Continuous Glucose Monitoring for Screening for Diabetes in Pregnancy:A Comparative Effectiveness Randomized Control Trial (PRECISE)
Phase: NA
Conditions: Gestational Diabetes
Sponsor: The University of Texas Health Science Center, Houston

IRB NUMBER: HSC-MS-22-0153 
IRB APPROVAL DATE: 07/05/2023 
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Continuous Glucose Monitoring for Screening for Diabetes in Pregnancy: 
A comparative effectiveness randomized control trial (PRECISE) 
 
NCT05430204    
 
Version Date: 07/05/2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

IRB NUMBER: HSC-MS-22-0153 
IRB APPROVAL DATE: 07/05/2023 
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Continuous Glucose Monitoring for 
Screening for Diabetes in Pregnancy: 
A comparative effectiveness randomized 
control trial (PRECISE) 
Study Protocol 
Principal Investigator: Michal Fishel Bartal, MD 
Co-investigators: 
Joycelyn Ashby Cornthwaite, CDCES 
Sarah Nazeer, MD 
Baha M. Sibai, MD 
Suneet P. Chauhan, MD 
Sean Blackwell, MD 
Division of Maternal-Fetal Medicine, Department of Obstetrics, 
Gynecology and Reproductive Sciences, The University of Texas Health 
Science Center at Houston 
Version Date: 03/01/2023 

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Contents 
STUDY PROTOCOL ............................................................................................................ 4 
1. 
BACKGROUND ........................................................................................................... 4 
Screening in pregnant population ..................................................................................... 5 
Continuous Glucose Monitoring in pregnancy ................................................................... 7 
2. 
RATIONALE FOR A CLINICAL TRIAL ......................................................................... 8 
3. 
HYPOTHESIS AND OBJECTIVE ................................................................................. 8 
3.1 Hypothesis: ................................................................................................................. 8 
3.2 Primary Objectives ...................................................................................................... 9 
3.3 PICO Question ............................................................................................................ 9 
4. 
STUDY DESIGN AND POPULATION .......................................................................... 9 
4.1 Study Design .............................................................................................................. 9 
4.2 Inclusion Criteria ......................................................................................................... 9 
4.3 Exclusion Criteria ........................................................................................................ 9 
5. 
METHODS AND ASSESSMENTS ............................................................................. 10 
5.1 Randomization and blinding ...................................................................................... 10 
5.2 Setting ...................................................................................................................... 10 
5.3 Recruitment .............................................................................................................. 10 
5.4 Intervention and procedures ......................................................................................11 
6. 
OUTCOME MEASURES ............................................................................................ 15 
6.1 Primary outcome ....................................................................................................... 15 
6.2 Secondary outcomes ................................................................................................ 16 
7. 
SAMPLE SIZE AND STATISTICAL METHODS ......................................................... 18 
7.1 Determination of Sample Size ................................................................................... 18 
7.2 Statistical and analysis plan ...................................................................................... 18 
7.3 Ancillary Studies ....................................................................................................... 19 
7.4 Feasibility .................................................................................................................. 20 
8. SAFETY MEASUREMENTS .......................................................................................... 19 
8.1 Definitions ................................................................................................................. 19 
8.2 Procedures for safety monitoring .............................................................................. 20 
9. 
ETHICAL CONSIDERATIONS ................................................................................... 20 
9.1 Informed consent .......................................................................................................20 
9.2 Institutional review board ...........................................................................................20 

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9.3 Subject confidentiality ............................................................................................... 20 
10. DATA HANDLING AND RECORD-KEEPING ............................................................... 21 
10.1 Access to source documents .................................................................................. 21 
10.2 Records Retention: ................................................................................................. 21 
10.3 Quality control assurance .........................................................................................21 
11. 
BUDGET ................................................................................................................ 21 
References ......................................................................................................................... 23 

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STUDY PROTOCOL 
1. BACKGROUND 
 
