Newborn Heart Research Articles

Spermine attenuates high glucose-induced myocardial fibrosis by regulating the cell cycle

Objective: To investigate the protective effect of spermine (Sp) on diabetic cardiomyopathy (DCM) and high glucose-induced cardiac fibroblasts (CFs), and to explore its mechanism.Methods: ①Animal experiments: 24 male Wistar rats were randomly divided into control group, type 1 diabetes group (TID) and spermine group (TID+Sp, each group n=8). TID rats were induced by streptozocin (STZ, 60 mg/kg), and TID+Sp rat were pretreated with spermine (Sp, 5 mg/(kg·d)) for 2 weeks before STZ injection. After 12 weeks of modeling, blood glucose, insulin levels, ejection fraction (EF) and shortening fraction (FS) were measured, and Masson staining and Sirius red staining were performed in the rat cardiac tissues. ②Cell experiments: primary CFs were extracted from newborn (1-3 d) Wistar rat hearts, and were randomly divided into control group, high-glucose group (HG) and HG+Sp group (n=6 per group). HG group was treated with 40 mmol/L glucose, and the HG+Sp group was pretreated with 5 μmol/L Sp for 30 min before HG treatment. The cell viability of CFs was detected by CCK8, the content of collagen in culture medium was analyzed by ELISA, and protein expressions of cell cycle related proteins (PCNA, CyclinD1 and P27) were detected by Western blot. Results: Compared with control group, the blood glucose and collagen content were increased, and the insulin level and heart function were decreased in the T1D group. Meanwhile, HG induced an increasing of the cell viability, the collagen content in the medium and the expressions of PCNA and CyclinD1, while the expression of P27 was down-regulated. Spermine could reduce the above changes, manifested as improving the cardiac function, regulating the expression of cyclin and reducing the level of myocardial fibrosis. Conclusion: Spermine can alleviate myocardial fibrosis in diabetic cardiomyopathy, which mechanism is related to the regulation of cell cycle.

Concurrence of Persistent Pulmonary Hypertension of the Newborn, Myocardial Ischemia, Supraventricular Tachycardia, and Congestive Heart Failure as a Harbinger of Neonatal Graves' Disease.

Concurrence of Persistent Pulmonary Hypertension of the Newborn, Myocardial Ischemia, Supraventricular Tachycardia, and Congestive Heart Failure as a Harbinger of Neonatal Graves' Disease.

Mononuclear diploid cardiomyocytes support neonatal mouse heart regeneration in response to paracrine IGF2 signaling.

Injury to the newborn mouse heart is efficiently regenerated, but this capacity is lost by one week after birth. We found that IGF2, an important mitogen in heart development, is required for neonatal heart regeneration. IGF2 originates from the endocardium/endothelium and is transduced in cardiomyocytes by the insulin receptor. Following injury on postnatal day 1, absence of IGF2 abolished injury-induced cell cycle entry during the early part of the first postnatal week. Consequently, regeneration failed despite the later presence of additional cell cycle-inducing activities 7 days following injury. Most cardiomyocytes transition from mononuclear diploid to polyploid during the first postnatal week. Regeneration was rescued in Igf2-deficient neonates in three different contexts that elevate the percentage of mononuclear diploid cardiomyocytes beyond postnatal day 7. Thus, IGF2 is a paracrine-acting mitogen for heart regeneration during the early postnatal period, and IGF2-deficiency unmasks the dependence of this process on proliferation-competent mononuclear diploid cardiomyocytes.

Special statement: Proposed quality metrics to assess accuracy of prenatal detection of congenital heart defects

