<=
/td>
![](3D"YahyaNMJ64No4Page532_files/image003.png")
![](3D"YahyaNMJ64No4Page532_files/image005.png")
Effect of Antenatal
Corticosteroids in Late Preterm Delivery on Neonatal Respiratory Morbidity:=
A
Randomized Controlled Trial
*Anisah Yahya1,
![](3D"YahyaNMJ64No4Page532_files/image007.png")
Background: The use of
antenatal corticosteroids beyond 34 weeks of gestation to prevent certain
neonatal complications remains a debate. This study sought to determine the
effect of the use of antenatal corticosteroids in late preterm delivery on
neonatal morbidity.
Methodology: It was a randomized double-blind pla=
cebo
and active-controlled multi-arm trial. There were two study groups and one
control group. It was conducted at the Department of Obstetrics and Gynaeco=
logy
and the Department of Paediatrics of Ahmadu Bello University Teaching Hospi=
tal
Zaria, Nigeria. Pregnant women at 34 weeks to 36 weeks 6 days of gestation
scheduled for elective delivery or who had emergency delivery were recruited
for the study.
The first st=
udy
group had 2 doses of 12mg intramuscular
dexamethasone and the second study group had 2 doses of 12mg
betamethasone. The control group h=
ad 2
doses of a placebo. The primary outcome was the incidence of respiratory
distress syndrome evidenced by tachypnoea with grunting, recession, or nasal
flaring with diffuse reticulogranular infiltrat=
e on
X-ray or respiratory distress requiring the need for respiratory support by=
72
hours of age. Secondary outcome measures included the need for neonatal
resuscitation at birth, admission into the Special Care Baby Unit/Neonatal
Intensive Care Unit, transient tachypnoea of the newborn, and apnoea.
Results: A total of 138 mothers and 146 prete=
rm
neonates were included. A pairwise analysis was done to test for differences
between the groups. There was no difference in the incidence of respiratory
distress syndrome between the groups. However, the need for neonatal resuscitation was significantly higher (RR: 7.0;
CI: 2.49-19.4; p =3D <0.001) in the placebo group when compared to the
betamethasone group and also significantly higher (RR:4.0; CI: 1.86-26.03; =
p=3D
0.01) in the placebo group when compared to the dexamethasone group.
Conclusion: Antenatal corticosteroids may decrea=
se
the need for neonatal resuscitation at birth in late preterm neonates.
Funding: The research was funded by the Terti=
ary
Education Trust Fund (TETFUND) of Nigeria.
Trial
registration: ClinicalTrial.gov, NCT03446937
Keywords: Antenatal Corticosteroids, Late Pret=
erm
Delivery, Neonatal Morbidity.
=
*Corresp= ondence: Anisah Yahya. Department of Obstetrics and Gynecology, College of Medical Sciences, Ahmadu Bello University/Ahmadu Bello University Teaching Hospital, Zaria, Nigeria Email: = ayahya@abu.edu.ng
This is an open access journal, and articles are distributed und=
er
the terms of the Creative Commons Attribution-Non-Commercial-Share Alike 4.0
License, which allows others to remix, tweak, and build upon the work
non-commercially, as long as appropriate credit is given and the new creati=
ons
are licensed under the identical terms.
How
to cite this article: Yahya A, Sul=
ayman
HU, Abdulkadir I, Lawal BB. Effect of Antenatal Corticosteroids in Late Pre=
term
Delivery on Neonatal Respiratory Morbidity: A Randomized Controlled Trial. =
Niger Med J 2023; 64 (4):532-544. Accep=
ted:
July 5, 2023. Published: September 21, 2023.
