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

Rationale: Innate immune responses marked by increases in tumor necrosis factor (TNF)-a have been associated with asthma butwhether 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 LPSstimulatedperipheral bloodmononuclear cells at birthand3months 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 hadincreased 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.