Congenital heart defects are a leading cause of neonatal morbidity and mortality. Accurate prenatal diagnosis of congenital heart defects can reduce morbidity and mortality by improving prenatal care, facilitating predelivery pediatric cardiology consultation, and directing delivery to facilities with resources to manage the complex medical and surgical needs of newborns with congenital heart defects. Unfortunately, less than one half of congenital heart defect cases are detected prenatally, resulting in lost opportunities for counseling, shared decision-making, and delivery at an appropriate facility. Quality improvement initiatives to improve prenatal congenital heart defects detection depend on the ability to measure the rate of detection at the level of providers, facilities, or populations, but no standard metric exists for measuring the detection of congenital heart defects at any level. The need for such a metric was recognized at a Cooperative Workshop held at the 2016 Annual Meeting of the Society for Maternal-Fetal Medicine, which recommended the development of a quality metric to assess the rate of prenatal detection of clinically significant congenital heart defects. In this paper, we propose potential quality metrics to measure prenatal detection of critical congenital heart defects, defined as defects with a high rate of morbidity or mortality or that require surgery or tertiary follow-up. One metric is based on a retrospective approach, assessing whether postnatally diagnosed congenital heart defects had been identified prenatally. Other metrics are based on a prospective approach, assessing the sensitivity and specificity of prenatal diagnosis of congenital heart defects by comparing prenatal ultrasound findings with newborn findings. Potential applications, limitations, challenges, barriers, and value for both approaches are discussed. We conclude that future development of these metrics will depend on an expansion of the International Classification of Diseases system to include specific codes that distinguish fetal congenital heart defects from newborn congenital heart defects and on the development of record systems that facilitate the linkage of fetal records (in the maternal chart) with newborn records.

An isolated retrograde-perfused newborn mouse heart preparation

The Langendorff-perfused model is a powerful tool to study biological responses in the isolated heart in the absence of confounders. The model has been adapted recently to enable study of the isolated mouse heart and the effects of genetic manipulation. Unfortunately, the small size and fragility of the mouse heart pose significant challenges, limiting application of the Langendorff model to the study of adult mice. Cardiac development is a complex and dynamic process that is incompletely understood. Thus, establishing an isolated-perfused heart model in the newborn mouse would be an important and necessary advance. Here we present a method to successfully cannulate and perfuse the isolated newborn murine heart. We describe the basic and fundamental physiological characteristics of the ex-vivo retrograde-perfused beating neonatal heart in wild-type C57Bl/6 male mice. Our approach will enable future study of the physiological and pharmacological responses of the isolated immature murine heart to enhance knowledge of how developmental cardiac biology impacts health and disease.•The Langendorff model is a powerful tool to study the heart without confounders.•An isolated-perfused newborn murine heart model has yet to be established.•We demonstrate the first successful isolated neonatal murine heart preparation.

Characteristics of Congenital Heart of Premature Newborns

AbstractCongenital heart disease is considered the most common malformation found in neonatology. The aim of this study was to characterize the congenital heart diseases of premature newborns in the Neonatal Intensive Care Unit (NICU) of a high-risk maternity unit. This was an observational retrospective, descriptive character study carried out in a maternity school, reference in high-risk gestation in the state of Rio Grande do Norte. The study was carried out with premature infants admitted to NICU, who presented some cardiological findings when performing the echocardiogram examination. Data collection was performed through the records of infants hospitalized from December 2016 to December 2017. A total of 371 records were evaluated. Fifty eight infants were diagnosed with congenital heart disease, and 38 of them had Persistence of the ductus arteriosus. The main diagnosed cardiopathies caused low pulmonary flow. About half of the pregnant women with cardiac infants presented some complications during pregnancy, and the most frequent was Urinary Tract Infection; 55 infants needed some ventilatory support, 14 had at least one extubation failure during the hospitalization period, and 8 presented atelectasis. Persistence of the ductus arteriosus was the most common cardiologic finding, and the most frequent congenital heart diseases were those that decreased pulmonary flow, diagnosed mostly in premature infants who needed some ventilation support, but who were discharged from hospital.Keywords: Infant, Premature. Intensive Care Units, Neonatal. Neonatology.ResumoCardiopatias congênitas (CC) são consideradas as malformações mais comuns encontradas na neonatologia. O objetivo deste estudo foi caracterizar as CC de recém-nascidos prematuros em Unidade de Terapia Intensiva Neonatal (UTIN) de uma maternidade de alto risco. Tratase de um estudo observacional retrospectivo, de caráter descritivo, realizado em uma maternidade escola, referência em gestação de alto risco do estado do Rio Grande do Norte. O estudo foi realizado com os bebês prematuros admitidos na UTIN, que apresentaram algum achado cardiológico ao realizar o exame de ecocardiograma. A coleta de dados foi realizada através dos prontuários dos bebês internados no período de dezembro de 2016 a dezembro de 2017. Foram avaliados 371 prontuários, sendo elencados para o estudo 58 bebês, 38 apresentaram persistência do canal arterial (PCA) e foram alocados no grupo PCA e 20 apresentaram outro tipo de CC e foram alocados no grupo CC. 55 bebês necessitaram do uso de algum suporte ventilatório, 14 apresentaram pelo menos uma falha de extubação durante o período de internação e 8 apresentaram atelectasia. Cerca de metade das gestantes com bebês cardiopatas apresentaram alguma intercorrência durante a gestação. A mais frequente foi à infecção do trato urinário. A PCA foi o achado cardiológico mais comum da amostra (65%) e dentre os 20 RN com diferentes CC, as que causam o baixo fluxo pulmonar foram as mais frequentes (70%), sendo encontradas em sua maioria em prematuros que necessitaram de algum suporte ventilatório, mas que receberam alta hospitalar.Palavras-chave: Recém-Nascido Prematuro. Unidade de Terapia Intensiva Neonatal. Neonatologia.

