LONG-TERM EFFECT OF THE INTRAUTERINE ENVIRONMENT - THE NORTHWESTERN-UNIVERSITY DIABETES IN PREGNANCY CENTER

We sought to test the hypothesis that long-term postnatal development may be modified by metabolic experiences in utero. We enrolled offspri ng of women with pregestational diabetes (this included type 1 and typ e 2 diabetes) and gestational diabetes in a prospective study from 197 7 to 1983. Fetal beta-cell function was assessed by measurement of amn iotic fluid insulin (AFI) concentration at 32-38 weeks' gestation. Pos tnatally, offspring were seen yearly for neuropsychological testing, m easurement of anthropometrics, and modified glucose tolerance testing Neuropsychological control subjects were followed longitudinally Addit ional control subjects had anthropometrics measured once, and a random subset of these had a single oral glucose challenge at 10-16 years. T he rates of major neuropsychological disturbances In our cohort did no t differ significantly from national estimates. However, aberrant mate rnal metabolism was associated with poorer intellectual performance an d psychomotor development. The macrosomia observed at birth in offspri ng of diabetic mothers (ODM) resolves by I year of age. Obesity recurs in childhood and by 14-17 years, the mean BMI is 24.6 +/- 5.8 kg/m(2) in ODM versus 20.9 +/- 3.4 kg/m(2) in control subjects. Obesity in ad olescence is associated with sex, mother's weight; and AFI concentrati on. Impaired glucose tolerance (IGT) is found in 36% of ODM and is als o associated with elevated amniotic fluid insulin in utero. In confirm ation of our original hypothesis, aberrant maternal metabolism is asso ciated with poorer intellectual and psychomotor development, obesity, and IGT in offspring. Excessive insulin secretion in utero, as assesse d by AFI concentration, is a predictor of both obesity and IGT in adol escence.