MRD at the end of induction and EFS in T-cell lymphoblastic lymphoma: Children's Oncology Group trial AALL1231.

ABSTRACT: Defining prognostic variables in T-lymphoblastic lymphoma (T-LL) remains a challenge. AALL1231 was a Children's Oncology Group phase 3 clinical trial for newly diagnosed patients with T acute lymphoblastic leukemia or T-LL, randomizing children and young adults to a modified augmented Berlin-Frankfurt-Münster backbone to receive standard therapy (arm A) or with addition of bortezomib (arm B). Optional bone marrow samples to assess minimal residual disease (MRD) at the end of induction (EOI) were collected in T-LL analyzed to assess the correlation of MRD at the EOI to event-free survival (EFS). Eighty-six (41%) of the 209 patients with T-LL accrued to this trial submitted samples for MRD assessment. Patients with MRD <0.1% (n = 75) at EOI had a superior 4-year EFS vs those with MRD ≥0.1% (n = 11) (89.0% ± 4.4% vs 63.6% ± 17.2%; P = .025). Overall survival did not significantly differ between the 2 groups. Cox regression for EFS using arm A as a reference demonstrated that MRD EOI ≥0.1% was associated with a greater risk of inferior outcome (hazard ratio, 3.73; 95% confidence interval, 1.12-12.40; P = .032), which was independent of treatment arm assignment. Consideration to incorporate MRD at EOI into future trials will help establish its value in defining risk groups. CT# NCT02112916.

Considerations and Determinants of Discharge Decisions among Prenatal Substance Exposed Infants.

Limited research has examined a comprehensive set of predictors when evaluating discharge placement decisions for infants exposed to substances prenatally. Using a previously validated medical record data extraction tool, the current study examined prenatal substance exposure, infant intervention (i.e., pharmacologic, or non-pharmacologic), and demographic factors (e.g., race and ethnicity and rurality) as predictors of associations with discharge placement in a sample from a resource-poor state (N = 136; 69.9% Non-Hispanic White). Latent class analysis (LCA) was used to examine whether different classes emerged and how classes were differentially related to discharge placement decisions. Logistic regressions were used to determine whether each predictor was uniquely associated with placement decisions. Results of the LCA yielded a two-class solution comprised of (1) a Low Withdrawal Risk class, characterized by prenatal exposure to substances with low risk for neonatal abstinence syndrome (NAS) and non-pharmacologic intervention, and (2) a High Withdrawal Risk class, characterized by a high risk of NAS and pharmacologic intervention. Classes were not related to discharge placement decisions. Logistic regressions demonstrated that meth/amphetamine use during pregnancy was associated with greater odds of out of home placement above other substance types. Future research should replicate and continue examining the clinical utility of these classes.

Assessing attitudes towards pediatric research participation across diverse populations: Psychometric properties of a novel tool.

BACKGROUND: Clinical trials play a crucial role in advancing medical knowledge and improving health outcomes. However, there is a recognized need for greater representation of marginalized groups to ensure that research findings can be generalized and effectively applied to all individuals. While the Pediatric Research Participation Questionnaire (PRPQ) was developed to assist pediatric clinical trials research by identifying benefits and barriers to research participation among children with chronic medical conditions, there is still limited insight into the structure of the PRPQ when administered in diverse samples, including the general pediatric population. Therefore, the current study examined the factor structure of the PRPQ in a general pediatric population to investigate whether rural-urban differences exist in the PRPQ factor structure. METHODS: Caregivers (N = 600) of children under age 18 completed the PRPQ in a population-based survey in Mississippi. Sampling was stratified to ensure equal representation in rural (n = 300) and urban areas (n = 300). Exploratory and confirmatory factor analyses were conducted to determine the factor structure of the PRPQ. RESULTS: A five-factor structure was identified, compromising: social pressure, direct benefit, reasons for participation, mistrust in research/researchers, reasons against participation. While results were similar among urban participants, a three-factor structure emerged for rural participants. CONCLUSIONS: This study contributes to the broader understanding of research participation among underrepresented groups. The findings suggest that clinical researchers should consider tailoring recruitment strategies to increase clinical trial participation among children in rural areas. Understanding factors that influence pediatric research participation, particularly among marginalized communities, is crucial for developing effective recruitment and retention strategies.