Maternal cadmium exposure in the mouse leads to increased heart weight at birth and programs susceptibility to hypertension in adulthood

Cadmium (Cd) is a toxic heavy metal ubiquitous in the environment. Maternal exposure to Cd is associated with fetal growth restriction, trace element deficiencies, and congenital malformations. Cd exposure during adulthood is associated with cardiovascular disease (CVD); however, the effects of maternal Cd exposure on offspring cardiovascular development and disease are not well-understood. Utilizing a mouse model of maternal Cd exposure, we show that offspring born to Cd-exposed mothers have increased heart weights at birth and susceptibility to hypertension during adulthood. Despite inefficient maternal-fetal transfer of Cd, maternal Cd alters fetal levels of essential trace elements including a deficiency in iron, which is required for cardiovascular system development, oxygen homeostasis, and cellular metabolism. RNA-seq on newborn hearts identifies differentially expressed genes associated with maternal Cd exposure that are enriched for functions in CVD, hypertension, enlarged hearts, cellular energy, and hypoxic stress. We propose that a maternal Cd exposure-induced iron deficiency leads to altered cellular metabolic pathways and hypoxic conditions during fetal development; this stress may contribute to increased heart weight at birth and the programming of susceptibility to hypertension in adulthood. These studies will give insights into potential mechanisms through which maternal Cd exposure impacts cardiovascular development and disease.

Parental emotional and hands-on work-Experiences of parents with a newborn undergoing congenital heart surgery: A qualitative study.

To explore both mothers' and fathers' experiences from prenatal or postnatal diagnosis of their newborn's congenital heart disease (CHD) to the first discharge after heart surgery in a Swiss university children's hospital. A qualitative research approach, based on a constructivist paradigm, was applied to explore participants' experiences and perceptions. Parents of nine children with moderate to severe CHD participated in semistructured joint couple interviews. Data were analyzed inductively via an iterative process, following the steps of thematic analysis. Between the child's CHD diagnosis and hospital discharge after neonatal cardiac surgery, the overarching theme for parents was being confronted with demanding emotional and hands-on work. This parental work included four themes with subthemes: Parents had to tackle a route through an unknown hospital world from receiving the CHD diagnosis and experiencing delivery to attending to their child in the pediatric intensive care unit and during surgery, as well as during the transfer to and the stay on the pediatric cardiac unit. They experienced an at times challenging interplay with health care professionals, performed teamwork as the nuclear family and managed concerned relatives and friends. Health care professionals should establish trustful relationships with parents, while accompanying families continuously, providing consistent, straightforward information, and expressing appreciation for the parents' exceptional emotional and hands-on work. Health care professionals' awareness of parent's experiences is vital to compassionate family-centered care.

Abstract 773: Neonatal and Adult Cardiac Transcriptome Analysis Reveals Distinct Mechanisms in Noncompaction Dilated Cardiomyopathy Development Induced by p.K69R-MLP (Muscle Lim Protein) Mutation i n vivo

