scholarly journals Pregestational diabetes mediates the association between maternal obesity and the risk of congenital heart defects

2021 ◽  
Author(s):  
Xiao‐Xia Wu ◽  
Ru‐Xiu Ge ◽  
Le Huang ◽  
Fu‐Ying Tian ◽  
Yi‐Xuan Chen ◽  
...  
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Maternal Obesity ◽  
Heart Defects ◽  
Pregestational Diabetes

scholarly journals Maternal Obesity and the Risk of Congenital Heart Defects: the Mediation Effect of Pregestational Diabetes

2021 ◽  
Author(s):  
Xiao-Xia Wu ◽  
Ru-Xiu Ge ◽  
Le Huang ◽  
Fu-Ying Tian ◽  
Yi-Xuan Chen ◽  
...  
Keyword(s):  
Risk Factor ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Maternal Education ◽  
Maternal Obesity ◽  
Heart Defects ◽  
Normal Weight ◽  
Mediation Effect ◽  
Pregestational Diabetes ◽  
Increased Risk

Abstract Background Congenital heart defects (CHDs) are the most common birth defects worldwide. Maternal obesity has been proposed as a risk factor for CHDs, but the results are controversial and inconclusive. Pregestational diabetes (PGDM) is well known as a risk factor for CHDs and is closely related to obesity. However, the effect of PGDM on the association between maternal obesity and CHDs has not been investigated.Objectives We aimed to explore the association between maternal obesity and CHDs and to further evaluate the mediation effect of PGDM on this association.Methods We involved 53708 mother-infant pairs with deliveries between 2017 and 2019 from the Birth Cohort in Shenzhen (BiCoS). Mothers were categorized into four groups: the underweight group (BMI < 18.5), normal weight group (18.5 ≤ BMI < 24), overweight group (24 ≤ BMI < 28) and obesity group (BMI ≥ 28). To evaluate the association between BMI and CHDs, we fit multivariable logistic regression models, adjusting for maternal age, maternal education level, mode of conception, parity, GDM and offspring sex. Mediation analysis was used to confirm the mediation effect of PGDM on the association between maternal obesity and CHDs.Results The proportion of obese individuals in the BiCoS was 2.11%. Overall, 372 (0.69%) infants were diagnosed with CHDs. The prevalence of CHDs in underweight, normal weight, overweight and obese individuals was 0.64%, 0.68%, 0.72% and 1.24%, respectively. Maternal obesity was associated with an increased risk of CHDs (OR=1.97, 95% CI 1.14–3.41). The offspring of women with PGDM were 6.88 times (95% CI 4.11–11.53) more likely to have CHDs than the offspring of mothers without PGDM. The mediation effect of PGDM on the association between maternal obesity and CHDs was significant (OR=1.18, 95% CI 1.06–1.32). The estimated mediation proportion was 24.83%.Conclusion Our findings suggested that maternal obesity was associated with CHDs and that PGDM partially mediated the association between maternal obesity and CHDs.

scholarly journals Say NO to ROS: Their Roles in Embryonic Heart Development and Pathogenesis of Congenital Heart Defects in Maternal Diabetes

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 436 ◽  
Author(s):  
Engineer ◽  
Saiyin ◽  
Greco ◽  
Feng
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Congenital Heart Defects ◽  
Heart Development ◽  
Congenital Heart ◽  
Heart Defects ◽  
Maternal Diabetes ◽  
Embryonic Heart ◽  
Pregestational Diabetes ◽  
Enos Uncoupling

