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.

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.

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.

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.

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.

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.

Reduction in Head Computed Tomography Ordering in Pediatric Emergency Patients: Effect of National Publication and Local Availability of Urgent Neurology Appointments.

OBJECTIVE: The objective of this study was to evaluate the effect of the Pediatric Emergency Care Applied Research Network (PECARN) blunt head trauma guidelines and implementation of urgent neurology follow-up (UNF) appointments on an observed decline in head computed tomography (CT) use for pediatric emergency department (PED) patients presenting with headache, seizure, and trauma. METHODS: Patients ages 0 to 18 years presenting to and discharged from an urban tertiary care PED with chief complaint of trauma, headache, and seizure between 2007 and 2013 were retrospectively included. The total number of head CTs obtained in the trauma, headache, and seizure groups was compared before and after the publication of the PECARN guidelines in 2009 and the implementation of urgent UNF within a week from PED discharge in 2011, respectively. RESULTS: Between 2007 and 2013, 24,434 encounters were identified with 2762 head CTs performed. Analysis demonstrated a decline in pediatric head CTs for trauma (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.8-2.2) after the publication of the PECARN study on blunt head trauma, for headache (OR, 1.4; 95% CI, 1.1-1.8) and seizure (OR, 1.9; 95% CI, 1.4-2.6) with UNF. However, cross comparison (headache and seizure with PECARN and trauma with UNF) also demonstrated similar significant declines. CONCLUSIONS: The decline in head CTs observed at our institution demonstrated a strong linear relationship, yet cannot be solely attributed to the PECARN blunt head trauma study or the implementation of UNF.

Risk of Concussion During Sports Versus Physical Education Among New Mexico Middle and High School Students.

OBJECTIVES: To measure the risk of concussion among New Mexico middle and high school students during both sports and physical education. METHODS: Athletic directors or athletic trainers in 147 schools were asked to report the number of concussions occurring during sports and physical education in the 2013 to 2014 school year. We calculated 1-year cumulative incidence rates. RESULTS: Of the 147 schools, 99 responded (67%). During the school year, 598 students were removed from athletics because of a concussion, a 1-year cumulative incidence of 3.5 per 100. The concussion rate during sports was 3.0: 3.5 for boys and 2.4 for girls (relative risk [RR] = 1.5; 95% confidence interval [CI] = 1.2, 1.7). An additional 335 students experienced concussions during physical education. Concussion rates during physical education were 60% higher than during sports (RR = 1.6; 95% CI = 1.4, 1.8). CONCLUSIONS: In our data, the risk of concussion was higher in physical education than in sports. This suggests that concussions should be tracked for a wide range of youth athletic activities, not just for sports. Monitoring cumulative incidence, in addition to other measures, may allow comparisons across schools and regions. More prevention efforts are needed.

A Conceptual Model and Clinical Framework for Integrating Mindfulness into Family Therapy with Adolescents.

Individual and group-based psychotherapeutic interventions increasingly incorporate mindfulness-based principles and practices. These practices include a versatile set of skills such as labeling and attending to present-moment experiences, acting with awareness, and avoiding automatic reactivity. A primary motivation for integrating mindfulness into these therapies is compelling evidence that it enhances emotion regulation. Research also demonstrates that family relationships have a profound influence on emotion regulation capacities, which are central to family functioning and prosocial behavior more broadly. Despite this evidence, no framework exists to describe how mindfulness might integrate into family therapy. This paper describes the benefits of mindfulness-based interventions, highlighting how and why informal mindfulness practices might enhance emotion regulation when integrated with family therapy. We provide a clinical framework for integrating mindfulness into family therapy, particularly as it applies to families with adolescents. A brief case example details sample methods showing how incorporating mindfulness practices into family therapy may enhance treatment outcomes. A range of assessment modalities from biological to behavioral demonstrates the breadth with which the benefits of a family-based mindfulness intervention might be evaluated.

Standard of Care for Neuropsychological Monitoring in Pediatric Neuro-Oncology: Lessons From the Children's Oncology Group (COG).

