003 1 -3998/87/2203-0302$02.0010
Vol. 22. No. 3, 1987
Printed rn U S A.
PEDIATRIC RESEARCH
Copynght (01987 Internat~onalPediatric Rescarch Foundation. Inc.
Brain Oxidative Phosphorylation following
Alteration in Head Position in Preterm and Term
Neonates
B. LAWSON, E. ANDAY, R. GUILLET, L. C. WAGERLE, B. CHANCE, AND M. DELIVORIAPAPADOPOULOS
Dcy~urtmc~nl.~
( jf'Pc.diu~r i a , Physlolog.~,Biochemt.stry and Bio~~hvsics,
The University of Pc~nnsvlvuniuSchool of
Medicine, Phlludclph~u,Penn.c,ylvunia 19104
ABS'I'RACT. An alteration in head position, which effects
cerebral blood flow, may increase the risk for intraventricular hemorrhage in the critically ill infant. The purpose of
this study was to evaluate in vivo cerebral oxidative metabolism as an index of tissue oxygen delivery reflecting
brain blood flow, in healthy preterm and term infants
following a change in head position. Cerebral phosphoenergetics using 31 phosphorus nuclear magnetic resonance
spectroscopy were measured in 10 preterm and eight term
infants following three different head positions: neutral,
prone, and supine. All infants were clinically stable at the
time of study. The phosphocreatine to inorganic phosphate
ratio, an indicator of bioenergetic reserve, was determined.
SD for phosphocreatine to inorganic phosThe mean
phate ratio in the neutral position in preterm and term
infants was 1.08 0.15 and 1 . I 2 0.21, respectively, and
did not change significantly following head turning. 'I'hese
data suggest that any alteration in cerebral blood flow as
a result of a change in head position in the healthy neonate
may be compensated by physiological and biochemical
regulations so that no changcs in brain oxidative phosphorylation are measurable. (Pediatr Res 22: 302-305, 1987)
+
+
+
Abbreviations
ICP, intracraniai pressure
" P MRS, phosphorus nuclear magnetic resonance spectroscopy
CBF, cerebral blood flow
PCr, phosphocreatine
PD, phosphodiesters
Pi, inorganic phosphate
PME, phosphomonoester
PDE, phosphodiester
The therapcutic management of anoxic brain insult and blunt
head trauma in adults and older children takes head position
into consideration ( I , 7 ) . However. optimal head position for
critically ill infants at risk for fluctuations in cerebral perfusion
and intracranial hemorrhage is controversial. Venographic studies in children indicate that a 90" head rotation results in obstruction of the ipsilateral internal jugular vein (3). This maneuver
impedes outflow from the brain, resulting in increased internal
jugular vein pressure and ICP when elastance is high. Anterior
Received Fcbruary 23. 1987; accepted Aprll 9. 1987.
Correspondence Dr. Endla K. Anday, D ~ v i s ~ oofn Neonatolog:. Hospital of the
Un~vcrsityof Pcnnsylvan~a.2 Maloney Bldg.. 36th and Spruce Street. Philadelphia.
PA 19 104.
fontanel tonometry measurements in asphyxiated infants shown
a rise in ICP following head rotation 90" from midline (4). A
previous investigation (5), using continuous wave Doppler technique to measure superior sagittal sinus blood velocity in healthy
term newborns, showed that turning the head effectively occluded the ipsilateral jugular vein and had profound effects on
blood flow velocity.
In order to evaluate the In vivo cellular metabolic response to
head position change, the present study used "P MRS, in stable
growing preterm and healthy term neonates. Since the relationship of low-to-no CBF to changes in MRS spectroscopy has been
documented (6, 7), an optimal head position that would minimize changes in cerebral oxidative metabolism was sought.
