Psychiatric and Medical Conditions in Transition-Aged Individuals With ASD

Transcription

1 Psychiatric and Medical Conditions in Transition-Aged Individuals With ASD Meghan N. Davignon, MD, a, b Yinge Qian, PhD, c Maria Massolo, PhD, c Lisa A. Croen, PhD c BACKGROUND AND OBJECTIVES: Children with autism spectrum disorder (ASD) have a variety of medical and psychiatric conditions and an increased use of health care services. There is limited information about the prevalence of psychiatric and medical conditions in adolescents and young adults with ASD. Our objective was to describe the frequency of medical and psychiatric conditions in a large population of diverse, insured transition-aged individuals with ASD. METHODS: Participants included Kaiser Permanente Northern California members who were enrolled from 2013 to 2015 and who were 14 to 25 years old. Individuals with ASD (n = 4123) were compared with peers with attention-deficit/hyperactivity disorder (n = ), diabetes mellitus (n = 2156), and typical controls with neither condition (n = ). RESULTS: Over one-third (34%) of individuals with ASD had a co-occurring psychiatric condition; the most commonly reported medical conditions included infections (42%), obesity (25%), neurologic conditions (18%), allergy and/or immunologic conditions (16%), musculoskeletal conditions (15%), and gastrointestinal (11%) conditions. After controlling for sex, age, race, and duration of Kaiser Permanente Northern California membership, most psychiatric conditions were significantly more common in the ASD group than in each comparison group, and most medical conditions were significantly more common in the ASD group than in the attention-deficit/hyperactivity disorder and typical control groups but were similar to or significantly less common than the diabetes mellitus group. CONCLUSIONS: Although more research is needed to identify factors contributing to this excess burden of disease, there is a pressing need for all clinicians to approach ASD as a chronic health condition requiring regular follow-up and routine screening and treatment of medical and psychiatric issues. abstract a Department of Pediatrics, The Permanente Medical Group, Inc, Oakland, California; b Kaiser Permanente Roseville Medical Center, Roseville, California; and c Division of Research, Kaiser Permanente Northern California, Oakland, California Dr Davignon helped design the study and collaborated in drafting the initial manuscript; Dr Croen conceptualized and designed the study and collaborated in drafting the initial manuscript; Dr Massolo collaborated in the conceptualization and design of the study and reviewed and revised the manuscript; Dr Qian conducted the initial and subsequent analyses, collaborated in creating tables and figures, and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted. DOI: doi. org/ / peds K Accepted for publication Sep 26, 2017 Address correspondence to Meghan N. Davignon, MD, Kaiser Roseville Medical Center, 1600 Eureka Rd, Building C, Roseville, CA meghan.davignon@ kp.org PEDIATRICS Volume 141, number s4, April 2018:e SUPPLEMENT ARTICLE

2 Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders characterized by impairments in communication, social interaction, and repetitive behavior. 1 The dramatic rise in ASD prevalence in children 2 over recent decades is resulting in increasing numbers of individuals with ASD transitioning from pediatric to adult medical services. Children with ASD have many comorbidities including seizure, sleep disorders, gastrointestinal (GI) disorders, behavioral problems, anxiety, and depression. 3 Authors of recent studies have indicated that adults with ASD also have elevated rates of psychiatric and major medical conditions. 4 Although the use and cost of health care services have been shown to be significantly elevated in adolescents with ASD, 5 robust estimates of the prevalence of medical and psychiatric conditions among adolescents and young adults with ASD are lacking. In this study, we examined the occurrence of medical and psychiatric conditions diagnosed in a large insured transition-aged ASD population and compared rates to age-matched individuals with other neurodevelopmental disorders, chronic medical conditions, and the general population. METHODS Study Population The study population was drawn from the membership of Kaiser Permanente Northern California (KPNC), a large integrated health care delivery system providing care to over 3.8 million residents in the greater San Francisco and Sacramento areas. KPNC members have similar socio-demographic characteristics to other community members locally and statewide, except at the extreme ends of the income distribution. 