Influenza vaccination during pregnancy and risk of selected major structural congenital heart defects, National Birth Defects Prevention Study 2006-2011.

Background: Although results from studies of first-trimester influenza vaccination and congenital heart defects (CHDs) have been reassuring, data are limited for specific CHDs.

Methods: We assessed associations between reported maternal influenza vaccination, 1 month before pregnancy (B1) through end of third pregnancy month (P3), and specific CHDs using data from a multisite, population-based case-control study. Analysis included 2,982 case children diagnosed with a simple CHD (no other cardiac involvement with or without extracardiac defects) and 4,937 control children without a birth defect with estimated delivery dates during 2006-2011.

Prepregnancy exposure to dietary arsenic and congenital heart defects.

Introduction: Arsenic crosses the placenta and accumulates in fetal tissues. In the United States, diet is the predominant route of arsenic exposure, but epidemiologic data are sparse regarding this exposure and development of birth defects. Using data from a large case-control study, we explored associations between maternal dietary arsenic exposure and congenital heart defects (CHDs), the most prevalent birth defects.

Increased interstage morbidity and mortality following stage 1 palliation in patients with genetic abnormalities.

Background: Hypoplastic left heart syndrome and single ventricle variants with aortic hypoplasia are commonly classified as severe forms of CHD. We hypothesised patients with these severe defects and reported genetic abnormalities have increased morbidity and mortality during the interstage period.

Methods And Results: This was a retrospective review of the National Pediatric Cardiology Quality Improvement Collaborative Phase I registry.

ANG II modulation of cardiac growth and remodeling in immature fetal sheep.

ANG II increases fetal blood pressure and stimulates fetal heart growth; however, little is known regarding its direct effects on cardiomyocytes in vivo. We sought to determine whether ANG II stimulates heart growth and cardiomyocyte hypertrophy and/or hyperplasia in utero in the immature fetal heart independent of the effects on cardiac afterload. In twin gestation, fetal sheep at ∼100 days gestation (term 145 days), one fetus received a chronic (6 days) infusion of ANG II alone (50 μg·kg(-1)·min(-1)) or ANG II plus nitroprusside (NTP) to attenuate the increase in blood pressure; noninstrumented twins served as controls.

Angiotensin II-induced cardiovascular load regulates cardiac remodeling and related gene expression in late-gestation fetal sheep.

Background: Angiotensin II (ANG II) stimulates fetal heart growth, although little is known regarding changes in cardiomyocyte endowment or the molecular pathways mediating the response. We measured cardiomyocyte proliferation and morphology in ANG II-treated fetal sheep and assessed transcriptional pathway responses in ANG II and losartan (an ANG II type 1 receptor antagonist) treated fetuses.

Methods: In twin-gestation pregnant sheep, one fetus received ANG II (50 μg/kg/min i.

Thyroid hormone is required for growth adaptation to pressure load in the ovine fetal heart.

Thyroid hormone exerts broad effects on the adult heart, but little is known regarding the role of thyroid hormone in the regulation of cardiac growth early in development and in response to pathophysiological conditions. To address this issue, we determined the effects of fetal thyroidectomy on cardiac growth and growth-related gene expression in control and pulmonary-artery-banded fetal sheep. Fetal thyroidectomy (THX) and/or placement of a restrictive pulmonary artery band (PAB) were performed at 126 ± 1 days of gestation (term, 145 days).

CaMKII determines mitochondrial stress responses in heart.

Myocardial cell death is initiated by excessive mitochondrial Ca(2+) entry causing Ca(2+) overload, mitochondrial permeability transition pore (mPTP) opening and dissipation of the mitochondrial inner membrane potential (ΔΨm). However, the signalling pathways that control mitochondrial Ca(2+) entry through the inner membrane mitochondrial Ca(2+) uniporter (MCU) are not known. The multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is activated in ischaemia reperfusion, myocardial infarction and neurohumoral injury, common causes of myocardial death and heart failure; these findings suggest that CaMKII could couple disease stress to mitochondrial injury.

Sex-specific programming of hypertension in offspring of late-gestation diabetic rats.

