IMPORTANCE: Exposure of young animals to commonly used anesthetics causes neurotoxicity including impaired neurocognitive function and abnormal behavior. The potential neurocognitive and behavioral ...effects of anesthesia exposure in young children are thus important to understand. OBJECTIVE: To examine if a single anesthesia exposure in otherwise healthy young children was associated with impaired neurocognitive development and abnormal behavior in later childhood. DESIGN, SETTING, AND PARTICIPANTS: Sibling-matched cohort study conducted between May 2009 and April 2015 at 4 university-based US pediatric tertiary care hospitals. The study cohort included sibling pairs within 36 months in age and currently 8 to 15 years old. The exposed siblings were healthy at surgery/anesthesia. Neurocognitive and behavior outcomes were prospectively assessed with retrospectively documented anesthesia exposure data. EXPOSURES: A single exposure to general anesthesia during inguinal hernia surgery in the exposed sibling and no anesthesia exposure in the unexposed sibling, before age 36 months. MAIN OUTCOMES AND MEASURES: The primary outcome was global cognitive function (IQ). Secondary outcomes included domain-specific neurocognitive functions and behavior. A detailed neuropsychological battery assessed IQ and domain-specific neurocognitive functions. Parents completed validated, standardized reports of behavior. RESULTS: Among the 105 sibling pairs, the exposed siblings (mean age, 17.3 months at surgery/anesthesia; 9.5% female) and the unexposed siblings (44% female) had IQ testing at mean ages of 10.6 and 10.9 years, respectively. All exposed children received inhaled anesthetic agents, and anesthesia duration ranged from 20 to 240 minutes, with a median duration of 80 minutes. Mean IQ scores between exposed siblings (scores: full scale = 111; performance = 108; verbal = 111) and unexposed siblings (scores: full scale = 111; performance = 107; verbal = 111) were not statistically significantly different. Differences in mean IQ scores between sibling pairs were: full scale = −0.2 (95% CI, −2.6 to 2.9); performance = 0.5 (95% CI, −2.7 to 3.7); and verbal = −0.5 (95% CI, −3.2 to 2.2). No statistically significant differences in mean scores were found between sibling pairs in memory/learning, motor/processing speed, visuospatial function, attention, executive function, language, or behavior. CONCLUSIONS AND RELEVANCE: Among healthy children with a single anesthesia exposure before age 36 months, compared with healthy siblings with no anesthesia exposure, there were no statistically significant differences in IQ scores in later childhood. Further study of repeated exposure, prolonged exposure, and vulnerable subgroups is needed.
Background Neurocognitive dysfunction is a known complication in children with chronic kidney disease (CKD). However, less is known about putative mechanisms or modifiable risk factors. The objective ...of this study was to characterize and determine risk factors for cognitive dysfunction in children, adolescents, and young adults with CKD compared with controls. Study Design Cross-sectional study. Setting & Participants The Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults With Chronic Kidney Disease (NiCK) Study included 90 individuals aged 8 to 25 years with CKD compared with 70 controls. Predictors CKD versus control, estimated glomerular filtration rate (eGFR), ambulatory blood pressure. Outcomes Performance on neurocognitive assessment with relevant tests grouped into 11 domains defined a priori by expert opinion. Results of tests were converted to age-normalized z scores. Measurements Each neurocognitive domain was analyzed through linear regression, adjusting for eGFR and demographic and clinical variables. For domains defined by multiple tests, the median z score of tests in that domain was used. Results We found significantly poorer performance in multiple areas of neurocognitive function among individuals with CKD compared with controls. Particular deficits were seen in domains related to attention, memory, and inhibitory control. Adjusted for demographic and clinical factors, we found lower performance in multiple domains with decreasing eGFRs (attention: β = 0.053, P = 0.02; visual spatial: β = 0.062, P = 0.02; and visual working memory: β = 0.069, P = 0.04). Increased diastolic load and decreased diastolic nocturnal dipping on ambulatory blood pressure monitoring were independently associated with impairments in neurocognitive performance. Limitations Unable to assess changes in neurocognitive function over time, and neurocognitive tests were grouped into predetermined neurocognitive domains. Conclusions Lower eGFR in children, adolescents, and young adults is associated with poorer neurocognitive performance, particularly in areas of attention, memory, and inhibitory control. Hypertension identified on ambulatory blood pressure monitoring may be an important risk factor, illustrating that neurocognitive function is an area of target-organ damage in CKD.
