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ORIGINA

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ARTICLES

www.jpeds.com THE JOURNAL OF PEDIATRICS

Near-Infrared Spectroscopy Measurements of Cerebral Oxygenation in


Newborns during Immediate Postnatal Adaptation
Jean-Claude Fauchere, MD, Gabriele Schulz, MD, Daniel Haensse, PhD, Esther Keller, MD, Jorg Ersch, MD,
Hans Ulrich Bucher, MD, and Martin Wolf, PhD

Objective In view of growing concerns regarding the optimal supplementation of oxygen at birth, we measured cerebral
oxygenation during the first minutes of life.
Study design Using near-infrared spectroscopy, changes in cerebral oxygenated hemoglobin (O 2Hb), dexoxy-genated
hemoglobin (HHb), and tissue oxygenation index (TOI) were measured during the first 15 minutes of life in 20 healthy newborn
infants delivered at term by elective cesarean section.
Results O2Hb and TOI increased rapidly within the first minutes of life (median slope for O2Hb, 3.4 mmol/Lymin; range, 1.4 to
20.6 mmol/Lymin; median slope for TOI, 4.2 %/min; range, -0.4 to 27.3%/min), and cerebral HHb decreased (median slope, -4.8
^mol/^min; range, -0.2 to -20.6 mmol/Lymin). O2Hb,TOI, and HHb all reached a plateau within 8 minutes.
Conclusions A significant increase in cerebral O2Hb and TOI and a significant decrease in HHb occur during immediate
adaptation in healthy term newborns, reaching a steady plateau at around 8 minutes after birth. (J Pediatr 2010;156:372-6).

lthough there is a substantial literature concerning the changes in peripheral arterial oxygen saturation (SpO 2) immediately afterbirth,1-3
there is much less information regarding the changes in cerebral oxygenation. This is of importance considering that worldwide, 5% to
10% of neonates require resuscitation.4,5 Over the last several decades, concerns regarding possible causes of impaired neurologic
outcome have focused on insufficient oxygenation during the perinatal period. However, based on the work of Ola Saugstad, Maximo Vento,
and other researchers, increasing attention is being given to the short- and long-term damage to newborns exposed to high oxygen
concentrations in the delivery room.6-13 The potential for injury from excessive oxygen exposure during the resuscitation of near-term or term
infants immediately after birth has been recognized only recently.14,15 Starting neonatal resuscitation in the delivery room with a lower fraction
of inspired oxygen (FiO2) has been proposed.16-18 There is a growing consensus among neonatologists regarding the need to reduce the FiO2 in
the delivery room; however, the optimal starting FiO2 value remains a matter of debate.19,20
Pulse oximetry is a noninvasive, continuous technique for monitoring SpO 2. When measured over the right hand or wirst, SpO2 is
representative of the oxygen saturation reaching the brain. Nevertheless, the changes in cerebral tissue oxygenation occurring during very early
postnatal adaptation are not fully known. Near-infrared spectroscopy (NIRS) is a well-described noninvasive technique that uses the
transparency of biological tissue to light in the near-infrared spectrum to measure cerebral tissue oxygenation.21-24 Newer near-infrared
spectrometers also can measure a quantitative tissue oxygenation index (TOI) as the ratio of cerebral oxygenated hemoglobin (O2Hb) in total
hemoglobin (O2Hb/ [O2Hb + deoxygenated hemoglobin (HHb)]). NIRS can be used to monitor cerebral hemodynamics in critically ill term and
preterm infants.21,25,26 In the present study, we measured the magnitude and timing of changes in O2Hb, HHb, TOI, and SpO2 in healthy term
newborns during the first minutes of life.

