Antenatal Myo-inositol Supplementation in Pre-existing Diabetes

Mean differences in cross-sectional comparisons and longitudinal changes in measured biometric parameters, derived size/weight estimates and Doppler assessments, as well as differences in the velocity of growth, peak/nadir in the velocity of growth and its gestational timing, and the fastest/slowest change in growth velocity and its gestational timing, with and without adjustment for important covariates.

Number and proportion, and relative risks, of macrosomia (birthweight >4000 g), low birthweight (<2500 g), Large-for-Gestational-Age (LGA; birthweight >90th centile), and Small-for-Gestational-Age (SGA; birthweight <10th centile), and mean differences or categorically-defined outcomes of birthweight, birth length, head circumference, abdominal circumference, mid-arm circumference, skinfold thickness, fat mass, fat-free mass, and percentage body fat (assessed by air displacement plethysmography, PEAPOD), with and without adjustment for important covariates. Continuous data to be standardised to z-scores, where appropriate.

Number and proportion, and relative risks, of neonatal respiratory distress (aetiology and treatment required), neonatal hypoglycemia, number of hypocount values <2.6 mmol/L, hyperbilirubinemia requiring phototherapy or exchange transfusion, neonatal sepsis (early and late onset, aetiology and treatment required), shoulder dystocia, birth trauma, hypoxic ischaemic encephalopathy/intracranial haemorrhage, neonatal unit admission, or stillbirth/neonatal death, as well as mean differences in the levels of glycaemia and bilirubinaemia, and in the duration of respiratory support, phototherapy and neonatal unit/hospital stay, with and without adjustment for important covariates. Continuous data to be standardised to z-scores, where appropriate.

Number and proportion, and relative risks of fetal hyperinsulinaemia or high C-peptide concentration, and mean difference in insulin or C-peptide concentrations in umbilical cord blood (where obtainable); with and without adjustment for important covariates

Mean differences and change in blood glucose levels (monitored through self-blood glucose monitoring or continuous glucose monitoring, CGM), other CGM parameters, markers of glycemic control, the frequency of participant-managed hypoglycemic episodes, proportional increases in metformin or insulin doses, and mean differences in daily insulin requirements per kilogram (kg) of body weight, proportion requiring other diabetes treatments, mean differences and change in HbA1C and HOMA-IR; with and without adjustment for important covariates. Continuous data to be standardised to z-scores, where appropriate.

Number and proportion, and relative risks, of pre-eclampsia/eclampsia, superimposed pre-eclampsia on chronic hypertension, and pregnancy-induced hypertension (as a composite and as individual complications), as well as difference in the gestational age of onset or diagnosis and severity of disorder, with and without adjustment for important covariates.

Number and proportion, and relative risks, of PPROM and preterm delivery (spontaneous and/or iatrogenic births), reasons for preterm birth, as well as the gestational ages at delivery and at PPROM will be presented, with and without adjustment for important covariates.

Mean differences in the total weight a woman gains during pregnancy, measured in kilograms (kg), as well as the rate of weight gain over the second and third trimesters of pregnancy (kg/week). Proportional differences in the categorisation of weight gain by the Institute of Medicine (IOM) guidelines as insufficient, appropriate, or excessive (considering the mother's pre-pregnancy BMI), with and without adjustment for important covariates

Mean differences and change from baseline in scores of maternal depression and anxiety symptoms on validated questionnaires (Edinburgh Postnatal Depression Scale and State-Trait Anxiety Inventory), and proportional differences between groups in those with higher and lower scores, with and without adjustment for important covariates. Continuous data to be standardised to z-scores, where appropriate.

Number and proportion, and relative risks, of caesarean section, primary caesarean section, emergency caesarean section, and instrumental delivery, with and without adjustment for important covariates.

Number and proportion, and relative risks, of major postpartum haemorrhage (primary and secondary), and mean differences in the volume of blood loss (primary and secondary), with and without adjustment for important covariates.

Number and proportion, and relative risks, of antenatal complications such as intrahepatic cholestasis, placental abruption and antepartum haemorrhage, and peripartum events encompassing type of onset/induction and progress of labour, requirement for labour augmentation, non-reassuring cardiotocography suggestive of fetal compromise, meconium-stained liquor, shoulder dystocia, perineal trauma, admission to high-dependency/intensive care unit, and other relevant complications, as well as mean differences in the duration of each stage of labour and entire labour, and length of maternal HDU/ICU/hospital stay, with and without adjustment for important covariates.

Mean differences in cross-sectional comparisons and longitudinal changes from baseline in maternal circulation and urinary concentrations of myo-inositol and the other 4 inositol isomers, and inositol metabolites, as well as mean differences in circulating fetal/cord concentrations of these inositols/inositol-metabolites at birth, and in placental and fetal membrane tissues; with and without adjustment for important covariates.

Differences in the characteristics and quantities of each element/class of the biochemical, metabolic, metabolomic, hormonal, chemoadipocytokine, proteomic, lipidomic, genomic, epigenomic and transcriptomic profiles as well as tissue tensile strength (where applicable) in maternal blood \& urine, fetal (umbilical cord) blood \& tissue, placenta and fetal membranes.

Descriptive and quantifiable differences in metagenomics and metatranscriptomics, reflecting microbial diversity, the relative abundance of key bacterial species, and metabolic activity in maternal and neonatal stool. Continuous data to be standardised to z-scores, where appropriate.