Although celiac disease (CD) is a common condition in the pediatric population, it is underdiagnosed, and in the absence of significant gastrointestinal symptoms, screening is not common.1 This is particularly true in the United States, whereas in European countries, screening has been adopted more commonly.2 Past literature has suggested that untreated CD is accompanied by extraintestinal manifestations, such as anxiety and depression, and/or behavioral issues, such as aggression or oppositional behavior.3,4 In a 2017 report,5 we presented findings suggesting that even before diagnosis of CD or knowledge of their child’s celiac disease autoimmunity (CDA) status, parents of young children with CDA reported higher levels of anxiety, depression, aggression, and sleep problems on the Child Behavior Checklist than parents of children without CDA. Our results were mixed in that these relationships were found in 3.5-year-old children but not in 4.5-year-old children. Nonetheless, this provided preliminary support for the connection between CDA and psychological and behavioral symptoms in an unbiased manner.
In the current issue of Pediatrics, Wahab et al6 report findings from a slightly older cohort of children. After controlling for gastrointestinal symptoms, parents of CDA-positive children reported more anxiety and oppositional behavior problems. Although similar, findings in the Wahab et al6 study did reveal differences in psychological functioning in older children, whereas findings in our study did not. There are several important methodologic differences between the study by Wahab et al6 and our previous work that may have contributed to the slight differences in our findings. First, the study populations were different; our participants were enrolled in the Environmental Determinants of Diabetes in the Young study, which followed children at genetic risk for type 1 diabetes from birth, whereas Wahab et al6 used the Generation R cohort, a general population cohort. Second, the methods of classifying CDA status (ie, 2 positive samples for tissue transglutaminase autoantibody [TGA] versus 1 positive sample for CDA-positive classification) and the time of CDA seroconversion were slightly different (ie, retrospectively determining first positive TGA result versus TGA testing at 1 point in time without elucidating the time of seroconversion) between the studies. These small, but relevant, differences likely influenced results. Finally, Wahab et al6 found significant differences in psychological and behavioral functioning between the CDA and non-CDA groups only after controlling for gastrointestinal symptoms. We did not include gastrointestinal symptoms in our 2017 article5 but had previously reported that parent report of gastrointestinal symptoms was decreased with older children.7 Given this finding, we hypothesized that gastrointestinal symptoms and psychological manifestations of CD may interact with child age. Inclusion of gastrointestinal symptoms in the Wahab et al6 analyses is a natural extension of our previous findings and helps to further highlight the complex relationship between extraintestinal symptoms and gastrointestinal symptoms in the presentation of pediatric CDA.
In conclusion, findings from the Wahab et al6 study, which was conducted in a general pediatric population, lend additional support to our previous work, which was focused on a population of children at risk for type 1 diabetes. Although there are methodologic differences between the studies, as highlighted above, both results suggest that pediatric health care providers should be cognizant of the potential emotional and behavioral manifestations of CD and should consider TGA screening for children presenting with these types of psychological or behavioral complaints. Future work is still needed to better understand the impact of a gluten-free diet (GFD) on the amelioration of psychological and behavioral symptoms because this has not been well studied to date. There is evidence that extraintestinal symptoms as a whole improve with a GFD and that psychiatric symptoms specifically decrease after following a GFD, although more work is needed on this topic because of small samples sizes and mixed results.8,9 These promising findings provide additional support for the relevance of addressing CDA and CD early in life to improve not only physical but also psychological functioning.
Dr Agardh's current affiliation is Department of Clinical Sciences, Lund University Clinical Research Center, Skåne University Hospital, Malmo, Sweden.
Opinions expressed in these commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees.
FUNDING: The TEDDY Study is funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Centers for Disease Control and Prevention (CDC), and JDRF. Funded by the National Institutes of Health (NIH).
COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2018-3933.
celiac disease autoimmunity
tissue transglutaminase autoantibody
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.