Background: The intrauterine environment strongly influences adult disease susceptibility. We used a rat model of third-trimester maternal diabetes to test the hypothesis that adult offspring exposed to hyperglycemia in utero display increased blood pressure and alterations in vascular responsiveness.

Methods: Diabetes was induced by streptozotocin injection to pregnant rats on gestation day 13 (term 21 d) and partially controlled with insulin injections.

Maternal Hyperglycemia Disrupts Histone 3 Lysine 36 Trimethylation of the IGF-1 Gene.

In utero environmental adaptation may predispose to lifelong morbidity. Organisms fine-tune gene expression to achieve environmental adaptation by epigenetic alterations of histone markers of gene accessibility. One example of epigenetics is how uteroplacental insufficiency-induced intrauterine growth restriction (IUGR), which predisposes to adult onset insulin resistance, decreases postnatal IGF-1 mRNA variants and the gene elongation mark histone 3 trimethylation of lysine 36 of the IGF-1 gene (H3Me3K36).

Maternal antioxidant blocks programmed cardiovascular and behavioural stress responses in adult mice.

Intra-uterine growth restriction is an independent risk factor for adult psychiatric and cardiovascular diseases. In humans, intra-uterine growth restriction is associated with increased placental and fetal oxidative stress, as well as down-regulation of placental 11β-HSD (11β-hydroxysteroid dehydrogenase). Decreased placental 11β-HSD activity increases fetal exposure to maternal glucocorticoids, further increasing fetal oxidative stress.

Programming of adult cardiovascular disease following exposure to late-gestation hyperglycemia.

Background: In utero exposure to hyperglycemia is becoming increasingly prevalent as the number of women entering pregnancy with type II diabetes, or developing gestational diabetes, increases. Both animal studies and epidemiologic investigations have found cardiovascular abnormalities in adult offspring of hyperglycemic mothers (OHM).

Objective: We hypothesized that adult OHM would have abnormal cardiac function in vivo and increased susceptibility to ischemia.

Transfusion effects on cardiomyocyte growth and proliferation in fetal sheep after chronic anemia.

Chronic fetal anemia results in significant cardiac remodeling. The capacity to reverse these effects is unknown. We examined the effects of transfusion on cardiomyocyte adaptations after chronic anemia in fetal sheep subjected to daily hemorrhage beginning at 109-d GA (term ∼145 d).

The effect of adrenalectomy on the cardiac response to subacute fetal anemia.

The mechanisms that stimulate fetal heart growth during anemia are unknown. To examine the hypothesis that adrenal hormones contribute to this process, we determined the effects of adrenalectomy (Adx) on heart growth and the activation of cardiac mitogen-activated protein kinases (MAPKs) in the presence and absence of fetal anemia. To identify mechanisms contributing to the initiation of cardiac growth, the duration of anemia was limited to a period shorter than that previously described to result in increased cardiac mass.

Quantitative assessment of the entire thoracic aorta from magnetic resonance images.

Objectives: Although magnetic resonance imaging is a primary modality for following patients with connective tissue diseases, only a limited amount of the image data is utilised. The purpose of this study was to show the clinical applicability of an automated four-dimensional analysis method of magnetic resonance images of the aorta and develop normative data for the cross-sectional area of the entire thoracic aorta.

Study Design: Magnetic resonance imaging was obtained serially over 3 years from 32 healthy individuals and 24 patients with aortopathy and a personal or family history of connective tissue disorder.

Essential roles of an intercalated disc protein, mXinbeta, in postnatal heart growth and survival.

Rationale: The Xin repeat-containing proteins mXinalpha and mXinbeta localize to the intercalated disc of mouse heart and are implicated in cardiac development and function. The mXinalpha directly interacts with beta-catenin, p120-catenin, and actin filaments. Ablation of mXinalpha results in adult late-onset cardiomyopathy with conduction defects.

Coronary endothelial function and vascular smooth muscle proliferation are programmed by early-gestation dexamethasone exposure in sheep.

Exposure of the early-gestation ovine fetus to exogenous glucocorticoids induces changes in postnatal cardiovascular physiology. We sought to characterize coronary artery vascular function in this model by elucidating the contribution of nitric oxide and reactive oxygen species to altered coronary vascular reactivity and examining the proliferative potential of coronary artery vascular smooth muscle cells. Dexamethasone (dex, 0.

