Meghan Miller, Erica D. Musser, Gregory S. Young, Brent Olson, Robert D. Steiner, Joel T. Nigg. Sibling Recurrence Risk and Cross-aggregation of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder. JAMA Pediatr. Published online December 10, 2018. doi:10.1001/jamapediatrics.2018.4076
Question What are the rates of within-diagnosis sibling recurrence and sibling cross-aggregation of attention-deficit/hyperactivity disorder and autism spectrum disorder among later-born siblings of diagnosed children?
Findings In this population-based study of 15 175 US children, compared with later-born siblings of nondiagnosed children, later-born siblings of those with autism spectrum disorder were more likely to be diagnosed with autism spectrum disorder or attention-deficit/hyperactivity disorder. In addition, compared with later-born siblings of nondiagnosed children, later-born siblings of children with attention-deficit/hyperactivity disorder were more likely to be diagnosed with attention-deficit/hyperactivity disorder or autism spectrum disorder.
Meaning Later-born siblings of children with autism spectrum disorder appear to be at elevated risk of attention-deficit/hyperactivity disorder and vice versa with implications for etiologic overlap and clinical monitoring.
Importance Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are believed to partially share genetic factors and biological influences. As the number of children with these diagnoses rises, so does the number of younger siblings at presumed risk for ADHD and ASD; reliable recurrence risk estimates within and across diagnoses may aid screening and early detection efforts and enhance understanding of potential shared causes.
Objective To examine within-diagnosis sibling recurrence risk and sibling cross-aggregation of ADHD and ASD among later-born siblings of children with either disorder.
Design, Setting, and Participants Using data extracted from medical records of 2 large health care systems in the United States, estimates of recurrence risk and cross-aggregation in later-born siblings of children with ADHD or ASD were compared with later-born siblings of children without these diagnoses. One data set included children seen between January 1, 1995, and December 31, 2013; the other included children born between January 1, 1998, and May 17, 2010. Participants included 15 175 later-born siblings of children with ADHD, ASD, and no known diagnosis. The study was conducted from October 2, 2017, to August 14, 2018.
Main Outcomes and Measures Diagnoses of ASD or ADHD in the later-born sibling, ascertained from medical records, were the primary outcomes of interest; moderators included sex, gestational age, and maternal age.
Results A total of 15 175 later-born siblings were classified by familial risk status based on the older child’s diagnostic status: ADHD risk (n = 730; male [51.92%]), ASD risk (n = 158; male [48.10%]), and no known risk (n = 14 287; male [50.73%]). Compared with later-born siblings of children without ADHD or ASD, later-born siblings of children with ASD were more likely to be diagnosed with ASD (odds ratio [OR], 30.38; 95% CI, 17.73-52.06) or ADHD in the absence of ASD (OR, 3.70; 95% CI, 1.67-8.21). Compared with later-born siblings of children without a diagnosis, later-born siblings of children with ADHD were more likely to be diagnosed with ADHD (OR, 13.05; 95% CI, 9.86-17.27) or ASD in the absence of ADHD (OR, 4.35; 95% CI, 2.43-7.79).
Conclusions and Relevance Later-born siblings of children with ASD or ADHD appear to be at elevated risk for the same disorder, but also of being diagnosed with the other disorder. These findings provide further support for shared familial mechanisms underlying ASD and ADHD, which may be useful for genetic and prospective developmental studies. Later-born siblings of children with ADHD or ASD should be monitored for both conditions.
"These findings provide further support for shared familial mechanisms underlying ASD and ADHD, which may be useful for genetic and prospective developmental studies," write Meghan Miller, PhD, from the University of California, Davis, Health System, Sacramento, and colleagues…
The researchers acknowledge study limitations, including the lack of information on parental psychopathology, comorbidities, or birth complications, that could have affected outcomes.
"Etiologically, our findings of sibling cross-aggregation are consistent with partially shared genetic mechanisms underlying ASD and ADHD," write Miller and colleagues.
"Practitioners may wish to share such information with families given the potential relevance of monitoring social communication, attention, and behavior regulation skills in later-born siblings of children with ASD or ADHD," they conclude.
In an accompanying editorial, Tony Charman, PhD, and Emily J. H. Jones, PhD, from King's College London and the University of London, United Kingdom, write: "These within- and cross-condition recurrence figures are of important clinical usefulness in terms of informing discussions with parents about the need for enhanced developmental surveillance for neurodevelopmental conditions, such as ASD and ADHD, in their younger children."
Charman and Jones note, however, that the small sample size and wide confidence intervals may limit the clinical utility of the data and suggest that caution be used when conveying this information to parents.
"Although studies such as the present one will help to provide accessible and clinically translatable estimates of recurrence, more specialist training or even specialist genetic counseling services might have to be developed to provide this information to families sensitively and clearly in the way that is increasingly the case for monogenic forms of neurodevelopmental conditions," conclude the editorialists.