The Effect of Early Screening and Intervention for Gestational Diabetes Mellitus on Pregnancy Outcomes (TESGO)

The Effect of Early Screening and Intervention for Gestational Diabetes Mellitus on Pregnancy Outcomes: the TESGO Randomized Trial

Context: Women with gestational diabetes have excessive fetus growth weeks earlier than the screening period recommended currently, suggesting that earlier screening and intervention may improve pregnancy outcomes and the health of the offspring.

Objective: To determine if early screening and intervention could alter pregnancy outcomes, the incidence of maternal diabetes after delivery, and growth and development of the offspring, compared to the standard group.

Design, Setting, Participants: We will conduct a multi-center open-label randomized controlled trial in 2068 pregnant women, who deliver a singleton and who have not been diagnosed with overt diabetes mellitus at National Taiwan University Hospital (NTUH) and NTUH Hsinchu Branch from 2018 to 2020.

Interventions: Gestational diabetes mellitus (GDM) is diagnosed by a 75g 2-hour OGTT at 18-20 weeks of GA for the early-screening group and at 24-28 weeks for the standard-screening group. The diagnostic cutoffs are according to the IADPSG criteria. GDM is diagnosed if one of the plasma glucose levels at fasting, 1-hour, and 2-hour during OGTT is above 92 mg/dL, 180 mg/dL, or 153 mg/dL respectively. Subjects who are diagnosed with GDM receive lifestyle intervention and self-monitoring of blood glucose. Pharmacological therapies are given when the target of glycemic control is not achieved within 4-6 weeks.

Main Outcome Measure: The primary outcome is a composite measure of pregnancy outcomes, including primary CS, birth weight >90th percentile, neonatal hypoglycemia, cord serum C-peptide >90th percentile, pregnancy-induced hypertension, preeclampsia, and birth trauma. The primary outcome is measured within the entire period of perinatal and neonatal intensive-care units (NICU) stay for infants and the entire period of gestation for pregnant women after randomization.

Conclusion: This study will test our hypothesis that early screening and intervention of GDM improves pregnancy outcomes as compared to standard practice.

Study Overview

• Status: Active, not recruiting
• Conditions: Pregnancy Complications; Gestational Diabetes Mellitus in Pregnancy
• Intervention / Treatment: Other: early screening and intervention; Other: standard screening and intervention

• Study Type: Interventional
• Enrollment (Actual): 967
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Department of Internal Medicine, National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age ≥ 20 years old
2. First prenatal visit before 14 weeks of GA
3. Deliver a singleton at medical centers, including National Taiwan University Hospital (NTUH), and NTUH, Hsinchu Branch.

Exclusion Criteria:

1. Diagnosed with preexisting diabetes
2. Twin or multiple births pregnancy
3. Current exposure to steroids
4. Cannot tolerate an OGTT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early-screen Group; The early screening group will be screened by a 75g 2-hour oral glucose tolerance test (OGTT) at 18-20 weeks of gestational age (GA). The time of early screening and intervention will be 6-8 weeks earlier than that of standard screening and intervention.	Other: early screening and intervention; The early screening group will be screened by a 75g 2-hour oral glucose tolerance test (OGTT) at 18-20 weeks of gestational age (GA). Gestational diabetes mellitus (GDM) is diagnosed according to the IADPSG criteria. Subjects diagnosed with GDM will receive nutrition counseling, and lifestyle intervention. Pharmacologic therapies exclusively with human insulin or insulin analogues will be given when the target of glycemic control is not achieved within 4 weeks. The process of screening and intervention in the early screening group is all the same with that in the standard screening group. The only difference between two groups is the time of screening and intervention (18-20 weeks vs. 24-28 weeks of GA).
Active Comparator: Standard-screen Group; The standard screening group will be screened by a 75g 2-hour oral glucose tolerance test (OGTT) at 24-28 weeks of gestational age (GA). The time of standard screening and intervention will be 6-8 weeks later than that of early screening and intervention.	Other: standard screening and intervention; The standard screening group will be screened by a 75g 2-hour oral glucose tolerance test (OGTT) at 24-28 weeks of gestational age (GA). Gestational diabetes mellitus (GDM) is diagnosed according to the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria, ie. if one of the plasma glucose levels at fasting, 1-hour, and 2-hour during OGTT is above 92 mg/dL, 180 mg/dL, and 153 mg/dL, respectively. Subjects diagnosed with GDM will receive nutrition counseling, and lifestyle intervention. Pharmacologic therapies exclusively with human insulin or insulin analogues will be given when the target of glycemic control is not achieved within 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TESGO composite outcome	the occurrence rate of any of the following adverse outcome, including primary cesarean section (CS), birth weight >90th percentile, cord serum C-peptide ≥90th percentile, neonatal hypoglycemia, pregnancy-induced hypertension, preeclampsia, birth trauma, hypoglycemia, cord serum C-peptide >90th percentile, gestational hypertension, preeclampsia and birth trauma	The primary outcome is measured within the entire period of perinatal and NICU stay for infants and the entire period of gestation for pregnant women after randomization, an average of 10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preterm delivery	the occurrence rate of preterm delivery	This secondary outcome is measured within the entire period of gestation for pregnant women after randomization, an average of 10 months
Jaundice	the occurrence rate of newborns with jaundice	This secondary outcome is measured within the entire period of perinatal and NICU stay for infants, an average of 2 weeks
Admission to NICU	the occurrence rate of newborns who need to be admitted to neonatal intensive care unit (NICU)	This secondary outcome is measured within the entire period of perinatal and NICU stay for infants, an average of 2 weeks
Fetal death or stillbirth	the occurrence rate of fetal death or stillbirth	This secondary outcome is measured within the entire period of perinatal and NICU stay for infants and the entire period of gestation for pregnant women after randomization, an average of 10 months
Fetal growth during pregnancy	measurement of fetal growth during pregnancy recorded by ultrasonography	The secondary outcome is measured within the entire period of gestation for pregnant women after randomization, an average of 10 months
Neonatal adiposity	measurement of neonatal adiposity recorded by skinfold caliper	The secondary outcome is measured within the entire period of perinatal and NICU stay for infants, an average of 2 weeks
Maternal incident diabetes	the incidence of maternal diabetes after delivery	This secondary outcome is measured during 3 years after delivery for eligible women
The growth and development of the offspring	measurement of the growth and development of the offspring, including body height, body weight, head circumference, and records of any major disease	This secondary outcome is measured during 3 years after delivery for eligible infants

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Hung-Yuan Li, Ph.D., National Taiwan University Hospital

