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Am J Respir Crit Care Med. 2013 Jul 1;188(1):35-41. doi: 10.1164/rccm.201207-1265OC.

Perinatal tumor necrosis factor-α production, influenced by maternal pregnancy weight gain, predicts childhood asthma.

Author information

1
Department of Pharmacology, The University of Arizona, Tucson, AZ, USA. mhalonen@arc.arizona.edu

Abstract

RATIONALE:

Innate immune responses marked by increases in tumor necrosis factor (TNF)-α have been associated with asthma but whether such alterations are evident before symptoms is not yet clear.

OBJECTIVES:

To determine if prevalence of childhood asthma or asthma-related traits is predicted by perinatal innate immune status and if maternal factors related to pregnancy influence asthma prevalence and innate immune status.

METHODS:

In the Tucson Infant Immune Study (a nonselected birth cohort), presence of eczema and wheezing in the child's first year and physician-diagnosed asthma through age 9 and asthma in the parents was obtained from parent-completed questionnaires. TNF-α, IL-6, IL-10, and IL-12 were measured in supernatants of LPS-stimulated peripheral blood mononuclear cells at birth and 3 months as was TNF-α in plasma. TNF-α single nucleotide polymorphisms were genotyped by Sequenom. Percent predicted FEV1/FVC was measured at age 9. Maternal weight gain during pregnancy and prepregnancy weight were ascertained from medical records.

MEASUREMENTS AND MAIN RESULTS:

Infants with persistently elevated LPS-induced TNF-α at birth and 3 months were at increased risk for childhood asthma (odds ratio [OR], 4.1; confidence interval [CI], 1.9-8.8; n = 233; P = 0.0003) and had decreased FEV1/FVC ratios at age 9. Children with mothers in the top tertile for pregnancy weight gain had increased risk for asthma (OR, 3.4; CI, 1.7-6.9; n = 225; P = 0.001) and persistently elevated TNF-α in early life (OR, 2.9; CI, 1.4-8.2; n = 195; P = 0.013). These relations were independent of maternal asthma and rhinitis.

CONCLUSIONS:

Persistently elevated LPS-induced TNF-α production early in life acts as a predictive biomarker for childhood asthma, and excess pregnancy weight gain in the mother seems to contribute to both.

PMID:
23590270
PMCID:
PMC3735244
DOI:
10.1164/rccm.201207-1265OC
[Indexed for MEDLINE]
Free PMC Article

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