Early Screening for Gestational Diabetes Mellitus in a Low Risk Population

Pre-eclampsia and hypertensive disorders of pregnancy

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.

Time frame: Up to 49 weeks, from the estimated date of conception (based on menstrual and ultrasound scan data) up to 6 weeks postpartum

Antenatal and Peripartum obstetric events

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.

Time frame: Up to 49 weeks, from the estimated date of conception (based on menstrual and ultrasound scan data) up to 6 weeks postpartum

Birthweight

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.

Time frame: At Birth

Neonatal complications and treatments

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.

Time frame: From Birth to 3 months post-delivery

Maternal depression and anxiety symptoms

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.

Time frame: 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)

Breastfeeding

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).

Time frame: Postpartum (~1 month; accept 3-6 weeks post-delivery)

Prevalences of pre-existing diabetes mellitus and postpartum dysglycaemia (diabetes and pre-diabetes)

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.

Time frame: Oral glucose tolerance test (OGTT) before 16 weeks of gestation and at around 6-12 weeks postpartum

Gestational diabetes incidence (early and late diagnosis)

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.

Time frame: 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)

Predictive performance of a novel machine-learning-derived algorithm

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.

Time frame: 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)

Continuous Glucose Monitor (CGM) Data Measurements and predictive performance

Identification of the key metrics from CGM evaluation that predict GDM, glucose intolerance, later pregnancy/postpartum dysglycaemia, and pregnancy and neonatal outcomes.

Time frame: 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)

Gingival crevicular fluid (GCF) and circulating biomarkers

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.

Time frame: 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)