Middle East Fertility Society Journal (2016) xxx, xxx–xxx

Middle East Fertility Society

Middle East Fertility Society Journal

www.mefsjournal.org
www.sciencedirect.com

ORIGINAL ARTICLE

Effects of antenatal dexamethasone administration

on fetal and uteroplacental Doppler waveforms in
women at risk for spontaneous preterm birth
Elwani Elsnosy, Omar M. Shaaban, Ahmed M. Abbas *, Heba H. Gaber,
Atef Darwish

Department of Obstetrics & Gynecology, Faculty of Medicine, Assiut University, Assiut, Egypt

Received 15 July 2016; revised 10 September 2016; accepted 26 September 2016

KEYWORDS Abstract Objective: Maternal administration of synthetic corticosteroids is essential to improve

Corticosteroids; fetal lung surfactant production and hasten the fetal lung maturity in women at risk for preterm
Dexamethasone; birth. The current study aimed to investigate the effects of dexamethasone exerted on fetal and
Doppler; uteroplacental circulation as measured by Doppler in pregnancies at risk for preterm birth after
Preterm birth 24 h of its administration.
Materials and methods: A prospectively registered study at www.ClinicalTrials.gov
(NCT02662790) was conducted in Women Health Hospital, Assiut, Egypt, included 50 pregnant
women with singleton pregnancies. Doppler studies were performed on the umbilical artery, fetal
middle cerebral artery (MCA), fetal descending aorta and maternal uterine arteries just before
dexamethasone administration and repeated 24 h after completion of the dexamethasone course.
Results: The mean age of the study group was 27.7 ± 4.5 years. There was a statistically signif-
icant difference between all Doppler indices in umbilical artery, fetal MCA and aorta in comparison
before and 24 h after maternal dexamethasone administration. Also uterine artery Pulsatility index
was significantly different (p = 0.001).
Conclusion: Maternal dexamethasone administration to pregnant women at risk of preterm
labor improves the blood flow of the maternal uterine artery, fetal MCA, descending aorta and
umbilical artery 24 h after its administration.
Ó 2016 Middle East Fertility Society. Production and hosting by Elsevier B.V. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

* Corresponding author at: Women Health Center, Assiut University,

Assiut, Egypt. 1. Introduction
E-mail address: ans1111eg@gmail.com (A.M. Abbas).
Peer review under responsibility of Middle East Fertility Society. Respiratory distress syndrome (RDS) as a consequence of
immature lung development is the principal cause of early
neonatal morbidity and mortality and contributes significantly
Production and hosting by Elsevier to high costs of neonatal intensive care (1).

