Neurobehavioral Outcomes In Children Research Articles

Exposure in utero to SGAs not linked to adverse neurobehavioral outcomes

Prenatal exposure to second‐generation antipsychotics (SGAs) did not increase risk of adverse childhood developmental or behavioral outcomes compared with antipsychotic‐unexposed children, a study examining preschool‐aged children has found. This was one of the largest studies to date that examined neurobehavioral outcomes in children exposed prenatally to SGAs, the investigators reported. Study results were published online March 13, 2024, in the Journal of Clinical Psychiatry.

Impact of sociodemographic disadvantage on neurobehavioral outcomes in children with newly diagnosed seizures and their unaffected siblings over 36 months.

This study was undertaken to determine the short-term and longer term impact of sociodemographic disadvantage on the emotional-behavioral status of youths with new onset epilepsy and their unaffected siblings at the time of diagnosis and the subsequent 3 years. Three hundred twelve youths with newly diagnosed epilepsies and 223 unaffected siblings, aged 6-16 years, were independently assessed regarding their emotional and behavioral status by their parents and teachers at baseline, and at 18 at 36 months later; youths with seizures also completed self-report measures of depression, anxiety, and hostility at those three time points. A sociodemographic disadvantage score was computed for each family (children with newly diagnosed seizures and their siblings), and families were separated into four categories from most disadvantaged to least disadvantaged. In both children and siblings, the least disadvantaged group exhibited the lowest level of neurobehavioral problems, whereas the most disadvantaged group showed a higher level of neurobehavioral problems across all the same behavior metrics. Findings remained stable and significant across all informants (parent, teacher, child) and across all time periods (throughout the 3-year period). Furthermore, both corrected and uncorrected linear regression analyses indicated that disadvantage was a more constant and stable predictor of behavioral and emotional problems over time compared to clinical seizure characteristics and abnormalities in magnetic resonance imaging and electroencephalographic testing. Sociodemographic disadvantage bears a strong relationship to youths with emotional and behavioral problems both at the time of diagnosis as well as prospectively. The relationship is robust and reflected in reports from multiple informants (parent, teacher, child self-report), evident in siblings as well, and possibly more explanatory than traditional clinical seizure variables. Future studies will be needed to determine whether this disadvantage factor is modifiable with early intervention.

Using High-Throughput Screening to Evaluate Perturbations Potentially Linked to Neurobehavioral Outcomes: A Case Study Using Publicly Available Tools on FDA Batch-Certified Synthetic Food Dyes.

There is growing evidence from human and animal studies indicating an association between exposure to synthetic food dyes and adverse neurobehavioral outcomes in children. However, data gaps persist for potential mechanisms by which the synthetic food dyes could elicit neurobehavioral impacts. We developed an approach to evaluate seven US FDA-batch-certified food dyes using publicly available high-throughput screening (HTS) data from the US EPA's Toxicity Forecaster to assess potential underlying molecular mechanisms that may be linked to neurological pathway perturbations. The dyes were screened through 270 assays identified based on whether they had a neurological-related gene target and/or were mapped to neurodevelopmental processes or neurobehavioral outcomes, and were conducted in brain tissue, targeted specific hormone receptors, or targeted oxidative stress and inflammation. Some results provided support for neurological impacts found in human and animal studies, while other results showed a lack of correlation with in vivo findings. The azo dyes had a range of activity in assays mapped to G-protein-coupled receptors and were active in assays targeting dopaminergic, serotonergic, and opioid receptors. Assays mapped to nuclear receptors (androgen, estrogen, and thyroid hormone) also exhibited activity with the food dyes. Other molecular targets included the aryl hydrocarbon receptor, acetylcholinesterase, and monoamine oxidase. The Toxicological Prioritization Index tool was used to visualize the results of the Novascreen assays. Our results highlight certain limitations of HTS assays but provide insight into potential underlying mechanisms of neurobehavioral effects observed in in vivo animal toxicology studies and human clinical studies.