![](3D"YahyaNMJ64No4Page532_files/image009.png")
Preterm birt=
h is a
significant cause of neonatal morbidity and mortality. The use of antenatal
corticosteroids before 34 weeks of gestation has been proven to prevent
respiratory distress syndrome and other morbidities in neonates. [1]
However, limited evidence is available for its use in the late preterm peri=
od. [2,
3]
Respiratory
distress syndrome is one of the most important causes of neonatal morbidity=
and
mortality in preterm births. Other causes of neonatal morbidity and mortali=
ty
in preterm neonates include intraventricular haemorrha=
ge,
sepsis, periventricular leucomalacia, and necro=
tizing
enterocolitis. In preterm neonates, surfactant insufficiency, immaturity, a=
nd
poor lung development result in respiratory distress in preterm infants. As
gestation advances, chances of survival improve due to the increasing matur=
ity
of the respiratory system. Even though black neonates are said to have lower
rates of respiratory distress syndrome compared to non-black neonates,
Even
though adequate fetal lung maturation for survival is expected to be achiev=
ed
by 34 weeks of gestation, neonatal and childhood complications are still co=
mmon
in preterm neonates delivered after 34 weeks of gestation when compared to
those delivered at term. [6, 7]This led to the recommendation by=
the
National Institute Of Child Health And Hum=
an
Development during a workshop in 2005 to direct research to evaluate
infants who are born between 34- and 36 weeks gestation, especially with re=
gard
to the benefits of the use of antenatal corticosteroids in the population. =
[8]
This study s=
ought
to determine the effect of antenatal corticosteroids on neonatal respiratory
distress syndrome and other neonatal complications in women at risk of late
preterm delivery in our clinical setting.
Trial Design=
The study wa=
s a
randomized double-blind placebo and actively controlled multi-arm trial.
Pregnant women at risk of late preterm delivery or scheduled for delivery in
the late preterm period were categorized into three groups. There were two
study groups and one control group.
Participants=
Pregnant wom=
en at
34 weeks 0 days to 36 weeks 6 days of gestation and a probability of delive=
ry
in the late preterm period irrespective of diagnosis including women with
medical conditions were recruited for the study. Probability of delivery is=
defined
as the presence of uterine contractions and cervical effacement of ≥ =
80%,
preterm labor which was defined as uterine
contractions and cervical dilatation of 3cm, and premature rupture of membr=
anes
which was defined as evidence of liquor drainage by the bedside.
Also, pregna=
nt
women scheduled for delivery in the late preterm period irrespective of
indication and route of delivery were recruited.
Women with u=
nsure
date, chorioamnionitis, foetal distress, and foetal congenital anomalies we=
re
excluded from the study. Women who also had antenatal corticosteroids during
the index pregnancy were excluded from the study. Also, women that carried
their pregnancy beyond 36 weeks 7 days (term) and those that had intrauteri=
ne
foetal death were excluded from the analysis.
Gestational =
age
was calculated from the date of the last menstrual period or early scan (be=
fore
20 weeks of gestation).
The study was
conducted between February 2018 and May 2019 at the Department of Obstetrics
and Gynecology and the Department of Paediatrics
Ahmadu Bello University Teaching Hospital, Shika, Nigeria. Recruitment was
stopped when the desired sample size was achieved.
Intervention=
The first st=
udy
group received 2 doses of 12mg intramuscular
dexamethasone sodium phosphate given 12 hours apar=
t.
(Produced by Taizhou Overseas International Ltd. 126-128 Qingnian
Road Jiaojiang, Taizhou, Zhejiang, China). This=
was
available as an already constituted clear liquid form. A
total of 3ml was given per dose.
The second s=
tudy
group received 2 doses of 12mg of intramuscular betamethasone sodium phosph=
ate given
12 hours apart (USP 12601, CAT No 1068004, Lot: R004E0, Twin brook Pkwy,
Rockville MD, +1-301-881-0666). This was available in powder form and
constituted in batches. The constituted drug appears in a clear liquid form=
. A
total of 3ml was given per dose. The constituted drug was stored for a maxi=
mum
of 120 days in the refrigerator according to the manufacturer’s instruction=
s.
The control =
group
received 2 doses of intramuscular water for injection as a placebo given 12
hours apart (Produced by Juhel Pharmaceutical L=
imited,
Nigeria). A total of 3ml was given per dose.
All drugs were constituted and dispensed by a research assistant f=
rom
the research unit of the pharmacy department of Ahmadu Bello University
Teaching Hospital in sterile syringes for immediate administration. All dru=
gs
were the same in appearance and volume.