Objective To assess the association between early anthropometric measurements, device-assisted feeding, and early neurodevelopment in infants with complex congenital heart diseases (CHDs). Study ...design Bayley Scales of Infant Development II were used to assess cognitive and motor skills in 72 infants with CHD at 6 and 12 months of age. Linear regression models were used to assess the association between mode of feeding and anthropometric measurements with neurodevelopment at 6 and 12 months of age. Results Of the 72 infants enrolled in the study, 34 (47%) had single-ventricle physiology. The mean Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) scores at 6 months of age were 92 ± 10 and 81 ± 14, respectively. At 12 months of age, the mean MDI and PDI scores were 94 ± 12 and 80 ± 16, respectively. Lower length-for-age z score ( P < .01) and head circumference-for-age z score ( P < .05) were independently associated with lower MDI at 6 months, and both increased hospital length of stay ( P < .01) and lower length-for-age z score ( P = .04) were associated independently with lower MDI at 12 months. Device-assisted feeding at 3 months ( P = .04) and lower length-for-age z score ( P < .05) were independently associated with lower PDI at 6 months. Both lower weight-for-age z score ( P = .04) and lower length-for-age z score ( P = .04) were associated independently with PDI at 12 months. Conclusion Neonates with complex CHD who required device-assisted feeding and those with lower weight and length and head circumference z scores at 3 months were at risk for neurodevelopmental delay at 6 and 12 months of age.
OBJECTIVE:Electrographic seizures (ES) and electrographic status epilepticus (ESE) are common in children in the pediatric intensive care unit (PICU) with acute neurologic conditions. We aimed to ...determine whether ES or ESE was associated with worse long-term outcomes.
METHODS:Three hundred children with an acute neurologic condition and encephalopathy underwent clinically indicated EEG monitoring and were enrolled in a prospective observational study. We aimed to obtain follow-up data from 137 subjects who were neurodevelopmentally normal before PICU admission.
RESULTS:Follow-up data were collected for 60 of 137 subjects (44%) at a median of 2.7 years. Subjects with and without follow-up data were similar in clinical characteristics during the PICU admission. Among subjects with follow-up data, ES occurred in 12 subjects (20%) and ESE occurred in 14 subjects (23%). Multivariable analysis indicated that ESE was associated with an increased risk of unfavorable Glasgow Outcome Scale (Extended Pediatric Version) category (odds ratio 6.36, p = 0.01) and lower Pediatric Quality of Life Inventory scores (23 points lower, p = 0.001). Among subjects without prior epilepsy diagnoses ESE was associated with an increased risk of subsequently diagnosed epilepsy (odds ratio 13.3, p = 0.002). ES were not associated with worse outcomes.
CONCLUSIONS:Among children with acute neurologic disorders who were reported to be neurodevelopmentally normal before PICU admission, ESE but not ES was associated with an increased risk of unfavorable global outcome, lower health-related quality of life scores, and an increased risk of subsequently diagnosed epilepsy even after adjusting for neurologic disorder category, EEG background category, and age.
To evaluate response rate, event-free survival (EFS), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors and to estimate ...control intervals without irradiation in children with no residual tumor after initial surgery and induction chemotherapy and with delayed irradiation in patients with residual tumor or metastatic disease at diagnosis.
Patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). Maintenance chemotherapy began after induction in children without progressive disease. Children with no residual tumors after induction therapy and no metastatic disease at diagnosis were not to receive radiation therapy unless their tumors progressed.
