Background Pre-gestational diabetes is associated with a range of adverse pregnancy outcomes, including an increased risk of major congenital anomalies. The impact on normally-formed offspring, however, is less well defined. This study utilised data from a long-running population-based survey of women with pre-gestational diabetes to explore the risks of foetal and infant death and examine which factors modify these risks.
Methods All normally-formed singleton pregnancies delivered at ≥20 weeks of gestation in the North of England during 1996-2008 were identified from the population-based Northern Perinatal Morbidity and Mortality Survey. Pregnancies affected by pre-gestational diabetes were identified from the Northern Diabetes in Pregnancy Survey, which also collects data on a range of clinical and sociodemographic variables. Relative risks (RRs) of foetal death (≥20 weeks gestation) and infant death were estimated by comparing the prevalence among women with and without pre-gestational diabetes. Predictors of foetal and infant death in women with pre-gestational diabetes were examined by logistic regression. Glycated haemoglobin concentrations (HbA1c) within three months peri-conception and in the third trimester (as markers of blood glucose concentration) were analysed by piecewise regression due to curvilinear associations.
Results There were 46 foetal deaths and 10 infant deaths among 1548 deliveries in women with pre-gestational diabetes. The prevalence of foetal death in women with diabetes was over four times greater than among those without (RR 4.54 [3.41, 6.05], p<0.0001), while the infant mortality rate was nearly two times greater, although the effect did not reach the conventional level for statistical significance (1.82 [0.98, 3.38], p=0.06). Increasing peri-conception HbA1c above 45mmol/mol (AOR 1.02 [1.01, 1.03], p=0.006), pre-pregnancy retinopathy (AOR 2.02 [1.05, 3.89], p=0.03), and lack of pre-pregnancy folate supplement use (AOR 2.44 [1.12, 5.25], p=0.03) were all independently associated with increased risks of fetal or infant death. In deliveries after 28 weeks only, increasing third-trimester HbA1c above 36mmol/mol was associated with an increased risk of fetal or infant death (AOR 1.05 [1.02, 1.08], p=0.001), with no apparent additional contribution from peri-conception HbA1c.
Conclusion Pre-gestational diabetes is associated with a substantially increased risk of fetal death in normally-formed offspring, the effect of which appears to be largely moderated by glycaemia control. Greater vigilance in the control of blood glucose, both before and throughout pregnancy, is needed if the risks of serious adverse pregnancy outcomes in women with pre-gestational diabetes are to be reduced towards the levels in healthy women.
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