DECIDE: A Comparative Effectiveness Trial of Metformin Versus Insulin for the Treatment of Gestational Diabetes

HDP will include either gestational hypertension or preeclampsia. Gestational hypertension will be defined as: systolic blood pressure of 140 mm Hg or more or diastolic blood pressure of 90 mm Hg or more on two occasions at least 4 hours apart after 20 weeks of gestation in a woman with a previously normal blood pressure. Preeclampsia will be defined as: above blood pressure criteria AND proteinuria (300 mg or more per 24 hour urine collection, protein/creatinine ratio of 0.3 mg/dL or more, or dipstick reading of 2+) OR thrombocytopenia (platelet count less than 100 109/L), renal insufficiency (serum creatinine greater than 1.1 mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease), impaired liver function (elevated blood concentrations of liver transaminases to twice normal concentration), pulmonary edema, new-onset headache or visual symptoms not attributed to other diagnoses.

Gestational weight gain between weight at first prenatal visit and weight at delivery based on z-score and defined as excess versus within Institute of Medicine (IOM) recommendations based on first pregnancy BMI.

Cesarean delivery or vaginal delivery

First degree: Injury to perineal skin only; Second degree: Injury to perineum involving perineal muscles but not involving anal sphincter; Third degree: Injury to perineum involving anal sphincter complex, including 3a: Less than 50% of external anal sphincter thickness torn; 3b: More than 50% external anal sphincter thickness torn; and 3c: Both external anal sphincter and internal anal sphincter torn; and Fourth degree: Injury to perineum involving anal sphincter complex (external anal sphincter and internal anal sphincter) and anal epithelium.

Preterm birth <37 weeks and <34 weeks based on project gestational age

Intubation, continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) for ventilation or cardiopulmonary resuscitation within first 72 hours of birth

Admitted to NICU or intermediate nursery ≥72 hours, any indication

Requiring oxygen support

Signs of respiratory distress with oxygen requirement and confirmed by chest x-ray.

Continuous measure, using standardized protocol as kg/m2.

BMI per the following classifications: Normal or underweight: < 25 kg/m2; Overweight: 25 to < 30 kg/m2; Class 1: 30 to < 35 kg/m2; Class 2: 35 to < 40 kg/m2; and Class 3: 40 kg/m2 or greater.

Waist circumference, continuous measures in cm

Hip circumference, continuous measures in cm

Waist - to - hip ratio, continuous measure

Triceps, subscapular, suprailiac skinfolds, continuous measures in cm

A1c > 6.5% OR fasting plasma glucose > 126 mg/dL OR OGTT > 200 mg/dL OR prior diagnosis per patient report

A1c 5.7% to 6.4% OR fasting plasma glucose 100 mg/dl to 125 mg/dL OR OGTT 140 to 199 mg/dL

Per American Heart Association criteria as below and/or antihypertensive medication or prior diagnosis per patient report, and defined as: Elevated: Systolic between 120-129 and diastolic less than 80 mm Hg; Stage 1: Systolic between 130-139 or diastolic between 80-89 mm Hg; and Stage 2: Systolic at least 140 or diastolic at least 90 mm Hg.

Fasting state, defined as a continuous measure and dichotomous at the following thresholds for each component: Total cholesterol: > 200 mg/dL; LDL cholesterol: > mg/dL; HDL cholesterol: < 40 mg/dL; Triglycerides: > 200 mg/dL.

Continuous measure, percentage.

BMI ≥85th%tile for age and sex.

BMI ≥95th%tile for age and sex.

Abdominal circumference; age- and sex-adjusted per WHO z-scores for arm circumference.

Triceps/subscapular skinfold thickness > 90th%tile for age and sex; individual and sum of measures.

The TSQM (version 1.4) comprises 14 items across four domains focusing on effectiveness (three items), side effects (five items), convenience (three items), and global satisfaction (three items) of the medication over the previous 2-3 weeks. With the exception of item 4 (presence of side effects; yes or no), all items have five or seven responses, scored from one (least satisfied) to five or seven (most satisfied). Item scores are summed to give four domain scores, which are in turn transformed to a scale of 0-100. Item 4 was not included for scoring.

A set of 5 questions developed in the Rowan et al. RCT assessing patient adherence, preferences, and experiences with metformin versus insulin for GDM (Rowan et al., NEJM, 2008).