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

  • Silvia M. LobmaierEmail author
  • A. Müller
  • C. Zelgert
  • C. Shen
  • P. C. Su
  • G. Schmidt
  • B. Haller
  • G. Berg
  • B. Fabre
  • J. Weyrich
  • H. T. Wu
  • M. G. Frasch
  • M. C. Antonelli
Maternal-Fetal Medicine



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.


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.


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].


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.


ANS Bivariate phase-rectified signal averaging BPRSA Fetal autonomic nervous system Fetal heart rate Fetal stress index FSI Prenatal stress PS 



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 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.

Compliance with ethical standards

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). registration number is NCT03389178. Written informed consent was received from participants prior to inclusion in the study.

Supplementary material

404_2019_5390_MOESM1_ESM.jpg (109 kb)
Supplementary file1 (JPG 108 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Obstetrics and Gynecology, Klinikum Rechts Der IsarTechnical University of MunichMunichGermany
  2. 2.Innere Medizin I, Department of Cardiology, Klinikum Rechts Der IsarTechnical University of MunichMunichGermany
  3. 3.Department of MathematicsDuke UniversityDurhamUSA
  4. 4.Institute of Medical Informatics, Statistics and EpidemiologyBuenos AiresArgentina
  5. 5.Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas Y Técnicas (CONICET), Facultad de Farmacia Y BioquímicaBuenos AiresArgentina
  6. 6.Facultad de Farmacia Y Bioquímica. Instituto de Fisiopatología Y Bioquímica Clínica (INFIBIOC)Universidad de Buenos AiresBuenos AiresArgentina
  7. 7.Department of MathematicsDuke UniversityDurhamUSA
  8. 8.Department of Statistical ScienceDuke UniversityDurhamUSA
  9. 9.Mathematics DivisionNational Center for Theoretical SciencesTaipeiTaiwan
  10. 10.Department of Obstetrics and GynecologyUniversity of WashingtonSeattleUSA
  11. 11.Instituto de Biología Celular Y Neurociencia “Prof. E. De Robertis”Facultad de Medicina, Universidad de Buenos AiresBuenos AiresArgentina

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