Origins of the “flame within”: Social and Physical Correlates of Inflammation

in U.S. Children.

Jennifer Beam Dowd, Hunter College,CUNY Institute for Demographic Research (CIDR)

Anna Zajacova, Allison Aiello, Center for Social Epidemiology and Population Health, University of

Michigan

Background and Motivation

Disparities in health by SES in the U.S. begin in childhood (Case, Lubotsky, Paxson 2002)

Biological pathways linking SES to health, especially in children, are not clear.

Early environments can shape developing physiological systems (critical and sensitive periods)

Background Data/MethodsResults Conclusions

Inflammation:

Integral part of the human stress and immune response

Pro-inflammatory cytokines regulate the production of acute-phase proteins such as C-reactive protein (CRP) which fight infection and promote repair of damaged issues.

Little is known about the predictors of low-grade inflammation in children

Background Data/Methods Results Conclusion

Contributors to inflammation

Independent predictors of increased inflammation in adults:

Higher BMI (inflammatory cytokines expressed in adipose tissue)

Smoking Poor sleep quality/short sleep Diet high in saturated and trans fat Chronic Infections

Background Data/Methods Results Conclusion

Health Consequences of Inflammation

Elevated CRP is associated with risk of: myocardial infarction, stroke, atherosclerosis insulin resistance, Type II diabetes vascular dementia, Alzheimer’s disease.

Life-long inflammatory burden may shape later life patterns of aging and mortality. (Crimmins and Finch 2006).

Background Data/Methods Results Conclusion

“Inflamm-aging”

Chronic immune activation, including a persistent inflammatory status, may drive what we considered “age” related declines in functioning and immune response–

Thus large differences across groups (race/ethnicity/SES) in burden of inflammation could play a role in observed differences in aging rates and longevity.

Background Data/Methods Results Conclusion

SES differences in Infection Burden in U.S. children:

Previous Work

Lower SES associated with higher CRP in U.S. adults

Mixed results for race/ethnicity-some studies show highest levels for blacks, some for Hispanics

European studies have not found social inequalities in CRP in childhood, differences emerge later.

To our knowledge, no existing studies looking at CRP disparities in U.S. childrenBackground Data/Methods Results Conclusion

Primary Research Questions

Are physical (infections, BMI, etc) and social (family income, race/ethnicity) risk factors associated with inflammation in U.S. children?

Do physical risk factors mediate the relationship between social factors and levels of inflammation in U.S. children?

Background Data/Methods Results Conclusion

Secondary Question

Hygiene hypothesis: Mixed evidence on whether higher infectious burden in childhood promotes better or worse regulation of inflammation later in life—

Are chronic infections related to inflammation in U.S. children? Are proxy measures of pathogen exposure related to inflammation in U.S. children?

Background Data/Methods Results Conclusion

Data

National Health and Nutrition Examination Survey (NHANES), 1999-2004

Cross-sectional, representative sample of non-institutionalized U.S. population

Face-to-face interview, medical exam, collection of blood and urine

Our sample consists of children aged 3-17, N= 6338

Background Data/Methods Results Conclusion

Measures: Outcome High Sensitivity C-reactive Protein (CRP) mg/L:

Distribution is right-skewed, transformed to Ln(CRP)

Background Data/Methods Results Conclusion

Measures: Physical Predictors

Infections: Positive Serostatus for

Cytomegalovirus (CMV)

Herpes Simplex Virus Type 1 (HSV-1)

Helicobacter Pylori (H Pylori)

Cryptosporidium

Toxoplasmosis

Hepatitis A Virus (HAV)

Infectious Burden (Factor Score)

Background Data/Methods Results Conclusion

Measures: Physical Predictors

Body Mass Index (BMI) (kg/m2)

Illness in the last 30 days (0/1)

Low birth weight (0/1)

Mother Smoked during pregnancy (0/1)

Currently a smoker in the Household (0/1)

Cotinine (log transformed)

Triclosan (log transformed, N=557)

White Blood Cell Count

Vitamin D (log transformed)

Background Data/Methods Results Conclusion

Measures: Social PredictorsAge (continuous)

Sex

Foreign Born (0/1)

Household size (continuous)

Race/ethnicity (White/Black/Mexican-American)

SES:

Poverty-Income Ratio (Ratio of Family Income to Poverty Line)

Years of Education of the Household Reference Person

Background Data/Methods Results Conclusion

Methods

OLS Regressions:

Ln(CRP)= α + β1(Social) +β2(Physical) + ε

Infection burden score created with M-Plus, confirmatory factor analysis with full-information maximum likelihood estimation

All analyses conducted with STATA 10.0 SVY commands to account for complex survey design

Background Data/Methods Results Conclusion

Descriptive Statistics

Results

Results

Conclusions

BMI and current/recent illness are strong predictors of CRP in U.S. children

Differences in CRP levels by income largely accounted for by BMI and recent illness.

Higher levels for Mexican-American race/ethnicity not explained by physical vars.

Conclusions

Hygiene Hypothesis: Still a mystery

--Pro: increased HH size associated with lower CRP, Being foreign-born associated with lower CRP

--Cons: infection coefficients all reflect positive effects on CRP, foreign-born effect explained by BMI, Triclosan coefficient negative

Conclusions/Next Steps

Higher BMI and potentially more frequent acute infections contribute to greater levels of low-grade inflammation among U.S. children with lower family income.

What explains higher levels for Mexican-American children?

Potential life-course health implications: aging, CVD, cognition and learning?

Acknowledgements

Thanks to collaborators Anna Zajacova and Allison Aiello, Research assistance from Megan Todd

Support from the NIH: 1R21NR011181-01