Autism spectrum disorders in children of parents with inflammatory bowel disease – a nationwide cohort study in Denmark

Figures & data

Table 1 Characteristics of children born in Denmark during 1994–2009 according to parental IBD, N=1,005,330

Characteristics	Parental CD (n=4,302)	Parental UC (n=7,586)	No parental IBD (n=993,442)
	n (%)	n (%)	n (%)
Parental IBD
Maternal	2,611 (60.7)	4,089 (53.9)	–
Paternal	1,691 (39.3)	3,497 (46.1)	–
Year of birth
1994–1999	1,075 (25.0)	2,025 (26.7)	384,742 (38.7)
2000–2004	1,393 (32.4)	2,537 (33.4)	306,827 (30.9)
2005–2009	1,834 (42.6)	3,024 (39.9)	301,873 (30.4)
Sex of child
Female	2,081 (48.4)	3,752 (49.5)	483,555 (48.7)
Male	2,221 (51.6)	3,834 (50.5)	509,887 (51.3)
Mode of delivery
Vaginal	3,114 (72.4)	5,687 (75.0)	815,705 (82.1)
Cesarean section	1,188 (27.6)	1,899 (25.0)	177,737 (17.9)
Birth weight (g)
<2500	282 (6.7)	453 (6.0)	51,619 (5.2)
2500–3499	1,967 (45.7)	3,226 (42.5)	412,183 (41.5)
≥3500	2,040 (47.4)	3,867 (51.0)	525,018 (52.9)
Missing	13 (0.3)	40 (0.5)	4,622 (0.5)
Gestational age (weeks)
<37	345 (8.0)	609 (8.0)	62,896 (6.3)
37–41	3,731 (86.7)	6,463 (85.2)	851,351 (85.7)
≥42	214 (5.0)	477 (6.3)	73,468 (7.4)
Missing	12 (0.3)	37 (0.5)	5,727 (0.6)
Mother’s age at child’s birth (years)
<25	463 (10.8)	568 (7.5)	132,701 (13.4)
25–34	3,292 (76.5)	5,905 (77.8)	746,095 (75.1)
≥35	547 (12.7)	1,113 (14.7)	114,646 (11.5)
Father’s age at child’s birth (years)
<25	232 (5.4)	245 (3.2)	62,659 (6.3)
25–34	2,986 (69.4)	5,040 (66.4)	680,175 (68.5)
≥35	1,084 (25.2)	2,301 (30.3)	250,608 (25.2)
Multiple gestation	159 (3.7)	316 (4.2)	40,515 (4.1)
Parental history of psychiatric disorder	149 (3.5)	243 (3.2)	23,784 (2.4)
Maternal smoking during pregnancy
No	3,153 (73.3)	6,285 (82.8)	755,672 (76.1)
≤10 cigarettes/day	743 (17.3)	817 (10.8)	159,583 (16.1)
>10 cigarettes/day	235 (5.5)	210 (2.8)	40,790 (4.1)
Missing	171 (4.0)	274 (3.6)	37,397 (3.8)

Abbreviations: CD, Crohn’s disease; IBD, inflammatory bowel disease; n/N, number of children; UC, ulcerative colitis; n/N, number of children.

Table 2 Incidence rates and crude and adjusted incidence rate ratios for ASD in Danish children born during 1994–2009, according to parental IBD status, (N=1,005,330)

Parental IBD	N	Children with ASD (n)	IR (per 10,000 PY)	Crude IRR (95% CI)	Adjusted IRRa (95% CI)
No parental IBD	993,442	8,025	9.0	1.0 (Ref)	1.0 (Ref)
Parental IBD	11,888	62	6.8	0.8 (0.6–1.1)	0.8 (0.6–1.0)
• Maternal IBD	6,700	31	6.0	0.7 (0.5–1.0)	0.7 (0.5–1.0)
• Paternal IBD	5,188	31	7.9	1.0 (0.7–1.4)	0.9 (0.6–1.3)
Parental CD	4,302	22	6.8	0.8 (0.6–1.3)	0.8 (0.5–1.2)
• Maternal CD	2,611	12	6.1	0.7 (0.4–1.3)	0.7 (0.4–1.2)
• Paternal CD	1,691	10	8.1	1.0 (0.5–1.8)	0.9 (0.5–1.7)
Parental UC	7,586	40	6.8	0.8 (0.6–1.1)	0.8 (0.6–1.1)
• Maternal UC	4,089	19	5.9	0.7 (0.4–1.1)	0.7 (0.4–1.1)
• Paternal UC	3,497	21	7.8	0.9 (0.6–1.4)	0.9 (0.6–1.4)

Notes:

a Adjusted for year of birth, sex, mother’s and father’s age at child’s birth, multiple gestation, maternal smoking during pregnancy, and parental history of psychiatric disorders.

