Childhood TBI May Elevate Risk for Secondary ADHD

Damian McNamara

March 26, 2018

Approximately one in four children hospitalized after mild to severe traumatic brain injury (TBI) develop secondary attention-deficit/hyperactivity disorder (ADHD), new research shows.  

Even though the risk for subsequent ADHD was greatest in the first year after a severe injury, researchers found children who experienced a mild or moderate injury still carried an elevated risk for developing the attention and behavioral disorder. 

"The main take-home message is that children with a history of TBI, even those with less severe injuries, have an increased risk for the development of new-onset attention problems, potentially many years after injury," lead study author, Megan E. Narad, PhD, from Cincinnati Children's Hospital Medicine Center, Ohio, told Medscape Medical News.

here are two things that were surprising from this study. First, those with moderate injuries — not the most severe — had two times the risk of developing secondary ADHD than those without TBI. While this was not statistically significant, it does suggest that injury severity isn't the whole story when it comes to development of attention problems following TBI," she said.

"The other interesting finding was that a number of children who developed secondary ADHD did so during the final two time points, 3.5 years and 7 to 10 years after injury, suggesting that difficulties can arise even many years after injury."

The study was published online March 19 in JAMA Pediatrics.

TBI Common

TBI and ADHD are both common. More than one million children, teenagers, and young adults are admitted to a US emergency department each year for TBI (MMWR Surveill Summ. 2017;66:1-16).

Other researchers report that with a prevalence of about 20%, ADHD is the most common psychiatric disorder in children following TBI (J Neuropsychiatry Clin Neurosci. 2012;24:427-436).

 "While previous studies suggest kids with a history of TBI are at risk for developing attention problems, they only followed kids 2 to 3 years after injury. Our study is unique in that we followed children 7 to 10 years after their injury," said Narad.

The risk factors associated with development of secondary ADHD in this population remain poorly understood, the researchers note. In addition to severity of injury, poor family functioning and lower socioeconomic status could play a role (Brain Inj. 2004;18:751-764).

To fill some gaps in the literature, Narad and colleagues studied 81 children hospitalized for TBI at one of four centers between 2003 and 2008.

They completed data collection for the final follow-up in 2015. The primary aim was to determine the long-term development of secondary ADHD in children after TBI compared with a control group of 106 children admitted for orthopedic injuries.

They assessed individual risk factors, such as age and severity of injury, as well as maternal education, family functioning, and other possible environmental predictors for secondary ADHD.

No participant had an ADHD diagnosis at study entry. In addition to the baseline assessment at a mean of 1.3 months after injury, evaluations for secondary ADHD were performed at 6, 12, and 18 months, as well as a mean of 3.4 and 6.8 years after admission for TBI.

Interestingly, the final evaluation was timed to coincide with children moving to the greater executive function and attention challenges of middle school.

Diagnosis of secondary ADHD was based on parent report of an ADHD diagnosis since enrollment, the child taking stimulant medication, and/or scores on a developmentally appropriate form of the Child Behavior Checklist.

Mean age at time of TBI was 5.1 years (range, 3 to 7 years), 58% of participants were boys, and 27% were of nonwhite ethnicity. Retention rates did not differ among the mild, moderate, or severe TBI groups, and 54% of the participants completed all six follow-up visits.

One in Four Affected

Forty-eight children, 25.7% of the 187 evaluated, met the definition for secondary ADHD. This group included 13 children with severe TBI, 6 with moderate TBI, 13 with complicated mild TBI, and 16 in the orthopedic injury control group.

Eight of the 13 participants with developed secondary ADHD after a severe injury did so within the first year. In contrast, 3 of the children with moderate TBI and 7 with complicated mild TBI developed the disorder beyond the first year after injury. This highlights "the importance of continued monitoring even years after TBI," the authors write.

The elevated risk for secondary ADHD was significantly higher among children in the severe TBI group than in controls (hazard ratio [HR], 3.62). The differences in the moderate group (HR, 1.73) and complicated mild group (HR, 1.67) were not significant.

