Delay in the Fetal Globin Switch in Infants of Diabetic Mothers

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Abstract
In the normal fetus, a switch from production of hemoglobin F (α2 γ2) to hemoglobin A (α2 β2) occurs at 28 to 34 weeks of gestation. In the fetus with β-hemoglobinopathy or β-thalassemia, this switch proceeds despite the morbidity that results when production of β-globin is abnormal or reduced. Since insulin has recently been shown to induce renewed expression of some inactive genes, we studied globin biosynthesis during the natural evolution of the fetal globin switch under conditions of hyperinsulinemia, which occurs in infants of diabetic mothers. Such infants develop in a hyperglycemic environment, which produces reactive hyperinsulinemia. The normal increase in β-globin production from pre-switch levels did not occur in 9 of 10 such infants at term, as compared with 11 normal infants, in whom the switch occurred by 36 to 39 weeks of gestation (P<0.0001). The delay in the switch from γ-globin to β-globin in this unique clinical setting may allow Identification of physiologic factors that can modulate developmental gene suppression. (N Engl J Med 1985;312:334–8.)