title: Perinatal tumor necrosis factor-α production, influenced by maternal pregnancy weight gain, predicts childhood asthma.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pharmacology, The University of Arizona, Tucson, AZ, USA. mhalonen@arc.arizona.edu
authors.forename: Marilyn
authors.initials: M
authors.lastname: Halonen
authors.forename: I Carla
authors.initials: IC
authors.lastname: Lohman
authors.forename: Debra A
authors.initials: DA
authors.lastname: Stern
authors.forename: Whitney L
authors.initials: WL
authors.lastname: Ellis
authors.forename: Janet
authors.initials: J
authors.lastname: Rothers
authors.forename: Anne L
authors.initials: AL
authors.lastname: Wright
mesh_terms: D001130:Arizona / Q000453:epidemiology; D001249:Asthma / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004485:Eczema / Q000453:epidemiology / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D018664:Interleukin-12 / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008297:Male; D011237:Predictive Value of Tests; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*; D011297:Prenatal Exposure Delayed Effects; D015995:Prevalence; D012135:Respiratory Sounds / Q000276:immunology; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology*; D015430:Weight Gain / Q000276:immunology*
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12