Silvia M Lobmaier1, A Müller2, C Zelgert3, C Shen4, P C Su4, G Schmidt2, B Haller5, G Berg6, B Fabre7, J Weyrich3, H T Wu4,8,9, M G Frasch10, M C Antonelli3,11. 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.
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.
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.
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