Congenital Malformations in Newborn Infants of Diabetic Women. Correlation With Maternal Diabetic Vascular Complications

Pedersen, Lars; Tygstrup, Inge; Pedersen, J.F.

doi:10.1097/00006254-196410000-00018

Cited by 21 publications

(23 citation statements)

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“…This is consistent with the well-documented pathogenic role of hyperglycaemia in pregnant women with Type 1 and Type 2 diabetes [1,2], and with some recent studies in GDM [6,7,8]. To our surprise, the main predictor of one or more major CM in the present study was higher pre-pregnancy BMI, a variable that was included as a potential confounder because it has been described as a predictor for major CM in the general population [13].…”

Section: Discussionsupporting

confidence: 93%

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In human gestational diabetes mellitus congenital malformations are related to pre-pregnancy body mass index and to severity of diabetes

et al. 2004

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Aims/hypothesis. This study analysed the relationship between congenital malformations (CM) and severity of gestational diabetes mellitus. Methods. A cohort of 2060 infants of mothers with gestational diabetes was studied. Universal screening and 3 rd Workshop-Conference criteria were used to diagnose gestational diabetes. The severity of diabetes was assessed on the basis of previous hyperglycaemia, blood glucose values in diagnostic OGTT, area under the glucose curve, gestational age and HbA 1 c at diagnosis, insulin requirements during pregnancy, and OGTT after delivery. Potentially confounding variables (age, pre-pregnancy BMI, smoking) were considered. The relationship of potential predictors with CM was analysed with several multivariate logistic regression analyses.Results. The rate of CM was 6% for minor and 3.8% for major malformations (1.4% heart, 0.8% renal/urinary, 0.7% skeletal, 0.3% hypospadias, 0.2% central nervous system, 0.2% cleft lip/palate, 0.1% digestive tract, 0.3% other). In the final models, forward logistic regression analysis identified pre-pregnancy BMI as the predictor of CM (area under receiver operating characteristic curve 0.616); in the backward analysis additional predictors were 1-h blood glucose in diagnostic OGTT and gestational age at diagnosis (area under receiver operating characteristic curve 0.646). Both BMI and severity of gestational diabetes were predictors of heart and minor CM, whereas BMI predicted renal/urinary CM and severity of diabetes predicted skeletal CM. Conclusions/interpretation. In these infants of mothers with gestational diabetes, severity of diabetes and pre-pregnancy BMI were predictors of CM, in accordance with the well-documented pathogenic role of BMI (in the general population) and hyperglycaemia (in diabetic pregnancy). BMI was the main predictor of more prevalent CM. [Diabetologia (2004) 47:509-514]

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Section: Discussionsupporting

confidence: 93%

“…Pre-pregnancy diabetes mellitus is a well-known risk factor for congenital malformations (CM) [1,2] related to hyperglycaemia during the first weeks of pregnancy when embryogenesis takes place [3]. This higher rate of CM is reduced in women receiving pre-pregnancy care [4].…”

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confidence: 99%

In human gestational diabetes mellitus congenital malformations are related to pre-pregnancy body mass index and to severity of diabetes

et al. 2004

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“…2 GDM complicates 1% to 3% of all pregnancies. 3 Different studies showed that congenital anomalies occur 3 -5 times more commonly in the Infant of Diabetic Mother (IDM) than in the general population 4,5,6 .These anomalies include Neural Tube Defects, Caudal Regression Syndrome, Renal Malformations and Congenital Heart Disease. The risk of fetal cardiac malformations in IDM has been found to be significant, most notably Atrial Septal Defect (ASD), Ventricular Septa Defect (VSD), Transposition of the Great Vessels, Truncus Arteriosus, Coarctation of Aorta and Hypertrophic Cardiomyopathy.…”