Any woman
who has had at least one dose of the intervention is considered to have had=
an
intervention.
Outcome meas=
ures
Primary outc=
ome
measure:
Respiratory
Distress:
(a) Tachypnoea with grunting, recessio=
n, or
nasal flaring with diffuse reticulogranular
infiltrate on X-ray.
(b)
Respiratory distress requiring=
the
need for respiratory support by 72 hours of age and will consist of one or =
more
of the following:
Requirement for intranasal oxygen for ≥ 4 ho=
urs
Requirement for Bubble Continuous Positive Airway
Pressure.
Secondary
outcome measures:
1. Transient
tachypnoea of the newborn: Respiratory distress resolved within 72 hours of=
life without
diffuse reticulogranular infiltrate.
2. Admission=
into
Special Care Baby Unit (SCBU)/Neonatal Intensive Care Unit (NICU):
Stay in the
SCBU/NICU for more than 12 hours within the first 72 hours of life excluding
admission after discharge. The period of observation is not considered as a=
dmission.
(All preterm neonates are routinely taken to the SCBU for observation
immediately after delivery.)
3. Apnoea: an unexplained episode of cessation of breathing for 20 seconds or longer, or<= o:p>
a shorter
respiratory pause associated with bradycardia, cyanosis, pallor, and/or mar=
ked
hypotonia.
4. Need for
resuscitation at birth: Failure of the newborn to cry and/or initiate
spontaneous breathing at birth. To be determined by skilled birth attendants
who conduct the delivery.
5. Neonatal =
hypoglycaemia:
Blood glucose level less than 2.2mmol/L at 3 hours after delivery.
6. Neonatal
sepsis: Hypothermia or pyrexia and clinical evidence of sepsis in any
organ/system.
7. Neonatal =
death.
8. Maternal
sepsis: Clinical evidence of endometritis characterized by pyrexia ≥ =
38.0
sub-involution of the uterus and foul-smelling lochia.
Sample
size
The sample s=
ize
for each group was determined by using the statistical formula for comparis=
on
of proportions as follows:
n=3D 1/ ((1-=
f)) ×
(2×〖(Z_α+Z_β)
〗2×P×(1-P))/〖
Where n =3D =
minimum
sample size
P0=3D the pr=
oportion
of participants in the control group that was expected to develop any
morbidity. A=
study
by Porto et al in Brazil reported that up to 23% (0.23) of late preterm
neonates developed some form of respiratory morbidity. Thus, this was used =
for
the calculation of the sample size for this study.
P1 =3D the
proportion of participants in the experimental group that was expected to
exhibit the
outcome of
interest which is respiratory morbidity. For the purpose of this study, a
reduction to 10% (0.10) was considered clinically significant in this study=
.
Zα =3D =
was
determined from a statistical table based on the value of the level of
significance. For
this study, =
it was
set at 0.05. Therefore, Zα=3D 1.96.
Zβ =3D =
was
determined from a statistical table based on the acceptable power of compar=
ison
between the 2
groups. For this study, a power of 80% (0.80) was used, therefore Zβ=3D
0.84.
f =3D was the
proportion of study participants who are expected to be lost to follow up. =
For
this
study f =3D =
10%
(0.1)
n =3D 49.1
Each group w=
as
rounded up to 50.
Randomization
The WINPEPI =
R
version 11.65 software was used to generate the table of random numbers.
The table of
random numbers was developed and kept with the research unit of the pharmac=
y
department, =
Ahmadu
Bello University Teaching Hospital, where the study drugs were kept and
dispensed for use once patients were recruited for the study. The randomiza=
tion
code was only made available to the principal investigator after the comple=
tion
of the trial for data analysis.
Patients who
fulfilled the inclusion criteria were enrolled by the team on call or manag=
ing
team as they presented to the hospital. After obtaining written consent, the
participants were requested to pick one of the brown envelopes that contain=
ed
the randomization number. A proforma was then filled out for the participan=
ts
indicating the randomization number. The randomization number was taken to =
the
pharmacy unit by the attending staff where the drugs were dispensed for
administration to the participants.