Gestational diabetes (GDM) is a condition in which carbohydrate intolerance 
develops during pregnancy. It remains one of pregnancy's most common medical 
complications, afflicting approximately 10% of all pregnancies in the United States 
(1). GDM is associated with maternal and fetal complications such as hypertensive 
disorders of pregnancy, birth injury, fetal macrosomia, cesarean section, neonatal 
complications, and increased risk of developing diabetes later in life (2). In addition, 
the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study found that 
maternal hyperglycemia is associated with adverse perinatal outcomes of increased 
birth weight and neonatal hyperinsulinemia (3, 4). Timely diagnosis and treatment of 
GDM improves both maternal and fetal outcomes (5, 6). 
To avert the multitude of the complications associated with GDM, universal 
screening is recommended at 24-28 weeks gestation (5, 7). Currently, screening and 
diagnosis of GDM can be made through various glucose challenge tests (8). Table 1 
lists the current recommendations by various policy for GDM screening (7, 9, 10). 
Table 1: GDM Screening Recommendations 
Organization (Year) 
Test 
Criteria for GDM 
diagnosis 
American Diabetes 
Association (2020) 
Universal screening 
One Step 
2h PG (75 g OGTT) 
Or 
Two Step 
1h GCT (50g OGCT)/3h 
OGTT (100g) 
FPG ≥ 92 mg/dL 
1h PG≥ 180 mg/dL 
2h PG ≥ 153 mg/dL 
Or 
1h ≥ 135 or 140mg/dL 
Fasting ≥ 95 or 105 mg/dL 
1hr ≥ 180 or 190 mg/dL 
2hr ≥ 155 or 165 mg/dL 
3hr ≥ 140 or 145 mg/dL 

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American College of 
Obstetrics & Gynecology 
(2018) 
Universal screening 
Two-Step 
1h PG (50 g OGCT) 
3hr (100g OGTT) 
As above 
National Institute for 
Health & Care Excellence 
(2015) 
Targeted high-risk screening 
One step 
2h PG (75 g OGTT) 
FPG ≥ 100mg/dL 
2hr PG ≥ 140 mg/dL 
WHO & FIGO (2013) 
Universal screening 
One step 
2h PG (75g OGTT) 
FPG ≥126 mg/dL 
2 h PG≥200 mg/dL 
International Association 
of the Diabetes and 
Pregnancy Study Group 
(2010 
Universal screening 
One step 
2h PG (75g OGTT) 
FPG ≥ 92 mg/dL 
1h PG≥ 180 mg/dL 
2h PG ≥ 153 mg/dL 
Most institutions follow the American College of Obstetrics & Gynecology 
(ACOG) recommendations of a two-step assessment during 24 to 28 weeks 
gestation (2). However, there are at least four limitations of the 50g oral glucose 
tolerance test (GCT) diagnostic values. First, the one-hour GCT was validated to 
determine the risk of developing Type II diabetes later in life; the diagnostic cut- 
off, however, is not centered on preventing adverse maternal or fetal outcomes. 
Second, a positive one-hour GCT result requires pregnant people to return to the 
clinic while fasting to complete a three-hour glucose challenge test (GCT). Third, 
the predictive value changes in different ethnicities due to the varying prevalence 
of GDM (11). Fourth, there is no available screening test for people who present 
late to care or those who cannot tolerate the GCT (such as people after bariatric 
surgery or with significant nausea and vomiting). For those patients the most 
common management would be to panel their blood sugars for at least 1 week. 

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Screening in pregnant population 
 
Other traditional diagnostic laboratory values, such as hemoglobin A1c 
and fasting blood glucose, used in non-pregnant states, have not been reliable or 
validated during pregnancy. HemoglobinA1c has poor sensitivity and specificity 
in the diagnosis of GDM, allowing for a high false-negative rate (12). Fasting 
blood glucose (FBG) was widely studied to decrease the burden associated with 
GTT, as it is associated with less cost and causes minor discomfort. However, no 
standardized criteria have been shown to provide reproducible GDM diagnosis 
(11). 
Despite the high prevalence of GDM and complications, very few 
randomized trials studying the optimal screening test have been conducted (13). 
A recent randomized trial comparing the single step to the two-step diagnosis 
showed no difference in perinatal outcomes (14). A Cochrane review in 2015 
cited that six small randomized control trials have been completed that have 
assessed optimal GDM screening. Of the six, only two studies compared the 
differences between recommended diagnostic tests (7). The findings are listed 
below. 
Table 2: Randomized trials on screening for GDM 
Title 
RCT 
N 
Findings 
Hillier et 
al/2020 (14) 
RCT: 75g GTT v. 
50g GCT/ 100g 
GTT 
23,792 No difference in the primary outcome of a diagnosis of 
GDM, LGA, CD, HDP, or perinatal composite 
Olarinoye et 
al./2004 (12) 
RCT: 75g GTT v. 
100g GTT 
248 
Higher prevalence of GDM in 75g GTT group, No 
difference in macrosomia or FBG 
Shirazian et 
al/2008 (15) 
WHO 75g GTT v. 
ADA 75g GTT 
670 
No difference in diagnosis of GDM, CD, macrosomia, 
instrumental birth 

