Cause of Death in Infants of Women with Pregestational Diabetes Mellitus and the Relationship with Glycemic Control

Abstract

Background: Perinatal mortality remains high among infants of mothers with type 1 and type 2 diabetes mellitus. Although high glucose levels have been implicated, the mechanism is not well understood. Aims: 1) to identify the causes of stillbirth and neonatal death in infants of women with type 1 and type 2 diabetes; 2) to determine whether the causes of perinatal mortality are the same for women with type 1 and type 2 diabetes; and 3) to ascertain the relationship between perinatal mortality and maternal glycemic control. Materials and methods: the case notes of women with type 1 and type 2 diabetes mellitus who had a stillbirth or neonatal death were identified and examined by 2 reviewers independently. Results: Ninety-three perinatal deaths were identified (59 women with type 1 diabetes; 34 women with type 2 diabetes). There were 73 stillbirths, 12 were early neonatal deaths, and 8 were late neonatal deaths. Eighteen deaths were attributed to congenital anomalies, 64 to antepartum asphyxia, 4 to intrapartum asphyxia, 3 to postnatal hyaline membrane disease, 2 to postnatal infection, 1 was unclassifiable, and 1 case had no details available. Median postmenstrual age at death was 34 weeks for both women with type 1 and type 2 diabetes. Congenital anomalies were less common in women with type 1 dia-betes than those with type 2 diabetes (rate ratio, 0.37 [95% confidence interval, 0.15–0.95]). The relationship between preconceptional and maximal maternal glycosylated hemoglobin (HbA1c) concentrations and birth weight was curvilinear: at low HbA1c levels, the fetal weight was normal; when HbA1c levels were moderately raised, there was macrosomia; very high HbA1c levels were associated with severe intrauterine growth restriction. Conclusion: We describe a relationship between HbA1c and fetal weight. We consider that this provides evidence that hyperglycemia not only causes fetal macrosomia but also an angiopathy affecting the utero-placental blood vessels and consequent fetal hypoxia. These observations provide further evidence that good pre- and periconceptional glycemic control is likely to be of great importance in improving the outcome of pregnancies of women with diabetes.