Original Paper Neonatology 2014;106:181–187 DOI: 10.1159/000362152

Received: December 9, 2013 Accepted after revision: March 7, 2014 Published online: July 5, 2014

Difference in Cerebral and Peripheral Hemodynamics among Term and Preterm Infants during the First Three Days of Life Tao Fujioka Takeshi Takami Hiroki Ishii Atsushi Kondo Daisuke Sunohara Hisashi Kawashima Department of Pediatrics, Tokyo Medical University, Tokyo, Japan

Abstract Background: The relationship between cerebral and peripheral hemodynamics during the early postnatal period has not been clarified. Objectives: To evaluate cerebral and peripheral oxygenation and blood volumes between term and preterm infants during the first 3 days of life. Materials and Methods: We performed near-infrared time-resolved spectroscopy on 32 term infants (term group) and 40 preterm infants (preterm group), with an optode placed on their forehead and upper arm. The cerebral blood volume (CBV), peripheral blood volume (PBV), cerebral Hb oxygen saturation (cSO2) and peripheral Hb oxygen saturation (pSO2) were measured at 3–6, 12, 24, 48 and 72 h after birth. Results: The CBV in the term group (2.45 ± 0.47 ml/100 g) was significantly higher than that in the preterm group (1.97 ± 0.33 ml/100 g). In contrast to the CBV, the PBV in the preterm group (3.63 ± 0.76 ml/100 g) was significantly higher than that in the term group (3.26 ± 0.56 ml/100 g). In the preterm group, there was a significant positive relationship between the CBVs and PBVs at each time point except at 72 h after birth. Despite the

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differences in blood volumes, there were no differences in the cSO2 and pSO2 between the two groups. Conclusions: The contrasting results in the CBV and PBV between the term and preterm infants might be explained by differences in the maturation of the physiological mechanism to control CBV and PBV. © 2014 S. Karger AG, Basel

Introduction

A drastic change in hemodynamics is known to occur during the transition period from intra- to extrauterine life. In premature infants, those changes occasionally lead to cerebral complications such as intraventricular hemorrhage [1]. Hence, it is essential to evaluate cerebral perfusion during the immediate postnatal period. On the other hand, there is a clinical observation that the blood supply to nonvital organs such as skeletal muscles shuts down before the supply to vital organs such as the brain and heart is cut off. Evaluation of peripheral perfusion might therefore give an early warning that the blood supply to vital organs is at risk of being compromised [2], but the relationship between cerebral and peripheral hemodynamics during the early postnatal period has not been clarified. Tao Fujioka, MD, PhD Department of Pediatrics Tokyo Medical University 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023 (Japan) E-Mail doc.tao-f0711 @ nifty.com

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Key Words Cerebral blood volume · Peripheral blood volume · Cerebral oxygenation · Peripheral oxygenation · Near-infrared time-resolved spectroscopy · Term infant · Preterm infant

Materials and Methods Study Participants We evaluated 32 term infants (term group) and 40 preterm infants (preterm group) who were admitted to the neonatal intensive care unit of Tokyo Medical University Hospital from May 1, 2009 to December 31, 2011. The inclusion criteria of this study were as follows: (1) subjects without chromosomal and/or syndromic abnormalities; (2) subjects who were not small for their gestational age (GA); (3) subjects without intraventricular hemorrhage, determined by cranial ultrasonography; (4) subjects who did not show severe metabolic acidosis (pH 0.05 >0.05 >0.05 >0.05

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Values are presented as median (with range), means ± SD or numbers. VD = Vaginal delivery; CD = cesarean delivery.

