Perinatal Tumor Necrosis Factor-α Production, Influenced by Maternal Pregnancy Weight Gain, Predicts Childhood Asthma

• Published in: American journal of respiratory and critical care medicine 2013-07, Vol.188 (1), p.35-41
• Main Authors: HALONEN, Marilyn, LOHMAN, I. Carla, STERN, Debra A, ELLIS, Whitney L, ROTHERS, Janet, WRIGHT, Anne L
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Arizona - epidemiology; Asthma - blood; Asthma - epidemiology; Asthma - immunology; Biological and medical sciences; Biomarkers - blood; Child; Child, Preschool; Chronic obstructive pulmonary disease, asthma; Cohort Studies; Eczema - epidemiology; Eczema - immunology; Female; Humans; Immunity, Innate - immunology; Infant; Infant, Newborn; Infant, Newborn, Diseases - blood; Infant, Newborn, Diseases - epidemiology; Infant, Newborn, Diseases - immunology; Intensive care medicine; Interleukin-10 - blood; Interleukin-10 - immunology; Interleukin-12 - blood; Interleukin-12 - immunology; Interleukin-6 - blood; Interleukin-6 - immunology; Male; Medical sciences; Pneumology; Predictive Value of Tests; Pregnancy; Pregnancy Complications - immunology; Prenatal Exposure Delayed Effects; Prevalence; Respiratory Sounds - immunology; Risk Factors; Surveys and Questionnaires; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - immunology; Weight Gain - immunology
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.201207-1265OC

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. 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. 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. 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. 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.