Association between Intermittent Hypoxemia and NICU Length of Stay in Preterm Infants.

INTRODUCTION: Length of hospitalization varies widely in preterm infants and can be affected by multiple maternal and neonatal factors including respiratory instability. Therefore, we aimed to determine the association between postnatal intermittent hypoxemia (IH) and prolonged hospitalization. METHODS: This prospective single-center cohort study followed infants born at <31 weeks of gestational age through 2 years corrected age with detailed oxygen saturation data captured from days 7 to 30 of age. RESULTS: 51/164 (31%) of infants were discharged after 400/7 weeks of corrected gestational age (CGA). A greater average daily number of IH events (OR per 10 events/day 1.33 [95% CI 1.03-1.72]), duration of events (OR per minute 1.14 [1.07-1.21]), and percent time with oxygen saturation <80% (OR per percent 1.88 [1.25-2.85]) on days 7-30 of age were all significantly associated with prolonged hospitalization past 400/7 weeks CGA. In survival analyses, infants with a greater average daily number of IH events (HR per 10 events/day 0.89 [0.81-0.98]), percent time with oxygen saturation <80% (HR per percent 0.79 [0.67-0.94]), and duration of events (HR per minute 0.93 [0.91-0.95]) on days 7-30 of age all had significantly lower probability of earlier discharge. In addition, there was a significant interaction with gestational age; the association between IH and prolonged hospitalization was stronger in more mature infants (p = 0.024). CONCLUSIONS: Physiological instability on days 7-30 of age, as manifested by IH, is significantly associated with prolonged hospitalization. IH likely represents both a marker of initial severity of illness and the beginning of biological cascades, leading to prematurity-associated morbidities.

Hypoxemia events in preterm neonates are associated with urine oxidative biomarkers.

BACKGROUND: Intermittent hypoxemia (IH) events are common in preterm neonates and are associated with adverse outcomes. Animal IH models can induce oxidative stress. We hypothesized that an association exists between IH and elevated peroxidation products in preterm neonates. METHODS: Time in hypoxemia, frequency of IH, and duration of IH events were assessed from a prospective cohort of 170 neonates (<31 weeks gestation). Urine was collected at 1 week and 1 month. Samples were analyzed for lipid, protein, and DNA oxidation biomarkers. RESULTS: At 1 week, adjusted multiple quantile regression showed positive associations between several hypoxemia parameters with various individual quantiles of isofurans, neurofurans, dihomo-isoprostanes, dihomo-isofurans, and ortho-tyrosine and a negative correlation with dihomo-isoprostanes and meta-tyrosine. At 1 month, positive associations were found between several hypoxemia parameters with quantiles of isoprostanes, dihomo-isoprostanes and dihomo-isofurans and a negative correlation with isoprostanes, isofurans, neuroprostanes, and meta-tyrosine. CONCLUSIONS: Preterm neonates experience oxidative damage to lipids, proteins, and DNA that can be analyzed from urine samples. Our single-center data suggest that specific markers of oxidative stress may be related to IH exposure. Future studies are needed to better understand mechanisms and relationships to morbidities of prematurity. IMPACT: Hypoxemia events are frequent in preterm infants and are associated with poor outcomes. The mechanisms by which hypoxemia events result in adverse neural and respiratory outcomes may include oxidative stress to lipids, proteins, and DNA. This study begins to explore associations between hypoxemia parameters and products of oxidative stress in preterm infants. Oxidative stress biomarkers may assist in identifying high-risk neonates.

Pilot Survey: Police Understanding of Autism Spectrum Disorder.

This piliot study assessed the experiences of police officers related to persons with Autism Spectrum Disorder (ASD) via a survey assessing prior experience, comfort, knowledge, and ability to identify autistic persons. Fifty-one officers completed the survey: 52.9% reported previous ASD training, 34.8% reported personal experience with ASD, and 56.9% endorsed low overall knowledge of ASD. Officers reported neutral comfort (mean 3.24) and moderate practical knowledge (mean 3.74) [Likert scale 1-5; 5 = highest]. Those with previous training or with personal experience reported higher comfort and knowledge. Those with personal experience were more likely to recognize features of ASD in clinical vignettes. Further study is necessary to understand what additional training about ASD may be helpful to police officers.

Social determinants of participant recruitment and retention in a prospective cohort study of pediatric mild traumatic brain injury.