Parenting and Neurobehavioral Outcomes in Children Born Moderate-to-Late Preterm and at Term

To compare the parenting environment and the relationships between parenting behaviors and concurrent child neurobehavioral outcomes at 2years of corrected age between children born moderate-to-late preterm (MLP; 32-36weeks of gestation) and at term (≥37weeks of gestation). Participants were 129 children born MLP and 110 children born at term and their mothers. Mothers' parenting behaviors (sensitivity, structuring, nonintrusiveness, nonhostility) were assessed at 2years of corrected age using the Emotional Availability Scales. Child cognitive and language development were assessed using the Bayley Scales of Infant and Toddler Development, and social-emotional competence using the Infant Toddler Social and Emotional Assessment. Mothers of children born MLP and at term displayed similar parenting behaviors overall, with slightly lower nonintrusiveness in mothers of children born MLP (adjusted mean difference -0.32 [-0.60, -0.04]; P=.03). In both groups of children, greater maternal sensitivity was associated with better cognitive development (P<.001 MLP; P=.02 term), increased maternal structuring was associated with better social-emotional competence (P=.02 MLP; P=.03 term), and higher maternal nonintrusiveness was associated with better cognitive, language, and social-emotional outcomes (all P<.04). Greater maternal sensitivity and structuring were associated with better language development in children born MLP but not in children born at term. Parenting behaviors are important for neurobehavioral outcomes in children born MLP and at term. Language development may be more strongly influenced by select parenting behaviors in children born MLP compared with children born at term.

Role of endocrine disrupting chemicals in children's neurodevelopment

Environmental stressors, like endocrine disrupting chemicals (EDC), are considered important contributors to the increased rates of neurodevelopmental dysfunctions. Considering the cumulative research on adverse neurodevelopmental effects associated with prenatal exposure to EDC, the purpose of this study was to review the available limited literature about the effects of postnatal exposure to EDC on child neurodevelopment and behaviour. Despite widespread children's exposure to EDC, there are a limited number of epidemiological studies on the association of this exposure with neurodevelopmental disorders, in particular in the postnatal period. The available research suggests that postnatal EDC exposure is related to adverse neurobehavioral outcomes in children; however the underlying mechanisms of action remain unclear. Timing of exposure is a key factor determining potential neurodevelopmental consequences, hence studying the impact of multiple EDC co-exposure in different vulnerable life periods could guide the identification of sensitive subpopulations. Most of the reviewed studies did not take into account sex differences in the EDC effects on children neurodevelopment. We believe that the inclusion of sex in the study design should be considered as the role of EDC on children neurodevelopment are likely sex-specific and should be taken into consideration when determining susceptibility and potential mechanisms of action.

A Review of Recent Studies on Bisphenol A and Phthalate Exposures and Child Neurodevelopment.

Purpose of Review: Bisphenol A and phthalate have been found in the environment, as well as in humans. In this narrative review pre- and postnatal bisphenol A and phthalate exposures, their relationship to neurodevelopment, and the behavioral outcomes of children are elucidated, focusing in particular on the recent case-control, cross-sectional, and longitudinal studies. This review also introduces some of the possible mechanisms behind the observed associations between exposures and outcomes. Recent Findings: Although bisphenol A and phthalate exposure have been reported to influence neurobehavioral development in children, there are various kinds of test batteries for child neurodevelopmental assessment at different ages whose findings have been inconsistent among studies. In addition, the timing and number of exposure assessments have varied. Summary: Overall, this review suggests that prenatal exposure to bisphenol A and phthalates may contribute to neurobehavioral outcomes in children. The evidence is still limited; however, Attention Deficit Hyperactivity Disorder (ADHD) symptoms, especially among boys, constantly suggested association with both prenatal and concurrent exposure to bisphenol A. Although there is limited evidence on the adverse effects of prenatal and postnatal bisphenol A and phthalate exposures provided, pregnant women and young children should be protected from exposure based on a precautionary approach.

