Aim

To examine the association of early growth with the risk of childhood asthma using data from European cohort studies.

Hypothesis

Previously, it has been shown that low birth weight is associated with increased risks of asthma, chronic obstructive airway disease, and impaired lung function (FEV1, FVC) in adults. In children, low birth weight is associated with increased risks of respiratory symptoms. The developmental plasticity hypothesis suggests that the associations between low birth weight and asthma are explained by early adaptive mechanisms in response to various exposures in fetal and early postnatal life. These adaptive mechanisms might be beneficial for short term survival but might also lead to increased susceptibility of development of asthma in childhood and, perhaps, adulthood. Developmental adaptations might include impaired lung development leading to lifelong smaller airways and impaired lung function. Low birth weight is not likely to be causal for asthma per se. The same birth weight might be the result of various growth patterns. Information about growth characteristics in early life enables identification of critical periods for specific exposures and development of asthma. Children with a low birth weight tend to have a postnatal catch up growth, which leads to increased risks of childhood obesity. Both catch up growth and obesity have been suggested to be associated with pulmonary functioning, respiratory symptoms and childhood asthma. However, studies so far showed inconsistent results, which might partly be due to methodological issues including differences in definitions of catch up growth, obesity and asthma outcomes and the adjustment for gestational age and other confounders.

Methods

Cohorts were identified through birth cohort registries. Studies were eligible if they included children from 1989 onwards, had information on at least preterm birth or birth weight and preschool wheezing (1-4 years) or school age asthma (5-10 years), and allowed to use original data. Pooled odds ratios from random effect models were calculated from the per cohort logistic regression analysis to assess the association between birth weight and asthma, and gestational age and asthma. Secondly a individual patient data meta-analysis will be performed to assess the interaction between gestational age and birth weight.

Exposure

Growth characteristics at birth (weight, gestational age) and at the age of 1 year (range 6-18 months; weight) will be used.

Outcomes

Information on preschool wheezing (no, yes) at the ages of 1-4 years, and school age wheezing (no, yes) and physician diagnosed asthma (no, yes) at the ages of 5-10 years will be collected. Cohorts that defined wheezing and doctor-diagnosed asthma with use of questions from the International Study on Asthma and Allergy in Childhood (ISAAC) (14) are preferred but not obligatory.

Covariates

Information about a large number of potential covariates will be collected including e.g. maternal age, BMI, education, history of asthma or atopy (eczema, hay fever or house dust mite allergy), smoking habits during pregnancy and in the first year after birth, parity or number of siblings at time of birth, gestational hypertension, gestational diabetes, children's sex, gestational age, ethnicity, breastfeeding status, daycare attendance in the first year of life and pet keeping.