Breastfeeding and genetic factors in the etiology of inflammatory bowel disease in children

Table 1 Clinical and epidemiological features of Crohn’s disease and ulcerative colitis

	CD	UC
Region of involvement	Any portion of gastrointestinal tract	Rectum and colon
Typical region of involvement	Ileum and colon	Rectum and extending proximally
Nature of inflammatory process	Segmental, transmural	Continuous, limited to mucosa
Extraintestinal manifestations	Oral aphthous ulcers, peripheral arthritis, erythema nodosum, digital clubbing, episcleritis, renal stones, and gallstones	Pyoderma gangrenosum, sclerosing cholangitis, chronic active hepatitis, and ankylosing spondylitis
Age at presentation	Bimodal; 1st peak in late teens; 2nd peak in late adulthood	Bimodal; 1st peak in late teens; 2nd peak in late adulthood
Gender difference	Women are slightly more likely than men to develop CD	Men are slightly more likely than women to develop UC

Table 2 Incidence of Crohn’s disease

Annual incidence per 100000	Time period	Geographic region	Data collection	Age group studied	References
0.73	1958-1960	Nottingham, England	Retrospective	Adults	[70]
3.63	1970-1972				[70]
6.1	1971-1980	Orebro, Sweden	Retrospective	Children ≤ 16 years old	[71]
13.39 (white males)	1977-1979	Baltimore SMSA	Retrospective	All	[10]
13.54 (white females)					[10]
11.29 (non-white males)					[10]
14.08 (non-white females)					[10]
0.66	1968	Scotland	Retrospective	Children ≤ 16 years old	[72]
2.29b	1983				[72]
0.00	1920-1929	Rochester, NY	Retrospective	All	[73]
5.03	1970-1979				[73]
3.90	1980-1989				[73]
< 1.0	1962-1969	Copenhagen	Prospective	All	[74]
4.1	1979-1987				[74]
1.30	1983-1988	South Glamorgan, Wales	Retrospective	Children < 16 years old	[75]
3.11	1989-1993				[75]
21.0	1940-1943	Olmsted County, MN	Retrospective	All	[76]
27.8	1964-1973				[76]
26.9	1984-1993				[76]
14.6	1989-1994	Manitoba, Canada	Retrospective	All	[77]
21.91	1981-1983	Scotland	Retrospective	Children < 19 years old	[78]
22.91	1990-1992				[78]
5.5	1990-1994	Iceland	Prospective	All	[79]
1.2	1984-1986	Sweden	Prospective	Children < 16 years old	[80]
1.3	1993-1995				[80]
25.2	1988-1990	Northern France	Prospective	All	[81]
25.8	1991-1993				[81]
25.9	1994-1996				[81]
26.4	1997-1999				[81]
2.00	1990-1994	Southeastern Norway	Prospective	Children < 16 years old	[82]
4.56	2000-2001	Wisconsin	Prospective	Children < 18 years old	[83]

¹Age-adjusted; ²Age- and gender-adjusted; ^bP < 0.0001 compared to 1968.

Table 3 Incidence of ulcerative colitis

Annual incidence per 100000	Time period	Geographic region	Data collection	Age group studied	References
12.92 (white males)	1977-1979	Baltimore SMSA	Retrospective	All	[10]
11.79 (white females)					[10]
11.29 (non-white males)					[10]
12.90 (non-white females)					[10]
1.91	1968	Scotland	Retrospective	Children ≤ 16 years old	[72]
31.56	1983				[72]
0.06	1920-1929	Rochester, NY	Retrospective	All	[73]
3.51	1970-1979				[73]
2.32	1980-1989				[73]
6.9	1962-1969	Copenhagen	Prospective	All	[84]
9.2	1980-1987				[84]
0.71	1983-1993	South Glamorgan, Wales	Retrospective	Children < 16 years old	[75]
14.3	1989-1994	Manitoba, Canada	Retrospective	All	[77]
16.5	1990-1994	Iceland	Prospective	All	[79]
1.4	1984-1986	Sweden	Prospective	Children < 16 years old	[80]
3.2a	1993-1995				[80]
24.2	1988-1990	Northern France	Prospective	All	[81]
24.3	1991-1993				[81]
23.9	1994-1996				[81]
23.5	1997-1999				[81]
2.14	1990-1994	Southeastern Norway	Prospective	Children < 16 years old	[77]
2.14	2000-2001	Wisconsin	Prospective	Children < 18 years old	[83]

¹Age-adjusted; ²Age- and gender-adjusted; ³P = 0.052 compared to 1968; ^aP < 0.05 compared to 1984-1986.

