C.H.L. Peters

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

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 ∼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.

Beat-to-beat detection of fetal heart rate: Doppler ultrasound cardiotocography compared to direct ECG cardiotocography in time and frequency domain.

In order to obtain power spectral information on the fetal heart rate in stages of pregnancy earlier than labor an algorithm has been developed to calculate the fetal heart rate on a beat-to-beat basis from Doppler ultrasound cardiotocographic signals. The algorithm was evaluated by comparing the calculated fetal heart rate with the heart rate determined from direct ECG signals measured with a scalp electrode. Heart rates were compared both in time and frequency domain. In the time domain the results achieved by both methods correlate well (correlation coefficient = 0.977 (p < 0.001)), in the frequency domain the results correlate even better (correlation coefficient = 0.991 (p < 0.001)). Based on these findings, it can be concluded that the developed algorithm provides a valuable tool for obtaining power spectral information on the fetal heart rate in stages of pregnancy earlier than labor.

Quantitative Analysis of Amplitude-Integrated Electroencephalogram Patterns in Stable Preterm Infants, with Normal Neurological Development at One Year

Background: The amplitude-integrated EEG (aEEG) is feasible for monitoring cerebral activity in preterm infants. However, quantitative data on normal patterns in these infants are limited. Objective: To study maturational aEEG changes in a cohort of stable preterm infants by automated quantification. Methods: In a cohort of stable preterm infants with gestational age (GA) <32 weeks and normal neurological follow-up at 1 year, weekly 4 h EEG recordings were performed. aEEG traces were obtained from channel C3-C4. The upper margin amplitude (UMA), lower margin amplitude (LMA) and bandwidth (BW) were quantitatively calculated using an expert software system. In addition, the relative duration of discontinuous background pattern (discontinuous background defined as activity with LMA <5 µV, expressed as DC-%) was calculated. Results: 79 aEEG recordings (4–6 recordings/infant) were obtained in 18 infants. Analysis of the first week recordings demonstrated a strong positive correlation between GA and LMA, while DC-% decreased significantly. Longitudinally, all infants showed increase of LMA. Multivariate analysis showed that GA and postnatal age (PA) both contributed independently and equally to LMA and DC-%. We found a strong correlation between postmenstrual age (GA + PA) and LMA and DC-%, respectively. Conclusion: To our knowledge, this is the first study where aEEG development was studied by automated quantification of aEEG characteristics in a cohort of stable preterm infants with a normal neurological development at 1 year of age. LMA and DC-% are simple quantitative measures of neurophysiologic development and may be used to evaluate neurodevelopment in infants.

Quantitative analysis of maturational changes in EEG background activity in very preterm infants with a normal neurodevelopment at 1 year of age

BACKGROUND The electroencephalographic (EEG) background pattern of preterm infants changes with postmenstrual age (PMA) from discontinuous activity to continuous activity. However, changes in discontinuity have been investigated by visual analysis only. AIM To investigate the maturational changes in EEG discontinuity in healthy preterm infants using an automated EEG detection algorithm. STUDY DESIGN Weekly 4h EEG recordings were performed in preterm infants with a gestational age (GA)<32weeks and normal neurological follow-up at 1year. The channel C3-C4 was analyzed using an algorithm which automatically detects periods of EEG inactivity (interburst intervals). The interburst-burst ratio (IBR, percentage of EEG inactivity during a moving time window of 600s) and mean length of the interburst intervals were calculated. Using the IBR, discontinuous background activity (periods with high IBR) and continuous background activity (periods with low IBR) were automatically detected and their mean length during each recording was calculated. Data were analyzed with regression and multivariate analysis. RESULTS 79 recordings were performed in 18 infants. All recordings showed a cyclical pattern in EEG discontinuity. With advancing PMA, IBR (R(2)=0.64; p<0.001), interburst interval length (R(2)=0.43; p<0.001) and length of discontinuous activity (R(2)=0.38; p<0.001) decreased, while continuous activity increased (R(2)=0.50; p<0.001). Multivariate analysis showed that all EEG discontinuity parameters were equally influenced by GA and postnatal age. CONCLUSION Analyzing EEG background activity in preterm infants is feasible with an automated algorithm and shows maturational changes of several EEG derived parameters. The cyclical pattern in IBR suggests brain organisation in preterm infant.