3.5

5.5

Term group Preterm group

p < 0.001

4.5 PBV (ml/100 g)

2.0 1.5

a

12

3.0 2.5

1.5

* * 3–6

3.5

2.0

*

1.0

4.0

*

2.5

24

*

CBV (ml/100 g)

3.0

0.5

p < 0.001

5.0

48

1.0

72

3–6

b

Hours after birth

12

24

95

80 p = 0.74 75

48

#

90

#

85

#

pSO2 (%)

cSO2 (%)

80 70

65

72

Hours after birth

p = 0.29

75 70 65

* * * 3–6

12

24

*

c

60 55 48

50

72

Hours after birth

d

*

55

*

60

3–6

12

24

48

72

Hours after birth

(40.9 ± 6.5 mm Hg; p < 0.001). There was no significant difference in the levels of PCO2 (term group, 39.9 ± 6.1 mm Hg; preterm group, 39.3 ± 7.2 mm Hg; p > 0.05) and Hb (term group, 17.5 ± 2.0 g/dl; preterm group, 17.3 ± 2.1 g/dl; p > 0.05) between the two groups. The SpO2 of the term group (98.3 ± 1.6%) was significantly higher than that of the preterm group (97.7 ± 1.9%; p < 0.001). The time course changes in CBV, PBV, cerebral Hb oxygen saturation (cSO2) and peripheral Hb oxygen saturation (pSO2) are shown in figure 2. The CBV in the term group (2.45 ± 0.47 ml/100 g) was significantly higher than  

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Neonatology 2014;106:181–187 DOI: 10.1159/000362152

that in the preterm group (1.97 ± 0.33 ml/100 g; p < 0.001) and the CBV showed a significant increase in the preterm group with time (p < 0.001; fig. 2a). The PBV in the preterm group (3.63 ± 0.76 ml/100 g) was significantly higher than that in the term group (3.26 ± 0.56 ml/100 g; p < 0.001) and showed a significant increase with time in the preterm group (p < 0.001; fig. 2b). There was no difference in the cSO2 (term group, 70.8 ± 3.6%; preterm group, 70.9 ± 4.1%; p = 0.75) and the pSO2 (term group, 73.5 ± 6.1%; preterm group, 72.9 ± 6.0%; p > 0.05) between the two groups. The cSO2 showed a significant increase with Fujioka/Takami/Ishii/Kondo/Sunohara/ Kawashima

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Fig. 2. Time course changes in CBV, PBV, cSO2 and pSO2 in the term and preterm groups. Time course changes in CBV (a), PBV (b), cSO2 (c) and pSO2 (d). # p < 0.05, significant changes in values of the term group; * p < 0.05, significant changes in values of the preterm group.

CBV (ml/100 g)

4.5 4.0

p = 0.85

3.5 3.0 2.5 2.0 1.5 1.0

1

3

p = 0.55

1

PBV (ml/100 g) 3–6 h

a 3.5 CBV (ml/100 g)

5

4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0

5

p = 0.61

1

3.5

p = 0.004 r = 0.45

3.0

3

5

4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0

p = 0.61

1

PBV (ml/100 g) 24 h

PBV (ml/100 g) 12 h

p = 0.005 r = 0.44

3.0

3

4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0

3.5

5

3.5 3.0

p = 0.016 r = 0.38

2.5

2.5

2.0

2.0

2.0

1.5

1.5

1.5

1.5

1.5

1.0

1.0

1.0

1.0

1.0

0.5

0.5

0.5

0.5

b

6.0

1.5

PBV (ml/100 g) 3–6 h

3.0

4.5

6.0

1.5

PBV (ml/100 g) 12 h

3.0

4.5

6.0

5

p = 0.30

3.0

2.5

4.5

3

3.5

2.0

3.0

1

PBV (ml/100 g) 72 h

2.5

1.5

p = 0.05

PBV (ml/100 g) 48 h

p = 0.004 r = 0.45

3.0

3

4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0

2.5 2.0

1.5

PBV (ml/100 g) 24 h

3.0

4.5

6.0

0.5

1.5

PBV (ml/100 g) 48 h

3.0

4.5

6.0

PBV (ml/100 g) 72 h

Fig. 3. Relationship between CBV and PBV in the term group (a) and in the preterm group (b). r = Pearson’s correlation coefficient.