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In the U.S., trends of obesity, sedentary lifestyle, cardiovascular disease, 
and many other risk factors that place patients at high risk of developing GDM 
are continuing to soar (16). However, with the adverse outcomes associated with 
GDM for both mother and infant, there is an urgent need to develop a 
comprehensive and standardized form of screening and diagnosis. 
Continuous Glucose Monitoring in pregnancy 
 
Continuous glucose monitoring systems putatively measure interstitial 
glucose values throughout the day, providing measurements every five minutes 
wirelessly. Providers are given many glucose values, including the mean, fasting, 
and range of glucose levels. Unlike a point of care value such as FBG or GTT 
result, CGM allows for much greater surveillance and detection of hyperglycemic 
episodes (9). Target values can be programmed into the receiver or mobile app, 
allowing for calculating time in range. 
Prospective studies evaluating the accuracy of CGM during GTT 
assessed the efficacy of CGM to detect hyperglycemic excursions (17). In 
addition, CGM has been studied in high-risk patient groups to identify 
hyperglycemic episodes. CGM has detected abnormal glucose profiles and 
provided caregivers specific glycemic trends in multiple populations at risk for 
abnormal glycemic trends, such as morbid obesity, critically ill, polycystic ovarian 
syndrome (9). 
Current two-step testing has many limitations, such as requiring a second 
diagnostic test that requires specific timing and prolonged laboratory stay (4 
hours) with further delaying treatment and diagnosis. Unfortunately, no current 

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data uses CGM as a screening tool for GDM. CGM is a promising, minimally 
invasive modality that will provide a more comprehensive evaluation of the 
glycemic profile of people. Thus, allowing a prompt diagnosis and treatment 
tailored to each person's glycemic discrepancies recorded by the CGM. 
2. RATIONALE FOR A CLINICAL TRIAL 
 
There are multiple reasons for a clinical trial comparing the traditional method of 
screening for GDM versus 
• Need for a diagnostic test that is based on maternal and neonatal outcomes. 
• No current consensus on the best screening test for GDM during pregnancy. 
• Non-pregnant diagnostic laboratory values, such as Hemoglobin A1c and fasting 
plasma glucose, do not have reliable diagnostic cut-offs during mid-pregnancy. 
• Need for a test that can efficiently diagnose GDM, which does not require 
additional, lengthy clinic visits. 
• The use of CGM permits for a complete glycemic profile as compared to the point 
of care glucose challenge test, thus allowing for a more specified and thorough 
treatment of GDM 
• Readily available CGM results allow for prompt, individualized treatment. 
• There are no current large, ongoing trials studying CGM as a screening tool for 
GDM. 

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3. HYPOTHESIS AND OBJECTIVE 
 
3.1 Hypothesis: 
 
We hypothesize that compared to usual care with the two- step screening 
method, CGM will increase detection of GDM and reduce maternal and neonatal 
adverse outcomes and health system costs related to GDM. CGM will also be 
shown to be highly cost-effective in preventing mother-infant dyads from 
developing maternal or neonatal adverse outcomes. Cost effectiveness may be 
achieved be either reducing maternal or neonatal health system costs without 
increasing the rate or heath system costs of adverse maternal or neonatal 
outcomes. By highly cost effective, we mean that CGM will lie within the 
dominant quadrant – i.e. the lower right quadrant – of the cost-effectiveness 
plane (Figure 1). 
Figure 1. Cost Effectiveness Plane 
3.2 Primary Objectives 
 
The objectives of this randomized controlled trial are: 

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• To evaluate whether CGM for diagnosis of GDM and improves maternal and 
neonatal outcomes related to GDM. 
• To evaluate whether CGM for GDM diagnosis reduces the health system costs 
for mother-infant dyads compared to usual care 
3.3 PICO Question 
 
Population: Pregnant individuals screening for GDM 
Intervention: CGM for GDM screening 
Comparison: Usual care with two step GDM screening 
Primary Outcome: Composite neonatal outcomes 
4. STUDY DESIGN AND POPULATION 
4.1 Study Design 
 
This is a single site, multi-clinic randomized controlled trial for pregnant people 
undergoing gestational diabetes screening in pregnancy. 
4.2 Inclusion Criteria 
 
• Maternal age of 18 years or older 
• 24-30 weeks gestation undergoing GDM screening 
4.3 Exclusion Criteria 
 
• Known diagnosis of Type I and II DM 
• History of bariatric surgery 
• Multiple gestation pregnancy 
• Major fetal anomalies 
• Unwilling to use CGM for GDM screening 

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• Incarcerated subjects 
• History of allergic reaction to any of CGM metals or adhesives in contact with the 
skin 
• People with incompatible cellular devices with G6PRO application 
5. METHODS AND ASSESSMENT 
 
