Journal of Perinatology (2014) 34, 192196

& 2014 Nature America, Inc. All rights reserved 0743-8346/14

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ORIGINAL ARTICLE

Effects of antenatal magnesium sulfate treatment on cerebral blood

ow velocities in preterm neonates
EY Imamoglu, T Gursoy, G Karatekin and F Ovali
OBJECTIVE: The objective of this study is to investigate the effects of antenatal magnesium sulfate (MgSO4) on cerebral blood ow
(CBF) velocities in preterm neonates.
STUDY DESIGN: In this prospective casecontrol study, we included 53 neonates born between 26 and 34 weeks of gestation.
Twenty neonates were exposed to MgSO4 antenatally and 33 were not. Serial daily Doppler ow measurements of middle cerebral
artery (MCA) were performed.
RESULT: Signicantly increased MCA mean velocities were found in the MgSO4 group. A progressive increase in serial Doppler
measurements of MCA mean velocity from day 1 to day 5 of life was detected in both groups.
CONCLUSION: There is signicant increase in MCA mean velocities in preterm neonates receiving antenatal MgSO4. This increment
in CBF velocities might explain the protective role of MgSO4 in ischemic events and hypoxic brain damage.
Journal of Perinatology (2014) 34, 192196; doi:10.1038/jp.2013.182; published online 30 January 2014
Keywords: doppler; middle cerebral artery; magnesium; prematurity

INTRODUCTION
The developing fetal brain is highly dependent on sustained blood
ow due to the lack of its own energy and nutrient reserves.1
In the immature brain, the thin peripheral vessels do not present
many collateral routes or anastomoses and their walls are immature. Thus, they cannot sustain effective blood ow and their
limited vasodilatation capacity cannot compensate the hypoxicischemic injury.2
Exposure to antenatal magnesium sulfate (MgSO4) treatment
and increased cord serum magnesium concentrations have been
associated with a decreased incidence of hypoxic brain damage.3,4
Neuroprotection is the inhibition of the biochemical response
to ischemia in order to prevent neuronal death. However, the
biochemical cascade during ischemia originates from insufciency
and failure of the microcirculation. Thus, preservation of the
microvasculature would lead to neuroprotection.5 MgSO4 has
been shown to have benecial hemodynamic effects by stabilizing
the blood pressure, reducing the constriction in cerebral arteries
and restoring the perfusion in preterm neonates.68
Cerebral blood ow (CBF) velocities have been validated as a
reliable indicator of CBF, and changes in CBF are assumed to have
a key role in the development of various cerebral lesions in
preterm infants.9,10
In this study, our aim was to investigate the effects of antenatal
MgSO4 on CBF velocities in preterm neonates.

maternal MgSO4 treatment antenatally (MgSO4 group) and 33 were not

(control group).
Neonates without antenatal Doppler examination and with absent/
reversed end diastolic velocity in umbilical artery were excluded from the
study. Neonates with clinical conditions such as congenital malformation,
chromosomal anomaly, perinatal asphyxia, sepsis, premature rupture of
membranes, choriamnionitis, polycythemia (Hb422 g dl  1), anemia
(Hbo10 g dl  1) and whose mothers had multiple pregnancies were not
included in the study (delayed cord clamping was not performed in any
case during delivery).
Gestational age was calculated from the beginning of the last menstrual
period of the mother and veried using early trimester ultrasonographic
data. Neonates with uncertain gestational age were excluded.
Twenty mothers had received an intravenous infusion of MgSO4 either
for preeclampsia (n 14) or tocolysis (n 6). A loading dose of 6 g was
infused over 30 min and was followed by a maintenance infusion of
0.8 g h  1 until the time of delivery according to our institution protocol.
Mothers having ritodrine for tocolysis were excluded from the study.
Maternal serum magnesium concentration just before labour was recruited
from the maternal records. Atomic absorption spectrophotometry (Cobas
Integra 800, Roche, Basel, Switzerland) was used to determine serum
magnesium levels in the maternal and umbilical cord blood. Maternal
cumulative MgSO4 dose and total infusion time (hours) were calculated.
The control group consisted of neonates born immediately after
reaching the hospital or whose mothers did not receive any MgSO4 or
tocolytic treatments but fullled the abovementioned enrollment criteria.
Informed consent was obtained from the parents, and study protocol
and consent forms were approved by local ethics committee.
Blood pressure was determined as an average of three measurements
made from the right upper arm before Doppler examination.