6 The Kaiser Health Plan provides insurance coverage for inpatient, outpatient, and mental health care provided at KPNC hospitals, clinics, and other approved facilities. All patient encounters are recorded in electronic medical records (EMRs). All individuals 14 to 25 years of age as of January 1, 2014, who were members of KPNC for at least 9 months in each calendar year from 2013 to 2015 were eligible for inclusion (N = ). Individuals with an ASD diagnosis recorded in the EMR before 2014 were considered cases (n = 4123; see Supplemental Table 3 for International Classification of Diseases, Ninth Revision [ICD-9] codes). Approximately 34% were diagnosed by specialists at a KPNC ASD evaluation center after a comprehensive clinical assessment, including the Autism Diagnostic Observation Schedule, 7 and 66% had a diagnosis recorded by nonspecialists on 2 separate occasions. Three comparison populations were chosen from among all individuals without any ASD diagnoses recorded in the EMR by the end of A neurodevelopmental group was randomly sampled from individuals with attention-deficit/hyperactivity disorder (ADHD; n = ; Supplemental Table 3). A medically defined group was composed of all individuals with diabetes mellitus (DM; n = 2156) in the KPNC diabetes registry. 8 A typical control (TC) group (n = ) was randomly sampled from individuals with no ADHD and DM diagnoses by the end of The ADHD and TC groups were sampled at a 5:1 ratio to cases and matched on sex and age group (14 17, 18 21, 22 25). Co-occurring Conditions All diagnoses were identified from the KPNC EMR. Over 1000 ICD-9 codes were grouped into 175 conditions (eg, epilepsy) within 20 categories (eg, neurology). The definition of specific conditions was guided by phenotype-wide association study methodology 9 and previously validated algorithms (Supplemental Table 3). Intellectual disability (ID), developmental disability, and genetic disorders were defined by diagnoses documented in the EMR anytime through Psychiatric and medical conditions were defined by diagnoses documented in the EMR from 2014 to Overweight and obesity were defined by the average BMI recorded in the 2-year study period (Supplemental Table 3). Statistical Analysis The prevalence of each condition was compared between ASD cases and each comparison group by using χ 2 tests. A separate multivariate logistic regression model was run for each condition to compare odds between cases and controls after controlling for sex, age, race, and total months of KPNC membership from 2013 to To address possible ascertainment bias, additional models were run also adjusting for the number of outpatient visits. The threshold for statistical significance was set at P <.05. All study procedures were approved by the KPNC Institutional Review Board. RESULTS The demographic characteristics of the study population are shown in Table 1. Among the 4123 individuals with ASD, the mean age was 18.4 years (SD 3.2 years), and the male to female ratio was 4:1. Individuals with ASD were more likely than TC and DM groups to be white, non-hispanic, and more likely than all 3 comparison groups to have Medicaid. Thirteen percent of transition-aged youth with ASD had a diagnosis of ID (15% mild, 9% moderate, 5% severe, 2% profound, 69% unspecified). The prevalence of ID increased with age (11% in year-olds, S336 DAVIGNON et al

3 TABLE 1 Demographic Characteristics of Transition-Aged Individuals Years of Age From KPNC, Characteristics ASD TC ADHD DM n = 4123 n = n = n = 2156 n (%) n (%) P n (%) P n (%) P Age group, y < (45.65) 9410 (45.65) 9410 (45.65) 638 (29.59) (34.00) 7010 (34.00) 7010 (34.00) 750 (34.79) (20.35) 4195 (20.35) 4195 (20.35) 768 (35.62) Sex <.0001 Female 797 (19.33) 3985 (19.33) 3985 (19.33) 1118 (51.86) Male 3326 (80.67) (80.67) (80.67) 1038 (48.14) Race <.0001 <.0001 <.0001 White, non-hispanic 2208 (53.55) 7502 (36.39) (57.74) 981 (45.50) White, Hispanic 286 (6.94) 1055 (5.12) 1277 (6.19) 168 (7.79) African American 339 (8.22) 1933 (9.38) 2330 (11.30) 260 (12.06) Asian 649 (15.74) 3910 (18.97) 1406 (6.82) 297 (13.78) Other 641 (15.55) 6215 (30.15) 3699 (17.94) 450 (20.87) Insurance <.0001 <.0001 <.0001 KP 3183 (77.20) (89.72) (87.00) 1826 (84.69) Medicaid 821 (19.91) 1590 (7.71) 2068 (10.03) 279 (12.94) Self-pay 119 (2.89) 530 (2.57) 612 (2.97) 51 (2.37) Mean age (SD), y (3.22) (3.18) (3.15) (3.35) <.0001 Mean length of membership in (SD), mo (0.63) (0.73) < (0.73) (0.82) <.0001 KP, Kaiser Permanente. 