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Effects of antenatal corticosteroids on maternal
serum indicators of infection in women at risk for
preterm delivery: A randomized trial comparing
betamethasone and dexamethasone
Azar Danesh, Mohsen Janghorbani, Shila Khalatbari
Department of Obstetrics and Gynecology, Medical School, Isfahan University of Medical Sciences, Department of Epidemiology and
Biostatistics, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran
Objective: To compare the eect of betamethasone and dexamethasone on maternal white blood cell (WBC) and dierential count,
erythrocyte sedimentation rate (ESR), Apgar score, maternal and fetal plasma glucose and length of admission to delivery, gestational
age at delivery in women at risk of preterm labor (PTL). Study Design: Two hundred and forty pregnant women at risk for PTL
with intact membranes or preterm premature rupture of the membranes (PPROM) were randomly allocated to receive either two
intramuscular injections of 12mg betamethasone at 24-h intervals or 4 injections of 6mg dexamethasone at 12-h intervals. Blood
tests for WBC and dierential count, ESR and fasting plasma glucose were drawn before betamethasone or dexamethasone injection
and after injection every 24 h for two days. Pregnancy outcome was assessed as Apgar score, fetal plasma glucose and length of
gestation. Result: In the preterm delivery group with intact membranes, no signicant dierences were found between the two
groups in the maternal serum indicators of infection. Te mean gestational age at delivery, 1-and 5-min Apgar score were higher in
the dexamethasone group than in the betamethasone group. In the PPROM group, a signicant rise in WBC count was occurred
(12.4 cells/mm
3
vs. 10.5 cells/mm
3
, P < 0.001), none of the other maternal serum indicators of infection and outcome variables
showed signicant dierences between the dexamethasone and betamethasone groups. Conclusions: Dexamethasone compared
to betamethasone signicantly increased WBC count in women with PPROM, but in women at risk of PTL with intact membranes
none of the maternal serum indicators of infection showed signicant dierences.
Key words: Betamethasone, dexamethasone, ecacy, gestational age. preterm premature rupture of membrane, pregnancy,
preterm
Address for correspondence: Prof. Mohsen Janghorbani, Department of Epidemiology and Biostatistics, School of Public Health, Isfahan University
of Medical Sciences, Isfahan, Iran. E-mail: janghorbani @ hlth.mui.ac.ir
Received: 16-03-2012; Revised: 16-08-2012; Accepted: 27-08-2012
betamethasone or dexamethasone.
[5-7]
Both are the
most potent agents in terms of their efect on the
fetus, and both have minimal side efects compared
with their benefts.
[8]
Although, they both have the
same biological activity and adverse efects, there
is considerable variation between countries as to
whether dexamethasone or betamethasone is preferred
by health practitioners, with many likely reasons
for these diferences including availability and cost
(dexamethasone is cheaper than betamethasone),
[9,10]
the impact of inconsistent fndings from observational
studies
[11]
and the infuence of opinion leaders.
[12]
A
Cochrane review published in 2008
[13]
that included
ten trials indicated that dexamethasone appears to
decrease the incidence of intraventricular hemorrhage
(IVH) compared to betamethasone. No statistically
significant differences were seen for respiratory
distress syndrome, bronchopulmonary dysplasia,
severe IVH, preventricular leukemia, perinatal death
or mean birth weight. The results for biophysical
parameters have been inconsistent,
[13,14]
but most
INTRODUCTION
Preterm birth with or without intact membranes
occurs in 5%-13% of all pregnancies, and intrauterine
infection is a major threat to the preterm fetus and
may increase neonatal morbidity and mortality.
[1]
The link between infection and preterm labor has
long been recognized and at least 40% of preterm
births are associated with intrauterine infection.
[2]
Antenatal corticosteroid therapy has become a
standard management of women with preterm
labor.
[3-6]
The recommended corticosteroids are either
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Danesh, et al.: Effects of betamethasone vs. dexamethasone on pregnancy outcome
Journal of Research in Medical Sciences | October 2012 | 912
studies have reported no clinically important diferences.
The two most serious side efects of corticosteroid therapy
are suppression of the hypothalamic-pituitary-adrenal
axis, and predisposition to infection. Neither has been
fully evaluated with specifc reference to preterm labor.
Nonetheless, the evidence of efects of dexamethasone and
betamethasone on maternal indicators of infection is not
sufcient to support dexamethasone or betamethasone,
so the drug of choice for antenatal corticosteroid therapy
is currently a topic of debate.
