Heart rate variability categories of fluctuation amplitude and complexity: diagnostic markers of fetal development and its disturbances

Abstract

Objective: In fetal diagnosis the myriad and diversity of heart rate variability (HRV) indices prevents a comparable routine evaluation of disturbances in fetal development and well-being. The work aims at the extraction of a small set of HRV key indices that could help to establish a universal, overarching tool to screen for any disturbance.

Approach: HRV indices were organized in categories of short-term (prefix s) and long-term (prefix l) amplitude fluctuations (AMP), complexity (COMP), and patterns (PATTERN) and common representatives for each category were extracted. This procedure was done with respect to the diagnostic value in the evaluation of the maturation age throughout the second and complete third trimester of pregnancy as well as to potential differences associated with maternal life-style factors (physical exercise, smoking), nutrient intervention (docosahexaenoic acid (DHA) supplementation), and complications of pregnancy (gestational diabetes mellitus (GDM), intra-uterine growth restriction (IUGR)).

Main results: We found a comprehensive minimal set that includes [lAMP: short term variation (STV), initially introduced in cardiotocography, sAMP: heart rate increase across one interbeat interval of phase rectified averaged signal - acceleration capacity (ACst1), lCOMP: scale 4 multi-scale entropy (MSE4), PATTERN: skewness] for the maturation age prediction, and partly overlapping [lAMP: STV, sAMP: ACst1, sCOMP: Lempel Ziv complexity (LZC)] for the discrimination of the deviations.

Significance: The minimal set of category-based HRV representatives allows for a screening of fetal development and well-being. These results are an important step towards a universal and comparable diagnostic tool for the early identification of developmental disturbances. Novelty & Significance Fetal development and its disturbances have been reported to be associated with a multiplicity of HRV indices. Furthermore, these HRV indices change with maturation. We propose the abstraction of HRV categories defined by short- and long-term fluctuation amplitude, complexity, and pattern indices that cover all relevant aspects of maturational age, behavioral influences and a series of pathological disturbances. The study data are provided by multiple centers. Our approach is an important step towards the goal of a standardized diagnostic tool for early identification of fetal developmental disturbances with respect to the reduction of serious complications in the later life.

Trial registration: ClinicalTrials.gov NCT01007110.

Figure 1:

correlation matrix

Figure 2:

Normal group of Jena data base, linear regression models describing HRV categories by fetal WGA, standardized regression coefficient Beta, 95 % CI of GA intervals: range 23 (20–26), range 26 (23–29), range 29 (26–32), range 32 (29–35), range 35 (32–38).