Section: Introductionmentioning

confidence: 99%

Pattern of Congenital Heart Disease in Infants of Diabetic Mother

Ferdousi

Sarker

Jahan³

et al. 2014

Bangladesh J Child Health

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“…The embryos exposed to hypoglycaemia demonstrated decreased glucose uptake and lactic acid formation, indicating decreased energy production via glycolysis that constitutes the pnncipal energy pathway at this stage of embryonic development. These results suggest that hypoglycaemia during critical periods of embryogenesis has adverse effects on the development of the embryo and these effects might be mediated through metabolic interruption of embryogenesis.Key words: Hypoglycaemia, rat embryo culture, congenital malformation, growth retardation.It is generally accepted that infants of insulin-dependent diabetic mothers have a higher incidence of congenital malformations [1][2][3][4]. A number of experiments of streptozotocin-induced diabetic animals [5,6] and studies in humans [7,8] have suggested that metabolic abnormalities such as hyperglycaemia in early pregnancy may be important factors causing congenital malformations.…”

mentioning

confidence: 99%

“…It is generally accepted that infants of insulin-dependent diabetic mothers have a higher incidence of congenital malformations [1][2][3][4]. A number of experiments of streptozotocin-induced diabetic animals [5,6] and studies in humans [7,8] have suggested that metabolic abnormalities such as hyperglycaemia in early pregnancy may be important factors causing congenital malformations.…”

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confidence: 99%

Effects of hypoglycaemia on early embryogenesis in rat embryo organ culture

Akazawa

Hashimoto

et al. 1987

Diabetologia

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Summary.As congenital malformations may be caused by perturbations of glycolytic flux on early embryogenesis [16], effects of hypogtycaemia were investigated by using rat embryo organ culture. Nine and one-half day old rat embryos were grown in vitro for 48 h (day 9 89 to 11 89 in the presence of hypoglycaemic serum for different hours during the culture period. Hypoglycaemic serum was obtained from rats given insulin intraperitoneally. On exposure to hypoglycaemic serum during the first 24 h of culture (day 9 89 to 10 89 embryos showed marked growth retardation and had increased frequencies of neural lesions (42.7% versus 0%, p < 0.01), in contrast to hypoglycaemic exposure during the second 24 h of culture (day 10~A to 11%), where only minor growth retardation and low frequencies of neural lesions (2.4% versus 0%, NS) were seen. Even exposure to hypoglycaemic serum for a relatively short period (8 h) during the first 24 h of culture resulted in neural lesions at the frequency of 9.3-13.3%. The embryos exposed to hypoglycaemia demonstrated decreased glucose uptake and lactic acid formation, indicating decreased energy production via glycolysis that constitutes the pnncipal energy pathway at this stage of embryonic development. These results suggest that hypoglycaemia during critical periods of embryogenesis has adverse effects on the development of the embryo and these effects might be mediated through metabolic interruption of embryogenesis.Key words: Hypoglycaemia, rat embryo culture, congenital malformation, growth retardation.It is generally accepted that infants of insulin-dependent diabetic mothers have a higher incidence of congenital malformations [1][2][3][4]. A number of experiments of streptozotocin-induced diabetic animals [5,6] and studies in humans [7,8] have suggested that metabolic abnormalities such as hyperglycaemia in early pregnancy may be important factors causing congenital malformations. Whole embryo organ culture techniques in rodents, in which the embryo can develop from early head-fold stage to tail-bud stage with 26-30 somites have been developed [9,10]. The morphogenetic events that occur in cultured embryos correspond to periods observed in human embryos during the 3rd-6th weeks of gestation which is the most susceptible period of teratogenesis in diabetic patients. It has been shown that the addition of excess glucose [11,12] or ketone bodies [13,14] to the culture medium have had teratogenic effects on cultured rat or mouse embryos.On the other hand, effects of hypoglycaemia, during early embryogenesis remain to be evaluated. Since the embryo during the early phase of organogenesis is critically dependent on glycolysis and inhibition of glycolytic flux during the early periods resulting in dysmorphogenesis [15,16], maternal hypoglycaemia during the vulnerable periods could be harmful to the embryo. Therefore, rat embryo organ culture was employed to test whether hypoglycaemia was associated with demonstrable abnormalities even during early embryogenesis and to determine its tempor...

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Congenital Malformations in Newborn Infants of Diabetic Women. Correlation With Maternal Diabetic Vascular Complications

Cited by 21 publications

References 0 publications

In human gestational diabetes mellitus congenital malformations are related to pre-pregnancy body mass index and to severity of diabetes

In human gestational diabetes mellitus congenital malformations are related to pre-pregnancy body mass index and to severity of diabetes

Pattern of Congenital Heart Disease in Infants of Diabetic Mother

Effects of hypoglycaemia on early embryogenesis in rat embryo organ culture

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