Assessment of Psychosocial and Neonatal Risk Factors for Trajectories of Behavioral Dysregulation Among Young Children From 18 to 72 Months of Age.

Importance: Emotional and behavioral dysregulation during early childhood are associated with severe psychiatric, behavioral, and cognitive disorders through adulthood. Identifying the earliest antecedents of persisting emotional and behavioral dysregulation can inform risk detection practices and targeted interventions to promote adaptive developmental trajectories among at-risk children. Objective: To characterize children's emotional and behavioral regulation trajectories and examine risk factors associated with persisting dysregulation across early childhood. Design, Setting, and Participants: This cohort study examined data from 20 United States cohorts participating in Environmental influences on Child Health Outcomes, which included 3934 mother-child pairs (singleton births) from 1990 to 2019. Statistical analysis was performed from January to August 2022. Exposures: Standardized self-reports and medical data ascertained maternal, child, and environmental characteristics, including prenatal substance exposures, preterm birth, and multiple psychosocial adversities. Main Outcomes and Measures: Child Behavior Checklist caregiver reports at 18 to 72 months of age, with Dysregulation Profile (CBCL-DP = sum of anxiety/depression, attention, and aggression). Results: The sample included 3934 mother-child pairs studied at 18 to 72 months. Among the mothers, 718 (18.7%) were Hispanic, 275 (7.2%) were non-Hispanic Asian, 1220 (31.8%) were non-Hispanic Black, 1412 (36.9%) were non-Hispanic White; 3501 (89.7%) were at least 21 years of age at delivery. Among the children, 2093 (53.2%) were male, 1178 of 2143 with Psychosocial Adversity Index [PAI] data (55.0%) experienced multiple psychosocial adversities, 1148 (29.2%) were exposed prenatally to at least 1 psychoactive substance, and 3066 (80.2%) were term-born (≥37 weeks' gestation). Growth mixture modeling characterized a 3-class CBCL-DP trajectory model: high and increasing (2.3% [n = 89]), borderline and stable (12.3% [n = 479]), and low and decreasing (85.6% [n = 3366]). Children in high and borderline dysregulation trajectories had more prevalent maternal psychological challenges (29.4%-50.0%). Multinomial logistic regression analyses indicated that children born preterm were more likely to be in the high dysregulation trajectory (adjusted odds ratio [aOR], 2.76; 95% CI, 2.08-3.65; P < .001) or borderline dysregulation trajectory (aOR, 1.36; 95% CI, 1.06-1.76; P = .02) vs low dysregulation trajectory. High vs low dysregulation trajectories were less prevalent for girls compared with boys (aOR, 0.60; 95% CI, 0.36-1.01; P = .05) and children with lower PAI (aOR, 1.94; 95% CI, 1.51-2.49; P < .001). Combined increases in PAI and prenatal substance exposures were associated with increased odds of high vs borderline dysregulation (aOR, 1.28; 95% CI, 1.08-1.53; P = .006) and decreased odds of low vs high dysregulation (aOR, 0.77; 95% CI, 0.64-0.92; P = .005). Conclusions and Relevance: In this cohort study of behavioral dysregulation trajectories, associations were found with early risk factors. These findings may inform screening and diagnostic practices for addressing observed precursors of persisting dysregulation as they emerge among at-risk children.

The Influence of Mediators on the Relationship Between Antenatal Opioid Agonist Exposure and the Severity of Neonatal Opioid Withdrawal Syndrome.

