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Association between childhood infection, serum inflammatory markers and intelligence: findings from a population-based prospective birth cohort study

  • N. MACKINNON (a1) (a2), S. ZAMMIT (a3) (a4), G. LEWIS (a5), P. B. JONES (a1) (a6) and G. M. KHANDAKER (a1) (a6)...

Summary

A link between infection, inflammation, neurodevelopment and adult illnesses has been proposed. The objective of this study was to examine the association between infection burden during childhood – a critical period of development for the immune and nervous systems – and subsequent systemic inflammatory markers and general intelligence. In the Avon Longitudinal Study of Parents and Children, a prospective birth cohort in England, we examined the association of exposure to infections during childhood, assessed at seven follow-ups between age 1·5 and 7·5 years, with subsequent: (1) serum interleukin 6 and C-reactive protein (CRP) levels at age 9; (2) intelligence quotient (IQ) at age 8. We also examined the relationship between inflammatory markers and IQ. Very high infection burden (90+ percentile) was associated with higher CRP levels, but this relationship was explained by body mass index (adjusted odds ratio (OR) 1·19; 95% confidence interval (CI) 0·95–1·50), maternal occupation (adjusted OR 1·23; 95% CI 0·98–1·55) and atopic disorders (adjusted OR 1·24; 95% CI 0·98–1·55). Higher CRP levels were associated with lower IQ; adjusted β = −0·79 (95% CI −1·31 to −0·27); P = 0·003. There was no strong evidence for an association between infection and IQ. The findings indicate that childhood infections do not have an independent, lasting effect on circulating inflammatory marker levels subsequently in childhood; however, elevated inflammatory markers may be harmful for intellectual development/function.

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Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

*Author for correspondence: Dr G. M. Khandaker, Department of Psychiatry, University of Cambridge, Box 189, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK (Email: gmk24@medschl.cam.ac.uk)

