Dietary intervention in gestational diabetes

Neonatal primary outcome measure:
Standardised birth weight (standardised for infant gender and gestational age at delivery); Timepoint(s): birth/36 weeks gestation - from hospital data at V3 and birth

Maternal primary outcome measure:
Maternal weight change (28-36 weeks), measured using Seca scales at V1 and V3

Neonatal secondary outcome measures:
1. Large for gestational age (using local, national and international centiles and customised centiles) at birth
2. Small for gestational age (using local, national and international centiles and customised centiles) at birth
3. Cord blood C-peptide measured using Diasorin liaison method at birth
4. Cord blood glucose measured using Hexokinase method on Siemen's analyser at birth
5. Amniotic fluid glucose measured using Hexokinase method on Siemen's analyser at birth
6. Neonatal anthropometry (length, weight, abdominal circumference, head circumference, skinfold thickness, mid upper arm circumference) measured using tape measure, Seca scales, Holtain calipers at birth and V4
7. Neonatal body composition measured using Peapod device at birth/V4
8. Neonatal hypoglycaemia (defined as a low blood glucose requiring intravenous dextrose) from hospital data at V4
9. Neonatal admission to the neonatal intensive care unit (NICU) from hospital data at V4
10. Neonatal feeding type on discharge from hospital, from hospital data, maternal questionnaire at V4
11. Neonatal nasogastric feeding from hospital data at V4
12. Duration of neonatal admission from hospital data at V4
13. Neonatal jaundice requiring phototherapy from hospital data at V4
14. Preterm delivery from hospital data at birth
15. Estimated gestational age at birth from hospital data, dataset calculation at birth
16. Apgar scores from hospital data at birth

Maternal secondary outcome measures:
1. Maternal weight and related measurements at 32 and 36 weeks and postpartum measured using Seca scales, Harpenden calipers, tape measure at V1, V2, V3 and V4
2. Maternal weight measured using Seca scales at V1, V2, V3 and V4
3. Maternal weight change (baseline to 32 weeks and 32 to 36 weeks) using dataset formula calculation at V3
4. Maternal BMI from dataset formula calculation at V1, V3 and V4
5. Maternal weight change (grams per week) from dataset formula calculation at V4
6. Velocity of maternal weight change (baseline to 32, 36 weeks and postpartum, and between each timepoint) from dataset formula calculation at V1, V2, V3, and V4
7. Maternal body composition at 6 weeks postpartum measured using DXA machine, Harpenden calipers, tape measure at V4
8. Maternal glycaemia on biochemical measurement (HbA1c and other biochemical measures of glycaemia) at 32 and 36 weeks and postpartum
9. Maternal glycaemia on continuous glucose monitoring at 32 and 36 weeks measured using Dexcom G6 CGM at V2 and V3:
9.1. Time in target (4.0 - 7.8 mmol/l) from Dexcom Clarity dataset at V1, V2, V3 and V4
9.2. Time below target (<4.0 mmol/l) from Dexcom Clarity dataset at V1, V2, V3 and V4
9.3. Time above target (>7.8 mmol/l) from Dexcom Clarity dataset at V1, V2, V3 and V4
9.4. Area under the curve for blood sugars >7.8 mmol/l from Dexcom Clarity dataset at V1, V2, V3 and V4
9.5. Area under the curve for blood sugars >6.7 mmol/l from Dexcom Clarity dataset at V1, V2, V3 and V4
9.6. Area under the curve for blood sugars <3.5 mmol/L from Dexcom Clarity dataset at V1, V2, V3 and V4
9.7. Area under the curve for blood sugars <2.8 mmol/L from Dexcom Clarity dataset at V1, V2, V3 and V4
9.8. Incidence of hypoglycaemic events from Dexcom Clarity dataset at V1, V2, V3 and V4
9.9. Mild-moderate episodes of hypoglycaemia <3.5mmol/l (mild) and <2.8 mmol/l (moderate) from data for area under the curve <3.5 mmol/l (mild) and <2.8 mmol/l (moderate) and duration of 20 minutes, from Dexcom Clarity dataset at V1, V2, V3 and V4