MATERIALS AND METHODS
Fz~ndurnenrulsofA4RS. Atomic nuclei, including 'H. I3C,and
"P, with an odd number of nucleons have an intrinsic magnetism. When an external magnetic field is applied to tissues
containing any of these nuclei, the nuclear dipoles align themselves parallel or antiparallel to the field. A second magnetic field
can then be applied which, if it is at precisely the right frequency,
will cause the alignment of the nuclei to "flip." The nuclei absorb
the radiofrequency energy and resonate. The resonant frequency
of a given nucleus depends on its chemical environment such
that, for example, the "P nuclei in different phosphorous containing compounds resonate at slightly different frequencies.
Therefore, the individual peaks in a magnetic resonance spectrum represent the absorption of radio waves by different compounds, including the three phosphorous atoms in ATP, PCr,
PD, Pi, and PME. The relative amounts of each of these compounds is reflected in the areas under each peak. In turn, the
metabolic activity of a tissue can be surmised by calculating the
ratios between these metabolites.
In mitochondria, ADP is converted to ATP by drawing on the
phosphorous from PCr, another high energy compound. When
cells are deprived of an external source of energy, ATP is maintained by the reservoir of PCr. Only when PCr is exhausted does
ATP fall, leaving ADP and Pi. The PCr/Pi and PCr/ATP ratios
are related to the phosphate potential (ATP/ADP x Pi and PCr/
Pi x Cr) and are thus an index of the energy status of the tissue.
Puticnts. Details of the in vlvo "P MRS technique in neonates
were reported previously (8). Eighteen infants were studied in
the magnetic resonance spectroscopy laboratory located within
the neonatal intensive care nursery of the Hospital of the University of Pennsylvania. All study infants were inborn and were
appropriate for gestational age. The term infants, following an
uneventful labor and delivery, were studied between days 1 and
3 of life. Preterm infants were studied when stable in room air
without evidence of chronic lung disease, ultrasonographic evi-
d c n c c ol' intr-:~crarl~al
hlcctl. clill~calsci/urc\. or- I,atcrlt i l u c t ~ ~ s It' a n ir1ll1111l ~ c x c ; ~ ~;iyit:~tcd
llc
c ~ ~ i.l.~cd.
ld
\111;111 ;1111011111\ 01'
ar-tcriosus. ho infants I-ccci\c*timedications at the time 01' the g l ~ ~ c o s\\:ltcr
c
~ C I -gr\
c ell. 11' :\I> I I I ~ ' : I I ~\\:I\
~
1101 L%:I\!
to ~ ~ o ~ i \ o l i ~ .
study.
the \tutl! \\as tcrmrnated ;iud tllv 111111111 1.ct~r1.11~~~1
to t11e3 11111.\1~1-!
"I' M l i S st~ltlicsmel-c d o n c to 1 11 aficr- a fi.etiing. 1.0s cac~li 1 t~~3ic:ll\t1ltl> Iil\tiYl l 1 11. \\ill) :I lli~oll:llol~l~i\t
~ l l ~ c ~ \ c ~ l l ;ti l l
study. thc i nl'ant \v:is ~,lacccl in a \l,cciall! clcsignctl \pcct~.c~\c.op\ t r ~ n c \ .L\'l1ilc, potc~~itr:tII ~ : I / : I I . ~ \ :~\\oc~r:rtc~I
\\it11 \ l l i S I I ~ , I S I I I ~
isolcttc (I'hospho I.ncrgctics). 4 4-em I-adiofi-cclucnc! sul-lire 2nd spcct~-o\col?!inc.lilcii. i~oii! L . \ ~ o \ L I I ' ~ lo: \ t a t ~ i(. I ) ( ' ) rna~:rlc~tiz
coil. locatctl in a stational-) position in the supine aspect ol'tllc
lieltls. tirnc-\a~-!rng iiiagnctic. iiclci (cil1/i1 I ) \\liic.l~ c.an in~liie~c~
e
hc:ld
carri:igc. \va\ placed o n the temporolxirietal s ~ ~ r l i i col'thc
clcctrical cur-rcrlts. and :~ti\orl~tlorl
o f crlcrg! !'ro11? r.:t~Iio f'r.c>dircrtly above tllc pinna ol'thc c:ir-. 'I.l~eisolcttc was tlicn ~nscrtccl clucrlc! clcctroi?iagl~ctrc.ficltis \\liicll c.ar1 ~ , r - o d ~l ~~ cca~t ~ ~110
ig.
into the horc 01' a 17.5-em s~1l,crcondtrctir1g magnet (I'liosptio
ad\ crsc e f k e t s ]la\ c to cl;~teI~ccrlI-cportcd. par-t~c,~~iar.l!
