Epigenetic differences in stress response gene FKBP5 among children with abusive vs accidental injuries.

BACKGROUND: Survivors of child abuse experience high rates of adverse physical and mental health outcomes. Epigenetic alterations in the stress response system, the FKBP5 gene specifically, have been implicated as one mechanism that may link abuse to lifelong health issues. Prior studies primarily included older individuals with a remote history of maltreatment; our objective was to test for differential methylation of FKBP5 in children with abusive vs accidental injuries at the time of diagnosis. METHODS: We conducted a cross-sectional pilot study of acutely injured children <4 years old at two children's hospitals (n = 82). Research personnel collected injury histories, buccal swabs (n = 65), and blood samples (n = 25) to measure DNA methylation. An expert panel classified the injuries as abusive, accidental, or indeterminate. RESULTS: Children with abusive as compared to accidental injuries had lower methylation of the FKBP5 promoter in buccal and blood cells, even after controlling for injury severity, socioeconomic status, and psychosocial risk factors. CONCLUSION: These findings suggest that epigenetic variation in FKBP5 may occur at the earliest indication of abuse and may be associated with delayed resolution of the HPA axis stress response. Additional testing for epigenetic differences in larger sample sizes is needed to further verify these findings. IMPACT: Children (<4 years old) with abusive compared to accidental injuries showed lower methylation of the FKBP5 promoter in buccal and blood cells at the time of initial diagnosis even after controlling for injury severity, socioeconomic status, and psychosocial risk factors. Early childhood physical abuse may impact the epigenetic regulation of the stress response system, including demethylation within promoters and enhancers of the FKBP5 gene, even at the earliest indication of abuse. The findings are important because unmitigated stress is associated with adverse health outcomes throughout the life-course.

Validation of a Clinical Decision Rule to Predict Abuse in Young Children Based on Bruising Characteristics.

Importance: Bruising caused by physical abuse is the most common antecedent injury to be overlooked or misdiagnosed as nonabusive before an abuse-related fatality or near-fatality in a young child. Bruising occurs from both nonabuse and abuse, but differences identified by a clinical decision rule may allow improved and earlier recognition of the abused child. Objective: To refine and validate a previously derived bruising clinical decision rule (BCDR), the TEN-4 (bruising to torso, ear, or neck or any bruising on an infant <4.99 months of age), for identifying children at risk of having been physically abused. Design, Setting, and Participants: This prospective cross-sectional study was conducted from December 1, 2011, to March 31, 2016, at emergency departments of 5 urban children's hospitals. Children younger than 4 years with bruising were identified through deliberate examination. Statistical analysis was completed in June 2020. Exposures: Bruising characteristics in 34 discrete body regions, patterned bruising, cumulative bruise counts, and patient's age. The BCDR was refined and validated based on these variables using binary recursive partitioning analysis. Main Outcomes and Measures: Injury from abusive vs nonabusive trauma was determined by the consensus judgment of a multidisciplinary expert panel. Results: A total of 21 123 children were consecutively screened for bruising, and 2161 patients (mean [SD] age, 2.1 [1.1] years; 1296 [60%] male; 1785 [83%] White; 1484 [69%] non-Hispanic/Latino) were enrolled. The expert panel achieved consensus on 2123 patients (98%), classifying 410 (19%) as abuse and 1713 (79%) as nonabuse. A classification tree was fit to refine the rule and validated via bootstrap resampling. The resulting BCDR was 95.6% (95% CI, 93.0%-97.3%) sensitive and 87.1% (95% CI, 85.4%-88.6%) specific for distinguishing abuse from nonabusive trauma based on body region bruised (torso, ear, neck, frenulum, angle of jaw, cheeks [fleshy], eyelids, and subconjunctivae), bruising anywhere on an infant 4.99 months and younger, or patterned bruising (TEN-4-FACESp). Conclusions and Relevance: In this study, an affirmative finding for any of the 3 BCDR TEN-4-FACESp components in children younger than 4 years indicated a potential risk for abuse; these results warrant further evaluation. Clinical application of this tool has the potential to improve recognition of abuse in young children with bruising.

Contribution of thirdhand smoke to overall tobacco smoke exposure in pediatric patients: study protocol.

