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Using a biokinetic model to quantify and optimize cortisol measurements for acute and chronic environmental stress exposure during pregnancy

Journal of Exposure Science & Environmental Epidemiology volume 24, pages 510–516 (2014)Cite this article

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Abstract

To fully understand the potentially harmful effects of prenatal stress exposure impacts, it is necessary to quantify long-term and episodic stress exposure during pregnancy. There is a strong body of research relating psychological stress to elevated cortisol levels in biomarkers. Recently, maternal hair has been used to measure cortisol levels, and provides the unique opportunity to assess stress exposure throughout gestation. Understanding how cortisol in the hair is related to more common biomarkers, such as, blood, saliva and urine is currently lacking. Therefore, we developed a biokinetic model to quantify the relationships between hair, blood, saliva and urine cortisol concentrations using published literature values. Hair concentrations were used to retrospectively predict peaks in blood and saliva concentrations over days and months. Simulations showed realistic values in all compartments when results were compared with published literature. We also showed that the significant variability of cortisol in blood leads to a weak relationship between long-term and episodic measurements of stress. To our knowledge, this is the first integrative biokinetic cortisol model for blood, urine, hair and saliva. As such, it makes an important contribution to our understanding of cortisol as a biomarker and will be useful for future epidemiological studies.

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References

  1. Wright R . Moving towards making social toxins mainstream in children’s environmental health. Curr Opin Pediatr 2009; 21: 222–229.

    Article  Google Scholar 

  2. Cory-Slechta DA, Weston D, Liu S, Allen JL . Brain hemispheric differences in the neurochemical effects of lead, prenatal stress, and the combination and their amelioration by behavioral experience. Toxicol Sci 2013; 132: 419–430.

    Article  CAS  Google Scholar 

  3. Sternthall MJ, Ciull BA, Chiu YH, Cohen S, Wright RJ . Associations among maternal childhood socioeconomic status, cord blood IgE levels, and repeated wheeze in urban children. J Allergy Clin Immunol 2011; 128: 337–345.

    Article  Google Scholar 

  4. Wright R . Prenatal maternal stress and early caregiving experiences: implications for childhood asmtha risk. Paediatr Perinat Epidemiol 2007; 21: 8–14.

    Article  Google Scholar 

  5. Reynolds RM, Labad J, Buss C, Ghaemmaghami P, Raikkonen K . Transmitting biological effects of stress in utero: implications for mother and offspring. Psychoneuroendocrinology 2013; 38: 1843–1849.

    Article  CAS  Google Scholar 

  6. Wadhwa PD, Entringer S, Buss C, Lu MC . The contribution of maternal stress to preterm birth: issues and considerations. Clin Perinatol 2011; 38: 351–384.

    Article  Google Scholar 

  7. Beydoun H, Saftlas AF . Physical and mental health outcomes of prenatal maternal stress in human and animal studies: a review of recent evidence. Paediatr Perinat Epidemiol 2008; 22: 438–466.

    Article  Google Scholar 

  8. Kurki T, Hiilesmaa V, Raitasalo R, Mattila H, Ylikorkala O . Depression and anxiety in early pregnancy and risk for preeclampsia. Obstetr Gynecol 2000; 95: 487–490.

    CAS  Google Scholar 

  9. Lansabergis PA, Hatch MC . Psychosocial work stress and pregnancy-induced hypertension. Epidemiology 1996; 7: 346–351.

    Article  Google Scholar 

  10. Lobel M, Dunkel-Schetter C, Scrimshaw SC . Prenatal maternal stress and prematurity: a prospective study of socioeconomically disadvantaged women. Health Psychol 1992; 11: 32.

    Article  CAS  Google Scholar 

  11. Barker D . Intrauterine programming of adult disease. Mol Med Today 1995; 9: 418–423.

    Article  Google Scholar 

  12. Wilson-Costello D . Is there evidence that long-term outcomes have improved with intensive care? Semin Fetal Neonatal Med 2007; 12: 344–354.

    Article  Google Scholar 

  13. Davis EP, Sandman CA . The timing of prenatal exposure to maternal cortisol and psychosocial stress is associated with human infant cognitive development. Child Dev 2010; 81: 131–148.

    Article  Google Scholar 

  14. Gutteling B, Weerth C, Willemsen-Swinkels SN, Huizink A, Mulder EJH, Visser GA et al. The effects of prenatal stress on temperament and problem behavior of 27-month-old toddlers. Eur Child Adolesc Psychiatry 2005; 14: 41–51.

    Article  Google Scholar 

  15. Gutteling B, Weerth C, Zandbelt N, Mulder EH, Visser GA, Buitelaar J . Does maternal prenatal stress adversely affect the child’s learning and memory at age six? J Abnorm Child Psychol 2006; 34: 787–796.