OBJECTIVES: (1) To evaluate the direct (un-mediated) and indirect (mediated) relationship between antenatal exposure to opioid agonist medication as treatment for opioid use disorder (MOUD) and the severity of neonatal opioid withdrawal syndrome (NOWS), and (2) to understand the degree to which mediating factors influence the direct relationship between MOUD exposure and NOWS severity. METHODS: This cross-sectional study includes data abstracted from the medical records of 1294 opioid-exposed infants (859 MOUD exposed and 435 non-MOUD exposed) born at or admitted to one of 30 US hospitals from July 1, 2016, to June 30, 2017. Regression models and mediation analyses were used to evaluate the relationship between MOUD exposure and NOWS severity (i.e., infant pharmacologic treatment and length of newborn hospital stay (LOS)) to identify potential mediators of this relationship in analyses adjusted for confounding factors. RESULTS: A direct (un-mediated) association was found between antenatal exposure to MOUD and both pharmacologic treatment for NOWS (aOR 2.34; 95%CI 1.74, 3.14) and an increase in LOS (1.73 days; 95%CI 0.49, 2.98). Delivery of adequate prenatal care and a reduction in polysubstance exposure were mediators of the relationship between MOUD and NOWS severity and as thus, were indirectly associated with a decrease in both pharmacologic treatment for NOWS and LOS. CONCLUSIONS FOR PRACTICE: MOUD exposure is directly associated with NOWS severity. Prenatal care and polysubstance exposure are potential mediators in this relationship. These mediating factors may be targeted to reduce the severity of NOWS while maintaining the important benefits of MOUD during pregnancy.

Impact of COVID-19 on Families with Children: Examining Sociodemographic Differences.

OBJECTIVE: The COVID-19 pandemic has exacerbated differences related to employment and family psychological health. However, empirical evidence examining COVID-19-linked differences concerning children and families remains scant. This study addresses this gap by examining sociodemographic differences associated with COVID-19 on family access to resources and family psychological health. METHOD: A telephone survey of 600 caregivers living in Mississippi was conducted from August 2020 to April 2021. Caregivers answered questions about levels of worry regarding themselves or their child contracting COVID-19 and impact of the pandemic on household income, access to resources, and family psychological health. RESULTS: Multivariate models demonstrated that Black caregivers (n = 273; 45.5%) had increased odds of agreeing that they worry about contracting COVID-19 (odds ratio [OR] = 2.57). Furthermore, as caregiver reported household annual income decreased, caregivers had increased odds of agreeing that they worry about contracting COVID-19 (OR = 1.16), lost job-related income (OR = 1.14), and had a hard time obtaining resources (OR = 1.16) because of the pandemic. No significant differences related to rural or urban residence were observed. CONCLUSION: The findings highlight the need for pragmatic responses that are attuned to differences by providing more equitable access to resources for families. The findings suggest that strategies addressing family worry, obtaining job-related income support, and helping families obtain tangible resources may positively affect family psychological health. As population changes in vaccination rates and COVID variants emerge, reassessment of family and community impact seems indicated. Limitations and future research directions are discussed.

Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma.

PURPOSE: To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL. PATIENTS AND METHODS: Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients. RESULTS: AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, P = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, P = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% v 86.4% ± 4.0%; P = .041); and 4-year OS (78.3% ± 4.9% v 89.5% ± 3.6%; P = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS (P = .412) and OS (P = .600). CONCLUSION: Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse.

Pediatric Cancer Survivorship: Impact Upon Hair Cortisol Concentration and Family Functioning.

A clearer understanding of the association between a biomarker of long-term stress reactivity and family functioning among pediatric cancer survivors may guide both survivorship research and clinical practice. The current study examined the relationship between a long-term measure of hypothalamic-pituitary-adrenal (HPA) activity (cortisol concentration; CORTHAIR) and parent-reported family functioning (Family Environment Scale; FES) in a cross-sectional sample of survivors (n = 26) and controls (n = 53). Child CORTHAIR was not different in survivors and controls, though treatment severity was significantly related to child survivor CORTHAIR. Child CORTHAIR and parent CORTHAIR were positively correlated. Cancer survivor parents reported greater FES Organization. Child CORTHAIR was inversely associated with FES Independence, while parent CORTHAIR was inversely correlated with FES Organization. Parent CORTHAIR and FES Independence were significant and unique predictors of child CORTHAIR. Our results provide preliminary evidence for a relationship between a stress biomarker, child CORTHAIR, and family functioning among pediatric cancer survivors and controls.

Predicting Young Adult Tobacco, Drug and Alcohol Use Among Participants in the CAMP Trial.

