Baroreceptor reflex sensitivity in human neonates: the effect of postmenstrual age

Abstract

We performed a cross-sectional study in human infants to determine if indices of R-R interval variability, systolic blood pressure (SBP) variability, and baroreceptor reflex sensitivity change with postmenstrual age (PMA: gestational age+postnatal age). The electrocardiogram, arterial SBP and respiration were recorded in clinically stable infants (PMA, 28-42 weeks) in the quiet sleep state in the first days after birth. (Cross-)spectral analyses of R-R interval series and SBP series were performed to calculate the power of low-frequency (LF, indicating baroreceptor reflex activity, 0.04-0.15 Hz) and high-frequency (HF, indicating parasympathetic activity, individualized between the p-10 and p-90 values of respiratory frequency) fluctuations, and transfer function phase and gain. The mean R-R interval, and LF and HF spectral powers of R-R interval series increased with PMA. The mean SBP increased with PMA, but not the LF and HF spectral powers of SBP series. In the LF range, cross-spectral analysis showed high coherence values (>0.5) with a consistent negative phase shift between R-R interval and SBP, indicating a approximately 3 s lag in R-R interval changes in relation to SBP. Baroreceptor reflex sensitivity, calculated from LF transfer gain, increased significantly with PMA, from 5 (preterm) to 15 ms mmHg-1 (term). Baroreceptor reflex sensitivity correlated significantly with the (LF and) HF spectral powers of R-R interval series, but not with the LF and HF spectral powers of SBP series. The principal conclusions are that baroreceptor reflex sensitivity and spectral power in R-R interval series increase in parallel with PMA, suggesting a progressive vagal maturation with PMA.

Figure 1. Spectral power curves of R–R interval and SBP series of a preterm infant measured at a postmenstrual age of 31 weeks

This figure shows the spectral power curves of R–R interval (A) and SBP (B) series. The spectral powers (R–R interval series, ms²; SBP series, mmHg²) are distributed as a function of frequency (Hz). The low-frequency (LF) band was defined between 0.04 and 0.15 Hz and is marked between vertical lines. The individual high-frequency (HF) band was defined between the 10th and 90th centile of the individual respiratory frequency (0.70 and 0.90 Hz, respectively) and is marked between vertical lines. In the LF band clear peaks in both power spectra are observed at 0.08 Hz, assumed to be attributed to oscillation of the baroreceptor reflex. A HF peak at 0.80 Hz is clearly visible in the SBP power spectrum and corresponds with the mean respiratory rate of the subject. In the R–R interval power spectrum a modest HF peak is visible.

Figure 2. The coherence and transfer function parameters of the same infant as in Fig. 1

This figure shows the coherence function for the linear relationship between R–R interval and SBP series (A) and corresponding transfer gain (B) and transfer phase (C) as a function of frequency (Hz). The vertical lines indicate the boundaries of the low-frequency (LF) and high-frequency (HF) bands. Note the high coherence values in both LF (0.73) and HF bands (0.79). The frequency value with highest coherence in LF was chosen to compute LF transfer gain and phase (indicated as dots). LF transfer gain and phase were 2.3 ms mmHg⁻¹ and 1.5 s, respectively. The negative phase relationship indicates that SBP fluctuations lead R–R interval changes by 1.5 s and are probably related to baroreceptor reflex activity. Likewise, at HF transfer gain and phase can be calculated: 0.9 ms mmHg⁻¹ and 0 s, respectively. At HF phase is zero, indicating SBP and R–R interval fluctuations are oscillating together and not related to baroreceptor reflex activity.

Figure 3. Correlation diagram between postmenstrual age and baroreceptor reflex sensitivity

Low-frequency (LF) transfer gain, as an estimate for baroreceptor reflex sensitivity, correlated significantly with postmenstrual age (PMA).