12% in year-olds, 19% in year-olds) and was higher in females (20%) than males (11%). In addition to their ASD diagnosis, 41% had received a developmental disorder (DD) diagnosis at some point in the past (20.7% global delay, 23% language disorder, 11% learning disorder, 4% motor delay). However, during the 2-year study period, only 4.3% had 1 or more of these diagnoses documented in their medical record (Table 2). Psychiatric Conditions Over one-third (34%) of individuals with ASD had a co-occurring psychiatric condition; the most common were ADHD (15%), anxiety (14%), depression (10%), and bipolar disorder (6%) (Table 2). In adjusted analyses, most psychiatric conditions were significantly more common in the ASD group than in each comparison group, with 2 exceptions. Depression was significantly more common in the ASD group versus the TC group but significantly less common in the ASD group versus the ADHD group, and drug abuse and/or dependence was significantly less common in the ASD group than in all 3 comparison groups (Table 2). Less common disorders associated with high morbidity or mortality were also significantly more prevalent in individuals with ASD compared with those in the control group, including schizophrenic disorders (ASD: 1%; versus TC: 0.3%, adjusted odds ratio [aor] = 3.6, 95% confidence interval (CI): ; versus ADHD: 0.6%, aor = 1.9, 95% CI: ; versus DM: 0.7%, aor = 2.0, 95% CI ) and suicide and self-inflicted injury (ASD: 0.7%; versus TC: 0.3%, aor = 3.6, 95% CI: ; no significant difference versus ADHD [0.9%] or DM [0.9%]). Medical Conditions The most common medical conditions in transition-aged individuals with ASD included infections (42%), obesity (25%), neurologic conditions (18%), allergy and/or immunology conditions (16%), musculoskeletal conditions (15%), and GI conditions (11%). Other conditions previously reported in children with ASD had a relatively lower prevalence, including sleep disorders (7%), endocrine conditions (3%), and metabolic (3%) disorders (Table 2, Fig 1). Compared with the TC group, individuals with ASD were at significantly increased risk for most medical conditions (Table 2, Fig 1). The highest risks were seen for epilepsy (aor = 11.9), genetic disorders (aor = 7.7), dyslipidemia (aor = 4.9), constipation (aor = 3.5), endocrine conditions (aor = 3.2), and sleep disorders (aor = 3.1). Antipsychotic medications, a known risk factor for obesity and dyslipidemia, 10 were used by 19% of individuals with ASD. However, among individuals who did not take antipsychotic medications, obesity and dyslipidemia remained significantly more common in the ASD group versus the TC group (obesity: 23% vs 15%, P <.0001; dyslipidemia: 2.5% vs 0.7%, P <.0001). Functional GI disorders, genitourinary and renal conditions, infectious diseases as a group, and hereditary and degenerative PEDIATRICS Volume 141, number s4, April 2018 S337

4 TABLE 2 Comparison of Psychiatric and Medical Conditions in Transition-Aged Individuals Years of Age With ASD, ADHD, DM, and TCs From KPNC, Condition n (%) aor (95% CI) a ASD, n = 4123 TC, n = ADHD, n = DM, n = 2156 ASD Versus TC ASD Versus ADHD ASD Versus DM Developmental disability b 177 (4.3) 23 (0.1) 228 (1.1) 22 (1.0) ( ) c 5.56 ( ) c ( ) c Global developmental delay 77 (1.9) 11 (0.05) 64 (0.3) 9 (0.4) ( ) c 7.80 ( ) c ( ) c Language disorder 73 (1.8) 2 (0.01) 25 (0.1) 1 (0.05) ( ) c ( ) c ( ) c Learning disorder 27 (0.6) 9 (0.04) 130 (0.6) 8 (0.4) ( ) 1.82 ( ) ( ) c Psychiatric conditions (includes ADHD) b 1419 (34.4) 1905 (9.2) 8883 (43.1) 534 (24.8) 4.97 ( ) c 0.70 ( ) c 1.84 ( ) c Psychiatric conditions (without ADHD d ) 1168 (28.3) 1905 (9.2) 5424 (26.3) 503 (23.3) 3.73 ( ) c 1.14 ( ) c 1.62 ( ) c Anxiety 595 (14.4) 776 (3.8) 2352 (11.4) 204 (9.5) 4.01 ( ) c 1.33 ( ) c 1.91 ( ) c ADHD d 602 (14.6) 0 (0.0) 6443 (31.2) 77 (3.6) d d 3.97 ( ) c Bipolar disorder 264 (6.4) 133 (0.6) 963 (4.7) 61 (2.8) 9.58 ( ) c 1.48 ( ) c 2.80 ( ) c Depression 410 (9.9) 821 (4.0) 2392 (11.6) 282 (13.1) 2.51 ( ) c 0.85 ( ) c 0.94 ( ) Disruptive, impulse, and conduct disorders 143 (3.5) 60 (0.3) 560 (2.7) 23 (1.1) ( ) c 1.35 ( ) c 3.91 ( ) c Drug