Comparison of Two Screening Strategies for Gestational Diabetes (GDM2)
Phase: NA
Conditions: Gestational Diabetes, Pregnancy, Glucose Intolerance
Sponsor: Esa M Davis, MD MPH FAAFP

 
 
 
 
 
GDM2 Study 
 
“Comparison of Two Screening Strategies for Gestational Diabetes” 
 
NIH Grant #: 1R01HD079647-01A1 
PittPRO ID: STUDY19070199 
ClinicalTrials.gov Identifier: NCT02309138  
 
 
 
 
 
 
 
 
 
Manual of Procedures 
Version V – December 1, 2019 
 
 
 
 
 
 
 
 
 
Principal Investigator: Esa M. Davis, MD, MPH 
University of Pittsburgh 
 

 
ii 
 
 
 
 

 
iii 
 
 
GDM2 Study Manual of Procedures, Version V: Table of Contents 
 
Study Investigators and Responsibilities .................................................................................... 9 
GDM2 Study Personnel and Responsibilities ........................................................................... 14 
Study Flow Chart and Randomization Schema ....................................................................... 21 
Recruitment Plan ........................................................................................................................ 25 
Magee-Womens Hospital Clinic Recruitment ........................................................................... 25 
Additional Recruitment Methods ............................................................................................... 26 
Screening Procedures ................................................................................................................. 28 
Eligibility Criteria ..................................................................................................................... 28 
Hypertension and Corticosteroid Medications .................................................................................... 29 
Documentation of Eligibility .............................................................................................................. 29 
Documentation of Study Participation in the EMR or Fax ....................................................... 30 
Screening Time Point Forms ..................................................................................................... 30 
Magee-Womens Hospital Clinical and Translational Research Center ................................ 32 
Visit 1: 50 g GCT......................................................................................................................... 32 
Preparation for Visit 1 (50 g GCT) ........................................................................................... 32 
Informed Consent ...................................................................................................................... 33 
50 gram Glucose Challenge Test .............................................................................................. 33 
IV Protocol .......................................................................................................................................... 34 
Visit 1 Forms ............................................................................................................................. 35 
Completing Visit 1 ..................................................................................................................... 36 
Visit 1 Results ............................................................................................................................ 36 
Critical Glucose Values ...................................................................................................................... 36 
Glucose Challenge Test Results 200 mg/dL ..................................................................................... 36 
Randomization Procedures ....................................................................................................... 37 
Blinding ..................................................................................................................................... 37 
Visit 2: 75 g or 100 g OGTT ....................................................................................................... 38 
Preparation for Visit 2 (75 g or 100 g OGTT) .......................................................................... 38 
75 g or 100 g Oral Glucose Tolerance Test .............................................................................. 38 
IV Protocol .......................................................................................................................................... 39 

 
iv 
 
 
Completion of Study Questionnaires ......................................................................................... 39 
Visit 2 Forms ............................................................................................................................. 39 
Postpartum Depression Questionnaire ................................................................................................ 41 
Completing Visit 2 ..................................................................................................................... 41 
75 g or 100 g OGTT Laboratory Results .................................................................................. 42 
“Mild GDM” ....................................................................................................................................... 43 
Unblinding Providers to OGTT Results .............................................................................................. 43 
Critical Glucose Values ...................................................................................................................... 43 
OGTT Result Reporting ...................................................................................................................... 44 
Visit 2 Results Back Entry ......................................................................................................... 44 
Delivery Time Point .................................................................................................................... 45 
Cord Blood Collection .............................................................................................................. 45 
Infant Skinfold Measurement .................................................................................................... 45 
Delivery Time Point Forms ....................................................................................................... 46 
Physician Beliefs Questionnaire ............................................................................................... 46 
Postpartum Telephone Encounters ........................................................................................... 47 
3, 6, and 9 Month Postpartum Phone Calls .............................................................................. 47 
3, 6, and 9 Month Postpartum Forms ....................................................................................... 47 
Visit 3: 12 Months Postpartum .................................................................................................. 49 
Preparation for Visit 3 .............................................................................................................. 49 
75 g Oral Glucose Tolerance Test ............................................................................................ 50 
IV Protocol .......................................................................................................................................... 50 
Visit 3 Forms ............................................................................................................................. 51 
Visit 3 Questionnaires and Assessments ............................................................................................. 52 
Postpartum Depression Questionnaire ................................................................................................ 53 
Completing Visit 3 ..................................................................................................................... 53 
Visit 3 Laboratory Results ......................................................................................................... 54 
Visit 3 Results Back Entry ......................................................................................................... 55 
Quest Diagnostics Visit ............................................................................................................. 55 
Data Abstraction ......................................................................................................................... 56 
Health Research Record Request (R3) ...................................................................................... 56 
R3 Data Collection .............................................................................................................................. 56 

 
v 
 
 
Data Collection Associated with Study Outcomes ............................................................................. 57 
Confidentiality .................................................................................................................................... 58 
Laboratory Procedures and Protocols ...................................................................................... 59 
Specimen Collection .................................................................................................................. 59 
Laboratory Processing and Long-Term Specimen Storage ...................................................... 59 
Visit 1 Laboratory Procedures ............................................................................................................ 60 
Visit 2 Laboratory Procedures ............................................................................................................ 60 
Cord Blood Laboratory Procedures .................................................................................................... 61 
Visit 3 Laboratory Procedures ............................................................................................................ 62 
Visits 2 and 3 Occurring on Saturdays ................................................................................................ 63 
Specimen and Laboratory Flow Charts .................................................................................... 64 
Clinical Laboratory Protocols ................................................................................................... 66 
Glucose ............................................................................................................................................... 66 
Insulin ................................................................................................................................................. 66 
Cholesterol .......................................................................................................................................... 66 
High Density Lipoprotein ................................................................................................................... 67 
Triglycerides ....................................................................................................................................... 67 
High-Sensitivity C-Reactive-Peptide .................................................................................................. 67 
C-Peptide............................................................................................................................................. 68 
Glycosylated Hemoglobin A1c ........................................................................................................... 68 
Adiponectin ......................................................................................................................................... 68 
Leptin .................................................................................................................................................. 68 
Non-Esterified Fatty Acids ................................................................................................................. 69 
Adherence and Retention ........................................................................................................... 70 
Study Withdrawal and Termination .......................................................................................... 70 
Data Management and Quality Control ................................................................................... 72 
Center for Research on Health Care Data Center .................................................................... 72 
Data Collection ................................................................................................................................... 72 
Manual Data Entry .............................................................................................................................. 72 
Data Quality and Integrity................................................................................................................... 73 
Data Corrections ................................................................................................................................. 73 
Data Security ....................................................................................................................................... 74 
Data and Safety Monitoring ....................................................................................................... 75 

 
vi 
 
 
Institutional Data and Safety Monitoring Board ...................................................................... 75 
Membership ........................................................................................................................................ 75 
IDSMB Responsibilities ..................................................................................................................... 75 
IDSMB Board Process ........................................................................................................................ 76 
IDSMB Meeting Formats .......................................................................................................... 76 
IDSMB Reports ......................................................................................................................... 77 
Letters from the IDSMB ............................................................................................................ 78 
Communication with the IDSMB/Access to Interim Data ......................................................... 78 
Confidentiality .................................................................................................................................... 78 
Adverse Event Reporting Guidelines ........................................................................................ 79 
Adverse Events (AEs) ................................................................................................................ 79 
Serious Adverse Events (SAEs) ................................................................................................. 79 
AE and SAE Assessment Guidelines Specific to the GDM² Trial .............................................. 81 
Event Severity using Common Terminology Criteria for Adverse Events (CTCAE) ........................ 82 
Event Relatedness ............................................................................................................................... 83 
Study Completion and Closeout ................................................................................................ 84 
Study Completion and Closeout Procedures ............................................................................. 84 
Early Termination of Study ....................................................................................................... 85 
Retention of Study Documentation ............................................................................................ 85 
Table of Changes from Version IV to Version V ..................................................................... 86 
3, 6, and 9 Month Postpartum Forms ....................................................................................... 88 
 
 
 

 
vii 
 
 
List of Abbreviations 
 
ACOG 
ADA 
American College of Obstetricians and Gynecologists 
American Diabetes Association 
AE 
Adverse Event 
BMI 
Body Mass Index 
BPA 
(Epic) Best Practice Alert 
CLB 
(UPMC) Clinical Laboratory Building 
Co-I 
Co-Investigator 
CRHC 
Center for Research on Health Care 
CRHC-DC 
Center for Research on Health Care – Data Center 
CSSD 
Computing Services and Systems Development 
CTRC 
Clinical and Translational Research Center 
CTSI 
Clinical and Translational Science Institute 
DM 
Diabetes Mellitus 
DOB 
Date of Birth 
DSMB 
Data Safety Monitoring Board (a.k.a. IDSMB) 
EBL 
ED 
Estimated Blood Loss 
Emergency Department 
EDC 
Estimated Date of Confinement 
EHR 
EMR 
Electronic Health Record (a.k.a. EMR) 
Electronic Medical Record (a.k.a. EHR) 
eSYSDM 
Electronic System for Data Management 
GA 
Gestational Age 
GDM 
Gestational Diabetes Mellitus 
GSPH 
Graduate School of Public Health 
GCT 
Glucose Challenge Test 
hsCRP 
High-sensitivity C-reactive Peptide 
IADPSG 
International Association of the Diabetes and Pregnancy Study Groups 
ICD 
Informed Consent Document 
IDSMB 
Institutional Data Safety Monitoring Board (a.k.a. DSMB) 
IRB 
Institutional Review Board 
LDR 
Labor and Delivery Room 
LGA 
Large for Gestational Age  
LMP 
Last Menstrual Period 
LTFU 
Lost to Follow-Up 
MFM 
Maternal-Fetal Medicine 
MRN 
Medical Record Number 
MWH 
Magee-Womens Hospital 

 
viii 
 
 
MWRI 
Magee-Womens Research Institute 
NICHD 
National Institute of Child Health and Human Development 
NICU 
Neonatal Intensive Care Unit 
NIH 
National Institutes of Health 
OB 
Obstetrician/Obstetrics 
OGTT 
Oral Glucose Tolerance Test  
OSPU 
Obstetric Specimen Procurement Unit 
PI 
Principal Investigator 
R3 
RA 
Health Research Records Request 
Research Assistant 
RC 
Research Coordinator 
SAE 
Serious Adverse Event 
SGA 
TOLAC 
Small for Gestational Age 
Trial of Labor After C-section 
UPMC 
University of Pittsburgh Medical Center 
 
 
 

 
9 
 
 
Study Investigators and Responsibilities 
 
 
GDM2 Principal Investigator 
 
Principal Investigator: Esa M. Davis, MD, MPH 
 
University of Pittsburgh School of Medicine 
Center for Research on Health Care 
230 McKee Place, Suite 600 
Pittsburgh, PA 15213 
Phone: 412-692-4843 
Email: emd55@pitt.edu 
 
Dr. Esa Davis, Associate Professor of Medicine, Clinical and Translational Science, is a family 
medicine physician. She will be responsible for supervision of all aspects of the research project, 
including conceptualization, protocol implantation, data analyses and interpretation, data safety 
monitoring, and publication and dissemination. She will ensure the ethical conduct of the study, 
which includes protecting human participants’ rights, safety, and welfare; protocol compliance; 
and adherence to institutional, state, and federal regulars and guidance. She will comply with the 
financial and administrative policies and regulations associated with the award, overall fiscal 
management of the project, and conflict of interest disclosure. 
 
 
 

 
10 
 
 
GDM2 Co-Investigators 
 
Co-Investigator/Site Principal Investigator: Hyagriv Simhan, MD, MSCR 
 
Magee-Womens Hospital 
Division of Maternal-Fetal Medicine 
300 Halket Street 
Pittsburgh, PA 15213 
Phone: 412-641-4222 or 412-641-6361 
Email: hsimhan@mwri.magee.edu 
 
Dr. Hyagriv Simhan, Professor, Director of Division of Maternal-Fetal Medicine and Executive 
Vice Chair of Obstetrical Services at Magee-Womens Hospital (MWH) has expertise in 
conducting clinical trials in pregnancy through the Maternal-Fetal Medicine network and will be 
actively involved in study implementation within MWH obstetrical clinics, data analyses and 
interpretation, and manuscript preparation. He will provide supervision of adverse events and 
clinical input when needed, He will participate in research team and data safety monitoring 
meetings. He will be responsible for making important study-related decisions in compliances 
with the ethical conduct and regulatory requirements of the study. 
 
 
Co-Investigator: Christina Scifres, MD 
 
Indiana University 
Division of Maternal-Fetal Medicine 
550 N. University Boulevard  
UH 2440 
Indianapolis, IN 46202 
Phone: 317-948-4103 
Email: cmscifre@iu.edu 
 
Dr. Christina Scifres, Associate Professor of Obstetrics and Gynecology and a specialist in 
maternal-fetal medicine, is a co-principal investigator on this research study. She was 
instrumental in the success of the pilot study and has been key in the conception and 
implementation of the current trial. She will provide clinical perspective and assist with the 
implementation of study procedures, and she will contribute to data analyses and interpretation 
of findings, publications, and presentations. She will participate in research team and data safety 
monitoring meetings. She will be responsible for making important study-related decisions in 

 
11 
 
 
compliance with the ethical conduct and regulatory requirements of the study and will assist in 
the management and leadership of this trial. 
 
 
Co-Investigator: Patrick Catalano, MD 
 
Tufts University 
Department of Obstetrics and Gynecology 
800 Washington Street 
Box 394 
Boston, MA 02111 
Phone: 617-636-4187 
Email: pcatalano@tuftsmedicalcenter.org  
 
Dr. Patrick Catalano, Professor and Vice Chair of Obstetrics and Gynecology and a specialist in 
maternal-fetal medicine, is a co-investigator on this research study. He will provide supervision 
and input on collection, analyses, and interpretation of the metabolic lab profiles at Visit 2 
(randomization) and Visit 3 (12-months postpartum). He will participate in research team 
meetings, data analyses and interpretation of findings, manuscript writing and dissemination to 
the IADPSG and the National Institutes of Health (NIH) Gestational Diabetes Mellitus (GDM) 
consensus committee. 
 
 
Co-Investigator and Study Biostatistician: Kaleab Z. Abebe, PhD 
 
University of Pittsburgh 
Center for Research on Health Care – Data Center 
200 Meyran Avenue, Suite 300 
Pittsburgh, PA 15213 
Phone: 412-246-6931 
Email: kza3@pitt.edu 
 
Dr. Kaleab Abebe, Associate Professor of Medicine, Biostatistics, and Clinical and Translational 
Science, will be responsible for supervising all aspects of data management and statistical 
analyses. He will work with CRHC-DC data managers and systems analysts to implement an 
online data management application, as well as oversee randomization and data safety 
monitoring. He will be responsible for generating monthly reports for the study team and 
quarterly reports for the Data Safety Monitoring Board (DSMB) and Institutional Review Board 

 
12 
 
 
(IRB). Dr. Abebe will oversee the primary statistical analysis of the current study and will work 
with the study team to disseminate the results through reports, abstracts, and manuscripts. 
 
 
 Co-Investigator: Tina Costacou, PhD 
  
University of Pittsburgh 
Diabetes and Lipid Research Clinic 
3512 Fifth Avenue 
Pittsburgh, PA 15213 
Phone: 412-383-2062 
Email: costacout@edc.pitt.edu 
  
Dr. Tina Costacou, Assistant Professor of Epidemiology, is a nutrition and diabetes 
epidemiologist. For this project, Dr. Costacou will provide input on diabetes measures and trial 
design. She will participate in research team meetings and provide input on recruitment, 
enrollment, and longitudinal retention, assist with problem-solving any issues that arise with 
study implementation, data analyses and interpretation, and assist with manuscripts. She will 
assist in making important study-related decisions in compliance with the scientific and ethical 
conduct of the study. 
  
 
Co-Investigator: Nancy Day, PhD, MPH 
 
University of Pittsburgh 
Department of Psychiatry 
3811 O’Hara Street 
Pittsburgh, PA 15213 
Phone: 412-681-3482 
Email: nday@pitt.edu 
  
Dr. Nancy Day, Professor of Psychiatry, Epidemiology, and Pediatrics, will assist in making 
important study-related decisions in compliance with the scientific and ethical conduct of the 
study. She will provide input on study aims, design, and measurement of variables. She will 
provide her expertise in observational design, measurement, managing follow-up and attrition, 
and analyses. Dr. Day will be involved in research team meetings to discuss study-related issues, 
data analyses, and interpretation and manuscript writing. 
 
 

 
13 
 
 
 
Co-Investigator: Lisa Bodnar, PhD, MPH, RD 
 
University of Pittsburgh 
Graduate School of Public Health 
130 DeSoto Street 
A742 Crabtree Hall 
Pittsburgh, PA 15261 
Phone: 412-624-9032 
Email: bodnar@edc.pitt.edu 
 
Dr. Lisa Bodnar, Associate Professor of Epidemiology, Obstetrics and Gynecology, and 
Psychiatry, is a registered dietitian and licensed nutritionist. Dr. Bodnar is a nutritional 
epidemiologist in the field of reproductive health. She will supervise the dietary recalls of 
participants at Visit 2 (baseline) and Visit 3 (12-months postpartum), as well as the infant 
feeding assessments. She will train the research study staff to administer the 24-hour Dietary 
Recalls for these visits. She will also participate in data analysis and interpretation of this 
variable. Dr. Bodnar will be involved in research team meetings to discuss study-related issues, 
data analyses, and interpretation and manuscript writing. 
 
