Introduction
Methods
Study Population
Demographic | Cases n (%) | Controls n (%) | p value |
---|---|---|---|
Sex
| <0.001 | ||
Male | 3198 (81.8) | 19,592 (50.7) | |
Female | 713 (18.2) | 19,015 (49.3) | |
Age as of Jun 2012
| 0.988 | ||
2–5 | 1051 (26.9) | 10,411 (27.0) | |
6–9 | 1767 (45.2) | 17,397 (45.0) | |
10–12 | 1,093 (27.9) | 10,801 (28.0) | |
Race/ethnicity
| <0.001 | ||
Asian | 749 (19.1) | 6544 (16.9) | |
Black | 282 (7.2) | 2933 (7.6) | |
Hispanic | 825 (21.1) | 9257 (24.0) | |
Native American | 16 (0.4) | 152 (0.4) | |
White | 1720 (44.0) | 15,801 (40.9) | |
Other | 319 (8.2) | 3922 (10.2) | |
Site
| 0.511 | ||
A | 457 (11.7) | 4334 (11.2) | |
B | 3274 (83.7) | 32,591 (84.4) | |
C | 180 (4.6) | 1684 (4.4) | |
Median Income, census tract | <0.001 | ||
Low (≤$55,000) | 1597 (41.6) | 17,278 (45.7) | |
Medium ($55,001–$70,000) | 933 (24.3) | 9539 (25.2) | |
High (>$70,000) | 1305 (34.0) | 10,993 (29.1) | |
Education past high school, census tract | 0.001 | ||
Low (<53%) | 1081 (28.2) | 11,712 (31.0) | |
Medium (53–72%) | 1536 (40.0) | 14,759 (39.0) | |
High (>72%) | 1218 (31.8) | 11,336 (30.0) |
Case and Control Definition
Medical Conditions
Statistical Analyses
Results
Comorbiditya
| ASD cases N (%) | Controls N (%) | Crude model OR (95% CI) | Adjusted model OR (95% CI)b
|
---|---|---|---|---|
Developmental delay
| ||||
Language delay |
1926 (49.25)
|
1376 (3.56)
|
26.25 (24.17–28.52)
|
23.30 (21.36–25.42)
|
Learning & cognitive disorder |
21 (0.54)
|
13 (0.03)
|
16.03 (8.02–32.03)
| 19.72 (9.34–41.61)c
|
Global delay |
693 (17.72)
|
476 (1.23)
|
17.25 (15.27–19.49)
|
17.16 (15.05–19.58)
|
Motor delay |
164 (4.19)
|
238 (0.62)
|
7.06 (5.77–8.63)
|
7.06 (5.67–8.79)
|
Mental Health
| ||||
Disruptive impulse conduct disorders |
204 (5.22)
|
120(0.31)
|
17.65 (14.05–22.17)
|
15.24 (11.96–19.42)
|
Attention-deficit/hyperactivity disorders |
250 (6.39)
|
195 (0.51)
|
13.45 (11.12–16.27)
|
11.61 (9.47–14.24)
|
Anxiety disorder |
125 (3.20)
|
134 (0.35)
|
9.48 (7.41–12.12)
|
10.22 (7.83–13.33)
|
Depression |
23 (0.59)
|
38 (0.10)
|
6.00 (3.57–10.09)
|
5.87 (3.36–10.27)
c
|
Adjustment disorders |
38 (0.97)
|
72 (0.19)
|
5.25 (3.54–7.79)
|
5.02 (3.31–7.59)
|
Tic disorder |
25 (0.64)
|
36 (0.09)
|
6.89 (4.13–11.49)
|
4.78 (2.80–8.14)
|
Other mental health |
71 (1.82)
|
122 (0.32)
|
5.83 (4.35–7.83)
|
5.74 (4.20–7.85)
|
Neurology
| ||||
Cerebral palsy |
45 (1.15)
|
106 (0.27)
|
4.23 (2.98-6.00)
|
4.92 (3.38–7.14)
|
Other disorders of central nervous system |
1454 (37.18)
|
5725 (14.83)
|
3.40 (3.17–3.65)
|
3.39 (3.15–3.65)
|
Epilepsy & recurrent seizures |
194 (4.96)
|
610 (1.58)
|
3.25 (2.76–3.83)
|
3.38 (2.84–4.02)
|
