Early Screening for Gestational Diabetes Mellitus in a Low Risk Population

NCT ID: NCT06704035

Last Updated: 2024-11-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-01
• Study Completion Date: 2026-11-30

Brief Summary

This new feasibility pilot study aims to refine the design and protocols for a larger trial that will investigate the potential benefits of early oral glucose tolerance test (OGTT) screening in a population traditionally defined as low-risk for development of gestational diabetes. The study will evaluate its potential effectiveness in reducing the risks of neonatal morbidity/mortality and obstetric complications. Additionally, a machine learning algorithm to predict gestational diabetes mellitus (GDM) risk based on routinely obtained clinical information at pregnancy booking, and minimally invasive methods, such as continuous glucose monitoring (CGM) and gingival crevicular fluid (GCF) sampling, are being explored to predict the risk of hyperglycaemia. This study aims to investigate the utility of early pregnancy screening to enable timely detection and management of early gestational diabetes development in a low-risk population, ultimately promoting better health outcomes for mothers and their babies.

Detailed Description

The Early Screening for Gestational Diabetes Mellitus in a Low-Risk Population (EaGeR) pilot study aims to inform a future trial that would evaluate whether early oral glucose tolerance test (OGTT) screening can improve pregnancy and neonatal outcomes among low-risk pregnant women in Singapore, a country that has one of the highest global incidences of gestational diabetes mellitus (GDM). GDM is associated with higher risks of neonatal and obstetric complications in the short-term, and in the long-term increased cardiometabolic risks in both mothers and their children.

The current local GDM screening practice comprises universal screening of all pregnancies (without pre-existing diabetes) with an OGTT around 24-28 weeks' gestation, and only offering early pregnancy screening to women with traditional high-risk factors for GDM development. The issue is that around 70% of diagnosed GDM cases in Singapore do not possess traditional high-risk factors, and they could have been potentially picked up earlier in gestation, if screened. Conversely, many women identified as high-risk in early pregnancy show normal glucose concentrations in an OGTT when screened in early gestation and when re-screened at 24-28 weeks. This study builds on findings from previous trials, which showed that early screening and treatment of mild glucose intolerance in high-risk women can reduce neonatal complications. The EaGeR Trial seeks to determine whether similar benefits can be achieved in an apparently low-risk Asian population.

This pilot study will recruit 120 low-risk pregnant women before 16 weeks' gestation. All participants will undergo an early OGTT before 16 weeks' and be randomly assigned to one of two arms: the experimental arm, where early OGTT results are revealed and immediate follow-up actions taken if GDM is diagnosed using the WHO 2013 criteria, and the control arm, where early OGTT results are concealed, with follow-up in accordance with standard care involving the routine OGTT screen at 24-28 weeks' gestation.

Data will be collected from the medical records to evaluate the primary and secondary outcomes which include pregnancy and neonatal events, as well as infant measures. Additionally, maternal symptoms and biomarkers, infant anthropometry and breastfeeding will be evaluated. Outcomes will be compared between study arms.

Further, the study will also test the utility of a newly developed machine learning algorithm as a novel and non-invasive method which uses clinical factors available at pregnancy booking to assess individual risk for GDM development. It will also explore the utility of other minimally invasive methods of continuous glucose monitoring (CGM) and gingival crevicular fluid (GCF) sampling at an early stage of pregnancy, in predicting the risk of GDM development.

This initial pilot study will help to refine the design and protocols of the definitive EaGeR Trial which will eventually guide the development of the optimal screening strategy for GDM among low-risk pregnant women in Singapore for improved neonatal and obstetric outcomes.

Conditions

Gestational Diabetes Mellitus (GDM); Glucose Intolerance During Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

Early OGTT Results Revealed

The results of the early OGTT conducted before 16 weeks' gestation will be revealed to the participants. If the results indicate gestational diabetes mellitus (GDM) by the WHO 2013 criteria, immediate follow-up actions, including appropriate treatments, will be taken. Those with a normal result will undertake the universally offered routine OGTT at 24-28 weeks' gestation.