abuse and/or dependence 63 (1.5) 458 (2.2) 1393 (6.8) 96 (4.4) 0.65 ( ) c 0.22 ( ) c 0.30 ( ) c OCD 94 (2.3) 41 (0.2) 204 (1.0) 13 (0.6) ( ) c 2.30 ( ) c 4.05 ( ) c Psychoses 70 (1.7) 77 (0.4) 178 (0.9) 15 (0.7) 4.83 ( ) c 2.01 ( ) c 2.36 ( ) c Tic disorder 61 (1.48) 5 (0.02) 139 (0.7) 3 (0.1) ( ) c ( ) c 2.18 ( ) c 7.08 Medical condition b Allergy and/or immune 666 (16.2) 2585 (12.5) 3220 (15.6) 500 (23.2) 1.33 ( ) c 1.02 ( ) 0.73 ( ) c Allergic rhinitis 154 (3.7) 498 (2.4) 659 (3.2) 68 (3.2) 1.62 ( ) c 1.13 ( ) 1.24 ( ) Atopic dermatitis and eczema 270 (6.6) 1081 (5.2) 1189 (5.8) 157 (7.3) 1.29 ( ) c 1.08 ( ) 1.00 ( ) Autoimmune disorders 148 (3.6) 456 (2.2) 705 (3.4) 1427 (66.2) 1.57 ( ) c 1.04 ( ) NC e Drug allergy 83 (2.0) 226 (1.1) 464 (2.2) 95 (4.4) 1.69 ( ) c 0.91 ( ) 0.61 ( ) c Cardiovascular 248 (6.0) 545 (2.6) 817 (4.0) 522 (24.2) 2.32 ( ) c 1.52 ( ) c 0.25 ( ) c Dyslipidemia 133 (3.2) 148 (0.7) 288 (1.4) 398 (18.5) 4.88 ( ) c 2.24 ( ) c 0.18 ( ) c Endocrine 127 (3.1) 199 (1.0) 349 (1.7) 1617 (75.0) 3.20 ( ) c 1.87 ( ) c NC Any endocrine without diabetes d 104 (2.5) 199 (1.0) 248 (1.2) 203 (9.4) 2.61 ( ) c 2.16 ( ) c 0.38 ( ) c Diabetes (types 1 and 2) d 25 (0.6) 0 (0.0) 107 (0.5) 1555 (72.1) d 1.18 ( ) d Thyroid disease (including autoimmune thyroid) 66 (1.6) 116 (0.6) 133 (0.6) 132 (6.1) 2.70 ( ) c 2.53 ( ) c 0.33 ( ) c Ear, nose, and throat 325 (7.9) 693 (3.4) 872 (4.2) 77 (3.6) 2.37 ( ) c 1.93 ( ) c 2.62 ( ) c Hearing impairment 80 (1.9) 156 (0.8) 226 (1.1) 26 (1.2) 2.54 ( ) c 1.80 ( ) c 1.71 ( ) c GI 446 (10.8) 1741 (8.4) 2568 (12.5) 542 (25.1) 1.29 ( ) c 0.87 ( ) c 0.44 ( ) c Constipation 70 (1.7) 98 (0.5) 177 (0.9) 34 (1.6) 3.47 ( ) c 2.05 ( ) c 1.09 ( ) Diarrhea 69 (1.7) 190 (0.9) 319 (1.6) 62 (2.9) 1.68 ( ) c 1.10 ( ) 0.66 ( ) c Functional disorders 169 (4.1) 972 (4.7) 1442 (7.0) 245 (11.4) 0.84 ( ) 0.58 ( ) c 0.47 ( ) c Gastroesophageal reflux disease 77 (1.9) 218 (1.1) 400 (1.9) 94 (4.4) 1.77 ( ) c 0.99 ( ) 0.58 ( ) c Upper GI motility problems 73 (1.8) 273 (1.3) 498 (2.4) 164 (7.6) 1.30 ( ) c 0.76 ( ) c 0.25 ( ) c Genetic f 133 (3.2) 81 (0.4) 163 (0.8) 26 (1.2) 7.66 ( ) c 4.09 ( ) c 3.26 ( ) c Genitourinary and/or renal 172 (4.2) 953 (4.6) 1307 (6.3) 401 (18.6) 0.87 ( ) 0.64 ( ) c 0.30 ( ) c S338 DAVIGNON et al

5 TABLE 2 Continued Condition n (%) aor (95% CI) a ASD, n = 4123 TC, n = ADHD, n = DM, n = 2156 ASD Versus TC ASD Versus ADHD ASD Versus DM Renal disorders 89 (2.2) 403 (1.9) 595 (2.9) 270 (12.5) 1.07 ( ) 0.75 ( ) c 0.24 ( ) c Hematology and/or oncology 159 (3.9) 553 (2.7) 736 (3.6) 194 (9.0) 1.41 ( ) c 1.09 ( ) 0.64 ( ) c Infectious disease 1731 (42.0) 8795 (42.7) (51.5) 1249 (57.9) 0.92 ( ) 0.64 ( ) c 0.55 ( ) c Bacterial 209 (5.1) 1138 (5.5) 1494 (7.2) 228 (10.6) 0.89 ( ) 0.69 ( ) c 0.56 ( ) c Mycoses 215 (5.2) 1311 (6.4) 1729 (8.4) 247 (11.5) 1.12 ( ) 0.87 ( ) 0.60 ( ) c Viral 54 (3.8) 335 (4.8) 456 (6.5) 81 (10.8) 0.80 ( ) c 0.61 ( ) c 0.46 ( ) Ear infections 81 (5.8) 213 (3.0) 323 (4.6) 33 (4.4) 1.70 ( ) c 1.26 ( ) c 1.18 ( ) GI 154 (3.7) 1324 (6.4) 1706 (8.3) 171 (7.9) 0.54 ( ) c 0.44 ( ) c 0.43 ( ) c Lower respiratory 159 (3.9) 633 (3.1) 914 (4.4) 146 (6.8) 1.20 ( ) c 0.86 ( ) 0.54 ( ) c Skin infections 403 (9.8) 1685 (8.2) 2239 (10.9) 374 (17.4) 1.14 ( ) c 0.89 ( ) 0.59 ( ) Upper respiratory infections 788 (19.1) 3996 (19.4) 5217 (25.3) 581 (27.0) 0.93 ( ) 0.70 ( ) c 0.72 ( ) Injury 327 (7.9) 2240 (10.9) 3288 (16.0) 324 (15.0) 0.68 ( ) c 0.47 ( ) c 0.50 ( ) c Fracture 237 (5.8) 1756 (8.5) 2500 (12.1) 260 (12.1) 0.64 ( ) c 0.45 ( ) c 0.47 ( ) c Injury of head and neck 124 (3.0) 755 (3.7) 1253 (6.1) 95 (4.4) 0.77 ( ) c 0.49 ( ) c 0.63 ( ) c Metabolic 143 (3.5) 200 (1.0) 345 (1.7) 392 (18.2) 3.71 ( ) c 2.06 ( ) c 0.21 ( ) c Lipoid metabolism 100 (2.4) 100 (0.5) 199 (1.0) 297 (13.8) 5.35 ( ) c 2.42 ( ) c 0.21 ( ) c Musculoskeletal 608 (14.8) 3726 (18.1) 4770 (23.1) 482 (22.4) 0.74 ( ) c 0.59 ( ) c 0.67 ( ) c Neurology 733 (17.8) 1886 (9.2) 2909 (14.1) 470 (21.8) 2.07 ( ) c 1.36 ( ) c 1.03 ( ) Cerebral palsy and other paralytic syndromes 93 (2.3) 60 (0.3) 104 (0.5) 14 (0.6) 7.37 ( ) c 4.65 ( ) c 4.94 ( ) c Epilepsy and recurrent seizures 352 (8.5) 160 (0.8) 364 (1.8) 64 (3.0) ( ) c 4.10 ( ) c ( ) c Hereditary and degenerative diseases of CNS 112 (2.7) 512 (2.5) 861 (4.2) 119 (5.5) 1.03 ( ) 0.65 ( ) c 0.62 ( ) c Migraine 106 (2.6) 599 (2.9) 950 (4.6) 133 (6.2) 0.79 ( ) c 0.57 ( ) c 0.58 ( ) c Syncope 82 (2.0) 274 (1.3) 434 (2.1) 45 (2.1) 1.43 ( ) c 0.96 ( ) 1.06 ( ) Nutrition 214 (5.2) 395 (1.9) 637 (3.1) 156 (7.24) 2.84 ( ) c 1.70 ( ) c 0.95 ( ) Nutrition metabolism and development 180 (4.4) 329 (1.6) 529 (2.6) 94 (4.4) 2.81 ( ) c 1.71 ( ) c 1.22 ( ) Overweight and obesity 1821 (44.2) 6646 (32.2) 7653 (37.1) 1211 (56.2) 1.73 ( ) c 1.37 ( ) c 0.78 ( ) c Overweight 784 (19.0) 3482 (16.9) 3751 (18.2) 535 (24.8) 1.16 ( ) c 1.05 ( ) 0.76 ( ) c Obesity 1037 (25.2) 3164 (15.4) 3902 (18.9) 676 (31.4) 1.96 ( ) c 1.49 ( ) c 0.94 ( ) Ophthalmology 164 (4.0) 642 (3.1) 672 (3.3) 170 (7.9) 1.33 ( ) c 1.13 ( ) 0.57 ( ) c Pulmonary 383 (9.3) 1578 (7.6) 2582 (12.5) 313 (14.5) 1.19 ( ) c 0.72 ( ) 0.66 ( ) Asthma 318 (7.7) 1306 (6.3) 2267 (11.0) 250 (11.6) 1.19 ( ) c 0.68 ( ) 0.68 ( ) Sleep 256 (6.2) 413 (2.0) 1057 (5.1) 131 (6.1) 3.13 ( ) c 1.26 ( ) c 1.24 ( ) Dyssomnia 215 (5.2) 356 (1.7) 928 (4.5) 99 (4.6) 2.98 ( ) c 1.21 ( ) c 1.40 ( ) c Smoking 235 (5.7) 2463 (12.0) 4447 (21.6) 386 (17.9) 0.40 ( ) c 0.20 ( ) c 0.28 ( ) c CNS, central nervous system; NC, not calculated; OCD, obsessive-compulsive disorder;, not applicable. a All analyses were adjusted for sex, age, race, and months of KPNC membership. b For the developmental disabilities category, individual conditions are listed if they had a prevalence of at least 0.5% in the ASD group. For all psychiatric and medical condition categories, individual conditions are listed if they had a prevalence of at least 1.5% in the ASD group and statistically significant findings in comparison with at least 1 comparison group (P <.05). c Statistically significant odds ratio. d The TC group was selected from among those who did not have an ADHD diagnosis and did not have a diabetes diagnosis; thus, comparisons between the ASD group and the TC group are not possible for these 2 conditions. e NC because the regression model did not converge. f Diagnosed at any time through September PEDIATRICS Volume 141, number s4, April 2018 S339

6 FIGURE 1 Percentage of psychiatric and medical conditions in 14- to 25-year-old individuals with ASD, ADHD, DM, and TCs, from KPNC, A, Allergy and/or Immune; B, Cardiovascular; C, Ear, Nose, and Throat; D, GI; E, Infectious Disease; F, Injury; G, Musculoskeletal; H, Neurology; I, Overweight and/or Obesity; J, Psychiatric; K, Pulmonary; L, Sleep. * denotes a statistically significant difference compared with the ASD group. disorders of the nervous system occurred at equal frequency in the ASD and TC groups; injury, musculoskeletal conditions, and migraines were significantly less common in the ASD group versus the TC group (Table 2). Comparisons between the ASD and ADHD groups were largely similar to those between the ASD group and the TC group, with the following notable exceptions: allergy and/or immunology conditions, diabetes, diarrhea, gastroesophageal reflux, hematology and/or oncology, overweight, and ophthalmologic conditions did not differ in frequency between the ASD group and the ADHD group. GI disorders, genitourinary and/or renal conditions, infectious diseases as a group, and pulmonary conditions (asthma) were all significantly less prevalent in the comparisons between the ASD group versus the ADHD group (Table 2). By contrast, compared with the DM group, individuals with ASD were at a similar or significantly lower risk of most medical conditions, with the exception of hearing impairment, genetic disorders, cerebral palsy, epilepsy, and dyssomnia, all of which S340 DAVIGNON et al

7 were significantly more common in the ASD group compared with the DM group (Table 2). Smoking was significantly less common in individuals with ASD than in each comparison group (Table 2). Additional adjustment for the number of outpatient visits resulted in slightly attenuated risk estimates, with only a few findings losing statistical significance: allergy and/or immunology (ASD versus DM), GI (ASD versus TD), and asthma (ASD versus TD) (data not shown). Prevalence of Conditions by Age and Sex Among individuals with ASD, most conditions increased with age (Fig 2). Infectious diseases and injury decreased with age, and musculoskeletal disorders fluctuated with age. For many conditions, agerelated changes in the comparison groups were in the same direction as the ASD group. Most conditions were more common in females than males, with the largest sex differences observed for allergy and/or immunologic conditions, infections, musculoskeletal conditions, neurologic conditions, and psychiatric conditions (Fig 3). For each major comorbidity category, case-control differences were in the same direction for both males and females. DISCUSSION In this large population of insured, transition-aged individuals, psychiatric and medical conditions were more prevalent in individuals with ASD than in typical or ADHD controls, and most conditions increased with age and were more common in females. Among individuals with ASD, the prevalence of ID (13.0%) was similar to the 16% prevalence reported for another population with a median age of 19 years, 11 although lower than previous reports for younger children 2 and older adults. 