Table 1 Characteristics of included studies

• Hollams [13]

• Prospective birth cohort started in 1989

• Conducted as part of West Australian Pregnancy Cohort (Raine Study): a longitudinal birth cohort, in which mothers (2900 volunteers) were enrolled for antenatal care at the main local tertiary maternity hospital

• Serum 25-hydroxyvitamin D levels measured at the age of 6 years

• Current asthma; defined as wheeze plus use of any asthma medication in the last 12 months, in children with a prior doctor diagnosis of asthma

• Vitamin D levels at age 6 years (Continuous outcome) analyzed as a predictor of subsequent clinical phenotypes at 14 years of age

Source of funding not reported

• Follow up: 8 years

• Measured using the enzyme immunoassay kit from Immunodiagnostic Systems Ltd (Scottsdale, AZ, USA)

• 8 years period between the point of measuring vitamin D levels and the assessment of asthma

• Reference group: sufficient level of vit D (> 75)

• Included in this study: 989 children assessed at the age of 6 (no further details provided about selection criteria or process); 693 were included in the analysis.

• Vitamin D values were ‘deseasonalized’

• Lung function; assessed by spirometry

• Bronchial hyperrsponsiveness (BHR); assessed by methacholine challenge.

• Perth, Western Australia, Australia

• Outcomes assessed at the age of 14 years

Van Oeffelen [12]

• Prospective birth cohort started in 1996

• Conducted as part of PIAMA birth cohort of 3963 newborns; pregnant women recruited from the general population when visiting one of 52 prenatal clinics

• Serum 25-hydroxyvitamin D levels measured at the age of 4 years

• Asthma and severe asthma diagnosed using the (ISAAC) [29] questionnaire answered by parents annually until 8 year of age

• Vitamin D levels categorized into tetriles (Reference: tertile 1)

Funded by the Netherlands Organisation for Health Research and Development, the Netherlands Asthma Foundation, the Netherlands Ministry of Health, Welfare and Sport, and the National Institute of Public Health and the Environment.

• Follow up: 5 years

• Serum extracted and directly stored in a refrigerator at -20C, and defrosted in 2008 to measure of vit. D levels

• Measured using a competitive enzyme immunoassay in microtiter plates (OCTEIA; IDS, Boldon, UK).

• 4 years period between the point of measuring vitamin D levels and the assessment of asthma

• Included in this study: 372 “selected” 4-year-old children (no further details provided about selection criteria or process); all were included in the analysis

• Storage time of serum samples proved to be no confounder and was therefore not added to the models.

• Categorized into tertiles (range; median):

• Bronchial hyperrsponsiveness (BHR) measured at 8 years of age; assessed by methacholine challenge

o Tertile 1: 23.1–60.2; 52.0

o Tertile 2: 60.7–78.8; 68.3

• Vitamin D values were ‘deseasonalized’

Netherlands

Tertile 3: 79.0–303.8; 97.0

Tolppanen [22]

• Prospective birth cohort started in 1991

• Conducted as part of the Avon longitudinal Study of Parents and children (ALSPAC): 14,062 live births from 14,541 enrolled pregnant women who were expected to give birth between 1^st of April 1991 and 31^st of December 1992

• Serum 25-hydroxyvitamin D2 and D3 levels measured at a mean age of 9.8 years

• Asthma and wheezing assessed (questionnaire to children) at the age of 15-16 years.

• Asthma and wheezing also assessed on a yearly basis (questionnaire to caregiver); not clear whether those data were included in the analysis

Funded by the UK Medical Research Council, the Wellcome trust, and the University of Bristol

• Follow up: 6 years

• 5-6 years period between the point of measuring vitamin D levels and the assessment of asthma

• Measured using high pressure liquid chromatography tandem mass spectrometer in the multiple reaction mode

• The exposures are standardized for age and sex and 25(OH)D3 is adjusted for season and ethnicity

• Interassay coefficients of

• Variation for 25(OH)D2 and 25(OH)D3 were < 10% across a working range of 1–250 ng/ml

• Lung function measured at a mean age of 15.5 years by spirometry according to the American Thoracic Society/European respiratory Society criteria. The best measurements from three reproducible flow-volume curves were used for analyses

• Included in this study (mean age of 9.8): 3323 children for the asthma outcome and 2,259 for spirometry (inclusion based on completeness of data on exposures, confounders, and outcome)

• South West England