 
 
 
 

 
14 
 
 
GDM2 Study Personnel and Responsibilities 
 
GDM2 Principal Study Staff 
  
Research Assistant: Alison Decker, BA 
 
University of Pittsburgh 
Center for Research on Health Care 
230 McKee Place, Suite 600 
Pittsburgh, PA 15213 
Phone: 412-647-0246 
Email: deckerap@upmc.edu  
 
Alison Decker will work with the study investigators and other staff in implementing this study. 
Study staff duties will include: scheduling appointments, completing phone assessments, and 
maintaining regular contact with study participants; run study visits and complete blood draws 
and study laboratory procedures; data collection and entry; maintain quality control for data 
correctness and completeness; update participants’ electronic medical records as needed; 
supervision of student workers; and coordination with ancillary studies. Study staff will monitor 
adverse events, serious adverse events, and protocol deviations, and report such events to the 
investigators in a timely manner. She will also maintain the staff calendar and work assignments, 
monitor study invoices, and act as the study’s IDSMB coordinator. 
  
 
Research Assistant: Kathleen (Ly) Meeder, MPH, CHES 
  
University of Pittsburgh 
Center for Research on Health Care 
230 McKee Place, Suite 600 
Pittsburgh, PA 15213 
Phone: 412-692-4312 
Email: lyk@upmc.edu  
 
Kathleen Meeder will work with the study investigators and other staff in implementing this 
study. Study staff duties will include: scheduling appointments, completing phone assessments, 
and maintaining regular contact with study participants; run study visits and complete blood 
draws and study laboratory procedures; data collection and entry; maintain quality control for 
data correctness and completeness; update participants’ electronic medical records as needed; 
supervision of student workers; and coordination with ancillary studies. Study staff will monitor 

 
15 
 
 
adverse events, serious adverse events, and protocol deviations, and report such events to the 
investigators in a timely manner. She will also prepare materials for and run weekly staff 
meetings and biannual co-investigator meetings, monitor dietary recalls and the ASA24 backend, 
create study newsletters for participants and providers, and act as the study’s recruitment lead 
and IRB coordinator. 
 
 
Research Assistant: Steven Orris, BS 
 
University of Pittsburgh 
Center for Research on Health Care 
230 McKee Place, Suite 600 
Pittsburgh, PA 15213 
Phone: 412-647-1468 
Email: orrissr@upmc.edu  
 
Steven Orris will work with the study investigators and other staff in implementing this study. 
Study staff duties will include: scheduling appointments, completing phone assessments, and 
maintaining regular contact with study participants; run study visits and complete blood draws 
and study laboratory procedures; data collection and entry; maintain quality control for data 
correctness and completeness; update participants’ electronic medical records as needed; 
supervision of student workers; and coordination with ancillary studies. Study staff will monitor 
adverse events, serious adverse events, and protocol deviations, and report such events to the 
investigators in a timely manner. He will act as the study’s delivery/postpartum time point lead, 
responsible for maintaining an accurate list of participants expected to deliver soon, and act as 
the study’s liaison with the Obstetric Specimen Procurement Unit at MWH. He will also be the 
study’s laboratory liaison at the UPMC Clinical Laboratory Building and Magee-Womens 
Research Institute, responsible for creating laboratory procedures and materials, creating 
specimen storage maps, and transporting specimens between labs for long-term storage at 
MWRI. 
 
 

 
16 
 
 
GDM2 Clinical Team 
  
Magee-Womens Hospital Clinical and Translational Research Center Administrator: 
Cindy Schatzman, RN 
  
Magee-Womens Hospital 
Clinical and Translational Research Center 
300 Halket Street, Suite 5500 
Pittsburgh, PA 15213 
Phone: 412-641-6111 
Email: schatzmancl@mail.magee.edu 
  
Cindy Schatzman, RN, will support the study by providing specified services at the Magee-
Womens Hospital Clinical and Translational Research Center (MWH CTRC), including glucose 
testing, phlebotomy, and nursing care for study participants. 
  
 
UPMC Automated Testing Laboratory Director: Octavia Peck-Palmer, PhD 
  
UPMC Clinical Laboratory Building 
3047 Euler Way, Room 3014 
Pittsburgh, PA 15213 
Office Telephone: 412-578-9489 
Email: palmerom@upmc.edu 
  
Dr. Octavia Palmer, Associate Professor of Pathology and Medical Director of the Automated 
Testing Laboratories at UPMC Presbyterian, will supervise sample processing and analysis of 
blood samples at the UPMC Clinical Laboratory Building. 
  
 
UPMC Special Chemistry and Immunoserology Laboratory Manager: Mary Jane Horenzy 
  
UPMC Clinical Laboratory Building 
Department of Special Chemistry 
3047 Euler Way, Room 4025 
Pittsburgh, PA 15213 
Phone: 412-647-3769 
Email: horenzymj@upmc.edu 
  
Mary Jane Horenzy, laboratory manager at the UPMC Special Chemistry and Immunoserology 
laboratories, will oversee the analysis of the A1c and insulin specimens. 
  
 
 
 

 
17 
 
 
Magee-Womens Research Institute Lab Liaison: Sharon Price 
  
204 Craft Avenue 
Pittsburgh, PA 15213 
Phone: 412-641-6148 
  
Sharon Price is the GDM2 Study’s liaison at the Magee-Womens Research Institute (MWRI), 
where all banked specimens from the study will be stored. 
  
 
Obstetric Specimen Procurement Unit Liaison: Lindsay Stewart 
  
Magee-Womens Hospital 
Obstetric Specimen Procurement Unit 
300 Halket Street 
Pittsburgh, PA 15213 
Phone: 412-354-4077 
Email: stewartl4@upmc.edu 
  
Lindsay Stewart is the GDM2 Study’s liaison with the Obstetric Specimen Procurement Unit 
(OSPU) at MWH. The OSPU team will identify study participants at delivery and collect cord 
blood specimens for c-peptide analyses. The OSPU team will process and store specimens until 
they are transferred from MWH to MWRI. 
  
 
 
  
 
 

 
18 
 
 
GDM2 Data Center Staff 
  
Data Center Information Systems Manager: Timothy Bragg 
  
University of Pittsburgh 
Center for Research on Health Care – Data Center 
200 Meyran Avenue, Suite 200 
Pittsburgh, PA 15213 
Phone: 412-692-4898 
Email: braggtj@upmc.edu 
  
Timothy Bragg is the GDM2 Study’s Information Systems Manager and is responsible for data 
management and supervision of Charlene Xie, the study’s Data Systems Analyst. 
  
 
Data Center Data Systems Analyst: Charlene Xie, MSIS 
  
University of Pittsburgh 
Center for Research on Health Care – Data Center 
200 Meyran Avenue, Suite 200 
Pittsburgh, PA 15213 
Phone: 412-246-6926 
Email: xiecx@upmc.edu 
  
Charlene Xie is responsible for designing and developing the study’s database. She is responsible 
for data management procedures, including the data flow and procedures for data entry, error 
identification, and correction quality control. 
  
 
Data Center Data Analyst: Diane Comer 
  
University of Pittsburgh 
Center for Research on Health Care – Data Center 
200 Meyran Avenue, Suite 200 
Pittsburgh, PA 15213 
Phone: 412-692-4896 
Email: dianecomer@pitt.edu 
 
Diane Comer is responsible for assisting Dr. Abebe with the study’s data analysis. 

 
19 
 
 
GDM2 Regulatory Staff 
  
University of Pittsburgh Institutional Review Board: Lisa DeSantes, BS, CIP 
  
University of Pittsburgh Institutional Review Board 
3500 Fifth Avenue 
Hieber Building, Main Office, Suite 106 
Pittsburgh, PA 15213 
Phone: 412-383-1488 
Email: lisa.desantes@pitt.edu 
  
Lisa DeSantes has reviewed and approved the GDM2 Study protocol and is responsible for 
reviewing study modifications, unexpected problems, and serious adverse events reportable to 
the Institutional Review Board (IRB). She will also answer questions related to University of 
Pittsburgh IRB guidelines and procedures. 
  
 
Clinical and Translational Science Institute, Data Safety and Monitoring Board 
Coordinators: Susan Sandusky and Samantha Hurst 
  
University of Pittsburgh Clinical and Translational Science Institute 
Forbes Tower, Suite 7057 
Atwood and Sennott Streets 
Pittsburgh, PA 15213 
  
Susan Sandusky: 
Phone: 412-383-1036 
Email: sls127@pitt.edu 
  
Samantha Hurst: 
Phone: 412-605-0264 
Email: seh142@pitt.edu 
  
Susan Sandusky and Samantha Hurst of the Clinical and Translational Science Institute (CTSI) 
will provide oversight of the GDM2 Study’s Data Safety and Monitoring Board (DSMB), 
ensuring safe conduct of this clinical trial. They have assisted in the identification of DSMB 
members. They will schedule and attend DSMB meetings and will prepare minutes and reports 
for those meetings. Ms. Sandusky and Ms. Hurst will schedule and attend follow-up (and, if 
needed, emergency) DSMB meetings and will subsequently prepare minutes and reports. 

 
20 
 
 
GDM2 Administrative Staff 
  
Center for Research on Health Care Grants Administrator: Patrick Reitz, MA 
  
University of Pittsburgh 
Center for Research on Health Care 
230 McKee Place, Suite 600 
Pittsburgh, PA 15213 
Phone: 412-692-4858 
Email: reitzpm@upmc.edu 
  
Patrick Reitz is the GDM2 Study’s grant administrator and will oversee that the grant received 
will be properly utilized according to its conditions and responsibilities. 
  
 
Administrative Coordinator: Kristee Rosen, MS 
  
University of Pittsburgh 
Center for Research on Health Care 
230 McKee Place, Suite 600 
Pittsburgh, PA 15213 
Phone: 412-692-4853 
Email: adamskj2@upmc.edu 
  
Kristee Rosen is the administrative coordinator for the Center for Research on Health Care 
(CRHC). She will supervise staff that will assist the study team by providing administrative 
support with general clerical activities, scheduling and coordinating study-related meetings, and 
purchasing study supplies. 
 

 
21 
 
 
Study Flow Chart and Randomization Schema 
 
         

 
22 
 
 
GDM2 Study Timeline (from grant) 
Study Activity/Months 
1-6 
6-12 
12-
18 
18-
24 
24-
30 
30-
36 
36-
42 
42-
48 
48-
54 
54-
60 
Orientation & Start-
Up 
x 
 
 
 
 
 
 
 
 
 
Finalize IRB 
x 
 
 
 
 
 
 
 
 
 
Enrollment 
 
x 
x 
x 
x 
 
 
 
 
 
Intervention 
 
x 
x 
x 
x 
x 
x 
x 
 
 
Postpartum Follow-up 
 
 
x 
x 
x 
x 
x 
x 
 
 
Data QA/Cleaning  
 
x 
x 
x 
x 
x 
x 
x 
x 
 
Primary & Secondary 
Analyses 
 
 
 
 
 
 
 
x 
x 
x 
Publication & 
Presentations 
 
 
 
 
 
 
 
x 
x 
x 
Study Meetings 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 

 
23 
 
 
 

 
24 
 
 
 
 

 
25 
 
 
Recruitment Plan 
 
The GDM2 Study’s goal is to recruit 920 pregnant women between 18w0d and 28w0d gestation. 
Participants will be women undergoing care in the following clinics: 
 
 Resident Outpatient Clinic – Red Unit (public) 
 Resident Outpatient Clinic – Blue Unit (public) 
 Resident Outpatient Clinic – Orange Unit (Midwives; public) 
 Resident Outpatient Clinic – Orange Unit (public) 
 Resident Outpatient Clinic – Yellow Unit (public) 
 Resident Outpatient Clinic – Pink Unit (public) 
 Resident Outpatient Clinic – Tan Unit (PAC; public) 
 Resident Outpatient Clinic – Tan Unit (Midwives; public) 
 OB/GYN Associates of Pittsburgh (private) 
 Maternal-Fetal Medicine (private) 
 University NIA OB/GYN Associates (private) 
 Midwives at Magee (private) 
 WomanCare Associates (3 clinics within MWH; private) 
 Wiesenfeld-Updike (private) 
 
We will use various recruitment methods, including physician letters, flyers, brochures, the Epic 
Best Practice Alert (BPA), the Pitt+Me research registry, the MWH electronic message boards, 
newsletters such as “UPMC Extra”, and the University of Pittsburgh’s “Read Green”, and 
TrialSpark, which uses social media as a recruitment tool. Recruitment materials can be found in 
Appendix A. 
 
 
Magee-Womens Hospital Clinic Recruitment 
 
Provider and Staff Orientation 
 
Before active recruitment begins, provider and staff orientation meetings will be held at the 
selected obstetrical clinics located at MWH. Drs. Davis and Simhan will present the protocol, 
explain study procedures, and ask for preferences regarding study participating and relaying 
results. These orientation meetings will acquaint providers and their staff with the project and 
will help to promote patient referrals to the study. Study staff will maintain ongoing contact with 
the selected clinics to keep providers and staff informed on study progress and to address any 
site-specific issues or problems with study implementation.  

 
26 
 
 
In-Clinic Recruitment 
 
Women undergoing care in the selected obstetrical clinics will be considered for enrollment in 
this study. Contact cards and drop boxes will be placed in several of the selected clinics’ waiting 
rooms. Study staff will collect these cards once a week and follow-up with potential participants 
by telephone or email. 
 
Potential participants can be pre-screened (informing the individual about the study and 
collecting their contact information) or screened (informing the individual about the study and 
completing the 11-item screening questionnaire) during their regular OB visits. If study staff is 
on-site, clinic staff or providers can ask potential participants if they would be willing to hear 
about the study. With the patient’s permission, study staff will present the study using the same 
script that is used for telephone screening. If the patient is interested, they can then be screened 
using the 11-item screening questionnaire. (See Appendix B.) Face-to-face screening will take 
place in a private area such as an exam room or consult office. 
 
 
Epic Best Practice Alert 
 
A Best Practice Alert (BPA) within the Epic outpatient record will alert providers when a 
potential participant is within the gestational age eligibility window and prompt them to ask if 
the potential participant is interested in participating in the study. If a potential participant is 
agreeable the BPA will be used to notify study staff, who will then contact them by phone to 
describe the study and screen them further for eligibility. 
 
 
Additional Recruitment Methods 
 
Posters, flyers, and brochures (see Appendix A) will be placed in exam rooms, waiting rooms, 
and restrooms within clinic offices, and on approved bulletin boards throughout MWH for 
patient self-referral, and to remind clinic staff to refer potential participants to the study. Flyers 
and brochures will also be distributed in public areas throughout the Pittsburgh metropolitan 
area, such as the WIC office in downtown. Letters and brochures are put into the new OB 
packets that are given to patients in the clinics. 
 
A “featured research study” description will be including in the “UPMC Extra” email newsletter 
that is sent to all UPMC employees, for interested women to self-refer to the study. Similarly, the 
University of Pittsburgh’s “Read Green” email newsletter will also be used to recruit potentially 
interested employees. A description of the study will be posted on CTSI’s Pitt+Me research 

 
27 
 
 
registry website for women to self-refer. Pitt+Me also distributes emails that will advertise the 
study to women who may be eligible based upon demographics and/or participant-chosen health 
areas of interest. Pitt+Me advertises over multiple social media avenues such as Twitter and 
Facebook. 
 
Another recruitment avenue through CTSI that will be utilized is the Pediatric PittNet. PittNet is 
a practice-based research network that works collaboratively with University of Pittsburgh 
researchers and pediatric primary care practices. Study advertisements will be on their website 
and message boards located in pediatric offices. PittNet also rotates featured research studies 
each month, and this study will be added to the rotation to be featured on their website and 
newsletter. 
 
Digital message boards throughout the UPMC Health System will be used to advertise the study. 
TV screens at the following UPMC hospitals will display a PowerPoint slide with a brief 
description of the study and contact information for interested women. 
 
 UPMC Magee-Womens Hospital 
 UPMC Children’s Hospital of Pittsburgh 
 UPMC East 
 UPMC McKeesport 
 UPMC Mercy 
 UPMC Passavant 
 UPMC Presbyterian 
 UPMC Shadyside 
 UPMC St. Margaret 
 
TrialSpark will be used as a recruitment source for the study. It uses advertisements on social 
media platforms such as Facebook and Twitter to direct interested women to fill out a pre-
screening form through TrialSpark’s unique GDM2 Study landing page (see Appendix A). 
 
 

 
28 
 
 
Screening Procedures 
 
Eligibility Criteria 
 
Study staff will contact patients expressing an interesting in study participation in-person or by 
telephone to determine eligibility. A pre-screening interview will be conducted, where the study 
will be explained in detail using an IRB-approved script (see Appendix A).  
 
After explaining the study in detail, study staff will ask for verbal consent to administer the 
screening questionnaire (see Appendix B). Screening information will be entered directly into 
the study database, which will automatically determine eligibility based on the study’s inclusion 
and exclusion criteria as follows: 
 
Participants are eligible to participate if they meet the following criteria: 
 
 Between the ages of 18-45 years of age 
 A singleton pregnancy at the time of screening between the gestational ages of 18w0d-
28w6d 
 
Participants are ineligible to participate if they meet any of the following criteria: 
 
 Pre-existing Type 1 or Type 2 Diabetes Mellitus 
 Diabetes diagnosed <24 weeks gestational age 
 Multiple gestations (e.g., twins) 
 Hypertension, requiring medication 
 Corticosteroid (IM, IV, or oral) use in the past 30 days 
 Major fetal congenital anomaly 
 Anticipated pre-term delivery because of maternal or fetal indications before 34 weeks 
gestational age 
 Inability to complete the glucose testing before 32 weeks gestational age 
 Advanced HIV 
 Severe liver disease (as indicated by elevated transaminase [AST] and/or alanine 
transaminase [ALT] values) 
 Dumping syndrome as a result of gastric bypass surgery, or other illness/surgery, that 
preclude them from drinking the glucola solution 
 
 
 
 

 
29 
 
 
Hypertension and Corticosteroid Medications 
 
For hypertension, treatment with low-dose/baby aspirin (LDASA/BASA) is acceptable. If a 
participant was on hypertension medication before pregnancy but was discontinued in their first 
trimester, they are eligible to participate.  
 