12 One reason for the lower prevalence may be that ID is typically identified and treated in school or community settings and thus not routinely noted in medical records. Prevalence of ID did increase with age, and our finding of 19% ID among 22- to 25-yearolds is consistent with our previous finding among all adults 18 years old, with a mean age of 29 years, 4 perhaps because of the need for a medical diagnosis of ID to qualify for social security income. Among individuals with language or learning disorders diagnosed at some point in the past, <2% had documentation of these disorders in the EMR during the transition years. Although language and learning skills may improve with age and treatment, significant deficits persist for the majority of individuals. 13, 14 Thus, it is suggested in our data that language and learning disabilities are underrecognized in transition-aged individuals with ASD. These DDs may impact the ability of patients to understand verbal and written information from medical providers and may contribute to behavioral and emotional difficulties. 10 Recognizing and accommodating the learning and communication needs of individuals with ASD is important for highquality medical care. 10 Approximately one-third of individuals with ASD had a psychiatric condition identified during the study period, a rate lower than the 54% previously reported for the KPNC adult population. 4 Although the prevalence of most psychiatric conditions increased with age, the rate in 22- to 25-year-olds was still lower than that reported among all adults, 4 which is consistent with expectations given that the typical age of onset for many conditions is in teen-aged and young adult years. 1 Of concern was the almost fourfold higher rate of suicide and self-inflicted injury among transitionaged individuals with ASD. Increased risks of suicide and self-harm have been reported previously in other populations of teenagers and adults with ASD. 4, 11 On a positive note, individuals with ASD had lower drug abuse and smoking rates, consistent with previous reports. 4, 15 Because these often begin as social behaviors, the difficulties with social cognition seen in those with ASD may be somewhat protective against these conditions. Our finding that most medical conditions were more prevalent in transition-aged individuals with ASD than those in TC groups is similar to observations in children and adults. 4, 16 Obesity is interesting to consider in relation to other comorbidities observed in the ASD group. Obesity in children with ASD has been linked to gross motor deficits limiting physical activity and with higher rates of poor sleep quality, constipation, selective eating, and other GI disturbances. 17 In addition, obesity has known associations with several chronic medical conditions, including diabetes, hyperlipidemia, hypertension, and cardiovascular disease, 10 all of which were elevated in the ASD group. Although GI and sleep conditions were more common in transitionaged individuals with ASD than individuals in age-matched TC groups, prevalence was lower than previously reported for children and adults with ASD. 4, 18, 19 We also observed a lower rate of migraines in the ASD group versus comparison groups, in contrast to a previous report in which authors indicated that children with autism are more likely than those without to have had frequent severe headaches or migraines. 16 Individuals with ASD and GI problems, sleep disorders, or headaches and/or migraines are more likely to have irritability, challenging behavior, social withdrawal, stereotypy, hyperactivity, inattention, and anxiety These symptoms may lead to psychiatric diagnoses PEDIATRICS Volume 141, number s4, April 2018 S341