Manganese transporter genetics and sex modify the association between environmental manganese exposure and neurobehavioral outcomes in children

Manganese transporter genetics and sex modify the association between environmental manganese exposure and neurobehavioral outcomes in children

Manganese transporter genetics and sex modify the association between environmental manganese exposure and neurobehavioral outcomes in children

There is increasing evidence that environmental manganese (Mn) exposure early in life can have negative effects on children's neurodevelopment and increase the risk of behavioral problems, including attention deficit hyperactivity disorder (ADHD). Factors that may contribute to differences in sensitivity to Mn exposure are sex and genetic variation of proteins involved in the regulation of Mn concentrations. Here we investigate if sex and polymorphisms in Mn transporter genes SLC30A10 and SLC39A8 influence the association between Mn exposure and ADHD-related behavioral problems in children.The SNPs rs1776029 and rs12064812 in SLC30A10, and rs13107325 in SLC39A8 were genotyped by TaqMan PCR or pyrosequencing in a population of Italian children (aged 11–14 years; n = 645) with a wide range of environmental Mn exposure. Mn in surface soil was measured in situ using XRF technology or modeled by geospatial analysis. Linear regression models or generalized additive models (GAM) were used for analyzing associations between soil Mn and neurobehavioral problems assessed by the Conners' behavior rating scales (self-, and parent-reported). Gene-environment interactions (Mn transporter genotype x soil Mn) were evaluated using a genetic score in which genotypes for the three SNPs were combined based on their association with blood Mn, as an indication of their influence on Mn regulation.We observed differences in associations between soil Mn and neurobehavior between sexes. For several self-reported Conners' scales, girls showed U-shaped relationships with higher (worse) Conners' scoring at higher soil Mn levels, and several parent-reported scales showed positive linear relationships between increasing soil Mn and higher Conner's scores. For boys, we observed a positive linear relationship with soil Mn for one Conner's outcome only (hyperactivity, parent-reported). We also observed some interactions between soil Mn and the genetic score on Conner's scales in girls and girls with genotypes linked to high blood Mn showed particularly strong positive associations between soil Mn and parent-reported Conners' scales.Our results indicate that sex and polymorphisms in Mn transporter genes contribute to differences in sensitivity to Mn exposure from the environment and that girls that are genetically less efficient at regulating Mn, may be a particularly vulnerable group.

Cardiac Arrest Outcomes in Children With Preexisting Neurobehavioral Impairment.

To describe survival and 3-month and 12-month neurobehavioral outcomes in children with preexisting neurobehavioral impairment enrolled in one of two parallel randomized clinical trials of targeted temperature management. Secondary analysis of Therapeutic Hypothermia after Pediatric Cardiac Arrest In-Hospital and Out-of-Hospital trials data. Forty-one PICUs in the United States, Canada, and United Kingdom. Eighty-four participants (59 in-hospital cardiac arrest and 25 out-of-hospital cardiac arrest), 49 males, 35 females, mean age 4.6 years (SD, 5.36 yr), with precardiac arrest neurobehavioral impairment (Vineland Adaptive Behavior Scales, Second Edition composite score < 70). All required chest compressions for greater than or equal to 2 minutes, were comatose and required mechanical ventilation after return of circulation. Neurobehavioral function was assessed using the Vineland Adaptive Behavior Scales, Second Edition at baseline (reflecting precardiac arrest status), and at 3 and 12 months postcardiac arrest, followed by on-site cognitive evaluation. Vineland Adaptive Behavior Scales, Second Edition norms are 100 (mean) ± 15 (SD); higher scores indicate better function. Analyses evaluated survival, changes in Vineland Adaptive Behavior Scales, Second Edition, and cognitive functioning. Twenty-eight of 84 (33%) survived to 12 months (in-hospital cardiac arrest, 19/59 (32%); out-of-hospital cardiac arrest, 9/25 [36%]). In-hospital cardiac arrest (but not out-of-hospital cardiac arrest) survival rate was significantly lower compared with the Therapeutic Hypothermia after Pediatric Cardiac Arrest group without precardiac arrest neurobehavioral impairment. Twenty-five survived with decrease in Vineland Adaptive Behavior Scales, Second Edition less than or equal to 15 (in-hospital cardiac arrest, 18/59 (31%); out-of-hospital cardiac arrest, 7/25 [28%]). At 3-months postcardiac arrest, mean Vineland Adaptive Behavior Scales, Second Edition scores declined significantly (-5; SD, 14; p < 0.05). At 12 months, Vineland Adaptive Behavior Scales, Second Edition declined after out-of-hospital cardiac arrest (-10; SD, 12; p < 0.05), but not in-hospital cardiac arrest (0; SD, 15); 43% (12/28) had unchanged or improved scores. This study demonstrates the feasibility, utility, and challenge of including this population in clinical neuroprotection trials. In children with preexisting neurobehavioral impairment, one-third survived to 12 months and their neurobehavioral outcomes varied broadly.