Lower levels of maternal education (HR, 0.33) and greater family dysfunction (HR, 3.22) were associated with increased risk for secondary ADHD. In an interaction-effects model, male sex (HR, 1.97) also emerged as a risk factor, and lower maternal education remained a risk factor (HR, 0.34).

Although family dysfunction did not reach statistical significance, the risk was higher in the TBI groups (HR, 4.24) than in the orthopedic injury control group (HR, 1.32). Follow-up of this subgroup of children is particularly critical because children with high levels of family dysfunction may be at particularly elevated risk for secondary ADHD.

Physicians treating children with a history of TBI should educate patients and families about a higher risk for development of attention challenges over time, Narad said. Clinicians should also monitor these patients over time for development of ADHD so that appropriate treatments can be pursued in a timely manner, she added.

Screening tools that assess symptoms of ADHD can be useful and appropriate for monitoring symptoms over time. Behavioral screening tools used routinely in primary care settings may be sufficient to monitor these children, she said, "as long as physicians use a different lens when reviewing the results of these screeners for patients with a history of TBI."

"Keeping an eye on the change in symptoms over time, and asking patients and families about symptoms or challenges they are experiencing in various settings, may be more important than a specific tool," Narad said. Vigilance is warranted even if many years have passed since the injury, the injury was modest, and/or the patient experienced a predominantly positive recovery, the authors noted.

Role of Family Functioning

Commenting on the findings for Medscape Medical News, Tricia Williams, PhD, CPsych, a neuropsychologist at the Hospital for Sick Children in Toronto, Ontario, Canada, said the paper is authored by a strong team of researchers with well-established expertise in the field.

"Their findings showed, not surprisingly, that children with severe TBI were most likely to develop secondary attention problems soon after the injury compared to children with orthopedic injuries."

"The most important take-away message from their article was the substantial influence of family functioning in outcomes of traumatic brain injury. This calls heed to practitioners to pay particularly close attention to the needs of children living within high family dysfunction, who are the highest risk for attention problems, and to advocate for better family support services as a way of optimizing outcomes."

"This is a very interesting and very well-designed study," Beth S. Slomine, PhD, co-director of the Center for Brain Injury Recovery at the Kennedy Krieger Institute in Baltimore, Maryland, told Medscape Medical News when asked to comment. A strength of this study is that it followed children with TBI 5 to 10 years after injury to look for development of symptoms of ADHD.

"The study provides important information about what pediatricians and clinicians in the community should be looking for when they are treating children with a history of traumatic brain injury," Slomine added. "It's important to identify these problems and appropriately intervene…because attention problems can affect children's functioning and many aspects of their lives."

"The other thing I thought was very interesting in their study was the impact of family factors in the development of ADHD. In the TBI literature more broadly, family factors — lower socioeconomic status and poorer family functioning — are associated with worse outcomes. So family factors certainly mediate outcomes in children with traumatic brain injury, and this study is one more piece of evidence speaking to that. So intervening at the family level is something that should also be considered," Slomine said.

The current research addresses a "very neglected area," with few studies looking at the development of ADHD after TBI, she said.

"We did some research here at Kennedy Krieger Institute looking at the development of secondary ADHD after traumatic brain injury and found similar risk factors. Severe traumatic brain injury was associated with increased risk for secondary ADHD in our study" (J Int Neuropsychol Soc. 2005;11:645-653].

Parent-reported ADHD history and symptoms could make the results susceptible to reporting bias, a potential limitation of the study. In addition, symptoms or impairment in other settings, such as school, were not included, and future studies could benefit from using a structured diagnostic interview and collection of teacher ratings.

Future research in this area is warranted to examine functional outcomes associated with secondary ADHD, as well as any differences in treatment indicated to treat ADHD arising after TBI vs primary ADHD.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development, A State of Ohio Emergency Medical Services Trauma Research Grant, and the National Center for Advancing Translational Sciences of the National Institutes of Health supported the study. Narad was supported by a grant from the National Institute of Child Health and Human Development. Williams and Slomine have disclosed no relevant financial relationships.

JAMA Pediatr . Published online March 19, 2018. Abstract

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