Other congenital anomalies of nervous system |
80 (2.05)
|
299 (0.77)
|
2.68 (2.09–3.43)
|
2.79 (2.15–3.61)
|
Abnormalities of Skull and Face |
141 (3.61)
|
510 (1.32)
|
2.79 (2.31–3.38)
|
2.56 (2.10–3.12)
|
Hereditary and degenerative diseases of central nervous system |
56 (1.43)
|
248 (0.64)
|
2.25 (1.68–3.01)
|
2.19 (1.61–2.96)
|
Paroxysmal |
221 (5.65)
|
1122 (2.91)
|
2.00 (1.73–2.32)
|
2.01 (1.73–2.35)
|
Disorders of peripheral nervous system | 27 (0.69) | 154 (0.40) | 1.74 (1.15–2.62) | 1.66 (1.08–2.54) |
Headache | 20 (0.51) | 154 (0.40) | 1.28 (0.80–2.05) | 1.24 (0.76–2.02) |
Other neurology | 46 (1.18) | 263 (0.68) | 1.74 (1.27–2.38) | 1.68 (1.20–2.35) |
Nutrition
| ||||
Symptom concerning nutrition metabolism and development |
1517 (38.79)
|
6429 (16.65)
|
3.17 (2.96–3.40)
|
3.18 (2.95–3.42)
|
Genetic conditions |
39 (1.00)
|
133 (0.34)
|
2.91 (2.04–4.17)
|
3.13 (2.15–4.54)
|
Ear, nose and throat conditions |
711 (18.18)
|
3097 (8.02)
|
2.55 (2.33–2.79)
|
2.47 (2.25–2.72)
|
Sleep
| ||||
Organic sleep apnea |
47 (1.20)
|
195 (0.51)
|
2.40 (1.74–3.30)
|
2.17 (1.55–3.03)
|
Dyssomnia |
189 (4.83)
|
851 (2.20)
|
2.25 (1.92–2.65)
|
2.11 (1.78–2.49)
|
Gastrointestinal conditions
| ||||
GERD |
262 (6.70)
|
1163 (3.01)
|
2.31 (2.01–2.65)
|
2.20 (1.90–2.55)
|
Diarrhea |
215 (5.50)
|
1217 (3.15)
|
1.79 (1.54–2.07)
|
1.72 (1.48–2.01)
|
Constipation |
323 (8.26)
|
2225 (5.76)
|
1.47 (1.30–1.66)
|
1.62 (1.43–1.84)
|
Upper GI diseases |
113 (2.89)
|
596 (1.54)
|
1.90 (1.55–2.33)
|
1.61 (1.30–1.99)
|
Upper GI motility |
269 (6.88)
|
1721 (4.46)
|
1.58 (1.39–1.81)
|
1.54 (1.34–1.77)
|
Functional disorders | 188 (4.81) | 1658 (4.29) | 1.13 (0.96–1.31) | 1.16 (0.99–1.36) |
Lower GI | 71 (1.82) | 645 (1.67) | 1.09 (0.85–1.39) | 1.00 (0.77–1.29) |
Other disease of esophagus |
47(1.20)
|
225 (0.58)
|
2.08 (1.51–2.85)
|
2.10 (1.51–2.91)
|
Other GI |
627 (16.03)
|
4727 (12.24)
|
1.37 (1.25–1.50)
|
1.37 (1.24–1.51)
|
Metabolic
| ||||
Fluid, electrolyte, and acid-base balance |
106 (2.71)
|
584 (1.51)
|
1.81 (1.47–2.24)
|
1.78 (1.43–2.21)
|
Overweight, obesity and other hyperalimentation |
102 (2.61)
|
640 (1.66)
|
1.59 (1.29–1.96)
|
1.63 (1.31–2.04)
|
Musculoskeletal |
562 (14.37)
|
3354 (8.69)
|
1.76 (1.60–1.94)
|
1.69 (1.53–1.86)
|
Ophthalmology |
676 (17.28)
|
4239 (10.98)
|
1.69 (1.55–1.85)
|
1.66 (1.52–1.83)
|
Pulmonary |
270 (6.90)
|
1970 (5.10)
|
1.38 (1.21–1.57)
|
1.28 (1.11–1.46)
|
Autoimmune
| ||||
Inflammatory bowel disease |
603 (15.42)
|
4618 (11.96)
|
1.34 (1.22–1.47)
|
1.34 (1.22–1.48)
|
Other autoimmune | 57 (1.46) | 374 (0.97) | 1.51 (1.14-2.00) | 1.54 (1.15–2.05) |
Other autoimmune dermatitis | 25 (0.64) | 186 (0.48) | 1.33 (0.87–2.02) | 1.40 (0.90–2.16) |
