The study population included women participating in the ACTS trial [13], a multi-centre randomised placebo controlled trial of antioxidant (vitamins C and E) supplements for the prevention of perinatal complications, who had an OGCT as screening for gestational diabetes. The methods and results of this trial have been reported previously [13]. Briefly, eligible women were: nulliparous, with a singleton pregnancy between 14 and 22 weeks of gestation with a normal blood pressure at the time of recruitment and who gave informed consent. Women with any of the following were ineligible: known multiple pregnancy, known lethal fetal anomaly, known thrombophilia, chronic renal failure, antihypertensive therapy or contraindication to vitamin C or E therapy including haemochromatosis or anticoagulant therapy. Randomisation was performed through a central telephone randomisation service. Women assigned to the vitamin group were provided a daily dose of 1000 mg vitamin C and 400 IU vitamin E until birth, and women in the control group were provided a matching placebo. An OGTT was offered between 24–30 weeks gestation, for those women who screened positive on OGCT test. The study protocol was approved by the research and ethics committees at the nine collaboration hospitals around Australia.
We compared demographic, obstetric and neonatal outcomes between women with BGDM and those who screened normal on OGCT. As the ACTS found no significant differences between the antioxidant and placebo groups for the risk of pre-eclampsia, intrauterine growth restriction or other serious outcomes for the infant, the analyses include the combined populations of women who received either antioxidant or placebo supplements.
Data collection
Pregnancy outcome data including OGCT and OGTT results were collected prospectively from women's medical records. Sociodemographic variables were collected either from women's medical records or self-completed questionnaires at trial entry and included: maternal age, ethnicity, body mass index (BMI), social-economic status as measured by socio-economic index for area (SEIFA) score [14], maternal education, smoking status, blood pressure at trial entry, and family history of pre-eclampsia. Complete outcome data were available for all 1877 women randomised.
Outcome variables
BGDM was defined as a positive OGCT (blood glucose ≥7.8 mmol/L 1 hour after a 50 g glucose load) and normal 75 g OGTT (fasting blood glucose <5.5 mmol/L and 2 hour blood glucose <7.8 mmol/L). Pregnancy outcomes assessed included: maternal adverse outcomes (a composite outcome defined as any of the following until six weeks postpartum: death, pulmonary oedema, eclampsia, stroke, thrombocytopenia, renal insufficiency, respiratory arrest, placental abruption, abnormal liver function, preterm prelabour rupture of membranes, major postpartum haemorrhage, postpartum pyrexia, pneumonia, deep-vein thrombosis, or pulmonary embolus requiring anticoagulant therapy) [13]; pregnancy induced hypertension (PIH); pre-eclampsia (defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure [Korokoff V] ≥90 mmHg on at least two occasions four or more hours apart, or both arising after 20 weeks' gestation and one or more of the following: proteinuria, renal insufficiency, liver disease, neurological problems, haematologic disturbances, or fetal growth restriction) [15]; antenatal hospitalisation; preterm prelabour rupture of the membranes; induction of labour; mode of birth; postnatal complications such as postpartum haemorrhage and infection; and length of hospital stay.
Neonatal outcomes included a composite outcome of death or infant adverse outcome defined as: stillbirth or death of a liveborn infant before hospital discharge, birthweight <3rd centile for gestational age, severe respiratory distress syndrome, chronic lung disease, intraventricular haemorrhage grade 3 or 4, cystic periventricular leukomalacia, retinopathy of prematurity grade 3 or 4, necrotizing enterocolitis, 5 minute Apgar score <4, seizures before 24 hours of age or requiring 2 or more drugs to control, hypotonia for ≥2 hours, stupor, decreased response to pain or coma, tube feeding for ≥4 days, care in the neonatal intensive care unit (NICU) >4 days, or use of ventilation for ≥24 hours [13]; gestational age at birth; preterm birth (<37 weeks); 5 minute Apgar score <7, infant body size at birth (weight, length and head circumference), small and large-for-gestational age (defined as a birth weight below the 10th percentile or above 90th percentile for gestation according to fetal sex on standardized birth-weight charts, respectively), macrosomia (defined as birthweight ≥4.5 kg), admission to NICU or neonatal nursery, respiratory distress syndrome, mechanical ventilation, antibiotics use after birth, encephalopathy (Sarnat 2 or 3 score) and length of hospital stay.
Statistical analysis
Statistical analysis was carried out using SAS software, version 9.1. Dichotomous variables were analysed using log-binomial regression and presented as relative risks, with 95% confidence intervals; and continuous variables, if normally distributed, were analysed using Student's t-test and presented as mean differences, with 95% confidence intervals; non-parametric tests were used for skewed data. Analyses were then adjusted for maternal age and BMI given the strong association of these factors with GDM. A p value of 0.05 or less was considered to indicate statistical significance.