Blinding
All drugs we=
re
constituted and dispensed by a research assistant from the research unit of=
the
pharmacy
department of Ahmadu Bello University Teaching Hospital in sterile syringes=
for
immediate administration. All drugs were exactly the same in appearance and
volume which was 3ml. Each drug was given as 6ml of clear fluid. The princi=
pal
investigator, research assistants, and special care baby unit/neonatal
intensive care unit staff were not aware of the group the women and neonates
belonged to because all drugs appeared exactly the same at the point of
administration.
Statistical
methods
The data obt=
ained
was analyzed using SPSS version 23.0. A pairwise analysis [9] was
done
to determine=
where
the differences exist between the groups. Pairwise analysis (betamethasone vs. placebo, dexamethasone vs. place=
bo,
betamethasone vs. dexamethasone) was done for statistical analysis. =
The
socio-demographic characteristics, reproductive profile, and perinatal
characteristics of the women and their neonates in the group were compared =
with
student t-test for continuous variables, Pearson’s Chi-Square (χ2=
)
test, and Fisher’s test for discrete variables with normal distribution and
Mann-Whitney U test for continuous variables or those with non-normal
distribution. P values for all tests were two-tailed and the level of
significance was defined at 1%. Relative risk with confidence interval was =
used
to determine the effects of corticosteroid treatment on perinatal and mater=
nal
outcomes. Maternal and perinatal characteristics of the participants that w=
ere
statistically significant between the groups were subjected to logistic
regression to determine their effect on the statistically significant outco=
me
measures.
Funding
The study was
funded by the Ahmadu Bello University Zaria Institutional Based Research
(IBR)Tertiary Education Trust Fund (TETFUND) of the Federal Republic of
Nigeria. DAPM/TETFUND/01/12.
However, the
funding body did not participate in the design, implementation, and write-u=
p of
the study.
Ethical appr=
oval
Ethical approval to conduct the study was sought from the Health Rese=
arch
and Ethics Committee of Ahmadu Bello University Teaching Hospital Shika. The
application was reviewed by the committee and permission to conduct the stu=
dy
was given on 07/08/2017 with reference number ABUTHZ/HREC/Y3/2017
(NHREC/10/12/2015; D-U-N-S-No 954524802; ABUTH/HREC/CL/05/).
Recruitment =
During the p=
eriod
of study, a total of 150 pregnant women were randomized for the study. Out =
of
these women, 5 women carried their pregnancies to term, 4 withdrew consent,=
2
were discharged home and subsequently lost to follow up and 1 had intrauter=
ine fetal death. The remaining 138 pregnant women were in=
cluded
in the study. Among these women, there were 6 sets of twins and a set of tr=
iplets.
This gave a total number of 146 neonates in the study. Of these neonates, 48
were exposed to antenatal placebo, 49 were exposed to antenatal betamethaso=
ne
and 49 were exposed to antenatal dexamethasone. (Figure 1.)
