Adverse Effects of α-2 Adrenergic Agonists and Stimulants in Preschool-age Attention-deficit/Hyperactivity Disorder: A Developmental-Behavioral Pediatrics Research Network Study.

OBJECTIVES: To characterize and compare the type and frequency of a range of common and uncommon adverse effects (AEs) associated with α-2 adrenergic agonist (A2A) and stimulant treatment of attention-deficit/hyperactivity disorder at preschool-age as well as to evaluate the impact of age on common AEs. STUDY DESIGN: This was a retrospective electronic medical record review of children <72 months of age (n = 497) evaluated at outpatient developmental-behavioral pediatric practices at 7 US academic medical centers within the Developmental-Behavioral Pediatrics Research Network. Data on AEs were abstracted for children who had treatment initiated by a developmental-behavioral pediatrician with an A2A or stimulant medication between January 2013 and July 2017; follow-up was complete by February 2019. RESULTS: A2A and stimulants had distinctive AE profiles. A2A compared with stimulants had a greater proportion with daytime sleepiness and headaches; stimulants had significantly greater proportions for most other AE, including moodiness/irritability, difficulty with sleep, appetite suppression, stomachaches, skin picking/repetitive behaviors, withdrawn behavior, and weight loss. Younger age was associated with disruptive behavior and difficulty with sleep. CONCLUSIONS: Stimulants had a greater rate of most AEs compared with A2A. AE profiles, together with efficacy, should inform clinical decision-making. Prospective randomized clinical trials are needed to fully compare efficacy and AE profiles of A2A and stimulants.

α2-Adrenergic Agonists or Stimulants for Preschool-Age Children With Attention-Deficit/Hyperactivity Disorder.

Importance: Attention-deficit/hyperactivity disorder (ADHD) is diagnosed in approximately 2.4% of preschool-age children. Stimulants are recommended as first-line medication treatment. However, up to 25% of preschool-age children with ADHD are treated with α2-adrenergic agonist medications, despite minimal evidence about their efficacy or adverse effects in this age range. Objective: To determine the frequency of reported improvement in ADHD symptoms and adverse effects associated with α2-adrenergic agonists and stimulant medication for initial ADHD medication treatment in preschool-age children. Design, Setting, and Participants: Retrospective electronic health record review. Data were obtained from health records of children seen at 7 outpatient developmental-behavioral pediatric practices in the Developmental Behavioral Pediatrics Research Network in the US. Data were abstracted for 497 consecutive children who were younger than 72 months when treatment with an α2-adrenergic agonist or stimulant medication was initiated by a developmental-behavioral pediatrician for ADHD and were treated between January 1, 2013, and July 1, 2017. Follow-up was complete on February 27, 2019. Exposures: α2-Adrenergic agonist vs stimulant medication as initial ADHD medication treatment. Main Outcomes and Measures: Reported improvement in ADHD symptoms and adverse effects. Results: Data were abstracted from electronic health records of 497 preschool-age children with ADHD receiving α2-adrenergic agonists or stimulants. Median child age was 62 months at ADHD medication initiation, and 409 children (82%) were males. For initial ADHD medication treatment, α2-adrenergic agonists were prescribed to 175 children (35%; median length of α2-adrenergic agonist use, 136 days) and stimulants were prescribed to 322 children (65%; median length of stimulant use, 133 days). Improvement was reported in 66% (95% CI, 57.5%-73.9%) of children who initiated α2-adrenergic agonists and 78% (95% CI, 72.4%-83.4%) of children who initiated stimulants. Only daytime sleepiness was more common for those receiving α2-adrenergic agonists vs stimulants (38% vs 3%); several adverse effects were reported more commonly for those receiving stimulants vs α2-adrenergic agonists, including moodiness/irritability (50% vs 29%), appetite suppression (38% vs 7%), and difficulty sleeping (21% vs 11%). Conclusions and Relevance: In this retrospective review of health records of preschool-age children with ADHD treated in developmental-behavioral pediatric practices, improvement was noted in the majority of children who received α2-adrenergic agonists or stimulants, with differing adverse effect profiles between medication classes. Further research, including from randomized clinical trials, is needed to assess comparative effectiveness of α2-adrenergic agonists vs stimulants.