Infections
| ||||
Bacterial | 241 (6.16) | 2262 (5.86) | 1.06 (0.92–1.21) | 1.06 (0.92–1.22) |
Viral | 2338 (59.78) | 21,789 (56.44) | 1.15 (1.07–1.23) | 1.10 (1.02–1.18) |
Ear | 2770 (70.83) | 26,381 (68.33) | 1.13 (1.05–1.21) | 1.07 (0.99–1.15) |
Eye | 1536 (39.27) | 15,226 (39.44) | 0.99 (0.93–1.06) | 0.94 (0.88–1.01) |
Gastrointestinal |
819 (20.94)
|
6908 (17.89)
|
1.22 (1.12–1.32)
|
1.19 (1.09–1.29)
|
Female genitourinary | 46 (1.18) | 1253 (3.25) | 0.35 (0.26–0.48) | 0.97 (0.71–1.32) |
Genitourinary | 130 (3.32) | 1847 (4.78) | 0.68 (0.57–0.82) | 1.09 (0.90–1.31) |
Lower respiratory |
1290 (32.98)
|
13,177 (34.13)
|
0.95 (0.89–1.02)
|
0.87 (0.81–0.94)
|
Upper respiratory | 3430 (87.70) | 33,734 (87.37) | 1.03 (0.93–1.14) | 0.95 (0.85–1.05) |
Lymph | 146 (3.73) | 1303(3.37) | 1.11 (0.93–1.32) | 1.00 (0.84–1.20) |
Mycoses | 939 (24.01) | 9165 (23.74) | 1.02 (0.94–1.10) | 1.10 (1.02–1.20) |
Skin | 754 (19.28) | 7583 (19.64) | 0.98 (0.90–1.06) | 0.95 (0.87–1.04) |
Other infection | 199 (5.09) | 1494 (3.87) | 1.33 (1.14–1.55) | 1.26 (1.08–1.48) |
Hematology
| ||||
Hematology anemia | 147 (3.76) | 1135 (2.94) | 1.29 (1.08–1.54) | 1.27 (1.06–1.52) |
Neoplasms | 108 (2.76) | 924 (2.39) | 1.16 (0.95–1.42) | 1.25 (1.01–1.54) |
Other hematology | 36 (0.92) | 262 (0.68) | 1.36 (0.96–1.93) | 1.31 (0.91–1.87) |
Allergy
| ||||
Allergic rhinitis | 266 (6.80) | 2101 (5.44) | 1.27 (1.11–1.45) | 1.15 (1.00-1.32) |
Atopic dermatitis | 825 (21.09) | 7279 (18.85) | 1.15 (1.06–1.25) | 1.10 (1.01–1.20) |
Conjunctivitis | 761 (19.46) | 6850 (17.74) | 1.12 (1.03–1.22) | 1.03 (0.94–1.12) |
Contact dermatitis and eczema | 838 (21.43) | 7729 (20.02) | 1.09 (1.01–1.18) | 1.07 (0.98–1.16) |
Drug allergy | 108 (2.76) | 805 (2.09) | 1.33 (1.09–1.63) | 1.29 (1.04–1.59) |
Food allergy | 112 (2.86) | 683 (1.77) | 1.64 (1.34-2.00) | 1.37 (1.11–1.69) |
Serious local reactions | 304 (7.77) | 3090 (8.00) | 0.97 (0.86–1.10) | 0.94 (0.83–1.06) |
Stevens-Johnson syndrome | 23 (0.59) | 159 (0.41) | 1.43 (0.92–2.22) | 1.25 (0.80–1.95) |
Urticaria | 277 (7.08) | 2388 (6.19) | 1.16 (1.02–1.32) | 1.08 (0.95–1.24) |
Other allergies | 398 (10.18) | 3446 (8.93) | 1.16 (1.04–1.29) | 1.07 (0.95–1.19) |
Genitourinary
| ||||
Genital tract | 166 (4.24) | 893 (2.31) | 1.87 (1.58–2.22) | 1.13 (0.95–1.34) |
Renal disorders | 112 (2.86) | 1231 (3.19) | 0.90 (0.74–1.09) | 1.18 (0.97–1.45) |
Injury
| ||||
Accidental poisoning | 1461 (37.36) | 14,032 (36.34) | 1.04 (0.98–1.12) | 1.12 (1.02–1.23) |
Fracture | 239 (6.11) | 2407 (6.23) | 0.98 (0.85–1.12) | 0.92 (0.80–1.07) |
Injury of head or neck | 456 (11.66) | 3570 (9.25) | 1.30 (1.17–1.44) | 1.19 (1.07–1.32) |