![](3D"YahyaNMJ64No4Page532_files/image011.png")
Figure 1: Screening,
Enrollment, Randomization and Follow-up
The baseline characteristics of the participants were similar across =
all
groups. (Tables 1 and 2) All group analyses showed a statistically signific=
ant
difference in both 1-minute and 5-minute APGAR. (Table 2) The betamethasone
group had higher 1minute and 5-minute APGAR when compared to the control gr=
oup
and the difference was statistically significant (p=3D 0.011) for 1-minute =
APGAR
but not significantly different for the 5-minute APGAR (p=3D 0.041) when pa=
irwise
analysis was done. Also, the dexamethasone group had higher 1-minute and
5-minute APGAR when compared to the control group but pairwise analysis sho=
wed
that the difference was not statistically significant (p=3D0.166; p=3D0.499
respectively). There was also no significant difference in the 1-minute and
5-minute APGAR between the betamethasone and dexamethasone groups (p=3D0.29=
6;
p=3D0.255 respectively) following a pairwise analysis. Other characteristic=
s did
not differ significantly between the groups. (Tables 1 and 2)
Table 1: <=
/span>Baseline Characterist=
ics
of Participants
|
=
Maternal
Profile |
=
Frequency
(%) |
=
|
||
|
=
Control =
(n=3D48) |
=
Betamethasone =
(n=3D49) |
=
Dexamethasone =
(n=3D49) |
=
p-value |
|
|
=
Socio-Demographic
Characteristics |
|
|
|
|
|
Mean age (years) |
28.4 ± 5.9 |
28.1 ± 6.3 |
27.7 ± 7.4 |
0.935 |
|
Tribe |
|
|
|
|
|
Hausa |
32 (66.7) |
27 (55.1) |
35 (71.4) |
0.614 |
|
Non-Hausa |
16 (33.3) |
22 (44.9) |
14 (28.6) |
|
|
Level of Education |
|
|
|
|
|
Informal |
3(6.2) |
3 (6.1) |
10 (20.4) |
0.129 |
|
Primary |
15 (31.2) |
21 (42.9) |
17 (34.7) |
|
|
Secondary |
22 (45.8) |
16 (32.7) |
14 (28.6) |
|
|
Tertiary |
8 (16.7) |
9 (18.4) |
8 (16.3) |
|
|
=
Reproductive
Characteristics |
|
|
|
|
|
Median Parity IQR |
1.5(0-3) |
2.0(1-3) |
2.0(1.3) |
0.369 |
|
Gestational Age at Delivery=
|
|
|
|
|
|
34week=
s -
34weeks 6days |
7 (14.6) |
6 (12.2) |
9 (18.4) |
0.131 |
|
35week=
s -
35weeks 6days |
10(20.8) |
14 (28.6) |
9(18.4) |
|
|
36week=
s -
36weeks 6days |
21 (43.8) |
20(40.8) |
23(46.9) |
|
|
37week=
s -
37weeks 6days |
10 (20.8) |
9 (18.4) |
8(16.3) |
|
|
Indication for Trial Entry<= o:p> |
|
|
|
|
|
Pre-eclampsia/eclampsia |
17 (35.4) |
18 (36.7) |
20 (40.8) |
0.776 |
|
Gestational/chronic hypertension |
2 (4.2) |
5 (10.2) |
5 (10.2) |
|
|
Pre-te=
rm labour with intact membrane |
18 (37.5) |
15 (30.6) |
12 (24.5) |
|
|
Ruptur=
ed
membrane |
7 (14.6) |
6 (12.2) |
6 (12.2) |
|
|
Others=
* |
4 (8.3) |
5 (10.2) |
6 (12.2) |
*Others: Hyp=
ocalcemia
in Pregnancy, Colorectal Cancer in pregnancy, Vaso-occlusive crises in
pregnancy, Suspected Macrosomia.
Table
2. Perinatal
Characteristics
|
Perinatal
Characteristics |
Frequency
(percentage) |
|||
|
Control (n=3D48) |
Betamethasone (n=3D49) |
Dexamethasone (n=3D49) |
p-value |
|
|
Mode of De=
livery |
|
|||
|
Vaginal delivery |
16 (33.3)<= o:p> |
26 (53.1)<= o:p> |
16 (32.7)<= o:p> |
0.069 |
|
Caesarean section |
32 (66.7)<= o:p> |
23 (46.9)<= o:p> |
33 (67.3)<= o:p> |
|
|
Dose recei=
ved |
|
|||
|
Complete dose |
33(68.8) |
30(61.2) |
34(69.4) |
0.414 |
|
Incomplete dose |
15(31.2) |
19(38.8) |
15(30.6) |
|
|
Neonatal
Characteristics |
|
|||
|
Sex |
|
|||
|
Male |
23 (47.9)<= o:p> |
20 (40.8)<= o:p> |
21 (42.9)<= o:p> |
0.779 |
|
Female |
25 (52.1)<= o:p> |
29 (59.2)<= o:p> |
28 (57.1)<= o:p> |
|
|
Mean Birth
Weight |
2.5 ± 0.4<= o:p> |
2.5 ± 0.4<= o:p> |
2.3 ± 0.4<= o:p> |
0.630 |
|
Mean APGAR=
at 1
min. |
7.0 ± 2.0<= o:p> |
7.8 ± 0.8<= o:p> |
7.5 ± 1.7<= o:p> |
0.001 |
|
Mean APGAR=
at 5
mins. |
8.4 ± 1.5<= o:p> |
9.0 ± 0.9<= o:p> |
8.6 ± 1.6<= o:p> |
0.001 |
The need for neonatal resuscitation was
significantly higher (RR: 7.0; CI: 2.49-19.4; p =3D <0.001) in the placebo group when compared to the betamethas=
one
group. (Table 3) and also significantly higher (RR:4.0; CI: 1.86-26.03;=
p=3D
0.01) in the placebo group when compared to the dexamethasone group. (Table=
3).