9.10. Nocturnal hypoglycaemia: glucose <3.5 mmol/l (mild) and <2.8 mmol/l (moderate) between 23.00-07.00 hours, from Dexcom Clarity dataset at V1, V2, V3 and V4
9.11. Time in hypoglycaemic range (<4 mmol/l; <2.5 mmol/l) from Dexcom Clarity dataset at V1, V2, V3 and V4
9.12. Peak and nadir blood glucose from Dexcom Clarity dataset at V1, V2, V3 and V4
9.13. Mean blood glucose from Dexcom Clarity dataset at V1, V2, V3 and V4
9.14. Mean nocturnal blood glucose from Dexcom Clarity dataset at V1, V2, V3 and V4
9.15. Mean postprandial blood glucose for 1, 2 & 4 hours after breakfast, lunch and dinner, from Dexcom Clarity dataset at V1, V2, V3 and V4
9.16. Standard deviation of blood glucose from Dexcom Clarity dataset at V1, V2, V3 and V4
9.17. Coefficient of variation of glucose measurements from Dexcom Clarity dataset at V1, V2, V3 and V4
9.18. Mean amplitude of glycemic excursions (MAGE) from Dexcom Clarity dataset at V1, V2, V3 and V4
10. Ultrasound measurements at baseline, 32 and 36 weeks, measured in absolute values and as a percentile and where relevant, as a categorical variable (<2.5th, <10th, >90th and >97.5th percentile):
10.1. Abdominal circumference (AC) from hospital data at V1, V2 and V3
10.2. Estimated fetal weight (EFW) from hospital data at V1, V2 and V3
10.3. Head circumference (HC) from hospital data at V1, V2 and V3
10.4. HC/AC ratio from hospital data at V1, V2 and V3
10.5. Umbilical artery flow studies from hospital data at V1, V2 and V3
10.6. Velocity of change of AC, HC, HC/AC and EFW from hospital data at V1, V2 and V3
10.7. Amniotic fluid index from hospital data at V1, V2 and V3
11. Cardiovascular variables at 32 and 36 weeks, and postpartum:
11.1. Blood pressure from Dinamap at V2, V3 and V4
11.2. Mean arterial pressure from Dinamap at V2, V3 and V4
11.3. Heart rate from Dinamap at V2, V3 and V4
11.4. Cardiac output from database formula calculation at V2, V3 and V4
12. Biochemical analysis of maternal blood at 32 and 36 weeks and 6 weeks postpartum:
12.1. Lipids including triglycerides measured using Siemens dimension methods
12.2. Insulin measured using Diasorin liaison method
12.3. Glucose measured using Siemens dimension hexokinase method
12.4. C-peptide measured using Diasorin liaison method
12.5. Liver function tests measured using Siemens dimension methods
12.6. Bile acids measured using Siemens dimension methods
12.7. C-reactive protein (including highly sensitive analyses) measured using Siemens dimension methods
12.8. Metabolomics using Metabolon Ltd or in house method using core facilities
12.9. Nutritional markers - Metabolon Ltd or in house method using core facilities
13. Indices of insulin production or beta-cell function - based on mathematical formulae in literature - for example Stumvoll index and Matsuda index, HOMA-B and HOMA-IR:
13.1. HOMA-IR and HOMA-B scores at 32 and 36 weeks and postpartum as per formulae in the literature
13.2. Matsuda scores (postpartum) - formula described in literature
13.3. Stumvoll index - formula described in literature
14. Maternal complications of pregnancy:
14.1. Pre-eclampsia from hospital data at V4
14.2. Polyhydramnios from hospital data at birth
14.3. Oligohydramnios from hospital data at birth
14.4. Threatened preterm labour from hospital data at birth
14.5. Antepartum haemorrhage from hospital data at birth
14.6. Postpartum haemorrhage from hospital data at V4
14.7. Cholestasis from hospital data at birth
14.8. Abnormal liver function tests in pregnancy from hospital data at birth
14.9. Infections from hospital data at V4
14.10. Maternal antenatal admissions from hospital data at birth
14.11. Pelvic girdle dysfunction from hospital data at birth
14.12. Carpal tunnel syndrome from hospital data at birth
14.13. Reduced fetal movements from hospital data at birth