Table 2. CBV values of the infants assessed by NIRS

Methods

Ref. No.

Subjects, n

GA, weeks

Birth weight, g

CBV, ml/100 g

CW-NIRS with changes in PCO2 CW-NIRS with changes in SaO2 NIR-SRS NIR-TRS FD-NIRS NIR-TRS NIR-TRS

4 8 9 15 19 Present study Present study

8 12 17 22 11 32 40

29.5 (28–32) 29 (25–40) 28 (23–41) 36.8±3.1 30.5 (28–34) 38.9 (37–42) 32.5 (28–36)

1,283 (890–2,630) 1,500 (826–4,400) 1,030 (640–1,030) 2,365±791 1,500±368 2,980±334 1,722±408

3.7±1.1 2.22±0.4 1.72±0.76 2.31±0.56 1.7±0.3 2.45±0.47 1.97±0.33

Values are presented as medians (with ranges) or means ± SD. CW-NIRS = Continuous wave NIRS; SaO2 = arterial oxygen saturation; NIR-SRS = spatially resolved NIRS; FD-NIRS = frequency domain NIRS.

time (p < 0.001) in the preterm group (fig. 2c). The pSO2 showed a significant decrease with time (p  < 0.001) in both groups (fig. 2d). There was no difference in the cerebral FTOE (term group, 0.28 ± 0.04; preterm group, 0.27 ± 0.05; p = 0.11) or the peripheral FTOE (term group, 0.25 ± 0.06; preterm group, 0.25 ± 0.06; p = 0.87) between the two groups. There were significant positive correlations between CBV and PBV at 3–6, 12, 24, and 48 h after birth in the preterm group, although there was no correlation between these variables in the term group (fig. 3). There was no correlation among MABP, CBV and PBV in both groups.

Cerebral and Peripheral Hemodynamics To the best of our knowledge, this is the first study to investigate cerebral and peripheral hemodynamics simultaneously among term and preterm infants using NIR-TRS during the early postnatal period. The study showed that the CBV in term infants was significantly higher than that in preterm infants during the first 3 days of life. There have been several studies on CBV in neonates measured by NIRS [4, 8, 9, 15, 19]. The CBVs of infants obtained using NIRS in these previous studies are summarized in table 2. It has been reported that CBV in-

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Discussion

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Neonatology 2014;106:181–187 DOI: 10.1159/000362152

PBV are affected by the same variable, which is likely to be blood pressure. It has been suggested that autoregulation is not active in critically ill premature infants [22, 23]. Thus, differences in the relationship between CBV and PBV among the groups might be due to differences in cerebral maturation, as the cerebrum is likely to be better developed in term infants than in preterm infants. However, these results were of single measurements of CBV and PBV, and thus we should be cautious of making any conclusions, and further studies should be performed. Oxygenation of Cerebral and Peripheral Tissue SO2 is determined mainly by the oxygen delivery to the tissue, the oxygen utilization in the tissue and the arterial and venous anatomical ratio. In the present study, the significant differences in the CBV, PBV and SpO2 between the two groups indicate a difference in oxygen delivery between term infants and preterm infants in cerebral and peripheral tissue. Nevertheless, there was no difference in the cSO2 and pSO2 between the two groups. Furthermore, no differences were detected between the two groups in cerebral and peripheral FTOE, which represent the ratio of oxygen utilization to oxygen delivery in cerebral and peripheral tissue, respectively. Yoxall and Weindling [24] showed a significant positive correlation between GA and cerebral oxygen consumption in human neonates. They speculated that an increase in the structural complexity and functional activity with increasing maturity leads to increased oxygen demand in the brain. On the other hand, oxygen consumption in the forearm has previously been reported as 7.9 ± 2.1 μM/100 ml/min in term infants [21] and as 23.9–26.8 μM/100 ml/ min in preterm infants [11, 12]. These results suggest differences in the metabolic rates of oxygen utilization in the cerebral and peripheral tissue among term and preterm infants. Under different oxygen consumption conditions in term and preterm infants, cerebral and peripheral oxygenation might be maintained at constant levels by the physiological mechanism controlling CBV and PVB that develops with maturation, and not by an increase in oxygen extraction.