There was no significant difference in both prim=
ary
outcome measures and other secondary outcome measures between the Betametha=
sone
vs. placebo and the Dexamethasone vs. placebo groups (Tables 3).
Table 3: Outcome
measures with Betamethasone vs placebo and Dexamethasone vs placebo
|
Outcome measure |
Betamethasone n=3D49 |
Placebo n=3D48 |
RR(CI) |
p-value |
Dexamethasone n=3D49 |
Placebo n=3D48 |
RR(CI) |
p-value |
|
Primary outcome |
||||||||
|
Respiratory
Distress Syndrome |
0(0) |
1(2.1) |
-* |
-* |
1(2.0) |
1(2.1) |
1.0(0.06-16.89) |
0.98 |
|
Secondary
outcome |
||||||||
|
Need
for neonatal resuscitation |
3(6.1) |
15(31.2) |
7.0(2.49-19.46) |
<0.001 |
5(10.2) |
15(31.3) |
4.0(1.86-26.03) |
0.01† |
|
Transient
tachypnoea |
0(0) |
1(2.1) |
0.5(0.05-4.60) |
0.05 |
0(0) |
1(2.1) |
-* |
-* |
|
Apnoea |
0(0) |
0(0) |
-* |
- * |
0(0) |
0(0) |
-* |
-* |
|
Neonatal
Hypoglycaemia |
4(8.2) |
2(4.2) |
0.5(0.10-2.40) |
0.36 |
7(14.3) |
2(4.2) |
0.5(0.09-2.81) |
0.42 |
|
Special
Care Baby Unit admission |
4(8.2) |
6(12.5) |
1.6(0.52-4.93) |
0.40 |
2(4.1) |
6(12.5) |
1.6(0.42-6.10) |
0.48 |
|
Neonatal
sepsis |
0(0) |
1(2.1) |
-* |
-* |
2(4.1) |
1(2.1) |
1.0(0.94-1.02) |
0.31 |
|
Neonatal
death |
0(0) |
0(0) |
-* |
-* |
0(0) |
0(0) |
-* |
-* |
|
Maternal
sepsis |
2(4.1) |
1(2.1) |
0.5(0.05-4.60) |
0.53 |
2(4.1) |
1(2.1) |
0.5(0.04-5.70) |
0.57 |
RR Relative risk, CI Confidence interval, *Not
estimated, † statistically significant
No significant differences were found between the Betamethasone Vs the
Dexamethasone groups in both primary and secondary outcome measures. (Table=
4).