    Article  Google Scholar 

  16. Hellhammer J, Fries E, Schweisthal OW, Schlotz W, Stone AA, Hagemann D . Several daily measurements are necessary to reliably assess the cortisol rise after awakening: state- and trait componenets. Psychoneuroendocrinology 2007; 32: 80–86.

    Article  CAS  Google Scholar 

  17. Hruschka DJ, Kohrt BA, Worthman CM . Estimating between- and within-individual variation in cortisol levels using multilevel models. Psychoneuroendocrinology 2005; 30: 698–714.

    Article  CAS  Google Scholar 

  18. Adam EK, Kumari M . Assessing salivary cortisol in large-scale, epidemiological research. Psychoneuroendocrinology 2009; 34: 1423–1436.

    Article  CAS  Google Scholar 

  19. Harville EW, Savitz DA, Dole N, Herring AH, Thorp JM . Stress questionnaires and stress biomarkers during pregnancy. J Women Health 2009; 18: 1425–1433.

    Article  Google Scholar 

  20. Rothenberger SE, Moehler E, Reck C, Resch F . Prenatal stress: course and interrelation of emotional and physiological stress measures. Psychopathology 2011; 44: 60–67.

    Article  Google Scholar 

  21. Gow R, Thomson S, Rieder M, Van Uum S, Koren G . An assessment of cortisol analysis in hair and its clinical applications. Forensic Sci Int 2010; 196: 32–37.

    Article  CAS  Google Scholar 

  22. Manenschijn L, Koper JW, Lamberts SWJ, van Rossum EFC . Evaluation of a method to measure long term cortisol levels. Steroids 2011; 76: 1032–1036.

    Article  CAS  Google Scholar 

  23. Kirschbaum C, Tietze A, Skoluda N, Dettenborn L . Hair as a retrospective calendar of cortisol production-Increased cortisol incorporation into hair in the third trimester of pregnancy. Psychoneuroendocrinology 2009; 34: 32–37.

    Article  CAS  Google Scholar 

  24. D’Anna-Hernandez KL, Ross RG, Natvig CL, Laudenslager ML . Hair cortisol levels as a retrospective marker of hypothalamic-pituitary axis activity throughout pregnancy: comparison to salivary cortisol. Physiol Behav 2011; 104: 348–353.

    Article  Google Scholar 

  25. McMaster A, Jangani M, Sommer P, Han N, Brass A, Beesley S et al. Ultradian cortisol pulsatility encodes a distinct, biologically important signal. Plos One 2011; 6: 1–9.

    Article  Google Scholar 

  26. Perogamvros I, Aarons L, Miller AG, Trainer PJ, Ray DW . Corticosteroid-binding globulin regulates cortisol pharmacokinetics. Clin Endocrinol 2011; 74: 30–36.

    Article  CAS  Google Scholar 

  27. Kasuya Y, Yokokawa A, Takashima S, Shibasaki H, Furuta T . Use of 11alpha-deuterium labeled cortisol as a tracer for assessing reduced 11beta-HSD2 activity in vivo following glycyrrhetinic acid ingestion in a human subject. Steroids 2005; 70: 117–125.

    Article  CAS  Google Scholar 

  28. Kasuya Y, Yokokawa A, Takayama S, Shibasaki H, Furuta T . Evaluation of 11 beta-HSD activities in vivo following oral administration of cortisol-13C4,2H1 to a human subject. Steroids 2003; 68: 167–176.

    Article  CAS  Google Scholar 

  29. Kraan GPB, Drayer NM, De Bruin R . Kinetics of cortisol metabolism and excretion. a hypothetic model based on the cumulative urinary radioactivity in eight multiple pituitary deficient patients. J Steroid Biochem Mol Biol 1992; 42: 169–177.

    Article  CAS  Google Scholar 

  30. R: A language and environment for statistical computing. R Foundation for Statistical Computing: Vienna, Austria. 2012.

  31. Stroupe SD, Harding GB, Forsthoefil MW, Westphal U . Kinetic and equilibrium studies on steroid interaction with human corticosteroif-binding globulin. Biochemistry 1978; 17: 177–182.

    Article  CAS  Google Scholar 

  32. Bacq Y, Zarka O, Brechot J, Mariotte N, Vol S, Tichet J et al. Liver function tests in normal pregnancy: a prospective study of 103 pregnant women and 103 matched controls. Hepatology 1996; 23: 1030–1034.

    Article  CAS  Google Scholar 

  33. Dorin RI, Pai HK, Ho JT, Lewis JG, Torpy DJ, Urban FK et al. Validation of a simple method of estimating plasma free cortisol: role of cortisol binding to albumin. Clin Biochem 2009; 42: 64–71.

    Article  CAS  Google Scholar 

  34. Kirschbaum C, Kudielka BM, Gaab J, Schommer N, Hellhammer DH . Impact of gender, menstrual cycle phase and oral contraceptives on the activity of the hypothalamus-pituitary- adrenal axis. Psychosom Med 1999; 61: 154–162.