http://dx.doi.org/10.1016/j.mefs.2016.09.007
1110-5690 Ó 2016 Middle East Fertility Society. Production and hosting by Elsevier B.V.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: Elsnosy E et al. Effects of antenatal dexamethasone administration on fetal and uteroplacental Doppler waveforms in women at risk
for spontaneous preterm birth, Middle East Fertil Soc J (2016), http://dx.doi.org/10.1016/j.mefs.2016.09.007
2 E. Elsnosy et al.
Maternal administration of synthetic corticosteroids
(betamethasone or dexamethasone) has been used for long
time to improve fetal lung surfactant production and hasten
the fetal lung maturity in women at risk for preterm birth
(2). Corticosteroids also reduce the occurrence of RDS, intra-
ventricular hemorrhage, necrotizing enterocolitis and overall
neonatal mortality in preterm infants (3). No serious side
effects have been reported after administration of corticos-
teroids during pregnancy, but some studies reported reduction
in fetal body movements, fetal breathing movements and heart
rate variation after betamethasone administration (4,5). These
effects are more obvious with betamethasone than dexametha-
sone. Repeated courses of steroids have been associated with
increased risk of fetal growth restriction (6).
Evaluation of fetal well-being with Doppler examination
of blood flow velocity waveforms after maternal corticos-
teroid administration is therefore essential to investigate
the fetal hemodynamic effects of exogenous corticosteroids.
Previous studies showed conflicting results regarding this
important subject and most of them were focusing on the
effect of steroids on pregnancies complicated with intrauter-
ine growth restriction (IUGR) (7–10). Also, most of previ-
ous studies investigated the effect of betamethasone on
fetal and uteroplacental blood flow (4,5,11,12), and few
studies only thoroughly investigated the effect of dexametha-
sone (13).
Thus, the current study aimed to investigate the effects
of dexamethasone exerted on fetal and uteroplacental
circulation as measured by Doppler ultrasonography in
pregnancies at risk for preterm birth after 24 h of its
administration.
2. Materials and methods
2.1. Study setting and design
The current study was a prospective cross sectional registered
study at www.ClinicalTrials.gov (NCT02662790). The study
was conducted in Women Health Hospital, Assiut, Egypt, dur-
ing the period from January to December 2014.
2.2. Study participants
Eligible participants were pregnant women with gestational
age from 24 to 34 weeks and at risk for preterm birth. Gesta-
tional age was calculated according to the date of the last men-
strual period and confirmed by first trimester ultrasound.
Patients at risk of preterm labor to be included were those with
preterm uterine contractions, placenta previa, and mild
preeclampsia. Meanwhile, Patients who were actively in labor,
presented with premature rupture of membranes, intrauterine
growth restriction (IUGR), and those who had received corti-
costeroids in their pregnancies and/or fetuses with suspected
structural abnormalities were excluded from participation.
Women who had any contraindication of corticosteroids
administration had also been excluded.
A written consent has been taken from all participants after
reading the patient information sheet and describing the non-
interventional nature of the study. Assiut Faculty of Medicine
Ethical Review Board approved the study.
Please cite this article in press as: Elsnosy E et al. Effects of antenatal dexamethasone administration on fetal and uteroplacental Doppler waveforms in women at risk
for spontaneous preterm birth, Middle East Fertil Soc J (2016), http://dx.doi.org/10.1016/j.mefs.2016.09.007
2.3. Study intervention
Eligible participants were evaluated through full history taking
and detailed anatomical scan by level II sonographer before
inclusion to confirm their gestational age and exclude any
structural anomalies.
Each woman received the recommended course of corticos-
teroids to induce fetal lung maturity consists of two doses of
12 mg dexamethasone (Dexamethasone 8 ml, Sigma) intra-
muscularly 12 h apart.
Doppler studies were performed just before dexamethasone
administration and repeated 24 h after completion of the dex-
amethasone course using a SonoAce X8 machine (Medison,
Korea) with 3.75 MHz curvilinear transabdominal probe. All
patients underwent Doppler examination by 2 different sono-
graphers (E.E. and A.M.A), both of them are level II experi-
enced sonographers. The second one was completely blinded
to the Doppler results obtained before dexamethasone admin-
istration by the first sonographer to exclude any operator bias.
Doppler examination was done with the fetus in a quiet
state, in the absence of fetal movements and fetal breathing
movements. The angle of insonation was optimized to be as
low as possible, never exceeding 45°. The sweep speed was
2.5 cm /s and the pulse repetition frequency ranged from 3.5
to 5.5 kHz. The Doppler spectrum was recorded during mater-
nal voluntary apnea.
Blood flow velocity waveforms were obtained from the
umbilical artery, fetal middle cerebral artery (MCA), fetal
descending aorta and maternal uterine arteries. Spectral pulsed
wave Doppler analysis was done after that; RI and PI were cal-
culated for each vessel. The formulas used for PI and RI were
PI = (S-D)/mean and RI = (S-D)/S respectively, when S is
the peak Doppler frequency shift and D is the minimum. At
least 5 uniform waveforms of the spectrum were recorded
and analyzed.
Blood flow velocity waveforms were recorded from the
umbilical artery in the free floating mid-portion of the umbil-
ical cord (14). Doppler signals were registered from the fetal
MCA in its proximal third. For an accurate measurement,
the fetal head was in the transverse plane. The MCA vessels
were located with color Doppler ultrasound overlying the ante-
rior wing of the sphenoid bone near the base of the skull (15).
Doppler signals were obtained from the uterine arteries in
the region of the lower uterine segment. Insonation of the uter-
ine artery was done at its crossover iliac artery (16). Velocity
waveforms from the fetal descending aorta were recorded at
the lower thoracic level just above the diaphragm, keeping
the angle of insonation of the Doppler beam below 45°.
The primary outcome of the study was detection of
changes in Doppler indices before and after dexamethasone
administration.
2.4. Statistical analysis
Collected data were reviewed and analyzed using the Statistic
Package for Social Science Version 18 (SPSS 18.0) for
windows. Qualitative data were expressed as frequency and
percentage. Chi-square (X2) test was used to examine the
relation between qualitative variables. Quantitative data were
presented in terms of mean and standard deviation, and 2 inde-
Antenatal dexamethasone administration on fetal and uteroplacental Doppler waveforms 3

pendent samples t-tests were used to compare them. The level

Table 2 Fetal and uteroplacental Doppler indices before and
of significance was taken at p-value of 60.05.
24 h after dexamethasone administration.