METHODS
In this prospective casecontrol study, we included a total of 53 neonates
between 26 and 34 weeks of gestation born at the Zeynep Kamil Maternity
and Childrens Training and Research Hospital, Istanbul, Turkey, between
December 2011 and December 2012. Twenty neonates were exposed to

Doppler ultrasonography measurements

During measurements, neonates were in a resting state and lying in a
supine position.1113 Environmental light intensity was low and constant.
Phototherapy was suspended during measurements. To avoid crying

Zeynep Kamil Maternity and Childrens Training and Research Hospital, Neonatal Intensive Care Unit Istanbul, Istanbul, Turkey. Correspondence: Dr EY Imamoglu, Zeynep Kamil
Kadn ve ocuk Hastalklar Egitim ve Arastrma Hastanesi Opr., Dr Burhanettin Ustunel Cad. No:10, Uskudar, Istanbul 34668, Turkey.
E-mail: ebruli013@hotmail.com
Received 26 September 2013; revised 15 November 2013; accepted 4 December 2013; published online 30 January 2014

Mg and CBF velocities

EY Imamoglu et al

193
episodes and stress conditions, gentle handling consisting of administration of oral dextrose drops in order to pacify the baby when needed,
stimulation of non-nutritional sucking, delicate touching and calm voice
tones was applied.10
The measurements have been made before the administration of daily
caffeine dose.14 Neonates who suffered from hypotension, exposed to
drug therapies that could change CBF velocity or arterial blood pressure
and any metabolic pathology were excluded from the study.1519 Flow
imaging and blood ow velocity were obtained with a color Doppler unit
(Philips En Visor C, Amsterdam, The Netherlands) and a multifrequency
5-12 MHz sector probe was used. In order to eliminate interobserver
variability, serial pulse-wave Doppler ultrasound measurements were made
by the same experienced neonatologist (EI), blinded to the group
assignment of the neonate.
Measurements of mean velocity have been made in the left and right
middle cerebral artery (MCA) on day 1, 2, 3, 4 and 5 of life. All measurements were performed after the rst 8-12 h of life in order to reduce
the possible effects of immediate postnatal cardiovascular adaptation on
owmetric data. Doppler ow measurements of MCA were performed
by scanning through the anterolateral fontanelle (temporal window).
The transducer is placed above the ear, B1 cm superior and anterior
to the external auditory meatus, posterior to the orbit and zygomatic arch,
with the marker in a horizontal position.20,21 With the transducer
angled slightly inferiorly, it overlays the appropriate window for
visualizing the midbrain, dened by the characteristic contour of the
cerebral peduncles anteriorly.21 The color gain was set to maximize
vascular signal and minimize tissue motion artifacts. The transducer
position was subsequently adjusted until visualization of the red MCA ow.
The angle between the ultrasound beam and the direction of blood ow
was kept below 151.22
To maintain accuracy, a minimum of ve sequential homogenous
cardiac cycles of optimal quality were subjected to real-time spectral
analysis. MCA mean ow velocity was obtained by integrating the area
under the velocity curve over one cardiac cycle.10 A minimum of three
measurements were obtained and then averaged. MCA mean velocity
served as a surrogate for CBF.2325 Examination time was B5 min.
Along with the Doppler studies, cranial ultrasonography was performed
in all cases. The grade of intraventricular hemorrhage was reported according to the criteria of Papile et al.26 The shunt across the patent ductus
arteriosus (PDA) was evaluated from a high parasternal/suprasternal view
by the same investigator (TG) experienced in echocardiography.27
Moreover, the presence of respiratory distress syndrome, phototherapy,
caffeine, ibuprofen and inotrope use were recorded.

