Elevated Maternal Hemoglobin A1cin Early Pregnancy and Major Congenital Anomalies in Infants of Diabetic Mothers

摘要

Perinatal mortality has decreased in pregnancies complicated by diabetes mellitus, but the incidence of major congenital anomalies has increased. Fetal malformations occur before 8 weeks of gestation (postmenstrual dates), when most diabetic pregnant women have not yet come to medical attention. Until recently, there has been no objective method to assess control of diabetes retrospectively during this important phase of embryogenesis. Hemoglobin A1cis a normal minor hemoglobin that is distinguished from hemoglobin A by the addition of a glucose moiety to the amino-terminal valine of the β chain. Measurement of hemoglobin A1cprovides an integrated, retrospective index of glucose control, reflecting the mean blood glucose concentration over the 4 to 8 weeks before its measurement.The purpose of this study was to determine whether diabetic women delivering infants with major congenital anomalies had higher hemoglobin A1cvalues in early pregnancy than did women delivering infants who were free of anomalies. Such a finding would suggest a more severe derangement of metabolic control in the former group.Fifteen (13 per cent) of 116 insulin-dependent diabetic women who were studied in the first trimester delivered infants with major congenital anomalies. Eight infants had congenital heart defects, three of which were fatal, and four infants had malformations of the brain, three of which were fatal. The mean initial hemoglobin A1clevel was significantly higher in the group delivering infants with major anomalies than in the group delivering infants without anomalies. There were no significant differences in maternal age or sex of infants between the two groups. The gestational age at the initial hemoglobin A1cmeasurement was later in the group whose infants had major anomalies. This difference, however, did not bias the hemoglobin A1ccomparisons, since a slight inverse relation between the week of initial sampling and the hemoglobin A1clevel was present in the group without anomalies, but not in the group with anomalies.Half of the mothers had initial hemoglobin A1cvalues less than or equal to 8.5 per cent, and they had a significantly lower incidence of infants with major congenital anomalies than did the group with hemoglobin A1clevels greater than 8.5 per cent. The incidence of major anomalies was similar in the groups with initial hemoglobin A1clevels of 8.6 to 9.9 and 10.0 per cent or higher.