Introduction: Pediatric and adult dilated cardiomyopathy (DCM) represent distinct pathological entities, however, the basis of this phenomena remains obscure. The pathogenic variant p.K69R in MLP/ CSRP3 induced DCM in adult Mlp K69R knock-in mice. A noncompacted ventricular wall and dilated ventricles were seen in embryonic and neonatal Mlp K69R hearts, reminiscent of that seen in infant variant carriers. Hypothesis: Mlp- K69R associated genetic modifiers govern DCM phenotypes in neonatal and adult heart. The study was to find genetic modifiers associated with divergent neonatal and adult phenotypes induced by Mlp- K69R. Methods: RNA extracted from neonatal and adult Mlp K69R and Mlp WT mouse myocardium was applied to Affymetrix microarray and QPCR analysis. Data were normalized, subjected to differentially expression genes and gene set enrichment analysis. Results: We found 1024 genes in adult and 252 genes in neonatal heart that were significantly altered in Mlp K69R vs WT littermates. 23 of these genes were mutually altered in adult and neonatal mutants. In adult mutants, 15 sarcomeric genes were significantly over-expressed compared to WT littermates. The mutation altered expression of genes involved in sarcolemmal and desmosomes unity. Calcium handling, integrin-associated networks, and heart failure-associated genes were upregulated in mutants vs WT littermates. In neonates, genes involved in cardiac and vascular development ( Rhox2c, Tbx3, Mir23a, Tbc1d7 ), cell adhesion and migration ( Tff2 ), and apoptosis ( Mir297a-2 ) were significantly altered. Two cardio-protective miRNAs, Mir98 and Mir451a , were highly reciprocally altered in both, adult and neonatal, mutant vs WT hearts. Their expression was increased in mutant adult hearts, but decreased in neonatal mutant hearts, suggesting novel candidates associated with K69R-MLP-induced DCM and noncompaction phenotypes. Conclusions: Differential transcriptomes in neonatal and adult hearts suggest that pathogenic K69R-MLP variant induces DCM and noncompaction phenotypes via distinct underlying genetic modifiers. Contrary to mutant adult mice, mutant newborn hearts show significant decrease in Mir98 and Mir451a, which may predispose them to developing myocardial noncompaction.

Abstract 148: Neonatal Mouse Heart Regeneration is Dependent on Mononuclear Diploid Cardiomyocytes and Paracrine IGF2 Signaling

In normal mice, injury to the newborn heart is efficiently regenerated, but this capacity is lost by one week after birth when most cardiomyocytes have become post-mitotic. Concurrently during the first week, most cardiomyocytes become polyploid. Despite this temporal association, the relation of polyploidization to neonatal heart regeneration has not been adequately examined. In this study, we find that IGF2, an important mitogenic factor in heart development, is required to support neonatal mouse heart regeneration. Following injury on postnatal day 1, absence of IGF2 abolished injury-induced cell cycle entry (as indicated by phospho-histone H3 staining) during the early part of the first postnatal week, when cardiomyocytes are still mononuclear and diploid. Consequently, regeneration failed despite the later presence of additional activities that support robust cell cycle entry 7 days following injury, a time when most cardiomyocytes are polyploid and no longer able to complete cytokinesis. IGF2 originates from the endocardium/endothelium lineage and is transduced by the insulin receptor; both features distinguish the action of IGF2 in neonatal heart regeneration from that in embryonic heart development. Regeneration in injured Igf2-deficient neonates was rescued by three different contexts that elevate the percentage of mononuclear diploid cardiomyocytes beyond postnatal day 7. Thus, IGF2 is the primary paracrine-acting mitogen for heart regeneration during the early postnatal period, and IGF2-deficiency unmasks the dependence of this process on proliferation-competent mononuclear diploid cardiomyocytes.

Effect of If Current Blockade on Newborn Rat Heart Isolated According to Langendorff.

The study examined the effects of hyperpolarization-activated funny current (If) on HR and coronary flow in Langendorff-isolated hearts from newborn rats. Blockade of If current with ZD7288 changed the examined cardiac parameters. The blocker in a concentration of 10-9 M decreased HR by 26.8% (p≤0.05). In concentrations 10-8, 10-7, 10-6, and 10-5 M ZD7288 produced minor differently directed effects. In a concentration of 10-5 M, ZD7288 reduced coronary flow in the isolated heart (p≤0.01). In other concentrations, the blocker produced no significant effects on coronary flow.