Abbreviations: ASD, autism spectrum disorders; CD, Crohn’s disease; CI, confidence interval; IBD, inflammatory bowel disease; IR, Incidence rate; IRR, incidence rate ratio; N/n, number of children; PY, person-years; Ref, reference; UC, ulcerative colitis.

Table 3 Association between parental IBD and type of ASD in offspring

	Infantile autisma		Asperger syndromea		Pervasive development disorder not specifieda		Atypical autisma
	Events (n)	Adjusted IRRb (95% CI)	Events (n)	Adjusted IRRb (95% CI)	Events (n)	Adjusted IRRb (95% CI)	Events (n)	Adjusted IRRb (95% CI)
No parental IBD	2,787	1.0 (Ref)	2,023	1.0 (Ref)	3,374	1.0 (Ref)	913	1.0 (Ref)
Parental IBD	33	1.1 (0.8–1.6)	12	0.7 (0.4–1.2)	23	0.7 (0.5–1.0)	5	0.6 (0.2–1.4)
• Maternal IBD	15	0.9 (0.5–1.5)	6	0.6 (0.3–1.3)	13	0.7 (0.4–1.2)	2	0.4 (0.1–1.6)
• Paternal IBD	18	1.4 (0.9–2.2)	6	0.8 (0.3–1.7)	10	0.7 (0.4–1.3)	3	0.8 (0.3–2.5)
Parental CD	10	0.9 (0.5–1.8)	4	0.7 (0.2–1.7)	10	0.8 (0.5–1.6)	1	0.3 (0.1–2.3)
• Maternal CD	5	0.8 (0.3–1.8)	4	0.5 (0.1–2.0)	7	1.0 (0.5–2.0)	–	NA
• Paternal CD	5	1.2 (0.5–2.9)	2	0.8 (0.2–3.3)	3	0.7 (0.2–2.1)	1	0.9 (0.1–6.1)
Parental UC	23	1.2 (0.8–1.8)	8	0.7 (0.3–1.3)	13	0.6 (0.4–1.1)	4	0.7 (0.3–1.9)
• Maternal UC	10	1.0 (0.5–1.8)	4	0.6 (0.2–1.6)	6	0.5 (0.2–1.2)	2	0.7 (0.2–2.6)
• Paternal UC	13	1.5 (0.9–2.5)	4	0.7 (0.3–2.0)	7	0.7 (0.3–1.5)	2	0.8 (0.2–3.1)

Notes:

a Children who have more than one ASD subtype diagnosis are counted according to each subtype;

b adjusted for year of birth, sex, mother’s and father’s age at child’s birth, multiple gestation, maternal smoking during pregnancy, and parental history of psychiatric disorders.

Abbreviations: ASD, autism spectrum disorders; CD, Crohn’s disease; CI, confidence interval; IBD, inflammatory bowel disease; IRR, incidence rate ratio; n, number of children; NA, not applicable; Ref, reference; UC, ulcerative colitis.

Table S1 ICD-8 and ICD-10 codes for IBD, autism spectrum disorders, and included psychiatric disorders

Diagnoses	ICD diagnostic codes
ASD	ICD-8: 299.00, 299.01
Infantile autism	ICD-10: F84.0
Atypical autism	ICD-10: F84.1
Asperger syndrome	ICD-10: F84.5
Pervasive developmental disorder not otherwise specified	ICD-10: F84.8, F89.9
Crohn’s disease	ICD-8: 563.01 ICD-10: K50
Ulcerative colitis	ICD-8: 563.19, 569.04 ICD-10: K51
Schizophrenia and other paranoid psychoses	ICD-8: 295, 297, 298.39 ICD-10: F20-29
Mood disorders	ICD-8: 296, 298.09,298.19, 300.49, 301.19 ICD-10: F30-39
Nervous conditions and personality disorders	ICD-8: 300 except 300.49, 301 except 301.19 ICD-10: F40, F60

Abbreviations: ASD, autism spectrum disorders; IBD, inflammatory bowel disease; ICD-8, International Classification of Diseases, 8th revision; ICD-10, International Classification of Diseases, 10th revision.