Two hundred ninety-nine infants were enrolled. Forty-two percent of patients responded to induction chemotherapy. At 5 years from study entry, the EFS rate was 27% +/- 3%, and the survival rate was 43% +/- 3%. There was no significant difference between the two arms in terms of response rate or EFS. For medulloblastoma, supratentorial primitive neuroectodermal tumor, ependymoma, and rhabdoid tumors, 5-year EFS rates were 32% +/- 5%, 17% +/- 6%, and 32% +/- 6%, and 14% +/- 7%, respectively. Fifty-eight percent of patients who were alive 5 years after study entry had not received radiation therapy.
Intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. Survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy.
Lead exposure in childhood lowers IQ scores, but its effect on children's behavior is less clear. Because IQ, per se, affects behavior, measuring the direct effect of lead requires measuring and then ...adjusting for IQ. In addition, either peak blood lead concentration, usually at 2 years old, or the lower blood lead level measured at school age may be the most relevant. Few studies have all of this information.
The purpose of this work was to differentiate the direct effect of lead on behavior and the indirect effect through IQ and to examine the strength of the association for peak and concurrent blood lead concentration.
Data come from a clinical trial of the chelating drug succimer to prevent cognitive impairment in 780 urban 12- to 33-month-olds with blood lead concentrations of 20 to 44 microg/dL. The children were followed from ages 2 to 7 years. The trial data were analyzed as a prospective observational study.
Blood lead concentration at 2 years old was not associated with Conners' Parent Rating Scale-Revised scores at 5 years of age or Behavioral Assessment Systems for Children scores at 7 years of age. Blood lead level at 7 years of age had direct effects on the Behavioral Assessment Systems for Children behavioral symptoms index, externalizing, and school problems at age 7.
Concurrent blood lead concentration was associated with externalizing and school problems scales at 7 years of age, and the effect was not entirely mediated through the effect of lead on IQ.
CKD has been linked with cognitive deficits and affective disorders in multiple studies. Analysis of structural and functional neuroimaging in adults and children with kidney disease may provide ...additional important insights into the pathobiology of this relationship. This paper comprehensively reviews neuroimaging studies in both children and adults. Major databases (PsychLit, MEDLINE, WorldCat, ArticleFirst, PubMed, Ovid MEDLINE) were searched using consistent search terms, and studies published between 1975 and 2012 were included if their samples focused on CKD as the primary disease process. Exclusion criteria included case reports, chapters, and review articles. This systematic process yielded 43 studies for inclusion (30 in adults, 13 in children). Findings from this review identified several clear trends: (1) presence of cerebral atrophy and cerebral density changes in patients with CKD; (2) cerebral vascular disease, including deep white matter hyperintensities, white matter lesions, cerebral microbleeds, silent cerebral infarction, and cortical infarction, in patients with CKD; and (3) similarities in regional cerebral blood flow between patients with CKD and those with affective disorders. These findings document the importance of neuroimaging procedures in understanding the effect of CKD on brain structure, function, and associated behaviors. Results provide a developmental linkage between childhood and adulthood, with respect to the effect of CKD on brain functioning across the lifespan, with strong implications for a cerebrovascular mechanism contributing to this developmental linkage. Use of neuroimaging methods to corroborate manifest neuropsychological deficits or perhaps to indicate preventive actions may prove useful to individuals with CKD.
Objective
To describe perinatal stress induced hyperinsulinism (PSIHI), determine the prevalence of neurodevelopmental differences, and identify risk factors for poor developmental prognosis.
Methods
...Subjects with a history of hyperinsulinism (HI) and perinatal stress and in whom resolution of the HI was demonstrated were included. Medical record review, caregiver interview, and three validated developmental assessments were completed.
Results
Of the 107 subjects (75% male), 36% were born between 32 and 37 weeks. Median age of hypoglycemia presentation was 0 days. Median age at HI diagnosis was 12 days (IQR 13.5). Median length of time for initiation of definitive treatment was 14 days (IQR 14).