BACKGROUND: Thirdhand smoke (THS) is the persistent residue resulting from secondhand smoke (SHS) that accumulates in dust, objects, and on surfaces in homes where tobacco has been used, and is reemitted into air. Very little is known about the extent to which THS contributes to children's overall tobacco smoke exposure (OTS) levels, defined as their combined THS and SHS exposure. Even less is known about the effect of OTS and THS on children's health. This project will examine how different home smoking behaviors contribute to THS and OTS and if levels of THS are associated with respiratory illnesses in nonsmoking children. METHODS: This project leverages the experimental design from an ongoing pediatric emergency department-based tobacco cessation trial of caregivers who smoke and their children (NIHR01HD083354). At baseline and follow-up, we will collect urine and handwipe samples from children and samples of dust and air from the homes of smokers who smoke indoors, have smoking bans or who have quit smoking. These samples will be analyzed to examine to what extent THS pollution at home contributes to OTS exposure over and above SHS and to what extent THS continues to persist and contribute to OTS in homes of smokers who have quit or have smoking bans. Targeted and nontargeted chemical analyses of home dust samples will explore which types of THS pollutants are present in homes. Electronic medical record review will examine if THS and OTS levels are associated with child respiratory illness. Additionally, a repository of child and environmental samples will be created. DISCUSSION: The results of this study will be crucial to help close gaps in our understanding of the types, quantity, and clinical effects of OTS, THS exposure, and THS pollutants in a unique sample of tobacco smoke-exposed ill children and their homes. The potential impact of these findings is substantial, as currently the level of risk in OTS attributable to THS is unknown. This research has the potential to change how we protect children from OTS, by recognizing that SHS and THS exposure needs to be addressed separately and jointly as sources of pollution and exposure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02531594 . Date of registration: August 24, 2015.

Is the Use of Physical Discipline Associated with Aggressive Behaviors in Young Children?

OBJECTIVE: To determine the association between use of physical discipline and parental report of physically aggressive child behaviors in a cohort of young children who were without indicators of current or past physical abuse. METHODS: The data for this study were analyzed from an initial cohort of patients enrolled in a prospective, observational, multicenter pediatric emergency department-based study investigating bruising and familial psychosocial characteristics of children younger than 4 years of age. Over a 7-month period, structured parental interviews were conducted regarding disciplinary practices, reported child behaviors, and familial psychosocial risk factors. Children with suspected physical abuse were excluded from this study. Trained study staff collected data using standardized questions. Consistent with grounded theory, qualitative coding by 2 independent individuals was performed using domains rooted in the data. Inter-rater reliability of the coding process was evaluated using the kappa statistic. Descriptive statistics were calculated and multiple logistic regression modeling was performed. RESULTS: Three hundred seventy-two parental interviews were conducted. Parents who reported using physical discipline were 2.8 (95% confidence interval [CI], 1.7-4.5) times more likely to report aggressive child behaviors of hitting/kicking and throwing. Physical discipline was used on 38% of children overall, and was 2.4 (95% CI, 1.4-4.1) times more likely to be used in families with any of the psychosocial risk factors examined. CONCLUSIONS: Our findings indicated that the use of physical discipline was associated with higher rates of reported physically aggressive behaviors in early childhood as well as with the presence of familial psychosocial risk factors.

A Controlled Trial Using Natural Language Processing to Examine the Language of Suicidal Adolescents in the Emergency Department.

What adolescents say when they think about or attempt suicide influences the medical care they receive. Mental health professionals use teenagers' words, actions, and gestures to gain insight into their emotional state and to prescribe what they believe to be optimal care. This prescription is often inconsistent among caregivers, however, and leads to varying outcomes. This variation could be reduced by applying machine learning as an aid in clinical decision support. We designed a prospective clinical trial to test the hypothesis that machine learning methods can discriminate between the conversation of suicidal and nonsuicidal individuals. Using semisupervised machine learning methods, the conversations of 30 suicidal adolescents and 30 matched controls were recorded and analyzed. The results show that the machines accurately distinguished between suicidal and nonsuicidal teenagers.

The Prevalence of Bruising Among Infants in Pediatric Emergency Departments.

STUDY OBJECTIVE: Bruising can indicate abuse for infants. Bruise prevalence among infants in the pediatric emergency department (ED) setting is unknown. Our objective is to determine prevalence of bruising, associated chief complaints, and frequency of abuse evaluations in previously healthy infants presenting to pediatric EDs. METHODS: We conducted a prospective, observational, multicenter study of infants aged 12 months or younger presenting to pediatric EDs. Structured sampling was used. Pediatric emergency medicine clinicians performed complete skin examinations to screen for bruising. Study investigators documented skin findings, date of visit, patient's age, chief complaint, and abuse evaluation. The primary outcome was prevalence of bruising. Secondary outcomes were prevalence of bruising based on chief complaint and frequency of abuse evaluation. Point estimates of bruise prevalence and differences in bruise prevalence between patient subgroups were calculated with 95% confidence intervals (CIs). RESULTS: Bruising was identified in 88 of 2,488 infants (3.5%; 95% CI 2.9% to 4.4%). Rates of bruising for infants 5 months and younger and older than 5 months were 1.3% and 6.4%, respectively (difference 5.1%; 95% CI 3.6% to 6.8%). For infants 5 months and younger, 83% of bruising was associated with a trauma chief complaint and only 0.2% of infants presenting with a medical chief complaint had bruising. Pediatric emergency medicine clinicians obtained abuse evaluations on 23% of infants with bruising, and that rate increased to 50% for infants 5 months and younger. CONCLUSION: Bruising prevalence in children 12 months and younger who were evaluated in pediatric EDs was low, increased within age strata, and was most often associated with a trauma chief complaint. Most bruised infants did not undergo an abuse evaluation.