8 FIGURE 2 Percentage of psychiatric and medical conditions by age in 14- to 25-year-old individuals with ASD, ADHD, DM, and TCs, from KPNC, A, Allergy and/or Immune; B, Cardiovascular; C, Ear, Nose, and Throat; D, GI; E, Infectious Disease; F, Injury; G, Musculoskeletal; H, Neurology; I, Overweight and/or Obesity; J, Psychiatric; K, Pulmonary; L, Sleep. * denotes a statistically significant difference compared with the ASD group. or treatment with psychotropic medications, which in turn may increase the risk of other health problems. Thus, although transitionaged individuals with ASD may experience relative health compared with children and adults, it is possible that certain medical conditions are underrecognized and undertreated in this age group, contributing to additional medical, behavioral, and mental health problems. There are likely many contributors to the elevated rates of co-occurring conditions seen in individuals with ASD. Self-recognition of differences from others and social isolation may lead to anxiety and S342 DAVIGNON et al

9 FIGURE 3 Percentage of psychiatric and medical conditions by sex in 14- to 25-year-old individuals with ASD, ADHD, DM, and TCs, from KPNC, A, Allergy and/or Immune; B, Cardiovascular; C, Ear, Nose, and Throat; D, GI; E, Infectious Disease; F, Injury; G, Musculoskeletal; H, Neurology; I, Overweight and/or Obesity; J, Psychiatric; K, Pulmonary; L, Sleep. * denotes a statistically significant difference compared with the ASD group. depression, and treatments used to address behavioral, psychiatric, and neurologic conditions may lead to or exacerbate other medical conditions, such as obesity, sleep, and GI problems. In addition, symptoms inherent to ASD, including sensory sensitivities and difficulties describing feelings and pain, interacting with others, transitioning, changing routines, and accommodating to unfamiliar people and places may make it more difficult for teenagers and young adults with ASD to access adequate medical PEDIATRICS Volume 141, number s4, April 2018 S343

10 care. 10 Finally, clinical providers may be unfamiliar with how to accommodate the unique needs of transition-aged individuals with ASD, contributing to less successful office visits. 10, 21 Our findings must be considered in light of study limitations. To focus on conditions for which transition-aged youth are actively being treated, diagnoses were identified only over a 2-year time period, potentially resulting in underascertainment of chronic conditions that are well controlled and require infrequent visits. However, all included participants were members of KPNC for at least 9 months out of 1 year during the 2-year study period and the previous year, making it highly probable that active medical problems were captured. Although efforts were made to classify ICD-9 codes appropriately, phenotypic categorization may have resulted in occasional misclassification. CONCLUSIONS Psychiatric and medical comorbidities were common in this large, insured population of transition-aged individuals with ASD. Although more research is needed to identify the intrinsic and extrinsic factors that contribute to this excess burden, there is a pressing need for all clinicians, particularly general pediatricians and adult physicians, to approach ASD as a chronic health condition requiring regular follow-up and routine screening and treatment of medical and psychiatric issues, as is the standard of care for other chronic medical conditions. ABBREVIATIONS ADHD: attention-deficit/hyperactivity disorder aor: adjusted odds ratio ASD: autism spectrum disorder CI: confidence interval DD: developmental disorder DM: diabetes mellitus EMR: electronic medical record GI: gastrointestinal ICD-9: International Classification of Diseases, Ninth Revision ID: intellectual disability KPNC: Kaiser Permanente Northern California TC: typical control PEDIATRICS (ISSN Numbers: Print, ; Online, ). Copyright 2018 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: Funded by Autism Speaks and the Working for Inclusive and Transformative Healthcare Foundation. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose. REFERENCES 1. American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; Christensen DL, Baio J, Van Naarden Braun K, et al; Centers for Disease Control and Prevention (CDC). Prevalence and characteristics of autism spectrum disorder among children aged 8 years autism and developmental disabilities monitoring network, 11 sites, United States, 2012 [published correction appears in MMWR Morb Mortal Wkly Rep. 2016;65(15):404]. MMWR Surveill Summ. 2016;65(3): Bauman ML. Medical comorbidities in autism: challenges to diagnosis and treatment. Neurotherapeutics. 