A participant is still eligible to enter the study if they can complete a 30-day washout period 
post-corticosteroid use, before completing the Visit 1 appointment within their eligibility 
window. If it is discovered that a participant was on corticosteroid medications within 30 days of 
Visit 1, they will not be withdrawn, but the medication use should be documented in the 
Concomitant Medication Form in the database.  
 
Once a participant has been enrolled in the study, if they start a corticosteroid medication, study 
staff should try to schedule Visit 2 (or Visit 3) after a 7-day washout period has been completed. 
If the participant will be out of window, then staff should still schedule the study participant to 
complete their visit in window. At that visit, staff should document the medication use in the 
Concomitant Medication Form.  
 
Hypertension medications 
Hypertension medications 
Corticosteroids 
(IV, IM, oral) 
Amlodipine 
Labetalol 
Betamethasone 
Atenolol 
Lisinopril 
Budesonide 
Bisoprolol 
Losartan 
Cortisone 
Carvedilol 
Methyldopa 
Dexamethasone 
Diazide 
Metoprolol 
Hydrocortisone 
Diltiazem 
Nadolol 
Methylprednisolone 
Enalapril 
Nifedipine 
Prednisolone 
Furosemide 
Triamterine 
Prednisone 
Hydrochlorothiazide (HCTZ) 
Valsartan 
  
 
 
Documentation of Eligibility 
 
If study staff have questions related to a potential participant’s eligibility, the option to keep the 
screening survey open is available in the study database, until the PI or Site PI can be consulted. 
 
Once primary eligibility has been established, study staff will complete a recruitment form, 
collect the participant’s contact information, and verify their gestational age (GA). At this time, 
the participant will be asked to give their verbal consent for study staff to enter the participant’s 
electronic medical record (EMR) in Epic. After obtaining verbal consent, study staff will verify 

 
30 
 
 
gestational age in the participant’s EMR, by checking the estimated date of confinement (EDC) 
and/or dating by ultrasound.  
 
GA will be calculated by the database by the weeks/days from date of the screening time point to 
the EDC entered into the database. If GA is between 18w0d and 28w6d, the participant is 
eligible to undergo their 50-gram Glucose Challenge Test (GCT) between 24w0d-28w6d through 
the GDM2 Study. If the participant’s GA is <18w0d, the participant will be placed into a 
“pending” category and will be re-contacted once they reach 18w0d. NOTE: If a potential 
participant is <14 weeks upon initial contact, they must be re-screened at 18w0d. Participants 
whose GA has exceeded 28w6d are ineligible and will be moved to the ineligible category within 
the database. 
 
 
Documentation of Study Participation in the EMR or Fax 
 
Once a participant has been screened and agreed to participate in the study, study staff will alert 
a participant’s provider of study participation via fax or the participant’s Epic EMR. (See 
Appendix G for Epic documentation templates.) This is important so that the provider does not 
order a 50 g GCT outside of the study, which would unblind the provider and participant, making 
the participant ineligible to participate. Different providers prefer different modes of notification. 
Desired mode of notification will be addressed a provider/staff orientation meetings and made 
known to study staff.  If a participant’s provider prefers fax or cannot be contacted through the 
Epic EMR system, a completed GDM2 cover sheet and study participation letter (see Appendix 
A) are to be faxed, and the originals and fax confirmation sheet retained. 
 
 
Screening Time Point Forms 
 
The following forms are to be completed at the screening time point:  
 
 Screening Survey Form: The screening form determines eligibility according to inclusion 
and exclusion criteria. 
 Recruitment Form: This form records the participant’s OB clinic, and where and how 
they learned about the GDM2 Study. The form also confirms that the participant is 
interested in study participation and that they have given verbal consent for their EMR to 
be reviewed to confirm eligibility and GA. Once their EMR number is captured, it is 
entered into this form and automatically entered into the participant’s Medical Record 
Number (MRN) Capture form. 

 
31 
 
 
 Contact Information Form: The contact form captures the participant’s name, date of 
birth (DOB), mailing address, email, telephone number, emergency contact information, 
and primary care provider information. 
 Gestational Age Verification Form: The participant’s last menstrual period (LMP) and 
EDC are entered into this form, which calculates the participant’s exact GA based upon 
the date of form completion. Once GA is established, the scheduled date of 50 g GCT 
testing can be entered. 
 Participant MRN Capture Form: This form will document the participant’s medical 
record numbers in Epic and CERNER, which will facilitate future data abstraction. 
 
The following forms will be used on an as-needed basis at the screening time point: 
 
 Protocol Deviation Form: This form is to be used for protocol deviations such as the 
enrollment of an ineligible participant, or in the rare case of breach of confidentiality. 
 Withdrawal and Termination Form: The withdrawal and termination form are to be used 
in circumstances where the participant is no longer interested in participation, is lost to 
follow-up (LTFU), or is withdrawn for administrative reasons. 
 
 
 
 

 
32 
 
 
Magee-Womens Hospital Clinical and Translational Research Center 
 
All study visits will take place at the Magee-Womens Hospital Clinical and Translational 
Research Center (MWH CTRC). The CTRC includes examination rooms, a phlebotomy area, 
consult and interview rooms, a reception area, and workstations for study staff. Registered nurses 
and laboratory technicians will assist the study team in administering the glucose testing, 
monitoring patients for adverse events (AE), and will provide phlebotomy and nursing services. 
 
Study staff will schedule participant visits through the CTSI portal. Initial access to the CTSI 
scheduling system can be obtained by contacting Cindy Schatzman, CTRC director. Study staff 
will alert the CTRC of cancelations through the CTSI portal, email, or by phone, as soon as 
possible. 
 
 
Visit 1: 50 g GCT 
 
Preparation for Visit 1 (50 g GCT) 
 
Once the participant is screened and determined to be eligible, study staff will: 
 
 Schedule the participant for their Visit 1 (50 g GCT) between 24w0d and 28w6d 
 Schedule Visit 1 in the CTSI portal and the GDM2 shared team Outlook calendar 
 Prepare paperwork for the visit, to include: 
o Informed consent document 
o CTRC Visit cover sheet 
o Research requisition form for the UPMC Clinical Laboratory Building (CLB), to 
be sent with the study specimen 
 Send the participant an appointment reminder and directions to the MWH CTRC via mail 
or email (see Appendix A)  
 Call, text, or email the participant with an appointment confirmation reminder the day 
before their scheduled visit  
o Participants should be reminded that they do not have to fast, and that their visit 
will take approximately 1 hour and 30 minutes 
 
 
 
 

 
33 
 
 
Informed Consent 
 
Upon arrival at the MWH CTRC, the participant will be taken by study staff to a private area 
where they will undergo the informed consent process. All study procedures, risks, and benefits 
will be explained in detail and the participant will be asked if they have any questions about the 
study. The participant will be asked if they understand all the terms of participation, and their 
comprehension of study concepts will be assessed. Both the participant and study member 
administering the informed consent process will sign the informed consent document (ICD). 
Study staff will retain the original ICD to file with participant documentation. Two additional 
copies of the ICD will be prepared: one will be given to the participant and one will be given to 
the CTRC director for their records. 
 
 
50 gram Glucose Challenge Test 
 
After the participant has been consented, study staff will give the participation the 50 gram 
glucola solution, to be ingested within 5-10 minutes. Once the participant has finished drinking 
the glucola, she will be provided with a timer set to 55 minutes to remind her when it is time for 
her blood draw (with a five minute cushion).  After the 50 g GCT has been administered, study 
staff and CTRC staff will monitor and assess the participant for any problems with the testing 
and treat accordingly. If severe symptoms persist, the Maternal-Fetal Medicine (MFM) fellow 
on-call will be notified. The MFM fellow will consult Dr. Simhan and a further course of 
treatment decided. The telephone number for the MFM fellow on-call is 412-641-2862. The PI 
will be notified and an adverse event (AE) report describing the event will be completed in the 
database. 
 
After the timer goes off, study staff will escort the participant to the CTRC phlebotomy area for 
their blood draw by the CTRC phlebotomist or trained study staff. The sample will be 
pneumatically tubed to the UPMC Clinical Laboratory Building (CLB) for processing. 
 
If the participant is unable to complete the 50 g GCT due to inability to drink the glucola 
solution, keep the solution down, becomes ill, or other issues arise, another attempt to complete 
the GCT may be scheduled before 28w6d GA. If participant cannot or does not repeat the test, 
the patient will be withdrawn from the study and her provider notified so that she may complete 
her testing through them. 
 
If a participant completes the 50 g GCT but refuses further participation in the study, study staff 
will withdraw the participant from the study. The participant’s provider will be alerted through 
the EMR or fax (see Appendix G), that their patient has been withdrawn from the study and that 

 
34 
 
 
they will be unblinded to the participant’s 50 g GCT result. The provider will follow up with 
their patient. 
 
 
IV Protocol 
 
The CTRC offers the use of MWH’s IV Team for participants that are difficult to draw blood 
from. The use of the IV Team should be arranged in advance with the CTRC, as the CTRC staff 
will need to prepare IV supplies and schedule the use of a recliner for the duration of the study 
visit. Once an IV is placed, the participant will remain in the phlebotomy area for the duration of 
the visit under the supervision of the CTRC nursing staff. Blood draws will then be completed at 
the usual intervals by the CTRC nursing staff. 
 
 
Height and Weight Measurements 
 
The participant’s height and weight assessment and demographic form can be completed while 
the participant waits 60 minutes for their blood draw. Study staff will measure the participant’s 
height and weight. Once these measurements are entered into the database, the database will 
calculate the participant’s body mass index (BMI). The CTRC provides a digital scale to 
measure weight and a stadiometer to measure height. 
 
Participants will be asked to remove their footwear, outerwear, and other objects that could alter 
height and weight measurements. The participant will be asked to step onto the scale and stand 
still over the center of the scale with body weight evenly distributed between both feet, arms 
hanging freely by the sides of the body with their head up and face forward. Weight will be 
recorded in pounds. 
 
Height will be measured with the participant having her back straight, heels making contact with 
the wall. The weight of the participant should be evenly distributed on both feet with her legs 
together. The stadiometer’s movable headpiece will then touch the participant’s head (hair 
pressed down) and height recorded in inches. 
 
 
 
 

 
35 
 
 
Visit 1 Forms 
 
The following study forms are to be completed at Visit 1: 
 
 Enrollment/Written Consent Form: The enrollment form documents the informed consent 
process and records participant agreement to have lab specimens banked. 
 Demographic Form: The demographic form will collect information such as the 
participant’s education level, employment status, and household income, race/ethnicity, 
and housing situation. 
 Baseline Clinical Data: The clinical data form captures the participant’s height and 
weight, and calculates BMI. 
 50gm Lab and Repeat Form: This form captures the date and completion of the 50 g test 
and prompts a repeat 50 g test, randomization, or notification that the participant is 
positive for GDM (and notification of their provider). The repeat lab form is to be used in 
cases where the participant did not complete a 50 g GCT. It captures the date and 
completion of the repeat lab test and prompts randomization, notification that the 
participant is positive for GDM and their provider is to be notified, or withdrawal from 
the study if the participant is unwilling or unable to complete the 50 g testing. 
 Randomization Form: This form contains the randomization “button”. Once the button is 
clicked, the form will indicate to which arm the participant has been randomized. 
 
The following forms will be used on an as needed basis at Visit 1: 
 
 Protocol Deviation Form: This form is used in the event of a protocol deviation, 
including but not limited to enrollment of an ineligible participant, failure to report 
AE/SAE in a timely manner, or breach of confidentiality, administration of wrong dose 
of glucola, or failure to follow lab procedures. 
 Adverse Event Form: The AE form will capture and document all adverse and serious 
adverse events and will prompt immediate review by the study physician in cases of 
SAEs. Additionally, this form will facilitate any notice to the DSMB and/or IRB. 
 (Concomitant) Medication Form: This form is used in the event that a participant is 
discovered to be using any medication during a visit, hypertension medications after the 
first trimester, or corticosteroid medications within a specified window (see Hypertension 
and Corticosteroid Medications in Screening Procedures section). 
 Withdrawal and Termination Form: The withdrawal and termination form is used when 
the participant is no longer interested in participation, is lost to follow-up, or was unable 
or unwilling to complete the 50 g GCT or repeat GCT. 

 
36 
 
 
 
Completing Visit 1 
 
Once the blood draw and all other Visit 1 procedures have been completed, study staff will issue 
the participant $10.00 in compensation on a University-issued payment card, plus a parking 
voucher for MWH or $5.00 for transportation reimbursement. If the $5.00 in transportation 
reimbursement is issued, this is to be issued separately as an expense reimbursement 
(nontaxable). Study staff will schedule Visit 2 before the participant leaves the CTRC. Staff will 
relay to the participant that if their 50 g GCT results come back with a value of 200 mg/dL or 
above, making them ineligible for the study, the participant and their provider will be informed. 
Study staff will write a progress note documenting Visit 1. 
 
 
Visit 1 Results 
 
The UPMC CLB should return the patient’s results via fax within 1-2 business days of the visit. 
Once the results are received, study staff will enter the glucose results into the study database. If 
the glucose value is <200 mg/dL, the participant will be randomized by the database into either 
the 75 gram or 100 gram Oral Glucose Tolerance Test (OGTT) study arms (see Randomization 
section for procedure). Study staff will write a progress note documenting the participant’s GCT 
result and randomization result. 
 
Critical Glucose Values 
 
If a participant’s blood glucose values are critical, indicating hypoglycemia (<55 mg/dL) or 
hyperglycemia (>250 mg/dL), the UPMC CLB will follow clinical procedure for clinical values 
by performing a repeat or verification test. If glucose values remain critical after the 
confirmatory test, study staff will be contacted by the UPMC CLB with the results and follow up 
with the participant. If participant is non-symptomatic and the database determines the glucose 
value to be a Severe Adverse Event, Dr. Davis is to be notified. For participants who exhibit 
symptoms of hypo/hyperglycemia, the Maternal-Fetal Medicine fellow on call is to be contacted 
at 412-641-2862 for consultation. Dr. Simhan will also be notified. These events will be 
documented in the participant’s progress notes and in the Adverse Event form. 
 
 
Glucose Challenge Test Results 200 mg/dL 
 
If a participant’s blood glucose result value is 200 mg/dL, they will be excluded from the study 
because they will be diagnosed with diabetes. Both the participant and her provider will be 

 
37 
 
 
unblinded to the value. Study staff will enter an information encounter in Epic or fax a letter with 
this information to non-Epic providers to relay the abnormal result so that appropriate treatment 
can be initiated (see Appendix G).  The provider may also be contacted by telephone. The study 
physician will call the participant with their diagnosis and let them know that their provider will 
be following up with them with a treatment plan. 
 
 
Randomization Procedures 
 
If the participant’s 50 g GCT is less than 200 mg/dL, they are randomized to Arm A (75 g 
OGTT) or Arm B (100 g OGTT) by the randomization form. Once the glucose value from the 50 
g GCT is entered and submitted into the database, study staff will open the randomization form 
in the database. The randomization form displays a “button”, which will then be clicked to 
randomize the participant to Arm A or Arm B. All baseline measures must be completed and 
entered into the database and Visit 1 closed out before randomization can be completed. 
Study participants are to be remain blinded to their randomized study arm until they arrive at the 
MWH CTRC for their Visit 2. When Visit 2 is scheduled, participants will be told that the 
randomization visit will take approximately 3.5 hours so as not to unblind them. The rationale 
for blinding participants to their study arm is preventing dropout based on the knowledge that 
they have been randomized to the longer test (i.e., 3 hour 100 g OGTT).  
 
 
Blinding 
 
Providers are blinded to which test their patient completed and the patient’s numerical test 
results. Study staff will notify providers as to whether or not their patient has GDM; they will not 
be told the specific glucose values. Providers will administer care based on the reported 
diagnoses. Study investigators, including the PI, will remain blinded to the randomization 
schema and study outcomes until the completion of the study. The PI or co-investigators will 
only be unblinded in the following cases: 
 
 50 g glucose value of 200 mg/dL 
 100 g OGTT fasting value >105 mg/dL or 2 hour value >200 mg/dL, if 50 g GCT >130 
mg/dL 
 Any severe adverse event that warrants further medical intervention 
 Symptomatic reactive hypoglycemia (<55 mg/dL) 
 
 
 

 
38 
 
 
Visit 2: 75 g or 100 g OGTT 
 
Preparation for Visit 2 (75 g or 100 g OGTT) 
 
Once the participant has been randomized, study staff will: 
 
 Schedule Visit 2 in the CTSI portal and the GDM2 shared team Outlook calendar 
 Prepare paperwork for the visit, to include: 
o CTRC Visit cover sheet 
o Research requisition forms for the UPMC Clinical Laboratory Building (CLB), to 
be sent with the study specimens 
o Visual aids and instructions for 24-hour dietary recall telephone visit (see 
Appendix D) 
 Send the participant an appointment reminder and directions to the MWH CTRC via mail 
or email (see Appendix A)  
 Call, text, or email the participant with an appointment confirmation reminder the day 
before their scheduled visit  
o Participants should be reminded to fast for 8 hours beforehand, and that their visit 
will take up to 3.5 hours 
 
 
75 g or 100 g Oral Glucose Tolerance Test 
 
Participants will arrive at the MWH CTRC for their Visit 2 in a fasting state. Visit 2 will 
preferably be scheduled in the morning such that participants will not need to wait an extended 
period of time to eat. This visit should not be scheduled after 11:30 am due to extended fasting 
time and the hours of the CTRC staff. Study staff will verbally confirm with the participant that 
they have fasted from food, drink (except water), chewing gum, and tobacco for the previous 8 
hours. 
 
Upon arrival to the CTRC, study staff will escort the participant to the phlebotomy area for their 
blood draw by the CTRC phlebotomist or trained study staff. The sample will be pneumatically 
tubed to the UPMC Clinical Laboratory Building (CLB) for processing. The fasting blood draw 
must be obtained before the glucola is given to the participant. 
 
