Skip to main content

Advertisement

SpringerLink
Log in

Fetal heart rate variability responsiveness to maternal stress, non-invasively detected from maternal transabdominal ECG

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Prenatal stress (PS) during pregnancy affects in utero- and postnatal child brain-development. Key systems affected are the hypothalamic–pituitary–adrenal axis and the autonomic nervous system (ANS). Maternal- and fetal ANS activity can be gauged non-invasively from transabdominal electrocardiogram (taECG). We propose a novel approach to assess couplings between maternal (mHR) and fetal heart rate (fHR) as a new biomarker for PS based on bivariate phase-rectified signal averaging (BPRSA). We hypothesized that PS exerts lasting impact on fHR.

Methods

Prospective case–control study matched for maternal age, parity, and gestational age during the third trimester using the Cohen Perceived Stress Scale (PSS-10) questionnaire with PSS-10 over or equal 19 classified as stress group (SG). Women with PSS-10 < 19 served as control group (CG). Fetal electrocardiograms were recorded by a taECG. Coupling between mHR and fHR was analyzed by BPRSA resulting in fetal stress index (FSI). Maternal hair cortisol, a memory of chronic stress exposure for 2–3 months, was measured at birth.

Results

538/1500 pregnant women returned the questionnaire, 55/538 (10.2%) mother–child pairs formed SG and were matched with 55/449 (12.2%) consecutive patients as CG. Maternal hair cortisol was 86.6 (48.0–169.2) versus 53.0 (34.4–105.9) pg/mg (p = 0.029). At 36 + 5 weeks, FSI was significantly higher in fetuses of stressed mothers when compared to controls [0.43 (0.18–0.85) versus 0.00 (− 0.49–0.18), p < 0.001].

Conclusion

Prenatal maternal stress affects the coupling between maternal and fetal heart rate detectable non-invasively a month prior to birth. Lasting effects on neurodevelopment of affected offspring should be studied.

Trial registration

Clinical trial registration: NCT03389178.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. O'Connor TG, Heron J, Golding J, Glover V, Team AS (2003) Maternal antenatal anxiety and behavioural/emotional problems in children: a test of a programming hypothesis. J Child Psychol Psychiatry 44(7):1025–1036

    Article  PubMed  Google Scholar 

  2. Van den Bergh BRH, van den Heuvel MI, Lahti M, Braeken M, de Rooij SR, Entringer S, Hoyer D, Roseboom T, Raikkonen K, King S et al (2017) Prenatal developmental origins of behavior and mental health: the influence of maternal stress in pregnancy. Neurosci Biobehav Rev. https://doi.org/10.1016/j.neubiorev.2017.07.003

    Article  PubMed  Google Scholar 

  3. Vidal AC, Benjamin Neelon SE, Liu Y, Tuli AM, Fuemmeler BF, Hoyo C, Murtha AP, Huang Z, Schildkraut J, Overcash F et al (2014) Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans. Genet Epigenet 6:37–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Rakers F, Rupprecht S, Dreiling M, Bergmeier C, Witte OW, Schwab M (2017) Transfer of maternal psychosocial stress to the fetus. Neurosci Biobehav Rev. https://doi.org/10.1016/j.neubiorev.2017.02.019

    Article  PubMed  Google Scholar 

  5. Rothenberger SE, Resch F, Doszpod N, Moehler E (2011) Prenatal stress and infant affective reactivity at five months of age. Early Hum Dev 87(2):129–136

    Article  PubMed  Google Scholar 

  6. Braithwaite EC, Ramchandani PG, O'Connor TG, van Ijzendoorn MH, Bakermans-Kranenburg MJ, Glover V, Netsi E, Evans J, Meaney MJ, Murphy SE (2013) No moderating effect of 5-HTTLPR on associations between antenatal anxiety and infant behavior. J Am Acad Child Adolesc Psychiatry 52(5):519–526

    Article  PubMed  PubMed Central  Google Scholar 

  7. Peltola MJ, Makela T, Paavonen EJ, Vierikko E, Saarenpaa-Heikkila O, Paunio T, Hietanen JK, Kylliainen A (2017) Respiratory sinus arrhythmia moderates the impact of maternal prenatal anxiety on infant negative affectivity. Dev Psychobiol 59(2):209–216

    Article  PubMed  Google Scholar 

  8. Blair MM, Glynn LM, Sandman CA, Davis EP (2011) Prenatal maternal anxiety and early childhood temperament. Stress 14(6):644–651

    Article  PubMed  Google Scholar 

  9. Lin Y, Xu J, Huang J, Jia Y, Zhang J, Yan C, Zhang J (2017) Effects of prenatal and postnatal maternal emotional stress on toddlers' cognitive and temperamental development. J Affect Disord 207:9–17