Normalized spectral power of fetal heart rate variability is associated with fetal scalp blood pH

BACKGROUND Spectral power of fetal heart rate variability is related to fetal condition. Previous studies found an increased normalized low frequency power in case of severe fetal acidosis. AIMS To analyze whether absolute or normalized low or high frequency power of fetal heart rate variability is associated with fetal scalp blood pH. STUDY DESIGN Prospective cohort study, performed in an obstetric unit of a tertiary care teaching hospital. SUBJECTS Consecutive singleton term fetuses in cephalic presentation that underwent one or more scalp blood samples, monitored during labour using ST-analysis of the fetal electrocardiogram. Ten-minute continuous beat-to-beat fetal heart rate segments, preceding the scalp blood measurement were used. OUTCOME MEASURES Absolute and normalized spectral power in the low frequency band (0.04-0.15 Hz) and in the high frequency band (0.4-1.5 Hz). RESULTS In total 39 fetal blood samples from 30 patients were studied. We found that normalized low frequency and normalized high frequency power of fetal heart rate variability is associated with fetal scalp blood pH. The estimated ß of normalized low frequency power was -0.37 (95% confidence interval -0.68 to -0.06) and the relative risk was 0.69 (95% confidence interval 0.51-0.94). The estimated ß of normalized high frequency power was 0.33 (95% confidence interval 0.01-0.65) and the relative risk was 1.39 (95% confidence interval 1.01-1.92). CONCLUSIONS Normalized low and normalized high frequency power of fetal heart rate variability is associated with fetal scalp blood pH.

11 A Simple Time Domain Estimate for Determining the Baroreceptor Reflex Mediated Heart Rate Response in Newborns

Introduction: The baroreceptor reflex mediated heart rate response is generally estimated by complex cross-spectral analysis (transfer function gain) between R-R interval and systolic blood pressure (SBP) fluctuations in the low frequency (LF, 0.04–0.15 Hz) band: The baroreceptor reflex sensitivity (BRS, ms/mmHg) (Andriessen, P. et al. Pediatr Res 2003;53:89–97).Aim: To evaluate the BRS with a simple time domain (t-BRS) estimate rather than a complex frequency domain (f-BRS) estimate.Methods: Forty-two infants (postconceptional age, range: 28–42 wk) were studied in the first days after birth whose intensive care management required an arterial catheter. Data analysis was performed on 192-s-long stationary segments during the quiet sleep state. f-BRS was estimated using transfer function analysis (LF transfer gain) based on cross-spectral analysis of R-R interval and SBP density curves, using 5 half-overlapping fast Fourier transform 64-s segments, at coherence values > 0.5 indicating statistical reliability. t-BRS was estimated by the ratio of SD of (R-R)i intervals (square root of variance or root-mean-square for the mean) divided by the SD of SBP beat-to-beat values in the 192-s-long segments.Statistics: linear regression analysis and difference of mean as function of mean of both methods with its 95% limits of agreement (Bland-Altman).Results: Time domain assessment of BRS (t-BRS) correlated significantly with LF cross-spectral analysis (f-BRS): r2 = 0.85; t-BRS = f-BRS + 1; p<0.01. The mean difference of both methods (f-BRS - t-BRS) was -1 mmHg/ms. The 95% limits of agreement were between -5 and +3 mmHg/ms.Conclusions: The baroreceptor reflex mediated heart rate response can reliable estimated by this simple time domain estimate and may be useful to determine in critical ill patients with signs or symptoms of cardiovascular instability. Low BRS implicates poor short-term regulation of BP fluctuations. Intensive care management should aim at reducing interventions causing blood pressure changes in these patients.

9 Baroreceptor Reflex Function in Newborns: The Effect of Postconceptional Age

Introduction: The baroreceptor reflex (BR) is the most prominent short-term compensator during blood pressure (BP) challenges.Aim: To study the effect of postconceptional age (PCA, gestational age + postnatal age) on baroreceptor reflex sensitivity (BRS) in 32 infants (PCA, range: 28–42 wk) during quiet sleep state in the first days after birth.Method: Cross-spectral power analysis between systolic blood pressure (SBP) and R-R fluctuations, using fast Fourier transform, was estimated in a low frequency (LF, 0.04–0.15 Hz), high frequency (HF, individualized between p-10 and p-90 value of respiratory frequency), and total frequency band (0.04–1.5 Hz). BRS was estimated using transfer function analysis (transfer gain or BRS, ms/mmHg; phase, s) between LF fluctuations of SBP and R-R.Results: With PCA the mean R-R interval and LF-, HF-, and total spectral power of R-R interval series increased significantly. PCA significantly correlated with LF transfer gain (BRS = 1.1 x PCA - 30 ms/mmHg, r = 0.80, p < 0.01). Median BRS was 4.6 (IQR, 3.1–5.4), 7.5 (IQR, 5.2–10.1) and 15.0 (IQR, 11.8–19.7) ms/mmHg for infants with a PCA between 28–32 wk (n=16), 32–37 wk (n=10), and 37–42 wk (n=6), respectively. For LF transfer phase no differences between PCA groups were found: SBP fluctuations lead R-R interval changes by approximately 3 s. BRS correlated significantly with LF-, HF-, and total spectral power values of the R-R interval series. By contrast, BRS did not show a significant correlation with the spectral values of SBP series.Conclusion: This study demonstrates that the capability of the BR to buffer spontaneous occurring BP fluctuations by R-R interval changes is limited in very preterm infants, but increases with PCA. An immature BR function may contribute to conditions that predispose to cerebral hemorrhagia/ischemia in the preterm infant. BR maturation with gestation seems to be an effect of progressive parasympathetic activity.