In the present trial, we compared the effects of the
betamethasone and dexamethasone on maternal white
blood cell (WBC) and differential count, erythrocyte
sedimentation rate (ESR), maternal and fetal plasma
glucose (PG), Apgar score, and length of gestation in
women at risk of preterm birth with or without intact
membranes.
MATERIALS AND METHODS
A randomized trial was conducted to evaluate the efects
of betamethasone and dexamethasone on maternal WBC
and diferential count, ESR, Apgar score, maternal and fetal
PG and length of gestation in women at risk for preterm
birth with or without intact membranes. The study protocol
was approved by the Institutional Review Board of Isfahan
University of Medical Sciences, Iran (project number
389484). Writen informed consent was obtained.
Participants
Pregnant low parity women between 24 and 34 weeks
gestation, who were hospitalized because they were at
risk for preterm birth with or without intact membranes,
were recruited from the obstetrics and gynecology
departments of Isfahan University of Medical Sciences,
Iran between February and November 2011. The inclusion
criteria were low parity pregnant women 16-45 years of
age, gestational age 2434 complete weeks, low Bishop
Score ( 5), nonsmoker, high risk of preterm labor (PTL)
either with intact membranes or preterm premature
rupture of membranes (PPROM) that justifed preventive
corticosteroid therapy, a singleton fetus, residence in
Isfahan, and hospitalization planned to last at least 3 days.
PTL was diagnosed in the presence of uterine contractions of
four in 20 min or eight in 60 min plus progressive change in
the cervix, cervical dilatation greater than 1 cm and cervical
efacement of 80% or greater.
[15]
PPROM was diagnosed in
the presence of a gush of fuid from the vagina followed
by persistent, uncontrolled leakage, or polling of fuid on
speculum examination with positive nitrazine and Fern
testing.
[16]
Women were excluded if they had evidence of
fetal distress, substantial abnormalities in neurological,
psychiatric, cardiac, endocrinological, hematologic,
hepatic, renal, or metabolic functions as determined by
history, physical examination and blood screening tests.
Other exclusion criteria were signs of infection (maternal
temperature >37.5C), positive urine culture and vaginal
bleeding due to placenta previa or placental abruption.
Randomization scheme
A total of 260 pregnant women at risk for PTL with either
intact membranes or PPROM were eligible for study.
Twenty women were excluded because they declined to
participate or did not meet the inclusion criteria. In all,
240 pregnant women were initially enrolled in the study,
frst treatment began with magnesium sulfate according to
ACOG (American College of Obstetrics and Gynecology)
commitee protocol
[17]
, then 120 women at risk for preterm
delivery with intact membranes and 120 women with
PPROM completed treatment without interruption and
continued in the study until delivery. Women were
randomized with a list of computer-generated numbers,
and the group assignments were concealed in an opaque
sealed envelope until just before entry into the study.
The first treatment group received two intramuscular
injections of 12 mg betamethasone at 24-h intervals as
betamethasone sodium (produced by local pharmaceutical
company Exir Pharmaceutical Lab., Tehran, Iran). The
second group received four intramuscular injections of
6 mg dexamethasone at 12-h intervals as dexamethasone
phosphate (produced by local pharmaceutical company
Iranhormone Pharmaceutical Lab., Tehran, Iran). At
enrolment, pretreatment evaluation in all women consisted
of demographic data, complete medical history and physical
examination. The allocation scheme is shown in Figure 1.
At enrollment, gestational age was determined by obstetric
estimates from the last menstrual period, standard obstetric
parameters and ultrasonography. Mean age of the women
(SD) was 27.2 (5.4) years (range 16 to 43 years).
Evaluation
Before corticosteroids were injected, blood was drawn for
peripheral WBC and diferential count, ESR, hemoglobin
(Hb) and maternal plasma glucose (PG). Blood was drawn
again for the same tests at 24 and 48 h. Hemoglobin and
WBC count were determined with a Coulter counter,
and ESR was determined by the conventional mm/s
sedimentation rate. Plasma glucose was measured with the
glucose oxidase method. All the women who participated in
the study were followed until delivery. Afer delivery cord
blood was drawn for fetal plasma glucose measurement.