Background: Prior studies have shown poor recruitment and retention of minoritized groups in clinical trials. Objective: To examine several social determinants as predictors of consent to participate and retention as part of a prospective, longitudinal cohort study of children 8-16 with either mild traumatic brain injury (mild TBI) or orthopedic injury (OI). Methods: Children and families were recruited during acute visits to emergency departments (ED) in two large children's hospitals in the midwestern United States for a prospective, longitudinal cohort study of children 8-16 with either mild TBI or OI. Results: A total of 588 (mild TBI = 307; OI = 281) eligible children were approached in the ED and 315 (mild TBI = 195; OI = 120) were consented. Children who consented did not differ significantly from those who did not consent in sex or age. Consent rates were higher among Black (60.9%) and multi-racial (76.3%) children than white (45.3%) children. Among the 315 children who consented, 217 returned for a post-acute assessment (mild TBI = 143; OI = 74), a retention rate of 68.9%. Participants who were multi-racial (96.6%) or white (79.8%) were more likely to return for the post-acute visit than those who were Black (54.3%). Conclusions: Racial differences exist in both recruitment and retention of participants in a prospective, longitudinal cohort of children with mild TBI or OI. Further work is needed to understand these differences to ensure equitable participation of minoritized groups in brain injury research.

Sex Differences in the Outcomes of Mild Traumatic Brain Injury in Children Presenting to the Emergency Department.

Sex differences after concussion have been studied largely in high school and college athletes, often without reference to comparison groups without concussion. This study sought to evaluate sex differences in outcomes among all children and adolescents presenting to the Emergency Department (ED) for either mild traumatic brain injury (TBI) or orthopedic injury (OI), regardless of mechanism of injury. The study involved a concurrent cohort, prospective study design with longitudinal follow-up. Participants were eight to 16 years old with mild TBI (n = 143) or OI (n = 73). They were recruited and completed an initial assessment at EDs at two children's hospitals. They returned for a post-acute assessment within two weeks of injury and for follow-up assessments at three and six months. Outcomes included child and parent proxy ratings of somatic and cognitive symptoms, and standardized tests of cognitive functioning and balance. Sex did not moderate group differences in balance, fluid or crystallized cognitive ability, or child or parent proxy ratings of somatic or cognitive symptoms. Both parents and children reported more somatic symptoms in girls than boys, but in both groups. Compared with the OI group, the mild TBI group showed significantly lower fluid cognitive ability at the post-acute assessment and significantly higher somatic and cognitive symptoms according to both child and parent proxy ratings across the first two weeks post-injury. The results suggest that sex does not moderate the outcomes of mild TBI in a pediatric ED population. Previous research pointing to sex differences after concussion may reflect the lack of comparison groups, as well as a focus on adolescents and young adults and sport-related concussion. Future research should investigate whether sex moderates the outcomes of pediatric mild TBI in adolescents but not in pre-adolescent children.

Normative and Psychometric Characteristics of the Health and Behavior Inventory Among Children With Mild Orthopedic Injury Presenting to the Emergency Department: Implications for Assessing Postconcussive Symptoms Using the Child Sport Concussion Assessment Tool 5th Edition (Child SCAT5).

OBJECTIVE: The study sought to present normative and psychometric data and reliable change formulas for the Health and Behavior Inventory (HBI), a postconcussive symptom rating scale embedded in the Child Sport Concussion Assessment Tool 5th edition (Child SCAT5). DESIGN: Prospective cohort study with longitudinal follow-up. SETTING: Pediatric emergency departments (EDs). PARTICIPANTS: As part of 3 studies conducted in the United States and Canada between 2001 and 2019, 450 children aged 8 to 16 years with mild orthopedic injuries were recruited during ED visits and assessed postacutely (M = 9.38 days, SD = 3.31) and 1 month and 3 months postinjury. Independent variables were rater (child vs parent), sex, and age at injury. MAIN OUTCOME MEASURE: HBI ratings. METHODS: Children and parents rated children's symptoms at each time point; parents also rated children's preinjury symptoms retrospectively. Normative data (mean, SD, skewness, kurtosis, and percentiles) were computed for child and parent ratings. Internal consistency was assessed using Cronbach alpha (α), and test-retest reliability and interrater agreement were assessed with intraclass correlations (ICCs). Reliable change formulas were computed using linear regression and mixed models. RESULTS: HBI ratings were positively skewed. Mean ratings and percentiles were stable over time. Child and parent ratings demonstrated good-to-excellent internal consistency (α 0.76-0.94) and moderate-to-good test-retest reliability (ICC 0.51-0.76 between adjacent assessments). However, parent-child agreement was poor to moderate (ICC 0.31-0.69). CONCLUSIONS: The HBI demonstrates acceptable normative and psychometric characteristics. Modest parent-child agreement highlights the importance of multiple informants when assessing postconcussive symptoms. The results will facilitate the use of the HBI in research and clinical practice.