5.1 Randomization and blinding 
o A non-clinical research team member will create computer-generated random 
sequences to ensure untampered randomization. A permutated block 
randomization in a random fashion 1:1 ratio will be employed to prevent 
imbalance in groups. 
o Randomization will be stratified by BMI ≥ 40 and clinic site at randomization 
o Blinding: The research team collecting data will be blinded to group allocation. 
We will not be able to blind the treating physician or patient to the CGM due to 
the nature of the intervention. 
5.2 Setting 
Recruitment will occur in outpatient clinic settings: 
• University of Texas, Houston (UTH) outpatient clinics: 
o UT physicians’ continuity clinic in the Texas Medical Center 
o Women's Health Center, Bellaire 
o Women’s Health Center, Memorial City 
o Women’s Health Center, Sugarland 

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5.3 Recruitment 
 
• Flyers and posters will be placed in clinic work rooms, patient rooms and clinic 
restrooms with recruitment and study procedure information. 
• The diabetes care and education specialist (CDCES) or research staff and 
collaborators will approach eligible individuals during their clinic appointment. 
• The research team will introduce continuous glucose monitoring and the 
G6/G7PRO CGM device per the manufacturer's use instructions. 
• Details of the study, risks and benefits of CGM in pregnancy will be discussed in 
a private room, and the informed consent form will be reviewed. Once all 
questions are answered and the individual is amenable to participant in the 
study, she will be asked to sign a consent form. A copy of consents will be given 
to the individual. In addition, patients will be approached about the study in either 
English or Spanish by research personnel fluent in the language. 
5.4 Intervention and procedures 
 
• After informed consent is completed; participants will be randomized into either 
one-hour GCT or CGM screening. 
• Group I will be comprised of one-hour 50g glucose challenge participants 
for diagnosis of GDM. 
• Group 2 will be participants that have CGM placement for diagnosis. 
• CGM will consist of using the Dexcom G6 Pro device (Figure 2). The device will 
be applied by a trained health care professional in the clinic. 
• The system will be set up according to the manufacturer's use instructions. 
• The device will be placed on the abdomen or the arm. 

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• The sensor will stay in place for a maximum of 7 days as recommended by the 
manufacturer. 
• In the event, CGM sensor malfunctions and values of at least three days are not 
available on Dexcom portal, sensor will be replaced. 
• Sensors will not be reused for other patients. 
• CGM will be placed for all study participants. 
• Group I participants, CGM will be blinded and diagnosis will be based on 1-hour 
glucose challenge test results as below. 
• 1-hour result ≤ 130 mg/dL, the participant will have passed the challenge 
test. 
• 1-hour result ≥ 130 mg/dL will complete a three-hour 100g glucose 
tolerance test. If two out of three values are elevated per Carpenter 
Coustan criteria (Table 3), the participant will be diagnosed with GDM and 
treated according to the standard of care. 
• Group 1 participants’ CGM data will not be observed until completion of study 
and will not be available to provider. 
• Group 1 participants will return transmitter at follow up visit after completion of 7 
days. If unable to bring to clinic visit, a prepaid postage will be provided to the 
participant to return the transmitter. 
Figure 2: Dexcom G6 Pro device 

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• Group 2 will use CGM for screening for diabetes. 
• The Dexcom G6/G7 Pro App will be downloaded on the patient's phone 
• A patient profile will be created on the Dexcom Clarity portal 
• The patient will receive an email to link their portal to the clinic's portal 
• If the patient's phone is not compatible with G6 Pro mobile app, the data will be 
blinded for her and the provider until the return of the device. Pick-up or mailing 
of the device will be planned for seven days after placement. 
• The patient will receive a message through Epic EMR to remove the CGM one 
week after placement 
• Group 2 will have the device in place for a total of 7 days and reviewed by the 
Diabetes team after 7-10 days after CGM placement. The recommended range 
for glucose during pregnancy is defined as 63-140 mg/dL (18). The time above 
range has been defined as ≥ 140 mg/dL, greater than 10% of total CGM 