~t t h i ~
1:ncl'gctics). Ski11 tcmpcratur-c. Ilcar-1 ralc. rcsp~rator-! rate. ant1 l?ecl~~cncb
I 11c. stuei!
range in \\liicli 0111- stutlie\ \\el-ise~on~luc.ti*~l.
transcu1;illcot~shloocj oxhgen 5alur-ation h e r e c o n t l n u o ~ ~ s lmon!
pr.o(ocol \\a\ r e \ i c n c d 2nd acceptcii I,! the, I 1ni\c.r.\1t! 111' I)c*linitor-cd. A total ol'li)ur- n o s ~ t i o n sin n h i c h the n:~ticnt \\as nlaccd
n
.~nci
s!I~ania ( ' o m n ~ i t t c co n Kcscar-c.11 111\oI\rng 1 I ~ ~ r n aSul>ici.t\
wcrc: lying o n tllc rigkt :intl/or lcfi \ltlC \Lit'h head in r;cutl-al
signed parental corlscnt \ \ a \ ol,ta~ncil ill all i.asi.5.
.\'/it/i\/ic~\Value\ 21-c c\~,i-csxcti as thc meal1 i- I S i ) ol'ti~cx
position to the hod!: Ibing s u p i ~ l c~vitllhead tur-ncd 90" to ttic
~ L I I . I I C 10
C ~ tlic Icli.
right: lying pl-one ( s l c c l ~ i r ~~g, o \ i ( i o n )~ i t l I1c;ld
l
rncan. Statistical a ~ i a l ! \ ~ s\ \ a s 1,ci'li)rlllcd I!, o r l ~ ~ - \ \ :;illal\si\
~!
01'
l>c'tt\c-c.ri
I k c h stud! was \tar-tctl 11) ol>t:ti~iingtlic lcli anti I-isht n c ~ ~ t l - a l \ 31-iancc \\ it11 ~'epca~cclnic.a\uri~rnc~ril\.I )ilIi.r.c~r~c~r*\
means n c r e dctC~-riiinctlh\ 1,:iir-cti I tc\t \\ 1 t l 1 I % o n f i ' ~ r o~.orl-i>c.n~
position lir-\t: prone a n d \l~l,inc positions u c r c rantiomi/cti.
fiepeal rncasLrr.crnc,r1[ ol'thi. lcf'l rlcr~tral[ ~ o \ i t i o n\+:IS per-fi)rnleti
at the crid of' the tc\tlng to c\.aluatc corlsistcnc.! ol' the 51~1dics
:lll(l [ > O ~ S ~ ~rcl;1tiol1',l1i~~
)IL~
of' ti111c I?Ol?l I:1st f~ctii11g.,111 \11l<iics
PME
were pcsli)rmcd \41th the inlillt Ihing in a 1101-i/ontal po\rtion.