Cardiovascular disorders | 30 (0.77) | 122 (0.32) | 2.44 (1.63–3.64) | 2.02 (1.30–3.13) |
Endocrine disorders | 30 (0.77) | 218 (0.56) | 1.36 (0.93-2.00) | 1.86 (1.25–2.77) |
Other
| ||||
Fever of unknown | 385 (9.84) | 3548 (9.19) | 1.08 (0.97–1.21) | 1.05 (0.93–1.20) |
Unspecified adverse effect of drug | 94 (2.40) | 737 (1.91) | 1.27 (1.02–1.57) | 1.23 (0.98–1.54) |
Asthma | 1014 (25.93) | 9564 (24.77) | 1.06 (0.99–1.15) | 0.94 (0.86–1.01) |
Associations of Condition Clusters Using Supervised Clustering
Cluster descriptiona
| ASD cases N (%) | Controls N (%) | Crude model OR (95% CI) | Adjusted model OR (95% CI)b
| Latency time in months, Mean (SD)c
|
---|---|---|---|---|---|
No mental health or developmental delay diagnosis
| |||||
No diagnoses of ear, nose & throat, nutrition, or ophthalmology | 769 (19.66 | 25,796 (66.81) | Reference | Reference | No comorbidities |
Ophthalmology, but no diagnoses of ear, nose & throat or nutrition | 134 (3.43) | 2850 (7.38) | 1.57 (1.29–1.90) | 1.50 (1.24–1.83) | 35.9 (21.9) |
Ear, nose & throat diagnosis, but no nutrition diagnosis | 116 (2.97) | 2062 (5.34) | 1.98 (1.61–2.43) | 1.93 (1.56–2.38) | 20.9 (18.1) |
Nutrition diagnosis, but no ear, nose & throat diagnosis | 308 (7.88) | 5004 (12.96) | 2.23 (1.94–2.56) | 2.19 (1.90–2.52) | 22.3 (21.8) |
Ear, nose & throat dx and nutrition diagnoses | 61 (1.56) | 554 (1.43) | 4.29 (3.22–5.71) | 4.21 (3.14–5.66) | 29.8 (25.7) |
Mental health (MH) diagnosis but no developmental delay
| |||||
MH diagnosis other than attention-deficit/hyperactivity disorder or disruptive impulse conduct disorder | 65 (1.66) | 269 (0.70) | 9.11 (6.73–12.31) | 9.12 (6.68–12.46) | 14.1 (17.8) |
Attention-deficit/hyperactivity disorder, but no disruptive impulse conduct disorder | 99 (2.53) | 128 (0.33) | 29.26 (21.53–39.78) | 23.10 (16.83–31.72) | 14.8 (15.5) |
Disruptive impulse conduct disorder | 106 (2.71) | 102 (0.26) | 44.29 (32.38–60.58) | 38.32 (27.55–53.31) | 15.2 (16.6) |
Developmental delay
| |||||
Motor delay but no language delay | 64 (1.64) | 181 (0.47) | 11.56 (8.42–15.88) | 10.56 (7.52–14.84) | 20.6 (16.0) |
Global delay or delay in cognitive or learning, but no language or motor delay | 26 (6.72) | 287 (0.74) | 31.67 (25.88–38.75) | 29.97 (24.24–37.07) | 15.2 (19.9) |
Language delay, but no dx of global delay, MH, or other disorders of central nervous system | 912 (23.32) | 883 (2.29) | 34.80 (30.56–39.64) | 28.82 (25.18–32.99) | 12.9 (14.4) |
Language delay and other disorders of central nervous system, but no global delay or MH diagnosis | 472 (12.07) | 309 (0.80) | 51.90 (43.45–61.99) | 42.84 (35.59–51.55) | 15.4 (15.7) |
