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

doi:10.1007/s00404-019-05390-8

. 2020 Feb;301(2):405-414.

doi: 10.1007/s00404-019-05390-8. Epub 2019 Nov 28.

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

Silvia M Lobmaier¹, A Müller², C Zelgert³, C Shen⁴, P C Su⁴, G Schmidt², B Haller⁵, G Berg⁶, B Fabre⁷, J Weyrich³, H T Wu^{4

8

9}, M G Frasch¹⁰, M C Antonelli^{3

11}

Affiliations

¹ Department of Obstetrics and Gynecology, Klinikum Rechts Der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany. silvia.lobmaier@tum.de.
² Innere Medizin I, Department of Cardiology, Klinikum Rechts Der Isar, Technical University of Munich, Munich, Germany.
³ Department of Obstetrics and Gynecology, Klinikum Rechts Der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.
⁴ Department of Mathematics, Duke University, Durham, NC, 27705, USA.
⁵ Institute of Medical Informatics, Statistics and Epidemiology, Buenos Aires, Argentina.
⁶ Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas Y Técnicas (CONICET), Facultad de Farmacia Y Bioquímica, Buenos Aires, Argentina.
⁷ Facultad de Farmacia Y Bioquímica. Instituto de Fisiopatología Y Bioquímica Clínica (INFIBIOC), Universidad de Buenos Aires, Buenos Aires, Argentina.
⁸ Department of Statistical Science, Duke University, Durham, NC, 27705, USA.
⁹ Mathematics Division, National Center for Theoretical Sciences, Taipei, Taiwan.
¹⁰ Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
¹¹ Instituto de Biología Celular Y Neurociencia "Prof. E. De Robertis", Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

PMID: 31781889
DOI: 10.1007/s00404-019-05390-8

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

Silvia M Lobmaier et al. Arch Gynecol Obstet. 2020 Feb.

. 2020 Feb;301(2):405-414.

doi: 10.1007/s00404-019-05390-8. Epub 2019 Nov 28.

Authors

Silvia M Lobmaier¹, A Müller², C Zelgert³, C Shen⁴, P C Su⁴, G Schmidt², B Haller⁵, G Berg⁶, B Fabre⁷, J Weyrich³, H T Wu^{4

8

9}, M G Frasch¹⁰, M C Antonelli^{3

11}

Affiliations

¹ Department of Obstetrics and Gynecology, Klinikum Rechts Der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany. silvia.lobmaier@tum.de.
² Innere Medizin I, Department of Cardiology, Klinikum Rechts Der Isar, Technical University of Munich, Munich, Germany.
³ Department of Obstetrics and Gynecology, Klinikum Rechts Der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.
⁴ Department of Mathematics, Duke University, Durham, NC, 27705, USA.
⁵ Institute of Medical Informatics, Statistics and Epidemiology, Buenos Aires, Argentina.
⁶ Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas Y Técnicas (CONICET), Facultad de Farmacia Y Bioquímica, Buenos Aires, Argentina.
⁷ Facultad de Farmacia Y Bioquímica. Instituto de Fisiopatología Y Bioquímica Clínica (INFIBIOC), Universidad de Buenos Aires, Buenos Aires, Argentina.
⁸ Department of Statistical Science, Duke University, Durham, NC, 27705, USA.
⁹ Mathematics Division, National Center for Theoretical Sciences, Taipei, Taiwan.
¹⁰ Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
¹¹ Instituto de Biología Celular Y Neurociencia "Prof. E. De Robertis", Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

PMID: 31781889
DOI: 10.1007/s00404-019-05390-8

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.

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

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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 - DOI - PubMed - PMC
1. 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 - DOI - PubMed - PMC
1. 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 - DOI - PubMed - PMC
1. 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 - DOI - PubMed - PMC
1. 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 - DOI - PubMed - PMC

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[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 - DOI - PubMed - PMC

[2] 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 - DOI - PubMed - PMC

[3] 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 - DOI - PubMed - PMC

[4] 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 - DOI - PubMed - PMC

[5] 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 - DOI - PubMed - PMC

[6] 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 - DOI - PubMed - PMC

[7] 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 - DOI - PubMed - PMC

[8] 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 - DOI - PubMed - PMC

[9] 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 - DOI - PubMed - PMC

[10] 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 - DOI - PubMed - PMC

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

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

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