The development of substance abuse in youth with asthma have seldom been examined with longitudinal research. The prospective and well-characterized CAMP cohort provides outcome data on youth with asthma over 13 years. This manuscript seeks to determine the contributions of asthma features and child behavioral/emotional functioning to subsequent tobacco, alcohol, and drug use in early adulthood. Childhood smoking exposures as well as parent report and youth report of substance use were prospectively assessed concurrently with assessments of asthma symptoms, study medication, and lung development. Logistic regression models evaluated predictors of adolescent and young adult tobacco, alcohol, and drug use. Use of tobacco products was reported by 33% of youth with mild/moderate asthma. Tobacco use was significantly associated with self-reported externalizing behaviors. Early life passive smoke exposure, especially in utero exposure, makes a significant contribution to tobacco use (OR1.58). Greater risk for tobacco use is conveyed by self-reported externalizing behaviors, which are consistently robust predictors of any future use of tobacco products, alcohol and drugs. These findings provide evidence for health care providers to use routine behavioral screening in youth with asthma.

Co-occurring attention-deficit/hyperactivity disorder and anxiety disorders differentially affect males and females with autism.

OBJECTIVE: To examine overlap and divergence of symptomatology in Autism Spectrum Disorder (ASD) with and without co-occurring Attention/Deficit Hyperactivity Disorder (ADHD) and/or Anxiety Disorder by age and sex. METHOD: Participants included 25,078 individuals registered in the SPARK cohort, age 6-18 years. SPARK participation includes online consent and registration, as well as parent-reported ASD, ADHD, and Anxiety Disorder diagnoses, developmental, medical, and intervention history, and standardized rating scales. Individuals with ASD, ASD + ADHD, ASD + Anxiety, or ASD + ADHD + Anxiety were compared on measures assessing social communication, restricted and repetitive behaviors (RRBs), and motor functioning, and differences between male and female profiles were examined. RESULTS: Significant differences in symptom presentation between females/males, school-age/adolescent individuals, and by co-occurring conditions (ASD/ADHD/Anxiety) are apparent, and the impact of co-occurring conditions differed by age and sex. Most notably, school-age femaleswith ASD without co-occurring conditions present with significantly fewer concerns about social communication skills and have better motor skills, but have more prominent RRBs as compared to same-aged males with ASD alone; co-occurring conditions were associated with increased social communication problems and motor concerns, most consistently for school-age females. CONCLUSIONS: School-age females with ASD are at highest risk for underestimation of autism-related symptoms, including underestimation of symptoms beyond core ASD features (motor skills). Further, across ages, particular consideration should be given when probing for social communication symptoms, RRBs, and motor skills in females with ASD alone, as well as with co-occurring ADHD and/or Anxiety. For females with co-occurring symptoms and conditions, use of symptom-specific measures in lieu of omnibus measures should be considered.

Capacity Building for a New Multicenter Network Within the ECHO IDeA States Pediatric Clinical Trials Network.

Introduction: Research capacity building is a critical component of professional development for pediatrician scientists, yet this process has been elusive in the literature. The ECHO IDeA States Pediatric Clinical Trials Network (ISPCTN) seeks to implement pediatric trials across medically underserved and rural populations. A key component of achieving this objective is building pediatric research capacity, including enhancement of infrastructure and faculty development. This article presents findings from a site assessment inventory completed during the initial year of the ISPCTN. Methods: An assessment inventory was developed for surveying ISPCTN sites. The inventory captured site-level activities designed to increase clinical trial research capacity for pediatrician scientists and team members. The inventory findings were utilized by the ISPCTN Data Coordinating and Operations Center to construct training modules covering 3 broad domains: Faculty/coordinator development; Infrastructure; Trials/Research concept development. Results: Key lessons learned reveal substantial participation in the training modules, the importance of an inventory to guide the development of trainings, and recognizing local barriers to clinical trials research. Conclusions: Research networks that seek to implement successfully completed trials need to build capacity across and within the sites engaged. Our findings indicate that building research capacity is a multi-faceted endeavor, but likely necessary for sustainability of a unique network addressing high impact pediatric health problems. The ISPCTN emphasis on building and enhancing site capacity, including pediatrician scientists and team members, is critical to successful trial implementation/completion and the production of findings that enhance the lives of children and families.