Do Externalizing and Internalizing Symptoms Moderate Medication Response in Preschool Attention-Deficit/Hyperactivity Disorder? A DBPNet Study.

OBJECTIVES: This study aimed to determine whether parent ratings of attention-deficit/hyperactivity disorder (ADHD) symptom severity or externalizing symptoms (EXT) or internalizing symptoms (INT) moderate response to stimulants (STIM) and alpha-2 adrenergic agonists (A2As) in preschool ADHD. METHODS: Health records for children treated with medication for ADHD and with parent rating scale data available (N = 309; age <72 months) were reviewed at 7 Developmental-Behavioral Pediatric Research Network sites. Severity of ADHD was defined as the number of ADHD symptoms occurring often or very often on DSM-IV-based parent rating scales. EXT or INT from standardized rating scales were categorized as T score <60, 60 to <70, or ≥70. Ordinal logistic regression models predicting response to medication were calculated. RESULTS: The median (interquartile range) age at ADHD diagnosis was 59 (54-65) months. One hundred eighty-three participants had ADHD symptom severity, and 195 had EXT or INT data. ADHD severity was not associated with medication response. Both EXT and INT were associated with medication response but with significant medication class by EXT/INT interactions. Children with higher EXT were less likely to respond to STIM, with percentage of nonresponders for T-score categories <60, 60 to <70, and ≥70 being 3.6%, 25.7%, and 33.3% (p = 0.016) and, for A2As, being 60%, 50%, and 33.3% (p = 0.55), respectively. A similar pattern was observed for INT categories: STIM 19.4%, 22.5%, and 50.0% (p = 0.002) and A2As 42.3%, 30%, and 42.3% (p = 0.48), respectively. CONCLUSION: For preschool ADHD, low ratings of EXT or INT are associated with a high likelihood of response to STIM. By contrast, response rates to STIM and A2As are more similar for children with high levels of EXT or INT.

Receipt of Behavioral Therapy in Preschool-Age Children with ADHD and Coexisting Conditions: A DBPNet Study.

OBJECTIVE: Practice guidelines from the American Academy of Pediatrics and Society for Developmental and Behavioral Pediatrics recommend evidence-based behavioral therapy (BT) as first-line treatment for preschool-age children with ADHD, prior to medication initiation. Thus, this study's objective is to present the frequency of physician-documented receipt of BT in preschool-age children with ADHD prior to medication initiation and to determine factors associated with receipt BT receipt. METHODS: This retrospective medical record review was conducted across 7 Developmental Behavioral Pediatrics Research Network (DBPNet) sites. Data were abstracted for children <72 months old seen by a DBP clinician and initiated on ADHD medication between 1/1/2013-7/1/2017. From narrative text of the medical records, BT receipt was coded as: parent training in behavior management (PTBM), Applied Behavior Analysis (ABA), other, or did not receive. RESULTS: Of the 497 children in this study; 225 children (45%) had reported receipt of any BT prior to ADHD medication initiation, with 15.9% (n = 79) receiving PTBM. Children with co-existing diagnoses of ASD or disruptive behavior disorder were more likely to receive BT than children without co-existing conditions (59.3% vs 69.0% vs 30.6%). There was significant site variability in reported receipt of BT, ranging from 22.4% to 74.1%, and sex and insurance were not associated with BT rates. CONCLUSION: The percentage of children with documented receipt of any BT, and particularly PTBM, was low across all sites and co-existing conditions. These findings highlight the universal need to increase receipt of evidence-based BT for all young children with ADHD.

Oculomotor assessments of executive function in preterm children.

OBJECTIVE: To use objective, nonverbal oculomotor tasks to assess executive function and infer the neural basis of impairments in preterm children. STUDY DESIGN: Cross-sectional study of preterm children age 9-16 years (n = 69; mean gestational age 29 weeks) and full-term controls (n = 43). Tasks assessed sensorimotor function (reflexive prosaccades); resistance to peripheral distracters (fixation); response inhibition, response preparation, and execution of a voluntary saccade (antisaccades); and spatial working memory (memory-guided saccades). Group differences were analyzed using ANOVA. We used linear regression to analyze the contributions of age, sex, gestational age, and white matter category to task performance. RESULTS: Preterm children did not differ from controls on basic sensorimotor function, response inhibition, and working memory. Compared with controls, preterm children showed greater susceptibility to peripheral distracters (P = .008) and were slower to initiate an inhibitory response (P = .003). Regression models showed contributions of age and white matter category to task performance. CONCLUSIONS: Preterm children show intact basic sensorimotor function and demonstrate difficulties in processes underlying executive control, including increased distractibility and prolonged response preparation. These limitations may reflect specific neural abnormalities in fronto-subcortical executive control of behavior.