Congenital heart defects (CHDs) are the most prevalent and serious birth defect, occurring in 1% of all live births. Pregestational maternal diabetes is a known risk factor for the development of CHDs, elevating the risk in the child by more than four-fold. As the prevalence of diabetes rapidly rises among women of childbearing age, there is a need to investigate the mechanisms and potential preventative strategies for these defects. In experimental animal models of pregestational diabetes induced-CHDs, upwards of 50% of offspring display congenital malformations of the heart, including septal, valvular, and outflow tract defects. Specifically, the imbalance of nitric oxide (NO) and reactive oxygen species (ROS) signaling is a major driver of the development of CHDs in offspring of mice with pregestational diabetes. NO from endothelial nitric oxide synthase (eNOS) is crucial to cardiogenesis, regulating various cellular and molecular processes. In fact, deficiency in eNOS results in CHDs and coronary artery malformation. Embryonic hearts from diabetic dams exhibit eNOS uncoupling and oxidative stress. Maternal treatment with sapropterin, a cofactor of eNOS, and antioxidants such as N-acetylcysteine, vitamin E, and glutathione as well as maternal exercise have been shown to improve eNOS function, reduce oxidative stress, and lower the incidence CHDs in the offspring of mice with pregestational diabetes. This review summarizes recent data on pregestational diabetes-induced CHDs, and offers insights into the important roles of NO and ROS in embryonic heart development and pathogenesis of CHDs in maternal diabetes.

scholarly journals Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: A systematic review

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252343
Author(s):  
Gitte Hedermann ◽  
Paula L. Hedley ◽  
Ida N. Thagaard ◽  
Lone Krebs ◽  
Charlotte Kvist Ekelund ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Gestational Diabetes ◽  
Cohort Studies ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Metabolic Disorders ◽  
Maternal Obesity ◽  
Heart Defects ◽  
Increased Risk ◽  
Maternal Overweight

Background Congenital heart defects (CHDs) are the most common congenital malformations. The aetiology of CHDs is complex. Large cohort studies and systematic reviews and meta-analyses based on these have reported an association between higher risk of CHDs in the offspring and individual maternal metabolic disorders such as obesity, diabetes, hypertension, and preeclampsia, all conditions that can be related to insulin resistance or hyperglycaemia. However, the clinical reality is that these conditions often occur simultaneously. The aim of this review is, in consequence, both to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia and CHDs in the offspring, as well as the significance of combinations, such as metabolic syndrome, as risk factors. Methods A systematic literature search of papers published between January 1, 1990 and January 14, 2021 was conducted using PubMed and Embase. Studies were eligible if they were published in English and were case-control or cohort studies. The exposures of interest were maternal overweight or obesity, hypertension, preeclampsia, diabetes, dyslipidaemia, and/or metabolic syndrome, and the outcome of interest was CHDs in the offspring. Furthermore, the studies were included according to a quality assessment score. Results Of the 2,250 identified studies, 32 qualified for inclusion. All but one study investigated only the individual metabolic disorders. Some disorders (obesity, gestational diabetes, and hypertension) increased risk of CHDs marginally whereas pre-gestational diabetes and early-onset preeclampsia were strongly associated with CHDs, without consistent differences between CHD subtypes. A single study suggested a possible additive effect of maternal obesity and gestational diabetes. Conclusions Future studies of the role of aberrations of the glucose-insulin homeostasis in the common aetiology and mechanisms of metabolic disorders, present during pregnancy, and their association, both as single conditions and–particularly–in combination, with CHDs are needed.

scholarly journals Sapropterin Treatment Prevents Congenital Heart Defects Induced by Pregestational Diabetes Mellitus in Mice

2018 ◽  
Vol 7 (21) ◽  
Author(s):  
Anish Engineer ◽  
Tana Saiyin ◽  
Xiangru Lu ◽  
Andrew S. Kucey ◽  
Brad L. Urquhart ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Pregestational Diabetes

scholarly journals Association between maternal obesity and metabolic disorders and congenital heart defects in the offspring: a literature review

2020 ◽  
Author(s):  
Gitte Hedermann ◽  
Paula L Hedley ◽  
Ida N Thagaard ◽  
Lone Krebs ◽  
Thorkild IA Sørensen ◽  
...  
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Metabolic Disorders ◽  
Maternal Obesity ◽  
Heart Defects ◽  
Chronic Hypertension ◽  
Mortality And Morbidity ◽  
Increased Risk ◽  
Early Onset Preeclampsia ◽  
The Individual

