Search strategy and data sources The search strategy for MEDLINE is provided in the online supplementary material and has also been described previously.11 Two reviewers (SD and ED) searched the electronic databases (including MEDLINE, EMBASE, Cochrane controlled trials register (CCTR) and CINHAL) and reference fairly lists of other studies and reviews between January 2010 and April 2010. Updated searches were carried out in July 2011 and November 2013. No date limits were applied to the search strategy. Studies identified from searching

electronic databases were combined, duplicates removed and papers were screened for relevance to the review based on the information contained in the title and abstract. Abstracts were screened by a second reviewer (SWT) and potentially eligible papers were identified. Inclusion/exclusion criteria Studies were included if (A) they captured exposure to an environmental factor identified as potentially relevant to the development of asthma; (B) the mean age of asthma outcome was ≤9 years. (C) Outcomes include diagnosis of asthma or data related to healthcare utilisation (hospital admissions, drug use), (D) the study design was either a meta-analysis,

systematic review, randomised control trial, non-randomised control trial or cohort study. If no evidence was apparent for an exposure, then studies meeting the lower Scottish Intercollegiate Guidelines Network criteria were considered, that is, case–control and case report studies (http://www.sign.ac.uk/guidelines/fulltext/50/annexb.html 21 Jun 2014). Study selection and data extraction The full text of references identified as potentially relevant was obtained and papers included

by applying the inclusion criteria, sometimes after discussion between reviewers (SD and SWT). Papers that were included in a systematic review were not included. For cohort studies where outcomes were reported at increasing ages after one exposure, only the most recent paper was included. A summary table included the following details from studies: study design, characteristics of the study population, study objectives and the key outcome(s) reported including what the primary asthma outcome was, for example, wheeze, physician diagnosed asthma, etc. Quality assessment Quality assessment of included papers was carried out using “Effective public health practice project quality assessment tool for quantitative studies” (http://www.ephpp.ca/PDF/Quality%20Assessment%20Tool_2010_2.pdf Entinostat accessed Jun 2014). Results are presented in the online supplementary material; due to the relatively large number of studies identified, a random 10% were chosen for quality assessment. Results Literature search There were 14 691 references identified from electronic databases and other studies. There were 207 full papers reviewed and 135 studies met the inclusion criteria (figure 1).