Background. It is not clear to what extent maternal metabolism during pregnancy affects the cognitive and behavioral function of the offspring by altering brain development in utero. To investigate this question, we correlated measures of metabolism in pregnant diabetic and nondiabetic women with the intellectual development of their offspring. Methods. The study included 223 pregnant women and their singleton offspring: 89 women had diabetes before pregnancy (pregestational diabetes mellitus), 99 had the onset of diabetes during pregnancy (gestational diabetes mellitus), and 35 had normal carbohydrate metabolism during their pregnancy. We correlated measures of maternal glucose and lipid metabolism (fasting plasma glucose levels, hemoglobin A1c levels, episodes of hypoglycemia, episodes of acetonuria, and plasma β-hydroxybutyrate and free fatty acid levels) with two measures of intellectual development in the offspring — the mental-development index of the Bayley Scales of Infant Development, given at the age of two years, and the Stanford–Binet Intelligence Scale, given at the ages of three, four, and five years and expressed as an average of the three scores. Results. After correction for socioeconomic status, race or ethnic origin, and patient group, the children's mental-development-index scores at the age of two years correlated inversely with the mothers' third-trimester plasma β-hydroxybutyrate levels (r = —0.21, P<0.01); the average Stanford–Binet scores correlated inversely with third-trimester plasma β-hydroxybutyrate (r = —0.20, P<0.02) and free fatty acid (r = —0.27, P<0.002) levels. No other correlations were significant. Including various perinatal events (e.g., prematurity and acidemia) in the analyses did not alter the results. Conclusions. Maternal diabetes during pregnancy may affect behavioral and intellectual development in the offspring. The associations between gestational ketonemia in the mother and a lower IQ in the child warrant continued efforts to avoid ketoacidosis and accelerated starvation in all pregnant women. (N Engl J Med 1991; 325:911–6.).
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