    Article  CAS  Google Scholar 

  35. Snyder WS, Cook MJ, Nasset GS, Karhausen LR, Howells GP, Tipton IH . Report of the Task Group on Reference Man vol. 23. Pergamon Press. 1974.

    Google Scholar 

  36. Young EA, Carlson NE, Brow MB . Twenty-four-hour acth and cortisol pulsatility in depressed women. Neuropsychopharmacology 2001; 25: 267–287.

    Article  CAS  Google Scholar 

  37. Finken MJJ, Andrews RC, Andrew R, Walker BR . Cortisol metabolism in healthy young adults: sexual dimorphism in activities of A-ring reductases, but not 11 beta-hydroxysteroid dehydrogenases. J Clin Endocrinol Metab 1999; 48: 3316–3321.

    Google Scholar 

  38. Linch CA, Whitting DA, Holland MM . Human hair histogenesis for the mitochondrial DNA forensic scientist. J Forensic Sci 2001; 46: 844–853.

    CAS  PubMed  Google Scholar 

  39. Magos L, Clarkson TW . The assessment of the contribution of hair to methyl mercury excretion. Toxicol Lett 2008; 182: 48–49.

    Article  CAS  Google Scholar 

  40. Stalder T, Steudte S, Miller R, Skoluda N, Dettenborn L, Kirschbaum C . Intraindividual stability of hair cortisol concentrations. Psychoneuroendocrinology 2012; 37: 602–610.

    Article  CAS  Google Scholar 

  41. Press WH, Flannery BP, Teukolsky SA, Vetterling WT . Numerical Recipes: The Art of Scientific Computing. Cambridge University Press. 2007.

    Google Scholar 

  42. Guo W, Wang Y, Morton BB . A signal extraction approach to modeling hormone time series with pulses and a changing baseline. J Am Stat Assoc 1999; 94: 746–756.

    Article  Google Scholar 

  43. Dettenborn L, Tietze A, Bruckner F, Kirschbaum C . HIgher cortisol content in hair among long-term unemployed individuals compared to controls. Pyschoneuroendocrinology 2010; 35: 1404–1409.

    Article  CAS  Google Scholar 

  44. Hamel AF, Meyer JS, Henchey E, Dettmer AM, Suomi SJ, Novak MA . Effects of shampoo and water washing on hair cortisol concentrations. Clin Chim Acta 2011; 412: 382–385.

    Article  CAS  Google Scholar 

  45. Field T, Diego M . Cortisol: the culprit prenatal stress variable. Int J Neurosci 2008; 118: 1181–1205.

    Article  CAS  Google Scholar 

  46. Gitau R, Cameron A, Fisk NM, Glover V . Fetal exposure to maternal cortisol. Lancet 1998; 352: 707–708.

    Article  CAS  Google Scholar 

  47. Demey-Ponsart E, Foidart JM, Sulon J, Sodoyez JC . Serum CBG, free and total cortisol and circadian patterns of adrenal function in normal pregnancy. J Steroid Biochem 1982; 16: 165–169.

    Article  CAS  Google Scholar 

  48. Sauvé B, Koren G, Walsh G, Tokmakejian S, Van Uum SHM . Measurement of cortisol in human hair as a biomarker of systemic exposure. Clin Invest Med 2007; 30: E183–E191.

    Article  Google Scholar 

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Acknowledgements

We thank the Center for Children’s Environmental Health Risks Research and the National Children’s Study for their collaboration on this work. This work was supported by the National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (Contract number HHSN267200700023C), the National Institute of Environmental Health Sciences (5R25ES021646 and 5P01 ES009601) and by USEPA (Grant number RD83451401 and RD832733).

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Authors and Affiliations

  1. Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, Washington, USA

    Marissa N Smith, William C Griffith, Melinda Vredevoogd, Eric M Vigoren & Elaine M Faustman

  2. Department of Epidemiology, University of Washington, Seattle, WA, USA

    Shirley A A Beresford

  3. Northwest Center for the National Children’s Study, University of Washington, Seattle, Washington, USA

    Shirley A A Beresford, Melinda Vredevoogd, Eric M Vigoren & Elaine M Faustman

  4. Cancer Epidemiology, Prevention and Control, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Shirley A A Beresford

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  1. Marissa N Smith
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Correspondence to Elaine M Faustman.

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Smith, M., Griffith, W., Beresford, S. et al. Using a biokinetic model to quantify and optimize cortisol measurements for acute and chronic environmental stress exposure during pregnancy. J Expo Sci Environ Epidemiol 24, 510–516 (2014). https://doi.org/10.1038/jes.2013.86

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  • DOI: https://doi.org/10.1038/jes.2013.86

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