Recruitment
The study was conducted between February 2018 and May 2019. Recruitment
was stopped
when desired sample size was achieved.
During the period 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 intrauterine fetal death. The
remaining 138 pregnant women were included in the study. Among these
women, there were 6 sets of twins and a set of triplets. 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 betamethasone
and 49 were exposed to antenatal dexamethasone.
DISCUSSION
MAIN FINDINGS
The incidence of respiratory distress syndrome among late preterm
neonates in the placebo group, betamethasone group and dexamethasone
group were 2.1%, 0% and 2% respectively. The incidence of respiratory
distress varies with race.(4) Low incidence of respiratory distress
syndrome have 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 categories of preterm births, its incidence is
lower in late preterm neonates. There was no significant difference
between the group exposed to placebo versus antenatal betamethasone (p=
0.98, RR 1.0, CI 0.09-11.55), the group exposed to placebo versus
antenatal dexamethasone (p=0.98, RR=1.0, CI 0.06-16.87) and the group
exposed to antenatal betamethasone versus antenatal dexamethasone
(p=0.31, RR=0.5, CI 0.09-2.42). This is similar to the findings of Porto
et al(10) where he reported 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=0.54, 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 that did not receive antenatal steroids and incidence
of 4% among those that received betamethasone and the difference
between the two groups was statistically significant(p=0.046, OR 0.21).
The fact that Balci et al(11) found a significant difference in the
incidence of respiratory distress in their study may be due to the fact
that they did an open label trial which may have introduced some bias
unlike our study and that by Porto et al(10) which were both randomized
double blinded. Though a similar double blind randomized controlled
trial by Gyamfi-Bannerman et al(12) found a statistically significant
higher incidence of 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 stillbirth or neonatal death rather than
respiratory distress alone. This may account for the difference in
findings.
The incidence of transient tachypnoea of the newborn was also low in
this study with one neonate (2.1%) in the group exposed to placebo
developing the outcome (Tables 2 and 3). Our finding of low incidence in
transient tachypnoea was not consistent with other reports.
Gyamfi-Bannerman et al(12)
reported an incidence of transient tachypnoea of the newborn among late
preterm neonates exposed to antenatal betamethasone 6.7% and 9.9% in
those exposed placebo (9.9%) (p=0.002, 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 for
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 compared to those exposed to placebo (p=0.010, RR 4.0, CI
1.86-26.03). This means that neonates born to women who received placebo
were 7 times more likely to need neonatal resuscitation at birth
compared to neonates born to women who received betamethasone and 4
times more likely to need resuscitation at birth compared to neonates
born to women 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=0.461).
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 1- and 5-minutes APGAR score that was
significantly higher in the betamethasone group when compared to the
placebo group. The result showed that after adjusting for 1- and
5-minute APGAR score there was a significant reduction in the likelihood
of need for neonatal resuscitation by about 85% (ExpB=0.157, p=0.005)
when betamethasone was used compared to placebo.
Other studies have also reported 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 is
of significance especially in our environment where many deliveries are
conducted 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
(12.5%), followed by the betamethasone group (8.2%) and least in the
dexamethasone group (4.1%). However, the differences observed were not
statistically significant (Tables 2, 3 and 4).
Apnoea was not reported in any of the study or control group. This may
be because continuous electronic recording of vital signs of the
neonates was not done in our study and apneic episodes are short in
duration. This has been observed in other studies where a lack of
correlation between nurses’ records with continuous electronically
recorded events have been demonstrated (13),(14). In a randomized
controlled trial on the use of betamethasone for women at risk for late
preterm 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 difference between the two groups (p=0.57).(12) Other
studies on the use of antenatal corticosteroids in late preterm neonates
did not report on apnoea. (10),(11)
The neonates exposed to antenatal dexamethasone had the highest
incidence of hypoglycemia (14.3%), followed by those exposed to
antenatal betamethasone (8.2%). The neonates exposed to placebo had the
lowest incidence of hypoglycemia (4.2%). However, the differences were
not statistically significant (Tables 2 ,3 and 4). Conflicting reports
exist in the literature with regards to incidence of hypoglycemia in
neonates following exposure to antenatal corticosteroids. While some
authors(12),(15) reported 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 near term and term fetuses also
showed an increased risk of neonatal hypoglycemia in women who received
antenatal corticosteroids at more than 34 weeks gestation.(15) However,
no adverse effects were reported in all the trials. This inconsistency
may be due to the fact that neonatal hypoglycemia is a common late term
neonatal complication irrespective of the use of antenatal
corticosteroids within the period.(16)
Incidence of neonatal and maternal sepsis were low and the differences
between the groups were not statistically significant. (Tables 2, 3 and
4). This is consistent with existing literature.(12)
STRENGTHS AND LIMITATIONS
The major strength of this study is the fact that it was a double blind
randomized controlled trial and both dexamethasone and betamethasone
were used as antenatal corticosteroids. However, it was conducted in a
single center which is a limitation.
CONCLUSION
This study found that the use of antenatal corticosteroids in late
preterm delivery did not have any significant effect on incidence of
respiratory distress syndrome and other neonatal morbidity but
significantly reduced the need neonatal resuscitation at birth.
RECOMMENDATIONS
In view of the findings in this study we recommend the use of antenatal
corticosteroids in women at risk of preterm delivery with the aim of
reducing the need for neonatal resuscitation at birth.
However, there is still the need for more trials on the effect of use of
antenatal corticosteroids in late preterm deliveries with the aim of
preventing neonatal morbidity and minimizing side effects on both mother
and neonates.
ACKNOWLEDGEMENT
We would like to acknowledge the staff of the labour ward and the
special care baby unit of Ahmadu Bello University Teaching Hospital for
their support during the period of the study.
DISCLOSURE OF INTEREST
The authors declare no conflict of interest. The authors do not have any
financial, personal, political, intellectual or religious
affiliations/relationships with any institution or organization that may
have influenced the research.
CONTRIBUTION TO AUTHORSHIP
AY was involved in the concept, design, definition of intellectual
content, literature search, data acquisition, data analysis, statistical
analysis, manuscript preparation,
manuscript editing and manuscript
review. HUS and IA were involved in the definition of intellectual
content, data acquisition, manuscript editing and review. BBL was
involved in data analysis, statistical analysis, manuscript editing and
manuscript review.
DETAILS OF ETHICAL APPROVAL
Ethical approval to conduct the study was sought from the Health
Research and Ethics Committee of Ahmadu Bello University Teaching
Hospital Shika. The application was reviewed by the committee and
permission to conduct the study 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/). The initial permission to conduct the study expired
on 07/08/2018 before the desired sample size was achieved. Permission
for extension of study period to 07/08/2018 was granted after due
process.
FUNDING
Funding was received from Institution Based Research funds of the
Tertiary Education Trust Fund of Nigeria. The funding is part of funding
for professional development and not for commercial or other purposes.
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