Cognitive Outcomes in Children with Mild Traumatic Brain Injury: An Examination Using the National Institutes of Health Toolbox Cognition Battery.

This study is the first to examine cognitive outcomes after pediatric mild TBI using the National Institutes of Health Toolbox Cognition Battery (NIHTB-CB), a computerized cognitive test battery. The NIHTB-CB includes two complex measures of attention and executive function that allow differentiation of accuracy and response speed. We compared performance on the NIHTB-CB among children 8-16 years of age with mild TBI (n = 143) versus children with orthopedic injuries (OIs; n = 74) recruited in emergency departments and followed for 6 months post-injury. Mixed-model analyses showed that the mild TBI group showed significantly lower Fluid Cognition composite scores than the OI group at 10 days (group intercept, p = 0.018); the magnitude of group differences declined modestly over time (group × time interaction, p = 0.055). Effect sizes were d = 0.34 at 10 days post-injury, d = 0.27 at 3 months, and d = 0.10 at 6 months. No significant effects of group or time were found for the Crystallized Cognition composite. Analyses of Fluid Cognition subtests indicated that children with mild TBI displayed deficits for as long as 3 months on measures of attention and executive function (e.g., cognitive flexibility, inhibitory control), but not on measures of explicit memory, working memory, or processing speed. The poorer performance of the mild TBI group on measures of attention and executive function was attributable largely to slowed reaction time, not decreased accuracy. The findings suggest that children with mild TBI demonstrate persistent deficits in fluid cognition that are most apparent on tasks that combine demands for both speed and executive function.

Radiologic common data elements rates in pediatric mild traumatic brain injury.

OBJECTIVE: The nosology for classifying structural MRI findings following pediatric mild traumatic brain injury (pmTBI) remains actively debated. Radiologic common data elements (rCDE) were developed to standardize reporting in research settings. However, some rCDE are more specific to trauma (probable rCDE). Other more recently proposed rCDE have multiple etiologies (possible rCDE), and may therefore be more common in all children. Independent cohorts of patients with pmTBI and controls were therefore recruited from multiple sites (New Mexico and Ohio) to test the dual hypothesis of a higher incidence of probable rCDE (pmTBI > controls) vs similar rates of possible rCDE on structural MRI. METHODS: Patients with subacute pmTBI (n = 287), matched healthy controls (HC; n = 106), and orthopedically injured (OI; n = 71) patients underwent imaging approximately 1 week postinjury and were followed for 3-4 months. RESULTS: Probable rCDE were specific to pmTBI, occurring in 4%-5% of each sample, rates consistent with previous large-scale CT studies. In contrast, prevalence rates for incidental findings and possible rCDE were similar across groups (pmTBI vs OI vs HC). The prevalence of possible rCDE was also the only finding that varied as a function of site. Possible rCDE and incidental findings were not associated with postconcussive symptomatology or quality of life 3-4 months postinjury. CONCLUSION: Collectively, current findings question the trauma-related specificity of certain rCDE, as well how these rCDE are radiologically interpreted. Refinement of rCDE in the context of pmTBI may be warranted, especially as diagnostic schema are evolving to stratify patients with structural MRI abnormalities as having a moderate injury.

Longitudinal relationships between early adolescent family functioning and youth adjustment: an examination of the moderating role of very low birth weight.

OBJECTIVE: To examine longitudinal relations between early adolescent family conflict and late adolescent psychosocial adjustment, and the moderating role of low birth weight. METHODS: Three groups of adolescents (48 with birth weight <750 g, 46 with birth weight 750-1499 g, and 51 term-born controls) and their parents completed ratings of family conflict at age 11 (Time 1). Parent, teacher, and youth reports of psychosocial functioning were obtained at ages 11 and 17 (Time 2). RESULTS: Birth weight moderated the relationship between Time 1 adolescent-perceived conflict and change in adolescent behavioral functioning. For adolescents with histories of <750 g birth weight, adolescent-perceived conflict predicted less adaptive changes in teacher-reported total behavior problems and externalizing problems. CONCLUSIONS: Small disruptions to the parent-child relationship have negative implications for the later well-being of adolescents with extreme levels of low birth weight. Clinical attention to resolving early adolescent conflict may promote adaptive adjustment.

Long-term parental and family adaptation following pediatric brain injury.

