Advertisement

Psychopharmacology

, Volume 214, Issue 1, pp 297–307 | Cite as

Prenatal alcohol exposure and cortisol activity in 19-month-old toddlers: an investigation of the moderating effects of sex and testosterone

  • Isabelle Ouellet-Morin
  • Ginette Dionne
  • Sonia J. Lupien
  • Gina Muckle
  • Sylvana Côté
  • Daniel Pérusse
  • Richard E. Tremblay
  • Michel Boivin
original investigation

Abstract

Rationale

Early exposure to stress and teratogenic substances have an impact on brain structures involved in cognition and mental health. While moderate-to-high levels of prenatal alcohol exposure (PAE) have repeatedly been associated with long-term neurodevelopmental deficits, no consensus has yet been reached on the detrimental effects of low-to-moderate PAE on the children’s functioning, including the limbic–hypothalamic–pituitary–adrenal axis.

Objectives

The study aims to examine the association between low PAE and cortisol response to unfamiliar situations in 19-month-old children and to determine whether this association was moderated by sex and testosterone levels.

Methods

Information regarding PAE, cortisol response to unfamiliar situations, and testosterone activity was available in a total of 130 children participating to the Québec Newborn Twin Study (Montréal, QC, Canada). Mother alcohol consumption during pregnancy was assessed via a semistructured interview conducted when the children were 6 months of age. The contribution of prenatal and postnatal confounds were examined.

Results

Disrupted patterns of cortisol activity were observed only in PAE males. Testosterone tended to be negatively associated with the cortisol response, but not for PAE males, suggesting an altered sensitivity to the inhibitory effects of testosterone in these participants.

Conclusions

Low levels of PAE were associated with disrupted cortisol activity, and males may be at higher risk. These findings challenge the existence of a “safe level” of alcohol consumption during pregnancy and have public health implications.

Keywords

Prenatal alcohol exposure Stress Teratogens Adversity Cortisol LHPA axis Sex differences Testosterone Children Alcohol Androgen Development Drinking Environmental Glucocorticoid Prenatal Sex differences 

Notes

Acknowledgments

This research was supported by grants from the National Health Research Development Program, the Social Sciences and Humanities Research Council of Canada, the Québec Ministry of Health and Social Services, the Canadian Institutes of Health Research, the Canada Research Chair program, the Fonds Québécois de la Recherche sur la Société et la Culture, and the Fonds de la Recherche en Santé du Québec. Isabelle Ouellet-Morin was supported by fellowships from the Canadian Institutes of Health Research and the CIHR Training Grant in Genes, Environment, and Health. The funding agencies have no further role in the study design, in the collection, analysis, interpretation of data, and in the writing of the manuscript. We are grateful to the parents and twins of the participating families. We thank Jocelyn Malo for coordinating the data collection and Helene Beaumont, Helene Paradis, Bei Feng, Bernadette Simoneau, and Jacqueline Langlois for the assistance in data management and statistical analyses (H.P. and B.F.).

Supplementary material

213_2010_1955_MOESM1_ESM.doc (42 kb)
Online Resource 1 (DOC 42 kb)