Limitations

There are some limitations in this study. The number of participants was small, and infants with various circulatory and respiratory conditions were included. Several factors such as respiratory condition [25], peripheral Fujioka/Takami/Ishii/Kondo/Sunohara/ Kawashima

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creases with postconceptional age and that the relationship between these variables can be explained by the results of anatomical studies of cerebral blood vessels [15, 20]. These previous reports support the current findings, as the mean GAs of infants from the studies which showed relatively low CBVs (1.7–1.97 ml/100 g) [9, 19] were shorter than those from studies which showed relatively high CBVs (2.31–2.45 ml/100 g) [15]. The reason for the higher CBV values obtained by continuous wave NIRS than those obtained in this study is unclear, even taking into account the immaturities of the preterm infants (mean GA, 29 weeks) [4, 8]. Methodological differences and different time windows of the measurements may have affected the results. In the present study, we evaluated blood volume and oxygenation of the upper arm as parameters of peripheral hemodynamics. In contrast to the CBV, the PBV in preterm infants was significantly higher than that in term infants. PBV is affected by peripheral blood flow (PBF) and Hb concentration. In the present study, there was no difference in Hb levels; therefore, a difference in PBV implies a difference in PBF between the term and preterm infants. Oxygen delivery, which is affected by PBF, in the forearm of term infants (mean GA, 39.5 weeks) has been reported as 25.6 μM/100 ml/min [21], and that of preterm infants (mean GA, 27–29 weeks) has been reported as 72.8–75.2 μM/100 ml/min [11, 12]. These results suggest that PBF in preterm infants is higher than that in term infants, which is consistent with our results. Pichler et al. [10] showed a significant negative correlation between MABP and peripheral Hb flow, and also demonstrated a significant positive correlation between GA and vascular resistance (VR). They speculated that an increase in VR leads to an increase in MABP, and a decrease in Hb flow and oxygen delivery. Our study showed significantly higher MABP levels in term infants than in preterm infants, which may indicate higher VR in term infants than in preterm infants. As a result of the increased VR, PBV might be decreased in the term infants, although we did not observe any relationship between MABP and PBV. Although many investigators have reported the relationships between blood pressure, cerebral perfusion, peripheral perfusion and systemic perfusion using NIRS, to the best of our knowledge there have been no reports that directly reveal the relationship between cerebral and peripheral perfusion. Interestingly, there was a significant positive correlation between CBV and PBV in preterm infants during the early postnatal period. This result suggests that, in preterm infants, both CBV and

temperature [10, 21] and external temperature are thought to play a part in determining cerebral or peripheral perfusion, but these factors were not investigated in the present study. Furthermore, the values of all the NIRTRS parameters were obtained from a regional, single measurement, and thus we should be cautious in interpreting the results. In conclusion, we evaluated the changes in cerebral and peripheral hemodynamics in term and preterm infants during the immediate postnatal period using an NIR-TRS system. We showed that CBV in term infants is significantly higher than that in preterm infants, and that

in contrast to cerebral perfusion, PBV in preterm infants is significantly higher than that in term infants. These differences might be due to differences in the maturity of the physiological mechanism that controls CBV and PBV between term and preterm infants. Acknowledgments The authors thank Dr. Helena Akiko Popiel (PhD, Lecturer) and Dr. Edward Barroga (PhD, Associate Professor) of the Department of International Medical Communications of Tokyo Medical University for editing and reviewing the manuscript.

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Difference in cerebral and peripheral hemodynamics among term and preterm infants during the first three days of life.

The relationship between cerebral and peripheral hemodynamics during the early postnatal period has not been clarified...
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