Co-existing mental and somatic conditions in Swedish children with the avoidant restrictive food intake disorder phenotype.

Background:Avoidant restrictive food intake disorder (ARFID) is a feeding and eating disorder, characterized by limited variety and/or quantity of food intake impacting physical health and psychosocial functioning. Children with ARFID often present with a range of psychiatric and somatic symptoms, and therefore consult various pediatric subspecialties; large-scale studies mapping comorbidities are however lacking. To characterize health care needs of people with ARFID, we systematically investigated ARFID-related mental and somatic conditions in 616 children with ARFID and >30,000 children without ARFID. Methods:In a Swedish twin cohort, we identified the ARFID phenotype in 6-12-year-old children based on parent-reports and register data. From >1,000 diagnostic ICD-codes, we specified mental and somatic conditions within/across ICD-chapters, number of distinct per-person diagnoses, and inpatient treatment days between birth and 18 th birthday (90 outcomes). Hazard ratios (HR) and incidence rate ratios (IRR) were calculated. Findings:Relative risks of neurodevelopmental, gastrointestinal, endocrine/metabolic, respiratory, neurological, and allergic disorders were substantially increased in ARFID (e.g., autism HR[CI 95% ]=9.7[7.5-12.5], intellectual disability 10.3[7.6-13.9], gastroesophageal reflux disease 6.7[4.6-9.9], pituitary conditions 5.6[2.7-11.3], chronic lower respiratory diseases 4.9[2.4-10.1], epilepsy 5.8[4.1-8.2]). ARFID was not associated with elevated risks of autoimmune illnesses and obsessive-compulsive disorder. Children with ARFID had a significantly higher number of distinct mental diagnoses (IRR[CI 95% ]=4.7[4.0-5.4]) and longer duration of hospitalizations (IRR[CI 95% ]=5.5[1.7-17.6]) compared with children without ARFID. Children with ARFID were diagnosed earlier with a mental condition than children without ARFID. No sex-specific differences emerged. Interpretation:This study yields the broadest and most detailed evidence of co-existing mental and somatic conditions in the largest sample of children with ARFID to date. Findings suggest a complex pattern of health needs in youth with ARFID, underscoring the critical importance of attention to the illness across all pediatric specialties. Funding:Fredrik and Ingrid Thurings Foundation, Mental Health Foundation. Research in context:Evidence before the study: Avoidant restrictive food intake disorder (ARFID) is an eating and feeding disorder that often develops in childhood and that is associated with co-existing conditions such as anxiety; depression; and endocrine/metabolic, gastrointestinal, and immunological disorders. We systematically searched Embase, including Medline, and PubMed databases using the terms ("avoidant restrictive food intake disorder" OR "ARFID") AND ("comorbidity" OR (("co-existing" OR "comorbid" OR "concurrent" OR "co-occurring") AND ("concern" OR "condition" OR "disorder" OR "illness" OR "problem"))) in title and abstract without language restrictions. Our search yielded 86 studies from 2013, when ARFID was first introduced as a diagnosis in DSM-5: most of these studies have been conducted in relatively small clinical samples, did not have a control group, or covered a limited range of mental and/or somatic conditions that often were reported as concerns rather than formal diagnoses . Further, we identified one systematic review (published in 2023) applying a more extensive search algorithm with similar terms, which reported that psychiatric comorbidity was common in ARFID, especially anxiety disorders (9-72%) and autism (8-55%). However, knowledge regarding medical treatment needs in ARFID is sparse; and potential effects of sex and age on co-existing conditions in ARFID throughout childhood and adolescence are unstudied, except for one study comparing comorbidities in 23 preschool vs. 28 school children with ARFID (published in 2023). The lack of large-scale studies on comorbidities in ARFID contributes to diagnostic misclassification and treatment delays, ultimately interfering with appropriate medical care. Added value of this study: This cohort study, based on high-quality Swedish Twin Registry data, utilized the, to our knowledge, largest sample of children and adolescents with ARFID (n=616) and without ARFID (controls, n=30,179) to date. We applied a large-scale approach to study a broad range of mental and somatic diagnoses, received in both inpatient and outpatient settings, from birth to 18 th birthday (or until censored). In addition to confirming previous evidence of frequently co-occurring conditions such as attention deficit hyperactivity disorder, autism, and gastrointestinal disorders in a larger sample, we demonstrated that ARFID is associated with an increased risk of a wide variety of perinatal and congenital conditions (e.g., fetal growth retardation; perinatal jaundice and infections; circulatory, digestive, and nervous system malformations), allergic and respiratory conditions (e.g., acute and chronic lower and upper respiratory disorders), and psychiatric and neurodevelopmental disorders (e.g., tic disorders; conduct disorders; developmental disorders of motor function, speech and language, and scholastic skills). Furthermore, our study revealed greater treatment needs in children with ARFID compared with controls, indicated by higher number of distinct per-person diagnoses and longer duration of inpatient treatment due to any mental or somatic diagnosis (accumulated over time). Moreover, mental conditions were more likely to be diagnosed at an earlier age in children with AFRID relative to controls. However, this study did not yield relevant effects of sex assigned at birth on relative risk of any analyzed condition in ARFID vs. controls. Implications of all the available evidence: Given the range and novelty of analyzed mental and somatic conditions, this study may generate hypotheses for future basic, epidemiological, and clinical research on the etiology, clinical presentation, and consequences of ARFID. Combined with previous evidence, we reveal the heterogenous and complex clinical presentations of the ARFID phenotype in childhood and adolescence. ARFID and its co-existing conditions require attention in the medical practice of multiple specialties (e.g., general pediatrics, pediatric endocrinology and gastroenterology, child and adolescent psychiatry, pediatric emergency care, family/internal medicine, and general practice) in order to develop multimodal diagnostic and treatment guidelines that improve treatment options for children and adolescents with ARFID.