Strengths and Limitations
This study has several strengths. To our knowledge, this is the largest
study to report on the neonatal impacts of ACS in women with
pre-gestational diabetes being delivered via caesarean section9. Furthermore, this is the first study to report on
the rates of use of ACS in women with pre-gestational diabetes prior to
elective caesarean sections.2-4 The exclusion of
multiple pregnancies, aneuploidy and structurally abnormal fetuses
removed potential confounders in interpretation of these data. Finally,
the inclusion of two study centres makes these findings more
generalisable.
The limitations of a retrospective study are acknowledged with its
findings inferior to a prospective randomized controlled trial. We were
only able to collect and use data that was collected as part of routine
antenatal care in this population. Unfortunately, this means that some
data regarding possible confounding factors were not available for
analysis. In particular, the impact of ACS on maternal glycaemic control
was unable to be reliably established due to the limited availability of
data such as maternal blood glucose levels during the pregnancy. We
included data concerning earliest and latest collected HbA1c in
pregnancy to provide a measure of baseline comparison between those who
received antenatal corticosteroids and those who did not. Notably, there
was no difference in these HbA1c levels between those who received ACS
compared to those who did not suggesting that there was not a
significant difference in the severity of baseline glycaemic control
between the two groups. While ACS are known to affect glycaemic control,
this would not be reflected in changes in HbA1c. We were unable to
collect information on whether women received repeat courses of ACS. The
risk of maternal hyperglycaemia after exposure to ACS has previously
been reported and it would be pertinent to assess the impact of maternal
glycaemic control on short and long term maternal and neonatal
outcomes.9,20 Although international guidelines
provide a framework for monitoring and management of maternal
hyperglycaemia post ACS administration,21,22 in this
cohort the decision for admission, rate of increase in insulin and
ongoing monitoring was at the discretion of the treating endocrinology
team. Institutional practice varied in this regard, with one site
admitting all women with pre-gestational diabetes receiving ACS whilst
the other managed them as outpatients.
Furthermore, the groups were not blinded to treatment which further
confounds the results of this study. The decision to administer ACS or
not was purely at the discretion of the treating clinician. During the
period of this study, hospital specific guidelines changed with respect
to the strength of the recommendation for ACS in this patient group,
whilst always acknowledging the limited evidence base and ultimately
allowing clinician discretion. It appears that clinicians were more
likely to administer ACS in cases where birth was scheduled at an
earlier gestation or where there were additional fetal concerns.
Furthermore, the nature of this retrospective study has prevented us
from examining long term neonatal outcomes, including the impact of
exposure to ACS on behavioural and neurodevelopmental outcomes. Although
long term cardiovascular outcomes of in utero exposure to antenatal
corticosteroid exposure in the non-diabetic population is largely
reassuring, exposure to ACS has been associated with increased insulin
resistance in response to oral glucose at 30-year follow up, the
clinical significance of which remains uncertain in the offspring of
women with diabetes.23
We also acknowledge the small sample size and retrospective nature of
this study may have impacted upon the ability to draw firm conclusions
about the shorter- and longer-term consequences of ACS in women with
diabetes prior to elective caesarean section. In particular, our small
sample size is potentially underpowered to assess the true association
between administration of ACS and the outcomes of respiratory distress
and sepsis. Nevertheless, this is the largest cohort of women with
pre-gestational diabetes reported to date. Given the varying prevalence
of this intervention, we feel that it is essential that the practice
undergo further scrutiny. The findings of our study may inform future
prospective study protocols to evaluate the impact of ACS in women with
diabetes. A pilot trial evaluating the feasibility of such a trial is
currently in progress, (PRECeDe Pilot: Prevention of neonatal
Respiratory distress with antenatal corticosteroids prior to Elective
Caesarean section in women with Diabetes - A Feasibility Randomised
Trial; ACTRN12619001475134)