Caregiver interviews were completed for 53 of 79 eligible subjects. Developmental concerns were reported by 51%. Neurodevelopmental assessments were completed by caregivers of 37 of the 53 enrolled subjects. The proportion of subjects scoring >1 SD and >2 SD away from the mean in the direction of concern on the major composite scores was significantly greater than in the general population (40.5% vs. 15.8%,
P
≤ 0.0001 and 18.9% vs. 2.2%,
P
≤ 0.0001, respectively).
Male sex, small for gestational age status (SGA), and treatment with continuous feeds were associated with assessment scores >1 SD from the mean (
P
< 0.05). SGA and preeclampsia were associated with assessment scores >2 SD from the mean (
P
< 0.05).
Conclusion
While the majority of infants presented with hypoglycemia in the first day of life, diagnosis and treatment occurred 12–14 days later. Children with PSIHI are at high risk of neurodevelopmental deficits and are more likely to perform below average on developmental assessment.
IntroductionMild obstructive sleep-disordered breathing (oSDB), characterised by habitual snoring without frequent apnoeas and hypopnoeas on polysomnography, is prevalent in children and commonly ...treated with adenotonsillectomy (AT). However, the absence of high-level evidence addressing the role of AT in improving health and behavioural outcomes has contributed to significant geographical variations in care and potential for surgery to be both overused and underused.Methods and analysisThe Pediatric Adenotonsillectomy Trial for Snoring (PATS) is a single-blinded, multicentre randomised controlled trial designed to evaluate the effect of AT in treating mild oSDB. Four hundred sixty eligible children, aged 3.0–12.9 years old, will be randomised to either early adenotonsillectomy or to watchful waiting with supportive care (WWSC) with a 1:1 ratio. The study’s coprimary endpoints are (1) change from baseline in executive behaviour relating to self-regulation and organisation skills as measured by the Behavioural Rating Inventory of Executive Function (BRIEF) Global Composite Score (GEC); and (2) change from baseline in vigilance as measured on the Go-No-Go (GNG) signal detection parameter (d-prime). A mixed effects model will be used to compare changes in the BRIEF GEC score and GNG score at 6 and 12 months from baseline between the AT arm and the WWSC arm.Ethics and disseminationThe study protocol was approved by the institutional review board (IRB) at Children’s Hospital of Philadelphia (CHOP) on 3 October 2014 (14–0 11 214). The approval of CHOP as the central IRB of record was granted on 29 February 2016. The results will be published in peer-reviewed journals and presented at academic conferences. The data collected from the PATS study will be deposited in a repository (National Sleep Research Resource, sleepdata.org) after completion of the study to maximise use by the scientific community.Trial registration numberNCT02562040; Pre-results.
Increases in peak blood lead concentrations, which occur at 18-30 months of age in the United States, are thought to result in lower IQ scores at 4-6 years of age, when IQ becomes stable and ...measurable. Data from a prospective study conducted in Boston suggested that blood lead concentrations at 2 years of age were more predictive of cognitive deficits in older children than were later blood lead concentrations or blood lead concentrations measured concurrently with IQ. Therefore, cross-sectional associations between blood lead and IQ in school-age children have been widely interpreted as the residual effects of higher blood lead concentrations at an earlier age or the tendency of less intelligent children to ingest more leaded dust or paint chips, rather than as a causal relationship in older children. Here we analyze data from a clinical trial in which children were treated for elevated blood lead concentrations (20-44 μg/dL) at about 2 years of age and followed until 7 years of age with serial IQ tests and measurements of blood lead. We found that cross-sectional associations increased in strength as the children became older, whereas the relation between baseline blood lead and IQ attenuated. Peak blood lead level thus does not fully account for the observed association in older children between their lower blood lead concentrations and IQ. The effect of concurrent blood level on IQ may therefore be greater than currently believed.
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Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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