Statistical analysis
Statistical analysis was performed by using SPSS software version 20.0 (IBM
Statistics, IBM, Somers, NY). The variables were investigated using visual
histograms, probability plots and ShapiroWilks test to determine whether
or not they are normally distributed. Descriptive analyses were presented
using meanss.d. for normally distributed variables, as medians (2575%)
for the non-normally distributed variables and as percentages for
categorical variables. Normally distributed variables were compared by
Students t-test, nonparametric variables by MannWhitneys U-test and
categorical variables by w2-test. Friedman tests were conducted to test
whether there is signicant change in MCA velocities in the consecutive
days. Correlation between maternal and cord blood magnesium levels was
evaluated by using Spearmans correlation coefcient.
Intraobserver variability was assessed in an arbitrary sample of 20
neonates. The measurements were repeated by the same investigator who
was blinded to the previous results. The coefcient of variation was
calculated in order to show intraobserver variability.

Demographic characteristics, hemodynamic and clinical variables of the neonates are shown in Table 1. There was no
signicant difference between the groups.
All attempts to obtain MCA mean velocities were successful. As
the changes of the hemodynamic variables in the left and right MCA
were similar and correlated signicantly, only the data of the left
MCA were presented. Signicantly increased MCA mean velocities
were found in the MgSO4 group compared with that in the control
group (Table 2). Figure 1 shows the progressive increase in serial
Doppler measurements of MCA mean velocity from day 1 to day 5
of life in both groups (Po0.001 in the control group and P 0.027 in
the MgSO4 group). There was no correlation between cord blood
Mg levels and MCA Doppler velocities in both groups (MgSO4 group:
r 0.25, P 0.29; control group: r  0.16, P 0.39).
There was no difference between the two groups in terms of
the presence of ductal patency during serial daily measurements
and ibuprofen use.

Table 1. Demographic characteristics, hemodynamic and clinical

variables of the preterm neonates involved in the study

Maternal age (years)

Gestational age (weeks)
Birth weight (g)

& 2014 Nature America, Inc.

Control
group
(n 33)

P-values

283.9
321.6
1497347

285.1
31.12
1533299

0.47
0.13
0.67

9 (45)
11 (55)

13 (40)
20 (60)

0.68

Gender (n)
Males (%)
Females (%)
SGA
5 min APGAR score
Cesarean section
Heart rate (bpm)
Mean arterial pressure
(mm Hg)
RDS
PDA
IVH
Caffeine therapy
Ibuprofen
Inotrope use
Phototherapy

6 (30%)
9 (8.29)
18 (90%)
14813.5
49.49.8
6
8
3
6
3
1
16

(30%)
(40%)
(15%)
(30%)
(15%)
(5%)
(80%)

3 (9.1%)
9 (89)
27 (81.8%)
14915.4
45.46.6
11
15
2
11
6
2
27

(33.3%)
(45.5%)
(6%)
(33.3%)
(18.2%)
(6.1%)
(81%)

0.07
0.62
0.42
0.95
0.11
0.8
0.7
0.52
0.8
0.54
0.87
0.9

Abbreviations: IVH, intraventricular hemorrhage; MgSO4, magnesium

sulfate; PDA, patent ductus arteriosus; RDS, respiratory distress syndrome;
SGA, small for gestatioal age.
Values are presented as means.d. for maternal age, gestational age, birth
weight, heart rate, mean arterial pressure. Five-minute APGAR score is
presented as median (2575%).

Table 2. Serial Doppler measurements of MCA-MV from day 1 to day 5

of life in two groups of preterm infants who were or were not exposed
to antenatal magnesium sulfate
MCA-MV (cm s  1)

RESULTS
Twenty neonates constituted the MgSO4 group and 33 neonates
constituted the control group. MgSO4 was administered for
treatment of preeclampsia in 14 cases and for tocolysis in 6
cases. Median total dose of MgSO4 given to the mother before
labour was 34.2 (12.554.4) g. Median total infusion time was 15
(3.826) h. Median serum magnesium levels in maternal and cord
blood were 5.5 (4.66.5) and 3.5 (3.14) mg dl  1, respectively.
Maternal serum magnesium levels were correlated with cord
blood magnesium levels of the neonates (r 0.62, P 0.004).