References

  1. Ashman SB, Dawson G, Panagiotides H, Yamada E, Wilkinson CW (2002) Stress hormone levels of children of depressed mothers. Dev Psychopathol 14:333–349PubMedCrossRefGoogle Scholar
  2. Bearer CF, Jacobson JL, Jacobson SW, Barr D, Croxford J, Molteno CD, Viljoen DL, Marais AS, Chiodo LM, Cwik AS (2003) Validation of a new biomarker of fetal exposure to alcohol. J Pediatr 143:463–469PubMedCrossRefGoogle Scholar
  3. Bearer CF, Stoler JM, Cook JD, Carpenter SJ (2004/2005) Biomarkers of alcohol use in pregnancy. Alcohol Res Health 28:38–43Google Scholar
  4. Blair C, Granger D, Peters Razza R (2005) Cortisol reactivity is positively related to executive function in preschool children attending head start. Child Dev 76:554–567PubMedCrossRefGoogle Scholar
  5. Burden MJ, Jacobson SW, Sokol RJ, Jacobson JL (2005) Effects of prenatal alcohol exposure on attention and working memory at 7.5 years of age. Alcohol Clin Exp Res 29:443–452PubMedCrossRefGoogle Scholar
  6. Coles CD, Platzman KA, Raskind-Hood CL, Brown RT, Falek A, Smith IE (1997) A comparison of children affected by prenatal alcohol exposure and attention deficit, hyperactivity disorder. Alcohol Clin Exp Res 21:150–161PubMedGoogle Scholar
  7. Day NL, Robles N, Richardson G, Geva D, Taylor P, Scher M, Stoffer D, Cornelius M, Goldschmidt L (1991) The effects of prenatal alcohol use on the growth of children at three years of age. Alcohol Clin Exp Res 15:67–71PubMedCrossRefGoogle Scholar
  8. Forget-Dubois N, Perusse D, Turecki G, Girard A, Billette JM, Rouleau G, Boivin M, Malo J, Tremblay RE (2003) Diagnosing zygosity in infant twins: physical similarity, genotyping, and chorionicity. Twin Res 6:479–485PubMedCrossRefGoogle Scholar
  9. Gabriel KI, Glavas MM, Ellis L, Weinberg J (2005) Postnatal handling does not normalize hypothalamic corticotropin-releasing factor mRNA levels in animals prenatally exposed to ethanol. Dev Brain Res 157:74–82CrossRefGoogle Scholar
  10. Glavas MM, Hofmann CE, Yu WK, Weinberg J (2001) Effects of prenatal ethanol exposure on hypothalamic–pituitary–adrenal regulation after adrenalectomy and corticosterone replacement. Alcohol Clin Exp Res 25:890–897PubMedCrossRefGoogle Scholar
  11. Goldberg S, Levitan R, Leung E, Masellis M, Basile VS, Nemeroff CB, Atkinson L (2003) Cortisol concentrations in 12- to 18-month-old infants: stability over time, location, and stressor. Biol Psychiatry 54:719–726PubMedCrossRefGoogle Scholar
  12. Goldsmith HH (1991) A zygosity questionnaire for young twins: a research note. Behav Genet 21:257–269PubMedCrossRefGoogle Scholar
  13. Goodyer IM, Park R, Herbert J (2001) Psychosocial and endocrine features of chronic first episode major depression in 8–16 year olds. Biol Psychiatry 50:351–357PubMedCrossRefGoogle Scholar
  14. Granger DA, Cicchetti D, Rogosch FA, Hibel LC, Teisl M, Flores E (2007) Blood contamination in children's saliva: prevalence, stability, and impact on the measurement of salivary cortisol, testosterone, and dehydroepiandrosterone. Psychoneuroendocrinology 32:724–733PubMedCrossRefGoogle Scholar
  15. Gunnar M, Vazquez DM (2006) Stress neurobiology and developmental psychopathology. In: Cicchetti D, Donald JC (eds) Developmental psychopathology. Wiley, Hoboken, pp 533–577Google Scholar
  16. Gunnar M, Quevedo K (2007) The neurobiology of stress and development. Annu Rev Psychol 58:145–173PubMedCrossRefGoogle Scholar
  17. Gunnar MR, Talge NM, Herrera A (2009) Stressor paradigms in developmental studies: what does and does not work to produce mean increases in salivary cortisol. Psychoneuroendocrinology 34:953–967PubMedCrossRefGoogle Scholar
  18. Halasz I, Aird F, Li L, Prystowsky MB, Redei E (1993) Sexually dimorphic effects of alcohol exposure in utero on neuroendocrine and immune functions in chronic alcohol-exposed adult rats. Mol Cell Neurosci 4:343–353PubMedCrossRefGoogle Scholar
  19. Haley DW, Handmaker NS, Lowe J (2006) Infant stress reactivity and prenatal alcohol exposure. Alcohol Clin Exp Res 30:2055–2064PubMedCrossRefGoogle Scholar
  20. Henderson J, Gray R, Brocklehurst P (2007) Systematic review of effects of low-moderate prenatal alcohol exposure on pregnancy outcome. BJOG 114:243–252PubMedCrossRefGoogle Scholar
  21. Jacobson JL, Jacobson SW (1994) Prenatal alcohol exposure and neurobehavioral development: where is the threshold? Alcohol Health Res World 18:30–36Google Scholar
  22. Jacobson JL, Jacobson SW (1999) Drinking moderately and pregnancy. Effects on child development. Alcohol Res Health 23:25–30PubMedGoogle Scholar
  23. Jacobson SW, Bihun JT, Chiodo LM (1999) Effects of prenatal alcohol and cocaine exposure on infant cortisol levels. Devel Psychopathol 11:195–208CrossRefGoogle Scholar
  24. Jacobson SW, Chiodo LM, Sokol RJ, Jacobson JL (2002) Validity of maternal report of prenatal alcohol, cocaine, and smoking in relation to neurobehavioral outcome. Pediatrics 109:815–825PubMedCrossRefGoogle Scholar
  25. Jacobson SW, Jacobson JL, Sokol RJ, Chiodo LM, Corobana R (2004) Maternal age, alcohol abuse history, and quality of parenting as moderators of the effects of prenatal alcohol exposure on 7.5-year intellectual function. Alcohol Clin Exp Res 28:1732–1745PubMedCrossRefGoogle Scholar
  26. Jones KL, Smith DW (1973) Recognition of the fetal alcohol syndrome in early infancy. Lancet 301:999–1001CrossRefGoogle Scholar
  27. Kable JA, Coles CD (2004) The impact of prenatal alcohol exposure on neurophysiological encoding of environmental events at six months. Alcohol Clin Exp Res 28:489–496PubMedCrossRefGoogle Scholar
  28. Kelly SJ, Dillingham RR (1994) Sexually dimorphic effects of perinatal alcohol exposure on social interactions and amygdala DNA and DOPAC concentrations. Neurotoxicol Teratol 16:377–384PubMedCrossRefGoogle Scholar
  29. Kelly SJ (1996) Alcohol exposure during development alters hypothalamic neurotransmitter concentrations. J Neural Transm 103:55–67PubMedCrossRefGoogle Scholar
  30. Kelly SJ, Day N, Streissguth AP (2000) Effects of prenatal alcohol exposure on social behavior in humans and other species. Neurotoxicol Teratol 22:143–149PubMedCrossRefGoogle Scholar
  31. Kesmodel U, Olsen SF (2001) Self reported alcohol intake in pregnancy: comparison between four methods. J Epidemiol Community Health 55:738–745PubMedCrossRefGoogle Scholar
  32. Klein J, Chan D, Koren G (2002) Neonatal hair analysis as a biomarker for in utero alcohol exposure. N Engl J Med 347:2086PubMedCrossRefGoogle Scholar
  33. Kodituwakku PW (2007) Defining the behavioral phenotype in children with fetal alcohol spectrum disorders: a review. Neurosci Biobehav Rev 31:192–201PubMedCrossRefGoogle Scholar
  34. Lacey JI (1956) The evaluation of autonomic responses: toward a general solution. Ann New York Acad Sci 67:123–163CrossRefGoogle Scholar
  35. Lan N, Hellemans KG, Ellis L, Viau V, Weinberg J (2009) Role of testosterone in mediating prenatal ethanol effects on hypothalamic-pituitary-adrenal activity in male rats. Psychoneuroendocrinology 34:1314–1328PubMedCrossRefGoogle Scholar
  36. Lee S, Imaki T, Vale W, Rivier C (1990) Effect of prenatal exposure to ethanol on the activity of the hypothalamic–pituitary–adrenal axis of the offspring: importance of the time of exposure to ethanol and possible modulating mechanisms. Mol Cell Neurosci 1:168–177PubMedCrossRefGoogle Scholar
  37. Maas CJM, Howx JJ (2004) Robustness issues in multilevel regression analysis. Statistica Neerlandica 58:127–137CrossRefGoogle Scholar
  38. Mattson SN, Riley EP (2000) Parent ratings of behavior in children with heavy prenatal alcohol exposure and IQ-matched controls. Alcohol Clin Exp Res 24:226–231PubMedCrossRefGoogle Scholar
  39. Mattson SN, Riley EP, Gramling L, Delis DC, Jones KL (1997) Heavy prenatal alcohol exposure with or without physical features of fetal alcohol syndrome leads to IQ deficits. J Pediatr 131:718–721PubMedCrossRefGoogle Scholar