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placement time. Based on the results of our prospective observational study of 
blinded CGM placement at time of one-hour GCT of pregnant people ≤ 30 weeks 
a CGM metric of time above range ≥ 10% was associated with higher rates of 
adverse neonatal outcomes. 
• The following criteria will currently be used to diagnose gestational diabetes in 
the CGM group: 
• Time above range (≥140 mg/dL) ≥ 10% of the time while using CGM or 
• Average glucose≥130 mg/dL or 
• Any glucose value ≥200 mg/dL 
• Group I will receive routine prenatal care follow-up depending upon one-hour 
glucose results as written above. 
• Group 2 will complete CGM and proceed with treatment if positive screening is 
found, as written above. 
• Management of GDM for both groups would include: 
• Consultation and follow up with Certified Diabetes Care and Education 
Specialist (CDCES) 
• The patients will be instructed to self-monitoring of blood glucose (SMBG) 
levels four times a day through a glucometer: fasting, 1-2 hour 
postprandial as recommended by the ACOG guidelines. 
• Patients will be managed according to the ACOG recommendations of 
goals (2): 
• Fasting: ≤ 95 mg/dL 
• 1 hour postprandial: ≤ 140 mg/dL 

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• 2 hour postprandial: ≤ 120 mg/dL 
• Initiation of medication if consistently elevated blood sugars following diet 
adjustment per provider discretion 
• Participants will be asked to continue to follow up as the standard of care. 
• No extra visits will be scheduled 
• Both groups will be followed throughout pregnancy, delivery, and postpartum. 
• A release of records form will be signed at randomization so that in case the 
participant delivers at another center; we can still obtain records from the 
delivery. 
• The research team will collect participant data, including demographic 
characteristics, medical history, obstetric history, labor course, and maternal and 
neonatal outcomes, by reviewing the electronic medical records and surveying 
the people during prenatal visits and the 6- week postpartum clinical 
appointment. 
• All participants will receive a $20 gift card after completing the diabetes 
screening (i.e., 1hGCT/3h OGTT if screened positive/7 days with GCM). 
• All participants will receive a $20 gift card following delivery. 
6. OUTCOME MEASURES 
 
6.1 Primary outcome: 
 
• Composite Adverse Neonatal Outcome including one or more of the followings: 
(time frame: from enrollment to discharge) 

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o Large for gestational age (LGA): weight over 90th percentile of the 
expected value according to gestational age (using the nomogram by 
Duryea EL et al). (19) 
o Shoulder dystocia: defined as the need for any extra maneuvers, other 
than gentle downward traction of the fetal head to deliver the fetal body 
after the fetal head has been delivered 
o Birth injury: skull, clavicular, humerus fracture, or brachial plexus injury 
o Neonatal hypoglycemia defined as requiring intravenous or oral glucose 
o Respiratory distress: the need for at least 4 hours of respiratory support 
with supplemental oxygen, continuous positive airway pressure, or 
ventilation at the first 24 hours of life 
o Fetal or neonatal death (within 28 days of birth) 
6.2 Secondary outcomes 
Maternal- 
o Feasibility of CGM use for GDM screening 
o Diabetic medication: use of any glycemic control agent during pregnancy 
or 6- week postpartum period. 
o Polyhydramnios during pregnancy not related to known fetal anomaly 
o Ultrasound diagnosis of estimated fetal weight >90%ile in the third 
trimester based on the (using the nomogram published by Duryea EL et 
al) (19) 
o Preterm birth: delivery less than 37 weeks of gestation 

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o Induction of labor 
o Pregnancy-induced hypertension: gestational hypertension, preeclampsia 
with or without severe features, HELLP syndrome, or eclampsia per 
ACOG guidelines. 
o Gestational hypertension: new-onset hypertension (systolic ≥ 140 
mm Hg or diastolic ≥ 90 mm Hg) without proteinuria 
o Preeclampsia: hypertension (systolic ≥ 140 mm Hg or diastolic ≥ 90 
mm Hg) with proteinuria or serum laboratory abnormalities 
(platelets ≤ 100,000, serum aspartate aminotransferase ≥ 80 
IU/mL, creatinine ≥ 1.2 mg/dL. They are classified as with or 
without severe features. 
▪ Severe features: systolic ≥ 160 mm Hg, diastolic ≥ 110 mm 
Hg, persistent headache, pulmonary edema, or any serum 
laboratory abnormalities as above 
▪ Proteinuria: protein excretion exceeding 300mg in 24 hours, 
a protein: creatinine ratio of ≥ 0.3 or 1+ proteinuria or greater 
on urine dipstick 
▪ HELLP Syndrome: hemolysis (serum bilirubin ≥ 1.2, low 
serum haptoglobin ≤ 25, lactate dehydrogenase (LDH) > 2 
times upper limit of normal based on laboratory-specific 
reference ranges or severe anemia unrelated to blood loss), 
elevated liver enzymes (aspartate aminotransferase (AST) 
or alanine aminotransferase (ALT) > 2 times the upper limit 

