Long-term effects of the intrauterine environment: The northwestern university diabetes in pregnancy center

Bernard L. Silverman*, Thomas A. Rizzo, Nam H. Cho, Boyd E. Metzger

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

448 Scopus citations


We sought to test the hypothesis that long-term postnatal development may be modified by metabolic experiences in utero. We enrolled offspring of women with pregestational diabetes (this included type 1 and type 2 diabetes) and gestational diabetes in a prospective study from 1977 to 1983. Fetal β- cell function was assessed by measurement of amniotic fluid insulin (AFI) concentration at 32-38 weeks' gestation. Postnatally, offspring were seen yearly for neuropsychological testing, measurement of anthropometrics, and modified glucose tolerance testing. Neuropsychological control subjects were followed longitudinally. Additional control subjects had anthropometrics measured once, and a random subset of these had a single oral glucose challenge at 10-16 years. The rates of major neuropsychological disturbances in our cohort did not differ significantly from national estimates. However, aberrant maternal metabolism was associated with poorer intellectual performance and psychomotor development. The macrosomia observed at birth in offspring of diabetic mothers (ODM) resolves by 1 year of age. Obesity recurs in childhood; and by 14-17 years, the mean BMI is 24.6 ± 5.8 kg/m2 in ODM versus 20.9 ± 3.4 kg/m2 in control subjects. Obesity in adolescence is associated with sex, mother's weight, and AFI concentration. Impaired glucose tolerance (IGT) is found in 36% of ODM and is also associated with elevated amniotic fluid insulin in utero. In confirmation of our original hypothesis, aberrant maternal metabolism is associated with poorer intellectual and psychomotor development, obesity, and IGT in offspring. Excessive insulin secretion in utero, as assessed by AFI concentration, is a predictor of both obesity and IGT in adolescence.

Original languageEnglish (US)
Pages (from-to)B142-B149
JournalDiabetes care
Issue numberSUPPL.2
StatePublished - Aug 1998

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing


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