Table 4: Outcome
measures with Betamethasone vs Dexamethasone
|
Outcome
measure |
Betamethasone n=3D49 |
Dexamethasone n=3D49 |
Relative
risk |
Confidence
interval |
p-value |
|
Primary
outcome |
|||||
|
Respiratory
Distress Syndrome |
0(0) |
1(2.0) |
- |
- |
- |
|
|
|||||
|
Need
for neonatal resuscitation |
3(6.1) |
5(44) |
0.5 |
0.21-1.50 |
0.18 |
|
Transient
tachypnoea |
0(0) |
0(0) |
- |
- |
-* |
|
Apnoea |
0(0) |
0(0) |
- |
- |
-* |
|
Neonatal
hypoglycaemia |
4(8.2) |
7(14.3) |
0.5 |
0.22-1.23 |
0.09 |
|
Special
Care Baby Unit admission |
4(8.2) |
2(4.1) |
2.0 |
0.68-6.09 |
0.15 |
|
Neonatal
sepsis |
0(0) |
2(4.1) |
1.7 |
1.53-1.90 |
0.43 |
|
Neonatal
death |
0(0) |
0(0) |
- |
- |
-* |
|
Maternal
sepsis |
2(4.1) |
2(4.1) |
1.0 |
0.27-3.56 |
0.62 |
*not estimated
A logistic regression analysis was done to determine the relationship
between the need for resuscitation at birth and the study group of the women
while adjusting for a 1-minute APGAR score that was significantly higher in=
the
betamethasone group when compared to the placebo group. The result showed t=
hat
after adjusting for 1-minute APGAR score there was a significant reduction =
in
the likelihood of need for neonatal resuscitation by about 85% (ExpB=3D0.157, p=3D0.005) when betamethasone was used =
compared
to placebo.
The incidence of respiratory distress syndrome among late preterm neo=
nates
was low in our study. The incidence of respiratory distress varies with rac=
e. [4]
A low incidence of respiratory distress syndrome has been reported among
blacks. [4] and may explain the low incidence of respiratory
distress in our study coupled with the fact that compared to other categori=
es
of preterm births, its incidence is lower in late preterm neonates. There w=
as
no significant difference in the incidence of respiratory distress syndrome
between the group exposed to placebo versus antenatal betamethasone (p=3D 0=
.98,
RR 1.0, CI 0.09-11.55), the group exposed to placebo versus antenatal
dexamethasone (p=3D0.98, RR=3D1.0, CI 0.06-16.87) and the group exposed to
antenatal betamethasone versus antenatal dexamethasone (p=3D0.31, RR=3D0.5,=
CI
0.09-2.42). This is similar to the findings of Porto et al [10] =
who
reported a low incidence of respiratory distress among late preterm neonates
exposed to antenatal betamethasone and those exposed to placebo (1.4% and 0=
.8%
respectively) with no significant difference in the incidence of respiratory
distress between the 2 groups (p=3D0.54, RR 1.90). However, this is not
consistent with the findings of Balci et al [11] who reported an
incidence of 16% among late preterm neonates who did not receive antenatal
steroids and an incidence of 4% among those who received betamethasone and =
the
difference between the two groups was statistically significant (p=3D0.046,=
OR
0.21). The study by Balci et al [11] found a significant differe=
nce
in the incidence of respiratory distress in their study possibly due to the
open-label trial method, which may have introduced some bias unlike our stu=
dy
and that by Porto et al [10] which were both randomized
double-blinded. A similar double-blind randomized controlled trial by
Gyamfi-Bannerman et al [12] found a statistically significant hi=
gher
incidence of the primary outcome in the late preterm neonates in the control
group, the primary outcome was a neonatal composite of treatment including =
the
use of CPAP or high flow nasal cannula at least for 2 hours, supplemental
oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4
hours, extracorporeal membrane oxygen, or mechanical ventilation or stillbi=
rth
or neonatal death rather than respiratory distress alone. This may account =
for
the difference in findings.
The incidence of transient tachypnoea in the newborn was also low in =
this
study with only one neonate (2.1%) in the group exposed to placebo developi=
ng
the outcome (Tables 3). Our findin=
g of
the low incidence of transient tachypnoea was not consistent with a report by Gyamfi-Bannerman et al[12] who rep=
orted
an incidence of transient tachypnoea of the newborn among late preterm neon=
ates
exposed to antenatal betamethasone as 6.7% and 9.9% in those exposed placebo
(9.9%) (p=3D0.002, RR 0.68 CI 0.53-0.87).
A higher incidence was reported by Porto et al [10] where=
24%
of late preterm neonates exposed to antenatal betamethasone and 22% of those
exposed to placebo developed transient tachypnoea. However, there was no
significant difference between the groups. The low incidence of transient
tachypnoea of the newborn in our study is in keeping with the low incidence=
of
respiratory distress syndrome noted in the study.
This study showed a statistically significant reduction in the need f=
or
neonatal resuscitation at birth among the neonates exposed to antenatal
betamethasone compared to those exposed to placebo (p <0.001, RR 7.0, CI
2.49-19.46) and also the neonates exposed to antenatal dexamethasone compar=
ed
to those exposed to placebo (p=3D0.010, RR 4.0, CI 1.86-26.03). This means that neonates born to women =
who
received a placebo were 7 times more likely to need neonatal resuscitation =
at
birth compared to neonates born to women who received betamethasone and 4 t=
imes
more likely to need resuscitation at birth compared to neonates born to wom=
en
who received dexamethasone. The use of betamethasone was associated with a =
40%
decrease in need for resuscitation at birth compared to the use of
dexamethasone though this was not statistically significant (p=3D0.461).
Other studies have also reported a decrease in the need for neonatal
resuscitation at birth in women exposed to antenatal corticosteroids when
compared with women exposed to placebo. [11, 12]. This finding i=
s of
significance especially in our environment so that women seen during the la=
te
preterm period with the probability of having a late preterm delivery can be
offered antenatal steroids because such deliveries may occur in the absence=
of
skilled birth attendants that can adequately offer neonatal resuscitation at
birth.
The need for admission into SCBU was highest among the placebo group.
However, the differences observed were not statistically significant (Table=
s 3,
4).
Apnoea was not reported in any of the study or control groups. This m=
ay
be because clinical monitoring was used to detect apnoea rather than a
continuous electronic recording of the vital signs of the neonates. This has been observed in other studies=
where
a lack of correlation between nurses’ records with continuous electronically
recorded events has been demonstrated. [13, 14]. In a randomized
controlled trial on the use of betamethasone for women at risk for late pre=
term
delivery, apnoea was reported to occur in 2.3% of the group that had
betamethasone and in 2.6% of the control group with no significant differen=
ce
between the two groups (p=3D0.57). [12] Other studies on the use=
of
antenatal corticosteroids in late preterm neonates did not report on apnoea=
. [10,
11]
The differences in the incidences of hypoglycemi=
a
between the groups were not statistically significant (Table 3,4). Conflict=
ing
reports exist in the literature with regard to the incidence of hypoglycemia in neonates following exposure to antena=
tal
corticosteroids. While some authors [5, 12] reported an increase=
in
the rate of hypoglycemia among infants exposed =
to
antenatal corticosteroids, others did not [6]. A systematic review and meta-analysis of
randomized controlled trials on the use of antenatal corticosteroids in the
near term and term foetuses also showed an increased risk of neonatal hypoglycemia in neonates whose mothers received anten=
atal
corticosteroids at more than 34 weeks gestation. [5] However, no
adverse effects were reported in all the trials. This inconsistency may be =
due
to the fact that neonatal hypoglycemia is a com=
mon
late preterm neonatal complication irrespective of the use of antenatal
corticosteroids within the period. [15] Incidence of neonatal and
maternal sepsis were low and the differences between the groups were not
statistically significant. (Tables=
3,
4). This is consistent with existing literature. [12]
Conclusion
This study found that the use of antenatal corticosteroids in late
preterm delivery significantly reduced the need for neonatal resuscitation =
at
birth but may not have an effect on the incidence of respiratory distress
syndrome and other neonatal and maternal morbidity.
In view of the findings in this study, we recommend the use of antena=
tal
corticosteroids in women at risk of preterm delivery with the aim of reduci=
ng
the need for neonatal resuscitation at birth. However, there is still the n=
eed
for larger trials on the effect of the use of antenatal corticosteroids in =
late
preterm deliveries to prevent neonatal morbidity and minimize side effects =
on
both mother and neonates.
Strengths and
limitations
The major strength of this study is the fact that it was a double-bli=
nd
randomized controlled trial and both dexamethasone and betamethasone were u=
sed
as antenatal corticosteroids. However, it was conducted in a single center with a small sample size which is a limitation=
.
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