Fetal origins of asthma.

There is convincing evidence that asthma has its origins in early life. We review the epidemiological and biological evidence for fetal exposures that may have a causal role in asthma development. However, those factors that provoke asthma exacerbations are not necessarily the same as those associated with disease induction. Epidemiological studies have identified many potential exposures linked to asthma but these do not confirm causality and have not been replicated by experiment. Asthma is a heterogeneous disease and there are developmental influences on at least two pathways, airway structure and airway inflammation. The fetus is not immunologically naive and intrauterine exposures can act directly to invoke immunological sensitisation leading postnatally to airway inflammation. Other potential mechanisms include indirect effects on airway and lung growth through fetal nutrition and epigenetic modifications of DNA expression by environmental exposures. Identifying the causal factors will provide the targets for interventions to prevent disease.