title: Transient environmental exposures on the developing immune system: implications for allergy and asthma.
abstract: OBJECTIVE
  Early environmental exposures have been extensively studied as potential causes of the observed increase in allergic disease over time. Transient fetal or neonatal exposures in particular are of interest in that they may occur during critical windows of immune system development. Due to the tremendous complexity of variables in early life, as well as the difficulty in randomizing many interventions, it is very difficult to properly study these exposures. Some progress, however, has been made and some more candidates for study may be emerging. Of particular interest are micronutrients, whose ever-changing use and immunomodulatory capabilities make them prime targets for study.
  
  
  RESULTS
  New risk factors for atopic disease have emerged from the pool of early life interventions, such as caesarian section, prolonged labor and infant multivitamin supplementation. Data are emerging regarding micronutrient status and supplementation and their effects on the developing immune system and risk for allergic disease. Clinical trials have yet to demonstrate much causality but, in some cases, it is too early to make any judgments.
  
  
  CONCLUSIONS
  The gold standard of randomized clinical trials has not borne out a number of proposed early-life allergic risk factors, while other trials are too incomplete to draw any conclusions so far. Properly designed studies for other risk factor interventions may still be achievable, provided that there is a proper understanding of the interventions, populations and outcomes.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIAID, NIH, Bethesda, Maryland 20892-1892, USA. jdmilner@niaid.nih.gov
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Milner
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gergen
mesh_terms: D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology* / Q000276:immunology*; D007223:Infant; D041943:Infant Formula; D007231:Infant, Newborn; D008895:Milk, Human / Q000276:immunology; D012307:Risk Factors; D014815:Vitamins / Q000276:immunology
chemical_list: D014815:Vitamins