Methods
Neonates born by elective cesarean section at term were eligible for the study. The exclusion criteria were a need for neonatal resuscitation, a
genetically defined syndrome, a congenital malformation, and absence of parental consent or good-quality
NIRS signals. At our perinatal center, neo-nates
born by cesarean section are routinely
under
the
supervision of

AV

Arteriovenous

FiO2

Fraction of inspired oxygen

FTOE

Fractional cerebral tissue oxygen extraction

HHb

Deoxygenated hemoglobin

HR

Heart rate

NIRS

Near-infrared spectroscopy

O2Hb

Oxygenated hemoglobin

SpO2

Peripheral arterial oxygen saturation

THI

Tissue hemoglobin index

TOI

Tissue oxygenation index

From the Department Obstetrics & Gynecology, Clinic of Neonatology, University


Hospital Zurich, Zurich, Switzerland (J.-C.F., G.S., D.H., E.K., J.E., H.B., M.W.)
and University of Utrecht and Wilhelmina Children's
Hospital, Utrecht, The Netherlands (E.K.)
The authors declare no conflicts of interest.
0022-3476/$ - see front matter. Copyright 2010 Mosby Inc. All rights reserved.
10.1016/j.jpeds.2009.09.050

Vol. 156, No. 3

a neonatologist for the first 10 to 15 minutes after birth. For this


study, each neonate was placed on a resuscitation table under a
radiant warmer with the head in the neutral position, and the head
and the right arm were cleansed. Using a pulse oximeter
(N-200/N-395; Covidien-Nellcor, Boulder, Colorado), SpO2 was
measured continuously over the right hand or wrist.
O2Hb, HHb, and TOI were measured with NIRS (NIRO
300; Hamamatsu Photonics, Hamamatsu, Japan). The NIRS sensor
contains a light source (with 775-, 810-, 850-, and 910-nm
wavelengths) and a detector with 3 segments (silicone photodiodes).
The emitter and receiver optodes were fixed in a probe holder to
ensure an interoptode distance of50 mm, and the optode was
connected to a preca-librated measuring unit of the spectrometer.
The specified path length of the NIRO was 19 cm, and the differential
path length factor was 3.8. Interference from light was prevented by
shielding the optode, which was placed on the skin overlying the
right forehead, avoiding the area of the sagittal sinus to measure
brain tissue oxygenation, and secured using stretch bandages. NIRS
measurements were started as soon as the pulsoximeter probe was
positioned on the right hand/wrist to measure preductal oxygen
saturation and heart rate (HR). To avoid artifacts, the neonate was
not disturbed over the next 10 to 15 minutes, except when necessary
for clinical reasons.
All data were stored electronically at a sample rate of 2 seconds
for subsequent analysis. All of the NIRS studies were performed by
the same investigators, who were not involved in the delivery room
care of the neonates. Written parental informed consent was
obtained before each study. The study design was approved by the
hospital's Ethics Committee.

March 2010

nate received any medication or required bag-and-mask


resuscitation. Twenty newborn infants had NIRS measurements of
the required quality. Three neonates were excluded from the
analysis, 2 for receiving supplemental oxygen and 1 born preterm at
34-3/7 weeks gestation, leaving 17 infants (8 girls and 9 boys) for
analysis.
The median gestational age was 38 1/7 weeks (range, 36 6/7 to 40
2/7 weeks), and the median birth weight was 3200 g (range, 2300 to
4190 g). The median umbilical artery pH was 7.30 (range, 7.20 to
7.38), and the median Apgar score values were 8 at 1 minute (range,
7 to 9; mean, 8.3), 9 at 5 minutes (range, 8 to 10; mean, 9.1), and 10 at
10 minutes (range, 8 to 10; mean, 9.6).
The median age at the start of NIRS measurement was 2 minutes
after birth (range, 1 to 4 minutes), and SpO2 measurements were
reliable within 1 minute after the sensor was placed. The Figure
shows the changes in TOI, SpO2,
FTOE, O2-AV difference, THI, HR, O2Hb, and HHb, given
as median and 25th and 75th percentile values for the group. The
changes in O2Hb, TOI, SpO2, and HHb reached a plateau within a
median of 8 minutes (range, 6.2 to 11.3 minutes), and were
statistically different from their starting point (O2Hb, P = .0001; TOI,
P = .0003; HHb, P = .00007; SpO2, P = .0007). Thereafter, these
variables remained on their newly reached level. The other variables
did not exhibit significant changes. O2Hb, TOI, and preductal SpO2
increased rapidly within the first minutes of life (median slopes:
O2Hb, 3.4 mmol/L/min [range, 1.4 to 20.6 mmol/L/min]; TOI,
4.2%/minute [range, -0.4 to 27.3%/minute]; SpO2, 4.6%/minute
[range, 0.2 to 15.3%/minute]), and HHb concentration decreased
(median slope, -4.8 mmol/L/min; range, -0.2 to -20.6 mmol/L/min).

