The main aim of this meta-analysis is to estimate the existence and the magnitude of the effect of exposure to pets - as an indirect marker of exposure to infectious agents - during pregnancy, infancy and/or childhood (i.e., up to age 12 years, according to NLM-MeSH) on the occurrence of atopic dermatitis in infants and children (i.e., age 0-12 years, according to NLM-MeSH), to bring evidence in favour of or against the "hygiene hypothesis".

Systematic literature searches in MEDLINE and EMBASE, restricted to English language

Only observational cohort and case-control studies will be included in the analyses. Cross-sectional studies will be excluded.

Atopic dermatitis is a clinical diagnosis. Most physicians involved in the care of patients with atopic dermatitis rely on the diagnostic criteria of Hanifin and Rajka (Hanifin JM, Rajka G.,1980) or Williams et al. (Williams HC et al, 1994). However, some cohort studies are based on the parental-reported presence of atopic dermatitis. We will collect data on the method of diagnosis used in each study, and - if study numbers will allow it - we will address potential differences in results across subgroups of diagnosis type.

Inclusion: Each cohort or case-control study identified will be included in the analysis if the exposure (to various pets or to pets overall) occurs during pregnancy, infancy and/or childhood, and outcome assessment is performed during infancy or childhood (i.e., up to 12 years of age).

Studies conducted at different ages will be excluded. Studies focused on prognosis, rather than occurrence, of atopic dermatitis will be excluded.

Each cohort and case-control study identified will be included in the analysis if it considers exposure to dogs, cats, other pets, or pets overall (i.e., pet ownership or regular contacts with pets) during pregnancy and/or infancy.

Exposures other than pets as well as other measures of pets exposure (e.g., sensitization to dogs or cats, dust sampling of pet allergens/endotoxins in the mattress or home) will be excluded.

We will include only cohort and case-control studies comparing subjects exposed vs. non-exposed to pets.

Primary outcomes

Incidence or presence of atopic dermatitis during infancy or childhood according to exposure to dogs, cats, and pets overall.

The endpoints will likely be different across studies, mostly incidence of atopic dermatitis by (or presence of atopic dermatitis) at 1 or 2 years of age. If study numbers will allow it, we will also examine the outcome at older ages (e.g., 4, 8 or 12 years).

Secondary outcomes

IgE-associated atopic dermatitis, if study numbers will allow this analysis. Also, if feasible, we will consider exposures to other specific pets (e.g., birds, guinea pigs, etc)

Same endpoints as for the primary outcome.

Two review team members will retrieve and assess independently potentially relevant articles, and will checking the reference list of all papers of interest to obtain other pertinent publications. Abstract and unpublished studies will not be included. No studies will be excluded a priori for weakness of design or data quality. Discrepancies between reviewers will be discussed and resolved. Two review team members will review all the studies and will abstract relevant information in a standard format. Potential discrepancies will be checked on the original articles and, if necessary, discussed and resolved.

We will extract information from each cohort and case-control study on timing of pet exposure in relation to disease occurrence, on diagnostic methods used to assess the occurrence of atopic dermatitis, and on which covariate(s) were adjusted for in the statistical models. As a clinical diagnosis of eczema is critical, we will check in each study whether assessment of eczema was performed by a clinician/study outcome assessor or was reported/diagnosed by parents. Similarly, we will check in each study whether adjustment for family history of atopic diseases has been performed (in fact, family history of atopy has been reported as an important confounder of the association between pets exposure and atopic dermatitis). No quality scores will be assigned to the studies. We will perform sensitivity analyses by excluding one study at a time from the meta-analysis. The presence of publication bias will be assessed by examination of funnel plot and by applying the tests proposed by Begg and Mazumdar, and by Egger.

We will pool the odds ratios (OR) of each study. Studies providing other measures of relative risk (i.e., hazard ratios, rate ratios, etc) will also be pooled together with ORs. We will, however, perform a sensitivity analysis by excluding studies providing estimates other than ORs. We will calculate summary estimates of the OR of atopic dermatitis using both fixed- and random-effects models. Heterogeneity between studies will be assessed using the chi-squared and I-squared tests. If significant heterogeneity is detected, we will present RRs from random-effects models, and from fixed-effects models otherwise.

We will compute summary estimates in several subgroups (at both an individual or study level), including geographic area, family history of allergic diseases, presence of adjustment for family history of atopy, age at assessment of atopic dermatitis, methods used to diagnose atopic dermatitis.

Full release of findings in a scientific journal.

Claudio Pelucchi

Istituto di Ricerche Farmacologiche Mario Negri

Via Giuseppe La Masa 19

20156 Milan

Italy

claudio.pelucchi@marionegri.it

None

Dr Claudio Pelucchi, Istituto di Ricerche Farmacologiche Mario Negri

20 August 2012

31 October 2012

European Research Council, grant agreement No. 250290

None known

English

Italy

Subject indexing assigned by CRD

Dermatitis, Atopic; Child; Infant; Pediatrics; Pets

06 September 2012

18 April 2013