Traffic-Related Air Pollution, APOEε4 Status, and Neurodevelopmental Outcomes among School Children Enrolled in the BREATHE Project (Catalonia, Spain).

Background:Traffic-related air pollution is emerging as a risk factor for Alzheimer's disease (AD) and impaired brain development. Individual differences in vulnerability to air pollution may involve the allele of Apolipoprotein E (APOE) gene, the primary genetic risk factor for AD.Objective:We analyzed whether the association between traffic air pollution and neurodevelopmental outcomes is modified by APOE status in children.Methods:Data on parent-reported behavior problems (total difficulties scores, Strengths and Difficulties Questionnaire), teacher-reported attention-deficit hyperactivity disorder (ADHD) symptom scores, cognitive performance trajectories (computerized tests of inattentiveness and working memory repeated 2–4 times during January 2012–March 2013), and APOE genotypes were obtained for 1,667 children age 7–11 y attending 39 schools in or near Barcelona. Basal ganglia volume (putamen, caudate, and globus pallidum) was measured in 163 of the children by MRI (October 2012–April 2014.) Average annual outdoor polycyclic aromatic hydrocarbons (PAHs), elemental carbon (EC), and nitrogen dioxide () concentrations were estimated based on measurements at each school (two 1-wk campaigns conducted 6 months apart in 2012).Results:APOE allele carriers had significantly higher behavior problem scores than noncarriers, and adverse associations with PAHs and were stronger or limited to carriers for behavior problem scores (P-interaction 0.03 and 0.04), caudate volume (P-interaction 0.04 and 0.03), and inattentiveness trajectories (P-interaction 0.15 and 0.08, respectively). Patterns of associations with the same outcomes were similar for EC.Conclusion:PAHs, EC, and were associated with higher behavior problem scores, smaller reductions in inattentiveness over time, and smaller caudate volume in APOE allele carriers in our study population, and corresponding associations were weak or absent among noncarriers. These findings support a potential role of APOE in biological mechanisms that may contribute to associations between air pollution and neurobehavioral outcomes in children. https://doi.org/10.1289/EHP2246

S74. Hemodynamic changes in the prefrontal cortex as measured by functional near-infrared spectroscopy and their relationships to neurobehavioral outcomes in children with FASD

Introduction Children with a history of prenatal alcohol exposure (PAE) have been found to have altered hemodynamic changes in the prefrontal cortical (PFC) as measured by functional near-infrared spectroscopy (fNIRS) relative to both typically developing children and those who have other neurobehavioral problems. The purpose of this study was to evaluate the relationships between indices of PFC functioning and the neurobehavioral outcomes in children with FASD and to determine if these relationships differed from other groups of children. Methods Levels of oxygenated (HBO) and deoxygenated (HBR) hemoglobin were assessed during a computer task designed to elicit arousal in children with a history of PAE ( n = 33) and children without PAE who were typically developing (Controls, n = 25) or had other neurobehavioral problems (Clinical Contrast group, n = 22). The task elicits emotional arousal by alternating positive (Win) and negative (Loss) arousal while playing a game. The linear relationships between neurobehavioral outcomes (behavioral problems and word generation skills) and the mean levels of HBO and HBR for each of the conditions were assessed for group differences using the Potthoff regression procedure, which allows for simultaneous and separate tests of regression intercepts and slopes across groups. Results Within the entire sample, indices of PFC activation were related to externalizing problem behaviors and word generation skills, a measure of executive functioning, but PFC activation in the lateral areas of the PFC differentiated children in the PAE group from both other groups. Specifically, slopes of the relationship between Left Lateral HBO levels and rule-breaking behavior were higher in children with PAE and slopes of the relationship between Lateral Left HBR levels and withdrawn/depression symptoms were more negative. Performance on a word generation task was differentially predicted by indices of Right Lateral PFC activation with children in the PAE group having more negative slopes in the linear relationships with HBR levels than both other groups. Conclusion Children with a history of PAE had unique characteristics in the relationships between the indices of PFC functioning and neurobehavioral problems that may be useful in differentiating alcohol-exposed children from typically developing children and those who have neurobehavioral problems not associated with PAE.

