Developmental milestones of the autonomic nervous system revealed via longitudinal monitoring of fetal heart rate variability

Background: Fetal heart rate variability (fHRV) of normal-to-normal (NN) beat intervals provides high-temporal resolution access to assess the functioning of the autonomic nervous system (ANS). Aim: To determine critical periods of fetal autonomic maturation. The developmental pace is hypothesized to change with gestational age (GA). Study design: Prospective longitudinal observational study. Subjects: 60 healthy singleton fetuses were followed up by fetal magnetocardiographic heart rate monitoring 4±11 times (median 6) during the second half of gestation. Outcome measure: FHRV parameters, accounting for differential aspects of the ANS, were studied applying linear mixed models over four predefined pregnancy segments of interest (SoI: <27; 27+0±31 +0; 31+1±35+0; >35+1 weeks GA). Periods of fetal active sleep and quiescence were accounted for separately. Results: Skewness of the NN interval distribution VLF/LF band power ratio and complexity describe a saturation function throughout the period of interest. A decreasing LF/HF ratio and an increase in pNN5 indicate a concurrent shift in sympathovagal balance. Fluctuation amplitude and parameters of short-term variability (RMSSD, HF band) mark a second acceleration towards term. In contrast, fetal quiescence is characterized by sequential, but low-margin transformations; ascending overall variability followed by an increase of complexity and superseded by fluctuation amplitude. Conclusions: An increase in sympathetic activation, connected with by a higher ability of parasympathetic modulation and baseline stabilization, is reached during the transition from the late 2nd into the early 3rd trimester. Pattern characteristics indicating fetal well-being saturate at 35 weeks GA. Pronounced fetal breathing efforts near-term mirror in fHRV as respiratory sinus arrhythmia.