Site-Level Variation in the Characteristics and Care of Infants With Neonatal Opioid Withdrawal.

BACKGROUND AND OBJECTIVES: Variation in pediatric medical care is common and contributes to differences in patient outcomes. Site-to-site variation in the characteristics and care of infants with neonatal opioid withdrawal syndrome (NOWS) has yet to be quantified. Our objective was to describe site-to-site variation in maternal-infant characteristics, infant management, and outcomes for infants with NOWS. METHODS: Cross-sectional study of 1377 infants born between July 1, 2016, and June 30, 2017, who were ≥36 weeks' gestation, with NOWS (evidence of opioid exposure and NOWS scoring within the first 120 hours of life) born at or transferred to 1 of 30 participating hospitals nationwide. Site-to-site variation for each parameter within the 3 domains was measured as the range of individual site-level means, medians, or proportions. RESULTS: Sites varied widely in the proportion of infants whose mothers received adequate prenatal care (31.3%-100%), medication-assisted treatment (5.9%-100%), and prenatal counseling (1.9%-75.5%). Sites varied in the proportion of infants with toxicology screening (50%-100%) and proportion of infants receiving pharmacologic therapy (6.7%-100%), secondary medications (1.1%-69.2%), and nonpharmacologic interventions including fortified feeds (2.9%-90%) and maternal breast milk (22.2%-83.3%). The mean length of stay varied across sites (2-28.8 days), as did the proportion of infants discharged with their parents (33.3%-91.1%). CONCLUSIONS: Considerable site-to-site variation exists in all 3 domains. The magnitude of the observed variation makes it unlikely that all infants are receiving efficient and effective care for NOWS. This variation should be considered in future clinical trial development, practice implementation, and policy development.

IDeA States Pediatric Clinical Trials Network for Underserved and Rural Communities.

The National Institutes of Health's Environmental Influences on Child Health Outcomes (ECHO) program aims to study high-priority and high-impact pediatric conditions. This broad-based health initiative is unique in the National Institutes of Health research portfolio and involves 2 research components: (1) a large group of established centers with pediatric cohorts combining data to support longitudinal studies (ECHO cohorts) and (2) pediatric trials program for institutions within Institutional Development Awards states, known as the ECHO Institutional Development Awards States Pediatric Clinical Trials Network (ISPCTN). In the current presentation, we provide a broad overview of the ISPCTN and, particularly, its importance in enhancing clinical trials capabilities of pediatrician scientists through the support of research infrastructure, while at the same time implementing clinical trials that inform future health care for children. The ISPCTN research mission is aligned with the health priority conditions emphasized in the ECHO program, with a commitment to bringing state-of-the-science trials to children residing in underserved and rural communities. ISPCTN site infrastructure is critical to successful trial implementation and includes research training for pediatric faculty and coordinators. Network sites exist in settings that have historically had limited National Institutes of Health funding success and lacked pediatric research infrastructure, with the initial funding directed to considerable efforts in professional development, implementation of regulatory procedures, and engagement of communities and families. The Network has made considerable headway with these objectives, opening two large research studies during its initial 18 months as well as producing findings that serve as markers of success that will optimize sustainability.

Self-reported and parent proxy reported functional impairment among pediatric cancer survivors and controls.