MgSO4
group
(n 20)

Day
Day
Day
Day
Day

1
2
3
4
5

MgSO4 group
21.2
22.1
24.8
23.2
27.7

(16.422.4)
(15.928.2)
(18.230.7)
(21.529.4)
(21.131.5)

Control group
15.8
17.8
18.1
20.3
22.2

(1318.5)
(14.320.3)
(16.323.3)
(17.225.2)
(1828)

P-values
0.001a
0.014a
0.005a
0.004a
0.022a

Abbreviations: MCA-MV, middle cerebral artery mean velocity; MgSO4,

magnesium sulfate.
a
Significant difference between two groups, values are presented as
median (2575%).

Journal of Perinatology (2014), 192 196

Mg and CBF velocities

EY Imamoglu et al

194

Figure 1. Serial Doppler measurements of middle cerebral artery

mean velocities from day 1 to day 5 of life in both groups. Solid line
presents the control group and dotted line presents the magnesium
sulfate group.

Intraobserver error was minimal (2%) and there was no

signicant difference between consecutive measurements.
DISCUSSION
In the cerebrovascular bed, increased magnesium ion concentration was shown to reduce the contractile responses of isolated
cerebral arteries resulting in vasodilatation.2831 MgSO4 treatment
has also vasodilatory effects on both cerebral circulation and
systemic arteries.3234 Belfort et al.34 investigated the effect of
MgSO4 on the cerebral circulation in patients with pregnancyinduced hypertension and showed a signicant increase in mean
velocity in the maternal MCA in response to intravenous MgSO4
that was interpreted as distal artery vasodilatation. Less is known
about antenatal effects of MgSO4 on the fetus and newborn
circulatory systems. In late-term goat fetuses, direct infusion of
MgSO4 increases the brain blood ow during acute hypoxemia.35
However, there are limited studies investigating the effects of
antenatal MgSO4 on neonatal circulation. In neonates, elevated
levels of MgSO4 may persist for up to 7 days, with an elimination
half life of 43.2 h.36 Therefore, we aimed to investigate whether
there was any change in MCA mean velocities or not with
serial daily Doppler measurements. To our knowledge, this is the
rst study in the literature performing serial daily Doppler
measurements of MCA in preterm neonates exposed to
antenatal MgSO4.
We did not measure CBF, but assessed its surrogate MCA mean
velocity. Although MCA mean velocity correlates well with CBF, we
cannot exclude the possibility that changes in MCA diameter
affected velocity without affecting ow, which was a limitation of
this study.2325
Absent and reversed end diastolic velocities in Doppler
examination of umbilical artery are late vascular responses
in growth-restricted fetus.37 These late Doppler ndings result
from altered forward cardiac function and abnormal organ
autoregulation, generally signifying the onset of compromise
and redistribution in organ blood ows.38 For this reason, we did
not include the neonates having these abnormal Doppler ndings
in our study.
Journal of Perinatology (2014), 192 196