The study staff will confirm the participant’s randomization group to verify that the participant 
receives the correct glucola. Once a participant’s randomization assignment has been verified, 
the participant will receive their glucola from the study staff, which should be ingested within 5-

 
39 
 
 
10 minutes. After the glucola has been ingested, the participant will be given a digital time to set 
for 55 minutes to remind them of their next blood draw.  
 
Study staff will monitor time in between blood draws and escort the participant to the 
phlebotomy area for their blood draws at the appropriate time intervals. Participants undergoing 
the 75 g test will have their blood drawn at the 1 hour mark and 2 hour mark, for a total of 3 
blood draws (including fasting blood draw). Participants undergoing the 100 g test will have 
their blood drawn at the 1 hour, 2 hour, and 3 hour marks, for a total of 4 blood draws (including 
fasting blood draw). During the course of Visit 2, study staff and the CTRC staff will monitor 
and assess the participant for any problems with the testing and treat accordingly. If severe 
symptoms from the test persist, the Maternal-Fetal Medicine fellow on call will consult with Dr. 
Simhan. The telephone number for the MFM fellow on call is 412-641-2862. 
 
 
IV Protocol 
 
The CTRC offers the use of MWH’s IV Team for participants that are difficult to draw blood 
from. The use of the IV Team should be arranged in advance with the CTRC, as the CTRC staff 
will need to prepare IV supplies and schedule the use of a recliner for the duration of the study 
visit. Once an IV is placed, the participant will remain in the phlebotomy area for the duration of 
the visit under the supervision of the CTRC nursing staff. Blood draws will then be completed at 
the usual intervals by the CTRC nursing staff. 
 
 
Completion of Study Questionnaires 
 
Between blood draws, participants will complete Visit 2 study questionnaires and a 24-hour 
dietary recall on a study iPad. (Note: The Baseline GDM Beliefs questionnaire is to be 
administered at the end of the visit, after all questionnaires and blood draws are completed, as 
this questionnaire assesses how participants felt about the whole of their GDM testing.) After the 
participant receives their last blood draw, they will be provided with a light snack supplied by 
the CTRC. 
 
 
Visit 2 Forms 
 
The following study forms will be completed at Visit 2 (see Appendix B): 
 
 24-Hour Dietary Recall: This form is a placeholder in the study database, prompting 
study staff to mark if the assessment was completed or reason for non-completion. 

 
40 
 
 
 24 Hour Dietary Recall Telephone: This form is a placeholder in the study database, 
prompting study staff to mark if the assessment was completed or reason for non-
completion. The second recall should be completed with participants over the phone at a 
random time, no earlier than 1 week after the visit and up to 4 weeks post-visit. 
 Mood Questionnaire: This form captures information regarding general wellbeing, 
physical health, and thoughts and feelings regarding pregnancy. 
 Postpartum Depression Questionnaire: This form assesses signs and symptoms of 
depression. This is a scored questionnaire, with a score of 13 or higher indicating the 
likely presence of depression. For a score of 13 or higher, or any answer besides “Never” 
for question #10 (“The thought of harming myself has occurred to me”), appropriate 
actions will be taken and clinical staff notified (see Postpartum Depression 
Questionnaire section above). 
 Health Habits Questionnaire: This form queries participants about their sleep schedule; 
exercise habits before and during pregnancy; tobacco, alcohol, and drug use before and 
during pregnancy; and eating habits. 
 Obstetrical History Questionnaire: This form collects general obstetrical history, 
including menstrual cycle, birth control, pre-pregnancy weight, and the outcomes of 
previous pregnancies (if applicable). 
 Family Health History Questionnaire: This form captures the participant’s family history 
of diabetes and weight/body type. 
 75gm or 100gm Fasting Glucose Lab Form: This form will capture the date and time of 
blood collection and processing completion, and the date the study staff received the 
results. It will record 2 hourly values or 3 hourly vales depending on whether the 
participant was randomized to the 75 g or 100 g test. In cases where the participant was 
not able to complete the first scheduled test but returned for a second attempt, a repeat lab 
form will be generated. This will capture the completion date and values of the repeat 
test. Regardless of a positive or negative diagnosis, the form will prompt study staff to 
record that they notified the participant and her provider of the results. If the test was not 
completed, the reason for non-completion will be recorded. 
 Clinical and Cytokine Lab Form: The clinical lab form will document the date and time 
of blood collection, the date and time of specimen processing, and the date the study staff 
received the results. Values for fasting glucose, insulin, lipid panel, and high-sensitivity 
c-reactive peptide (hsCRP) are recorded on this form. 
 Baseline Patient Beliefs Questionnaire: This form, to be administered after the rest of 
Visit 2 has been completed, will ask participants about their experience and personal 
perspectives on screening for GDM. 
 
 
 

 
41 
 
 
The following forms will be used on an as needed basis at Visit 2: 
 
 Protocol Deviation Form: This form is used in the event of a protocol deviation, 
including but not limited to enrollment of an ineligible participant, failure to report 
AE/SAE in a timely manner, breach of confidentiality, administration of wrong dose of 
glucola, or failure to follow lab procedures. 
 Adverse Event Form: The AE form will capture and document all adverse and serious 
adverse events and will prompt immediate review by the study physician in cases of 
SAEs. Additionally, this form will facilitate any notice to the DSMB and/or IRB. 
 (Concomitant) Medication Form: This form is used in the event that a participant is 
discovered to be using any medication during a visit, hypertension medications after the 
first trimester, or corticosteroid medications within a specified window (see Hypertension 
and Corticosteroid Medications in Screening Procedures section). 
 Withdrawal and Termination Form: The withdrawal and termination form is used when 
the participant is no longer interested in participation, is lost to follow-up, or was unable 
or unwilling to complete Visit 2 or a repeat test. 
 
 
Postpartum Depression Questionnaire 
 
After the participant has completed their study questionnaires (except the Baseline GDM Beliefs 
questionnaire), study staff will review the forms for completeness and review the Postpartum 
Depression questionnaire score. If the participant scores 13 or higher, or answers question 10 
(“The thought of harming myself has occurred to me”) with any response other than “Never”, 
study staff will contact the participant’s OB to notify them and offer mental health resources to 
the participant.  
 
In extreme cases, where the threat of self-harm is evident, the participant is to be sent to the 
MWH emergency department (ED) for immediate treatment. Drs. Davis and Simhan are to be 
immediately notified and Dr. Simhan will follow up with the patient to determine the outcome of 
the ED evaluation. In these extreme cases, a Severe Adverse Event form will be completed. 
 
 
Completing Visit 2 
 
Once the blood draws and all other Visit 2 procedures have been completed, study staff will 
issue the participant $30.00 in compensation on a University-issued payment card, plus a parking 
voucher for MWH or $5.00 for transportation reimbursement. If the $5.00 in transportation 
reimbursement is issued, this is to be issued separately as an expense reimbursement 

 
42 
 
 
(nontaxable). Study staff will tell the participant to expect a telephone call the following business 
day with the results of their OGTT. Study staff will also give the participant instructions and 
visual materials to complete the second 24-hour dietary recall, which will occur randomly within 
the following 2 weeks. The participant will be told that they will be paid $10.00 to their payment 
card after the second recall has been completed. Study staff will document Visit 2 in the 
participant’s progress notes. 
 
 
75 g or 100 g OGTT Laboratory Results 
 
The UPMC Clinical Laboratory will relay glucose and clinical lab results to study staff via fax 
within one to two business days. Clinical labs (lipid panel, high-sensitivity c-reactive peptide, 
and insulin) and glucose values will then be entered into the database, which will make the 
diagnosis of GDM based on criteria for the respective OGTT tests.  
 
Diagnostic criteria of GDM differs between Arm A (75 g OGTT) and Arm B (100 g OGTT) as 
follows: 
 
Participants randomized to Arm A (75 g OGTT) will be diagnosed under IADPSG criteria. 
A positive GDM diagnosis under IADPSG criteria is 1 abnormal value from the 75 g test: 
Fasting glucose value 
1 hour glucose value 
2 hour glucose value 
92 mg/dL 
180 mg/dL 
153 mg/dL 
 
 
Participants randomized to Arm B (100 g OGTT) will be diagnosed under Carpenter-
Coustan criteria. A positive GDM diagnosis under Carpenter-Coustan criteria is 50 g GCT 
130 mg/dL (value from Visit 1) and 2 abnormal values from the 100 g test: 
Fasting glucose value 1 hour glucose value 2 hour glucose value 3 hour glucose value 
95 mg/dL 
180 mg/dL 
155 mg/dL 
140 mg/dL 
 
 
 
 

 
43 
 
 
“Mild GDM” 
 
For the purposes of study outcomes, the study database will automatically designate participants 
completing the 100 g OGTT (Arm B) that meet one of the three criteria listed below as “Mild 
GDM”.  
 
1. 50 g GCT 130 mg/dL and 0 or 1 abnormal values from 100 g OGTT (by Carpenter-
Coustan criteria) 
2. 50 g GCT <130 mg/dL and 1, 2, 3, or 4 abnormal values from 100 g OGTT (by 
Carpenter-Coustan criteria) 
3. 100 g OGTT fasting value 92 mg/dL 
 
This is not a clinical diagnosis, and participants meeting these criteria will be reported to 
providers as having a negative GDM diagnosis as they would not have been diagnosed under 
current clinical criteria. For the purposes of this study, all participants designated as having 
“Mild GDM” will be selected to return for Visit 3 at 12-months postpartum. 
 
 
Unblinding Providers to OGTT Results 
 
If a participant’s 50 g GCT value is 130 mg/dL, and their 100 g OGTT fasting value is 105 
mg/dL or 2 hour value is 200 mg/dL, their provider will be unblinded to their results for ethical 
and safety reasons, so treatment for GDM can be initiated. These participants would not 
normally be diagnosed in clinical practice because they had a normal 50 g GCT. These safety 
thresholds were used in the HAPO Study (Metzger, BE, et al., N Engl J Med 2008). Study staff 
will alert the participant’s provider of their results through Epic (or fax for Epic non-users). The 
study physician will also notify participants via telephone. 
 
 
Critical Glucose Values 
 
If a participant’s blood glucose values are critical, indicating hypoglycemia (<55 mg/dL) or 
hyperglycemia (>250 mg/dL), the UPMC CLB will follow clinical procedure for clinical values 
by performing a repeat or verification test. If glucose values remain critical after the 
confirmatory test, study staff will be contacted by the UPMC CLB with the results and follow up 
with the participant. If participant is non-symptomatic and the database determines the glucose 
value to be a Severe Adverse Event, Dr. Davis is to be notified. For participants who exhibit 
symptoms of hypo/hyperglycemia, the Maternal-Fetal Medicine fellow on call is to be contacted 
at 412-641-2862 for consultation. Dr. Simhan will also be notified. These events will be 
documented in the participant’s progress notes. 

 
44 
 
 
 
OGTT Result Reporting 
 
Participants will be notified of their 75 g or 100 g OGTT results within 1 or 2 business days of 
testing. Study staff will notify participants of a negative diagnosis by telephone or letter. In cases 
of positive GDM diagnosis, study staff will notify the study physician, who will directly call the 
participant with her diagnosis, answer any questions, and relay that she is to follow up with her 
provider for treatment. The participant’s providers will be notified via Epic letter and encounter 
or a fax, informing them of the positive or negative GDM diagnosis. Study staff will also 
document results and notifications in the participant’s progress notes. Epic encounters and letters 
are from Dr. Simhan, Department of Maternal-Fetal Medicine, routed to the participant’s OB 
provider. (See Appendix G.) 
 
 
Visit 2 Results Back Entry 
 
Once all participants have completed their Visit 2 and delivered, study staff will back-enter all 
Visit 2 glucose results into participants’ Epic EMR for clinical use post-study. At this time, 
providers will be unblinded to the specific numeric results of their patients’ testing, and whether 
they completed the 75 g or 100 g OGTT. Participants may also request that a paper copy of their 
results be sent to them after they deliver. 
 

 
45 
 
 
Delivery Time Point 
 
Cord Blood Collection 
 
The study staff will maintain an ongoing list of participants who have completed their 
randomization visit and are approaching their Estimated Date of Confinement (EDC). The list 
will facilitate the collection of umbilical cord blood samples and infant assessment at delivery by 
Obstetric Specimen Procurement Unit (OSPU) staff and study staff. Study staff will provide an 
updated list on a monthly basis to the OSPU staff so that the procurement team is aware of which 
patients are in the study and their anticipated delivery dates. OSPU staff and study staff will also 
use Augr, a clinical application, which sends notifications when study participants have been 
admitted to MWH. (See Laboratory Procedures and Protocols section for additional information 
regarding cord blood collection procedures.) 
 
If OSPU staff know a participant is in a labor and delivery room (LDR), they will leave blood 
tubes for the LDR nurses to collect study specimens. LDR nurses have been instructed where to 
find GDM2 delivery collection packets in the OSPU office if a participant is admitted to LDR 
and OSPU staff are not available. Some cord blood samples may not be obtained if a participant 
delivers when OSPU staff is unavailable. OSPU does not collect specimens during obstetric 
emergencies or precipitous deliveries, etc.  
 
 
Infant Skinfold Measurement 
 
A flank skinfold measurement will be obtained on infants 24-48 hours after delivery. Study staff 
will obtain the skinfold measurements during regular business hours of 8:30 am to 5:00 pm, 
Monday through Friday, and occasional Saturdays. Study staff will visit participants in their 
postpartum room, where they will also give the participant their delivery gift. The flank skinfold 
is a diagonal fold taken just above the iliac crest along the midaxillary line. At least two 
measurements should be obtained with the skinfold calipers. The time of the measurements 
should also be recorded on a paper infant skinfold assessment form. Staff will then enter this 
information into the study database. 
 
Some skinfold measurements will not be able to be obtained if a participant delivers or the infant 
reaches 24-48 hours on a weekend or holiday when staff are unavailable, or if the parents refuse 
the measurements. Not all infants will be clinically able to undergo skinfold assessment.  
 
 
 

 
46 
 
 
Exclusion criteria for the skinfold assessment are as follows: 
 
 Infant admission to the NICU 
 Cannot pass “car seat test” 
 Infant requires external warming 
 <35 weeks of gestational age 
 
 
Delivery Time Point Forms 
 
The following forms are to be completed at the delivery time point: 
 
 Delivery Cord Blood Collection for C-Peptide Form: This form will collect the date and 
time of cord blood collection, date and time of processing, type and amount of specimen 
collected, and record the c-peptide value. 
 Delivery Infant Assessment Form: This form will record the date, time, and completion 
of the infant skinfold measurements, If the assessment was not completed, reason for 
non-completion will be recorded. 
 Infant Medical Record Number Form: This form will document the infant’s medical 
record number for purposes of data abstraction. Study staff will collect the MRN from the 
infant’s EMR. 
 
The following forms will be used on an as needed basis at the delivery time point: 
 
 Protocol Deviation Form: This form is used in the event of a protocol deviation, 
including but not limited to deviation from the cord blood collection or infant skinfold 
assessment protocols, or a breach of confidentiality. 
 Withdrawal and Termination Form: The withdrawal and termination form is used when 
the participant is no longer interested in participation, is lost to follow-up, or can no 
longer participate in the study.  
 
 
Physician Beliefs Questionnaire 
 
The Physician Beliefs Questionnaire will be used to assess providers’ views on current GDM 
testing strategies. An electronic RedCap survey will be sent via email to providers within the 
clinics the study recruited from, once all study participants have delivered.  
 
 

 
47 
 
 
Postpartum Telephone Encounters 
 
Those participants with a positive diagnosis of GDM, study diagnosis of “mild GDM”, and a 
random group without GDM, will be followed by study staff through telephone assessments at 3, 
6, and 9 months postpartum. These participants will also complete Visit 3 at 12 months 
postpartum. Those participants identified as “true normal” or participants without GDM are 
randomly selected for this postpartum follow-up by programming sequences within the study 
database, created by the data center. After the delivery time point is closed out in the study 
database, the study database will indicate to study staff whether that specific participant has been 
selected for postpartum follow-up. 
 
 
3, 6, and 9 Month Postpartum Phone Calls 
 
The window to complete the 3, 6, and 9 month postpartum phone calls starts two weeks before 
the “target date” and ends 4 weeks after the “target date”. Example: If a participant delivers on 
12/1/2017, her 3 month “target date” is 3/1/18, and her window to complete the 3 month phone 
assessment is 2/15/18 to 3/29/18.  
 
Study staff will administer the phone assessments, which collect basic information regarding the 
overall health and wellbeing of participants and their infant feeding practices. These phone 
encounters are also designed to keep study staff in contact with participants in between the 
delivery and Visit 3 (12 months postpartum) time points. Through continuing contact, 
participants may be more likely to participate in the 12 month postpartum follow-up and the 
study staff will be able to document participant health status or changes in contact information. 
 
 
3, 6, and 9 Month Postpartum Forms 
 
The following forms are to be completed at the 3, 6, and 9 month postpartum time points: 
 
 Health Outcomes Form: This form queries participants about visits to the emergency 
department, hospitalizations, contraception, pregnancy, or any new information regarding 
their and their baby’s health. 
 Infant Feeding Questionnaire: This form captures basic information regarding 
breastfeeding, formula feeding, and solid food feeding. The form also captures the 
infant’s height, weight, and general health in the previous 3 months. 
 
 
 

 
48 
 
 
The following forms will be used on an as needed basis at the 3, 6, and 9 month postpartum time 
points: 
 
 Protocol Deviation Form: This form is used in the event of a protocol deviation, 
including but not limited to a breach of confidentiality. 
 Infant Status Form: This form is used to document any notable changes in the infant’s 
status or custody situation (e.g., death, adoption, loss of custody, hospitalization, etc.) 
 Withdrawal and Termination Form: The withdrawal and termination form is used when 
the participant is no longer interested in participation, is lost to follow-up, or can no 
longer participate in the study.  
 
