Journal of APPLIED BIOMEDICINE
ISSN 1214-0287 (on-line)
ISSN 1214-021X (printed)
Volume 8 (2010), No 4, p 209-211
DOI 10.2478/v10136-009-0029-1
Assessing variability in neonatal blood pressure, notably in hypotension
Germaine Cornelissen, Franz Halberg, Elena Vasilievna Syutkina, Galina Victorovna Yatsyk, Anatoly Victorovich Masalov, Othild Schwartzkopff, Dana Johnson
Address: Germaine Cornelissen, Halberg Chronobiology Center, University of Minnesota - MMC 8609, 420 Delaware Street SE, Minneapolis, MN 5545, USA
corne001@umn.edu
Received 10th March 2010.
Revised 14th June 2010.
Published online 2nd July 2010.
Full text article (pdf)
Abstract in xml format
Summary
Key words
Introduction
Subjects and Methods
Results
Discussion
Conclusion
Acknowledgement
References
SUMMARY
New reports corroborate our prior finding that hypotension in infancy is associated with impaired neurodevelopment later in childhood. We had also found that neurological deficit is further associated with a more pronounced circadian variation in transcutaneous pO2 (tcpO2). New evidence in adulthood prompts the recommendation to automatically monitor vital signs for continued surveillance, relying on the methods of chronobiology for data analysis as-one-goes. This applies notably early in extra-uterine life when infants may be particularly sensitive to ischemic cerebral injury secondary to systemic hypotension. Monitoring at this sensitive lifetime stage has also provided a glimpse of unseen effects of the cosmos on the patterns of blood pressure variability, detected by chronomics.
KEY WORDS
blood pressure; chronomics; circadian; ischemic cerebral injury; hypotension; neurological development
INTRODUCTION
Irrespective of treatment, infants with low blood
pressure (BP) have worse neurodevelopment than
infants with acceptable BP (Batton et al. 2009).
Metabolite ratios from near-term proton magnetic
resonance spectroscopy were not predictive of Bailey
scores at 18 to 24 months adjusted age (Augustine et
al. 2008). These relatively recent reports prompt us to
revisit results from an earlier study (Syutkina et al.
1999) to illustrate how the methods of chronobiology
may be useful for risk assessment, so that
prophylactic measures may be implemented in a
timely manner.
In the case of cardiovascular disease risk
assessment, population studies suggested that
circadian characteristics of BP and heart rate (HR) in
early extrauterine life may be influenced by much
lower-frequency cycles spanning decades (Halberg et
al. 1990, Syutkina et al. 2003), verifiable on an
individualized basis in adulthood (Halberg et al.
2008b). Whereas circadians are our focus herein, the
merit of keeping the data archived serves not only for
an individualized assessment of neurological
development later in infancy, but it also provides for
population-based meta-analyses examining a host of
putative influences, including those from the cosmic
environment (Halberg et al. 2001).
SUBJECTS AND METHODS
Eight infants (6M, 2F) born at gestational ages 35-37
weeks with a birth weight between 1750 and 2400 g
were monitored each for 25 hours between the ages of
2 and 14 days. All infants were clinically stable. None
had serious neurological problems or abnormal
ultrasound findings.
Blood gases (pO2 and pCO2) were continuously
recorded transcutaneously using the TCM-222
monitor (Radiometer, Denmark). Records were
digitized for consecutive 2-minute intervals. Systolic
(S) and diastolic (D) BP and HR were measured
non-invasively at 20- to 30-minute intervals with the
BX5 monitor (Colin Medical Instruments, Komaki,
Japan).
Each record was analyzed by cosinor (Halberg
1980, Cornélissen and Halberg 2005), involving the
least squares fit of a 24-hour cosine curve to the data,
yielding estimates of the MESOR (M, a
rhythm-adjusted mean), double amplitude (2A, a
measure of the extent of predictable change within a
day), and acrophase (phi, a measure of the timing of
overall high values recurring each day). Trough and
peak values were assessed as the bathymetron
(=M-A) and acrometron (= M+A), respectively to
approximate the lowest and highest values anticipated
to recur each day.
Six years later, the same children had neurological
and psychological exams, including electro-encephalography, on the basis of which they were
classified into two groups with more (N=5) or less
(N=3) severe abnormalities.
Results from monitoring during the perinatal span
were compared by Student t-test between the two
groups at the significance level 2alpha=0.05.
RESULTS
A statistically significantly lower circadian trough of
SBP (64.2±2.2 vs. 79.7±4.8 mmHg) and DBP
(38.8±1.7 vs. 48.5±3.1 mmHg) and a statistically
significantly higher circadian tcpO2 peak (92.0±2.9
vs. 78.0±2.4 mmHg) between the ages of 2 and
14 days predicted future neurological deficit assessed
at 6 years of age. Neurological deficit was also
associated with a statistically significantly more
prominent circadian variation in tcpO2.
DISCUSSION
Preterm infants may be susceptible to ischemic
cerebral injury, secondary to systemic hypotension,
because of the occurrence of a pressure-passive
cerebral circulation (Lou et al. 1979). Spans of
relative ischemia tend to occur regularly as part of the
circadian variation of cerebral blood volume
determined by near-infrared spectrophotometry
(Syutkina et al. 1999).
In adulthood, an excessive circadian amplitude of
BP carries a risk greater than that associated with
high BP (Cornelissen et al. 2007, Halberg et al.
2007). This condition and other vascular variability
disorders can greatly increase cardiovascular disease
risk beyond that of an elevated BP MESOR (Halberg
et al. 2009). A cosinor approach (Halberg 1980,
Cornelissen and Halberg 2005) separated groups of
children and newborns with a positive vs. negative
family history of high BP and/or related vascular
disease, a positive history being associated with a
larger BP variability (Halberg et al. 1986). One must
be aware, however, for vascular disease risk
assessment of the long cycles that can jeopardize a
test based solely on circadian variability (Halberg et
al. 1990). In the future, a minimal 7-day record of BP
is recommended for routine neonatal screening
(Cornelissen et al. 1987, Syutkina et al. 2003) as soon
as affordable unobtrusive instrumentation permits.
CONCLUSION
The availability of automatic BP monitoring in the
NICU and of methodology to easily assess the
circadian and infradian variation from
around-the-clock week-long measurements could be
taken advantage of to draw guidelines for the
important, yet still problematic decision when to
provide therapy for low BP in preterm infants (Batton
et al. 2009), and to monitor the response to treatment.
Conclusions from this more recent study are in
keeping with our original report (Syutkina et al.
1999). While they are particularly pertinent during the
neonatal span, they apply equally at all ages, as
apparent from an international consensus (Halberg et
al. 2008a).
ACKNOWLEDGEMENT
Support GM-13981 (FH) and University of
Minnesota Supercomputing Institute (GC, FH).
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