As the mortality of pediatric cancers has decreased, focus on neuropsychological morbidities of treatment sequelae have increased. Neuropsychological evaluations are essential diagnostic tools that assess cognitive functioning and neurobiological integrity. These tests provide vital information to support ongoing medical care, documenting cognitive morbidity and response to interventions. We frame standards for neuropsychological monitoring of pediatric patients with CNS malignancy or who received cancer-directed therapies involving the CNS and discuss billing for these services in the United States in the context of clinical research. We describe a cost-effective, efficient model of neuropsychological monitoring that may increases access to neuropsychological care.

Neuropsychological functioning of children treated for acute lymphoblastic leukemia: impact of whole brain radiation therapy.

OBJECTIVES: To provide one of the first prospective reports examining neuropsychological outcomes for children treated with 1800 cGy whole brain radiotherapy (WBRT) and prophylactic chemotherapy versus prophylactic chemotherapy alone for acute lymphoblastic leukemia (ALL). Acute and long-term neuropsychological toxicities associated with WBRT are compared. METHODS: This multisite study included 188 children, ages 4-21 years at enrollment, who were assessed with standardized neuropsychological tests at 9, 21, and 48 months after diagnosis with intermediate risk ALL. All participating children were receiving treatment on a parent study CCG105. RESULTS: Verbal intelligence (VIQ) scores for children receiving WBRT was significantly lower than VIQ for prophylactic chemotherapy at the 48-month time point (p < 0.05). A significant cross-level interaction between time since diagnosis and treatment condition was observed (p < 0.05). WBRT did not result in differences in PIQ; both groups of children demonstrated comparable increases in PIQ. Neuropsychological findings at 48 months after diagnosis indicated diminished performance in neuromotor, visual-motor coordination, and executive functioning for children receiving WBRT. Academic achievement was unaffected by WBRT at 4 years after diagnosis. CONCLUSIONS: The measurement of verbal and performance IQ as a primary endpoint in ALL clinical trials is critical to characterizing neuropsychological late effects. A trajectory of decline in neuropsychological functioning, specifically verbal IQ, was observed. Missing data within the trial occurred at random and did not impact results observed. The impact of WBRT becomes evident at 48 months after diagnosis, suggesting the need for long-term follow-up beyond the time frame typically used in Phase III trials.

Monitoring and Assessment of Neuropsychological Outcomes as a Standard of Care in Pediatric Oncology.

Central nervous system cancers or exposure to CNS-directed therapies increase risk for neuropsychological deficits. There are no accepted guidelines for assessment of neuropsychological functioning in this population. A multifaceted literature search was conducted and relevant literature reviewed to inform the guidelines. Studies of neuropsychological outcomes are widely documented in the pediatric oncology literature. There is strong evidence of need for neuropsychological assessment, but insufficient evidence to guide the timing of assessment, nor to recommend specific interventions. Children with brain tumors and others at high risk for neuropsychological deficits should be monitored and assessed for neuropsychological deficits.

Parental stress predicts functional outcome in pediatric cancer survivors.

BACKGROUND: Childhood cancer survivors are at risk for long-term neurocognitive and psychosocial morbidities. Research has seldom examined the relationship between these morbidities; thus, little empirical evidence exists concerning overall salience and how morbidities converge to impair day-to-day functioning. An increased understanding of functional impairment resulting from the pediatric cancer experience can inform early risk identification as well as sources for intervention. The purpose of this study was to characterize the frequency/severity of functional impairment and identify significant neurocognitive and psychosocial determinants of functional impairment. METHODS: Fifty child-parent dyads were enrolled. Children were aged 7-19 years who were at least 2 years postdiagnosis with leukemia/lymphoma and were recruited through a pediatric oncology late effects clinic. Parents completed questionnaires, rating their own adjustment to their child's illness as well as their child's level of functional impairment, while a brief neuropsychological exam was administered to children. RESULTS: Twenty-six percent of the sample evidenced clinically significant functional impairment. Regression analyses indicated that neurocognitive deficits did not predict functional impairment, whereas parental stress was a significant predictor. CONCLUSIONS: Although children demonstrated both neurocognitive deficits and functional impairments, results favor psychosocial factors, such as parental stress, as a predictor of overall functional impairment. The implications of this study suggest that late effects aggregate to impact day-to-day functioning in pediatric cancer survivor populations and parental stress may serve as a marker for heightened risk. The results suggest that broader functional domains, especially school and self-care domains, should be evaluated and considered when identifying potential targets for psychosocial interventions.

