Pregnancy Outcomes and Maternal Insulin Sensitivity: Design and Rationale of a Multi-Center Longitudinal Study in Mother and Offspring (PROMIS)

The worldwide prevalence of overweight and obesity in women of reproductive age is rapidly increasing and a risk factor for the development of gestational diabetes (GDM). Excess adipose tissue reduces insulin sensitivity and may underlie adverse outcomes in both mother and child. The present paper describes the rationale and design of the PRegnancy Outcomes and Maternal Insulin Sensitivity (PROMIS) study, an exploratory cohort study to obtain detailed insights in insulin sensitivity and glucose metabolism during pregnancy and its relation to pregnancy outcomes including early infancy growth. We aim to recruit healthy pregnant women with a body mass index (BMI) ≥ 25 kg/m(2) before 12 weeks of gestation in Northern Netherlands. A total of 130 woman will be checked on fasted (≤7.0 mmol/L) or random (≤11.0 mmol/L) blood glucose to exclude pregestational diabetes at inclusion. Subjects will be followed up to six months after giving birth, with a total of nine contact moments for data collection. Maternal data include postprandial measures following an oral meal tolerance test (MTT), conducted before 16 weeks and repeated around 24 weeks of gestation, followed by a standard oral glucose tolerance test before 28 weeks of gestation. The MTT is again performed around three months postpartum. Blood analysis is done for baseline and postprandial glucose and insulin, baseline lipid profile and several biomarkers of placental function. In addition, specific body circumferences, skinfold measures, and questionnaires about food intake, eating behavior, physical activity, meal test preference, mental health, and pregnancy complications will be obtained. Fetal data include assessment of growth, examined by sonography at week 28 and 32 of gestation. Neonatal and infant data consist of specific body circumferences, skinfolds, and body composition measurements, as well as questionnaires about eating behavior and complications up to 6 months after birth. The design of the PROMIS study will allow for detailed insights in the metabolic changes in the mother and their possible association with fetal and postnatal infant growth and body composition. We anticipate that the data from this cohort women with an elevated risk for the development of GDM may provide new insights to detect metabolic deviations already in early pregnancy. These data could inspire the development of new interventions that may improve the management of maternal, as well as offsrping complications from already early on in pregnancy with the aim to prevent adverse outcomes for mother and child.