"1' M l i S c \ a m i n a t i o n s \\cr-c per-fi)rmcd at I .I I c\la ( ' I 1 ti-c,24.3 MI I / ) . Sl,cc,tr-a \\ere
clucncy 00. 1 MI I / : "I' I'~.ccl~~enc)
b i l i S slxctr-omctcr-. I3cti)l-c
collcctctl using a l'hosplio I<ric~-gctlcs
collection ol'\pcct~-a.liclti hornogcr~cit>was adJustcti \\lth tlic ' 1 i
M R S \igrral li-om tissue \vatel. l i ~ ra n intcl-val ol' I mlii fi)~
rnaxim:rl spcctr-al r-csol~~lion
ol' a ~ ~ ~ ~ r o i i m a 0.4
l c l ! pprn. I)ata
wcl-c acquil-cd u\ing the li)llo\iing ~ ~ a r a m c t e r -ps :~ ~ l sdcl:~!
c
4 s:
p ~ ~ l s\vidth
c
50 his: sweep \ ~ i ( i l h1000 111. ,I total 01' 240 ti-cc
induction tlcci~!s \\el-c s~gn:il a\el-aged g i \ i n g a total stuti! tlmc
in each position of' I0 min. Salnpling o l ' p h o s p t i r - I Scoml,oi~nils
a hcrnisl,hc~-ic\ o l l ~ r n c
by the sul-l'acc coil ~ n \ o l \ c al~l)rosimatcl>
\
with a 2-en1 rad111\ (0).Altho~rghpar-t o l ' t h c M l i S sigr~alc , o ~ ~ l d
he dcl-ivcd I'rom scalp muscles. thc.sc arc \,el-! thin in rlic neonate
ant1 t11crcfi)rc contr-ihutc minimall? to the "I' MKS signal. I.ourlc1 t r a ~ i s f i ~ r r ~ ~ a t curbe
i o r l . t i t ~ i ~ and
~ g . peak rncasur'cmerlts \ ~ c r - c
1-ig. I . "I' \[,cct~-~i~ii
oI'I>rairi 111 .I 0-(!a!-olC lic:1111i\ > I O \ \ I I ~ > lilcliiad o n c with tllc aid of'a spcctr-:rl an;~l!sis program ( 1 0 ) . b\.lcasurcs
o
f
34
\
\
A
~>~l\lcollc.c[>~lollLil
Llgc Ll\lllg t l l e ~ I 5 I c\1:1 1 ' l l ~ l \ [ l l l , l
tllle
i11f;1111
ol'ar-cas under- i h c~u r l c s l i ~ rthe ( i . 11'. anti y c o m p o n e n t s ot'
l~~icrgct~cs
\pc~~trol?iclc1-.
SI>LYII.:II
cI:it:i \\ci-' ~~ht:i~ric~I
li~r lii 1x1111 L I ~ I I :II ~
A'I.1'. IY'r, I'i. l)i). : i r ~ I I'MI.. \i,crc : i c c ~ ~ r ~ ~ ~ ~:iriti
l : i t ctiispl:~>cti
cI
111
3-\
~>uI\c
dcla!
\\ll~cli
C : I L I \ ~ \ pal-tlals,ituratiori o f ~ l1'\11
i
~
~ pc.ah. ('11cniie~al
the lorn1 ofgl-aphic output as ~vcllas final c l u a n t i t a t i ~ cdut:~.I h c
s I i i l ~ \ of rcfon:lnc,c~i ( 1 : I \ I \ ~ ~ r c :I'\ll:.
1)i. J)l)l:. 1Tr. , t , ,i., I I ~ L I -,
I'<'r/l'i ratio was used In the arlal\\is as i t is related t o the
phosphate potential a n d thus a measure ol' hiocnergctic r-cser-\c pllo\l>hatc\ o f ,"\ 1'. 1. . I \ I S I \ \lgllal ~:itcn\~t!I llc 1Y.r !I)I I J I I O I \
calculated from \~gnal.lrca\. \\iiicli alc proprrioiial 10 c~onccli~1-,~t~~,li
( 1 1).
-
'I.:~blc I .
( '/ti11(~0/(l(11c1 t i t
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oi1(1/ ( , ~ I Ittr/(/tt/.i
I
\ / i / ( I t ( ~~t.1111
/
7111\/I<.?
4gc :it
\fud\
I%11-111
\\I
( ~ ~ ~ 1 ~ l I l O l l ; l ~
1'. ,111cllt
(fi)
:igc ( w k )
Sex
I
2
3
4
3000
3700
28x0
32(10
I
M
I
1
5
0
?XOO
40
40
40
40
30
M
I anti ?