BACKGROUND: A unique and limiting component in the research on functional impairment among children has been the exclusive use of parent proxy reports about child functioning; and there is limited information regarding the impact of pediatric cancer treatment on children's day-to-day functioning and how this is related to neurocognitive functioning. The objective of the current study was to examine a novel measure of self-reported functional impairment, and explore the relationship between self-reported and parent-reported child functional impairment in pediatric cancer survivors compared to controls. METHODS: A cross-sectional cohort of survivors (n = 26) and controls (n = 53) were recruited. Survivors were off treatment an average of 6.35 years (SD = 5.38; range 1-15 years) and demonstrated an average "medium" Central Nervous System treatment intensity score. Participants completed measures of functional impairment (FI), intellectual assessment (RIST) and executive functions (NIH Examiner), while parents reported on children's functional impairment. RESULTS: Survivors were similar to controls in functional impairment. Regardless of group membership, self-reported FI was higher than parent-reported FI, although they were correlated and parent report of FI significantly predicted self-reported FI. Across groups, increased impairment was associated with four of seven Examiner scores. CONCLUSIONS: Research regarding self-reported functional impairment of cancer survivors and its association with parent-reported functional impairment and neurocognitive deficits has been limited. Our results suggest that self-reported FI appears to be a reasonable and viable outcome measure that corresponds with and adds incremental validity to parent reported FI. While low treatment intensity may confer relative sparing of functional impairment among survivors, children report higher FI levels than parents, suggesting that FI can be of clinical utility. In conclusion, pediatric cancer survivors should be screened for self-reported functional difficulties.

Longitudinal pain and pain interference in long-term survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

BACKGROUND: The objective of this study was to characterize the prevalence and risk of pain, pain interference, and recurrent pain in adult survivors of childhood cancer in comparison with siblings. METHODS: This study analyzed longitudinal data from survivors (n = 10,012; 48.7% female; median age, 31 years [range, 17-57 years]; median time since diagnosis, 23 years) and siblings (n = 3173) from the Childhood Cancer Survivor Study. Survivors were diagnosed between 1970 and 1986 at 1 of 26 participating sites. Associations between risk factors (demographics, cancer-related factors, and psychological symptoms) and pain, pain interference, and recurrent pain (5 years apart) were assessed with multinomial logistic regression. Path analyses examined cross-sectional associations between risk factors and pain outcomes. RESULTS: Twenty-nine percent of survivors reported moderate to severe pain, 20% reported moderate to extreme pain interference, and 9% reported moderate to severe recurrent pain. Female sex, a sarcoma/bone tumor diagnosis, and severe/life-threatening chronic medical conditions were associated with recurrent pain. Depression and anxiety were associated with increased risk for all pain outcomes. Poor vitality mediated the effects of anxiety on high pain and pain interference (root mean square error of approximation, 0.002). CONCLUSIONS: A large proportion of adult survivors report moderate to severe pain and pain interference more than 20 years after their diagnosis. Increased screening and early intervention for pain interference and recurrent pain are warranted.

The contribution of neurocognitive functions to academic and psychological outcomes in pediatric cancer: A latent profile analysis.

This study aimed to identify the impact of neurocognitive functioning on academic and psychological domains using a novel person-centered latent profile analysis approach. We further examined the contribution of identified risk factors (e.g., age at diagnosis, treatment) on latent class membership. 101 pediatric oncology patients and survivors (M age = 11.2, 35.6% female; 47.5% African American; M time since diagnosis = 3.4 years) completed neuropsychological evaluations at a university medical center between February 2004 and June 2017. Neurocognitive, academic, and emotional-behavioral functioning were examined using validated measures. Discreet, homogenous neurocognitive subgroups (latent classes) were identified using latent profile analysis. Demographic and medical factors were evaluated as predictors of latent class. A 3-class model indicated excellent class separation (range: .00-.04) and homogeneity (range: .94-.99). Classes were distinguished by differential cognitive patterns. Class 2 (52%) and Class 3 (25%) displayed overall normative functioning; however, Class 3 displayed significantly poorer attention than the other two classes. Class 1 (23%) demonstrated Borderline neurocognitive, low average academic, and poorer emotional-behavioral and inhibition/executive control functioning. Class membership was predicted by race and whole brain radiation dose. Latent profile analysis identified discrete groups in neurocognitive functioning in this heterogeneous pediatric cancer population. Class membership was predicted by race, whole brain radiation dose, and referral source. Other medical variables (e.g., diagnosis, age at diagnosis) were not significant predictors of neurocognitive function in our sample.

Willingness of women to participate in obstetrical and pediatric research involving biobanks.