 

 
49 
 
 
Visit 3: 12 Months Postpartum 
 
Those study participants selected to complete the 3, 6, and 9 month postpartum follow-up 
encounters will be asked to return for a follow-up 75 g OGTT assessment at 12 months 
postpartum (Visit 3), to be tested for impaired glucose tolerance (“pre-diabetes”) or Type 2 
diabetes mellitus.  
 
The target window for Visit 3 is between 11 and 14 months postpartum. Participants may choose 
to schedule the infant assessment portion and the 75 g OGTT at separate times/dates within the 
Visit 3 target window. 
 
 
Preparation for Visit 3 
 
Once a participant has been scheduled for her Visit 3, study staff will: 
 
 Schedule Visit 3 in the CTSI portal and the GDM2 shared team Outlook calendar 
 Prepare paperwork for the visit, to include: 
o CTRC Visit cover sheet 
o Research requisition forms for the UPMC Clinical Laboratory Building (CLB), to 
be sent with the study specimens 
o Infant assessment form 
o Visual aids and instructions for 24-hour dietary recall telephone visit (see 
Appendix D) 
 Send the participant an appointment reminder and directions to the MWH CTRC via mail 
or email (see Appendix A)  
 Call, text, or email the participant with an appointment confirmation reminder the day 
before their scheduled visit  
o Participants should be reminded to fast for 8 hours beforehand, and that their visit 
will take 2.5 hours 
 
Study staff will review the medical records of participants diagnosed with GDM to determine 
whether they completed postpartum glucose testing (75 g OGTT, A1c, etc.). If a participant has 
been diagnosed with prediabetes or diabetes before Visit 3, they will not complete the 75 g 
OGTT at Visit 3 but will still have their fasting blood draw. 
 
 

 
50 
 
 
75 g Oral Glucose Tolerance Test 
 
Participants will arrive at the MWH CTRC in a fasting state. The visit will preferably be 
scheduled in the morning such that participants will not wait an extended period of time to eat. 
This visit should not be scheduled after 12:30 pm due to extended fasting time and the hours of 
the CTRC staff. Study staff will verbally confirm with the participant that they have fasted from 
food, drink (except water), chewing gum, and tobacco for the previous 8 hours. Staff will also 
verbally re-consent the participant by reviewing Visit 3 procedures and ensuring the participant’s 
agreement to continue participation in the study. This verbal re-consent will be documented in 
the participant’s progress notes.  
 
Study staff will then escort the participant to the phlebotomy area for their blood draw by the 
CTRC phlebotomist or trained study staff. The sample will be pneumatically tubed to the UPMC 
Clinical Laboratory Building (CLB) for processing. The fasting blood draw must be obtained 
before the glucola is given to the participant. 
 
Once the fasting blood draw has been completed, the participant will receive their glucola from 
the study staff, which should be ingested within 5-10 minutes. After the glucola has been 
ingested, the participant will be given a digital time to set for 55 minutes to remind them of their 
next blood draw.  
 
Study staff will monitor time in between blood draws and escort the participant to the 
phlebotomy area for their blood draws at the appropriate time intervals. Participants will have 
their blood drawn at the 1 hour mark and 2 hour mark, for a total of 3 blood draws (including 
fasting blood draw). During the course of Visit 3, study staff and the CTRC staff will monitor 
and assess the participant for any problems with the testing and treat accordingly. If severe 
symptoms from the test persist, the Maternal-Fetal Medicine fellow on call will consult with Dr. 
Simhan. The telephone number for the MFM fellow on call is 412-641-2862. 
 
 
IV Protocol 
 
The CTRC offers the use of MWH’s IV Team for participants that are difficult to draw blood 
from. The use of the IV Team should be arranged in advance with the CTRC, as the CTRC staff 
will need to prepare IV supplies and schedule the use of a recliner for the duration of the study 
visit. Once an IV is placed, the participant will remain in the phlebotomy area for the duration of 
the visit under the supervision of the CTRC nursing staff. Blood draws will then be completed at 
the usual intervals by the CTRC nursing staff. 
 
 

 
51 
 
 
Visit 3 Forms 
 
The following forms are to be completed at Visit 3: 
 
 24-Hour Dietary Recall: This form is a placeholder in the study database, prompting 
study staff to mark if the assessment was completed or reason for non-completion. 
 24 Hour Dietary Recall Telephone: This form is a placeholder in the study database, 
prompting study staff to mark if the assessment was completed or reason for non-
completion. The second recall should be completed with participants over the phone at a 
random time, no earlier than 1 week after the visit and up to 4 weeks post-visit. 
 75gm Fasting Glucose Lab Form: This form captures the date and completion of the 75 g 
test and determines if a participant is positive for diabetes or prediabetes (and if their 
physician is to be notified). If the test needs to be repeated, this form captures the repeat 
testing information. 
 Clinical and Cytokine Form: This form documents the date and time of blood collection, 
the date and time of specimen processing, and the date that the study team received the 
results. Values for fasting glucose, insulin, lipid panel, A1c, and cytokines including 
hsCRP, adiponectin, leptin, and free fatty acids are recorded on this form. 
 Postpartum Depression Questionnaire: This form assesses signs and symptoms of 
depression. This is a scored questionnaire, with a score of 13 or higher indicating the 
likely presence of depression. For a score of 13 or higher, or any answer besides “Never” 
for question #10 (“The thought of harming myself has occurred to me”), appropriate 
actions will be taken and clinical staff notified. 
 Health Outcomes Form: This form asks participants about visits to the ED, 
hospitalizations, and any new information regarding their or their baby’s health. 
 Infant Feeding Questionnaire: This form asks questions regarding breastfeeding, formula 
feeding, and solid food feeding, height, weight, and general health over the last 3 months. 
 Health Since Birth Questionnaire: This form captures the participant’s health and weight 
since they delivered. 
 12-Month Mood Questionnaire: This form captures information regarding general 
wellbeing, physical health, and thoughts and feelings in the past month. 
 12-Month Health Habits Questionnaire: This form queries participants regarding their 
general health and wellbeing, including sleep and exercise habits, and information 
regarding weight gain and loss postpartum. 
 Urine Pregnancy Test Form: This form confirms that the urine pregnancy test has been 
completed and records positive/negative result. 
 Clinical Data Form 12-Month Visit: The clinical data form captures the participant’s 
weight and calculates BMI using their height obtained at Visit 1. 

 
52 
 
 
 Infant Assessment Form: This form captures the infant’s length, weight, head 
circumference, and skinfold caliper assessments. 
 
The following forms will be used on an as needed basis at Visit 3: 
 
 Confirmation of DM Testing: This form will document that study staff reviewed the 
participant’s EMR for postpartum glucose testing, and the results if available. 
 Protocol Deviation Form: This form is used in the event of a protocol deviation, 
including but not limited to failure to report AE/SAE in a timely manner, breach of 
confidentiality, administration of wrong dose of glucola, or failure to follow lab 
procedures. 
 Infant Status Form: This form is used to document any notable changes in the infant’s 
status or custody situation (e.g., death, adoption, loss of custody, hospitalization, etc.) 
 (Concomitant) Medication Form: This form is used in the event that a participant is 
discovered to be using any medication during a visit, or corticosteroid medications within 
a specified window (see Hypertension and Corticosteroid Medications in Screening 
Procedures section). 
 Adverse Event Form: The AE form will capture and document all adverse and serious 
adverse events and will prompt immediate review by the study physician in cases of 
SAEs. Additionally, this form will facilitate any notice to the DSMB and/or IRB. 
 Withdrawal and Termination Form: The withdrawal and termination form is used when 
the participant is no longer interested in participation, is lost to follow-up, or was unable 
or unwilling to complete Visit 2 or a repeat test. 
 
 
Visit 3 Questionnaires and Assessments 
 
Between blood draws, participants will complete Visit 3 study questionnaires and a 24-hour 
dietary recall on a study iPad. After the participant receives their last blood draw, they will be 
provided with a light snack supplied by the CTRC. 
 
All participants will undergo a urine pregnancy test, as approximately 5% of women are 
expected to become pregnant by the 12 month postpartum visit. Pregnancy is likely to change the 
participant’s metabolic profile, including glucose values. Pregnant participants may choose to 
complete the 75 g test at their own discretion. Study staff will offer the option of sending the 75 
g OGTT results to their OB providers, which may be used in lieu of a standard clinical 50 g GCT 
(at their provider’s discretion). For pregnant participants who choose this option, results will be 
evaluated according to IADPSG criteria and routed to their OB provider. 
 

 
53 
 
 
Infants will undergo anthropometric measurements at Visit 3 using the MetroHealth Medical 
Research Unit protocol found in Appendix E. The study staff will be trained to administer these 
measurements, which will include length/height, weight, head circumference, and skinfold 
caliper assessments of the infant’s triceps, subscapular area, and flank. 
 
 
Postpartum Depression Questionnaire 
 
After the participant has completed their study questionnaires, study staff will review the forms 
for completeness and review the Postpartum Depression questionnaire score. If the participant 
scores 13 or higher, or answers question 10 (“The thought of harming myself has occurred to 
me”) with any response other than “Never”, study staff will check in with the participant to 
ensure that their providers are aware and offer mental health resources to the participant. If the 
participant agrees, study staff will notify the participant’s provider of their depression screening 
via Epic.  
 
In extreme cases, where the threat of self-harm is evident, the participant is to be sent to the 
MWH emergency department (ED) for immediate treatment. Drs. Davis and Simhan are to be 
immediately notified and Dr. Simhan will follow up with the patient to determine the outcome of 
the ED evaluation. In these extreme cases, a Severe Adverse Event form will be completed. 
 
 
Completing Visit 3 
 
Once the blood draws and all other Visit 3 procedures have been completed, study staff will 
issue the participant $30.00 in compensation on a University-issued payment card, plus a parking 
voucher for MWH or $5.00 for transportation reimbursement. If the $5.00 in transportation 
reimbursement is issued, this is to be issued separately as an expense reimbursement 
(nontaxable).  
 
Study staff will tell the participant to expect a telephone call the following business day with the 
results of their testing. Study staff will also give the participant instructions and visual materials 
to complete the second 24-hour dietary recall, which will occur randomly within the following 2 
weeks. The participant will be told that they will be paid $10.00 to their payment card after the 
second recall has been completed. Study staff will document Visit 3 in the participant’s progress 
notes. 
 
After Visit 3, the study staff or investigators may contact the participant by phone, letter, or 
email, for clarifications of any missing, discrepant, or unclear information reported on the data 
collection forms or abstracted from their EMR, if necessary. 

 
54 
 
 
 
 
Visit 3 Laboratory Results 
 
The UPMC Clinical Laboratory will relay glucose and clinical lab results to study staff via fax 
within one to two business days. Clinical labs (lipid panel, high-sensitivity c-reactive peptide, 
insulin, and HgbA1c) and glucose values will then be entered into the database, which will make 
the diagnosis of prediabetes (impaired glucose tolerance) or Type 2 diabetes, based on the 
current American Diabetes Association (ADA) criteria, which are as follows: A diagnosis of 
Type 2 diabetes will be made if 1 values are abnormal: 
 
Fasting glucose value 
1 hour glucose value 
2 hour glucose value 
126 mg/dL 
Not used for diagnosis 
200 mg/dL 
 
 
A diagnosis of impaired glucose tolerance (prediabetes) will be made if 1 values are within 
the following ranges: 
 
Fasting glucose value 
1 hour glucose value 
2 hour glucose value 
100-125 mg/dL 
Not used for diagnosis 
140-199 mg/dL 
 
 
The database will also indicate elevated lipid values, of which the participant will be 
notified by the PI: 
 
Triglycerides 
Cholesterol 
200 mg/dL 
160 mg/dL 
 
 
If their results indicate diabetes or prediabetes, participants will be notified of their results by a 
study physicians and told to follow up with their primary care provider for treatment. A letter 
and informational encounter will be entered into the participant’s Epic EMR or faxed to Epic 
non-users to inform providers of the diagnosis. A paper copy of the results will also be mailed to 
the participant for her personal records. (See Appendix G.) 
 
If the participant’s results are negative for diabetes, prediabetes, or elevated lipids, study staff 
will call the participant to inform her of her non-diagnosis. A paper copy of the result will be 
mailed to the participant for her personal records. (See Appendix G.)  
 

 
55 
 
 
 
Visit 3 Results Back Entry 
 
Once all participants have completed their Visit 3, study staff will back-enter Visit 3 glucose and 
A1c results into participants’ Epic EMR for providers’ reference. For participants whose results 
indicate pre-diabetes or Type 2 diabetes mellitus, their glucose and A1c results will be entered 
into their Epic EMR immediately and routed to their primary care providers. Paper hard copies 
of the full results will also be sent to participants for their personal records. 
 
 
Quest Diagnostics Visit 
 
If a participant is unable to return to MWH to complete her Visit 3, the study may offer 
participants the option to complete their Visit 3 at a Quest Diagnostics location convenient to 
them. At Quest Diagnostics, they will complete a 75 g OGTT, pregnancy test, and have their 
weight measured, all identically to the procedures that would have been undertaken at MWH. If 
a participant completes their Visit 3 at a Quest Diagnostics location, it is preferable that the 
questionnaires are completed on the same day as testing. The only assessments that study staff 
would be unable to obtain are the anthropometric infant measurements.  
 
If a participant agrees to complete Visit 3 at a Quest Diagnostics location, study staff will mail 
them a prefilled laboratory requisition and instructions. The requisition will use the participant’s 
study ID and DOB only (no other identifying information such as name) and instruct Quest 
Diagnostics staff to bill the GDM2 account. Results will be faxed to the GDM2 office, similarly 
to the UPMC lab’s results, and staff will inform the participant of her results per usual protocol. 
Once the results are received, study staff will issue payment for Visit 3 to the participant. The 
payment will be the same as if the participant had returned to MWH for her visit ($30.00, and 
parking validation or $5.00 for transportation reimbursement). 
 
 
 

 
56 
 
 
Data Abstraction 
 
Health Research Record Request (R3) 
 
The Health Research Record Request (R3) team is a single point-of-contact for researchers to 
request access to components of UPMC-based electronic medical records for research purposes. 
The GDM2 Study will work with the R3 team to facilitate data abstraction for independent out 
outcome variables and covariates from the participants’ maternal and neonatal EMR. The 
research team will follow-up with the entire maternal and infant pair cohort with the assistance 
of the R3 team. Variables will be selected and requested by the PI. 
 
 
R3 Data Collection 
 
Once written consent is provided and the participant completes the first study visit, at least one 
prenatal and two postpartum EHR data abstractions of their records will be conducted. R3 staff 
will abstract information at various time points of the GDM2 Study. The following data will be 
collected: 
 
 General demographic information will be collected, including maternal age, race, and 
type of insurance coverage 
 Pre-pregnancy weight; all measured prenatal weights; pregnancy-induced hypertension 
and associated gestational age; delivery or postpartum weight; and last recorded weight 
prior to pregnancy 
 Obstetric history and medical history including type of contraception, medications and 
medical diagnoses at baseline and delivery, as well as blood pressures at time of delivery 
 Last menstrual period before pregnancy; patient-reported pre-pregnancy weight at the 
first prenatal visit; type of delivery; prenatal and delivery complications 
 Number of cigarettes before pregnancy and at each trimester; quantity and frequency of 
alcohol and drug use 
 Information regarding any treatment for gestational diabetes – we will ascertain the 
existence of GDM treatment including any of the following: medical nutritional therapy; 
self-monitoring of glucose; insulin therapy with initial dose, dose at delivery, and total 
maximum dosage; or oral hypoglycemic agents such as glyburide or metformin with 
initial dose; dose at delivery, and total maximum dosage 
 Number of ultrasounds and tests for assessment of fetal wellbeing (biophysical profiles, 
non-stress tests), date of delivery, and gestational age at delivery 
 Information regarding neonatal course, including need for NICU or special care nursery 
admission; need for intubation or additional respiratory support as well as duration of 

 
57 
 
 
such support; hypoglycemia (defined as blood glucose <40 mg/dL in the first 24 hours of 
life); and hyperbilirubinemia requiring phototherapy, will also be collected 
 Labs, diagnostic imaging/tests, and medical history (e.g., height, weight, blood pressure, 
and diagnoses) from the outpatient, ED, and inpatient record on the maternal and infant 
pair cohort 
 
NOTE: The EHR also enables the retrieval of clinical and administrative data from certain other 
area hospitals in the event that women delivery or present to the emergency department at a 
hospital other than MWH, through the use of “Care Everywhere”. 
 
 
Data Collection Associated with Study Outcomes 
 
To assess the study’s main outcomes, data abstraction through the R3 system will collect the 
following data: 
 
 Small for gestational age (SGA, defined as birth weight 10th percentile for gestational 
age) or large for gestational age (LGA, defined as birth weight 90th percentile for 
gestational age): assessed using the birth weight and gestational age from the delivery 
record (SGA and LGA will be defined using sex-specific U.S. birth weight curves 
corrected for implausible ultrasound estimates (Talgi N, et al., Pediatrics 2014). 
Macrosomia will be defined in two ways: birth weight 4000 grams and birth weight 
4500 grams. 
 Cesarean delivery: defined as either primary or repeat C-section. We will also include 
information on the primary indication for the C-section, including prior C-section with no 
TOLAC (trial of labor after C-section), failure to progress, fetal intolerance to labor, 
breech presentation, placentia previa or other placental abnormalities, and other. 
 Fetal growth and body composition measured using length and weight 
 Maternal composite: (1) 3rd or 4th degree vaginal lacerations; (2) postpartum hemorrhage 
(definied as an estimated blood loss >1000 mL after vaginal delivery or >1500 mL after 
C-section, with or without need for blood transfusion); (3) pre-eclampsia and 
hypertensive disorders or pregnancy (defined according to ACOG diagnostic criteria) – 
will be obtained from the delivery and ICD-9 and -10 diagnostic codes in the EHR 
 Neonatal composite: (1) hypoglycemia (defined as blood glucose <40 mg/dL in the first 
24 hours of life, measured by heel stick within 1 hour after delivery); (2) 
hyperbilirubinemia requiring phototherapy (bilirubin measured transcutaneously from 36 
hours post-delivery and as needed); (3) stillbirth (absence of fetal heart tones before 
delivery); (4) birth trauma (defined as shoulder dystocia or brachial plexus injuries) – will 
be obtained from the lab section of the neonatal EHR 

 
58 
 
 
Confidentiality 
 
The collection of sensitive information about participants is limited to the amount necessary to 
achieve the aims of the research. R3 computer-based files will only be made available to 
personnel involved in the study with access privileges and passwords. Prior to accessing any 
study-related information, personnel will be required to sign statements agreeing to protect the 
security and confidentiality of identifiable information. 
 