Hand- held Precordial Doppler Ultrasound Detects Heart Rate Faster than Electrocardiogram in Neonatal Resuscitation

Background: A fast and accurate newborn heart rate (HR) assessment is critical to neonatal resuscitation. The 7th edition of Neonatal Resuscitation Program (NRP) guidelines recommends initial use of precordial auscultation (PA) and then the use of pulse oximetry (PO) and electrocardiogram (ECG) if the HR is unobtainable via PA or if advanced resuscitation is necessary. Studies have shown that PA is inaccurate. PO and ECG are subject to …

A Transcriptomic Model of Postnatal Cardiac Effects of Prenatal Maternal Cortisol Excess in Sheep.

In utero treatment with glucocorticoids have been suggested to reprogram postnatal cardiovascular function and stress responsiveness. However, little is known about the effects of prenatal exposure to the natural corticosteroid, cortisol, on postnatal cardiovascular system or metabolism. We have demonstrated an increased incidence of stillbirth in sheep pregnancies in which there is mild maternal hypercortisolemia caused by infusion of 1 mg/kg/d cortisol. In order to model corticosteroid effects in the neonate, we created a second model in which cortisol was infused for 12 h per day for a daily infusion of 0.5 mg/kg/d. In this model we had previously found that neonatal plasma glucose was increased and plasma insulin was decreased compared to those in the control group, and that neonatal ponderal index and kidney weight were reduced and left ventricular wall thickness was increased in the 2 week old lamb. In this study, we have used transcriptomic modeling to better understand the programming effect of this maternal hypercortisolemia in these hearts. This is a time when both terminal differentiation and a shift in the metabolism of the heart from carbohydrates to lipid oxidation are thought to be complete. The transcriptomic model indicates suppression of genes in pathways for fatty acid and ketone production and upregulation of genes in pathways for angiogenesis in the epicardial adipose fat (EAT). The transcriptomic model indicates that RNA related pathways are overrepresented by downregulated genes, but ubiquitin-mediated proteolysis and protein targeting to the mitochondria are overrepresented by upregulated genes in the intraventricular septum (IVS) and left ventricle (LV). In IVS the AMPK pathway and adipocytokine signaling pathways were also modeled based on overrepresentation by downregulated genes. Peroxisomal activity is modeled as increased in EAT, but decreased in LV and IVS. Our results suggest that pathways for lipids as well as cell proliferation and cardiac remodeling have altered activity postnatally after the in utero cortisol exposure. Together, this model is consistent with the observed increase in cardiac wall thickness at necropsy and altered glucose metabolism observed in vivo, and predicts that in utero exposure to excess maternal cortisol will cause postnatal cardiac hypertrophy and altered responses to oxidative stress.

VITAMIN C PREVENTS STRESS INDUCED CARDIOMYOPATHY IN PRENATAL NOISE EXPOSED RODENTS

Potency of oral vitamin C to prevent cardiomyopathy in prenatal noise exposed newborn Wistar rats was studied by comparing the cardiomyocyte numbers and the extracellular matrix expressions (ECM) to controls. Twenty-four newborns (NR) of 32 pregnant mothers were divided equally into 4 groups: K1 (distilled water [DW]), K2 (150 mg/kg of BW oral vitamin C once daily [VC]), P1 (4 hours daily of white noise at 95 dB [WN]+DW), and P2 (WN+VC). VC and WN were given from D1 till birth and from D15 till birth, respectively. The hearts of NR were harvested, and processed for histology slides (2 midsagittal 4 μ cut slides/ animal) stained with hematoxyllin-eosin and Masson trichrome for the cardiomyocytes and ECM quantification at the ventricles using Image Raster 3.0 and ImageJ, respectively. Pictures from 8 visual fields/ slide were taken and analyzed in duplicate (400x magnifications under a light microscope). Data were analyzed using SPSS 17; significance level of p<0.05. In P1, the cardiomyocite cell numbers was significantly lowest (p<0.001); whilst the ECM was significantly highest than K1, K2, P2 (p<0.001 and p<0.005, respectively). Here, vitamin C could prevent the adverse effect of prenatal noise exposures in the ventricle myocardium of newborn rats. Keywords: cardiomyopathy, hypertrophy, prenatal noise, vitamin C

Diabetic Pregnancy and Maternal High-Fat Diet Impair Mitochondrial Dynamism in the Developing Fetal Rat Heart by Sex-Specific Mechanisms