40
I
M
M
M
I
II
-7
7
X
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I3
14
IS
I0
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IX
?OX0
3370
2Oiil
2i00
I060
1x20
'I 30
1x40
1280
1046
14hO
1720
1070
40
30
?(I
31
74
34
12
?2
37
3?
3 -3
35
(cia)\)
1
810
7
I
o/o
s;o
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7,JO
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h a11ti 14
I7 ;111d2 I
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II
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( I min/4 miri)
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PME
304
LAWSON ET AL
Table 2. PCr/Pi ratio in--preterm and--trrin infbnts .fi~llowing
alteration
ofhead
position (mean k SD)
---Head position
-
--
Group
Preterm
-
Rlght neutral-
p
p
p
-
1 08 ? 0 09
(range 0 9 4 1 23)
(range 0.93-1.37)
~
p
p
~
p
-
- -
~-~
-
- ~ .
Suplne
-
1 1 1 k 0 19
(range 0 85- 1 46)
1.13 + 0.17
Term
Left neutral
--
-
108k015
(range 0 87- 1 33)
l .00 + 0.23
1.09 k 0.18
(range
0.71-1.36)-.
.
(range 0.89-1.47)
tion when necessary. All differences were considered significant
when p < 0.05.
+ 0 28
(range 0 77- 1 60)
1.05 k 0.25
(rangc 0.79-1.48)
Term
A
Prone
1 05
a
Preterm
RESULTS
.4 total of 18 infants, 10 preterm and eight term, were studied
(Table 1). All infants were healthy and clinically had a normal
neurological examination for age. An example of a "P MRS
from a preterm and term infant are shown in Figures I and 2,
respectively. The seven labeled peaks are evident in both sets of
patients. The cu, P, and y components of ATP magnesium
complemented ATP probably include contributions from other
nuclei triphosphate. The peak labeled PDE is attributable to P D
and membrane phospholipids (12). The PCr/Pi ratio, an indicator of bioenergetic activity, was calculated in each position.
Control spectra for each infant were considered the spectra
obtained with the head in neutral position. After these were
obtained from the left and right hemispheres, the baby was placed
either prone or supine so that the head was turned 90". The
spectra obtained in thcse positions also showed the characteristic
resonance peaks.
The mean value + S D for PCr/Pi in preterm infants was: left
neutral I . l 1 0.19 and right neutral 1.08 + 0.09 (Table 2). No
significant difference was seen in the PCr/Pi values for term
infants with the head in the supine and prone positions. The
term infants had a mean t S D for PCr/Pi ratio of: left neutral
1.00 t 0.23 and right neutral 1.13 0.17 (Table 2). Statistical
analysis showed no significant change in PCr/Pi ratio with head
position changes between or within groups (Fig. 3).
W Neutral
L Neutral
L Supine
L Prone
+
+
Infant Head Posltion
Fig. 3. Effect of varying head position on PCr/Pi ratio in healthy
preterm and term infants. PCr/Pi ratio is the mean value derived from
the I0 preterm and eight term infants in each head position. Error hart
represents 1 SD. Differences between and within groups are not significant.
DISCUSSION
Previous studies demonstrated increased intracranial pressure
following head position changes in healthy and particularly in
birth asphyxiated infants, with the exaggerated response in asphyxiated infants most likely due to a decrease in cerebral
autoregulation (13-15). This has led to speculation as to an
optimal head position whereby fluctuations in cerebral blood
flow could be minimized to decrease the risk of intracranial and
or intraventncular hemorrhage in the critically ill neonate. While
"P MRS has been used to assess cerebral metabolism in infants,
previous studies were obtained in neonates suffering from hypoxic ischemic episodes, such as asphyxia neonatorum. In the
investigation by Hope rt al. (16), six normal term and preterm
infants were studied for comparison with the asphyxiated newborn subjects. The present study represents one of the largest
series of healthy infants measured with "P MRS and provides
insight into the basic characteristic peaks of control 31Pspectra.