 

 
59 
 
 
Laboratory Procedures and Protocols 
 
Specimen Collection 
 
At Visit 1, one 5.0 mL gold top tube will be collected at the 1-hour time point for glucose testing. 
 
At Visit 2, three 5.0 mL gold top tubes and one 3.5 mL lavender top tube will be collected at the 
fasting time point for fasting glucose, lipid panel, insulin, and high-sensitivity C-reactive peptide 
(hsCRP) testing. One 5.0 mL gold top tube will then be collected at each hourly time point (1 
and 2 hours for the 75 g OGTT; 1, 2, and 3 hours for the 100 g OGTT) for glucose testing. 
 
At delivery, one 3.5 mL gold top tube, one 5.0 mL lavender top tube, and one 5.0 mL gold top 
tube will be collected, in that specific order. 
 
At Visit 3, three 5.0 mL gold top tubes and one 3.5 mL lavender top tube will be collected at the 
fasting time point for fasting glucose, lipid panel, insulin, hemoglobin A1c, and high-sensitivity 
C-reactive peptide (hsCRP) testing. One 5.0 mL gold top tube will then be collected at each 
hourly time point (1 and 2 hours for the 75 g OGTT). 
 
For Visits 2 and 3 occurring on Saturdays, one extra 3.5 mL lavender top tube will be drawn at 
fasting. 
 
See Page 63 for Specimen and Laboratory Flow Chart. 
 
Laboratory Processing and Long-Term Specimen Storage 
 
All samples will be processed at the UPMC Clinical Laboratory Building with the exception of 
specimens collected at delivery, which will be processed by the MWH OSPU team. 
 
All glucose tests, lipid panels, and high-sensitivity C-reactive peptide tests will be run at the 
UPMC Automated Testing Lab. The UPMC CLB will also run insulin tests at the 
Immunoserology Lab, and hemoglobin A1c at the Special Chemistry Lab. 
 
Non-esterified free fatty acids, adiponectin, and leptin will be analyzed at the UPMC CLB or 
Indiana University Metabolic Lab (TBD). 
 
All plasma and serum aliquots will be stored long-term at the Magee-Womens Research 
Institute. 
 

 
60 
 
 
 
Visit 1 Laboratory Procedures 
 
The 50 g 1-hour glucose specimen and a completed research requisition (see Appendix C) will 
be sent from MWH to the UPMC Clinical Laboratory Building (CLB Station #350) via 
pneumatic tube for processing. The CLB will process the glucose testing. Results will then be 
faxed to study staff within 1 business day. Specimens from Visit 1 will not be banked in long-
term storage. 
 
 
Visit 2 Laboratory Procedures 
 
The fasting specimens and corresponding completed research requisition will be sent from MWH 
to the UPMC CLB (Station #350) via pneumatic tube for processing. The CLB will process the 
fasting glucose, insulin, lipid panel, and hsCRP. The additional two or three hourly glucose 
specimens will also be sent to the CLB with corresponding completed research requisitions by 
pneumatic tube. All results will be faxed to study staff within 1 or 2 business days. Fasting 
adiponectin, leptin, and non-esterified fatty acids will be processed at a separate time, after all 
participants complete their Visit 2. 
 
Study staff will retrieve an extra gold top tube and lavender top tube directly from the automated 
testing line at the Automated Testing Lab on the 5th floor of the CLB. CLB staff will centrifuge 
the tubes and store them until they are retrieved by study staff. These residual specimens will be 
retrieved by scanning the tube labels printed by CLB staff, sending them to the automated testing 
line.  
 
Once tubes are processed and received, study staff will aliquot the plasma or serum from each 
specimen into cryovials and temporarily freeze (-20C) and store them in the Palmer Lab (Room 
3027) freezer. Total aliquots to be frozen in cryovials include: 4 fasting serums, 2 fasting 
plasmas, and 1 serum aliquot from each hourly glucose specimen, of 1 mL each. If the 
participant does not consent to banking of specimens for future research tests, study staff will 
only prepare two 1 mL fasting serum aliquots for cytokine analyses. 
 
Study staff will prepare labels for each cryovial, which specify the participant’s study ID, blood 
draw date and time, date and time of freezing, study arm, specimen type (serum or plasma), 
study arm, and numerical order within the batch. After each sample is aliquoted, labeled, and 
frozen, study staff will complete a specimen collection record to log all prepared samples, noting 
if there will be fewer samples or less volume in a specific aliquot than expected. The Palmer Lab 
(Room 3027) will temporarily hold frozen specimens in labeled boxes provided by this study. 

 
61 
 
 
 
For long-term storage, study staff will compile specimen collection records, label specimen 
boxes with study and PI information, and transport the specimen boxes from the Palmer Lab to 
the Magee-Womens Research Institute (MWRI) within an insulated box of dry ice (to be 
provided by the CTRC). Study staff have badge access to the MWRI lab where study specimens 
will be stored. One freezer with specimens is located on the 5th floor of MWRI, where lab 
benches may be used by study staff to prepare specimen boxes for storage.  
 
Specimen maps will be prepared, with boxes placed and mapped by rows and columns with 
alphanumerical identification. Specimen collection records will be compiled, specimen maps 
updated and organized by study staff at each transfer, and all records will be kept in binders in 
the study office. 
 
Separate boxes are required for each of the following: fasting serum for cytokine analysis, 
fasting serum, fasting plasma, 1-hour serum, 2-hour serum, and 3-hour serum. Samples will be 
transferred between lab bench and freezer on dry ice during the entire process. Study staff will 
organize fasting serums to be used for cytokine analysis into two groups: participants who 
completed the study at delivery, and participants selected to return for the 12-month postpartum 
follow-up at Visit 3. All remaining samples will be frozen (-80C) and stored long-term at 
MWRI. 
 
 
Cord Blood Laboratory Procedures 
 
Venous umbilical cord blood will be collected at delivery by OSPU staff for the analysis of C-
peptide. Cord blood procurement supplies will be provided on an ongoing basis to the OSPU 
team, to include 5.0 mL gold top tubes, 3.5 mL gold top tubes, 2 mL cryovial tubes, blank 
cryovial labels, and labeled specimen boxes for storage. Each month, study staff will provide the 
OSPU staff with an updated list of expected participant deliveries for the upcoming month and 
prepared research requisitions for each participant. 
 
When a study participant delivers, the OSPU staff will obtain cord blood samples with the kit 
provided, and enter specimen and collection information (Cord Blood Collection form) into the 
study database at the delivery time point. 2 plasma aliquots and 2 serum aliquots of 1 mL each 
will be collected and banked from the delivery specimens. 
 
 
 
 

 
62 
 
 
Visit 3 Laboratory Procedures 
 
The fasting specimens and corresponding completed research requisition will be sent from MWH 
to the UPMC CLB (Station #350) via pneumatic tube for processing. The CLB will process the 
fasting glucose, insulin, lipid panel, hsCRP, and A1c. The additional two hourly glucose 
specimens will also be sent to the CLB with corresponding completed research requisitions by 
pneumatic tube. All results will be faxed to study staff within 1 or 2 business days. Fasting 
adiponectin, leptin, and non-esterified fatty acids will be processed at a separate time, after all 
participants complete their Visit 3. 
 
Study staff will retrieve the lavender top from the Special Chemistry lab on the 3rd floor of the 
CLB, after it has been used for A1c testing. This tube will be taken to the 5th floor Automated 
Testing Lab and centrifuged there. Study staff will also retrieve an extra gold top tube directly 
from the automated testing line at the Automated Testing Lab on the 5th floor of the CLB. CLB 
staff will centrifuge the tubes and store them until they are retrieved by study staff. These 
residual specimens will be retrieved by scanning the tube labels printed by CLB staff, sending 
them to the automated testing line.  
 
Once tubes are processed and received, study staff will aliquot the plasma or serum from each 
specimen into cryovials and temporarily freeze (-20C) and store them in the Palmer Lab (Room 
3027) freezer. Total aliquots to be frozen in cryovials include: 4 fasting serums, 2 fasting 
plasmas, and 1 serum aliquot from each hourly glucose specimen, of 1 mL each. 
 
Study staff will prepare labels for each cryovial, which specify the participant’s study ID, blood 
draw date and time, date and time of freezing, study arm, specimen type (serum or plasma), and 
numerical order within the batch. After each sample is aliquoted, labeled, and frozen, study staff 
will complete a specimen collection record to log all prepared samples, noting if there will be 
fewer samples or less volume in a specific aliquot than expected. The Palmer Lab (Room 3027) 
will temporarily hold frozen specimens in labeled boxes provided by this study. 
 
For long-term storage, study staff will compile specimen collection records, label specimen 
boxes with study and PI information, and transport the specimen boxes from the Palmer Lab to 
the Magee-Womens Research Institute (MWRI) within an insulated box of dry ice (to be 
provided by the CTRC). Study staff have badge access to the MWRI lab where study specimens 
will be stored. One freezer with specimens is located on the 5th floor of MWRI, where lab 
benches may be used by study staff to prepare specimen boxes for storage.  
 
Specimen maps will be prepared, with boxes placed and mapped by rows and columns with 
alphanumerical identification. Specimen collection records will be compiled, specimen maps 

 
63 
 
 
updated and organized by study staff at each transfer, and all records will be kept in binders in 
the study office. 
 
Separate boxes are required for each of the following: fasting serum for cytokine analysis, 
fasting serum, fasting plasma, 1-hour serum, and 2-hour serum. Samples will be transferred 
between lab bench and freezer on dry ice during the entire process. All samples will be frozen  
(-80C) and stored long-term at MWRI. 
 
 
Visits 2 and 3 Occurring on Saturdays 
 
For Visits 2 and 3 occurring on Saturdays, one extra 3.5 mL lavender top tube will be drawn at 
fasting in addition to the usual specimens. One 5.0 mL gold top tube and the extra 3.5 mL 
lavender top tube will be held at the CTRC for study staff to aliquot fasting samples there. 2 
fasting plasma aliquots and 2 fasting serum aliquots will be spun down, aliquoted, and frozen per 
usual procedure as noted above in the CTRC lab, and stored temporarily in CTRC freezers until 
study staff are able to retrieve them for transport to long-term storage at MWRI. A specimen 
collection record will be completed. The remaining fasting samples (2 5.0 mL gold top tubes and 
1 3.5 mL lavender top tube) and hourly glucoses will be tubed to the CLB for processing as 
usual. Study staff will aliquot and freeze these samples on the following business day per usual 
procedure. 
 
 

 
64 
 
 
Specimen and Laboratory Flow Charts 
 
Visit 1: 50 g GCT 
 
Blood Draw 
Time Point 
# and Type Tube(s) 
Drawn 
Test(s) Run 
# Plasma 
Aliquot(s) 
# Serum 
Aliquot(s) 
1-hour 
1 – 5.0 mL gold top 
 
Glucose 
N/A 
N/A 
 
Visit 2: 75 g OGTT 
 
Blood Draw 
Time Point 
# and Type Tube(s) 
Drawn 
Test(s) Run 
# Plasma 
Aliquot(s) 
# Serum 
Aliquot(s) 
Fasting 
3 – 5.0 mL gold 
1 – 3.5 mL lavender* 
 
Glucose 
 
Lipid panel 
o 
Triglycerides 
o 
Cholesterol 
o 
VLDL 
o 
LDL 
o 
HDL 
 
hsCRP 
 
Insulin 
4 
2 
1-hour 
1 – 5.0 mL gold top 
 
Glucose 
1 
0 
2-hour 
1 – 5.0 mL gold top 
 
Glucose 
1 
0 
 
Visit 2: 100 g OGTT 
 
Blood Draw 
Time Point 
# and Type Tube(s) 
Drawn 
Test(s) Run 
# Plasma 
Aliquot(s) 
# Serum 
Aliquot(s) 
Fasting 
3 – 5.0 mL gold 
1 – 3.5 mL lavender* 
 
Glucose 
 
Lipid panel 
o 
Triglycerides 
o 
Cholesterol 
o 
VLDL 
o 
LDL 
o 
HDL 
 
hsCRP 
 
Insulin 
4 
2 
1-hour 
1 – 5.0 mL gold top 
 
Glucose 
1 
0 
2-hour 
1 – 5.0 mL gold top 
 
Glucose 
1 
0 
3-hour 
1 – 5.0 mL gold top 
 
Glucose 
1 
0 
 
*For Visits 2 occurring on Saturdays, one extra 3.5 mL lavender top tube will be drawn, to be processed and 
aliquoted at the CTRC 

 
65 
 
 
Delivery Time Point 
 
Blood Draw 
Time Point 
# and Type Tube(s) 
Drawn 
Test(s) Run 
# Plasma 
Aliquot(s) 
# Serum 
Aliquot(s) 
Delivery 
(Cord Blood) 
1 – 3.5 mL gold 
1 – 5.0 mL lavender 
1 – 5.0 mL gold 
(to be drawn in this 
specific order) 
 
C-peptide 
2 
 
2 
 
Visit 3: 75 g OGTT 
 
Blood Draw 
Time Point 
# and Type Tube(s) 
Drawn 
Test(s) Run 
# Plasma 
Aliquot(s) 
# Serum 
Aliquot(s) 
Fasting 
3 – 5.0 mL gold 
1 – 3.5 mL lavender* 
 
Glucose 
 
Lipid panel 
o 
Triglycerides 
o 
Cholesterol 
o 
VLDL 
o 
LDL 
o 
HDL 
 
hsCRP 
 
Insulin 
 
A1c 
4 
2 
1-hour 
1 – 5.0 mL gold top 
 
Glucose 
1 
0 
2-hour 
1 – 5.0 mL gold top 
 
Glucose 
1 
0 
 
 
 

 
66 
 
 
Clinical Laboratory Protocols 
 
Testing for glucose, insulin, lipids, high-sensitivity C-reactive peptide (hsCRP), glycosylated 
hemoglobin A1c, and c-peptide will occur at the UPMC Clinical Laboratory Building under the 
supervision of Dr. Octavia Palmer. Protocols for these tests are available in their entirety and 
may be obtained by contacting study staff or Jeffrey Tischler, Lead Medical Technologist at the 
CLB (tiscjt@upmc.edu). 
 
 
Glucose 
 
Glucose is measured using Beckman Coulter AU680 and AU5800 analyzers. In the Beckman 
Coulter AU System Glucose procedure, glucose is phosphorylated by hexokinase (HK) in the 
presence of adenosine triphosphate (ATP) and magnesium ions to produce glucose-6-phosphate 
(G-6-P) and adenosine diphosphate (ADP). Glucose-6-phosphate dehydrogenase (G6P-DH) 
specifically oxidizes G-6-P to 6-phosphogluconate with the concurrent reduction of 
nicotinamide adenine dinucleotide (NAD+) to nicotinamide adenine dinucleotide, reduced 
(NADH). The change in absorbance at 340/380 nm is proportional to the amount of glucose 
present in the sample. 
 
 
Insulin 
 
Insulin is measured using IMMULITE® 2000. Insulin is a solid-phase, enzyme-labeled 
chemiluminescent immunometric assay. The solid phase (bead) is coated with monoclonal 
murine anti-insulin antibody.  The patient sample and the reagent is incubated together with 
the coated bead for 60 minutes. During this time, insulin in the sample forms the antibody 
sandwich complex with the monoclonal murine anti-insulin antibody on the bead, enzyme 
conjugated polyclonal sheep anti-insulin antibody and enzyme conjugated monoclonal murine 
anti-insulin antibody in the reagent. Unbound patient sample and enzyme conjugate are then 
removed by centrifugal washes. Finally, chemiluminescent substrate is added to the reaction 
tube containing the bead and the signal is generated in proportion to the bound enzyme. 
 
 
Cholesterol 
 
Cholesterol is processed and analyzed with cholesterol esters in serum are hydrolyzed by 
cholesterol esterase (CHE). The free cholesterol produced is oxidized by cholesterol oxidase 
(CHO) to cholest-4-en-3-one with the simultaneous production of hydrogen peroxide (H202), 

 
67 
 
 
which oxidatively couples with 4-aminoantipyrine and phenol in the presence of peroxidase 
to yield a chromophore. 
 
 
High Density Lipoprotein 
 
HDL is measured using the Beckman Coulter AU System HDL-Cholesterol test (HDL-C) is a 
two reagent homogenous system for the selective measurement of serum or plasma HDL- 
Cholesterol in the presence of other lipoprotein particles. The assay is comprised of two 
distinct phases. In phase one, free cholesterol in non-HDL-lipoproteins is solubilized and 
consumed by cholesterol oxidase, peroxidase, and DSBmT to generate a colorless end product.  
In phase two, a unique detergent selectively solubilizes HDL-lipoproteins. The HDL 
cholesterol is released for reaction with cholesterol esterase, cholesterol oxidase, and a 
chromogen system to yield a blue color complex, which can be measured bichromatically at 
600/700nm. The resulting increase in absorbance is directly proportional to the HDL-C 
concentration in the sample. 
 
