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

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.

[1]  G. Berg,et al.  Hair Cortisol Measurement by an Automated Method , 2019, Scientific Reports.

[2]  Marek Malik,et al.  Assessment of mean respiratory rate from ECG recordings for risk stratification after myocardial infarction. , 2014, Journal of electrocardiology.

[3]  M. Mennes,et al.  Prenatal stress and the developing brain: Risks for neurodevelopmental disorders , 2018, Development and Psychopathology.

[4]  J. Ecker,et al.  Obstetric Care Consensus No. 5: Severe Maternal Morbidity Screening and Review , 2016, Obstetrics and gynecology.

[5]  Deutsche Gesellschaft für Gynäkologie und Geburtshilfe Archives of gynecology and obstetrics , 1987 .

[6]  F. Resch,et al.  Prenatal stress and infant affective reactivity at five months of age. , 2011, Early human development.

[7]  Enrico Ferrazzi,et al.  Phase-rectified signal averaging method to predict perinatal outcome in infants with very preterm fetal growth restriction- a secondary analysis of TRUFFLE-trial. , 2016, American journal of obstetrics and gynecology.

[8]  R. D. de Bie,et al.  The impact of maternal stress on pregnancy outcome in a well-educated Caucasian population. , 2005, Paediatric and perinatal epidemiology.

[9]  Marijke A. K. A. Braeken,et al.  Prenatal developmental origins of behavior and mental health: The influence of maternal stress in pregnancy , 2017, Neuroscience & Biobehavioral Reviews.

[10]  G. Gutiérrez-Ospina,et al.  Evaluating Stress during Pregnancy: Do We Have the Right Conceptions and the Correct Tools to Assess It? , 2018, Journal of pregnancy.

[11]  D. Ebert,et al.  The German Version of the Perceived Stress Scale (PSS-10): Evaluation of Dimensionality, Validity, and Measurement Invariance With Exploratory and Confirmatory Bifactor Modeling , 2019, Assessment.

[12]  J. Kurths,et al.  Influence of paced maternal breathing on fetal–maternal heart rate coordination , 2009, Proceedings of the National Academy of Sciences.

[13]  W. Holzgreve,et al.  Maternal laboratory stress influences fetal neurobehavior: Cortisol does not provide all answers , 2010, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[14]  Martin G. Frasch,et al.  Efficient Fetal-Maternal ECG Signal Separation from Two Channel Maternal Abdominal ECG via Diffusion-Based Channel Selection , 2017, Front. Physiol..

[15]  S. Chokron,et al.  Effects of prenatal stress on fetal and child development: A critical literature review , 2014, Neuroscience & Biobehavioral Reviews.

[16]  V. Mesch,et al.  Hair cortisol: A new tool for evaluating stress in programs of stress management. , 2015, Life sciences.

[17]  K. Munir,et al.  Prenatal stress and risk for autism , 2008, Neuroscience & Biobehavioral Reviews.

[18]  A. Papageorghiou,et al.  Consensus definition of fetal growth restriction: a Delphi procedure , 2016, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[19]  W. Fifer,et al.  Effects of Women’s Stress-Elicited Physiological Activity and Chronic Anxiety on Fetal Heart Rate , 2003, Journal of developmental and behavioral pediatrics : JDBP.

[20]  M. Mennes,et al.  Prenatal stress and the developing brain: Risks for neurodevelopmental disorders — ERRATUM , 2018, Development and Psychopathology.

[21]  U. Ceglarek,et al.  Evaluation of hair cortisol and cortisone change during pregnancy and the association with self-reported depression, somatization, and stress symptoms , 2018, Stress.

[22]  L. Glass Synchronization and rhythmic processes in physiology , 2001, Nature.

[23]  K. Pirke,et al.  Maternal trait anxiety, emotional distress, and salivary cortisol in pregnancy , 2010, Biological Psychology.

[24]  Georg Schmidt,et al.  Bivariate phase-rectified signal averaging--a novel technique for cross-correlation analysis in noisy nonstationary signals. , 2009, Journal of electrocardiology.

[25]  J. Buitelaar,et al.  Psychological measures of prenatal stress as predictors of infant temperament. , 2002, Journal of the American Academy of Child and Adolescent Psychiatry.