The 3 ' P spectra obtained in our normal term and preterm
subjects identifies 7 peaks and are similarly to previous investigations.
Unlike the previous study by Cady et al. (17), we noted a lower
PCr/Pi ratio in the healthy newborn infant. Part of this difference
could be attributed to a saturation factor (18) that was instilled
into the computation, because at a 2.25-s pulse interval, full
relaxation of the atoms was not allowed but could be corrected
for by a factor. In our studies we used a 4-s pulse interval and
although we may have been saturating some of the larger peaks,
such as PME and Pi, we used a correction factor of 1.05 which
was within our significance level and could make the PCr/Pi
higher. Thus all data can be corrected for saturation.
Further, it is possible to calculate from the range of the data
on Table 2 that an average change of 50.25 in PCr/Pi ratio could
have occurred following alteration of head position. From this
\ye can calculate based on Michaelis-Menten kinetics (19): V/
K,/ADP + K2/Pi + K3/S) where V = rate of
V,,, = 1/(1
oxidative metabolism, V,,, = maximum rate of oxidative metabolism, S = substrate, and K = rate constant, what the change
of tissue PO2 would be, given this difference. If a reasonable
assumption about the parsimony of oxygen delivery to the neonate brain can be made, a change of tissue PO2 of a factor slightly
greater than 2 could have occurred within the error limits observed. Since PCr/Pi is an oxygen indicator itself, we can calculate from the range of our data what would be the possible change
of tissue oxygen that could have occurred within our S D as a
factor of 2. This calculation emphasizes that while no detectable
effects on the PCr/Pi ratio were found in the present study, it is
possible that small perturbations could have been appreciated if
the SE were smaller.
As the process of energy metabolism must take place in a n
aerobic environment, 31P MRS is a quantitative measure of
aerobic metabolism and oxygen delivery to tissues (20). During
periods of anaerobic metabolism, as in asphyxia, and in low flow
states as intraventricular hemorrhage (7, 16), the ability to regenerate ATP and PCr is lowered. Recent studies, in our institutions
as well as in others, have shown a correlation of PCr/Pi to
+
('l~;Kl:l3KAI. O X I I I A 1 IVI-. M E T A B O L I S M IN H E I . . r H \ r S 1 : O S A I'I'S
asphyxia1 episodes
(8. 10).
Othcr- studies have shomn
305
"P MKS
to be a gootl i n d i c a t o r of' r-eco\cr-> of b r a i n ILnctio11 during
e x p e r i m e n t a l aspllyxial episodes w h e n cor-related t o clcctr-ocncephalograplly a n d I-cgional
'I'he
lindings
in
('131: (7).
t h e present stud!
arc consistent \\.it11 the
fluid. b l o o d . and
initial changc
b! v o l u m e s l i i l i s in the
M o n r - o c - K c l l i c h g p o t h e s ~ sthat tho b r a i n . spinal
o t h e r intr-acranial contents arc constant. so that a n
in
volume ol'onc compartment
o t h e r cornpar-trne~its.I-esultirig
prcssur-c ( 2 1 ). Rasctl
on
i c a n t pcrtur-bationc in
in hc;id
in
is
offict
111inirnal change
in
intr-acmrlial
p r c ~ i o s~t l~~sd i e sthat showed that
I('1'
signif:
a~id
b l o o d flo\v velocit> occurred a f i c r
in thc nor-nial t e r m and health\
ma) be compensated bb pli!siological and t x o c h c m ~ c a regulations
l
s o that n o change i n b r a i n
o x i d a i i v c phosphor-ylatiori as measurctl b? l l P MKS in a health!
neonate i s detectable.
a cliangc
prclcrm
p o s i t ~ o lc
l \cn
inli~nt.these
alterations
..
.
mcraholltc\ In \\11olc .~n~m:ll\
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