CONCLUSIONS: Whereas overall functioning was in the normal range, behavioral and adaptive function was poorer with older age, even in this very young group of children. Explanatory mechanisms for this association between poorer developmental function and older age need to be identified.