Table 4 Factors affecting development of IBD

Factor	Effect	Findings
Cigarette smoking	Protective factor for UC	Pooled OR for UC = 0.41 (0.34-0.48); χ2 = 11.52 (P < 0.001)[12]
	Risk factor for CD	Pooled OR for CD = 2.0 (1.65-2.47); χ2 = 48.4 (P < 0.001)[12]
Passive cigarette smoke	Uncertain	No effect[2585]
		UC [ψ = 0.50 (0.25-1.00), n = 163][86]
		CD [ψ = 5.32 (1.09-25.9), n = 39 age and sex-matched pairs][87]
		UC [ψ = 2.19 (0.75-6.41), n = 33 age and sex-matched pairs][87]
Oral contraceptive use	Risk factor for UC	Pooled RR for UC = 1.29 [(0.94-1.77) adjusted for smoking]
		Pooled RR for UC = 1.68 [(0.97-2.88) unadjusted for smoking]
	Risk factor for CD	Pooled RR for CD = 1.44 [(1.12-1.86) adjusted for smoking]
		Pooled RR for CD = 1.68 [(0.97-2.88) unadjusted for smoking]
Diet	Protective factor for CD
	Vitamin C	ψ = 0.48 and ψ = 0.23 for medium and high intake, respectively, vs low intake, Ptrend = 0.02[17]
	Risk factors for UC
	Sucrose	[Sucrose] ψ = 2.05 and ψ = 4.22 for medium and high intake, respectively, vs low intake, Ptrend = 0.02
	Animal fat	[Animal fat] ψ = 2.02 and ψ = 4.09 for medium and high intake, respectively, vs low intake, Ptrend = 0.02
	Cholesterol	[Cholesterol] ψ = 2.14 and ψ = 4.57 for medium and high intake, respectively, vs low intake, Ptrend = 0.02
	Soft drinks	[Soft drinks] ψ = 1.84 and ψ = 3.39 for medium and high intake, respectively, vs low intake, vs Ptrend = 0.02[17]
Infections	Risk factor for CD/possible risk factor for UC	CD patients had a higher rate of gastroenteritis than did controls (6/57 vs 1/114, P = 0.005)[8]
		UC patients and controls did not differ (4/51 vs 1/102, P = NS)[8]
	Gastroenteritis	Children with CD were more likely than unaffected siblings to have had diarrheal illness [RR = 2.7 (95% CI 1.5-5.8) P < 0.02, n = 294] Children with UC were more likely than unaffected siblings to have had diarrheal illness [RR = 3.2 (95% CI 1.15-8.75), P = 0.03, n = 231][20]
	Diarrheal illness in infancy
	Risk factor for CD and UC	Recurrent respiratory infections were significantly more common in CD patients and in UC patients than their controls (102/298 vs 156/601 and 73/194 vs 106/393, respectively, both P < 0.01)[7]
	Recurrent respiratory infections	Adults with CD had an increased frequency of childhood infections compared to neighbor controls [ψ = 4.67, (95% CI 2.65-8.23) n = 322 cases, 262 controls][24]
	Childhood infections	Adults with UC had more frequent childhood infections than neighbor controls [ψ = 2.37 (95% CI 1.19-4.71) (n = 181 cases, 141 controls)][24]
Antibiotic use	Risk factor for CD	Patients with CD used antibiotics more frequently than controls (P < 0.01)[7]
		Adults with CD had more frequent treatment with antibiotics for both otitis [ψ = 2.07 (95% CI 1.03-4.14)] and pharyngitis [ψ = 2.14 (95% CI 1.20-3.84)] than controls[24]
Perinatal factors	Risk factor for UC
	Number of older siblings	For UC, the odds ratios for having one, two, and three or more older siblings were 1.08 (1.03-1.14), 1.09 (1.01-1.16), and 1.12 (1.02-1.23), respectively (n = 15823 cases; 79546 controls)[27]
	Protective factor for CD
	Number of younger siblings	For CD, the odds ratios for having one, two, and three or more younger siblings were 0.93 (0.88-0.99), 0.89 (0.82-0.96), and 0.83 (0.75-0.92), respectively (n = 12668 cases; 63035 controls)[27]