3. Results Doppler indices Before 24 h after p-

The study had included 50 participants at risk of preterm birth
for different reasons. We anticipated the risk of preterm birth
on the basis of preterm uterine contractions (n = 33), placenta
previa (n = 13) and mild preeclampsia (n = 6). The mean age
of the study group was 27.7 ± 4.5 years. At the time of dexam-
ethasone administration, mean gestational age was 30.9
± 2.7 weeks, and in 17 (34%) pregnancies, gestational age
was <30 weeks.
Twenty-three (46%) of the study participants delivered
within 4 days after receiving the full dose of dexamethasone.
Eleven (22%) women delivered after 5–7 days, nine (18%)
women delivered between 8 and 15 days and finally seven
(14%) women who continued pregnancy more than 2 weeks
after end of the course. Cesarean sections were performed in
35 (70%) patients. Only one stillborn was delivered vaginally
due to placental abruption in association with preeclampsia.
The demographic data and data on the outcomes of pregnan-
cies are presented in Table 1.
There was a statistically significant difference between all
Doppler indices in umbilical artery, fetal MCA and aorta in
comparison before and 24 h after maternal dexamethasone
administration. Also uterine artery PI was significantly differ-
ent before and 24 h after dexamethasone, while no significant
difference in uterine artery RI (Table 2).
4. Discussion
The current study evaluated the different Doppler indices of
pregnant women in high risk of fetal prematurity before and
24 h after dexamethasone administration. The study showed
beneficial effect of dexamethasone administration on 50 preg-
nant women with gestational age ranged from 24 to 34 weeks
as evident by the decrease in the Doppler indices of umbilical
artery, fetal descending aorta, MCA and uterine artery. All
study participants were in high risk of preterm birth as they
either are in a threatened preterm labor or need early termina-
Table 1 Demographic characteristics and neonatal outcome
of the study participants.
Maternal characteristics
Age (years); mean ± SD (Range) 27.7 ± 4.5 (18–35)
Parity; median (Range) 4 (0–8)
Gestational age (weeks + days)
At examination; mean ± SD (Range) 30.9 ± 2.7
(24 + 0 to 33 + 5)
At delivery; mean ± SD (Range) 31.3 ± 2.9
(24 + 3 to 36 + 3)
Neonatal characteristics
Birth weight (gm); mean ± SD 1235.3 ± 750.72
Referral to PCU; n (%) 30 (60)
1 min Apgar score < 7; n (%) 33 (66)
5 min Apgar score < 7; n (%) 22 (44)
Female gender; n (%) 34 (68)
PCU; pediatric care unit.
Dexamethasone Dexamethasone Value
Mean ± SD Mean ± SD
Umbilical artery PI 1.09 ± 0.4 1.05 ± 0.39 0.001
Umbilical artery RI 0.66 ± 0.14 0.63 ± 0.14 0.001
Fetal aorta PI 1.91 ± 0.44 1.89 ± 0.44 0.040
Fetal aorta RI 0.9 ± 0.55 0.87 ± 0.55 0.001
Fetal MCA PI 2.19 ± 0.72 2.15 ± 0.72 0.001
Fetal MCA RI 0.86 ± 0.12 0.83 ± 0.13 0.001
Uterine artery PI 0.9 ± 0.27 0.87 ± 0.26 0.001
Uterine artery RI 0.56 ± 0.11 0.53 ± 0.11 0.147
MCA; middle cerebral artery, PA; pulsatility index, RI; resistance
index.
Bold values indicate statistical significant difference at <0.05.
tion of pregnancy before age of maturity for maternal indica-
tions as preeclampsia.
Umbilical artery Doppler indices showed statistically signif-
icant reduction 24 h after dexamethasone administration. Our
results agreed with Wallace and Baker study who reported an
association between betamethasone treatment and decreased
placental vascular resistance as reflected by waveforms
obtained from umbilical artery (17). This is similarly agreed
by Nozaki et al. who found a reduction in the umbilical artery
PI within 24 h following antenatal corticosteroid therapy (10).
Two studies on growth-restricted preterm fetuses demon-
strated no effects of betamethasone on PI in the umbilical
artery (7,8). This may be due to difference in study population
as they included only pregnant women with IUGR, while in
our study included all women at risk of preterm birth. The vas-
cular distribution of blood flow is variable in the IUGR fetuses
as compared with normal growth fetuses.
With regard to fetal descending Aorta Doppler indices of
our study population demonstrated significant reduction in
the vascular resistance after dexamethasone administration.
Up to our knowledge, the current study was the first to
describe a decrease in PI and RI of the descending Aorta
24 h after antenatal dexamethasone administration. Senat
and Ville examined the effect of steroids on blood flow wave-
forms in IUGR fetuses and found no significant changes of PI,
RI values in the different vessels during the dexamethasone
course (7). PI and RI recorded from descending aorta were
similar before, 24–48 h and 4–7 days after first injection was
given to the mother. We could not cite any study that test
the Doppler flow in descending aorta of healthy but premature
fetuses.
Middle cerebral artery was also examined in our study
before and 24 h after dexamethasone administration. MCA
Doppler indices decreased after the treatment. These findings
are in agreement with the results of Chitrit et al. who observed
a transient and significant decrease in fetal MCA (PI, RI) after
maternal dexamethasone administration (13). However some
studies disagree with our results as Senat and Ville and Wijn-
berger et al., but they were on growth-restricted preterm
fetuses; no effect was found from betamethasone on PI in fetal
MCA (7,8). In the latter study circulation in fetuses was stud-
ied for up to 14 days, indicating that placental insufficiency

