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)