White matter microstructure on diffusion tensor imaging is associated with conventional magnetic resonance imaging findings and cognitive function in adolescents born preterm.

AIM: Diffusion tensor imaging (DTI) was used to evaluate white matter architecture after preterm birth. The goals were (1) to compare white matter microstructure in two cohorts of preterm- and term-born children; and (2) within preterm groups, to determine if sex, gestational age, birthweight, white matter injury score from conventional magnetic resonance imaging (MRI), or IQ was associated with DTI measures. METHOD: Participants (n=121; 66 females, 55 males) were aged 9 to 16 years. They comprised 58 preterm children (site 1, n=25; and site 2, n=33) born at less than 36 weeks' gestation (mean 29.4 wks; birthweight 1289g) and 63 term children (site 1, n=40; site 2, n=23) born at more than 37 weeks' gestation. DTI was analyzed using tract-based spatial statistics. Diffusion measures were fractional anisotropy, axial, radial, and mean diffusivity. RESULTS: In no region of the white matter skeleton was fractional anisotropy lower in the preterm group at either site. Within the preterm groups, fractional anisotropy was significantly associated with white matter injury score, but not sex, gestational age, or birthweight. At site 1, fractional anisotropy was associated with IQ. INTERPRETATION: DTI contributes to understanding individual differences after preterm birth but may not differentiate a relatively high-functioning group of preterm children from a matched group of term-born children.

Update on environmental risk factors for attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurobehavioral disorder affecting 5% to 10% of children. Although considered to be a highly familial disorder, ADHD heritability estimates of 60% to 80% highlight the considerable role that environmental factors may still play in disorder susceptibility. Proposed ADHD environmental risk factors include prenatal substance exposures, heavy metal and chemical exposures, nutritional factors, and lifestyle/psychosocial factors. This paper reviews the literature published in 2010 investigating the association between environmental risk factors and ADHD or related symptomatology. Sources of risk factor exposure and the proposed mechanism by which each exposure is linked to ADHD-related neurobehavioral changes are also reported. Methodologic limitations of the current literature are discussed, and guidelines for future study are proposed. An improved understanding of the role that environmental factors play in ADHD etiology is critical to future ADHD prevention efforts.

Responding to Discriminatory Patient Requests.

CASE: Julia is a 13-year-old White adolescent girl who was referred for psychological counseling given concerns related to mood, nonadherence, and adjustment secondary to her new diagnosis of type 1 diabetes. The family lives in a rural town located several hours from the academic medical center where she was diagnosed. After several months on a waitlist, the family was contacted to schedule a telehealth appointment with a predoctoral psychology trainee. When the scheduler informed the mother that her daughter would be scheduled with Ms. Huang, the mother abruptly stopped the conversation stating, "I do not want to waste everyone's time" and initially declined the appointment offered. When the scheduler asked about her hesitance, the mother disclosed previous interactions with doctors at the hospital who were "not born in the United States" that she felt were "textbook" (e.g., smiling even when discussing a new chronic medical condition) and "hard to understand" (i.e., because of different dialect/accent). The mother shared that she found these experiences to be stressful and felt the interactions had negatively affected Julia's care. When informed about the length of the waitlist for another clinician, the mother agreed to initiate services with the trainee.The supervising psychologist shared the mother's concerns and comments with Ms. Huang. After discussion, Ms. Huang agreed to provide intervention services, "as long as the family was willing." During the initial telehealth sessions, Ms. Huang primarily focused on building rapport and strengthening the therapeutic alliance with the family. During this time, Julia's mother was reluctant to incorporate suggested parent management strategies at home. Julia also made minimal improvement in her medical management (i.e., A1c levels remained high), had difficulty using behavioral coping strategies, and experienced ongoing mood symptoms (i.e., significant irritability, sleep difficulties, and depressive symptoms). Ms. Huang began to wonder whether the family's resistance and inability to implement recommendations were in some part because of the family's initial concerns and reluctance to engage in therapy with her as a clinician.Should Ms. Huang address the previously identified concerns with the patient and her family? What should be considered when determining how to approach this situation to ensure provision of both the best care for this patient and support for this trainee?