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of normal based on laboratory-specific reference ranges) 
and low platelet count (≤ 100,000) 
o 
Eclampsia: seizures 
o Admission for poor glucose control 
o Primary cesarean section 
o Postpartum hemorrhage: defined as ≥ 1000ml or need for blood 
transfusion 
o Endometritis 
o Wound complications 
o Diagnosis of type 2 diabetes during postpartum (according to the 1h 75g 
GTT) 
Neonatal: 
o Large for gestational age (LGA): weight over 90th percentile of the 
expected value according to gestational age (using the nomogram by 
Duryea EL et al). (19) 
o Shoulder dystocia: defined as the need for any extra maneuvers, other 
than gentle downward traction of the fetal head to deliver the fetal body 
after the fetal head has been delivered 
o Birth injury: skull, clavicular, humerus fracture, or brachial plexus injury 
o Neonatal hypoglycemia defined as requiring intravenous or oral glucose 
o Respiratory distress: the need for at least 4 hours of respiratory support 
with supplemental oxygen, continuous positive airway pressure, or 
ventilation at the first 24 hours of life 
19 
 
 
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o Fetal or neonatal death (within 28 days of birth) 
o Apgar score < 7 at 5 min 
o Neonatal intensive care unit (NICU) admission 
o NICU length of stay 
o Neonatal hypoglycemia: ≤40 mg/dL in the first 24 hours of life and less 
than 50 mg/dL after or requiring medical therapy 
o Neonatal polycythemia defined as hematocrit (Hct) or hemoglobin (Hgb) 
level above the upper limit of normal (>2 standard deviations) for 
gestational and postnatal age. 
o Neonatal hyperbilirubinemia requiring phototherapy 
o Maximum bilirubin level 
o Umbilical cord pH (arterial and venous) 
o Need for intravenous glucose therapy 
o Small for gestational age, defined as a weight below 10th percentile of the 
expected value according to gestational age (using the nomogram 
published by Duryea EL et al) (19) 
Mother-Infant Dyad 
• Total health system costs for mothers and infants 
• Cost-effectiveness of CGM relative to usual care, assessed as the total 
incremental maternal and neonatal health system costs (savings) per 
prevented mother-infant dyad from developing a maternal adverse outcome 
(preterm birth, induction of labor, pregnancy-induced hypertension, admission 
for poor glucose control, primary cesarean section, postpartum hemorrhage, 
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endometritis or wound complications) or a neonatal adverse outcome (LGA, 
shoulder dystocia, birth injury, neonatal hypoglycemia, respiratory distress, 
fetal or neonatal death within 28 days of birth). 
Costs will be assessed from the health system perspective based on the total 
costs for all the services provided to both the participating women and their 
neonates from randomization through either 6-weeks postpartum or discharge 
home (whichever is later). Hospital costs incurred within the Memorial Hermann 
Hospital System (MHHS) will be obtained from claims data and will be based on 
hospital-specific costs as assigned in the cost-accounting system for each of the 
14 hospitals of the MHHS. Hospital costs incurred at hospitals outside of MHHS 
will be estimated based on mean costs of these encounters at MHHS. Costs for 
inpatient and outpatient services provided by the UTH physicians will be 
estimated based on UTH claims data and Relative Value Units (RVUs) from the 
Medicare Fee Schedule. The costs for the intervention group will be augmented 
by the acquisition costs of the Dexcom G6 Pro device, which will be based on the 
average wholesale price as listed in the Micromedex Redbook. All costs will be 
inflated to the year of analysis based on the Consumer Price Index for medical 
services. 
7. SAMPLE SIZE AND STATISTICAL METHODS 
 
7.1 Determination of Sample Size 
 
As stated above, based on the results of our prospective observational study of 
blinded CGM placement at time of one-hour GCT of pregnant people ≤ 30 weeks 

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gestation we would like to adjust the sample size for this trial. A CGM metric of time 
above range ≥ 10% was associated with higher rates of adverse neonatal outcomes of 
preterm birth, intravenous glucose therapy and longer hospitalization. The findings of 
this study serves as the basis of diagnosis of GDM through CGM for our trial. Based on 
the results of this prospective trial the estimated rate of the primary outcome was 40%. 
In this trial we would include a more diverse population with a lower rate of factors 
associated with GDM such as lower BMI, different race and ethnicity. Our assumption is 
that the rate of the primary outcome will be 25%. 
Sample size calculations using a Bayesian analysis with different probability 
thresholds are presented in Table 4. In order to detect a 30% reduction in the rate of 
adverse neonatal outcome between the control and intervention with 90% power and a 
Bayesian posterior probability of 75% (of any reduction), 734 individuals (367 per group) 
will need to be diagnosed with GDM. With a 10% loss to follow up, 816 people in total 
will need to be enrolled. A total of 1020 individuals would need to be approached, to 
accommodate an expected enrollment rate of 80%. 
7.2 Statistical and analysis plan 
 