Direct and transgenerational effects of low doses of perinatal di-(2-ethylhexyl) phthalate (DEHP) on social behaviors in mice.

Di-(2-ethylhexyl) phthalate (DEHP) is an endocrine disrupting chemical commonly used as a plasticizer in medical equipment, food packaging, flooring, and children’s toys. DEHP exposure during early development has been associated with adverse neurobehavioral outcomes in children. In animal models, early exposure to DEHP results in abnormal development of the reproductive system as well as altered behavior and neurodevelopment. Based on these data, we hypothesized that developmental exposure to DEHP would decrease social interactions and increase anxiety-like behaviors in mice in a dose-dependent manner, and that the effects would persist over generations. C57BL/6J mice consumed one of three DEHP doses (0, 5, 40, and 400 μg/kg body weight) throughout pregnancy and during the first ten days of lactation. The two higher doses yielded detectable levels of DEHP metabolites in serum. Pairs of mice from control, low, and high DEHP doses were bred to create three dose lineages in the third generation (F3). Average anogenital index (AGI: anogenital distance/body weight) was decreased in F1 males exposed to the low dose of DEHP and in F1 females exposed to the highest dose. In F1 mice, juvenile pairs from the two highest DEHP dose groups displayed fewer socially investigative behaviors and more exploratory behaviors as compared with control mice. The effect of DEHP on these behaviors was reversed in F3 mice as compared with F1 mice. F1 mice exposed to low and medium DEHP doses spent more time in the closed arms of the elevated plus maze than controls, indicating increased anxiety-like behavior. The generation-dependent effects on behavior and AGI suggest complex mechanisms by which DEHP directly impacts reproductive and neurobehavioral development and influences germline-inherited traits.

Correlates of Pediatric CPAP Adherence.

Obstructive sleep apnea (OSA) is a common pediatric condition characterized by recurrent partial or complete cessation of airflow during sleep, typically due to inadequate upper airway patency. Continuous positive airway pressure (CPAP) is a therapeutic option that reduces morbidity. Despite efforts to promote use, CPAP adherence is poor in both pediatric and adult populations. We sought to determine whether demographics, insurance status, OSA severity, therapeutic pressure, or comorbid conditions were associated with pediatric CPAP adherence. A retrospective review of adherence download data was performed on all pediatric patients with initiation or adjustment of CPAP treatment over a one-year period with documented in-laboratory CPAP titration. Patients were grouped as CPAP adherent or non-adherent, where adherence was defined as > 70% nightly use and average usage ≥ 4 hours per night. Differences between the groups were analyzed by χ(2) test. Overall, nearly half of participants were CPAP adherent (49%, 69/140). Of the demographic data collected (age, ethnicity, sex, insurance status), only female sex was associated with better adherence (60.9% vs 39.5% of males adherent; odds ratio [OR] = 2.41, 95%CI = 1.20-4.85; p = 0.01). Severity of OSA (diagnostic apnea-hypopnea index [AHI] and degree of hypoxemia), therapeutic pressure, and residual AHI did not impact CPAP adherence (p > 0.05). Patients with developmental delay (DD) were more likely to be adherent with CPAP than those without a DD diagnosis (OR = 2.55, 95%CI = 1.27-5.13; p = 0.007). Female patients with trisomy 21 tended to be more adherent, but this did not reach significance or account for the overall increased adherence associated with female sex. Our study demonstrates that adherence to CPAP therapy is poor but suggests that female sex and developmental delay are associated with better adherence. These findings support efforts to understand the pathophysiology of and to develop adherence-promoting and alternative interventions for pediatric OSA.

