DISCUSSION
In this prospective randomized controlled trial study, pregnant women in
the unblinded group did not show any significant differences in the
primary outcomes of GDM development and OGTT plasma glucose
concentrations. However, the unblinded group did display a trend towards
better glycaemic control seen with higher time spent in target glucose
range percentages (3.5-7.8 mmol/L) in the first, followed by the early
second and third trimesters of pregnancy, and lower time spent below the
glucose range percentages (<3.5mmol/L) in the first and early
second trimesters. There were no significant differences seen in the
%TAR, mean, %CV, SD and MAGE values between the two CGM groups.
To the best of our knowledge, this is the first study to compare CGM
sensor users with and without CGM feedback in women without pre-existing
Type 1 or Type II Diabetes, early in pregnancy before the diagnosis of
GDM. Our study did not show a reduction in GDM prevalence between the
unblinded group over the blinded group users. To date, there has been
only one RCT reporting the beneficial effects of CGM feedback using a
real-time CGM sensor, comparing it to capillary glucose monitoring and
users with masked CGM feedback in pregnant women with type 1 diabetes
(CONCEPTT) trial. In this study, the improved neonatal outcomes reported
with the receipt of CGM feedback were attributed to reduced exposure to
maternal hyperglycaemia as mothers spent more time within their target
glucose range 16. The null associations with GDM
development were also reflected by the null associations in the plasma
FG,1hPG, and 2hPG levels between the two study arms.
Direct comparisons to the CONCEPTT study are difficult due to
differences in study design. The CONCEPTT study recruited pregnant women
who were already diabetic in whom careful monitoring of glucose levels
was anyway required for insulin dose adjustment. Such participants would
be anticipated to be more motivated in self-management of their glucose
levels through lifestyle modification. By comparison, our study
participants were healthy at recruitment in early pregnancy, and before
any diagnosis of GDM. In contrast to our study which provided
participants with a new CGM device after an interval of 6-9 weeks, the
CONCEPTT study participants had their CGM replaced every month.
Participants in the CONCEPTT study were also provided a real-time CGM
which provides alerts and active alarms, transmits a continuous stream
of glucose data in real time, and has been shown to be more effective in
promoting better glycaemic control. In contrast, our study participants
received an intermittently scanned CGM sensor which requires the user to
purposely scan the sensor to obtain the same information, and lacks
alerts and alarms. 21 Furthermore, we have noted that
out of the 79 participants in the unblinded group who remained in the
study after recruitment, almost half (43%) failed to provide at least
50% of the CGM glucose data from not scanning their sensor regularly.
The low compliance to have sensors scanned at least every 8 hours would
mean that not all participants in this group have fully benefitted from
the CGM feedback.
Our study showed that there was overall better glycaemic control
throughout the pregnancy as seen from higher %TIR in the unblinded
group. There was also trend of lower %TBR in the unblinded group during
the first and early second trimester. Our observations on time spent in
target glucose range concurred with those of the CONCEPTT study which
compared glycaemic control parameters in a group receiving CGM feedback
compared to those without at 34 weeks gestation 16. In
contrast to our findings, the CONCEPTT study found no significant
difference in women with glucose values below the target range and a
reduced percentage of women who spent time above the target glucose
range 16. These discrepancies in findings are mainly
attributed to the population of non-Type I or Type II diabetic women in
our study sample. GDM patients and non-GDM pregnant patients have mild
hyperglycaemia, and higher incidences of hypoglycaemia compared to
patients with Type 1 or Type II Diabetes 22. In our
study, the percentages of participants who spent time above the target
glucose range were low, with a median less than 1% and minimum and
maximum percentages between 0-2%, as most of the women in this sample
were healthy and less likely to be hyperglycaemic.
There were no differences in the mean glucose, SD, %CV and MAGE values
except for higher mean concentrations in the unblinded group at the time
points (9-13 weeks and 18-23 weeks. In contrast to our study, the
CONCEPTT study reported significantly reduced glucose SD, lower MAGE,
and non-significantly reduced glucose coefficient of variation,
suggesting less glycaemic variability and better glycaemic control in
the users of the unblinded real-time CGM group 16.
These findings may possibly be explained by the use of the
intermittently scanned CGM in our study which has been shown to be less
successful in controlling mean glucose values and %CV23 compared to the real-time CGM. Our observations
suggest participants in the unblinded group were more motivated to use
the sensor for tracking their daily behaviours. However, despite this,
the self-reported data showed that 44% of participants in this group
did not modify their diet nor physical activity level, and 68% did not
keep track of their dietary intake despite receiving CGM feedback.
Future studies examining CGM feedback in pregnant patients who are
healthy at the time of recruitment should be coupled with better patient
education and personal guidance to achieve better glycaemic control and
glycaemic variability CGM parameters 24.
Our study is the first to compare CGM with feedback and without in
healthy pregnant women without Type I or II diabetes at recruitment.
Overall, this study showed high acceptability of CGM sensor use during
pregnancy. The CGM feedback motivated users in the unblinded group to
track their daily behaviours through accessing information that they
found relevant and of value. There was an overall higher satisfaction
rate in the users of the unblinded group with a lower percentage of
users reporting adverse events – the most common being skin reactions,
such as erythema, and/or itching and pain at the sensor insertion site.
The strengths of our trial include its longitudinal design to capture
glucose data throughout pregnancy from the first to the third trimester,
and the long CGM wear time of up to 14 days which provides a better
capture of free-living glycaemic variability. However, our trial has
limitations, the current recruited sample size in this pilot RCT might
not have sufficient power to provide a conclusive answer to our primary
hypothesis despite achieving our minimum recruitment number of 60
participants in each study arm based on the rule of thumb for pilot RCTs20. This also makes our study findings less
generalizable, and would require replication with a larger sample size.
We have also noted that patients might have benefited from better CGM
education and personalized guidance on the interpretation of the glucose
readings obtained to be better able to make suitable lifestyle
adjustments to further improve glycaemic control. Furthermore, although
efforts were made to ensure compliance to CGM scans in the unblinded
group users, almost half failed to provide complete CGM data.