Non-linear Methods Predominant in Fetal Heart Rate Analysis: A Systematic Review

The analysis of fetal heart rate variability has served as a scientific and diagnostic tool to quantify cardiac activity fluctuations, being good indicators of fetal well-being. Many mathematical analyses were proposed to evaluate fetal heart rate variability. We focused on non-linear analysis based on concepts of chaos, fractality, and complexity: entropies, compression, fractal analysis, and wavelets. These methods have been successfully applied in the signal processing phase and increase knowledge about cardiovascular dynamics in healthy and pathological fetuses. This review summarizes those methods and investigates how non-linear measures are related to each paper's research objectives. Of the 388 articles obtained in the PubMed/Medline database and of the 421 articles in the Web of Science database, 270 articles were included in the review after all exclusion criteria were applied. While approximate entropy is the most used method in classification papers, in signal processing, the most used non-linear method was Daubechies wavelets. The top five primary research objectives covered by the selected papers were detection of signal processing, hypoxia, maturation or gestational age, intrauterine growth restriction, and fetal distress. This review shows that non-linear indices can be used to assess numerous prenatal conditions. However, they are not yet applied in clinical practice due to some critical concerns. Some studies show that the combination of several linear and non-linear indices would be ideal for improving the analysis of the fetus's well-being. Future studies should narrow the research question so a meta-analysis could be performed, probing the indices' performance.

Maternal Serotonin Reuptake Inhibitor Antidepressants Have Acute Effects on Fetal Heart Rate Variability in Late Gestation

Background: Prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants increases risk for adverse neurodevelopmental outcomes, yet little is known about whether effects are present before birth. In relation to maternal SRI pharmacokinetics, this study investigated chronic and acute effects of prenatal SRI exposure on third-trimester fetal heart rate variability (HRV), while evaluating confounding effects of maternal depressed mood.Methods: At 36-weeks' gestation, cardiotocograph measures of fetal HR and HRV were obtained from 148 pregnant women [four groups: SRI-Depressed (n = 31), SRI-Non-Depressed (n = 18), Depressed (unmedicated; n = 42), and Control (n = 57)] before, and ~5-h after, typical SRI dose. Maternal plasma drug concentrations were quantified at baseline (pre-dose) and four time-points post-dose. Mixed effects modeling investigated group differences between baseline/pre-dose and post-dose fetal HR outcomes. Post hoc analyses investigated sex differences and dose-dependent SRI effects.Results: Maternal SRI plasma concentrations were lowest during the baseline/pre-dose fetal assessment (trough) and increased to a peak at the post-dose assessment; concentration-time curves varied widely between individuals. No group differences in fetal HR or HRV were observed at baseline/pre-dose; however, following maternal SRI dose, short-term HRV decreased in both SRI-exposed fetal groups. In the SRI-Depressed group, these post-dose decreases were displayed by male fetuses, but not females. Further, episodes of high HRV decreased post-dose relative to baseline, but only among SRI-Non-Depressed group fetuses. Higher maternal SRI doses also predicted a greater number of fetal HR decelerations. Fetuses exposed to unmedicated maternal depressed mood did not differ from Controls.Conclusions: Prenatal SRI exposure had acute post-dose effects on fetal HRV in late gestation, which differed depending on maternal mood response to SRI pharmacotherapy. Importantly, fetal SRI effects were sex-specific among mothers with persistent depressive symptoms, as only male fetuses displayed acute HRV decreases. At trough (pre-dose), chronic fetal SRI effects were not identified; however, concurrent changes in maternal SRI plasma levels suggest that fetal drug exposure is inconsistent. Acute SRI-related changes in fetal HRV may reflect a pharmacologic mechanism, a transient impairment in autonomic functioning, or an early adaption to altered serotonergic signaling, which may differ between males and females. Replication is needed to determine significance with postnatal development.