Methods
Study design
This observational, non-intervention study was conducted at two academic-based clinical sites: the University of Pennsylvania, Philadelphia, Pennsylvania, USA and the International Diabetes Center at Park Nicollet, St Louis Park, Minnesota, USA.
Major eligibility criteria included age 18 years and older, singleton pregnancy under routine prenatal care at or before gestational time of 16 weeks, 6 days (determined by ultrasound), HbA1c less than 6.5% (48 mmol/mol) and no pre-gravid diabetes diagnosis, no signs of abnormalities in fetal or placental development, no use of oral systemic steroids or medication intended to lower blood glucose, and willing/able to wear a Dexcom CGM device (see online supplemental table 1 for complete listing of inclusion and exclusion criteria). Electronic informed consent was obtained from each participant.
A blinded Dexcom G6 Pro was placed during the clinical visit, and the participant instructed on its care and mailing of the transmitter to the coordinating center after 10 days. A new sensor was placed at each standard care office visit and/or at home approximately every 10 days if a sensor was worn continuously. Training of sensor insertion was performed through virtual methods (ie, video conferencing) remotely or in person. Participants were encouraged to insert new sensors at home between visits, but this was optional. Participants voluntarily entered meal start times onto a mobile application during weeks 18–22 and 32–34 of gestation. As per usual care, an OGTT was performed between 24 and 28 weeks. At conclusion of pregnancy, data were recorded for adverse pregnancy outcomes (APOs).
For this paper, the cohort was limited to participants with an uncomplicated pregnancy, which was defined as a pregnancy without large for gestational age, hypertensive disorders, or GDM based on OGTT. Participants included in the analysis were required to have an HbA1c <5.7% (<39 mmol/mol) at screening, a completed OGTT, an APO assessment at delivery, and at least 14 days of CGM data during their gestational period with at least 10 days of CGM data in the second trimester.
Statistical methods
CGM-measured glycemic metrics were calculated using all available CGM data during gestation. To be included in the main analysis cohort, the participant must have at least 14 days of CGM data with 10 days in the second trimester. A minimum of 252 and 84 hours of CGM data was required for daytime and night-time (defined as midnight–06:00) CGM metric tabulations, respectively. For CGM metrics summarized within each trimester and 4-week period, a minimum of 10 days of CGM data was required within each period. The difference in mean glucose by trimester was tested using a repeated measures linear regression model, and the association between body mass index (BMI) and mean glucose was tested using a linear regression model.
Post-prandial metrics were calculated from CGM data during the 4 hours after a self-reported meal start time. Participants were required to have at least five meals with a CGM-measured glucose level 15 min prior to, 30 min after, 1 hour after, 2 hours after, and 3 hours after the reported mealtime to be included in the analysis. Post-prandial peak was defined as the maximum CGM-measured glucose value within the 4 hours after a reported meal time; time to post-prandial peak was defined as the time between the reported mealtime and post-prandial peak. Meals with another reported meal within the 2 hours prior to 3 hours after were excluded. Post-prandial metrics were also explored by trimester, for which at least five meals meeting the minimum data requirements were also required within each trimester.
Outcomes were summarized as means and SDs or summary statistics appropriate to the distribution. Multiple comparisons were adjusted using the Benjamini-Hochberg adaptive false discovery rate.10 Significance was assessed at the α=0.05 level. Analyses were performed with SAS software, V.9.4 (SAS Institute).
Data and resource availability
Data will be made available on a publicly available website (https://www.jaeb.org/) at a later date.