2010;7(3): Croen LA, Zerbo O, Qian Y, et al. The health status of adults on the autism spectrum. Autism. 2015;19(7): Croen LA, Najjar DV, Ray GT, Lotspeich L, Bernal P. A comparison of health care utilization and costs of children with and without autism spectrum disorders in a large group-model health plan. Pediatrics. 2006;118(4). Available at: www. pediatrics. org/ cgi/ content/ full/ 118/ 4/ e Krieger N. Overcoming the absence of socioeconomic data in medical records: validation and application of a census-based methodology. Am J Public Health. 1992;82(5): Lord C, Rutter M, DiLavore PC, Risi S, Gotham K, Bishop, SL. ADOS-2: Autism Diagnostic Observation Schedule. 2nd ed. Torrance, CA: Western Psychological Services; Karter AJ, Ferrara A, Liu JY, Moffet HH, Ackerson LM, Selby JV. Ethnic disparities in diabetic complications in an insured population. JAMA. 2002;287(19): Denny JC, Ritchie MD, Basford MA, et al. PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations. Bioinformatics. 2010;26(9): Nicolaidis C, Kripke CC, Raymaker D. Primary care for adults on the autism spectrum. Med Clin North Am. 2014;98(5): Schendel DE, Overgaard M, Christensen J, et al. Association of psychiatric and neurologic comorbidity with mortality among persons with autism spectrum disorder in a Danish population. JAMA Pediatr. 2016;170(3): Buck TR, Viskochil J, Farley M, et al. Psychiatric comorbidity and medication use in adults with autism spectrum disorder. J Autism Dev Disord. 2014;44(12): Magiati I, Tay XW, Howlin P. Cognitive, language, social and behavioural S344 DAVIGNON et al

11 outcomes in adults with autism spectrum disorders: a systematic review of longitudinal follow-up studies in adulthood. Clin Psychol Rev. 2014;34(1): Gerber PJ. The impact of learning disabilities on adulthood: a review of the evidenced-based literature for research and practice in adult education. J Learn Disabil. 2012;45(1): Mangerud WL, Bjerkeset O, Holmen TL, Lydersen S, Indredavik MS. Smoking, alcohol consumption, and drug use among adolescents with psychiatric disorders compared with a population based sample. J Adolesc. 2014;37(7): Kohane IS, McMurry A, Weber G, et al. The co-morbidity burden of children and young adults with autism spectrum disorders. PLoS One. 2012;7(4):e Zuckerman KE, Hill AP, Guion K, Voltolina L, Fombonne E. Overweight and obesity: prevalence and correlates in a large clinical sample of children with autism spectrum disorder. J Autism Dev Disord. 2014;44(7): Aldinger KA, Lane CJ, Veenstra- VanderWeele J, Levitt P. Patterns of risk for multiple co-occurring medical conditions replicate across distinct cohorts of children with autism spectrum disorder. Autism Res. 2015;8(6): Chaidez V, Hansen RL, Hertz-Picciotto I. Gastrointestinal problems in children with autism, developmental delays or typical development. J Autism Dev Disord. 2014;44(5): Sullivan JC, Miller LJ, Nielsen DM, Schoen SA. The presence of migraines and its association with sensory hyperreactivity and anxiety symptomatology in children with autism spectrum disorder. Autism. 2014;18(6): Zerbo O, Massolo ML, Qian Y, Croen LA. A study of physician knowledge and experience with autism in adults in a large integrated healthcare system. J Autism Dev Disord. 2015;45(12): PEDIATRICS Volume 141, number s4, April 2018 S345

12 Psychiatric and Medical Conditions in Transition-Aged Individuals With ASD Meghan N. Davignon, Yinge Qian, Maria Massolo and Lisa A. Croen Pediatrics 2018;141;S335 DOI: /peds K Updated Information & Services References Permissions & Licensing Reprints including high resolution figures, can be found at: This article cites 19 articles, 1 of which you can access for free at: #BIBL Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: Information about ordering reprints can be found online:

13 Psychiatric and Medical Conditions in Transition-Aged Individuals With ASD Meghan N. Davignon, Yinge Qian, Maria Massolo and Lisa A. Croen Pediatrics 2018;141;S335 DOI: /peds K The online version of this article, along with updated information and services, is located on the World Wide Web at: Data Supplement at: Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, Copyright 2018 by the American Academy of Pediatrics. All rights reserved. Print ISSN: