Skip to main content
SpringerLink
Log in

Influence of prenatal maternal stress on umbilical cord blood cytokine levels

  • Original Article
  • Published:
Archives of Women's Mental Health Aims and scope Submit manuscript

Abstract

Purpose

Prenatal maternal stress (PNMS) is known to influence fetal programming and development. Thus far, the effects of PNMS on the developing immune system have mainly been documented in animal studies. This study aimed to examine the association between PNMS and immune cytokine profiles in the umbilical cord blood of newborn human infants.

Methods

PNMS, including perceived stress, numbers of stressful life events experiences (both partner and health related), and state and trait anxiety, was assessed with five questionnaires and interviews from 43 pregnant women during the second trimester. Seven key cytokines important for immune function, i.e., IL-12, IL-1β, IL-4, IL-5, IL-6, IL-8, and TNF-α, were analyzed in cord blood by bead-based ELISA method (Luminex 200). Logistic regression was used to estimate the associations of PNMS scores and cytokine levels.

Results

Increased levels of IL-1β, IL-4, IL-5, IL-6, and IL-8 were significantly associated with at least one of the maternal stress assessments, while the levels of IL-12 and TNF-α were not significantly associated with any of the PNMS measurements examined.

Conclusion

These preliminary findings suggest that PNMS may influence cytokine levels in newborn infants, in particular Th2-related cytokines. This report supports previous findings in animal studies and could suggest that newborns born to mothers with elevated PNMS have a predisposition to immune-related disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Akdis M et al (2011) Interleukins, from 1 to 37, and interferon-gamma: receptors, functions, and roles in diseases. J Allergy Clin Immunol 127(701-721):e701–e770. doi:10.1016/j.jaci.2010.11.050

    Article  Google Scholar 

  • Andersson NW, Hansen MV, Larsen AD, Hougaard KS, Kolstad HA, Schlunssen V (2016) Prenatal maternal stress and atopic diseases in the child: a systematic review of observational human studies Allergy 71:15-26. doi:10.1111/all.12762

  • Cameron MJ, Kelvin DJ (2003) Cytokines and chemokines--their receptors and their genes: an overview. Adv Exp Med Biol 520:8–32

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Qian L, Rialdi A, Mystal E, Ly J, Finik J, Davey T, Lambertini L, Nomura Y (2014) Influences of maternal stress during pregnancy on the Epi/genome: comparison of placenta and umbilical cord blood. J Depress Anxiety 3:3–152

    Google Scholar 

  • Christian LM (2012) Psychoneuroimmunology in pregnancy: immune pathways linking stress with maternal health, adverse birth outcomes, and fetal development. Neurosci Biobehav Rev 36:350–361. doi:10.1016/j.neubiorev.2011.07.005

    Article  PubMed  Google Scholar 

  • Coe CL, Lubach GR, Shirtcliff EA (2007) Maternal stress during pregnancy predisposes for iron deficiency in infant monkeys impacting innate immunity. Pediatr Res 61:520–524. doi:10.1203/pdr.0b013e318045be53

    Article  CAS  PubMed  Google Scholar 

  • Cohen S, Janicki-Deverts D, Miller GE (2007) Psychological stress and disease. JAMA 298:1685–1687. doi:10.1001/jama.298.14.1685

    Article  CAS  PubMed  Google Scholar 

  • Cohen S, Kamarck T, Mermelstein R (1983) A global measure of perceived stress. J Health Soc Behav 24:385–396

    Article  CAS  PubMed  Google Scholar 

  • Dipietro JA (2012) Maternal stress in pregnancy: considerations for fetal development. J Adolesc Health 51:S3–S8. doi:10.1016/j.jadohealth.2012.04.008

    Article  PubMed  PubMed Central  Google Scholar 

  • Dohrenwend BSKL, Askenasy AR, Dohrenwend BP (2002) The Psychiatric Epidemiology Research Interview Life Events Scale. Free Press, New York

    Google Scholar 

  • Dunkel Schetter C (2011) Psychological science on pregnancy: stress processes, biopsychosocial models, and emerging research issues. Annu Rev Psychol 62:531–558. doi:10.1146/annurev.psych.031809.130727

    Article  PubMed  Google Scholar 

  • Eisenberger NI, Cole SW (2012) Social neuroscience and health: neurophysiological mechanisms linking social ties with physical health. Nat Neurosci 15:669–674. doi:10.1038/nn.3086

    Article  CAS  PubMed  Google Scholar 

  • Entringer S, Kumsta R, Nelson EL, Hellhammer DH, Wadhwa PD, Wust S (2008) Influence of prenatal psychosocial stress on cytokine production in adult women. Dev Psychol 50:579–587. doi:10.1002/dev.20316

    Article  CAS  Google Scholar 

  • First MB, Spitzer RL, Gibbins M, Williams J (2002) Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition With Psychotic Screen (SCID-I/P W/PSY SCREEN). Biometrics Research, New York State Psychiatric Institute, New York

    Google Scholar 

  • Glaser R, Kiecolt-Glaser JK (2005) Stress-induced immune dysfunction: implications for health. Nat Rev Immunol 5:243–251. doi:10.1038/nri1571

    Article  CAS  PubMed  Google Scholar 

  • Glover V (2014) Maternal depression, anxiety and stress during pregnancy and child outcome; what needs to be done Best practice & research Clinical obstetrics & gynaecology 28:25-35 doi:10.1016/j.bpobgyn.2013.08.017

  • Glover V (2015) Prenatal stress and its effects on the fetus and the child: possible underlying biological mechanisms Advances in neurobiology 10:269-283 doi:10.1007/978-1-4939-1372-5_13

  • Greenland S (1989) Modeling and variable selection in epidemiologic analysis. Am J Public Health 79:340–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kay G, Tarcic N, Poltyrev T, Weinstock M (1998) Prenatal stress depresses immune function in rats. Physiol Behav 63:397–402

    Article  CAS  PubMed  Google Scholar 

  • Kinsella MT, Monk C (2009) Impact of maternal stress, depression and anxiety on fetal neurobehavioral development. Clin Obstet Gynecol 52:425–440. doi:10.1097/GRF.0b013e3181b52df1

    Article  PubMed  PubMed Central  Google Scholar 

  • Li-Weber M, Krammer PH (2003) Regulation of IL4 gene expression by T cells and therapeutic perspectives. Nat Rev Immunol 3:534–543. doi:10.1038/nri1128

    Article  CAS  PubMed  Google Scholar 

  • Littleton HL, Bye K, Buck K, Amacker A (2010) Psychosocial stress during pregnancy and perinatal outcomes: a meta-analytic review. J Psychosom Obstet Gynaecol 31:219–228. doi:10.3109/0167482X.2010.518776

    Article  PubMed  Google Scholar 

  • McEwen BS (2007) Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev 87:873–904. doi:10.1152/physrev.00041.2006

    Article  PubMed  Google Scholar 

  • Nast I, Bolten M, Meinlschmidt G, Hellhammer DH (2013) How to measure prenatal stress? A systematic review of psychometric instruments to assess psychosocial stress during pregnancy. Paediatr Perinat Epidemiol 27:313–322. doi:10.1111/ppe.12051

    Article  PubMed  Google Scholar 

  • O'Connor TG et al. (2013) Prenatal maternal anxiety predicts reduced adaptive immunity in infants Brain, behavior, and immunity 32:21-28 doi:10.1016/j.bbi.2013.02.002

  • O’Donnell KJ, Glover V, Holbrook JD, O’Connor TG (2014) Maternal prenatal anxiety and child brain-derived neurotrophic factor (BDNF) genotype: effects on internalizing symptoms from 4 to 15 years of age Development and psychopathology 26:1255-1266 doi:10.1017/S095457941400100X

  • Pincus-Knackstedt MK et al (2006) Prenatal stress enhances susceptibility of murine adult offspring toward airway inflammation. J Immunol 177:8484–8492

    Article  CAS  PubMed  Google Scholar 

  • Prescott SL, Macaubas C, Smallacombe T, Holt BJ, Sly PD, Holt PG (1999) Development of allergen-specific T-cell memory in atopic and normal children. Lancet 353:196–200. doi:10.1016/S0140-6736(98)05104-6

    Article  CAS  PubMed  Google Scholar 

  • Rice F, Jones I, Thapar A (2007) The impact of gestational stress and prenatal growth on emotional problems in offspring: a review. Acta Psychiatr Scan 115:171–183. doi:10.1111/j.1600-0447.2006.00895.x

    Article  CAS  Google Scholar 

  • Ridker PM (2007) Inflammatory biomarkers and risks of myocardial infarction, stroke, diabetes, and total mortality: implications for longevity. Nutr Rev 65:S253–S259

    Article  PubMed  Google Scholar 

  • Sapolsky RM (2004) Why zebras don't get ulcers: An updated guide to stress, stress related diseases, and coping. Freeman WH, 2nd edn. April 15, 1998

  • Spielberger CD (1989) State-trait anxiety inventory: bibliography. Consulting Psychologists Press, Palo Alto

  • Spielberger CD, Sydeman SJ (1994) State-Trait Anxiety Inventory and State-Trait Anger Expression Inventory. In: Maruish ME (ed) The use of psychological testing for treatment planning and outcome assessment. Lawrence Erlbaum Associates, Hillsdale, pp 292–321

  • Tuchscherer M, Kanitz E, Otten W, Tuchscherer A (2002) Effects of prenatal stress on cellular and humoral immune responses in neonatal pigs. Vet Immunol Immunopathol 86:195–203

    Article  CAS  PubMed  Google Scholar 

  • Veru F, Laplante DP, Luheshi G, King S (2014) Prenatal maternal stress exposure and immune function in the offspring Stress (Amsterdam, Netherlands) 17:133-148 doi:10.3109/10253890.2013.876404

  • Wright RJ et al. (2010) Prenatal maternal stress and cord blood innate and adaptive cytokine responses in an inner-city cohort Am J Respir Crit Care Med 182:25-33 doi:10.1164/rccm.200904-0637OC

Download references

Acknowledgments

The authors wish to acknowledge the following funding sources: K01MH080062 and R01MH102729 from NIMH (to YN) and Queens College Research Enhancement Grant (to YN), Mount Sinai Children’s Environmental Health Center Pilot Fund (to JC, YN) and R01 HD067611/R01ES022223 (to JC). The authors also wish to acknowledge Yula Ma for technical assistance on cytokines analyses and the Human Immune Monitoring Core Shared Resource Facility.

Author information

Authors and Affiliations

  1. Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark

    Niklas W. Andersson

  2. Sydney Medical School, Faculty of Medicine, University of Sydney, Concord Hospital, Sydney, Australia

    Niklas W. Andersson

  3. Department of Psychology, Queens College, the City University of New York (CUNY), Flushing, New York, USA

    Niklas W. Andersson, Jenny Ly & Yoko Nomura

  4. Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA

    Qian Li, Yoko Nomura & Jia Chen

  5. The Graduate Center, CUNY, New York, NY, USA

    Carrie W. Mills & Yoko Nomura

  6. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Jenny Ly & Yoko Nomura

  7. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Jia Chen

  8. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Jia Chen

Authors
  1. Niklas W. Andersson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carrie W. Mills
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jenny Ly
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoko Nomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jia Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoko Nomura.

Ethics declarations

The study was approved by the Institutional Review Boards at Icahn School of Medicine at Mount Sinai and Queens College, City University of New York.

Conflict of interest

The authors have no conflicts of interest to declare.

Additional information

Niklas W. Andersson and Qian Li first author

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Andersson, N.W., Li, Q., Mills, C.W. et al. Influence of prenatal maternal stress on umbilical cord blood cytokine levels. Arch Womens Ment Health 19, 761–767 (2016). https://doi.org/10.1007/s00737-016-0607-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00737-016-0607-7

Keywords

Search

Navigation