CONGENITAL-MALFORMATIONS IN PREGNANCIES COMPLICATED BY NIDDM - INCREASED RISK FROM POOR MATERNAL METABOLIC CONTROL BUT NOT FROM EXPOSURE TOSULFONYLUREA DRUGS

OBJECTIVE - To determine whether the use of oral hypoglycemic agents d uring early pregnancy is associated with a risk of congenital malforma tions in infants of mothers with non-insulin-dependent diabetes mellit us (NIDDM) independent of maternal metabolic control. RESEARCH DESIGN AND METHODS - From a prospectively collected database of pregnancies c omplicated by diabetes al a large urban medical center, we identified 332 consecutive infants born to women with NIDDM who did not participa te in a preconceptional diabetes care program. Stepwise logistical reg ression was used to identify maternal characteristics that were indepe ndently associated with risks of major and minor congenital malformati ons in infants. RESULTS - Overall, 56 (16.9%) of the 332 infants were born with congenital anomalies (11.7% major anomalies and 5.1% minor a nomalies). Analysis of data from subgroups of women who were treated w ith diet therapy, exogenous insulin, or sulfonylurea compounds during the first 8 weeks of gestation did not reveal statistically significan t differences in major or minor malformation rates among the three gro ups. Stepwise logistic regression analysis revealed two maternal chara cteristics that were independently associated with major malformations in infants: maternal HbA(1c) al initial presentation for care (direct relationship; P = 0.0007) and the maternal age at onset of diabetes ( inverse relationship; P = 0.009). The risk of major malformations was unrelated to the mode of antidiabetic therapy during early pregnancy. No relationship was found between maternal glycemia or treatment modal ity and rates of minor congenital anomalies. CONCLUSIONS - These data indicate that, in the absence of special preconceptional care, NIDDM i s associated with a risk for major congenital anomalies that is in the range reported for pregnancies complicated by insulin-dependent diabe tes mellitus, Moreover, the risk in individual patients appears to be related to maternal glycemic control rather than to the mode of antidi abetic therapy during early pregnancy.