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

Silvia M. Lobmaier, Alexander Mueller+11 more|arXiv (Cornell University)|Nov 28, 2019

Maternal Mental Health During Pregnancy and Postpartum50 references8 citations

TL;DR

This study investigates fetal heart rate variability (fHR) responsiveness to maternal stress using non-invasive transabdominal ECG. By applying bivariate phase-rectified signal averaging (BPRSA) to quantify coupling between maternal and fetal heart rate, it demonstrates a significantly higher fetal stress index (FSI) in fetuses of stressed mothers (median FSI 0.43) compared to controls (0.00), indicating lasting prenatal stress effects in the third trimester.

ABSTRACT

Objective: We hypothesized that prenatal stress (PS) exerts lasting impact on fetal heart rate (fHR). We sought to validate the presence of such PS signature in fHR by measuring coupling between maternal HR (mHR) and fHR. Study design: Prospective observational cohort study in stressed group (SG) mothers with controls matched for gestational age during screening at third trimester using Cohen Perceived Stress Scale (PSS) questionnaire with PSS-10 equal or above 19 classified as SG. Women with PSS-10 less than 19 served as control group (CG). Setting: Klinikum rechts der Isar of the Technical University of Munich. Population: Singleton 3rd trimester pregnant women. Methods: Transabdominal fetal electrocardiograms (fECG) were recorded. We deployed a signal processing algorithm termed bivariate phase-rectified signal averaging (BPRSA) to quantify coupling between mHR and fHR resulting in a fetal stress index (FSI). Maternal hair cortisol was measured at birth. Differences were assumed to be significant for p value less than 0.05. Main Outcome Measures: Differences for FSI between both groups. Results: We screened 1500 women enrolling 538 of which 16.5 % showed a PSS-10 score equal or above 19 at 34+0 weeks. Fifty five women eventually comprised the SG and n=55 served as CG. Median PSS was 22.0 (IQR 21.0-24.0) in the SG and 9.0 (6.0-12.0) in the CG, respectively. Maternal hair cortisol was higher in SG than CG at 86.6 (48.0-169.2) versus 53.0 (34.4-105.9) pg/mg. 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)]. Conclusion: Our findings show a persistent effect of PS affecting fetuses in the last trimester.

Motivation & Objective

• To investigate whether prenatal stress (PS) leaves a measurable physiological signature in fetal heart rate (fHR) variability.
• To validate the presence of a prenatal stress signature in fHR by quantifying coupling between maternal heart rate (mHR) and fHR.
• To assess the association between maternal perceived stress and fetal neurodevelopmental reactivity using non-invasive fECG monitoring.
• To correlate findings with maternal hair cortisol levels at birth as a biological marker of stress.

Proposed method

• Conducted a prospective observational cohort study at Klinikum rechts der Isar, Munich, with singleton third-trimester pregnant women.
• Classified mothers into stressed group (SG) and control group (CG) based on Cohen’s Perceived Stress Scale (PSS-10 ≥19 vs. <19).
• Recorded transabdominal fetal electrocardiograms (fECG) to extract fetal and maternal heart rate signals.
• Applied bivariate phase-rectified signal averaging (BPRSA) to quantify dynamic coupling between mHR and fHR, yielding a fetal stress index (FSI).
• Measured maternal hair cortisol at birth as a biological marker of prolonged HPA-axis activation.
• Used non-parametric tests to compare FSI and cortisol levels between groups, with significance set at p < 0.05.

Experimental results

Research questions

• RQ1 Does maternal perceived stress in the third trimester correlate with measurable changes in fetal heart rate variability?
• RQ2 Can fetal stress reactivity be non-invasively detected via transabdominal ECG using BPRSA-based coupling analysis?
• RQ3 Is there a significant difference in fetal stress index (FSI) between fetuses of stressed and non-stressed mothers?
• RQ4 Do elevated maternal hair cortisol levels at birth correlate with higher FSI in fetuses of stressed mothers?

Key findings

• The stressed group (SG) had a significantly higher median PSS-10 score (22.0, IQR 21.0–24.0) compared to the control group (CG) (9.0, IQR 6.0–12.0).
• Maternal hair cortisol was significantly higher in the SG (86.6 pg/mg, IQR 48.0–169.2) than in the CG (53.0 pg/mg, IQR 34.4–105.9).
• At 36+5 weeks, the fetal stress index (FSI) was significantly higher in the SG (0.43, IQR 0.18–0.85) than in the CG (0.00, IQR -0.49–0.18).
• The FSI difference between groups was statistically significant (p < 0.05), indicating measurable fetal reactivity to maternal stress.
• The study confirms a persistent effect of prenatal stress on fetal heart rate variability in the last trimester.
• The non-invasive BPRSA method successfully detected stress-related fHR variability changes linked to maternal psychological and biological stress markers.