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

Abstract

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]

Gestational diabetes and adverse perinatal outcomes from 716,152 births in France in 2012

“…We found that GDM did not alter the risk of nervous system malformations. The incidence of these malformations was much lower than the incidence of cardiac malformations, as previously reported by other authors [22,25]. One hypothesis is that early hyperglycaemic exposure of the embryo has different teratogenic effects on cardiac and nervous system tissues.…”

“…The excess risk of cardiac malformations observed in this group persisted after the exclusion of women with undiagnosed pregestational diabetes, indicating that mechanisms other than periconceptional maternal blood glucose levels may increase the risk of cardiac malformations [21]. In addition to the severity of diabetes, pre-pregnancy BMI in mothers with GDM was previously shown to be a predictor of congenital malformations in infants [22]. Other teams have shown that high maternal BMI is associated with an increased risk of malformations that is independent of maternal blood glucose levels [23,24].…”

Proinsulin in development: new roles for an ancient prohormone

“…Indeed, congenital defects are still more frequent in infants of diabetic mothers than in the general population, in spite of adequate hyperglycaemia control in a large proportion of diabetic pregnant women. Recent reports have observed that the correlation between congenital malformations in infants of diabetic mothers and pre-pregnancy BMI is higher than that between congenital malformations and maternal blood glucose values [92], and that oxidative stress makes an important contribution to the increase in neural tube defects [93]. In addition, obesity and hyperinsulinaemia have been suggested as risk factors for neural tube defects in the general population [94].…”

What is the Risk of Having Offspring with Cleft Lip/Palate in Pre-Maternal Obese/Overweight Women When Compared to Pre-Maternal Normal Weight Women? A Systematic Review and Meta-Analysis

“…Oddy et al [55] referred to normal weight as a BMI of between 20 to < 25, which is not according to WHO recommendation and reported the outcome of orofacial cleft in general. In one of the articles, weight was classified according to tertiles and also they did not report the outcome of cleft but only reported congenital malformations [56]. Villamor et al [57], classified weight according to change in weight and so it was excluded.…”

“…Studies in which orofacial cleft was grouped as a single entity and not subdivided were excluded because it is known that both CP and CLP have different aetiology. Diabetes is considered a confounding variable when examining the association between obesity and orofacial cleft [56]. All studies included in this review did report…”