Statistical analysis
Outcomes in the betamethasone and dexamethasone groups
were compared with Students t-test for independent samples
and analysis of variance with repeated measures over time;
comparisons between baseline and post-treatment periods
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Danesh, et al.: Effects of betamethasone vs. dexamethasone on pregnancy outcome
Journal of Research in Medical Sciences | October 2012 | 913
Table 1: Characteristics of pregnant women by treatment group at baseline
Characteristics Treatment group Difference (95% CI)
Dexamethasone mean (SD) Betamethasone mean (SD)
Preterm delivery with intact membranes
Number 60 60 -
Maternal age (years) 28.1 (5.3) 26.9 (5.7) 1.2 (-0.9, 3.1)
Gestational age at registration (weeks) 30.6 (2.3) 30.9 (2.8) -0.3 (-1.2, 0.6)
Pulse rate (no.) 83.1 (4.9) 84.4 (4.8) -1.3 (-3.1, 0.4)
Temperature (C) 36.9 (0.2) 36.9 (0.2) 0.0 (-0.07, 0.08)
Fasting plasma glucose (mg/dL) 96.5 (13.4) 97.4 (19.6) -0.9 (-7.0, 5.2)
WBC (cells/mm
3
) 10.31 (1.90) 10.38 (2.72) -0.07 (-0.09, 0.08)
Neutrophil count (%) 70.3 (7.6) 72.8 (7.8) -2.5 9-5.3, 0.2)
Hemoglobin (g) 12.3 (1.2) 12.1 (1.1) 0.2 (-0.2, 0.6)
Platelet count ( 10
3
/mm
3
) 210.7 (46.5) 202.0 (51.7) 8.7 (-9.1, 26.5)
Erythrocyte sedimentation rate (mm/h) 21.6 (13.1) 26.3 (14.6) -4.7 (-9.8, 0.5)
Systolic blood pressure (mm Hg) 98.7 (5.9) 98.8 (7.7) -0.1 (-2.6, 2.3)
Diastolic blood pressure (mm Hg) 66.2 (6.1) 66.0 (6.4) 0.2 (-2.0, 2.5)
Preterm premature rupture of membranes
Number 60 60 -
Age (years) 26.7 (5.2) 27.1 (5.3) -0.4 (-2.2, 1.6)
Gestational age at registration (weeks) 30.1 (2.7) 30.0 (2.8) 0.1 (-0.9, 1.1)
Pulse rate (no.) 82.3 (5.0) 83.1 (5.0) -0.8 (-2.5, 1.0)
Temperature (C) 36.9 (0.2) 36.9 (0.2) 0.0 (-0.09, 005)
Fasting plasma glucose (mg/dL) 95.0 (12.7) 94.3 (12.5) 0.7 (-4.0, 5.3)
WBC (cells/mm
3
) 10.60 (2.14) 9.39 (2.31) 1.21 (0.4, 2.0)**
Neutrophil count (%) 72.0 (8.3) 71.6 (9.3) 0.4 (-2.8, 3.5)
Hemoglobin (g) 11.9 (1.1) 12.1 (1.5) -0.2 (-0.6, 0.3)
Platelet count (10
3
/mm
3
) 203.3 (50.6) 205.4 (57.3) -2.1 (-21.6, 17.3)
Erythrocyte sedimentation rate (mm/h) 29.0 (22.1) 21.9 (12.4) 7.1 (0.5, 13.5)*
Systolic blood pressure (mm Hg) 101.0 (7.7) 99.3 (7.7) 1.7 (-1.1, 4.4)
Diastolic blood pressure (mm Hg) 68.1 (5.9) 65.8 (5.9) 2.3 (0.2, 4.4)*
*P < 0.05, **P < 0.01. CI=Confdence interval; WBC=White blood cell count
Figure 1: Design of the study
Assessed for eligibility (n=260)
Randomized (n=120)
Completed (n=60)
Excluded (n=20)
Not meeting inclusion criteria
(n=15)
Refused to participate (n= 5)
Enrollment
Completed (n=60)
Allocated to
betamethasone (n=
60)
Received allocated
Preterm labor with intact
membranes (n=120)
Premature rupture of
membranes (n=120)
Randomized (n=120)
Allocated to
dexamethasone (n=
60)
Received allocated
Allocated to
betamethasone (n=
60)
Received allocated
Allocated to
dexamethasone (n=
60)
Received allocated
Completed (n=60) Completed (n=60)
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Danesh, et al.: Effects of betamethasone vs. dexamethasone on pregnancy outcome
Journal of Research in Medical Sciences | October 2012 | 914
were done with pairedStudents t-tests. Comparisons
between proportions were done with the chisquared
or Fishers exact test. All analyses were done with SPSS
version 18 sofware for Windows