  40. Mattson SN, Goodman AM, Caine C, Delis DC, Riley EP (1999) Executive functioning in children with heavy prenatal alcohol exposure. Alcohol Clin Exp Res 23:1808–1815PubMedGoogle Scholar
  41. Mattson SN, Schoenfeld AM, Riley EP (2001) Teratogenic effects of alcohol on brain and behavior. Alcohol Res Health 25:185–191PubMedGoogle Scholar
  42. Meaney MJ (2001) Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 24:1161–1192PubMedCrossRefGoogle Scholar
  43. Miller GE, Chen E, Zhou ES (2007) If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. Psychol Bull 133:25–45PubMedCrossRefGoogle Scholar
  44. Mullen M, Snidman N, Kagan J (1993) Free-play behavior in inhibited and uninhibited children. Infant Behav Dev 16:383–389CrossRefGoogle Scholar
  45. Nathanson V, Jayesinghe N, Roycroft G (2007) Is it all right for women to drink small amounts of alcohol in pregnancy? No. BMJ 335:857PubMedCrossRefGoogle Scholar
  46. Oberlander TF, Jacobson SW, Weinberg J, Grunau RE, Molteno CD, Jacobson JL (2010) Prenatal alcohol exposure alters biobehavioral reactivity to pain in newborns. Alcohol Clin Exp Res 34:681–692PubMedCrossRefGoogle Scholar
  47. O’Brien P (2007) Is it all right for women to drink small amounts of alcohol in pregnancy? Yes. BMJ 335:856PubMedCrossRefGoogle Scholar
  48. Ouellet-Morin I, Boivin M, Dionne G, Lupien SJ, Arsenault L, Barr RG, Perusse D, Tremblay RE (2008) Variations in heritability of cortisol reactivity to stress as a function of early familial adversity among 19-month-old twins. Arch Gen Psychiatry 65:211–218PubMedCrossRefGoogle Scholar
  49. Pereira ADC, Olsen J, Ogston S (1993) Variability of self reported measures of alcohol consumption: implications for the association between drinking in pregnancy and birth weight. J Epidemiol Community Health 47:326–330CrossRefGoogle Scholar
  50. Ramsay D, Lewis M (2003) Reactivity and regulation in cortisol and behavioral responses to stress. Child Dev 74:456–464PubMedCrossRefGoogle Scholar
  51. Ramsay DS, Bendersky MI, Lewis M (1996) Effect of prenatal alcohol and cigarette exposure on two- and six-month-old infants’ adrenocortical reactivity to stress. J Pediatr Psychol 21:833–840PubMedCrossRefGoogle Scholar
  52. Rasbash J, Browne W, Goldstein H, Yang M, Plewis I, Healy M et al (2000) A user’s guide to MlwiN, version 2. 1. University of London, Institute of EducationGoogle Scholar
  53. Riley EP, McGee CL (2005) Fetal alcohol spectrum disorders: an overview with emphasis on changes in brain and behavior. Exp Biol Med 230:357–365Google Scholar
  54. Rudeen PK, Weinberg J (1993) Prenatal ethanol exposure: changes in regional brain catecholamine content following stress. J Neurochemistry 61:1907–1915CrossRefGoogle Scholar
  55. Sanchez MM (2006) The impact of early adverse care on HPA axis development: nonhuman primate models. Horm Behav 50:623–631PubMedCrossRefGoogle Scholar
  56. Sayal K (2007) Alcohol consumption in pregnancy as a risk factor for later mental health problems. Evid Based Ment Health 10:98–100PubMedCrossRefGoogle Scholar
  57. Sayal K, Heron J, Golding J, Emond A (2007) Prenatal alcohol exposure and gender differences in childhood mental health problems: a longitudinal population-based study. Pediatrics 119:e426–e434PubMedCrossRefGoogle Scholar
  58. Schneider ML, Moore CF, Kraemer GW, Roberts AD, DeJesus OT (2002) The impact of prenatal stress, fetal alcohol exposure, or both on development: perspectives from a primate model. Psychoneuroendocrinology 27:285–298PubMedCrossRefGoogle Scholar
  59. Schneider ML, Moore CF, Kraemer GW (2004) Moderate level alcohol during pregnancy, prenatal stress, or both and limbic–hypothalamic–pituitary–adrenocortical axis response to stress in rhesus monkeys. Child Dev 75:96–109PubMedCrossRefGoogle Scholar