    Article  PubMed  Google Scholar 

  10. Graignic-Philippe R, Dayan J, Chokron S, Jacquet AY, Tordjman S (2014) Effects of prenatal stress on fetal and child development: a critical literature review. Neurosci Biobehav Rev 43:137–162

    Article  CAS  PubMed  Google Scholar 

  11. Beijers R, Buitelaar JK, de Weerth C (2014) Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis. Eur Child Adolesc Psychiatry 23(10):943–956

    Article  PubMed  Google Scholar 

  12. Kirschbaum C, Pirke K-M, Hellhammer DH (1993) The ‘Trier Social Stress Test’—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28(1–2):76–81

    Article  CAS  PubMed  Google Scholar 

  13. van den Bergh BRH, Dahnke R, Mennes M (2018) Prenatal stress and the developing brain: Risks for neurodevelopmental disorders. Dev Psychopathol 30(3):743–762

    Article  PubMed  Google Scholar 

  14. Rash JA, Thomas JC, Campbell TS, Letourneau N, Granger DA, Giesbrecht GF (2016) Developmental origins of infant stress reactivity profiles: a multi-system approach. Dev Psychobiol 58(5):578–599

    Article  CAS  PubMed  Google Scholar 

  15. O'Donnell KJ, Meaney MJ (2017) Fetal origins of mental health: the developmental origins of health and disease hypothesis. Am J Psychiatry 174(4):319–328

    Article  PubMed  Google Scholar 

  16. Van Leeuwen P, Geue D, Thiel M, Cysarz D, Lange S, Romano MC, Wessel N, Kurths J, Gronemeyer DH (2009) Influence of paced maternal breathing on fetal-maternal heart rate coordination. Proc Natl Acad Sci USA 106(33):13661–13666

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bauer A, Barthel P, Muller A, Kantelhardt J, Schmidt G (2009) Bivariate phase-rectified signal averaging—a novel technique for cross-correlation analysis in noisy nonstationary signals. J Electrocardiol 42(6):602–606

    Article  PubMed  Google Scholar 

  18. Schumann AY, Kantelhardt JW, Bauer A, Schmidt G (2008) Bivariate phase-rectified signal averaging. Phys A 387(21):5091–5100

    Article  Google Scholar 

  19. Gordijn SJ, Beune IM, Thilaganathan B, Papageorghiou A, Baschat AA, Baker PN, Silver RM, Wynia K, Ganzevoort W (2016) Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol 48(3):333–339

    Article  CAS  PubMed  Google Scholar 

  20. American College of O, Gynecologists, the Society for Maternal-Fetal M, Kilpatrick SK, Ecker JL (2016) Severe maternal morbidity: screening and review. Am J Obstet Gynecol 215(3):B17–B22

    Article  Google Scholar 

  21. Cohen S, Kamarck T, Mermelstein R (1983) A global measure of perceived stress. J Health Soc Behav 24(4):385–396

    Article  CAS  PubMed  Google Scholar 

  22. Huizink AC, de Medina PG, Mulder EJ, Visser GH, Buitelaar JK (2002) Psychological measures of prenatal stress as predictors of infant temperament. J Am Acad Child Adolesc Psychiatry 41(9):1078–1085

    Article  PubMed  Google Scholar 

  23. Pluess M, Bolten M, Pirke KM, Hellhammer D (2010) Maternal trait anxiety, emotional distress, and salivary cortisol in pregnancy. Biol Psychol 83(3):169–175

    Article  PubMed  Google Scholar 

  24. Klein EM, Brahler E, Dreier M, Reinecke L, Muller KW, Schmutzer G, Wolfling K, Beutel ME (2016) The German version of the Perceived Stress Scale—psychometric characteristics in a representative German community sample. BMC Psychiatry 16:159

    Article  PubMed  PubMed Central  Google Scholar 

  25. Reis D, Lehr D, Heber E, Ebert DD (2017) The German Version of the Perceived Stress Scale (PSS-10): Evaluation of dimensionality, validity, and measurement invariance with exploratory and confirmatory bifactor modeling. Assessment 26(7):1246–1259. https://doi.org/10.1177/1073191117715731

    Article  PubMed  Google Scholar 

  26. Krabbendam L, Smits L, de Bie R, Bastiaanssen J, Stelma F, van Os J (2005) The impact of maternal stress on pregnancy outcome in a well-educated Caucasian population. Paediatr Perinat Epidemiol 19(6):421–425

    Article  PubMed  Google Scholar 

  27. Li R, Frasch MG, Wu HT (2017) Efficient fetal–maternal ECG signal separation from two channel maternal abdominal ECG via diffusion-based channel selection. Front Physiol 8:277

    Article  PubMed  PubMed Central  Google Scholar 

  28. Sinnecker D, Dommasch M, Barthel P, Muller A, Dirschinger RJ, Hapfelmeier A, Huster KM, Laugwitz KL, Malik M, Schmidt G (2014) Assessment of mean respiratory rate from ECG recordings for risk stratification after myocardial infarction. J Electrocardiol 47(5):700–704