Pezzati et al.39 obtained normal standards of CBF velocity in

healthy preterm and term infants relating to the rst hours of life,
a period in which the owmetric modications could be inuenced
in a signicant manner by postnatal adaptation.10 Thus, we
performed our Doppler measurements after the 8-12 h of life.
In another study evaluating the effect of antenatal tocolytic
administration of MgSO4 and ritodrine on CBF velocity in preterm
neonates by Pezzati et al.40, they measured CBF velocities in the
anterior cerebral artery, right and left MCA in the rst hours of life
(28 h) and did not nd any signicant difference in blood ow
velocities in the three cerebral arteries between the two treatment
groups. They made a comparison in between the MgSO4 and
ritodrine groups; however, they did not have any control group in
which no tocolytic medication was used. This was a major
limitation of their study, as ritodrine as a tocolytic agent may affect
CBF velocities.10 Besides, their measurements of CBF velocities
were lower than those in our both the MgSO4 and the control
group, which may be explained by the time of their measurements as they had made the measurements in the rst 28 h,
which was early when compared with our study. On the other
hand, Rantonen et al.41 performed serial Doppler examinations
of anterior cerebral artery and internal carotid artery at the
mean ages of 6, 12, 24, 36, 48, 72 and 96 h and 1 week in
preterm neonates exposed to antenatal MgSO4 (n 19), ritodrine
treatment (n 17) and in 19 nonexposed preterm controls. They
found that maternal MgSO4 had no signicant effect on blood
ow velocities in the neonatal cerebral vessels. As MCA mean
velocity is a surrogate for CBF, we preferred to perform our
measurements on MCA in order to evaluate CBF.22 In contrast to
the study of Rantonen et al.,41 we found increased MCA mean
velocities in the MgSO4 group when compared with control group
from day 1 to day 5 of life. However, they did not give the actual
results of CBF velocities, instead they gave the cerebral perfusion
pressure and blood ow indices, which were calculated values
that also included the blood pressure values in the equation.
Hence, we could not compare our results with theirs.
Romagloni et al.10 provided normal reference values of CBF
velocities in healthy preterm infants in the rst month of life (day
1, 3, 7, 14, 21 and 28). MCA mean velocities of our control group
were found similar to those reference values. They also showed
the existence of a progressive increase of systolic, diastolic and
mean ow velocities in the anterior cerebral artery and MCA as
the postnatal age increases, such as that observed in our study
population in both the MgSO4 and the control groups, and related
this progressive increase in CBF velocities to the progressive
opening of cerebral vascular bed associated with a reduction of
microcirculation resistances. Theoretically, vasodilators should be
able to increase blood ow via a change in vessel diameter at the
entrance of microcirculation.42 In addition to vasodilatory effects,
infusion of MgSO4 is also associated with other potential promicrocirculatory effects, such as an increase in red blood cell
deformability, reduction of platelet aggregation, anti-inammatory effects and maintenance of endothelial integrity.4346
Through all these mechanisms, MgSO4 could facilitate the
decrease in microcirculation resistances in the cerebrovascular
bed and improve microvascular perfusion, and this may explain
the increase in MCA ow velocities observed in our study.
Shokry et al.47 studied 48 preterm neonates divided into two
groups based on maternal exposure to MgSO4 (n 28) or not
(n 20), and performed CBF velocity measurements on anterior
cerebral artery and MCA. They found signicantly lower peak
systolic, mean and end diastolic velocities in these cerebral
arteries, and also a signicantly higher incidence of PDA in the
MgSO4 group. They concluded that magnesium relaxed ductal
muscles with resultant ductal patency and decreased cerebral
perfusion was associated with an increased incidence of PDA. In
our study, contrary to their study, PDA incidence was similar in
both groups. On the other hand, Elimian et al.48 studied 190
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Mg and CBF velocities

EY Imamoglu et al

195
neonates exposed to MgSO4 and 211 neonates not exposed to
MgSO4. Similar to our results, they found no difference between
groups with regard to the rates of PDA. Effects of ibuprofen on
MCA Doppler measurements were not evaluated. This was a
limitation of our study.
There are several studies reporting that maternal administration
of MgSO4 was associated with a reduced risk of intraventricular
hemorrhage in infants.4,49 In our study, we did not nd any signicant difference in terms of intraventricular hemorrhage between
the two groups. Morover, similar to our results, Crowther et al.50
did not nd any effect of MgSO4 on the rate of intraventricular
hemorrhage, and they speculated that any neuroprotective effect
of MgSO4 on motor dysfunction might work through stabilization
of CBF and ameliorating the effects of ischemic episodes, which
might be explained by increased CBF.
In conclusion, this is the rst study in the literature highlighting
the increase in MCA mean velocities in preterm neonates
receiving antenatal MgSO4. This increment in CBF velocities might
explain the protective role of MgSO4 in ischemic events and
hypoxic brain damage.
CONFLICT OF INTEREST
The authors declare no conict of interest.