 
Triglycerides 
 
The triglycerides in the sample are hydrolyzed by a combination of microbial lipases to give 
glycerol and fatty acids. The glycerol is phosphorylated by adenosine triphosphate (ATP) in 
the presence of glycerol kinase (GK) to produce glycerol-3-phosphate. The glycerol-3-
phosphate is oxidized by molecular oxygen in the presence of GPO (glycerol phosphate 
oxidase) to produce hydrogen peroxide (H2O2) and dihydroxyacetone phosphate. The formed 
H2O2 reacts with 4- aminophenazone and N,N-bis(4-sulfobutyl)-3,5-dimethylaniline, 
disodium salt(MADB) in the presence of peroxidase (POD) to produce a chromophore, which 
is read at 660/800 nm. The increase in absorbance at 660/800 nm is proportional to the 
triglyceride content of the sample. 
 
 
High-Sensitivity C-Reactive-Peptide 
 
Immune complexes formed in solution scatter light in proportion to their size, shape, and 
concentration. Turbidimeters measure the reduction of incidence light due to reflection, 
absorption, or scatter. In the Beckman Coulter AU System procedure, the measurement of 
the rate of decrease in light intensity transmitted (increase in absorbance) through particles 
suspended in solution is the result of complexes formed during the antigen-antibody 
reaction between the CRP of the patient serum and the rabbit anti-CRP antibodies coated on 
latex particles. 

 
68 
 
 
C-Peptide 
 
C-peptide is a solid-phase, two-site chemiluminescent immunometric assay. The solid phase 
(bead) is coated with monoclonal murine anti-C-peptide antibody. The patient sample and the 
reagent are incubated together with the coated bead for 30 minutes. During this time, C-peptide 
in the sample forms the antibody sandwich complex with monoclonal murine anti-C-peptide 
antibody on the bead and enzyme-conjugated monoclonal murine anti-C-peptide antibody in 
the reagent. Unbound patient sample and enzyme conjugate are then removed by centrifugal 
washes. Finally, chemiluminescent substrate is added to the reaction tube containing the bead 
and the signal is generated in proportion to the bound enzyme. 
 
 
Glycosylated Hemoglobin A1c 
 
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 uses nonporous ion-
exchange high performance liquid chromatography (HPLC) for rapid, accurate, and precise 
separation of HbAlc from other hemoglobin fractions. Analysis is carried out without off-
line specimen pretreatment or interference from Schiff base. The analyzer dilutes the whole 
blood specimen with Hemolysis & Wash Solution, and then injects a small volume of the 
treated specimen onto the TSKgel Glyco HSi Variant Column. Separation is achieved by 
utilizing differences in ionic interactions between the cation exchange group on the column 
resin surface and the hemoglobin components. The hemoglobin fractions (designated as Ala, 
Alb, F, LAlc+, SAIC, AO, and H- Var) are subsequently removed from the column material 
by performing a stepwise elution using Elution Buffers HSi Variant 1, 2, and 3 with different 
salt concentrations. The separated hemoglobin components pass through the LED 
photometer flow cell where the analyzer measures changes in absorbance. The analyzer 
integrates and reduces the raw data, and then calculates the relative percentages of each 
hemoglobin fraction. The analyzer prints the numerical results and plots a chromatogram 
showing changes in absorbance versus retention time for each peak fraction. An analysis 
requires 1.6 minutes. 
 
 
Adiponectin 
 
TBD 
 
 
Leptin 
 
TBD 

 
69 
 
 
Non-Esterified Fatty Acids 
 
TBD 
 

 
70 
 
 
Adherence and Retention 
 
The GDM2 primary investigator and study team have extensive knowledge of cohort studies and 
clinical trials with similar participants; this will be valuable in the retention of participants. 
Based on experience, several strategies will be applied to maximize adherence and minimize 
drop-out: 
 
 We will limit the number of in-person study visits to three (two during pregnancy, one at 
12 months postpartum), and schedule study appointments on the same day as prenatal 
visits when possible. 
 Participants will remain blinded to which test they are randomized until they return for 
Visit 2. This will minimize drop-out based on participants’ knowledge that they have 
been randomized to the longer test 
  Study staff will maintain regular contact with participants prior to reach study 
appointment, reminding participants of their appointments and reviewing preparation 
instructions. 
 Study staff will also visit participants at MWH after they deliver, to complete the infant 
assessment and deliver a small baby gift. Participants will be told at this time whether or 
not they have been selected for postpartum follow-up, and what to expect if they have 
been selected. 
 Scheduled telephone assessments at 3, 6, and 9 months postpartum for those selected 
participants will also serve to keep study staff in contact with participants. 
 We will request the name and telephone number of an emergency contact or someone 
who will “always know where the participant is.”  
 We will update participants’ contact information as needed. Contact information may be 
gleaned from the participant’s Epic EMR. 
 We will offer monetary compensation for study visits on a University-issued debit card, a 
small gift at delivery, and transportation reimbursement or parking validation for study 
visits. 
 We will conduct initial orientation sessions with the clinics we plan to recruit from, and 
will frequently correspond with them regarding the study protocol. 
 
 
Study Withdrawal and Termination 
 
A drop-out or attrition rate of approximately 15% is expected and has been accounted for in the 
statistical sample size. Potential participants will be made aware at telephone screening and 
during informed consent that their participation is voluntary and that they may withdraw from 

 
71 
 
 
the study at any time for any reason. It will be emphasized that withdrawal will have no bearing 
on a participant’s current or future medical care. 
 
To formally withdraw consent for participation, participants are advised to provide a written and 
dated notice of their decision, to be sent to the principal investigator at the address listed on the 
informed consent document. Additionally, participants may withdraw in-person or through any 
method they choose to contact study staff (email, telephone, text, etc.).  
 
Participants will also be told that it is possible to be removed from the study by the investigators 
in the following cases: participant meeting exclusion criteria; participant’s medical care has been 
transferred outside of MWH; participant is unable to complete study visits within expected 
timeframe; or participant experiences several prenatal complications or pre-term delivery. 
 
All of the above information will be provided to participants in the informed consent document. 
Study staff will complete and submit the Withdrawal and Termination Form (see Appendix B) in 
the study database in cases of dropout, exclusion, or other circumstances where study 
participation is inappropriate. 
 
 

 
72 
 
 
Data Management and Quality Control 
 
Center for Research on Health Care Data Center 
 
The Center for Research on Health Care Data Center (CRHC-DC) will work with the principal 
investigator and study team to standardize all procedures and training in areas such as participant 
recruitment, measurement, assessment, data entry, data management, and data security. 
 
The CRHC-DC provides state-of-the-art data management and analysis services to the 
University of Pittsburgh’s researchers. Their mission is to provide investigators with consistent, 
high-quality information technology including database development, data management, and 
statistical services. The CRHC-DC team provides expertise in all phases of research, and is 
committed to quality assurance and research integrity. The CRHC-DC offers secure equipment 
to provide data management, storage, and analysis services while ensuring high security and 
confidentiality of research data and samples. 
 
 
Data Collection 
 
Study questionnaires and forms are paperless, and an electronic System for Data Management 
(eSYSDM) for this project has been developed based on the study protocol. eSYSDM facilitates 
the generation of clean datasets by guiding interviewers through the data collection process in 
such a way as to display only questions and screens that are appropriate for the particular 
participant, eliminating the possibility of most incorrect entries. eSYSDM also performs 
important tracking functions by monitoring screening information, eligibility status, follow-up 
interviews due, and study group assignment to ensure that the required data collection 
instruments are administered within the time constraints dictated by the study protocol. The 
eSYSDM will be stored on a local network accessible only to select research team members with 
password privileges. All files will be backed-up daily, archived weekly, and stored. 
 
 
Manual Data Entry 
 
Data will be entered on PCs, laptops, and tablets; this allows for mobile computing and better 
functionality. Study personnel are assigned unique login credentials to access only the data they 
are permitted to manage. Only designated study staff will have access to the database (including 
participant’s personal information); the PI will have limited access to the database to prevent 
unblinding. 
 

 
73 
 
 
Before beginning study procedures where data collection and tracking are involved, study staff 
will log onto the device they are using through a secure web server. An additional log-in and 
password is then required to access the database. Once the screening process has been started in 
the database, participant ID numbers are generated and data capture and tracking begins. 
 
 
Data Quality and Integrity 
 
Data quality and integrity will be ensured by the following: 
 
 Standard methods of data collection and recording specified in this manual of procedures 
 Staff will attend a formal workshop on research integrity at the beginning of the study or 
upon hire, and will attend refresher courses as dictated by the University of Pittsburgh’s 
research regulations 
 Random audits on a sample of participants to verify accuracy and completion of study 
data collection 
 
Other data quality assurance measures will include detailed documentation of computer 
operations and data editing procedures, and meetings with study staff to review any changes in 
procedure. The CRHC0DC also has specific data quality measurements that will be 
implemented. These include verifying the data, out-of-range data checks, and repeated evaluation 
of the data process. 
 
 
Data Corrections 
 
Corrections to data are to be held to a minimum. Making sure that data is secure from 
unauthorized changes or access is important to ensure the data’s accuracy and integrity. Only 
database programmers and statisticians assigned to the GDM2 project will have rights to the 
database, files, and directories that contain project data. The CRHC-DC programmer will use 
version control software to manage changes made to databases and websites. All revisions are 
kept and can only be accessed by the programmer. 
 
In cases where study staff determine data submitted in a study questionnaire requires 
modification, the CRHC-DC will be notified of the incorrect data entry and make the appropriate 
changes. Both the CRHC-DC team and study staff will track these changes. 
 
 
 
 

 
74 
 
 
Data Security 
 
The CRHC-DC maintains numerous secure servers and computers, which provide access to both 
the internet and the CRHC-DC intranet. Servers are located in a secured server room which 
contains an alarm system, temperature control, and a double lock on the door with a tracking 
keycard entry system. All servers use hardware fault tolerance methods, and are housed in a 
secure rack with dedicated UPS power sources, to assure the 24/7 uptime and continued 
availability of data.  
 
The CRHC-DC’s servers utilize 128-bit SSL security for online real-time data entry. The 
center’s SQL server, which is used for database and data storage, also offers 128-bit SSL 
security and has limited access via network firewall. The CRHC-DC website and database 
development server is located behind a firewall with access only available to the developers on 
the intranet. The University of Pittsburgh’s Computing Services and Systems Development 
(CSSD) department ensures that all software and hardware are running at optimal performance 
and systems are secure to the latest industry standards. CSSD will scan production servers on a 
monthly schedule to review performance. 
 
 

 
75 
 
 
Data and Safety Monitoring 
 
Institutional Data and Safety Monitoring Board 
 
An Institutional Data and Safety Monitoring Board (IDSMB) has been created and organized by 
the Clinical and Translational Science Institute (CTSI) at the University of Pittsburgh, to review 
the GDM2 Study and ensure the wellbeing of the study’s participants. This independent panel of 
experts has been established to monitor the study’s progress, efficacy, and safety. 
 
 
Membership 
 
The members of the IDSMB have been selected by the IDSMB Coordinators with suggestions 
put forth by the PI. The IDSMB is composed of experts in maternal-fetal medicine, obstetrics 
and gynecology, pediatrics, and biostatistics. Members of the IDSMB are independent and are 
not affiliated with the study in any way, and have no financial, scientific, or other conflict of 
interest. Study collaborators and personnel are not eligible to serve on the study’s IDSMB. 
 
Katherine Himes, MD, MS has been elected to serve as the IDSMB Chairperson. Dr. Himes is 
responsible for overseeing IDSMB meetings in consultation with the IDSMB coordinators. Dr. 
Himes will also oversee safety with the IDSMB coordinators; they are to be contacted in cases of 
severe adverse events or unanticipated problems. 
 
 
IDSMB Responsibilities 
 
The initial responsibility of the IDSMB was to approve the GDM2 Study. The IDSMB met for 
the first time on February 25, 2015, to review the Institutional Review Board (IRB) approval 
letter and IRB-approved protocol and informed consent document. The IDSMB voted and 
approved the study to begin. 
 
The IDSMB agreed to meet every 6 months during the course of the study to: 
 
1. Review the research protocol, informed consent document, and plans for data and safety 
monitoring; 
2. Evaluate the progress of the study, including periodic assessments of data quality and 
timeliness, participant recruitment, accrual and retention, participant risk vs. benefit, 
adverse events, unanticipated problems, performance of the trial sites, and other factors 
affecting study outcomes; 

 
76 
 
 
3. Consider factors external to the study when relevant information becomes available, such 
as scientific or therapeutic developments that may have an impact on the safety of 
participants or the ethics of the study; 
4. Review clinical center performance, make recommendations, and assist in the resolution 
of problems reported by the PI; 
5. Protect the safety of the study participants; 
6. Report on the safety and progress of the study; 
7. Make recommendations to the PI, and if required, to the NIH, concerning continuation, 
termination, or other modifications of the study based on the observed beneficial or 
adverse effects of the treatment under study; 
8. Monitor the confidentiality of the study data and the results of monitoring; 
9. Assist the PI by commenting on any problems with study conduct, enrollment, sample 
size, and/or data collection. 
 
 
IDSMB Board Process 
 
IDSMB meetings are confidential, and therefore closed to the public. The PI, study staff, study 
statistician, and other members of the study team as necessary, will attend the meetings. The 
Chairperson can call an emergency meeting of the IDSMB at any time after reviewing any 
serious adverse event report, unanticipated problem report, or should questions of participant 
safety arise. 
 
 
IDSMB Meeting Formats 
 
The IDSMB meetings consist of an open session and two closed sessions; these formats may be 
modified as needed. 
 
 
Open Session 
 
Open IDSMB meetings will be attended by the IDSMB members, IDSMB coordinators, 
principal investigator, study staff, and will always include the study biostatistician. Issues 
discussed will include conduct and progress of the study, including patient accrual, compliance 
with protocol, data quality, adherence, and safety. Patient-specific data and treatment group data 
may not be presented in the open session. 
 
 
 

 
77 
 
 
Closed Session (without the PI and study staff) 
 
These closed sessions will be attended by the IDSMB members, IDSMB coordinators, and the 
study biostatistician. Discussions in closed meetings are confidential, as unblended outcome data 
may be reviewed. The IDSMB may request unmasking of data for either safety or efficacy 
reasons or if there are developments in risks or benefits to participants. 
 
Closed Session 
 
Only the IDSMB members and IDSMB coordinators will attend these closed sessions. 
Information will be discussed that was presented in the open and other closed sessions, and 
decisions made regarding continuation or termination of the study, protocol modification, or 
other changes relevant to the conduct of the study. The IDSMB will also vote on the frequency 
of the next meeting. 
 
Should the IDSMB decide to issue a termination of the study, a full vote is necessary. In the 
event of a split vote, majority vote will rule and a minority report appended. Reasons for 
termination include and are not limited to: 
 
 Serious adverse events in the intervention or dominating subgroup 
 Greater than expected beneficial effects 
 Statistically significant difference by the end of the study is improbably 
 Logistical or data quality problems that cannot be corrected 
 Recruitment issues 
 
 
IDSMB Reports 
 
Reports are to follow the IDSMB report template. Meeting documents/reports will be prepared 
by the PI’s study data analyst or study staff and distributed to the IDSMB coordinators at least 
one week prior to a scheduled meeting. Further information or modifications to these 
documents/reports may be requested by the IDSMB. Following the meeting, the minutes are 
shared with the IDSMB members only and are confidential. A copy of the minutes is kept in the 
IDSMB file. 
 
 
 
 

 
78 
 
 
Letters from the IDSMB 
 
A formal letters containing the recommendations for continuation and action items/modifications 
will be prepared by the IDSMB chair and coordinators and will be sent to the IDSMB members 
and principal investigator. It is the responsibility of the PI to distribute the meeting summary to 
all co-investigators, the study sponsor, and to the IRB during the study’s annual review. 
 
 
Communication with the IDSMB/Access to Interim Data 
 
Access to the accumulating endpoint data will be limited to as small a group as possible. 
Limiting the access to interim data to the IDSMB members will relieve the PI of the burden of 
deciding whether it is ethical to continue to randomize participants and will help protect the 
study from bias in participant entry and/or evaluation. 
 
 
Confidentiality 
 
The study visits will be conducted at the CTRC at Magee-Womens Hospital, which is equipped 
to ensure the protection of patient privacy. The collection of sensitive information about 
participants will be limited to the amount necessary to achieve the aims of the research so that no 
unnecessary sensitive information is collected. 
 
Paper-based records will be kept in a secure location and only be available to study personnel. 
Computer-based files will be made accessible to study personnel by access privileges and 
passwords. Prior to accessing any study-related information, personnel will be required to sign 
statements agreeing to protect the security and confidentiality of identifiable information. 
Whenever feasible, identifiers will be removed from study-related information and data. 
 
If a participant withdraws from the study, any personal medical information that was recorded or 
samples obtained for the research study before the withdrawal may continue to be used by the 
study. 
 
During data collection, the personal identifiers on study questionnaires and samples are replaced 
by a unique study ID. After the required data retention period, the link between the assigned tudy 
ID and the participant’s identity will be destroyed so that nothing can be tracked back to the 
individual. The data will then be rendered completely anonymous. 
 
 

 
79 
 
 
Adverse Event Reporting Guidelines 
 
During the course of the study, all adverse events (AEs) and serious adverse events (SAEs) will 
be monitored, documented, and if causal, reported to the IDSMB and IRB. AEs and SAEs will 
be captured in the study database using the Adverse Events form. The form will prompt study 
staff to notify the PI of SAEs for review. Every effort will be made to follow a participant who 
has had a negative reaction to any study intervention or procedure. 
 
 
Adverse Events (AEs) 
 
An adverse event (AE) is any unfavorable medical occurrence, which may include abnormal 
signs (e.g., abnormal physical exam or laboratory finding), symptoms, or disease, temporally 
associated with, but not necessarily considered related to, the participant’s participation in the 
study. These events are usually of a non-serious nature and are not reportable in accordance with 
the University of Pittsburgh Institutional Review Board’s (IRB) guidelines for “Reportable 
Events” as they do not pose a risk to study participants. 
 