    Article  PubMed  Google Scholar 

  29. Cooper GA, Kronstrand R, Kintz P (2012) Society of hair T: society of hair testing guidelines for drug testing in hair. Forensic Sci Int 218(1–3):20–24

    Article  CAS  PubMed  Google Scholar 

  30. Iglesias S, Jacobsen D, Gonzalez D, Azzara S, Repetto EM, Jamardo J, Gomez SG, Mesch V, Berg G, Fabre B (2015) Hair cortisol: a new tool for evaluating stress in programs of stress management. Life Sci 141:188–192

    Article  CAS  PubMed  Google Scholar 

  31. Gonzalez D, Jacobsen D, Ibar C, Pavan C, Monti J, Fernandez Machulsky N, Balbi A, Fritzler A, Jamardo J, Repetto EM et al (2019) Hair cortisol measurement by an automated method. Sci Rep 9(1):8213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lobmaier SM, Huhn EA, Pildner von Steinburg S, Müller A, Schuster T, Ortiz JU, Schmidt G, Schneider KT (2012) Phase-rectified signal averaging as a new method for surveillance of growth restricted fetuses. J Maternal Fetal Neonatal Med 25(12):2523–2528

    Article  CAS  Google Scholar 

  33. Lobmaier SM, Mensing van Charante N, Ferrazzi E, Giussani DA, Shaw CJ, Müller A, Ortiz JU, Ostermayer E, Haller B, Prefumo F et al (2016) Phase-rectified signal averaging method to predict perinatal outcome in infants with very preterm fetal growth restriction—a secondary analysis of TRUFFLE-trial. Am J Obst Gynecol 215(5):630.e631–630.e637

  34. Frasch MG, Muller T, Wicher C, Weiss C, Lohle M, Schwab K, Schubert H, Nathanielsz PW, Witte OW, Schwab M (2007) Fetal body weight and the development of the control of the cardiovascular system in fetal sheep. J Physiol 579(Pt 3):893–907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Glass L (2001) Synchronization and rhythmic processes in physiology. Nature 410(6825):277–284

    Article  CAS  PubMed  Google Scholar 

  36. Monk C, Myers MM, Sloan RP, Ellman LM, Fifer WP (2003) Effects of women’s stress-elicited physiological activity and chronic anxiety on fetal heart rate. J Dev Behav Pediatr 24(1):32–38

    Article  PubMed  Google Scholar 

  37. Makino I, Matsuda Y, Yoneyama M, Hirasawa K, Takagi K, Ohta H, Konishi Y (2009) Effect of maternal stress on fetal heart rate assessed by vibroacoustic stimulation. J Int Med Res 37(6):1780–1788

    Article  CAS  PubMed  Google Scholar 

  38. Fink NS, Urech C, Berger CT, Hoesli I, Holzgreve W, Bitzer J, Alder J (2010) Maternal laboratory stress influences fetal neurobehavior: cortisol does not provide all answers. J Maternal Fetal Neonatal Med 23(6):488–500

    Article  CAS  Google Scholar 

  39. Kinsella MT, Monk C (2009) Impact of maternal stress, depression and anxiety on fetal neurobehavioral development. Clin Obstet Gynecol 52(3):425–440

    Article  PubMed  PubMed Central  Google Scholar 

  40. Gao Y, Huang Y, Li X (2017) Interaction between prenatal maternal stress and autonomic arousal in predicting conduct problems and psychopathic traits in children. J Psychopathol Behav Assess 39(1):1–14

    Article  CAS  PubMed  Google Scholar 

  41. Kinney DK, Munir KM, Crowley DJ, Miller AM (2008) Prenatal stress and risk for autism. Neurosci Biobehav Rev 32(8):1519–1532

    Article  PubMed  PubMed Central  Google Scholar 

  42. Neuhaus E, Bernier RA, Beauchaine TP (2016) Children with Autism Show Altered Autonomic Adaptation to Novel and Familiar Social Partners. Autism Res 9(5):579–591

    Article  PubMed  Google Scholar 

  43. Dreiling M, Schiffner R, Bischoff S, Rupprecht S, Kroegel N, Schubert H, Witte OW, Schwab M, Rakers F (2017) Impact of chronic maternal stress during early gestation on maternal–fetal stress transfer and fetal stress sensitivity in sheep. Stress 21(1):1–10. https://doi.org/10.1080/10253890.2017.1387534

    Article  CAS  PubMed  Google Scholar 

  44. Braig S, Grabher F, Ntomchukwu C, Reister F, Stalder T, Kirschbaum C, Rothenbacher D, Genuneit J (2016) The association of hair cortisol with self-reported chronic psychosocial stress and symptoms of anxiety and depression in women shortly after delivery. Paediatr Perinat Epidemiol 30(2):97–104