ACKNOWLEDGEMENTS
We express our gratitude to the families who gave us permission to evaluate their
babies.

REFERENCES
1 Alvarez-Daz A, Hilario E, de Cerio FG, Valls-i-Soler A, Alvarez-Daz FJ. Hypoxicischemic injury in the immature brain-key vascular and cellular players. Neonatology 2007; 92(4): 227235.
2 Bauer R, Zwiener U, Buchenau W, Bergmann R, Beyer R, Beyer GJ et al. Interaction
between systemic circulation and brain injuries in newborns. Exp Pathol 1991;
42(4): 197203.
3 Ilves P, Blennow M, Kutt E, Magi ML, Kudrjavtseva G, Lagercrantz H et al.
Concentrations of magnesium and ionized calcium in umbilical cord blood in
distressed term newborn infants with hypoxic-ischemic encephalopathy. Acta
Paediatr 1996; 85(11): 13481350.
4 FineSmith RB, Roche K, Yellin PB, Walsh KK, Shen C, Zeglis M et al. Effect of
magnesium sulfate on the development of cystic periventricular leukomalacia in
preterm infants. Am J Perinatol 1997; 14(5): 303307.
5 Takahashi M, Macdonald RL. Vascular aspects of neuroprotection. Neurol Res 2004;
26(8): 862869.
6 de Haan HH, Gunn AJ, Williams CE, Heymann MA, Gluckman PD. Magnesium sulfate
therapy during asphyxia in near-term fetal lambs does not compromise the fetus
but does not reduce cerebral injury. Am J Obstet Gynecol 1997; 176(1 Pt1): 1827.
7 Macdonald RL, Curry DJ, Aihara Y, Zhang ZD, Jahromi BS, Yassari R. Magnesium
and experimental vasospasm. J Neurosurg 2004; 100(1): 106110.
8 Schiff SJ, Somjen GG. Hyperexcitability following moderate hypoxia in hippocampal tissue slices. Brain Res 1985; 337(2): 337340.
9 van de Bor M, Walther FJ. Cerebral blood ow velocity in healthy term infants. Am
J Med Sci 1991; 301(2): 9196.
10 Romagnoli C, Giannantonio C, De Carolis MP, Gallini F, Zecca E, Papacci P. Neonatal
color Doppler US study: normal values of cerebral blood ow velocities in preterm
infants in the rst month of life. Ultrasound Med Biol 2006; 32(3): 321331.
11 Anthony MY, Evans DH, Levene MI. Neonatal cerebral blood ow velocity
responses to changes in posture. Arch Dis Child 1993; 69(3): 304308.
12 Pellicer A, Gaya F, Madero R, Quero J, Cabanas F. Noninvasive continuous monitoring of the effects of head position on brain hemodynamics in ventilated
infants. Pediatrics 2002; 109(3): 434440.
13 Ichihashi K, Iino M, Eguchi Y, Uchida A, Honma Y, Momoi M. Effect of head position
to the cerebral arterial ow in neonates. Early Hum Dev 2002; 69(1-2): 3546.
14 Hoecker C, Nelle M, Poeschl J, Beedgen B, Linderkamp O. Caffeine impairs cerebral and intestinal blood ow velocity in preterm infants. Pediatrics 2002; 109(5):
784787.
15 Kempley ST, Gamsu HR. Arterial blood pressure and blood ow velocity in major
cerebral and visceral arteries. I. Interindividual differences. Early Hum Dev 1993;
34(3): 227232.

& 2014 Nature America, Inc.