Prenatal Substance Exposure and Infant Discharge Placement: Results From the ACT NOW Study.

It is critical that researchers gather evidence of factors that identify infants at risk of out-of-home placement based on types of substance exposures and demographic characteristics. This study applied a validated medical record data extraction tool on data derived from a multi-site (N = 30) pediatric clinical trials network (ISPCTN) study of Neonatal Opioid Withdrawal (ACT NOW study). Participants included 1808 birthing parent-infant dyads with documented NOWS scoring or prenatal opioid exposure. Non-Hispanic White pregnant persons comprised the largest proportion of the sample (69.8%), followed by Non-Hispanic Black (11.6%), Non-Hispanic Multiracial and Other race (8.5%), and Hispanic (6.2%). Most notably, infant prenatal substance exposure across alcohol, cocaine, meth/amphetamine, and opioids, had the lowest possibility of discharging to parent(s). Additionally, latent class analysis identified distinct classes of substance use during pregnancy that were associated with different probabilities of discharging to parent(s). Specifically, less than half of infants (47%-49%) in the Poly-use and Meth/amphetamine classes were discharged to their parent(s). Severity of infant withdrawal symptoms influenced placement decisions within the Poly-use and Prescription Opioid classes. Findings can inform standard practices for increasing support for pregnant persons and substance-exposed infants including identification, subsequent referrals, communication with Child Protective Services, and plans of safe care.

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.

The feasibility and cost of neonatal screening for prenatal alcohol exposure by measuring phosphatidylethanol in dried blood spots.

BACKGROUND: Accurate confirmation of prenatal alcohol exposure (PAE) is required as a diagnostic criterion for the majority of children adversely affected by PAE who do not manifest the physical features associated with fetal alcohol syndrome. A number of ethanol biomarkers have been used to assess PAE, often with suboptimal results. The purpose of this study was to evaluate the feasibility and cost of PAE screening in newborns by measuring phosphatidylethanol (PEth) in dried blood spot (DBS) cards. METHODS: The feasibility of collecting an additional DBS card during routine newborn screening and the background prevalence of PAE were evaluated in a de-identified sample of newborn children delivered at the University of New Mexico Hospital. Electronic orders to collect DBS cards from newborns who continue to bleed after the routine newborn screen, glucose, or hematocrit testing were initiated for all infants delivered during a 4-week time frame. Specimens were sent to a contract laboratory for PEth analysis by liquid chromatography-tandem mass spectrometry. A cost analysis was conducted to compare the cost of PAE screening by PEth in DBS versus PEth in conventional blood specimens and by meconium fatty acid ethyl esters. RESULTS: From 230 collected cards, 201 (87.4%) had at least 1 full blood spot (amount sufficient for PEth analysis), and 6.5% had PEth >20 ng/ml indicative of potential PAE in late pregnancy. PAE screening by PEth in DBS is logistically simpler and less expensive compared with 2 other screening approaches. CONCLUSIONS: These results indicate that screening for PAE in DBS cards is a feasible procedure and that a majority of infants have enough blood after the routine heel prick to fill an additional card. Moreover, screening by PEth analysis from DBS cards is cost-efficient. The acceptability of such screening by parents and corresponding ethical issues remain to be investigated.

Children's Oncology Group's 2013 blueprint for research: behavioral science.

Behavioral science has long played a central role in pediatric oncology clinical service and research. Early work focused on symptom relief related to side effects of chemotherapy and pain management related to invasive medical procedures. As survival rates improved, the focused has shifted to examination of the psychosocial impact, during and after treatment, of pediatric cancer and its treatment on children and their families. The success of the clinical trials networks related to survivorship highlights an even more critical role in numerous domains of psychosocial research and care. Within the cooperative group setting, the field of behavioral science includes psychologists, social workers, physicians, nurses, and parent advisors. The research agenda of this group of experts needs to focus on utilization of psychometrically robust measures to evaluate the impact of treatment on children with cancer and their families during and after treatment ends. Over the next 5 years, the field of behavioral science will need to develop and implement initiatives to expand use of standardized neurocognitive and behavior batteries; increase assessment of neurocognition using technology; early identification of at-risk children/families; establish standards for evidence-based psychosocial care; and leverage linkages with the broader behavioral health pediatric oncology community to translate empirically supported research clinical trials care to practice.

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.

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.