Use of biobanks for future genetic/genomic testing has increased. Biospecimens are increasingly being collected from infants/children; however, little is known about attitudes towards collection of biospecimens from postpartum women and their child. Using a hypothetical consent, this study investigated willingness to participate and attitudes, beliefs, and concerns related to consent materials requesting the biobanking genetic samples. A cross-sectional mixed methods design included women who reviewed a hypothetical consent related to biobanking genetic samples. Women were asked about their willingness to participate, followed by a focus group about biobanks and genetic/genomic testing. Post-focus group questionnaires assessed willingness to participate, the influence of study characteristics, and attitudes about genetic testing. Women (N = 37) were 29.0± 7.3 years of age (range 19-44); 51% had children and 28% were currently pregnant. A total of 46% were Hispanic (H), 38% were White non-Hispanic (WNH), and 16% were Native American (NA). Seventy-six percent (28/37) initially indicated that they would participate in the hypothetical study. Race and ethnicity impacted whether women would participate. Fewer NA women indicated that they would participate compared with H women and with WNH women (p < 0.02). Age, pregnancy status, having children, education level, insurance status, and income had no impact on participation decision and willingness to biobank specimens. NA and H women indicated that they were less likely than WNH women to agree to participate in a long-term biobank study. Given the importance of determining the genetic influence of health and disease, it is critical to attend to the questions and concerns of minority women regarding genetic studies.

Normalized Cortisol Reactivity Predicts Future Neuropsychological Functioning in Children With Mild/Moderate Asthma.

Cortisol reactivity to adrenocorticotropic hormone (ACTH) has been associated with neuropsychological processes including attention and memory in children with asthma. While cortisol reactivity to a psychological stressor is often considered a measure of current neuroendocrine functioning, this study examines the association of the cortisol reactivity and subsequent neuropsychological functioning. Using prospective data from the Childhood Asthma Management Program (CAMP), we explored the predictive ability of cortisol reactivity to ACTH and children's later attention and memory using traditional and an alternative cortisol reactivity (normalized cortisol) measures. Cortisol reactivity was assessed at study entry and 1-year follow-up, and neuropsychological functioning was assessed at 3-year follow-up. Cortisol reactivity was assessed through plasma cortisol concentrations collected at baseline (CORTBASELINE) and 30 min post-ACTH challenge (CORTPOST-A CTH). An alternative measure of cortisol reactivity was developed through post-ACTH stimulation cortisol, normalized by cortisol by baseline (CORTNORM -ACTH). CORT B ASELINE positively predicted year 3 attention, while CORTNORM -ACTH negatively predicted attention, suggesting convergence of cortisol variables in prediction of neuropsychological function. Year 1 CORTACTH positively predicted child memory at year 3; Year 1 CORTNORM-ACTH negatively predicted year 3 sustained attentions. These findings demonstrate that HPA reactivity, including the application of normalized cortisol reactivity, can predict subsequent neuropsychological functioning of children with mild to moderate asthma.

Prenatal Opioid Exposure: Neurodevelopmental Consequences and Future Research Priorities.

Neonatal opioid withdrawal syndrome (NOWS) has risen in prevalence from 1.2 per 1000 births in 2000 to 5.8 per 1000 births in 2012. Symptoms in neonates may include high-pitched cry, tremors, feeding difficulty, hypertonia, watery stools, and breathing problems. However, little is known about the neurodevelopmental consequences of prenatal opioid exposure in infancy, early childhood, and middle childhood. Even less is known about the cognitive, behavioral, and academic outcomes of children who develop NOWS. We review the state of the literature on the neurodevelopmental consequences of prenatal opioid exposure with a particular focus on studies in which NOWS outcomes were examined. Aiming to reduce the incidence of prenatal opioid exposure in the near future, we highlight the need for large studies with prospectively recruited participants and longitudinal designs, taking into account confounding factors such as socioeconomic status, institutional variations in care, and maternal use of other substances, to independently assess the full impact of NOWS. As a more immediate solution, we provide an agenda for future research that leverages the National Institutes of Health Environmental Influences on Child Health Outcomes program to address many of the serious methodologic gaps in the literature, and we answer key questions regarding the short- and long-term neurodevelopmental health of children with prenatal opioid exposure.