Neurobehavioral Outcomes After Cardiac Arrest

Research Article| June 01 2016 Neurobehavioral Outcomes After Cardiac Arrest AAP Grand Rounds (2016) 35 (6): 65. https://doi.org/10.1542/gr.35-6-65 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Neurobehavioral Outcomes After Cardiac Arrest. AAP Grand Rounds June 2016; 35 (6): 65. https://doi.org/10.1542/gr.35-6-65 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: cardiac arrest, out-of-hospital cardiac arrest Slomine BS, Silverstein FS, Christensen JR, et al. Neurobehavioral outcomes in children after out-of-hospital cardiac arrest. Pediatrics. 2016; 137(4): e20153412; doi: https://doi.org/10.1542/peds.2015-3412Google Scholar Investigators from multiple institutions sought to determine the neurobehavioral outcomes 12 months following out-of-hospital cardiac arrest (OH-CA) among children who were comatose following resuscitation. Participants in the current study consisted of a subgroup of children who had been enrolled in a clinical trial, Therapeutic Hypothermia After Pediatric Cardiac Arrest, Out-Of-Hospital (THAPCA-OH), to determine whether targeted temperature management to hypothermia (33.0°C) was more beneficial than targeting to normothermia (36.8°C). Neurobehavioral function was assessed by caregiver responses on the Vineland Adaptive Behavior Scales-Second Edition (VABS-II). The VABS-II measures functional skills and provides age-corrected standard scores. A baseline score, based on functioning before OH-CA, was obtained from caregivers within 24 hours of enrollment and compared to scores obtained 12 months after the event. Only participants with normal (>70) baseline composite VABS-II scores were eligible for this study. The primary outcome was change in VABS-II scores from baseline to follow-up in each study child; statistical significance of the change was assessed with paired t-tests. Regression models were used to identify independent associations with change in composite VABS-II scores. Of the 295 children, aged 2 days to 18 years, enrolled in the THAPCA-OH study, 96 were alive at 12 months post-arrest. Among these 96 survivors, 87 had normal baseline composite VABS-II scores and were eligible for the current study. Follow-up was completed in 85 of the 87. VABS-II composite, domain, and subdomain scores in study participants declined significantly between baseline and the 12-month follow-up (P < .001 for all comparisons). Mean baseline scores ranged from 95–106; mean follow-up scores ranged from 68–81. The mean change in composite VABS-II score was −21 for children <3 years of age, −28 for children 3–6 years of age and −46 for children ≥6 years of age. At 12-month follow-up, 49% (42/85) of the children had normal VABS-II scores (≥70) and 38% (32/85) had composite scores within 15 points of their baseline. Most children also demonstrated below average cognitive functioning at the 12-month followup. Treatment with hypothermia did not influence neurobehavioral outcomes. In the multivariate analysis, older age at the time of arrest and higher baseline VABS-II score were independent predictors of decline in composite VABS-II scores following OH-CA. The investigators conclude that significant neurobehavioral deficits persist in children surviving OH-CA who were comatose after resuscitation. Younger age at the time of arrest was associated with better neurobehavioral outcome. Dr Anderson has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. Pediatric OH-CA is a rare event occurring in ~8/100,000 person-years (compared to 126/100,000 person-years in the adult population).1 Children who experience in-hospital cardiac arrest undergo more rapid resuscitation and presumably have less incremental brain injury.2 The results of the current study not only highlight the poor survival... You do not currently have access to this content.

Neurobehavioral Outcomes in Children After Out-of-Hospital Cardiac Arrest.