Data Analysis
All continuously measured NIRS data were evaluated individually.
Fractional cerebral oxygen tissue extraction (FTOE) was calculated
as (SpO2 -TOI)/SpO2,andoxygen-arteriovenous (AV) difference
(O2-AV difference) was calculated as SpO2 - TOI. Median values and
the
25th
and
75th
percentiles were
calculated
for
O2Hb,HHb,TOI,tis-sue hemoglobin index (THI), FTOE, O2-AV
difference, HR, and SpO2 over the measurement period and shown
graphically in 1-minute intervals for the whole group. These values
were compared at 2 time periods: during the first minute of
measurement (starting point) and at 8 minutes of measurement
(plateau phase). Statistical analyses were done with the paired
Student t-test using StatView version 5.01 for Windows (SAS Inc.,
Cary, North Carolina). The slope (change in concentration per
minute) was calculated for all variables for the part of adapatation
with the largest concentration changes before the beginning of the
plateau phase.

Results
All neonates in the study were born by uncomplicated elective
cesarean section and had a normal Apgar score. No neo-

Discussion

We have investigated the adaptive changes in cerebral tissue


oxygenation occurring during the adaptation from intrauter-ine to
extrauterine life in healthyterm infants born byelective cesarean
section. We observed a steady increase in cerebral O2Hb, TOI, and
SpO2 to a steady state by around 8 minutes of life, with a
simultaneous decrease in cerebral HHb. TOI and SpO2 tracked one
another very closely. Interestingly, FTOE and O2-AV difference
remained constant, indicating that oxygen consumption did not
change significantly during this time period.
Two previous studies have examined these changes in the first
minutes of life using NIRS. Peebles et al27 reported a single patient,
and Isobe and Kusaka28 measured O2Hb, HHb, total hemoglobin
concentration, and hemoglobin oxygen saturation in the brain tissue
of 7 term infants immediately after birth.28 Two of these infants were
delivered vaginally, and 5 were delivered by cesarean section (3
elective, 2 emergency). One of the latter infants had severe growth
restriction. We studied infants with no signs of fetal distress and no
history of intrauterine growth restriction, to evaluate a group of
healthy newborns.

Figure. Cerebral O2Hb, HHb, TOI, THI, FTOE, O2-AV difference, HR, and preductal SpO2 for the whole group during the first
minutes of life.

No study to date has assessed the changes in brain tissue


oxygenation using TOI immediately after birth. In contrast to O2Hb
and HHb, which are values relative to the starting point, TOI is an
absolute value, which thus can be measured serially in the same
patient. Naulaers et al29 measured normal

TOI values over the first 3 days of life in premature infants under 30
weeks gestation and found a significant increase in median TOI,
from 57% on day 1 to 76% on day 3. This increase was independent
of gestational age. These authors also found that although NIRS is
very sensitive to movement, TOI