OBJECTIVE: To determine whether parents of children with traumatic brain injuries (TBI) report increased injury-related burden, distress, and family dysfunction and to examine the effects of attrition on the results. METHODS: Children with severe TBI, moderate TBI, and orthopedic injuries were followed at six time points from baseline to 6 years after injury. Parents completed measures of injury-related burden, psychological distress, and family functioning at each assessment. Mixed model analysis was used to examine long-term changes. RESULTS: Attrition was higher among families in the severe TBI group with lower burden thereby amplifying group differences. The severe TBI group reported higher injury-related burden over time after injury than the other groups. Family functioning was moderated by social resources. Families of children with severe TBI and low resources reporting deteriorating functioning over the follow-up interval. CONCLUSIONS: Although environmental advantages moderate long-term effects on family functioning, families of children with severe TBI experience long-standing injury-related burden.

Interpersonal stressors and resources as predictors of parental adaptation following pediatric traumatic injury.

The authors examined the relationship of preinjury interpersonal resources and stressors to parental adaptation following pediatric traumatic brain injury (TBI) and orthopedic injury. Parents of children with severe TBI (n = 53), moderate TBI (n = 56), and orthopedic injuries (n = 80) were assessed soon after injury, 6 and 12 months after the initial evaluation, and at an extended follow-up with a mean of 4 years postinjury. General linear model analyses provide support for both main and moderating effects of stressors and resources on parental adjustment. Support from friends and spouse was associated with less psychological distress, whereas family and spouse stressors were associated with greater distress. The results also reveal a marked decline in injury-related stress over follow-up for families in the severe TBI group who reported a combination of high stressors and high resources. The decline suggests that interpersonal resources attenuated long-term family burden because of severe TBI. The findings are discussed in terms of their implications for intervention following TBI.

Longitudinal outcomes of very low birth weight: neuropsychological findings.

To investigate the effects of very low birth weight (VLBW, &1500 g) on the development of neuropsychological skills, we assessed 67 children with birth weight <750 g, 64 with birth weight 750-1499 g, and 67 term-born controls. Growth modeling of raw scores from mean ages 7-14 years revealed persistent VLBW sequelae. Even when adjusting for IQ, the <750 g group scored more poorly than the term-born group on measures of language processing, verbal list learning, and perceptual-motor and organizational abilities. This group also made slower age-related progress than the control group on tests of perceptual-motor and executive functions. Environmental factors moderated group differences in change on other cognitive measures. These results revealed further evidence for slower skill development in both VLBW groups relative to controls, as well as"catch-up" growth in the 750-1499 g group on some measures. The findings suggest age-related changes in the cognitive sequelae of VLBW that depend on the skill assessed, the degree of VLBW, and environmental factors.

Parent-adolescent interactions after traumatic brain injury: their relationship to family adaptation and adolescent adjustment.

OBJECTIVE: To examine changes in parent-adolescent interactions after traumatic brain injury (TBI) and their relationship to parent and adolescent adjustment. DESIGN: Concurrent cohort, cross-sectional study. Analysis of variance was used to examine group differences and regression analysis to assess associations between interactional measures and concurrent adjustment. SETTING: Four hospitals in north-central Ohio. PARTICIPANTS: Adolescents with severe TBI (25), moderate TBI (22), and orthopedic injuries (35) and their parents. MAIN OUTCOME MEASURES: Observer ratings of parent-adolescent interactions, Conflict Behavior Questionnaire (CBQ), Family Burden of Injury Interview (FBII), Brief Symptom Inventory (BSI), Family Assessment Device (FAD), Child Behavior Checklist, Vineland Adaptive Behavior Scale, and Children's Depression Inventory. RESULTS: No group differences were found on ratings of parent-adolescent interaction or the parent or child CBQ. However, observed criticism/coldness and self-rated conflict had stronger associations with the FBII, BSI, and FAD in the severe TBI group than in the orthopedic injury group, suggesting that conflict is more disruptive after TBI. Ratings of criticism/coldness and parent and adolescent CBQ scores were also associated with parent and adolescent adjustment. CONCLUSIONS: Results support the utility of observational measures in assessing dyadic interactions after TBI.

A prospective study of long-term caregiver and family adaptation following brain injury in children.

OBJECTIVE: We examined long-term differences in family adaptation following traumatic brain injuries (TBI) and orthopedic injuries. DESIGN: Families of children with severe TBI (n = 53), moderate TBI (n = 56), and orthopedic injuries (n = 80) were assessed at baseline, 6 months, and 12 months post injury and at an extended follow-up an average of 4.1 years post injury. Caregiver and family outcomes were examined using mixed model analysis. RESULTS: Patterns of adaptation over time varied across groups but indicated long-standing injury-related stress and burden in the severe TBI group. CONCLUSIONS: Severe TBI results in persistent caregiver stress for a substantial proportion of families.