Association between antenatal cytokine production and the development of atopy and asthma at age 6 years

Macaubas, C., de Klerk, N. H., Holt, B. J., Wee, C., Kendall, G., Firth, M, Sly, P. D. and Holt, P. G. (2003) Association between antenatal cytokine production and the development of atopy and asthma at age 6 years. Lancet, 362 9391: 1192-1197. doi:10.1016/S0140-6736(03)14542-4

Author Macaubas, C.
de Klerk, N. H.
Holt, B. J.
Wee, C.
Kendall, G.
Firth, M
Sly, P. D.
Holt, P. G.
Title Association between antenatal cytokine production and the development of atopy and asthma at age 6 years
Journal name Lancet   Check publisher's open access policy
ISSN 0140-6736
Publication date 2003-10
Sub-type Article (original research)
DOI 10.1016/S0140-6736(03)14542-4
Volume 362
Issue 9391
Start page 1192
End page 1197
Total pages 6
Place of publication London, United Kingdom
Publisher The Lancet Publishing Group
Language eng
Formatted abstract
Background: Various lines of evidence suggest that antenatal factors are important in determining susceptibility to atopy and asthma. One possible mechanism is cytokines, production of which in the placenta is high throughout gestation and which protect placental integrity via control of local immunological homoeostasis. We investigated antenatal cytokine concentrations in a prospective birth cohort, intensively monitored for atopy and asthma outcomes at age 6 years.

Methods: Cryopreserved cord-blood serum samples from 407 children were assayed for interleukins 4, 5, 6, 10, 12, and 13, interferon γ, and tumour necrosis factor α (TNFα). Associations between family, antenatal, and perinatal factors, cord-blood cytokine concentrations, and atopy or asthma outcomes were analysed by logistic regression. Causal effects of cytokines on outcomes were estimated by propensity scores based on family, antenatal, and perinatal factors.

Findings: Detectable cord-blood concentrations of interleukin 4 and interferon γ were each associated with lower risk of physician-diagnosed asthma (adjusted odds ratios 0.60 [95% CI 0.37-0.99] and 0.60 [0.37-0.97] respectively), current asthma (0.59 [0.33-1.00] and 0.39 [0.22-0.71]), and current wheeze (0.55 [0.32-0.93] and 0. 52 [0.31-0.90]) and atopy (sensitisation to some inhalant allergens) outcomes at 6 years. High concentrations of TNFα were associated with lower risk of atopy but not with asthma risk. These associations were broadly unaltered by propensity-score adjustment. Maternal smoking was associated with higher risk of both wheeze at 6 years and lower concentrations of interleukin 4 and interferon γ in cord blood.

Interpretation: The mechanism underlying attenuated T-helper-1/T-helper-2 cytokine production in high-risk children also apparently operates in control of cytokine production in the fetoplacental unit. The finding that this mechanism is dysregulated by maternal smoking suggests it is a target for antenatal environmental factors relevant to asthma aetiology.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Faculty of Health and Behavioural Sciences -- Publications
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Created: Wed, 17 Nov 2010, 11:37:52 EST