Abstract

Introduction: Diabetes in pregnancy is associated with an increased rate of stillbirth. There are a wide variety of factors that have been implicated including placental insufficiency, hypoxia, hyperinsulinemia and impaired cardiac function. Furthermore, there is evidence that diabetic pregnancies have an increased rate of fetal cardiomyopathy as compared to non-diabetic pregnancies. Prior studies have indicated that this association can also be an etiology for diabetic stillbirth. The purpose of this study was to determine if diabetic pregnancies have an increased risk of fetal cardiomyopathy identified on fetal autopsy as compared to non-diabetic women with a stillbirth in a cohort of pregnancies that had evaluation with a fetal autopsy.

Materials and methods: Retrospective cohort study of women with a stillbirth who consented to fetal autopsy at an academic medical center from 2011 to 2017. Stillbirth was defined as an intrauterine fetal demise at ≥20 weeks’ gestation. Women with diabetes defined as pre-gestational diabetes type 1, pre-gestational diabetes type 2, and gestational diabetes were compared to women without diabetes. Primary outcome was fetal cardiomyopathy. Other etiologies for stillbirth were also evaluated and classified according to the Stillbirth Collaborative Research Network (SCRN) initial causes of fetal death. Fisher exact test, χ2 test, and Mann Whitney U tests were performed as appropriate, with p < .05 considered significant. Generalized linear models were performed for fetal organ weights controlling for gestational age of delivery, maternal chronic hypertension, delivery body mass index, and birthweight.

Results: A total of 78 women elected to have fetal autopsy examinations during the study period. Of these, 75 had complete information available for review. A total of 60 women did not have diabetes and 15 women had diabetes. Of pregnancies complicated by diabetes, 11 had insulin dependent diabetes and 4 had non-insulin dependent diabetes. Fetal cardiomyopathy was diagnosed on autopsy for 7 (46.7%) of pregnancies with diabetes and 2 (3.3% of pregnancies without diabetes (RR 14.00 [95% CI 3.23–60.65], p < .001). These associations were still significant even when analyzing only those pregnancies without fetal congenital heart disease (7 [46.7%] diabetic pregnancies with cardiomyopathy versus 1 [2.0%] nondiabetic pregnancy with cardiomyopathy, RR 23.80 [95% CI 3.17–178.46], p < .001). There was no difference between diabetic and non-diabetic pregnancies in regards to other causes for stillbirth. Stillbirths in pregnancies with diabetes also had larger fetal heart, liver, and adrenal weights on fetal autopsy.

Conclusion: Women with diabetes have 14 times the risk of fetal cardiomyopathy identified at fetal autopsy as compared to women without diabetes. As the prediction and prevention of diabetic stillbirth is limited, information on potential causes of stillbirth may help future research identify those pregnancies at the greatest risk for adverse outcome.