References

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1. World Health Organization. The Global Burden of Disease: 2004 Update. 2008, p. 146 (http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/index.html).
2. Kwong, JC, et al. OB of IDSAG. Ontario Burden of Infectious Disease Study. 2010, p. 197 (http://www.publichealthontario.ca/en/eRepository/ONBOIDS_EXECUTIVE_SUMMARY.pdf).
3. Khandaker, GM, et al. A population-based prospective birth cohort study of childhood neurocognitive and psychological functioning in healthy survivors of early life meningitis. Annals of Epidemiology 2015; 25: 236242.
4. Khandaker, G, et al. Long-term outcomes of infective encephalitis in children: a systematic review and meta-analysis. Developmental Medicine and Child Neurology 2016; 58: 11081115.
5. Murphy, K, Travers, P, Walport, M. Janeway's Immunobiology. New York: Garland Science, 2008.
6. Danesh, J, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. The New England Journal of Medicine 2004; 350: 13871397.
7. Ridker, PM, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000; 101: 17671772.
8. Chaturvedi, AK, et al. C-reactive protein and risk of lung cancer. Journal of Clinical Oncology 2010; 28: 27192726.
9. Wang, T, et al. A prospective study of inflammation markers and endometrial cancer risk in postmenopausal hormone nonusers. Cancer Epidemiology, Biomarkers & Prevention 2011; 20: 971977.
10. Pradhan, AD, et al. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001; 286: 327334.
11. Miwa, K, et al. Interleukin-6, interleukin-6 receptor gene variant, small-vessel disease and incident dementia. European Journal of Neurology 2016; 23: 656663.
12. Metcalf, SA, et al. Serum C-reactive protein in adolescence and risk of schizophrenia in adulthood: a prospective birth cohort study. Brain, Behavior, and Immunity 2016; 59: 253259.
13. Karin, M, Lawrence, T, Nizet, V. Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. Cell 2006; 124: 823835.
14. Barker, D, et al. Fetal origins of adult disease: strength of effects and biological basis. International Journal of Epidemiology 2002; 31: 12351239.
15. Labouesse, MA, Langhans, W, Meyer, U. Long-term pathological consequences of prenatal infection: beyond brain disorders. American Journal of Physiology 2015; 309: R1R12.
16. Khandaker, GM, et al. Prenatal maternal infection, neurodevelopment and adult schizophrenia: a systematic review of population-based studies. Psychological Medicine 2013; 43: 239257.
17. Adams Waldorf, KM, McAdams, RM. Influence of infection during pregnancy on fetal development. Reproduction 2013; 146: R151R162.
18. Iwashyna, TJ, et al. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 2010; 304: 1787.
19. Khandaker, GM, Jones, PB. Cognitive and functional impairment after severe sepsis. JAMA 2011; 305: 673674; author reply 674.
20. Khandaker, GM, et al. Childhood Epstein-Barr virus infection and subsequent risk of psychotic experiences in adolescence: a population-based prospective serological study. Schizophrenia Research 2014; 158: 1924.
21. Boyd, A, et al. Cohort profile: the “children of the 90s” – the index offspring of the Avon Longitudinal Study of Parents and Children. International Journal of Epidemiology 2012/04/18. 2013; 42: 111127.
22. Boyd, A, et al. Cohort profile: the “Children of the 90s” – the index offspring of the Avon Longitudinal Study of Parents and Children. International Journal of Epidemiology 2013; 42: 111127.
23. Weschler, D, Golombok, S, Rust, J. Wechsler Intelligence Scale for Children, 3rd edn (WISC-III). New York: The Psychological Corporation, 1992.
24. Khandaker, GM, et al. A population-based longitudinal study of childhood neurodevelopmental disorders, IQ and subsequent risk of psychotic experiences in adolescence. Psychological Medicine 2014; 44: 32293238.
25. Finch, AJ, Childress, WB. A comparison of WISC selected subtest short forms with MR children. Mental Retardation 1975; 13: 2021.
26. Siebald, C, et al. Association between childhood psychiatric disorders and psychotic experiences in adolescence: a population-based longitudinal study. Comprehensive Psychiatry 2016; 69: 4552.
27. Canivez, GL, Watkins, MW. Long-term stability of the Wechsler Intelligence Scale for Children – third edition. Psychological Assessment 1998; 10: 285291.
28. Lazosky, A, et al. Quality of life after septic illness. Journal of Critical Care 2010; 25: 406412.
29. Lee, EL, et al. General intelligence is associated with subclinical inflammation in Nepalese children: a population-based plasma proteomics study. Brain, Behaviour, and Immunity 2016; 46: 253263.
30. Benros, ME, Sorensen, HJ, Nielsen, PR, Nordentoft, M, Mortensen, PB, Petersen, L. The association between infections and general cognitive ability in young men – a nationwide study. PLoS ONE 2015; 10: e0124005.
31. Garay, PA, McAllister, AK. Novel roles for immune molecules in neural development: implications for neurodevelopmental disorders. Frontiers in Synaptic Neuroscience 2010; 2: 116.
32. Miller, AH, Maletic, V, Raison, CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological Psychiatry 2009; 65: 732741.
33. Khandaker, GM, et al. Association of serum interleukin 6 and C-reactive protein in childhood with depression and psychosis in young adult life. JAMA Psychiatry 2014; 71: 11211128.
34. Park, N-J, Kang, D-H. Inflammatory cytokine levels and breast cancer risk factors: racial differences of healthy Caucasian and African American women. Oncology Nursing Forum 2013; 40: 490500.
35. Coe, CL, et al. Population differences in proinflammatory biology: Japanese have healthier profiles than Americans. Brain, Behavior, and Immunity 2011; 25: 494502.
36. Dowd, JB, Todd, M. Does self-reported health bias the measurement of health inequalities in U. S. adults? Evidence using anchoring vignettes from the health and retirement study. Journal of Gerontology 2011; 66: 478489.
37. Herz, U, et al. The influence of infections on the development and severity of allergic disorders. Current Opinion in Immunology. 2000; 12: 632640.
38. Illi, S, et al. Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study. BMJ (Clinical research ed) 2001; 322: 390395.

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