Pre-existing diabetes, maternal glycated haemoglobin, and the risks of fetal and infant death: a population-based study.

Aims/hypothesis: Pre-existing diabetes is associated with an increased risk of stillbirth, but few studies have excluded the effect of congenital anomalies. This study used data from a long-standing population-based survey of women with pre-existing diabetes to investigate the risks of fetal and infant death and quantify the contribution of glycaemic control.
Methods: All normally formed singleton offspring of women with pre-existing diabetes (1,206 with type 1 diabetes and 342 with type 2 diabetes) in the North of England during 1996-2008 were identified from the Northern Diabetes in Pregnancy Survey. RRs of fetal death (≥20 weeks of gestation) and infant death were estimated by comparison with population data from the Northern Perinatal Morbidity and Mortality Survey. Predictors of fetal and infant death in women with pre-existing diabetes were examined by logistic regression.
Results: The prevalence of fetal death in women with diabetes was over four times greater than in those without (RR 4.56 [95% CI 3.42, 6.07], p < 0.0001), and for infant death it was nearly doubled (RR 1.86 [95% CI 1.00, 3.46], p = 0.046). There was no difference in the prevalence of fetal death (p = 0.51) or infant death (p = 0.70) between women with type 1 diabetes and women with type 2 diabetes. There was no evidence that the RR of fetal and infant death had changed over time (p = 0.95). Increasing periconception HbA1c concentration above 49 mmol/mol (6.6%) (adjusted odds ratio [aOR] 1.02 [95% CI 1.00, 1.04], p = 0.01), prepregnancy retinopathy (aOR 2.05 [95% CI 1.04, 4.05], p = 0.04) and lack of prepregnancy folic acid consumption (aOR 2.52 [95% CI 1.12, 5.65], p = 0.03) were all independently associated with increased odds of fetal and infant death.
Conclusions/interpretation: Pre-existing diabetes is associated with a substantially increased risk of fetal and infant death in normally formed offspring, the effect of which is largely moderated by glycaemic control.