This study examined 12-month neurobehavioral outcomes in children who survived out-of-hospital cardiac arrest (OH-CA), were comatose after resuscitation, and were enrolled in a clinical trial to evaluate targeted temperature management to hypothermia (33.0°C) or normothermia (36.8°C) (Therapeutic Hypothermia after Pediatric Cardiac Arrest, Out-of-Hopsital [THAPCA-OH]; NCT00878644). Baseline functioning was assessed by caregiver responses on the Vineland Adaptive Behavior Scales-Second Edition (VABS-II) soon after OH-CA (based on functioning before OH-CA); children with broadly normal baseline functioning (VABS-II ≥70) were included in the THAPCA-OH primary outcome. VABS-II was completed again 12 months later. Then, face-to-face cognitive evaluations were completed. Analyses evaluated changes in VABS-II composite, domain, and subdomain scores and cognitive functioning at follow-up. Ninety-six of 295 enrolled children were alive at 12 months; 87 of 96 had broadly normal baseline functioning (VABS-II ≥70). Follow-up was obtained on 85/87. Forty-two of 85 had VABS-II ≥70 at 12 months. VABS-II composite, domain, and subdomain scores declined significantly between baseline and 12-month follow-up (P < .001). Declines were greatest in older children. Most children displayed well below average cognitive functioning. Older age at cardiac arrest and higher baseline VABS-II scores were predictive of greater decline in neurobehavioral function. Treatment with hypothermia did not influence neurobehavioral outcomes. This is the largest study exploring long-term neurobehavioral outcomes in children surviving OH-CA who were comatose after resuscitation. Results revealed significant neurobehavioral morbidity across multiple functional domains, based both on caregiver reports and performance on objective cognitive measures, in survivors 1 year later.

Placental DNA Methylation Related to Both Infant Toenail Mercury and Adverse Neurobehavioral Outcomes

Prenatal exposure to mercury (Hg) is associated with adverse neurobehavioral outcomes in children. As Hg can interfere with normal placental functioning, as well as cross the placenta and target th...

Diffusion Tensor Imaging Properties and Neurobehavioral Outcomes in Children with Hydrocephalus

White matter structural alterations and the correlation with neuropsychological deficits in children with hydrocephalus have not been well investigated. In this prospective study, the objectives were the following: 1) to apply DTI to detect in vivo white matter alterations based on diffusion properties in children with acute hydrocephalus, 2) to quantify early neuropsychological deficits, and 3) to explore the correlation between potential neuropsychological deficits and abnormalities in functionally related white matter. A total of 44 children, 24 with hydrocephalus and 20 controls, were enrolled in the study. DTI indices, FA, MD, AD, and RD, were evaluated in the gCC, sCC, PLIC, and ALIC. The ABAS-II was used as a broad screener of development, including conceptual, social, practical, and motor skills. The correlation between the Motor Scale and DTI indices in the PLIC was analyzed. DTI analyses showed that the gCC and sCC in children with hydrocephalus had lower FA and higher MD, driven by the increased RD with statistical significance (P < .05) or trend-level significance (P = .06). The PLIC and ALIC had significantly higher AD in children with hydrocephalus (P < .05). On the ABAS-II, parent ratings of general adaptive skills, conceptual skills, and motor skills were significantly lower in children with hydrocephalus (all at P < .05). The MD and RD values in the PLIC were found to have trend-level or significant correlation with the Motor Scale (P = .057, .041, respectively). DTI reveals alterations in the white matter structure in children with hydrocephalus with preliminary findings suggesting correlation with clinical motor deficits.

Effects of Positive Airway Pressure Therapy on Neurobehavioral Outcomes in Children with Obstructive Sleep Apnea

Positive airway pressure therapy is frequently used to treat obstructive sleep apnea in children. However, it is not known whether positive airway pressure therapy results in improvements in the neurobehavioral abnormalities associated with childhood sleep apnea. We hypothesized that positive airway pressure therapy would be associated with improvements in attention, sleepiness, behavior, and quality of life, and that changes would be associated with therapy adherence. Neurobehavioral assessments were performed at baseline and after 3 months of positive airway pressure therapy in a heterogeneous group of 52 children and adolescents. Adherence varied widely (mean use, 170 ± 145 [SD] minutes per night). Positive airway pressure therapy was associated with significant improvements in attention deficits (P < 0.001); sleepiness on the Epworth Sleepiness Scale (P < 0.001); behavior (P < 0.001); and caregiver- (P = 0.005) and child- (P < 0.001) reported quality of life. There was a significant correlation between the decrease in Epworth Sleepiness Scale at 3 months and adherence (r = 0.411; P = 0.006), but not between other behavioral outcomes and adherence. Behavioral factors also improved in the subset of children with developmental delays. These results indicate that, despite suboptimal adherence use, there was significant improvement in neurobehavioral function in children after 3 months of positive airway pressure therapy, even in developmentally delayed children. The implications for improved family, social, and school function are substantial. Clinical trial registered with www.clinicaltrials.gov (NCT 00458406).