Group Type: EXPERIMENTAL

Early OGTT Results Revealed

Intervention Type: DIAGNOSTIC_TEST

Early pregnancy screening with a three-time point (fasting, 1h, 2h) 75g oral glucose tolerance test before 16 weeks' gestation with plasma glucose results revealed to the patient and clinician for appropriate management of any diabetes (gestational and type 2, if diagnosed) from early pregnancy onwards.

Early OGTT Results Concealed

Participants in this arm will undergo an early oral glucose tolerance test (OGTT) before 16 weeks' gestation, however, the results will be concealed from the participants and study investigators, and results will not be acted upon (unless they are suggestive of pre-existing type 2 diabetes mellitus as reviewed by an independent clinician, in which case appropriate follow-up will be arranged). All participants (except those with results suggestive of type 2 diabetes) will undertake the routine OGTT at 24-28 weeks' gestation, as per standard care.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Early OGTT Results Revealed

Early pregnancy screening with a three-time point (fasting, 1h, 2h) 75g oral glucose tolerance test before 16 weeks' gestation with plasma glucose results revealed to the patient and clinician for appropriate management of any diabetes (gestational and type 2, if diagnosed) from early pregnancy onwards.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

1. Pregnant women aged 21-39 years at recruitment

2. Singleton pregnancy

3. Less than 16 weeks pregnant at recruitment

4. Intend to receive antenatal care and give birth at the National University Hospital

Exclusion Criteria

1. Known pre-existing type 1 or type 2 diabetes mellitus at recruitment

2. Classified as high-risk for GDM at pregnancy booking using the traditional checklist:

2.1) Age ≥40 years 2.2) Overweight/obese, i.e., body mass index (BMI) ≥25.0 kg/m2 2.3) First degree relative with diabetes mellitus 2.4) Previously delivered a baby ≥4 kg 2.5) Previously diagnosed with GDM 2.6) Impaired glucose tolerance (IGT) or impaired fasting glycaemia (IFG) on previous testing 2.7) Polycystic ovarian syndrome (PCOS) 2.8) Poor obstetric history (e.g. recurrent pregnancy loss, previous intrauterine death, congenital malformations) 2.9) History of chronic hypertension, hyperlipidaemia or cardiovascular disease 2.10) Glycosuria ≥ 2+ on urine dipstick

3. Taking systemic steroid medication or metformin

4. Participation in another intervention trial

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National University of Singapore

OTHER

Sponsor Role: collaborator

Agency for Science, Technology and Research

OTHER

Sponsor Role: collaborator

National University Hospital, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

National University Hospital

Singapore, , Singapore

Countries

Singapore

Central Contacts

Gladys Woon, BSc

Role: CONTACT

gladys_woon@nuhs.edu.sg

+65 6516 4134

Facility Contacts

Gladys Woon, BSc

Role: primary

gladys_woon@nuhs.edu.sg

+65 6516 4134

References

Teo E, Hassan N, Tam W, Koh S. Effectiveness of continuous glucose monitoring in maintaining glycaemic control among people with type 1 diabetes mellitus: a systematic review of randomised controlled trials and meta-analysis. Diabetologia. 2022 Apr;65(4):604-619. doi: 10.1007/s00125-021-05648-4. Epub 2022 Feb 9.

Reference Type: BACKGROUND

PMID: 35141761 (View on PubMed)

Majewska A, Stanirowski PJ, Wielgos M, Bomba-Opon D. Efficacy of Continuous Glucose Monitoring on Glycaemic Control in Pregnant Women with Gestational Diabetes Mellitus-A Systematic Review. J Clin Med. 2022 May 23;11(10):2932. doi: 10.3390/jcm11102932.

Reference Type: BACKGROUND

PMID: 35629058 (View on PubMed)

HAPO Study Cooperative Research Group; Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, Hadden DR, McCance DR, Hod M, McIntyre HD, Oats JJ, Persson B, Rogers MS, Sacks DA. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008 May 8;358(19):1991-2002. doi: 10.1056/NEJMoa0707943.