16 Kempley ST, Gamsu HR. Arterial blood pressure and blood ow velocity in major
cerebral and visceral arteries. II. Effects of colloid infusion. Early Hum Dev 1993;
35(1): 2530.
17 Menke J, Michel E, Rabe H, Bresser BW, Grohs B, Schmitt RM et al. Simultaneous
inuence of blood pressure, PCO2, and PO2 on cerebral blood ow velocity in
preterm infants of less than 33 weeks gestation. Pediatr Res 1993; 34(2): 173177.
18 Tyszczuk L, Meek J, Elwell C, Wyatt JS. Cerebral blood ow is independent of
mean arterial blood pressure in preterm infants undergoing intensive care.
Pediatrics 1998; 102(2 Pt 1): 337341.
19 Pryds O, Greisen G, Friis-Hansen B. Compensatory increase of CBF in preterm
infants during hypoglycaemia. Acta Paediatr Scand 1988; 77(5): 632637.
20 van Wezel-Meijler G. Performing cranial ultrasound examinations. In: Heilmann U
(ed). Neonatal Cranial Ultrasonography, Guidelines for the Procedure and Atlas of
Normal Anatomy. Springer Verlag: Berlin, Heidelberg, 2007, pp 1635.
21 Mitchell DG, Merton D, Needleman L, Kurtz AB, Goldberg BB, Levy D et al. Neonatal brain: color Doppler imaging. Part I. Technique and vascular anatomy.
Radiology 1988; 167(2): 303306.
22 Noori S, Wlodaver A, Gottipati V, McCoy M, Schultz D, Escobedo M. Transitional
changes in cardiac and cerebral hemodynamics in term neonates at birth.
J Pediatr 2012; 160(6): 943948.
23 Raju TN. Cerebral Doppler studies in the fetus and newborn infant. J Pediatr 1991;
119(2): 165174.
24 Greisen G, Johansen K, Ellison PH, Fredriksen PS, Mali J, Friis-Hansen B. Cerebral
blood ow in the newborn infant: comparison of Doppler ultrasound and
133
xenon clearance. J Pediatr 1984; 104(3): 411418.
25 Hansen NB, Stonestreet BS, Rosenkrantz TS, Oh W. Validity of Doppler measurements of anterior cerebral artery blood ow velocity: correlation with brain blood
ow in piglets. Pediatrics 1983; 72(4): 526531.
26 Papile LA, Burstein J, Burstein R, Kofer H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights
less than 1500 gm. J Pediatr 1978; 92(4): 529534.
27 Kluckow M, Evans N. Early echocardiographic prediction of symptomatic patent
ductus arteriosus in preterm infants undergoing mechanical ventilation. J Pediatr
1995; 127(5): 774779.
28 Allen GS, Gross CJ, Henderson LM, Chou SN. Cerebral arterial spasm. Part 4:
in vitro effects of temperature, serotonin analogues, large nonphysiological
concentrations of serotonin, and extracellular calcium and magnesium on serotonin-induced contractions of the canine basilar artery. J Neurosurg 1976; 44(5):
585593.
29 Altura BT, Altura BM. Withdrawal of magnesium causes vasospasm while elevated
magnesium produces relaxation of tone in cerebral arteries. Neurosci Lett 1980;
20(3): 323327.
30 Seelig JM, Wei EP, Kontos HA, Choi SC, Becker DP. Effect of changes in magnesium
ion concentration on cat cerebral arterioles. Am J Physiol 1983; 245(1): 2226.
31 Euser AG, Cipolla MJ. Resistance artery vasodilation to magnesium sulfate during
pregnancy and the postpartum state. Am J Physiol Heart Circ Physiol 2005; 288(4):
15211525.
32 Aloamaka CP, Ezimokhai M, Morrison J, Cherian T. Effect of pregnancy on
relaxation of rat aorta to magnesium. Cardiovasc Res 1993; 27(9): 16291633.
33 Belfort MA, Moise Jr. KJ. Effect of magnesium sulfate on maternal brain blood ow
in preeclampsia: a randomized, placebo-controlled study. Am J Obstet Gynecol
1992; 167(3): 661666.
34 Belfort MA, Saade GR, Moise Jr. KJ. The effect of magnesium sulfate on maternal
and fetal blood ow in pregnancy-induced hypertension. Acta Obstet Gynecol
Scand 1993; 72(7): 526530.
35 Tanaka S, Sameshima H, Ikenoue T, Sakamoto H. Magnesium sulfate exposure
increases fetal blood ow redistribution to the brain during acute non-acidemic
hypoxemia in goats. Early Hum Dev 2006; 82(9): 597602.
36 Dangman BC, Rosen TS, James LS. Magnesium levels in infants of mothers treated
with MgSO4. Pediatr Res 1977; 11: 415.
37 Baschat AA. Venous Doppler evaluation of the growth-restricted fetus. Clin Perinatol 2011; 38(1): 103112.
38 Ferrazzi E, Bozzo M, Rigano S, Bellotti M, Morabito A, Pardi G et al. Temporal
sequence of abnormal Doppler changes in the peripheral and central circulatory
systems of the severely growth-restricted fetus. Ultrasound Obstet Gynecol 2002;
19(2): 140146.
39 Pezzati M, Dani C, Biadaioli R, Filippi L, Biagiotti R, Giani T et al. Early postnatal
doppler assessment of cerebral blood ow velocity in healthy preterm and term
infants. Dev Med Child Neurol 2002; 44(11): 745752.
40 Pezzati M, Giani T, Gambi B, Dani C, Bertini G, Biagiotti R et al. Inuence of
maternal magnesium sulphate and ritodrine treatment on cerebral blood ow
velocity of the preterm newborn. Acta Obstet Gynecol Scand 2001; 80(9): 818823.
41 Rantonen T, Kaapa P, Gronlund J, Ekblad U, Helenius H, Kero P et al. Maternal
magnesium sulfate treatment is associated with reduced brain-blood ow perfusion in preterm infants. Crit Care Med 2001; 29(7): 14601465.