[26]  C. Kirschbaum,et al.  The 'Trier Social Stress Test'--a tool for investigating psychobiological stress responses in a laboratory setting. , 1993, Neuropsychobiology.

[27]  T. Kamarck,et al.  A global measure of perceived stress. , 1983, Journal of health and social behavior.

[28]  R. Bernier,et al.  Children with Autism Show Altered Autonomic Adaptation to Novel and Familiar Social Partners , 2016, Autism research : official journal of the International Society for Autism Research.

[29]  M. Bakermans-Kranenburg,et al.  No Moderating Effect of 5-HTTLPR on Associations Between Antenatal Anxiety and Infant Behavior , 2013, Journal of the American Academy of Child and Adolescent Psychiatry.

[30]  M. Meaney,et al.  Fetal Origins of Mental Health: The Developmental Origins of Health and Disease Hypothesis. , 2017, The American journal of psychiatry.

[31]  C. Monk,et al.  Impact of maternal stress, depression and anxiety on fetal neurobehavioral development. , 2009, Clinical obstetrics and gynecology.

[32]  T. Schuster,et al.  Phase-rectified signal averaging as a new method for surveillance of growth restricted fetuses , 2012, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[33]  O. Witte,et al.  Transfer of maternal psychosocial stress to the fetus , 2017, Neuroscience & Biobehavioral Reviews.

[34]  Martin G. Frasch,et al.  Fetal body weight and the development of the control of the cardiovascular system in fetal sheep , 2007, The Journal of physiology.

[35]  T. Paunio,et al.  Respiratory sinus arrhythmia moderates the impact of maternal prenatal anxiety on infant negative affectivity , 2017, Developmental psychobiology.

[36]  T. Campbell,et al.  Developmental origins of infant stress reactivity profiles: A multi-system approach. , 2016, Developmental psychobiology.

[37]  C. Kirschbaum,et al.  The Association of Hair Cortisol with Self-Reported Chronic Psychosocial Stress and Symptoms of Anxiety and Depression in Women Shortly after Delivery. , 2016, Paediatric and perinatal epidemiology.

[38]  E. Iversen,et al.  Maternal Stress, Preterm Birth, and DNA Methylation at Imprint Regulatory Sequences in Humans , 2014, Genetics & epigenetics.

[39]  R. Kronstrand,et al.  Society of Hair Testing guidelines for drug testing in hair. , 2012, Forensic science international.

[40]  T. Vrijkotte,et al.  Determinants of cortisol during pregnancy – The ABCD cohort , 2017, Psychoneuroendocrinology.

[41]  E. Davis,et al.  Prenatal maternal anxiety and early childhood temperament , 2011, Stress.

[42]  T. O'Connor,et al.  Maternal antenatal anxiety and behavioural/emotional problems in children: a test of a programming hypothesis. , 2003, Journal of child psychology and psychiatry, and allied disciplines.

[43]  S. Porges The polyvagal theory: New insights into adaptive reactions of the autonomic nervous system , 2009, Cleveland Clinic Journal of Medicine.

[44]  O. Witte,et al.  Impact of chronic maternal stress during early gestation on maternal–fetal stress transfer and fetal stress sensitivity in sheep , 2018, Stress.

[45]  Jan W. Kantelhardt,et al.  Bivariate phase-rectified signal averaging , 2008, 0804.2798.

[46]  Yanfen Lin,et al.  Effects of prenatal and postnatal maternal emotional stress on toddlers' cognitive and temperamental development. , 2017, Journal of affective disorders.

[47]  Xiaobo Li,et al.  Interaction between Prenatal Maternal Stress and Autonomic Arousal in Predicting Conduct Problems and Psychopathic Traits in Children , 2016, Journal of Psychopathology and Behavioral Assessment.

[48]  J. Buitelaar,et al.  Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis , 2014, European Child & Adolescent Psychiatry.

[49]  Y. Konishi,et al.  Effect of Maternal Stress on Fetal Heart Rate Assessed by Vibroacoustic Stimulation , 2009, The Journal of international medical research.

[50]  Leonard Reinecke,et al.  The German version of the Perceived Stress Scale – psychometric characteristics in a representative German community sample , 2016, BMC Psychiatry.