Risk of birth defects associated with maternal pregestational diabetes: a population-based cohort study in northern Italy

Maternal diabetes preceding pregnancy, whether type-1 or type-2, appears to increase the risk of birth defects in the offspring, though several aspects of this relation are still unknown or controversial. We conducted a large population-based cohort study in the Northern Italy region of Emilia-Romagna using administrative databases and a Birth Defects Registry. From hospital discharge records we identified all diabetic pregnancies during 1997-2010, and a population of non-diabetic parturients matched for age, province of residence, year and hospital of delivery. We collected where available information on drug prescriptions, from which we inferred the type of diabetes. We found 62 malformed infants out of 2,269 births among diabetic women, and 162 out of 10,648 births among non-diabetic women. The prevalence ratio (PR) of malformation associated with maternal pregestational diabetes was 1.73 (95% confidence interval 1.28-2.33). Period of birth and type of diabetes strongly influenced the PR, with higher values estimates in the earliest periods and in type-2 diabetic women compared with type-1 diabetic mothers. The latter group exhibited no excess risk in the most recent period, 2006-2010, possibly owing to improvements in metabolic control over time. Most subgroups of anomalies had PRs above 1, but relevant and statistically more precise excess risks were seen for cardiovascular, genitourinary, musculoskeletal, and chromosomal abnormalities. The present study indicates that maternal diabetes increases the risk of specific birth defects in offspring, particularly for type-2 diabetes, whereas for type-1 diabetic mothers in the most recent years, this was not the case.