Reference Type: BACKGROUND

PMID: 18463375 (View on PubMed)

Li LJ, Huang L, Tobias DK, Zhang C. Gestational Diabetes Mellitus Among Asians - A Systematic Review From a Population Health Perspective. Front Endocrinol (Lausanne). 2022 Jun 16;13:840331. doi: 10.3389/fendo.2022.840331. eCollection 2022.

Reference Type: BACKGROUND

PMID: 35784581 (View on PubMed)

Simmons D, Hague WM, Teede HJ, Cheung NW, Hibbert EJ, Nolan CJ, Peek MJ, Girosi F, Cowell CT, Wong VW, Flack JR, McLean M, Dalal R, Robertson A, Rajagopal R. Hyperglycaemia in early pregnancy: the Treatment of Booking Gestational diabetes Mellitus (TOBOGM) study. A randomised controlled trial. Med J Aust. 2018 Nov 5;209(9):405-406. doi: 10.5694/mja17.01129. Epub 2018 May 28.

Reference Type: BACKGROUND

PMID: 29793404 (View on PubMed)

Vinter CA, Tanvig MH, Christensen MH, Ovesen PG, Jorgensen JS, Andersen MS, McIntyre HD, Jensen DM. Lifestyle Intervention in Danish Obese Pregnant Women With Early Gestational Diabetes Mellitus According to WHO 2013 Criteria Does Not Change Pregnancy Outcomes: Results From the LiP (Lifestyle in Pregnancy) Study. Diabetes Care. 2018 Oct;41(10):2079-2085. doi: 10.2337/dc18-0808. Epub 2018 Jul 30.

Reference Type: BACKGROUND

PMID: 30061318 (View on PubMed)

Harper LM, Jauk V, Longo S, Biggio JR, Szychowski JM, Tita AT. Early gestational diabetes screening in obese women: a randomized controlled trial. Am J Obstet Gynecol. 2020 May;222(5):495.e1-495.e8. doi: 10.1016/j.ajog.2019.12.021. Epub 2020 Jan 9.

Reference Type: BACKGROUND

PMID: 31926951 (View on PubMed)

Minschart C, Beunen K, Benhalima K. An Update on Screening Strategies for Gestational Diabetes Mellitus: A Narrative Review. Diabetes Metab Syndr Obes. 2021 Jul 5;14:3047-3076. doi: 10.2147/DMSO.S287121. eCollection 2021.

Reference Type: BACKGROUND

PMID: 34262311 (View on PubMed)

Logan KM, Emsley RJ, Jeffries S, Andrzejewska I, Hyde MJ, Gale C, Chappell K, Mandalia S, Santhakumaran S, Parkinson JR, Mills L, Modi N. Development of Early Adiposity in Infants of Mothers With Gestational Diabetes Mellitus. Diabetes Care. 2016 Jun;39(6):1045-51. doi: 10.2337/dc16-0030. Epub 2016 May 12.

Reference Type: BACKGROUND

PMID: 27208326 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27208333 (View on PubMed)

Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS; Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 2005 Jun 16;352(24):2477-86. doi: 10.1056/NEJMoa042973. Epub 2005 Jun 12.

Reference Type: BACKGROUND

PMID: 15951574 (View on PubMed)

Chaparro A, Zuniga E, Varas-Godoy M, Albers D, Ramirez V, Hernandez M, Kusanovic JP, Acuna-Gallardo S, Rice G, Illanes SE. Periodontitis and placental growth factor in oral fluids are early pregnancy predictors of gestational diabetes mellitus. J Periodontol. 2018 Sep;89(9):1052-1060. doi: 10.1002/JPER.17-0497.

Reference Type: BACKGROUND

PMID: 29790168 (View on PubMed)

Abouzaid M, Howidi N, Badran Z, Mohammed G, Mousa NA. The potential role of the gingival crevicular fluid biomarkers in the prediction of pregnancy complications. Front Med (Lausanne). 2023 Jun 5;10:1168625. doi: 10.3389/fmed.2023.1168625. eCollection 2023.