An intention to treat analysis will be conducted. All outcomes will be analyzed using 
generalized linear models (GLMs) and will include stratifying variables of BMI and clinic 
site as covariates. Primary outcome and all other binary outcomes will be analyzed with 
a logistic model. Secondary outcomes will be analyzed using appropriate distributional 
assumptions, i.e. negative binomial for counts and normal for continuous outcomes. We 
will report relative risks or group mean differences and 95% confidence intervals (CIs). 
Differences in costs will be assessed using a generalized linear model (GLM) with log- 

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link and gamma distribution. We will also compute the incremental cost-effectiveness 
ratio (ICER) of the total health system costs (savings) per prevented mother-infant dyad 
from developing an adverse outcome using a joint GLM with log link for costs and probit 
for maternal or neonatal adverse outcomes. We will induce dependency between costs 
and the adverse outcomes through shared random effects in the joint model. 
Planned Bayesian analysis: 
We will also conduct a Bayesian analysis of the primary outcome and of costs and 
cost-effectiveness. Sample size calculations using a Bayesian analysis with different 
probability thresholds are presented in Table 4. The composite primary outcome will be 
evaluated with a Bayesian binomial model. Finally, we conservatively set a neutral prior 
probability centered at a relative risk (RR) of 1.0 (i.e., a priori no effect on the outcome) 
and a 95% credible interval of 0.3-3.3 encompassing the largest likely effect size for 
major outcomes in randomized trials. This neutral prior will also be used to assess cost 
differences between the two treatment groups. Finally, we will report RR and 95% 
credible intervals and the probability of reduced adverse neonatal outcomes and costs, 
as well as the probability that the ICER will fall in the dominant quadrant of the cost- 
effectiveness plane (Figure 1). 
Table 4: Bayesian power to declare efficacy depending on level of evidence (probability threshold) 
 
Control 
Rate 
Treatment 
Rate 
# 
patients 
/group 
 
Prob(RR<1) > specified threshold 
70% 
75% 
80% 
85% 
90% 
95% 
0.4 
0.24 
60 
0.92 
0.89 
0.85 
0.79 
0.71 

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0.4 
0.28 
120 
0.93 
0.89 
0.85 
0.82 
0.75 
0.4 
0.24 
110 
0.98 
0.98 
0.96 
0.93 
0.90 
0.4 
0.28 
210 
0.98 
0.97 
0.96 
0.94 
0.90 
0.35 
0.245 
236 
0.98 
0.97 
0.95 
0.93 
0.89 
0.80 
0.30 
0.21 
294 
0.98 
0.97 
0.95 
0.93 
0.89 
0.80 
0.25 
0.175 
367 
0.98 
0.97 
0.95 
0.93 
0.89 
0.80 
0.20 
0.14 
484 
0.97 
0.96 
0.95 
0.92 
0.88 
0.80 
Interim analysis after 50% enrollment will be performed to assess the frequency 
of the primary and secondary outcomes. At that point, a decision will be made to see if 
there is a need to adjust the sample size. 
7.3 Ancillary Studies 
 
1. Satisfaction survey: All participants will be given a short, anonymized survey after 
completing their screening test. The aim of the survey is to assess participant 
satisfaction with the screening method they received and care provided throughout 
study period. The survey will take less than five minutes to complete. The survey will be 
scored in a Likert-type scale allowing for results to undergo descriptive analysis. 
2. Procedure specific satisfaction surveys: We would like to administer a satisfaction 
survey specific to each screening arm: routine care and CGM placement. Participants 
will be given a short, anonymized survey after completing their screening test. The aim 
of the survey is to assess participant’s experience, perception and satisfaction with the 
2-step glucose tests and CGM application. The surveys will take less than five minutes 
to complete. The surveys will be scored in a Likert-type scale allowing for results to 
undergo descriptive analysis. 

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3. Pre-specified secondary analysis: We have planned for a pre-specified secondary 
analysis after completion of data analysis. There are as follows: 
• Blood sugars using blinded CGM with 1-hour GCT results and composite 
maternal and adverse outcomes. 
• Evaluation of one-hour screening GCT threshold and composite maternal and 
adverse outcomes. 
• Evaluation of one abnormal value during 3-hour GTT and composite maternal 
and adverse outcomes. 
• Risk factors and adverse outcomes associated with ultrasound diagnosed 
large for gestational age fetus. 
• Risk factors and adverse outcomes associated with large for gestational age 
neonates. 
• Fetal growth or amniotic fluid abnormalities during third trimester ultrasound 
exam among GDM. 
• Gestational diabetic outcomes with and without Hypertensive Disorder of 
Pregnancy. 
• Compliant versus non-compliant gestational diabetic: risk factors and 
associated adverse outcomes. 
• The racial and ethnic disparity among gestational diabetics. 
• Risk factors associated with neonatal hypoglycemia. 
• Evaluation of time above range using CGM and associated neonatal 
outcomes. 

