Hygiene hypothesis in inflammatory bowel disease: A critical review of the literature

Table 1 Key studies examining the association between IBD and proxy measures of the 'hygiene hypothesis'

Author	Sample	Study design	Variables examined
Gilat, 1987[50]	14 centres from 9 countries UC = 197; CD = 302 Diagnosis before 20 yr, all patients < 25 yr old Age-sex match controls	Case control Questionnaires	Siblings, birth order, breast feeding, infection, eczema, family history, vaccination, pregnancy factors
Rigas, 1993[84]	New York, USA Diagnosed between 1986-1990 CD = 68; UC = 39 Pediatric gastroenterology controls = 202	Case control Questionnaires	Sibship size, maternal age at birth, month of birth, breastfeeding, maternal smoking one more
Gent et al, 1994[92]	UK UC = 231; CD = 133 16-87 yr Age-sex matched controls from same general practice as cases	Case control Home interview	Housing in infancy, presence of a lavatory, hot water tap, separate bathroom
Duggan et al, 1998[93]	UK Consecutive weekly attendees at IBD clinics UC = 213, CD = 110 (aged over 15 yr) Aged-Sex match controls from hospital patients undergoing elective surgery	Case control Questionnaire	Previous surgery, childhood domestic circumstances before age 11 yr (heating, day care, toilets, fixed bathroom, bedroom sharing)
Sicilia et al, 2001[87]	Spain Gastroenterologists recruited incident cases of CD patients aged 10-79 yr = 103 Outpatient clinic patient controls matched for age, sex and urban/rural.	Case control Population based study Structured interview 95% response rate	Number of persons in home, number of bathrooms, availability of hot water
Montgomery et al, 2002[88]	Swedish inpatient register UC = 15 823; CD = 12 668 Controls from Swedish Census, Births & Deaths Register: age and location matched 79 546; 63 035, respectively	Case control Swedish Multi-generation register linking cases and controls with family history information	Siblings
Feeney et al, 2002[16]	UK (Grew up in UK) 16-45 yr CD = 139; UC = 137 attendees at Gastroenterology clinics	Case control General hospital Questionnaire	Hp seroprevalence, family, hot water tap, nursery attendance, indoor toilets, swimming pool use, number or cars, number of house moves, urban/rural location, pets
Hampe et al, 2003[89]	Germany Consecutive IBD patients identified from German Crohn's & Colitis association = 2351 Controls unaffected first degree relatives = 3364	Case controls Questionnaire	Availability of tap water, toilet, central heating, siblings and community size
Amre et al, 2006[22]	Canada Newly diagnosed CD < 20 yr old = 194 Orthopaedic patients controls matched for timing of diagnosis & area of residence	Hospital based Case control Structured questionnaires – mothers mostly answered for patients	Siblings, breastfeeding, day care, place of residency, hot water tap, toilets, number of inhabitants, number of rooms, availability of private bed, personal hygiene, pet ownership, infection, smoking history