SummaryCongenital heart defects (CHDs) are the most common congenital malformation and will, in severe cases, have a serious impact on neonatal mortality and morbidity. The aetiology of CHDs is complex. Large cohort studies have reported an association between increased risk of CHDs in the offspring and individual maternal metabolic disorders such as diabetes, hypertension, preeclampsia, and obesity. All conditions that can be related to insulin resistance and possibly metabolic syndrome (MetS). The aim of this review is to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia, and MetS, or combinations thereof and CHDs in the offspring. A literature search was performed using PubMed and Embase databases. Of the 2,076 potentially relevant identified studies, 30 qualified for inclusion. Only one study dealt with the combination of more than one maternal metabolic condition as risk factor for CHDs in the offspring. All other studies investigated the individual metabolic disorders and their association with CHDs. Some disorders (chronic hypertension, gestational diabetes, and obesity) increased risk of CHDs marginally whereas pregestational diabetes and early-onset preeclampsia were highly associated with CHDs. Future studies on the combination of several metabolic disorders in the same pregnancy and their association with CHDs are needed.

scholarly journals Sapropterin Treatment Prevents Congenital Heart Defects Induced by Pregestational Diabetes in Mice

2018 ◽  
Author(s):  
Anish Engineer ◽  
Tana Saiyin ◽  
Xiangru Lu ◽  
Andrew S. Kucey ◽  
Brad L. Urquhart ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Fetal Heart ◽  
Heart Defects ◽  
Lineage Tracing ◽  
Endocardial Cushions ◽  
Pregestational Diabetes ◽  
Diabetes In Mice ◽  
Enos Uncoupling

ABSTRACTAimsTetrahydrobiopterin (BH4) is a co-factor of endothelial nitric oxide synthase (eNOS), which is critical to embryonic heart development. We aimed to study the effects of sapropterin (Kuvan®), an orally active synthetic form of BH4 on eNOS uncoupling and congenital heart defects (CHDs) induced by pregestational diabetes in mice.MethodsAdult female mice were induced to pregestational diabetes by streptozotocin and bred with normal males to produce offspring. Pregnant mice were treated with sapropterin or vehicle during gestation. CHDs were identified by histological analysis. Cell proliferation, eNOS dimerization and reactive oxygen species (ROS) production were assessed in the fetal heart.ResultsPregestational diabetes results in a spectrum of CHDs in their offspring. Oral treatment with sapropterin in the diabetic dams significantly decreased the incidence of CHDs from 59% to 27% and major abnormalities, such as atrioventricular septal defect and double outlet right ventricle were absent in the sapropterin treated group. Lineage tracing reveals that pregestational diabetes results in decreased commitment of second heart field progenitors to the outflow tract, endocardial cushions, and ventricular myocardium of the fetal heart. Notably, decreased cell proliferation and cardiac transcription factor expression induced by maternal diabetes were normalized with sapropterin treatment. Furthermore, sapropterin administration in the diabetic dams increased eNOS dimerization and lowered ROS levels in the fetal heart.ConclusionsSapropterin treatment in the diabetic mothers improves eNOS coupling, increases cell proliferation and prevents the development of CHDs in the offspring. Thus, sapropterin may have therapeutic potential in preventing CHDs in pregestational diabetes.

scholarly journals Maternal obesity and congenital heart defects: a population-based study

2010 ◽  
Vol 91 (6) ◽  
pp. 1543-1549 ◽  
Author(s):  
James L Mills ◽  
James Troendle ◽  
Mary R Conley ◽  
Tonia Carter ◽  
Charlotte M Druschel
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Maternal Obesity ◽  
Heart Defects ◽  
Population Based ◽  
Population Based Study

scholarly journals OC12.03: Maternal obesity and congenital heart defects in the offspring: a Danish nationwide cohort study

2021 ◽  
Vol 58 (S1) ◽  
pp. 36-36
Author(s):  
G. Hedermann ◽  
I.N. Thagaard ◽  
P.L. Hedley ◽  
L. Krebs ◽  
C.M. Hagen ◽  
...  
Keyword(s):  
Cohort Study ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Maternal Obesity ◽  
Heart Defects

scholarly journals N-Acetylcysteine prevents congenital heart defects induced by pregestational diabetes

2014 ◽  
Vol 13 (1) ◽  
pp. 46 ◽  
Author(s):  
Hoda Moazzen ◽  
Xiangru Lu ◽  
Noelle L Ma ◽  
Thomas J Velenosi ◽  
Brad L Urquhart ◽  
...  
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Pregestational Diabetes
Sign in / Sign up

Export Citation Format

Share Document