Is there a reduction of congenital abnormalities in the offspring of diabetic pregnant women after folic acid supplementation? A population-based case-control study.

The objective of the present study was to estimate the preventive effect of folic acid for structural birth defects (i.e. congenital abnormalities [CAs]) in the offspring of pregnant women with diabetes mellitus type 1 (DM-1). The occurrence of medically recorded DM-1 in pregnant women who had malformed fetuses/newborns (cases) and delivered healthy babies (controls) with or without folic acid supplementation was compared in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities. The case group included 22,843 offspring, and there were 79 (0.35%) pregnant women with DM-1, while the control group comprised of 38,151 newborns, and 88 (0.23%) had mothers with DM-1. Case mothers with DM-1 associated with a higher risk of total rate of CAs in their offspring (OR with 95% CI: 1.5, 1.1-2.0) compared to the total rate of CAs in the offspring of non-diabetic case mothers. This higher risk can be explained by four specific types/groups of CAs: isolated renal a/dysgenesis; obstructive CA of the urinary tract; cardiovascular CAs; and multiple CAs, namely caudal dysplasia sequence. However, there was no higher rate of total CAs in the children of pregnant women with DM-1 after folic acid supplementation; in addition, neural-tube defect and renal a/dysgenesis did not occur. However, this benefit cannot be explained by the CA reduction effect of folic acid during the critical period of major CAs. In conclusion, there was a certain reduction in maternal teratogenic effect of DM-1 after folic acid supplementation during pregnancy, but the explanation of this effect requires further study.