    Article  PubMed  Google Scholar 

  45. Bleker LS, Roseboom TJ, Vrijkotte TG, Reynolds RM, de Rooij SR (2017) Determinants of cortisol during pregnancy—the ABCD cohort. Psychoneuroendocrinology 83:172–181

    Article  CAS  PubMed  Google Scholar 

  46. Scharlau F, Pietzner D, Vogel M, Gaudl A, Ceglarek U, Thiery J, Kratzsch J, Hiemisch A, Kiess W (2017) Evaluation of hair cortisol and cortisone change during pregnancy and the association with self-reported depression, somatization, and stress symptoms. Stress 21(1):43–50. https://doi.org/10.1080/10253890.2017.1392507

    Article  CAS  PubMed  Google Scholar 

  47. Porges SW (2009) The polyvagal theory: new insights into adaptive reactions of the autonomic nervous system. Cleve Clin J Med 76(Suppl 2):S86–90

    Article  PubMed  PubMed Central  Google Scholar 

  48. Gonzalez-Ochoa R, Sanchez-Rodriguez EN, Chavarria A, Gutierrez-Ospina G, Romo-Gonzalez T (2018) Evaluating stress during pregnancy: do we have the right conceptions and the correct tools to assess it? J Pregnancy 2018:4857065

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

MCA was awarded with the August Wilhelm Scheer Professorship Program (TUM) twice for a 6 months period stay at the Klinik und Poliklinik für Frauenheilkunde, Technische Universität München, Klinikum rechts der Isar, Munich for the start-up of the FELICITy project and a Hans Fischer Senior Fellowship from IAS-TUM (Institute for Advanced Study-TUM, Munich).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Klinikum Rechts Der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany

    Silvia M. Lobmaier, C. Zelgert, J. Weyrich & M. C. Antonelli

  2. Innere Medizin I, Department of Cardiology, Klinikum Rechts Der Isar, Technical University of Munich, Munich, Germany

    A. Müller & G. Schmidt

  3. Department of Mathematics, Duke University, Durham, NC, 27705, USA

    C. Shen & P. C. Su

  4. Institute of Medical Informatics, Statistics and Epidemiology, Buenos Aires, Argentina

    B. Haller

  5. Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas Y Técnicas (CONICET), Facultad de Farmacia Y Bioquímica, Buenos Aires, Argentina

    G. Berg

  6. Facultad de Farmacia Y Bioquímica. Instituto de Fisiopatología Y Bioquímica Clínica (INFIBIOC), Universidad de Buenos Aires, Buenos Aires, Argentina

    B. Fabre

  7. Department of Mathematics, Duke University, Durham, NC, 27705, USA

    H. T. Wu

  8. Department of Statistical Science, Duke University, Durham, NC, 27705, USA

    H. T. Wu

  9. Mathematics Division, National Center for Theoretical Sciences, Taipei, Taiwan

    H. T. Wu

  10. Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA

    M. G. Frasch

  11. Instituto de Biología Celular Y Neurociencia “Prof. E. De Robertis”, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

    M. C. Antonelli

Authors
  1. Silvia M. Lobmaier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Zelgert
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. C. Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B. Haller
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G. Berg
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. B. Fabre
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J. Weyrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. H. T. Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. M. G. Frasch
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. M. C. Antonelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SML and MCA: protocol and project development, data collection and management, data analysis, and manuscript writing and editing. MF: data collection management, data analysis, and manuscript writing and editing. CZ and JW: patient recruitment, data collection, and manuscript writing and editing. AM and GS: data analysis, manuscript writing and editing. BH: statistical analysis and advice, manuscript writing and editing. CS and PCS: machine learning analysis, manuscript editing. HTW: machine learning analysis and manuscript writing and editing. BF and GB: cortisol analysis in hair samples, manuscript writing and editing.

Corresponding author

Correspondence to Silvia M. Lobmaier.

Ethics declarations

Conflict of interest

HTW and MGF hold a provisional and a PCT patent on fetal ECG technology.

Ethical approval

The study protocol is in strict accordance with the Committee of Ethical Principles for Medical Research from TUM and has the approval of the “Ethikkommission der Fakultät für Medizin der Technischen Universität München” (registration number 151/16S). ClinicalTrials.gov registration number is NCT03389178. Written informed consent was received from participants prior to inclusion in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (JPG 108 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lobmaier, S.M., Müller, A., Zelgert, C. et al. Fetal heart rate variability responsiveness to maternal stress, non-invasively detected from maternal transabdominal ECG. Arch Gynecol Obstet 301, 405–414 (2020). https://doi.org/10.1007/s00404-019-05390-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-019-05390-8

Keywords

Search

Navigation