Adverse events that take place during the course of the study will be classified under the 
Common Terminology Criteria for Adverse Events (CTCAE), a descriptive terminology used for 
Adverse Event (AE) reporting. AEs will be categorized as expected or unexpected, in terms of 
the nature, severity, or frequency, as outlined in the consent form. AEs will be graded using the 
CTCAE system and relatedness assessed by the PI, and presented to the IDSMB members at 
IDSMB meetings. 
 
 
Serious Adverse Events (SAEs) 
 
Serious adverse events (SAEs) or “unanticipated problems involving risk to participants or 
others” are characterized as symptoms which are harmful to the participant and result in 
significant outcomes, which are reportable to the IRB and IDSMB. 
 
Examples of serious adverse events include: 
 Death 
 Life-threatening medical events that place a participant at immediate risk of death from 
the event as it occurred 
 Results in inpatient hospitalization or prolongation of existing hospitalization 
 Results in persistent or significant disability or incapacity as a result of the study 
intervention 

 
80 
 
 
 Events that, based upon appropriate medical judgment, may jeopardize the participant’s 
health, and may require medical or surgical intervention to prevent one of the other 
outcomes listed in this definition 
 
The flow chart below provides an algorithm for determining whether an adverse event meets the 
definition of an “unanticipated problems involving risk to participants or others”: 
 
Adverse Events which follow the above figure, that meet the criteria of unexpected, fatal or 
life- threatening, and related or possibly related to the research intervention must be reported 
to the IRB and the IDSMB Chair and Safety Officer (Dr. Katherine Himes) within 24 hours of 
learning of the event. If necessary, a subsequent follow-up report with the details of the event 
will be submitted as well.  
 
All other reportable adverse events will be submitted to the IRB within 10 business days of the 
investigator learning of the event.  Reportable events will be submitted through the University 
of Pittsburgh IRB’s PittPRO system; the “Reportable Event” online submission process must 
be used in order to submit a report. The smart form questions will prompt a response to 
questions related to the adverse event. 

 
81 
 
 
SAE and AE reporting guidelines and further instructions on submitting a report in the PittPRO 
system can be found in the University of Pittsburgh website, http://www.irb.pitt.edu/. 
 
 
AE and SAE Assessment Guidelines Specific to the GDM² Trial 
 
Key Criteria: to determine if the event is unexpected, related to participation in the research 
study and involves risk to human participants or others. 
 
If an adverse event meets the criterion of unexpected, related or possibly related, and poses risk 
of harm to other participants, study staff will notify the principal investigator within 24 hours, 
who will then inform and the IDSMB Chair and Safety Officer (Dr. Katherine Himes). Dr. 
Himes will review and submit the event to the IDSMB, who will discuss the IDSMB 
recommendations and submit the SAE to the University of Pittsburgh IRB. 
 
In cases of an SAE, the following schematic is to be used: 
 
 
To evaluate GDM2 Study AEs and SAEs, a licensed medical professional will apply the 
following assessment criteria: 
 
Unexpected Medical Events 
 
These are medical events that are not described in the current IRB-approved protocol or 
informed consent, taking into account the characteristics of the participant population being 
studied (i.e. pregnant women). 
 
 
 
 
CTRC Staff  
or Study Staff 
Primary 
Investigator 
or Medical 
Professional 
IDSMB 
IRB 

 
82 
 
 
Expected Medical Events 
 
 Symptoms and risk related to normal pregnancy progression such as nausea, vomiting, 
fatigue, urinary frequency, increased or decreased appetite, transient dizziness, mild 
back or breast pain or discomfort, mild mood changes, miscarriage, preterm delivery, 
stillbirth, low birth weight, problems with placenta, and birth defects 
 Symptoms related to fasting for at least 8 hours and related hypoglycemia: headache, 
nausea, and lightheadedness 
 Symptoms related to hypoglycemia such as fainting, fast heart rate, sweating, 
shakiness, difficulty paying attention, sudden moodiness or irritability, loss of 
consciousness 
 Symptoms related to venous blood draw such as bruising, bleeding, swelling, and 
pain, fainting, lightheadedness, and infection at the injection site 
 Symptoms related to consuming the glucose solution for the diabetes testing such as 
brief nausea, vomiting, tiredness, lightheadedness, and upset stomach 
 
While the above medical events may be expected, they will be collected for outcome purposes. 
 
 
Event Severity using Common Terminology Criteria for Adverse Events (CTCAE) 
 
Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with 
unique clinical descriptions of severity for each AE based on these general guidelines: 
 
 Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
 Grade 2: Moderate; minimal, local or noninvasive intervention indicated limiting 
age- appropriate instrumental activities of daily living. 
 Grade 3: Severe or medically significant but not immediately life threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-
care. 
 Grade 4: Life-threatening consequences; urgent intervention indicated. 
 Grade 5: Death related to AE. 
 
 
 

 
83 
 
 
Event Relatedness 
 
Very Likely Related: The incident, experience, or outcome is more likely than not caused study 
procedures. 
 A reasonable time course would be within the 1-4 hours the participant is receiving 
oral glucose tolerance testing. 
 Symptoms abate once the study product is discontinued and patient has received a 
snack or drink. 
 Symptoms are not explained by other factors such as concomitant medications or 
current illness 
 
Probable: There is reasonable possibility that the incident, experience or outcome may have been 
caused by study procedures. 
 A reasonable time course would be within 24 hours the participant either fasting for 
the study or receiving the oral glucose tolerance testing. 
 Symptoms may be explained by other factors such as concomitant medications or 
current illness 
 
Possible: There is a possibility that the incident, experience or outcome may have been caused 
by study procedures. 
 A reasonable time course would be within 25-48 hours the participant fasting for the 
study, receiving the OGTT, or final blood draw. 
 Symptoms may be explained by other factors such as concomitant medications, current 
illness, or other healthcare procedures. 
 
Doubtful: There is a reasonable doubt that the incident, experience or outcome was not caused 
by study procedures. 
 Symptoms may be explained by other factors such as concomitant medications, current 
illness, or other healthcare procedures. 
 
Not Related: There is complete assurance that the incident, experience or outcome could not 
have been caused by any study procedures. 
 
 

 
84 
 
 
Study Completion and Closeout 
 
Study Completion and Closeout Procedures 
 
This study will be complete when the target enrollment number has been reached and all 
research procedures have been completed, or allotted time to complete the study has 
passed. If the investigator is no longer using identifiable data for analysis, the study 
completion process may be initiated as no further IRB oversight is required. The study 
will not close until the sponsor conducts the final closeout visit, as an intervention or 
interaction with participants may be needed to complete the research data. 
 
The investigator must submit a final report for the Early Termination or Study Completed 
activities for IRB review via the PittPRO website. 
 
The following are to be addressed to the IRB for the final report: 
 
 Since the study began, how many participants have been entered into this research study 
at all sites under the authority of the University of Pittsburgh IRB? Do not include those 
participants who failed to meet the inclusion criteria during screening. 
 Total number of participants approved to undergo research related procedures at all sites 
under the authority of the University of Pittsburgh IRB. 
 Did participant accrual reflect the ethnic and racial demographics of Pittsburgh and the 
surrounding area and/or the relevant patient population of the UPMC; or the 
demographics of the alternate site(s) where this research is being conducted? 
 Have there been any unanticipated problems that were not previously reported that 
meet the University of Pittsburgh reporting guidelines? If yes, you must 
immediately submit an unanticipated problem report, which must be available for 
the IRB's consideration during review of this final report. 
 Have you already provided, or do you plan to provide, your study participants with 
a summary of study results? 
 Summarize the outcomes and conclusions of this study. Describe the extent to which 
the specific aims of this study were addressed and discuss the study's impact on the 
relevant scientific/medical issues. 
 
A final Data and Safety Monitoring Plan (DSMP) report is to be uploaded into PittPRO as 
described in the approved study. 
 
 
 
 

 
85 
 
 
Early Termination of Study 
 
The study may be canceled or stopped prematurely before targeted enrollment numbers have 
been reached and/or all required research procedures have been completed. The study sponsor, 
PI, federal agency, or local IRB may terminate the study early for reasons including but not 
limited to: change in risk/benefit assessment, loss of funding, new information, etc. 
 
 
Retention of Study Documentation 
 
The investigators may continue to use and disclose, for research purposes, identifiable 
information related to participation in this research study for a minimum of five years after 
final reporting or publication of a project. Following the required data retention period, 
secured long- term retention of any documents will occur and they will be rendered 
anonymous. The majority of documents (both electronic and paper) will be de-identified from 
the start of the study. After the study has been closed, study-related files may be given to the 
PI for long-term storage. 

 
86 
 
 
Table of Changes from Version IV to Version V 
 
Pg 
Header 
Description of Change 
- 
- 
Updated: All references to WePay changed to “University 
issued payment card” (WePay system phased out end of 
2018 and replaced with Vincent system) 
- 
- 
Removed: All references to study ID card (did not use) 
- 
- 
Updated: All references to OSIRIS changed to PittPRO – 
new IRB system 
- 
- 
Updated: All references to Heinz Lab (closed in 2018) 
changed to UPMC Clinical Laboratory Building (CLB) 
vii-
viii 
List of 
Abbreviations 
Updated: List of Abbreviations 
10-
11 
GDM2 Co-
Investigators 
Updated: Contact information for Dr. Scifres and Dr. 
Catalano 
14 
GDM2 Principal 
Study Staff 
Removed: Project Coordinator (Alexandra Illes) 
14-
15 
GDM2 Principal 
Study Staff 
Updated: Study staff responsibilities after departure of 
coordinator 
16 
GDM2 Clinical 
Team 
Removed: GSPH Heinz Laboratory Director (Dr. Joseph 
Zmuda) and Manager (Beth Hauth) 
17 
GDM2 Clinical 
Team 
Updated: Replaced David Lykins with Sharon Price 
(MWRI Lab Liaison) 
18 
GDM2 Data Center 
Staff 
Added: Diane Comer (CRHC-DC Data Analyst) 
19 
GDM2 Regulatory 
Staff 
Updated: Replaced Ann Lee with Lisa DeSantes (IRB) 
24 
Recruitment Plan 
Added: Added WomanCare, Wiesenfeld/Updike, UOA 
NIA, OGAP, and OPC clinics in list of clinics 
24 
Recruitment Plan 
Removed: OPC Purple and Western PA Women’s Health 
24 
Recruitment Plan 
Updated: Identified clinics as public or private providers 
25 
In-Clinic 
Recruitment 
Removed: Introductory letter recruitment (did not use) 
25-
26 
Additional 
Recruitment 
Methods 
Added: WIC Office, list of UPMC hospitals, digital 
message boards 
27 
Screening 
Procedures 
Updated: Clarified that dumping syndrome caused by 
gastric bypass surgery precludes participation, not gastric 
bypass surgery per se 

 
87 
 
 
27 
Screening 
Procedures 
Updated: Clarified severe liver disease indicated by 
elevated AST/ALT values 
28 
Hypertension and 
Corticosteroid 
Medications 
Updated: Clarified that low-dose or baby aspirin (LDASA 
or BASA) is acceptable 
28 
Hypertension and 
Corticosteroid 
Medications 
Updated: Added list of common hypertension and 
corticosteroid medications 
31 
Magee-Womens 
Hospital Clinical and 
Translational 
Research Center 
Updated: Corrected location of MWH CTRC 
32 
50 gram Glucose 
Challenge Test 
Added: Study samples are tubed from MWH to UPMC 
CLB for testing 
33 
IV Protocol 
Added: Section regarding use of MWH IV team for study 
visits 
34 
 
Visit 1 Forms 
Removed: Positive GDM Results – Notification Form 
(does not exist in database, notification of providers 
documented in Form 11 – 50gm Lab and Repeat Lab) 
34 
Visit 1 Forms 
Added: Description of Concomitant Medication Form 
35 
Critical Glucose 
Values 
Updated: All critical glucose values are documented as 
Adverse Events (AE); only contacted Dr. Davis when 
database AE form indicated critical value is a Serious 
Adverse Event (SAE) 
36 
Blinding 
Updated: Clarified cases in which the PI or co-I’s are 
unblinded 
37 
75 g or 100 g Oral 
Glucose Tolerance 
Test 
Updated: Latest time Visit 2 scheduled is 11:30 am 
instead of 11:00 am 
37 
75 g or 100 g Oral 
Glucose Tolerance 
Test 
Added: Study samples are tubed from MWH to UPMC 
CLB for testing 
38 
Visit 2: IV Protocol 
Added: Use of MWH IV team for study visits 
39 
Visit 2 Forms 
Added: Postpartum Depression Questionnaire – Score of 
13 OR answer of anything other than “Never” to Question 
10 regarding thoughts of self-harm  
39 
Visit 2 Forms 
Updated: 24-Hour Dietary Recall Telephone - Follow-up 
dietary recall to be completed at either 32w0d or up to 2 
weeks after Visit 2 

 
88 
 
 
39 
Visit 2 Forms 
Removed: 75gm or 100gm Repeat Fasting Glucose Lab 
Form – integrated into Form 14 ; 75gm or 100gm Fasting 
Glucose Lab 
39 
Visit 2 Forms 
Removed: Positive GDM Results – Notification Form 
(does not exist in database, notification of providers 
documented in Form 14 – 75gm or 100gm Fasting Glucose 
Lab) 
40 
Visit 2 Forms 
Added: Description of Concomitant Medication Form 
40 
Postpartum 
Depression 
Questionnaire 
Updated: Study staff offer to contact providers to notify 
of high EPDS score, and offer resources; in severe cases, 
will be reported as SAE 
41 
75 g or 100 g OGTT 
Laboratory Results 
Updated: “C-reactive peptide” to high sensitivity C-
reactive peptide 
41 
75 g or 100 g OGTT 
Laboratory Results 
Removed: Cytokines run at Visit 2 (not run in real time at 
Visit 2) 
41 
75 g or 100 g OGTT 
Laboratory Results 
Updated: Clarified 75 g OFTT diagnosis is ≥ 1 (one or 
more) abnormal value(s); 100 g OGTT diagnosis is ≥ 2 
(two or more) abnormal values (previously noted as only 1 
or only 2) 
41-
42 
“Mild GDM” 
Added: Section regarding “Mild GDM” results 
42 
Unblinding 
Providers to OGTT 
Results 
Added: Citation for HAPO Study 
42 
Critical Glucose 
Values 
Added: Any results indicating hypo- or hyperglycemia are 
reported as Adverse Events 
43 
Visit 2 Results Back 
Entry 
Added: Section regarding back entry of Visit 2 results to 
participants’ EMR, for clinical use post-study 
44 
Delivery Time Point 
Added: OSPU also does not collect specimens in cases of 
medical emergency or precipitous delivery 
44 
Infant PEA POD 
Assessment 
Removed: Entire section – PEA POD never used in study 
due to unavailability (substituted skinfold measurements 
instead) 
44 
Infant Skinfold 
Measurement 
Updated: Infant skinfold measurements will be obtained 
between 24-48 hours after delivery 
44 
Infant Skinfold 
Measurement 
Added: Parents may also refuse skinfold measurements 
47 
3, 6, and 9 Month 
Postpartum Forms 
Added: Description of Infant Status Form 
49 
Visit 3 IV Protocol 
Added: Use of MWH IV team for study visits 

 
89 
 
 
50 
Visit 3 Forms 
Removed: Positive GDM Results – Notification Form 
(does not exist in database, notification of providers 
documented in Form 14 – 75gm Fasting Glucose Lab) 
51 
Visit 3 Forms 
Added: Description of Infant Status Form and 
Concomitant Medication Form 
51 
Visit 3 
Questionnaires and 
Assessments 
Added: Participants who are pregnant at Visit 3 may 
choose to have their 75 g OGTT results sent to their OB 
provider in lieu of their regular GDM testing 
52 
Postpartum 
Depression 
Questionnaire 
Updated: Study staff offer to contact providers to notify 
of high EPDS score, and offer resources; in severe cases, 
will be reported as SAE 
52 
Completing Visit 3 
Updated: Follow-up dietary recall is not scheduled, to 
avoid biasing patient 
53 
Visit 3 Laboratory 
Results 
Updated: Clarified diagnostic criteria for impaired 
glucose tolerance and Type 2 diabetes (one or more 
abnormal values) 
53-
54 
Visit 3 Laboratory 
Results 
Added: Database will also prompt staff to notify PI of 
high triglycerides or cholesterol values, to notify 
participant 
54 
Visit 3 Results Back 
Entry 
Added: Section regarding back entry of Visit 3 results to 
participants’ EMR, for clinical use post-study 
54 
Quest Diagnostics 
Visit 
Updated: Clarified that participants will complete a 75 g 
OGTT at Quest Diagnostics, and option is only available 
for Visit 3 
55-
57 
Data Abstraction 
Updated: CARe service has been replaced by Health 
Record Research Request (R3) service 
56 
Data Collection 
Associated with 
Study Outcomes 
Added: ICD-10 procedure and diagnostic codes also used 
in R3 data abstraction 
58-
62 
Laboratory 
Procedures and 
Protocols 
Updated: Study staff handle all lab procedures, did not 
use research technician 
58 
Specimen Collection 
Added: Section listing specimens collected at each visit 
59-
60 
Visit 2 Laboratory 
Procedures 
Updated: Cytokine labs not run in real time; analyzing lab 
TBD by PI 
61 
Visit 3 Laboratory 
Procedures 
Updated: Cytokine labs not run in real time; analyzing lab 
TBD by PI 
62 
Visits 2 and 3 
Occurring on 
Saturdays 
Added: Section regarding special specimen collection and 
laboratory procedures for Visits 2 and 3 occurring on 
Saturdays 

 
90 
 
 
63-
64 
Specimen and 
Laboratory Flow 
Charts 
Updated: Specimen and Laboratory Flow Charts; cytokine 
labs not run in real time, analyzing lab TBD 
67-
68 
Clinical Laboratory 
Protocols 
Updated: Cytokine processing procedures and lab TBD 
69 
Adherence and 
Retention 
Removed: Study website and Facebook page never 
implemented