  60. Schneider ML, Moore CF, Barnhart TE, Larson JA, DeJesus OT, Mukherjee J, Nickles RJ, Converse AK, Roberts AD, Kraemer GW (2005) Moderate-level prenatal alcohol exposure alters striatal dopamine system function in rhesus monkeys. Alcohol Clin Exp Res 29:1685–1697PubMedCrossRefGoogle Scholar
  61. Seale JV, Wood SA, Atkinson HC, Lightman SL, Harbuz MS (2005) Organizational role for testosterone and estrogen on adult hypothalamic-pituitary-adrenal axis activity in the male rat. Endocrinol 146:1973–1982CrossRefGoogle Scholar
  62. Sood B, Delaney-Black V, Covington C, Nordstrom-Klee B, Ager J, Templin T, Janisse J, Martier S, Sokol RJ (2001) Prenatal alcohol exposure and childhood behavior at age 6 to 7 years: I. Dose–response effect. Pediatrics 108:E34PubMedCrossRefGoogle Scholar
  63. Statistics Canada (1995) National longitudinal survey of children: survey instruments for 1994–95 data collection, cycle 1. Catalogue no. 89F0077XIE. Statistics Canada, OttawaGoogle Scholar
  64. Streissguth A (2007) Offspring effects of prenatal alcohol exposure from birth to 25 years: the Seattle Prospective Longitudinal Study. J Clin Psychol Med Settings 14:81–101CrossRefGoogle Scholar
  65. Streissguth A, O’Malley K (2000) Neuropsychiatric implications and long-term consequences of fetal alcohol spectrum disorders. Semin Clin Neuropsychiatry 5:177–190PubMedCrossRefGoogle Scholar
  66. Streissguth AP, Barr HM, Sampson PD (1990) Moderate prenatal alcohol exposure: effects on child IQ and learning problems at age 7 1/2 years. Alcohol Clin Exp Res 14:662–669PubMedCrossRefGoogle Scholar
  67. Susman EJ (2006) Psychobiology of persistent antisocial behavior: stress, early vulnerabilities and the attenuation hypothesis. Neurosci Biobehav Rev 30:376–389PubMedCrossRefGoogle Scholar
  68. Tabachnick BG, Fidell LS (1996) Using multivariate statistics, 3rd edn. HarperCollins College, New YorkGoogle Scholar
  69. van Bakel HJ, Riksen-Walraven JM (2004) Stress reactivity in 15-month-old infants: links with infant temperament, cognitive competence, and attachment security. Dev Psychobiol 44:157–167PubMedCrossRefGoogle Scholar
  70. Wacha VH, Obrzut JE (2007) Effects of fetal alcohol syndrome on neuropsychological function. J Dev Phys Disabil 19:217–226CrossRefGoogle Scholar
  71. Warren KR, Foudin LL (2001) Alcohol-related birth defects—the past, present, and future. Alcohol Res Health 25:153–158PubMedGoogle Scholar
  72. Weinberg J, Sliwowska JH, Lan N, Hellemans KG (2008) Prenatal alcohol exposure: foetal programming, the hypothalamic–pituitary–adrenal axis and sex differences in outcome. J Neuroendocrinol 20:470–488PubMedCrossRefGoogle Scholar
  73. Zhang X, Sliwowska JH, Weinberg J (2005) Prenatal alcohol exposure and fetal programming: effects on neuroendocrine and immune function. Exp Biol Med 230:376–388Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Isabelle Ouellet-Morin
    • 1
  • Ginette Dionne
    • 2
  • Sonia J. Lupien
    • 3
  • Gina Muckle
    • 2
  • Sylvana Côté
    • 4
    • 5
  • Daniel Pérusse
    • 6
  • Richard E. Tremblay
    • 4
    • 7
    • 8
  • Michel Boivin
    • 2
  1. 1.MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of PsychiatryKing’s College LondonLondonUK
  2. 2.School of PsychologyUniversité LavalQuébecCanada
  3. 3.Center for Human Stress Research, Fernand-Seguin Research CenterUniversité de MontréalMontréalCanadaH1N 3V2
  4. 4.International Laboratory for Child and Adolescent Mental Health DevelopmentINSERM U669Paris cedex 14France
  5. 5.Department of Social and Preventive Medicine, Faculté de MédecineUniversité de MontréalMontréalCanada
  6. 6.Department of AnthropologyUniversité de MontréalMontréalCanada
  7. 7.Department of Pediatrics, Psychiatry and PsychologyUniversité de MontréalMontréalCanada
  8. 8.School of Public Health and Population ScienceUniversity College DublinDublin 4Ireland

Personalised recommendations