Language delay and MH, but no global delay | 133 (3.40) | 46 (0.12) | 103.67 (70.96–151.46) | 78.54 (53.46–115.39) | 32.7 (25.5) |
Language delay and global delay | 409 (10.46) | 138 (0.36) | 104.64 (83.37–131.34) | 101.71 (79.92–129.44) | 14.9 (15.7) |
Cluster descriptiona
| ASD cases N (%) | Controls N (%) | Crude model OR (95% CI) | Adjusted modelb
OR (95% CI) | Latency Time in months mean (SD)c
|
---|---|---|---|---|---|
No developmental delay diagnosis
| |||||
No diagnoses of ear, nose & throat, nutrition, ophthalmology, musculoskeletal, or constipation | 1146 (29.30) | 25,216 (65.31) | Reference | Reference | No comorbidities |
Constipation, but no dx of gastroesophageal reflux disease, ear, nose & throat, nutrition, ophthalmology, musculoskeletal | 66 (1.69) | 1067 (2.76) | 1.35 (1.04–1.75) | 1.46 (1.12–1.90) | 46.5 (27.2) |
Musculoskeletal, but no diagnoses of ear, nose & throat, nutrition, or ophthalmology | 121 (3.09) | 1,783 (4.62) | 1.55 (1.27–1.89) | 1.45 (1.19–1.78) | 43.7 (27.1) |
Ophthalmology, but no diagnoses of nutrition or ear, nose & throat | 191 (4.88) | 2620 (6.79) | 1.63 (1.38–1.91) | 1.59 (1.34–1.87) | 50.3 (27.0) |
Ear, nose & throat, but no diagnoses of nutrition, or ophthalmology | 105 (2.68) | 1340 (3.47) | 1.83 (1.48–2.26) | 1.75 (1.41–2.18) | 31.2 (26.4) |
Nutrition diagnosis but no seizures | 395 (10.10) | 4713 (12.21) | 1.99 (1.76–2.24) | 1.99 (1.75–2.25) | 36.3 (30.3) |
Ear, nose & throat and ophthalmology, but no nutrition diagnosis | 26 (0.66) | 149 (0.39) | 4.09 (2.66–6.30) | 3.73 (2.38–5.87) | 35.9 (34.1) |
Constipation and gastroesophageal reflux disease, but no diagnoses of ear, nose & throat, nutrition, ophthalmology, musculoskeletal | 13 (0.33) | 55 (0.14) | 5.09 (2.71–9.56) | 5.15 (2.66–9.97) | 39.5 (20.1) |
Nutrition and seizure diagnoses | 17 (0.43) | 73 (0.19) | 5.50 (3.16–9.57) | 5.63 (3.13–10.15) | 40.4 (25.2) |
Developmental delay diagnosis
| |||||
Motor delay but no language delay | 41 (1.05) | 167 (0.43) | 5.23 (3.64–7.50) | 4.75 (3.20–7.05) | 24.4 (18.0) |
Global delay or delay in cognitive or learning, but no language or motor delay | 208 (5.32) | 273 (0.71) | 18.15 (14.80-22.27) | 17.15 (13.81–21.29) | 19.9 (24.2) |
Language delay, but no dx of global delay, or other disorders of central nervous system | 909 (23.24) | 810 (2.10) | 25.26 (22.38–28.51) | 20.70 (18.28–23.48) | 16.5 (17.2) |
Language delay and other disorders of central nervous system, but no global delay | 399 (10.20) | 239 (0.62) | 36.08 (30.09–43.26) | 29.81 (24.64–36.06) | 14.4 (16.9) |
Language delay and global delay | 274 (7.01) | 104 (0.27) | 62.60 (48.71–80.45) | 60.82 (46.67–79.25) | 15.6 (16.1) |