14.14. Duration of maternal admission at delivery from hospital data at V4
15. Course of gestational diabetes:
15.1. Insulin required (type, dose, time of initiation) from hospital data at birth
15.2. Metformin required (dose, time of initiation) from hospital data at birth
15.3. Other medication required for glucose control from hospital data at birth
16. Delivery modality:
16.1. Delivery type from hospital data at birth
16.2. Timing of labour from hospital data at birth
16.3. Duration of labour from hospital data at birth
16.4. Induction of labour from hospital data at birth
16.5. Pharmacological treatment during induction, labour and delivery from hospital data at birth
16.6. Caesarean section rate from hospital data at birth
16.7. Elective vs emergency Caesarean sections from hospital data at birth
16.8. First vs repeat Caesarean sections from hospital data at birth
17. Maternal quality of life at 32 and 36 weeks and postpartum measured using EQ5D5K at V1, V3 and V4
17.1. Maternal mobility measured using EQ5D5K at V1, V3 and V4
17.2. Maternal self-care measured using EQ5D5K at V1, V3 and V4
17.3. Maternal usual activities measured using EQ5D5K at V1, V3 and V4
17.4. Maternal pain/discomfort measured using EQ5D5K at V1, V3 and V4
17.5. Maternal anxiety and depression measured using EQ5D5K at V1, V3 and V4
17.6. Maternal global health rating measured using EQ5D5K at V1, V3 and V4
17.7. Changes in quality of life measurements (baseline, 32, 36 weeks and 6 weeks postpartum) - database formula calculation
18. Maternal eating behaviour (baseline and postpartum) measured using TFEQ at V1, V3 and V4
18.1. Maternal hunger measured using TFEQ at V1, V3 and V4
18.2. Maternal emotional eating measured using TFEQ at V1, V3 and V4
18.3. Maternal uncontrolled eating measured using TFEQ at V1, V3 and V4
18.4. Maternal restraint measured using TFEQ at V1, V3 and V4
19. Food diary analysis at 32 and 36 weeks and 6 weeks postpartum:
19.1. Reported total calorie input from food diary analysis at V2, V3 and V4
19.2. Intake of carbohydrate, protein and fat (g and % of total) from food diary analysis at V2, V3 and V4
19.3. Glycaemic index of carbohydrate from food diary analysis at V2, V3 and V4
19.4. Saturated vs monounsaturated vs polyunsaturated fat from food diary analysis at V2, V3 and V4
19.5. Number of portions of fruit and vegetables eaten per day from food diary analysis at V2, V3 and V4
19.6. Dietary adherence - number, calorie content and nature of non-dietbox foods eaten at 32 and 36 weeks from food diary analysis at V2 and V3
19.7. Timing of non-adherence to dietboxes from food diary analysis at V2 and V3
19.8. Effects of non-adherence upon CGM measures of glycaemic control (including all the CGM measurements above) - database formula calculation at V2 and V3
19.9. Consistency between reported food intake and CGM glucose concentrations - database formula calculation at V2 and V3
20. Postpartum measurements:
20.1. Postpartum OGTT glucose concentrations and area under the curve from Dexcom Clarity database at V4
20.2. Postpartum maternal anthropometry (height, weight, waist circumference, hip circumference, skinfold thickness, mid upper arm circumference) measured using Seca scales, tape measure, Harpenden calipers at V4
20.3. Postpartum fat mass and fat-free mass measured using DXA machine at V4
21. Infant feeding choices at 6 weeks postpartum measured using maternal questionnaire at V4
22. Infant feeding behaviour measured using maternal questionnaire at V4
23. Additional safety-related analyses:
23.1. Small for gestational age (SGA) and intrauterine growth restriction (IUGR) from hospital data at birth
23.2. Adverse pregnancy outcomes:
23.2.1. Stillbirth from hospital data at birth
23.2.2. Neonatal death from hospital data at V4
23.2.3. Major congenital anomaly from hospital data at V4