Association between arsenic exposure and behavior among first-graders from Torreón, Mexico

Previous studies suggest adverse effects of arsenic exposure on children’s cognitive function. In this study, we examined the potential association between arsenic exposure and children’s behavior. Five hundred and twenty-six children, 6–7 years old, living near a metal foundry in Torreón, Mexico, participated in the study. Arsenic exposure was measured as total urinary arsenic (UAs) and arsenic metabolites—monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) concentrations. Children’s behavior was assessed by Conners Behavior Rating Scales for parents and teachers. The median (interquartile range) concentrations of UAs, MMA and DMA were 55.2 (39.7), 6.7 (5.9) and 39.3 (28.5) μg/L, respectively. The mean behavior scores from parent and teacher ratings were within the clinically normal range ( T<65). The relationship between behavior and urinary arsenic was modeled in linear and logistic regression models, with UAs, MMA and DMA tested in separate models and entered as quartiles. No significant association was found between any measure of urinary arsenic and parent ratings of behavior. However, higher UAs was modestly associated with higher scores on the Oppositional, Cognitive Problems and ADHD sub-scales of the teacher ratings; a dose–response relationship was not established between UAs quartiles and behavior. Higher urinary DMA was associated with higher ratings on the Oppositional, Cognitive Problems and ADHD Index by teachers. The associations between UAs and behavior became statistically non-significant after adjustment for the Peabody Picture Vocabulary Test scores, suggesting that the harmful effects of arsenic on behavior may be secondary to arsenic-induced cognitive deficits. These data suggest a potential adverse association between arsenic and children’s behavior and indicate a need to further study the effects of arsenic and arsenic metabolites on neurobehavioral outcomes in children.

Multicenter cohort study of in-hospital pediatric cardiac arrest*

1) To describe clinical characteristics, hospital courses, and outcomes of a cohort of children cared for within the Pediatric Emergency Care Applied Research Network who experienced in-hospital cardiac arrest with sustained return of circulation between July 1, 2003 and December 31, 2004, and 2) to identify factors associated with hospital mortality in this population. These data are required to prepare a randomized trial of therapeutic hypothermia on neurobehavioral outcomes in children after in-hospital cardiac arrest. Retrospective cohort study. Fifteen children's hospitals associated with Pediatric Emergency Care Applied Research Network. Patients between 1 day and 18 years of age who had cardiopulmonary resuscitation and received chest compressions for >1 min, and had a return of circulation for >20 mins. None. A total of 353 patients met entry criteria; 172 (48.7%) survived to hospital discharge. Among survivors, 132 (76.7%) had good neurologic outcome documented by Pediatric Cerebral Performance Category scores. After adjustment for age, gender, and first documented cardiac arrest rhythm, variables available before and during the arrest that were independently associated with increased mortality included pre-existing hematologic, oncologic, or immunologic disorders, genetic or metabolic disorders, presence of an endotracheal tube before the arrest, and use of sodium bicarbonate during the arrest. Variables associated with decreased mortality included postoperative cardiopulmonary resuscitation. Extending the time frame to include variables available before, during, and within 12 hours following arrest, variables independently associated with increased mortality included the use of calcium during the arrest. Variables associated with decreased mortality included higher minimum blood pH and pupillary responsiveness. Many factors are associated with hospital mortality among children after in-hospital cardiac arrest and return of circulation. Such factors must be considered when designing a trial of therapeutic hypothermia after cardiac arrest in pediatric patients.