Please cite this article in press as: Elsnosy E et al. Effects of antenatal dexamethasone administration on fetal and uteroplacental Doppler waveforms in women at risk
for spontaneous preterm birth, Middle East Fertil Soc J (2016), http://dx.doi.org/10.1016/j.mefs.2016.09.007
4 E. Elsnosy et al.
was probably not severe enough to indicate early delivery.
Moreover, Senat and Ville examined the effect of steroids on
blood flow waveforms in IUGR fetuses and found no signifi-
cant changes of PI, RI values in the different vessels after dex-
amethasone course. However, the MCA PI showed a trend to
decrease within the course and after the treatment was
stopped. The trend might be explained by either the physiolog-
ical decrease in resistance in the fetal brain with gestation that
expected to be even more marked in IUGR fetuses, or the early
sign of redistribution of the blood flow (7).
There was statistical significant reduction in the uterine
artery Doppler indices before and 24 h after dexamethasone
administration in the present study. These findings are in
agreement with data published by Chitrit et al. who observed
similar transient and significant decrease in uterine artery PI
and RI after maternal dexamethasone administration in
healthy fetus (13). Also, Wallace and Baker reported an asso-
ciation between betamethasone treatment and decrease in uter-
ine artery flow velocity waveforms in their study (17).
However, Thuring et al. reported that there was no significant
influence of betamethasone therapy on Doppler indices in uter-
ine circulation in pregnancies with imminent preterm delivery
(18).
Ballard and Ballard analyzed the pharmacokinetics of dex-
amethasone and betamethasone and found that the two rec-
ommended regimens should produce only minor differences
in the circulating level of glucocorticoid activity in the treated
fetus, with lower peak levels for dexamethasone but a some-
what longer time of elevated activity (19). There is no evidence
that these effects on blood flow are harmful to the fetus, how-
ever more concerning are data suggesting a neurotoxic effect of
dexamethasone.
A study on human placentas by Clifton et al. showed that
the mechanism behind dexamethasone-induced vasodilatation
might be an endothelium independent mechanism, as they did
not find any involvement of endothelium-derived products
such as prostaglandin I2 and nitric oxide (20). Wijnberger
et al. concluded that the underlying mechanisms responsible
for the alterations in fetoplacental circulation after antenatal
betamethasone administration are not clear (8).
Derks et al. reported in their experimental studies that fetal
sheep showed increased blood pressure after injection of
betamethasone (21). The human fetus in a similar way possibly
increases its blood pressure, and this could explain the
improved fetoplacental perfusion. Also, reduced placental
resistance as a result of nitric oxide mediated vasodilatation
due to increased secretion of placental corticotropin releasing
hormone may be another explanation (22). The difference
between normally grown and growth-restricted fetuses in their
hemodynamic response could be explained by decreased fetal
nitric oxide synthesis in IUGR (23).
One of the limitations of the current study that umbilical
artery PH was not measured after delivery for accurate assess-
ment of neonatal outcome due to low facilities in our hospital,
so we depended only on Apgar score. The second limitation
that we could not match the Doppler results with the gesta-
tional age was due to small sample size of included study par-
ticipants. Further studies with larger sample size are needed to
confirm our results.
In conclusion, maternal dexamethasone administration to
pregnant women at risk of preterm labor improves the blood
flow of the maternal uterine artery, fetal MCA, descending
Please cite this article in press as: Elsnosy E et al. Effects of antenatal dexamethasone administration on fetal and uteroplacental Doppler waveforms in women at risk
for spontaneous preterm birth, Middle East Fertil Soc J (2016), http://dx.doi.org/10.1016/j.mefs.2016.09.007
aorta and umbilical artery 24 h after its administration. The
beneficial effect of its administration is consistent regardless
of the gestational age and fetal weight.
Conflict of interest
The authors declare that they have no conflict of interest.
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Please cite this article in press as: Elsnosy E et al. Effects of antenatal dexamethasone administration on fetal and uteroplacental Doppler waveforms in women at risk
for spontaneous preterm birth, Middle East Fertil Soc J (2016), http://dx.doi.org/10.1016/j.mefs.2016.09.007