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• Maternal hypoglycemia using CGM and composite maternal and adverse 
outcomes. 
• Maternal breastfeeding and diabetes status and associated maternal and 
neonatal outcomes. 
• Maternal breastfeeding, obesity and diabetes status and associated maternal 
and neonatal outcomes. 
• Maternal breastfeeding and CGM glycemic profile and associated maternal 
and neonatal outcomes. 
• Incremental cost for prevention of Type II DM in life using a model method. 
7.4 Feasibility 
 
Our clinics see greater than 250 people a week and approximately 6,000 deliveries 
at our four participating centers. We aim to enroll about ten people per week, based on 
the previous prospective CGM in pregnancy study. Assuming 10% of people will decline 
to participate, we will expect to recruit 816 people in 2 years. 
8. SAFETY MEASUREMENTS 
 
8.1 Definitions 
 
Serious adverse events will be monitored throughout the study, though not 
anticipated. 
8.2 Procedures for safety monitoring 
 
A review of available experimental and observational literature has shown benefit in 
outcomes associated with CGM use in pregnant and non-pregnant people with the 
minimal risk associated with the device (20). 

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9. ETHICAL CONSIDERATIONS 
 
9.1 Informed consent 
 
All study candidates will be given a full explanation of the study procedure and 
allowed to read the entire consent form. In addition, they will be given an opportunity to 
ask any questions. After all, questions have been answered, and the Investigator is 
confident that the participant understands the requirements of the study, the participant 
will sign the consent form. In addition, the participant will receive a copy of the informed 
consent. 
9.2 Institutional review board 
 
The Principal Investigator will obtain approval of the research protocol from the IRB. 
Per U.S. law, the study will be registered in www.clinicaltrials.gov for public access. 
9.3 Subject confidentiality 
 
A study number will be assigned to each participant prior to collecting the data. This 
will maintain the subject's anonymity as they will be de-identified. There will be a record 
of the participants at the study site to each assigned study number. 
The research staff completed the required Collaborative Institution Training Initiative 
(CITI Training). Access to personal information will be limited to investigators only. 
Therefore, they are required to keep all information confidential. 
In addition, Electronic Medical Record, Epic, will be used for pre-screening of 
individual characteristics. Once identified, participant will be approached via EPIC 
secured portal messaging system and/or contacted via phone for presentation of 
research study. If interested, individual will be scheduled a research portal visit. 

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A secure research portal created by University of Texas, Houston Epic Personnel 
will maintain a screening and actively enrolled participant list. Access will only be 
granted to those included on the IRB. 
The participants will be de-identified when data is reported in any format, including 
but not limited to medical journals or scientific meetings. 
10. DATA HANDLING AND RECORD-KEEPING 
 
10.1 Access to source documents 
 
Research personnel will perform data collection through the abstraction of 
participant electronic medical records from multiple sites. Demographics, variables, and 
outcomes will be collected and entered into a Redcap database and the Dexcom data 
capture platform. Attached to this protocol is a detailed list of variables that will be 
collected. Data will be obtained from randomization up until 6 weeks postpartum. 
10.2 Records Retention: 
 
Data will be collected and de-identified in the UTHealth Redcap system. At the time 
of study completion, approved protocol and all other supporting documents pertaining to 
the project will be retained. Data will be de-identified and available for future analysis. 
Following completion of the study and analysis of data, the de-identified data will be 
shared to Dexcom Inc. 
10.3 Quality control assurance 
 
The Principal Investigator and co-investigators will go through all the files to verify 
that the data is reliable and complete. Verification will be completed through 
assessment by Principal Investigator and co-investigator. 

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11. BUDGET 
 
This study has been awarded the Learning Health Care (LHC) award. LHC is an 
award granted to University of Texas, Houston faculty that have proposed a study that 
is a quality improvement project or interventional study that advances patient care and 
outcomes. 
The remainder of funding required for the entirety of this study will be provided by 
DexCom, Inc., a Delaware corporation located at 6340 Sequence Drive, San Diego, 
California 92121. Projected study costs are depicted in the attached excel sheet. 

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