Early Screening for Gestational Diabetes Mellitus in a Low Risk Population

Not Applicable

Not yet recruiting

• Conditions: Gestational Diabetes Mellitus (GDM); Glucose Intolerance During Pregnancy

• Registration Number: NCT06704035
• Lead Sponsor: National University Hospital, Singapore

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.

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-10-17
• Study First Submitted QC: 2024-11-21
• Last Update Submitted: 2024-11-21
• Study First Posted: 2024-11-25
• Last Update Posted: 2024-11-25
• Study Start: 2024-12-01
• Primary Completion: 2026-04-30
• Study Completion: 2026-11-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 120

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Composite of perinatal/neonatal morbidity/mortality	At birth to one month postpartum	Display at least one of the following outcomes: preterm birth \<37 weeks' gestation, large for gestational age neonate \>90th centile of birthweight, birth trauma, shoulder dystocia, neonatal hypoglycaemia, neonatal respiratory distress, jaundice requiring phototherapy, stillbirth/neonatal death.

Secondary Outcome Measures

Name	Time	Method
Pre-eclampsia and hypertensive disorders of pregnancy	Up to 49 weeks, from the estimated date of conception (based on menstrual and ultrasound scan data) up to 6 weeks postpartum	Number and proportion of participants who experience new onset hypertension in pregnancy, pre-eclampsia, eclampsia, or superimposed pre-eclampsia on chronic hypertension, with or without signs of progressive multi-system disorder or end-organ involvement, including cases of atypical pre-eclampsia where hypertension is not the predominant feature.
Antenatal and Peripartum obstetric events	Up to 49 weeks, from the estimated date of conception (based on menstrual and ultrasound scan data) up to 6 weeks postpartum	Number and proportion of participants who experience antenatal complications, undergo caesarean section, suffer perineal trauma, experience postpartum haemorrhage, or require other delivery interventions, including labour induction, extended labour duration, use of oxytocin, instrumental delivery, and high dependency care.
Birthweight	At Birth	Raw birthweight, macrosomia defined as birthweight \>4000g, low birthweight \<2500g, Large for Gestational Age (\>90th centile) and Small for Gestational Age (\<10th centile) using customised/standardised birthweight references.
Neonatal complications and treatments	From Birth to 3 months post-delivery	Admission to neonatal unit (including level of unit and length of stay), infant weight gain, hyperbilirubinaemia, infections, treatments (including antibiotics, iv/tube feeding, blood products, oxygen, breathing aids) and other neonatal conditions requiring medical care.
Maternal depression and anxiety symptoms	Before 16 weeks' gestation, at around 24-28 weeks gestation (accepted up to 32 weeks and 6 days), postpartum (~1 month; accept 3-6 weeks post-delivery)	Scores of maternal depression and anxiety symptoms on validated questionnaires (Edinburgh Postnatal Depression Scale and Generalized Anxiety Disorder-7 Scale). The scores on the Edinburgh Postnatal Depression Scale range from 0 to 30, with higher scores indicating more depression symptoms. The scores on the Generalized Anxiety Disorder-7 range from 0 to 21, where higher scores indicate more anxiety symptoms.
Breastfeeding	Postpartum (~1 month; accept 3-6 weeks post-delivery)	Interviewer-administered questionnaire to evaluate the incidence and timing of skin-to-skin post-delivery, first suckle, duration of exclusivity of breastfeeding, and intake of formula feeds (timing of onset, duration, and frequency).
Prevalences of pre-existing diabetes mellitus and postpartum dysglycaemia (diabetes and pre-diabetes)	Oral glucose tolerance test (OGTT) before 16 weeks of gestation and at around 6-12 weeks postpartum	Pre-existing diabetes is identified based on glucose concentrations in a 75g OGTT defined by the World Health Organization (WHO) diagnostic criteria for non-pregnant adults. The following values are used to diagnose pre-existing diabetes: fasting glucose (0-hour): ≥ 7.0 mmol/L or 2-hour post-load glucose: ≥ 11.1 mmol/L. If either of these is met during the early pregnancy OGTT and post-partum OGTT (6-12 weeks post-delivery), the participant is diagnosed with pre-existing diabetes. Postpartum OGTT results will be obtained from medical records. Pre-diabetes postpartum will be identified by a 75g OGTT following the 2006 WHO criteria: Impaired fasting glucose (IFG) will be diagnosed when fasting plasma glucose (FPG) is between 6.1-6.9 mmol/L, while impaired glucose tolerance (IGT) will be defined by a 2-hour plasma glucose of 7.8-11.0 mmol/L.
Gestational diabetes incidence (early and late diagnosis)	Pregnancy Oral Glucose Tolerance Test (OGTT) before 16 weeks of gestation and/or at around 24-28 weeks of gestation (accept all results till 32 weeks and 6 days)	GDM is diagnosed based on criteria set by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) and WHO (2013). If at least one plasma glucose value meet the following criteria during a 75g three time point OGTT, it will indicate GDM: fasting glucose: ≥ 5.1 mmol/L, 1-hour post-load glucose: ≥ 10.0 mmol/L or 2-hour post-load glucose: ≥ 8.5 mmol/L.
Predictive performance of a novel machine-learning-derived algorithm	Up to 54 weeks, from the estimated date of conception (based on menstrual and ultrasound scan data) up to the time of latest OGTT (32 weeks and 6 days gestation or OGTT at 6-12 weeks postpartum)	A novel machine-learning-derived algorithm, specifically designed for the Singapore pregnant population, will use clinical data collected in early pregnancy (including maternal age, ethnicity, mean arterial blood pressure) to predict GDM development. The sensitivity, specificity, positive predictive and negative predictive value, receiver operating characteristic curve (ROC curve) will be evaluated for GDM and glucose intolerance as well as for pregnancy and neonatal outcomes.
Continuous Glucose Monitor (CGM) Data Measurements and predictive performance	Up to 48 weeks, from recruitment up to the time of latest OGTT (32 weeks and 6 days gestation or OGTT at 6-12 weeks postpartum)	Identification of the key metrics from CGM evaluation that predict GDM, glucose intolerance, later pregnancy/postpartum dysglycaemia, and pregnancy and neonatal outcomes.
Gingival crevicular fluid (GCF) and circulating biomarkers	Up to 48 weeks, from recruitment up to the time of latest OGTT (32 weeks and 6 days gestation or OGTT at 6-12 weeks postpartum)	Identification of the key biomarkers from metabolomic, proteomic, and transcriptomic analyses on gingival crevicular fluid samples and blood obtained in early pregnancy that associate with GDM and glucose intolerance, later pregnancy/postpartum dysglycaemia, and pregnancy and neonatal outcomes.

Trial Locations

Locations (1)

National University Hospital; 🇸🇬 Singapore, Singapore