THE JOURNAL OF PEDIATRICS . www.jpeds.com


March 2010

was less sensitive to movement and very stable, with a standard


deviation of only around 2%. The increase in TOI seems to be
explained, at least partly, by the increase in cerebral blood flow, as
observed by several authors.30,31
The optimal FiO2 during neonatal resuscitation remains a subject
of debate. SpO2 is used in some delivery rooms to titrate the FiO2 of
supplemental oxygen. Against this background, the International
Liaison Committee on Resuscitation called for more data to enable
evidence-based recommendations regarding the role of pulse
oximetry measurements immediately after birth.5 Rabi et al2 have
suggested that pulse oximetry may play a role in adjusting the
oxygen concentration beyond 2 minutes of life, but that the initial
decision on whether to initiate oxygen supplementation should be
based on clinical evaluation. Although we fully agree with the
second part of this statement, the use of SpO2 values for the first 7 to
10 minutes of life has the potential to lead to an overuse of
supplemental oxygen, rather than reduce unnecessary oxygen
exposure to a population of patients at risk for oxidant injury, for
several reasons. First, SpO2 changes substantially immediately after
birth,5,12,32,33 meaning that one would have to know, minute by
minute, the normal SpO2 values to be able to determine optimal oxygen delivery based on the actual SpO2 readings. Second, the wide
SpO2 ranges reported in all studies further complicate the clinicial
decision. Furthermore, and even more importantly, caution must
prevail before assuming that the range of SpO2 values measured in
healthy term and near-term infants also applies to more preterm
infants or to sick pre-term and term neonates.3 On the other hand,
using a pulse oximeter during the first 10 minutes of life has the
advantage of providing a continuous HR reading, and in helping to
reduce the FiO2, for instance in infants with tcSO2 $
95%.18
A limitation of the present study is that our study group does not
fully represent a normal group of newborns. To track the changes in
cerebral oxygenation immediately after birth, we performed this
study in neonates born by elective cesarean section. We chose this
mode of delivery because of the ease of access to these neonates
immediately after birth. Healthy infants delivered vaginally would
constitute the ''true'' normal group. Persuading parents to be
separated from their healthy infants for study purposes only is problematic after normal deliveries. Despite this limitation, the plateau of
steady SpO2 values in our neonates was reached at around 8
minutes, which is in line with the results ofKam-lin et al.3
Importantly, this same group showed that maternal anesthesia,
either spinal or general, did not further influence
SpO .

We used NIRS with TOI to move from SpO2 to the organ of


interest. Although still considered mainly a research tool, NIRS has
the potential to provide the clinician with important information in
various clinical situations. As noted by van Bel et al, 24 the present
technical state of NIRS-monitored cerebral oxygenation is not
sufficiently precise to allow the use of TOI as a robust quantitative
measure. This fact does not preclude to increasingly use TOI to
monitor trends in cerebral oxygenation in conjunction with the
conventional means such as pulse oxymetry and arterial pO 2.

Vol. 156, No. 3

ORIGINAL
ARTICLES
A better understanding of the normal adaptive changes in cerebral
oxygenation in the immediate postnatal period is useful for a more
brain-oriented neonatal medical approach that addresses concerns
about insufficient tissue oxygenation and excessive supplemental
oxygen exposure immediately after birth. Increased insight into
cerebral oxygenation will allow for expanded research in neonates
with disturbed adaptation. n
We express our gratitude to the parents for allowing us to study their
infants, as well as the midwifes and physicians involved in the management
of the neonates in the labor ward. We also thank Professor Theo Gasser and
Dr Valentin Rousson (Department ofBiostatistics, University ofZurich) for
statistical counseling. Esther Keller participated in this research project as
part ofher medical curriculum (University of Utrecht, Wilhelmina
Children's Hospital Utrecht, The Netherlands).
Submitted for publication Jan 21, 2009; last revision received Jun 16, 2009; accepted Sep
21, 2009.
Reprint requests: Jean-Claude Fauchere, MD, Neonatology Clinic, Perinatal Center,
Department of Obstetrics & Gynecology, University Hospital, Frauenklinikstrasse 10,
CH-8091 Zurich, Switzerland. E-mail: jean-claude. fauchere@usz.ch.

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