Publications and helpful links

General Publications

• Landon MB, Rice MM, Varner MW, Casey BM, Reddy UM, Wapner RJ, Rouse DJ, Biggio JR Jr, Thorp JM, Chien EK, Saade G, Peaceman AM, Blackwell SC, VanDorsten JP; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. Mild gestational diabetes mellitus and long-term child health. Diabetes Care. 2015 Mar;38(3):445-52. doi: 10.2337/dc14-2159. Epub 2014 Nov 20.
• Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008 Jul 3;359(1):61-73. doi: 10.1056/NEJMra0708473. No abstract available.
• Tisi DK, Burns DH, Luskey GW, Koski KG. Fetal exposure to altered amniotic fluid glucose, insulin, and insulin-like growth factor-binding protein 1 occurs before screening for gestational diabetes mellitus. Diabetes Care. 2011 Jan;34(1):139-44. doi: 10.2337/dc10-0607. Epub 2010 Sep 20.
• Qiu C, Vadachkoria S, Meryman L, Frederick IO, Williams MA. Maternal plasma concentrations of IGF-1, IGFBP-1, and C-peptide in early pregnancy and subsequent risk of gestational diabetes mellitus. Am J Obstet Gynecol. 2005 Nov;193(5):1691-7. doi: 10.1016/j.ajog.2005.04.015.
• Asvold BO, Eskild A, Jenum PA, Vatten LJ. Maternal concentrations of insulin-like growth factor I and insulin-like growth factor binding protein 1 during pregnancy and birth weight of offspring. Am J Epidemiol. 2011 Jul 15;174(2):129-35. doi: 10.1093/aje/kwr067. Epub 2011 May 27.
• Valensise H, Larciprete G, Vasapollo B, Novelli GP, Menghini S, di Pierro G, Arduini D. C-peptide and insulin levels at 24-30 weeks' gestation: an increased risk of adverse pregnancy outcomes? Eur J Obstet Gynecol Reprod Biol. 2002 Jul 10;103(2):130-5. doi: 10.1016/s0301-2115(02)00048-9.
• Ning Y, Williams MA, Vadachkoria S, Muy-Rivera M, Frederick IO, Luthy DA. Maternal plasma concentrations of insulinlike growth factor-1 and insulinlike growth factor-binding protein-1 in early pregnancy and subsequent risk of preeclampsia. Clin Biochem. 2004 Nov;37(11):968-73. doi: 10.1016/j.clinbiochem.2004.07.009.
• Lappas M. Insulin-like growth factor-binding protein 1 and 7 concentrations are lower in obese pregnant women, women with gestational diabetes and their fetuses. J Perinatol. 2015 Jan;35(1):32-8. doi: 10.1038/jp.2014.144. Epub 2014 Jul 31.
• Sovio U, Murphy HR, Smith GC. Accelerated Fetal Growth Prior to Diagnosis of Gestational Diabetes Mellitus: A Prospective Cohort Study of Nulliparous Women. Diabetes Care. 2016 Jun;39(6):982-7. doi: 10.2337/dc16-0160. Epub 2016 Apr 7.
• Gillman MW, Oakey H, Baghurst PA, Volkmer RE, Robinson JS, Crowther CA. Effect of treatment of gestational diabetes mellitus on obesity in the next generation. Diabetes Care. 2010 May;33(5):964-8. doi: 10.2337/dc09-1810. Epub 2010 Feb 11.
• de Mello VD, Pulkkinen L, Lalli M, Kolehmainen M, Pihlajamaki J, Uusitupa M. DNA methylation in obesity and type 2 diabetes. Ann Med. 2014 May;46(3):103-13. doi: 10.3109/07853890.2013.857259. Epub 2014 Apr 30.
• Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr. 2007;27:363-88. doi: 10.1146/annurev.nutr.27.061406.093705.
• Lehnen H, Zechner U, Haaf T. Epigenetics of gestational diabetes mellitus and offspring health: the time for action is in early stages of life. Mol Hum Reprod. 2013 Jul;19(7):415-22. doi: 10.1093/molehr/gat020. Epub 2013 Mar 20.
• International Association of Diabetes and Pregnancy Study Groups Consensus Panel; Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, Damm P, Dyer AR, Leiva Ad, Hod M, Kitzmiler JL, Lowe LP, McIntyre HD, Oats JJ, Omori Y, Schmidt MI. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010 Mar;33(3):676-82. doi: 10.2337/dc09-1848. No abstract available.
• Metzger BE, Buchanan TA, Coustan DR, de Leiva A, Dunger DB, Hadden DR, Hod M, Kitzmiller JL, Kjos SL, Oats JN, Pettitt DJ, Sacks DA, Zoupas C. Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care. 2007 Jul;30 Suppl 2:S251-60. doi: 10.2337/dc07-s225. No abstract available. Erratum In: Diabetes Care. 2007 Dec;30(12):3154.
• Workgroup on Hypoglycemia, American Diabetes Association. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005 May;28(5):1245-9. doi: 10.2337/diacare.28.5.1245. No abstract available.
• Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, Heller SR, Rodriguez H, Rosenzweig J, Vigersky R. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 2013 May;36(5):1384-95. doi: 10.2337/dc12-2480. Epub 2013 Apr 15.

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2018
• Primary Completion (Actual): December 13, 2021
• Study Completion (Estimated): December 13, 2023

Study Registration Dates

• First Submitted: April 18, 2018
• First Submitted That Met QC Criteria: May 1, 2018
• First Posted (Actual): May 14, 2018

Study Record Updates

• Last Update Posted (Actual): August 24, 2023
• Last Update Submitted That Met QC Criteria: August 23, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: randomized controlled trial; early intervention; pregnancy outcomes; gestational diabetes mellitus; early screening
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Pregnancy Complications; Diabetes, Gestational; Pregnancy in Diabetics
• Other Study ID Numbers: 201710072RINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No