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

PLoS One. 2018 Jul 17;13(7):e0200799. doi: 10.1371/journal.pone.0200799. eCollection 2018.

Abstract

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by sequential, but low-margin transformations; ascending overall variability followed by an increase of complexity and superseded by fluctuation amplitude.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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autonomic Nervous System / embryology*
  • Autonomic Nervous System / growth & development*
  • Female
  • Fetal Development*
  • Gestational Age
  • Heart Rate / physiology
  • Heart Rate, Fetal / physiology*
  • Humans
  • Infant, Newborn
  • Longitudinal Studies
  • Magnetocardiography
  • Monitoring, Physiologic
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy Trimester, Third
  • Prospective Studies

Grants and funding

All authors except PS and TG are supported by German Research Foundation: Development of a clinically suitable marker of fetal autonomic maturation (DFG: Ho 1634/15-12, Schn 775/7-1). DH and US are supported by: Biomagnetic investigations of fetal autonomic and central nervous maturation and its disturbances due to intrauterine growth restriction and glucocorticoid administration (DFG: Ho 1634/12-2, Schn 775/2-3).