Journal of Perinatology (2014), 192 196

Mg and CBF velocities

EY Imamoglu et al

196
42 Pranskunas A, Vellinga NA, Pilvinis V, Koopmans M, Boerma EC.
Microcirculatory changes during open label magnesium sulphate infusion
in patients with severe sepsis and septic shock. BMC Anesthesiol 2011;
11: 12.
43 Schauf B, Becker S, Abele H, Klever T, Wallwiener D, Aydeniz B. Effect of magnesium on red blood cell deformability in pregnancy. Hypertens Pregnancy 2005;
24(1): 1727.
44 Gries A, Bode C, Gross S, Peter K, Bohrer H, Martin E. The effect of intravenously
administered magnesium on platelet function in patients after cardiac surgery.
Anesth Analg 1999; 88(6): 12131219.
45 Mazur A, Maier JA, Rock E, Gueux E, Nowacki W, Rayssiguier Y. Magnesium and
the inammatory response: potential physiopathological implications. Arch Biochem Biophys 2007; 458(1): 4856.
46 Dong JF, Cruz MA, Aboulfatova K, Martin C, Choi H, Bergeron AL et al. Magnesium
maintains endothelial integrity, up-regulates proteolysis of ultra-large von

Journal of Perinatology (2014), 192 196

47

48

49

50

Willebrand factor, and reduces platelet aggregation under ow conditions.

Thromb Haemost 2008; 99(3): 586593.
Shokry M, Elsedfy GO, Bassiouny MM, Anmin M, Abozid H. Effects of antenatal
magnesium sulfate therapy on cerebral and systemic hemodynamics in preterm
newborns. Acta Obstet Gynecol Scand 2010; 89(6): 801806.
Elimian A, Verma R, Ogburn P, Wiencek V, Spitzer A, Quirk JG. Magnesium sulfate
and neonatal outcomes of preterm neonates. J Matern Fetal Neonatal Med 2002;
12(2): 118122.
Kuban KC, Leviton A, Pagano M, Fenton T, Strassfeld R, Wolff M. Maternal toxemia
is associated with reduced incidence of germinal matrix hemorrhage in premature babies. J Child Neurol 1992; 7(1): 7076.
Crowther CA, Hiller JE, Doyle LW, Haslam RR. Australasian Collaborative Trial of
Magnesium Sulphate (ACTOMg SO4) Collaborative Group. Effect of magnesium
sulfate given for neuroprotection before preterm birth: a randomized controlled
trial. JAMA 2003; 290(20): 26692676.

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