Prospective population based survey of outcome of pregnancy in diabetic women: results of the Northern Diabetic Pregnancy Audit, 1994

Hawthorne, Gillian; Robson, Stephen C.; Ryall, E.A.; Sen, Debbie; Roberts, Sue; Platt, Martin Ward

doi:10.1136/bmj.315.7103.279

Cited by 254 publications

(190 citation statements)

References 10 publications

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“…The incidence of congenital malformation in type 1 diabetic pregnancy is estimated to be 4.2% to 9.4% compared with approximately 1% in the general population [1][2][3]. Although a planned pregnancy with optimal blood glucose control and folic acid supplements at the time of conception reduces the risk of congenital malformations, a recent prospective study showed that the incidence of congenital malformations is still elevated in women with type 1 diabetes [4].…”

Section: Introductionmentioning

confidence: 99%

Prevention of neural tube defects by loss of function of inducible nitric oxide synthase in fetuses of a mouse model of streptozotocin-induced diabetes

et al. 2009

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Aims/hypothesis Maternal diabetes during pregnancy increases the risk of congenital malformations such as neural tube defects (NTDs). Although the mechanism of this effect is uncertain, it is known that levels of nitric oxide synthase (NOS) and nitric oxide are elevated in embryos of a mouse model of diabetes. We postulated that overproduction of nitric oxide causes diabetes-induced congenital malformations and that inhibition of inducible NOS (iNOS) might prevent diabetic embryopathy. Methods Mice were rendered hyperglycaemic by intraperitoneal injection of streptozotocin. The incidence of congenital malformations including NTDs was evaluated on gestational day 18.5. We assessed the involvement of iNOS in diabetesinduced malformation by administering ONO-1714, a specific inhibitor of iNOS, to pregnant mice with streptozotocininduced diabetic mice and by screening mice with iNOS deficiency due to genetic knockout (iNos −/− ). Results ONO-1714 markedly reduced the incidence of congenital anomalies, including NTDs, in fetuses of a mouse model of diabetes. It also prevented apoptosis in the head region of fetuses, indicating that iNOS is involved in diabetesrelated congenital malformations. Indeed, no NTDs were observed in fetuses of diabetic iNos −/− mice and the incidence of other malformations was also markedly reduced. Conclusions/interpretation We conclude that increased iNOS activity during organogenesis plays a crucial role in the pathogenesis of diabetes-induced malformations and suggest that inhibitors of iNOS might help prevent malformations, especially NTDs, in diabetic pregnancy.

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Section: Introductionmentioning

confidence: 99%

Prevention of neural tube defects by loss of function of inducible nitric oxide synthase in fetuses of a mouse model of streptozotocin-induced diabetes

et al. 2009

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“…Macrosomia is a frequent complication in pregnancies of women with type 1 diabetes [1][2][3][4]. Macrosomia may lead to short-term complications such as increased rates of Caesarean section, shoulder dystocia and neonatal hypoglycaemia [5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…It is generally agreed that the rate of macrosomia decreases when diabetic control in pregnant women with type 1 diabetes is tightened [13,14]. However, even in patients with near-normal HbA 1 c levels, macrosomia rates remain high [2,4,5]. Several studies on the relationship between HbA 1 c levels and birthweight have been published [15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Sibling birthweight as a predictor of macrosomia in women with type 1 diabetes

2005

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Aims/hypothesis: The aim of this study was to establish the value of maternal HbA 1 c levels and older sibling birthweight as predictors of birthweight and macrosomia in the offspring of women with type 1 diabetes. Subjects and methods: A total of 214 pregnancies of 107 women with type 1 diabetes were studied. Regression analysis was performed to test the predictive value of the birthweight of the first-born infant, HbA 1 c levels, maternal BMI, maternal age and time between subsequent births on the birthweight of the second-born infant. Birthweights were corrected for sex and gestational age. The percentages of first-and second-born infants with macrosomia (weight >90th centile) were calculated and compared. Results: Only the birthweight of earlier born infants was significantly related to that of second-born infants (p<0.001) and 40-50% of the variation in the birthweight of second-born infants could be explained by the birthweight of the firstborn infants. About 85% of the mothers who gave birth to a macrosomic infant had a macrosomic infant in a subsequent pregnancy. Conclusions/interpretation: Although it is clear that glycaemic control contributes to birthweight in women with type 1 diabetes, the birthweight of an earlier born infant appears to be a much better predictor of the birthweight of a subsequent infant than HbA 1 c levels during pregnancy. It may, therefore, be used to identify patients at risk of giving birth to a macrosomic infant. Daily home monitoring of glucose levels, rather than HbA 1 c levels, should be used for assessment of maternal glycaemia during pregnancy.

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“…However, congenital malformations, which occur within the first 8 weeks of pregnancy, have been particularly difficult to avoid. The frequency of congenital malformations in the offspring of diabetic mothers is estimated to be 6 -13%, a two-to fivefold increase over that in the nondiabetic population (3)(4)(5)(6)(7). The malformations associated with diabetic pregnancy affect many major organs, including the central nervous system, heart, skeleton, kidney, gastrointestinal system, and genitalia (5,6).…”

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confidence: 99%

Diacylglycerol Production and Protein Kinase C Activity Are Increased in a Mouse Model of Diabetic Embryopathy

et al. 2002

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Activation of the diacylglycerol-protein kinase C (DAG-PKC) cascade by excess glucose has been implicated in vascular complications of diabetes. Its involvement in diabetic embryopathy has not been established. We examined DAG production and PKC activities in embryos and decidua of streptozotocin (STZ)-diabetic or transiently hyperglycemic mice during neural tube formation. STZ diabetes significantly increased DAG and total PKC activity in decidua (1.5-and 1.4-fold, respectively) and embryos (1.7-and 1.3-fold, respectively) on day 9.5. Membrane-associated PKC ␣, ␤II, ␦, and were increased in decidua by 1.25-to 2.8-fold. Maternal hyperglycemia induced by glucose injection on day 7.5, the day before the onset of neural tube formation, also increased DAG, PKC activity, and PKC isoforms (1.1-, 1.6-, and 1.5-fold, respectively) in the embryo on day 9.5. Notably, membrane-associated PKC activity was increased 24-fold in embryos of diabetic mice with structural defects. These data indicate that hyperglycemia just before organogenesis activates the DAG-PKC cascade and is correlated with congenital defects.

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Prospective population based survey of outcome of pregnancy in diabetic women: results of the Northern Diabetic Pregnancy Audit, 1994

Cited by 254 publications

References 10 publications

Prevention of neural tube defects by loss of function of inducible nitric oxide synthase in fetuses of a mouse model of streptozotocin-induced diabetes

Prevention of neural tube defects by loss of function of inducible nitric oxide synthase in fetuses of a mouse model of streptozotocin-induced diabetes

Sibling birthweight as a predictor of macrosomia in women with type 1 diabetes

Diacylglycerol Production and Protein Kinase C Activity Are Increased in a Mouse Model of Diabetic Embryopathy

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