Reference Type: BACKGROUND

PMID: 37342498 (View on PubMed)

Monteiro LJ, Varas-Godoy M, Monckeberg M, Realini O, Hernandez M, Rice G, Romero R, Saavedra JF, Illanes SE, Chaparro A. Oral extracellular vesicles in early pregnancy can identify patients at risk of developing gestational diabetes mellitus. PLoS One. 2019 Jun 26;14(6):e0218616. doi: 10.1371/journal.pone.0218616. eCollection 2019.

Reference Type: BACKGROUND

PMID: 31242249 (View on PubMed)

Ozcaka O, Ceyhan-Ozturk B, Gumus P, Akcali A, Nalbantsoy A, Buduneli N. Clinical periodontal status and inflammatory cytokines in gestational diabetes mellitus. Arch Oral Biol. 2016 Dec;72:87-91. doi: 10.1016/j.archoralbio.2016.08.012. Epub 2016 Aug 11.

Reference Type: BACKGROUND

PMID: 27552375 (View on PubMed)

Subbarao KC, Nattuthurai GS, Sundararajan SK, Sujith I, Joseph J, Syedshah YP. Gingival Crevicular Fluid: An Overview. J Pharm Bioallied Sci. 2019 May;11(Suppl 2):S135-S139. doi: 10.4103/JPBS.JPBS_56_19.

Reference Type: BACKGROUND

PMID: 31198325 (View on PubMed)

Di Filippo D, Ahmadzai M, Chang MHY, Horgan K, Ong RM, Darling J, Akhtar M, Henry A, Welsh A. Continuous Glucose Monitoring for the Diagnosis of Gestational Diabetes Mellitus: A Pilot Study. J Diabetes Res. 2022 Oct 17;2022:5142918. doi: 10.1155/2022/5142918. eCollection 2022.

Reference Type: BACKGROUND

PMID: 36299907 (View on PubMed)

Afandi B, Hassanein M, Roubi S, Nagelkerke N. The value of Continuous Glucose Monitoring and Self-Monitoring of Blood Glucose in patients with Gestational Diabetes Mellitus during Ramadan fasting. Diabetes Res Clin Pract. 2019 May;151:260-264. doi: 10.1016/j.diabres.2019.01.036. Epub 2019 Feb 26.

Reference Type: BACKGROUND

PMID: 30822494 (View on PubMed)

Yu Q, Aris IM, Tan KH, Li LJ. Application and Utility of Continuous Glucose Monitoring in Pregnancy: A Systematic Review. Front Endocrinol (Lausanne). 2019 Oct 11;10:697. doi: 10.3389/fendo.2019.00697. eCollection 2019.

Reference Type: BACKGROUND

PMID: 31681170 (View on PubMed)

Kumar M, Chen L, Tan K, Ang LT, Ho C, Wong G, Soh SE, Tan KH, Chan JKY, Godfrey KM, Chan SY, Chong MFF, Connolly JE, Chong YS, Eriksson JG, Feng M, Karnani N. Population-centric risk prediction modeling for gestational diabetes mellitus: A machine learning approach. Diabetes Res Clin Pract. 2022 Mar;185:109237. doi: 10.1016/j.diabres.2022.109237. Epub 2022 Feb 4.

Reference Type: BACKGROUND

PMID: 35124096 (View on PubMed)

Chong YS, Cai S, Lin H, Soh SE, Lee YS, Leow MK, Chan YH, Chen L, Holbrook JD, Tan KH, Rajadurai VS, Yeo GS, Kramer MS, Saw SM, Gluckman PD, Godfrey KM, Kwek K; GUSTO study group. Ethnic differences translate to inadequacy of high-risk screening for gestational diabetes mellitus in an Asian population: a cohort study. BMC Pregnancy Childbirth. 2014 Oct 2;14:345. doi: 10.1186/1471-2393-14-345.

Reference Type: BACKGROUND

PMID: 25273851 (View on PubMed)

Simmons D, Immanuel J, Hague WM, Teede H, Nolan CJ, Peek MJ, Flack JR, McLean M, Wong V, Hibbert E, Kautzky-Willer A, Harreiter J, Backman H, Gianatti E, Sweeting A, Mohan V, Enticott J, Cheung NW; TOBOGM Research Group. Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy. N Engl J Med. 2023 Jun 8;388(23):2132-2144. doi: 10.1056/NEJMoa2214956. Epub 2023 May 5.

