Glycaemic control during early pregnancy and fetal malformations in women with type I diabetes mellitus.

Aims/hypothesis: To assess the relation between glycaemic control in early pregnancy and the risk of congenital malformations in offspring of mothers with Type I (insulin-dependent) diabetes mellitus.

Methods: From 1988-1997, we prospectively collected data from 691 pregnancies and 709 offspring of 488 women with Type I diabetes in a specific geographic area in Southern Finland. Glycated haemoglobin A1c at less than 14 weeks of gestation was used as the indicator of glycaemic control. The malformations were diagnosed either by ultrasonography in pregnancy or during the neonatal period. We also studied 729 non-selected control pregnancies in women without diabetes.

Results: The numbers of major fetal malformations were 30 (4.2%) in patients with Type I diabetes and 10 (1.2%) in the control subjects (relative risk 3.1; 95% confidence interval: 1.6 to 6.2). Even women whose HbA1c was only slightly raised (5.6 to 6.8%, i.e. 2.0 to 5.9 standard deviation units) showed a relative risk of 3.0 (95% confidence interval: 1.2 to 7.5). Haemoglobin A1c retained its statistically significant association with the occurrence of malformations after adjusting for White's class, age at onset of diabetes, duration of diabetes, parity, smoking and participation in pre-pregnancy counselling.

Conclusions/interpretation: Even a slightly raised HbA1c during early pregnancy in women with Type I diabetes carries an increased risk for fetal malformations. Therefore normoglycaemia should be strived for during early pregnancy.