Disproportionate Representation of Children of Color and Parents with Disabilities in the Child Welfare System: The Intersection of Race/Ethnicity, Immigration Status, and Disability.

CASE: An almost 5-year-old girl is referred to a developmental-behavioral clinician for developmental evaluation because of language and learning concerns. Her developmental screening in the primary pediatrics office showed scores concerning for delays in communication, social-emotional, gross, and fine motor domains. Her mother has concerns about her language. Her mother's primary language is Spanish, but the patient and her siblings speak primarily English. She speaks in short phrases and sentences with grammatical errors. Her mother understands approximately 75% of what she says, and strangers understand approximately 50%. She uses gestures and facial expression, is social and friendly, demonstrates pretend play, and plays well with her siblings and other children her age. She has occasional meltdowns, but there are no other major behavioral concerns. She feeds herself with utensils and is able to dress herself. She toilet trained recently, at about age 4.5 years.She did not receive early intervention before age 3 years and had no previous evaluations. She did not attend preschool or child care. Her mother reported that they were referred to the school district twice, but she had trouble requesting the evaluation.She lives with her parents and 2 brothers. The patient's parents immigrated to the United States from Mexico 7 years ago. They are both farm workers, and extended family members are in Mexico. On reviewing family history, the clinician learns that the patient's mother had trouble learning and attended school until she was 12 years old. She did not receive extra help at school. The child's mother said that she forgets things and "has trouble with reading and writing fast." The patient's 10-year-old brother has an individualized education plan and is in a substantially separate classroom. He has inclusion activities of recess, art, and music. He receives speech-language therapy and academic support for reading and writing. The patient's mother becomes tearful and shares that Child Protective Services was notified because of her inability to request the school evaluation, but a case was not opened.Developmental evaluation reveals expressive language at a 33-month-old level and receptive language at a 39-month-old level. Cognitive testing shows extremely low verbal comprehension, borderline visual spatial skills, and fluid reasoning in the low average range. Working memory and processing speed fall in the borderline range. The clinician learns at a follow-up visit that the patient's mother was evaluated by state disability services and has mild intellectual disability.What is your next step in management? What feedback or resources would you provide to the pediatric clinician and family?

Racism as an Adverse Childhood Experience: An Interactive Workshop to Train Pediatricians to Address Racism in Clinical Care.

OBJECTIVE: The objective of this study was to address critical gaps in pediatric medical education by developing and evaluating an interactive educational workshop on racism as an adverse childhood experience (ACE). METHODS: A team of developmental-behavioral pediatrics professionals used a best-practice curriculum development model of Kern's 6 steps to develop the workshop curriculum. Based on a targeted needs assessment, goals and objectives to address the topics of race and racism in clinical practice were developed. A variety of educational strategies (e.g., audience polls, videos, didactic presentations, experiential activities, and peer-guided case-based discussion and practice) were used to appeal to varied learning styles. Selection of strategies was guided by self-determination theory, an adult learning model that addresses the needs of autonomy, competence, and relatedness. The workshop was implemented at 2 national pediatric meetings and evaluated using participant polls and written program evaluation. RESULTS: The workshop curriculum was well-received. Participants endorsed improvements in comfort level in talking about race/racism and demonstrated a significant change in preparation or comfort level for skills-based activities, including counseling families and offering resources to address experiences with racism, postworkshop. Participants endorsed intent to change clinical practice by discussing the issues of race and indicated a desire to receive additional training. CONCLUSION: An interactive educational workshop on racism as an ACE was effective in improving pediatric professionals' comfort level and self-rated skills. Desire for a longer educational session suggests receptivity to longitudinal approaches. Replication and refinement of the educational workshop could clarify effective components of this approach. We advocate for longitudinal training curricula that incorporate observable behavior change and skills to increase and further evaluate the impact. Health care provider education and training to implement antiracism efforts in clinical encounters with patients and families can serve as an entry point to the complex process of addressing racism at multiple levels in health care.