Reference Type: BACKGROUND

PMID: 37144983 (View on PubMed)

American Diabetes Association Professional Practice Committee. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022 Jan 1;45(Suppl 1):S17-S38. doi: 10.2337/dc22-S002.

Reference Type: BACKGROUND

PMID: 34964875 (View on PubMed)

Griffin ME, Coffey M, Johnson H, Scanlon P, Foley M, Stronge J, O'Meara NM, Firth RG. Universal vs. risk factor-based screening for gestational diabetes mellitus: detection rates, gestation at diagnosis and outcome. Diabet Med. 2000 Jan;17(1):26-32. doi: 10.1046/j.1464-5491.2000.00214.x.

Reference Type: BACKGROUND

PMID: 10691156 (View on PubMed)

Wicklow B, Retnakaran R. Gestational Diabetes Mellitus and Its Implications across the Life Span. Diabetes Metab J. 2023 May;47(3):333-344. doi: 10.4093/dmj.2022.0348. Epub 2023 Feb 8.

Reference Type: BACKGROUND

PMID: 36750271 (View on PubMed)

Pathirana MM, Lassi ZS, Ali A, Arstall MA, Roberts CT, Andraweera PH. Association between metabolic syndrome and gestational diabetes mellitus in women and their children: a systematic review and meta-analysis. Endocrine. 2021 Feb;71(2):310-320. doi: 10.1007/s12020-020-02492-1. Epub 2020 Sep 15.

Reference Type: BACKGROUND

PMID: 32930949 (View on PubMed)

Chen LW, Soh SE, Tint MT, Loy SL, Yap F, Tan KH, Lee YS, Shek LP, Godfrey KM, Gluckman PD, Eriksson JG, Chong YS, Chan SY. Combined analysis of gestational diabetes and maternal weight status from pre-pregnancy through post-delivery in future development of type 2 diabetes. Sci Rep. 2021 Mar 3;11(1):5021. doi: 10.1038/s41598-021-82789-x.

Reference Type: BACKGROUND

PMID: 33658531 (View on PubMed)

Yew TW, Chi C, Chan SY, van Dam RM, Whitton C, Lim CS, Foong PS, Fransisca W, Teoh CL, Chen J, Ho-Lim ST, Lim SL, Ong KW, Ong PH, Tai BC, Tai ES. A Randomized Controlled Trial to Evaluate the Effects of a Smartphone Application-Based Lifestyle Coaching Program on Gestational Weight Gain, Glycemic Control, and Maternal and Neonatal Outcomes in Women With Gestational Diabetes Mellitus: The SMART-GDM Study. Diabetes Care. 2021 Feb;44(2):456-463. doi: 10.2337/dc20-1216. Epub 2020 Nov 12.

Reference Type: BACKGROUND

PMID: 33184151 (View on PubMed)

Sanchez-Ramos L, Bernstein S, Kaunitz AM. Expectant management versus labor induction for suspected fetal macrosomia: a systematic review. Obstet Gynecol. 2002 Nov;100(5 Pt 1):997-1002.

Reference Type: BACKGROUND

PMID: 12423867 (View on PubMed)

Boulvain M, Stan C, Irion O. Elective delivery in diabetic pregnant women. Cochrane Database Syst Rev. 2000;2001(2):CD001997. doi: 10.1002/14651858.CD001997.

Reference Type: BACKGROUND

PMID: 10796277 (View on PubMed)

Nguyen CL, Pham NM, Binns CW, Duong DV, Lee AH. Prevalence of Gestational Diabetes Mellitus in Eastern and Southeastern Asia: A Systematic Review and Meta-Analysis. J Diabetes Res. 2018 Feb 20;2018:6536974. doi: 10.1155/2018/6536974. eCollection 2018.

Reference Type: BACKGROUND

PMID: 29675432 (View on PubMed)

Other Identifiers

2023/00970

Identifier Type: -

Identifier Source: org_study_id