AIMS - To determine whether there is a causal, independent intra-uterine effect of maternal BMI and glycemic profile on offspring adiposity and glycemic profile over the lifecourse

HYPOTHESIS - The developmental overnutrition hypothesis describes how intra-uterine conditions affect lifelong risk of offspring obesity. High maternal glycose, free fatty acid, and amino acid concentrations to which the fetus is exposured during pregnancy are proposed to result in permanent changes in appetite control, neuroendocrine functioning, or energy metabolism, leading to increased birth size and greater adiposity in later life. Since maternal BMI is positively associated with insulin resistance and glucose intolerance, and therefore higher plasma concentrations of glucose, fetal overnutrition is more likely among mothers with greater BMI during pregnancy.

EXPOSURE VARIABLES - Maternal pre-pregnancy BMI and glycemic profile during pregnancy (antenatal glucose/insulin)

OUTCOME VARIABLES - Offspring adiposity (BMI and DXA measure) from age 9 to 17

CONFOUNDING VARIABLES - maternal smoking, maternal age at delivery, paternal BMI, parental occupation, parental education, maternal parity, child sex

MEDIATORS - Offspring birthweight

INSTRUMENTAL VARIABLES - allelic score for maternal BMI and glycemic profile, generated from adiposity and insulin/glucose single nucleotide polymorphisms respectively.