Background: Assessing fetal heart rate variability (fHRV) can aid in non-invasively assessing fetal well-being and tracking fetal neurodevelopment. However, poor data quality often impedes such analyses. Recently, algorithms extracting fetal R-peaks from abdominal ECG measurements have been improved, while HRV methodologies have been developed which are more robust to noise and missing data. One example is phase rectified signal averaging (PRSA), which graphically shows the rate and magnitude of heart rate (HR) decelerations and has been used in identifying fetal complications such as acidemia and intra-uterine growth restriction. However, it is largely unknown how gestational age (GA) affects PRSA, limiting its clinical interpretation. Therefore, here we investigate how PRSA changes with healthy fetal autonomic development.
Methods: Repeated abdominal ECG measurements (n=184) were obtained from 29 healthy pregnancies. Deceleration capacity (DC), which quantifies the response in HR to decelerations (as observed in PRSA) was calculated with the highest quality five-minute segment per measurement. To capture the possibly dynamic changes in fHRV, results were grouped into seven GA bins of approximately four weeks each, spanning 13-41 weeks of gestation. A Kruskal-Wallis H-test was performed to assess differences across groups with a Dunn's posthoc test with Bonferroni correction to test for between-group differences.
Results: DC changes significantly (p-value<0.01) across gestation. Furthermore, DC decreases significantly from early gestation (4.5 (4.1–7.3) ms; 13–16 weeks GA) to mid-gestation (1.2 (0.9–1.8) ms; 20–24 weeks GA) and thereafter increases significantly again in later gestation (2.1 (1.5–3.5) ms; 32–36 weeks GA).
Conclusion: We hypothesize that the high DC values in early pregnancy reflect an underdeveloped fetal autonomic nervous system. As the sympathetic branch matures towards mid-pregnancy, DC decreases. In later pregnancy, the maturing parasympathetic branch and myelination of the nerves allow quicker HR responses as reflected by increased DC. Consequently, PRSA analysis reflects the trajectory of fetal autonomic development.