Automated analysis of four-dimensional magnetic resonance images of the human aorta.

The purpose of the study was to demonstrate the accuracy and clinical utility of an automated method of image analysis of 4D (3D + time) magnetic resonance (MR) imaging of the human aorta. Serial MR images of the entire thoracic aorta were acquired on 32 healthy individuals. Graph theory based segmentation was applied to the images and cross sectional area (CSA) was determined for the entire length of thoracic aorta.

Three-dimensional thrombus segmentation in abdominal aortic aneurysms using graph search based on a triangular mesh.

An abdominal aortic aneurysm (AAA) is the area of a localized widening of the abdominal aorta, with a frequent presence of thrombus. Segmentation and quantitative analysis of the thrombus in AAA are of paramount importance for diagnosis, risk assessment and determination of treatment options. The proposed thrombus segmentation method utilizes the power and flexibility of the 3-D graph search approach based on a triangular mesh.

4-D cardiac MR image analysis: left and right ventricular morphology and function.

In this study, a combination of active shape model (ASM) and active appearance model (AAM) was used to segment the left and right ventricles of normal and Tetralogy of Fallot (TOF) hearts on 4-D (3-D+time) MR images. For each ventricle, a 4-D model was first used to achieve robust preliminary segmentation on all cardiac phases simultaneously and a 3-D model was then applied to each phase to improve local accuracy while maintaining the overall robustness of the 4-D segmentation. On 25 normal and 25 TOF hearts, in comparison to the expert traced independent standard, our comprehensive performance assessment showed subvoxel segmentation accuracy, high overlap ratios, good ventricular volume correlations, and small percent volume differences.

Cardiomyopathy in offspring of diabetic rats is associated with activation of the MAPK and apoptotic pathways.

Background: Maternal diabetes affects the developing fetal cardiovascular system. Newborn offspring of diabetic mothers can have a transient cardiomyopathy. We hypothesized that cardiomyopathic remodeling is associated with activation of the mitogen activated protein kinase (MAPK) signaling and apoptotic pathways.

Congenital aortic disease: 4D magnetic resonance segmentation and quantitative analysis.

Automated and accurate segmentation of the aorta in 4D (3D+time) cardiovascular magnetic resonance (MR) image data is important for early detection of congenital aortic disease leading to aortic aneurysms and dissections. A computer-aided diagnosis (CAD) method is reported that allows one to objectively identify subjects with connective tissue disorders from 16-phase 4D aortic MR images. Starting with a step of multi-view image registration, our automated segmentation method combines level-set and optimal surface segmentation algorithms in a single optimization process so that the final aortic surfaces in all 16 cardiac phases are determined.

Programming of growth, insulin resistance and vascular dysfunction in offspring of late gestation diabetic rats.

ODM (offspring of diabetic mothers) have an increased risk of developing metabolic and cardiovascular dysfunction; however, few studies have focused on the susceptibility to disease in offspring of mothers developing diabetes during pregnancy. We developed an animal model of late gestation diabetic pregnancy and characterized metabolic and vascular function in the offspring. Diabetes was induced by streptozotocin (50 mg/kg of body weight, intraperitoneally) in pregnant rats on gestational day 13 and was partially controlled by twice-daily injections of insulin.

Vascular nitric oxide and superoxide anion contribute to sex-specific programmed cardiovascular physiology in mice.

Intrauterine environmental pertubations have been linked to the development of adult hypertension. We sought to evaluate the interrelated roles of sex, nitric oxide, and reactive oxygen species (ROS) in programmed cardiovascular disease. Programming was induced in mice by maternal dietary intervention (DI; partial substitution of protein with carbohydrates and fat) or carbenoxolone administration (CX, to increase fetal glucocorticoid exposure).

Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria.

Exposure to an adverse intrauterine environment is recognized as an important risk factor for the development of cardiovascular disease later in life. Although oxidative stress has been proposed as a mechanism for the fetal programming phenotype, the role of mitochondrial O(2)(*-) (superoxide radical) production has not been explored. To determine whether mitochondrial ROS (reactive oxygen species) production is altered by in utero programming, pregnant ewes were given a 48-h dexamethasone (dexamethasone-exposed, 0.