Direct relationship of antepartum glucose control and fetal erythropoietin in human Type 1 (insulin-dependent) diabetic pregnancy

Abstract

Summary. In the present study the antepartum relationship between maternal diabetic glucose control and fetal hypoxaemia was examined in 44 Type i (insulin-dependent) diabetic and 23 non-diabetic control pregnancies. Maternal HbAlc was used to assess maternal integrated blood glucose control while fetal metabolic control was evaluated by antepartum glucose, insulin, and C-peptide determinations in amniotic fluid at elective caesarean delivery. Fetal hypoxaemia was assessed indirectly by fetal umbilical vein plasma erythropoietin level at delivery. A prospectively developed statistical pathway model was used to examine the relationship of these variables. In applying forced stepwise multiple regression with this model, we observed in the diabetic subjects that mean maternal HbA~c during the last month of pregnancy correlated significantly with fetal umbilical venous erythropoietin at delivery (r = 0.57,p < 0.001). Additional significant contributions to umbilical venous erythropoietin were found for amniotic fluid glucose and amniotic fluid insulin when these two independent variables were added in stepwise fashion (p < 0.01). We conclude that in diabetic pregnancy, antepartum control of maternal hyperglycaemia is a significant factor associated with fetal hypoxaemia. We speculate that this effect is mediated through perturbations which accelerate fetal metabolism and which is expressed by amniotic fluid levels of glucose and insulin.Key words: Erythropoietin, HbAlc, fetus, oxygenation, diabetes mellitus.Although in recent years the outcome of diabetic pregnancies has dramatically improved, fetal and neonatal morbidity and mortality remain increased relative to normal pregnancies [1,2]. Some of the pathological features observed in offspring of these pregnancies have been shown to be associated with maternal hyperglycaemia (eg., respiratory distress syndrome, congenital malformations, and neonatal hypoglycaemia); others have not. Among the latter are the increased incidence of late gestation fetal death, antepartum and intrapartum fetal distress, and neonatal polycythaemia. We and others have speculated that these features of diabetic pregnancies have their origins in chronic and/or acute fetal hypoxaemia [3][4][5].The purpose of the present study was to indirectly examine the antepartum relationship between chronic maternal hyperglycaemia and fetal oxygenation in Type 1 (insulin-dependent) diabetic pregnancies delivered by elective caesarean section before the confounding effect of labour [6]. To do so, we prospectively developed a hypothetical pathway model for statistical analyses in which chronic maternal hyperglycaemia was related to chronic fetal hypoxaemia through several intermediate steps. Subjects and methods SubjectsAfter obtaining approval by the Ethical Committee at the University of Helsinki and after obtaining each patient's consent, control and Type i (insulin-dependent) diabetic subjects carrying singleton fetuses were studied at the Women's Hospital of the University Central Hospital of Helsink...

Increased fetal leptin in Type I diabetes mellitus pregnancies complicated by chronic hypoxia

“…This is in accordance with previous studies of infants of diabetic mothers [18,23], whereas a negative correlation has been reported between EPO and Hb in normal and Rh-isoimmunised fetuses [24]. There is evidence that in infants of diabetic mothers erythropoiesis is qualitatively abnormal [25].…”

Trends in maternal BMI, glycaemic control and perinatal outcome among type 1 diabetic pregnant women in 1989–2008

“…Maternal hyperglycaemia increases the risk of fetal chronic hypoxia [21]. We and others have previously shown a positive correlation between late pregnancy HbA 1c values and amniotic fluid or cord blood erythropoietin (EPO) concentration as well as a negative correlation between amniotic fluid EPO levels and UA pH and pO 2 levels at birth [31][32][33][34]. The HbA 1c reflects the average glucose level over the preceding 6-8 weeks but does not give information on hyperglycaemic peaks.…”

Elevated zinc protoporphyrin/heme ratios in umbilical cord blood after diabetic pregnancy

“…[1][2][3][4] Both chronic fetal hyperglycemia and hyperinsulinemia increase cellular oxygen consumption. 1,3,4 The resulting hypoxemia stimulates fetal erythropoiesis and accelerates erythrocyte iron delivery. 1,3,4 Iron is shunted into erythrocyte mass and away from developing organs and tissues.…”

“…1,3,4 The resulting hypoxemia stimulates fetal erythropoiesis and accelerates erythrocyte iron delivery. 1,3,4 Iron is shunted into erythrocyte mass and away from developing organs and tissues. [2][3][4][5] Iron is an essential nutrient for normal perinatal growth and development.…”

“…1,3,4 Iron is shunted into erythrocyte mass and away from developing organs and tissues. [2][3][4][5] Iron is an essential nutrient for normal perinatal growth and development. Although infants born to women with poorly controlled diabetes may experience impaired childhood intellectual development, 6 only recently has the role of brain iron deficiency been explored.…”