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

Marilyn Halonen, I. Carla Lohman, Debra A. Stern, Whitney L. Ellis, Janet L Rothers, Anne L Wright

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)35-41
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume188
Issue number1
DOIs
StatePublished - Jul 1 2013

Fingerprint

Weight Gain
Asthma
Tumor Necrosis Factor-alpha
Mothers
Pregnancy
Odds Ratio
Confidence Intervals
Parturition
Eczema
Respiratory Sounds
Interleukin-12
Rhinitis
Innate Immunity
Interleukin-10
Medical Records
Single Nucleotide Polymorphism
Interleukin-6
Biomarkers
Parents
Physicians

Keywords

  • Asthma etiology
  • Biomarker
  • Innate cytokines

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Perinatal tumor necrosis factor-α production, influenced by maternal pregnancy weight gain, predicts childhood asthma. / Halonen, Marilyn; Lohman, I. Carla; Stern, Debra A.; Ellis, Whitney L.; Rothers, Janet L; Wright, Anne L.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 188, No. 1, 01.07.2013, p. 35-41.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Halonen, Marilyn

AU - Lohman, I. Carla

AU - Stern, Debra A.

AU - Ellis, Whitney L.

AU - Rothers, Janet L

AU - Wright, Anne L

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N2 - 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.

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