Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial

Abstract

Background: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes.

Methods: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA_1c). The primary outcome was change in HbA_1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527.

Findings: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA_1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy).

Interpretation: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use.

Funding: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research.

Figure 1

Trial profile for (A) participants in the pregnancy trial and (B) participants in the planning pregnancy trial CGM=continuous glucose monitoring. HbA_1c= glycated haemoglobin. *Central laboratory HbA_1c data were not available at randomisation for nine CGM group participants (six lost or not collected, two withdrawals, and one pregnancy loss) and 11 control group participants (nine lost or not collected, one withdrawal, and one pregnancy loss) and not available for an additional ten participants in the CGM group and 12 participants in the control group at 34 weeks. †CGM data unavailable. CGM data were available for 77 CGM participants using real-time sensor and 77 control group participants using an iPro2 masked sensor. ‡Central laboratory HbA_1c measurements were not available for eight participants in the CGM group (five lost or not collected and three withdrawals) and six control group participants (five lost or not collected and one withdrawal). §CGM data not available. CGM data were available for 39 CGM participants using real-time sensor and 52 control group participants using an iPro2 masked sensor.

Figure 1

Trial profile for (A) participants in the pregnancy trial and (B) participants in the planning pregnancy trial CGM=continuous glucose monitoring. HbA_1c= glycated haemoglobin. *Central laboratory HbA_1c data were not available at randomisation for nine CGM group participants (six lost or not collected, two withdrawals, and one pregnancy loss) and 11 control group participants (nine lost or not collected, one withdrawal, and one pregnancy loss) and not available for an additional ten participants in the CGM group and 12 participants in the control group at 34 weeks. †CGM data unavailable. CGM data were available for 77 CGM participants using real-time sensor and 77 control group participants using an iPro2 masked sensor. ‡Central laboratory HbA_1c measurements were not available for eight participants in the CGM group (five lost or not collected and three withdrawals) and six control group participants (five lost or not collected and one withdrawal). §CGM data not available. CGM data were available for 39 CGM participants using real-time sensor and 52 control group participants using an iPro2 masked sensor.

Figure 2

Primary glycaemic outcome showing participants' HbA_1c levels according to pregnancy status Mean HbA_1c (95% CI) is shown at each assessment time for participants who had data at baseline and the time of the outcome assessment (24 and 34 weeks' gestation in the pregnancy trial and at 12 and 24 weeks from randomisation or at time of confirmed pregnancy in the pregnancy planning trial). Data are also shown for participants in the planning pregnancy trial who conceived before 24 weeks and stayed in the trial during pregnancy. CGM=continuous glucose monitoring. HbA_1c=glycated haemoglobin.

Figure 3

Neonatal outcomes of pregnancy trial participants (A) Neonatal birthweight centiles are shown with box plots. The horizontal line in the middle of each box represents the median, and the lower and upper boundaries of the box represent the 25th and 75th percentiles, respectively. Whiskers are drawn to the smallest value that is within 1·5 × IQR below the 25th percentile. Values outside of the whiskers are drawn individually. These data are based on customised growth charts (gestation-related optimal weight) that adjust infant birthweight for maternal parity, ethnicity, height, and weight, and for infant sex and gestational age. (B) The Kaplan-Meier plot shows infants' length of hospital stay from delivery until hospital discharge.