Increased erythropoiesis and elevated erythropoietin in infants born to diabetic mothers and in hyperinsulinemic rhesus fetuses.

Widness, John A.; Susa, John B.; Garcia, Joseph F.; Singer, Don B.; Sehgal, Prabhat K.; Oh, William; Schwartz, Robert; Schwartz, Herbert C.

doi:10.1172/jci110078

Cited by 220 publications

(112 citation statements)

References 17 publications

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“…[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.…”

Section: Introductionmentioning

confidence: 99%

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

2006

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Objective: Offspring of diabetes patients may suffer from tissue iron deficiency. Erythrocyte zinc protoporphyrin/heme (ZnPP/H) ratios measure impaired iron status. The aim of the study was to examine whether cord ZnPP/H ratios were associated with pregnancy glycemic control.Methods: ZnPP/H was measured in cord blood from 31 pregnancies with insulin-treated diabetes (diabetes group) and compared to population normal values. Maternal glycemic control was assessed by daily glucose log, glycosylated hemoglobin and birth weight.Results: Median cord ZnPP/H was higher in the diabetes group than the population normal values (106 (65.2 to 146.8) mM/M vs 68.2 (37.6 to 98.8) mM/M, P<0.0001). Ratios were directly correlated to surrogates of control (glycosylated hemoglobin, P ¼ 0.05, and birth weight, P<0.04). Cord ZnPP/H ratios from pregnancies with pre-existing and gestational diabetes were similar.Conclusion: Because cord ZnPP/H was higher in large offspring of diabetic pregnancy, it might identify greater iron utilization for fetal erythropoiesis.

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Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

2006

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“…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.…”

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confidence: 95%

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

et al. 1990

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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...

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“…Both maternal glycaemic control in diabetic pregnancies and pre-eclampsia affect cord plasma leptin concentrations [13,14] and amniotic fluid and cord plasma EPO concentrations are also increased in such pregnancies [18,19,20]. Neither the number of pre-eclamptic mothers nor the maternal HbA 1C significantly differed, however, between the hypoxic and non-hypoxic group of infants.…”

Section: Discussionmentioning

confidence: 99%

“…Increased fetal plasma and amniotic fluid EPO concentrations have been observed in pregnancies complicated by pre-eclampsia, intrauterine growth restriction, and maternal diabetes [18,19].…”

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confidence: 99%

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

et al. 2000

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Leptin is an adipocyte-derived hormone involved in energy metabolism and fuel homeostasis [1±3]. It could also be important in fetal development because both the leptin gene and leptin receptors are expressed in numerous fetal tissues [4,5]. In addition, leptin has been shown to stimulate fetal erythroid development and to have angiogenic activity [6,7].In term infants, cord blood leptin concentrations correlate directly with birth weight [8±11]. Maternal diabetes mellitus and pre-eclampsia are also associated with increased cord blood leptin concentrations [12±14]. It has been postulated that hypoxic conditions during pre-eclampsia augment placental production of leptin [14]. Erythropoietin (EPO), which regulates the synthesis of bone marrow progenitor cells and erythrocytes [15], is produced in the fetal liver and near term also in the kidney [15]. The main stimulator of EPO production is tissue hypoxia [15,16]. Erythropoietin has also been shown to be produced by placental trophoblast cells. Whether EPO expression in placenta is regulated by hypoxia and the proportion of placental EPO of all EPO in feto-placental circulation is not known [17]. Because EPO is not stored, plasma EPO concentrations are an indicator of the rate of EPO synthesis. Fetal plasma EPO concentrations correlate well with those of amniotic fluid EPO before labour both in normal and in abnormal pregnancies [18]. In response to moderate to severe tissue hypoxia, a sta- Diabetologia (2000) AbstractAims/hypothesis. The purpose of this study was to examine whether fetal leptin concentration correlates with severity of chronic or subchronic fetal hypoxia as indicated by increased fetal concentrations of erythropoietin in fetuses of mothers with Type I (insulin dependent) diabetes mellitus. Methods. We measured leptin and erythropoietin concentrations in cord plasma and amniotic fluid with radioimmunoassay in 25 pregnancies (gestational age 37.2 ± 1.0 weeks). Fetuses with amniotic fluid erythropoietin over 22.5 mU/ml were classified as hypoxic (n = 9) and those with amniotic fluid erythropoietin below 22.5 mU/ml (n = 16) as non-hypoxic. Results. The hypoxic fetuses had significantly higher cord leptin concentrations than non-hypoxic fetuses

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Increased erythropoiesis and elevated erythropoietin in infants born to diabetic mothers and in hyperinsulinemic rhesus fetuses.

Cited by 220 publications

References 17 publications

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

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

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

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

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