Infants born to diabetic or obese mothers are at greater risk of heart disease at birth and throughout life, but prevention is hindered because underlying mechanisms remain poorly understood. Using a rat model, we showed that prenatal exposure to maternal diabetes and a high-fat diet caused diastolic and systolic dysfunction, myocardial lipid accumulation, decreased respiratory capacity, and oxidative stress in newborn offspring hearts. This study aimed to determine whether mitochondrial dynamism played a role. Using confocal live-cell imaging, we examined mitochondrial dynamics in neonatal rat cardiomyocytes (NRCM) from four prenatally exposed groups: controls, diabetes, high-fat diet, and combination exposed. Cardiac expression of dynamism-related genes and proteins were compared, and gender-specific differences were evaluated. Findings show that normal NRCM have highly dynamic mitochondria with a well-balanced number of fusion and fission events. Prenatal exposure to diabetes or a high-fat diet impaired dynamism resulting in shorter, wider mitochondria. Mechanisms of impaired dynamism were gender-specific and protein regulated. Females had higher expression of fusion proteins which may confer a cardioprotective effect. Prenatally exposed male hearts had post-translational modifications known to impair dynamism and influence mitophagy-mediated cell death. This study identifies mitochondrial fusion and fission proteins as targetable, pathogenic regulators of heart health in offspring exposed to excess circulating maternal fuels.

Impact of a mobile application for heart rate assessment in simulated neonatal resuscitation: a randomised controlled cross-over study

BackgroundClinical assessment of newborn heart rate (HR) at birth has been reported to be inaccurate. NeoTapAdvancedSupport (NeoTapAS) is a free-of-charge mobile application that showed good accuracy in HR estimation. This...

Experimental myocardial necrosis course during alginate hydrogel implantation, saturated with extract of cryopreserved piglet heart fragments (histological examination).

Background. New methods for therapy and prevention of complications in acute myocardial necrosis are aimed to limit the necrosis areas, and to prevent the heart rupture and heart failure development. With this aim, during the heart muscle remodeling one applies the alginate implants, which not only prevent the cardiac aneurysm, but may be a depot of biologically active substances and/or cell suspensions as well, ensuring thereby the diffusion of the latter into the affected area. Objective. To analyze the histological material of the hearts after cryonecrosis and the introduction of alginate implants into the damage zone saturated with a cryopreserved extract of heart fragments of the piglets in dynamics. Methods. The experimental studies were carried out in 78 outbred male rats. Myocardial necrosis was simulated by affecting the left ventricular wall by means of cryoinstrument with 3 mm applicator diameter at working surface temperature of -195°C for 30 s. Either alginate implant or the implant, saturated with the piglet heart extract (PHE) was injected into cryonecrosis area. The extract was derived from cryopreserved fragments of newborn piglet hearts. Results. It was established the fact, that in the animals of all experimental groups after cryoexposure to the heart, the myocardial remodeling proceeded by the classical pathway from an aseptic inflammation to the formation of connective tissue scar. The use of alginate implants, saturated with cryopreserved heart fragments of piglets accelerated the reparative processes in the heart and reduced the degree of remodeling of the left ventricular myocardium. Conclusion. Analysis of histological preparations of the heart showed that in the animals with myocardial cryonecrosis after introducing an alginate implant, and especially the PHE-saturated alginate implant, a newly formed scar tissue with mature collagen fibers and blood vessels developed in the affected area in earlier terms (to days 7 and 14, respectively), as compared to myocardial cryonecrosis, that suggested the trophic restoration in affected area of the myocardium.

Oximetry and neonatal examination for the detection of critical congenital heart disease: a systematic review and meta-analysis.

Background: Undiagnosed congenital heart disease in the prenatal stage can occur in approximately 5 to 15 out of 1000 live births; more than a quarter of these will have critical congenital heart disease (CCHD). Late postnatal diagnosis is associated with a worse prognosis during childhood, and there is evidence that a standardized measurement of oxygen saturation in the newborn by cutaneous oximetry is an optimal method for the detection of CCHD. We conducted a systematic review of the literature and meta-analysis comparing the operational characteristics of oximetry and physical examination for the detection of CCHD. Methods: A systematic review of the literature was conducted on the following databases including published studies between 2002 and 2017, with no language restrictions: Pubmed, Science Direct, Ovid, Scopus and EBSCO, with the following keywords: oximetry screening, critical congenital heart disease, newborn OR oximetry screening heart defects, congenital, specificity, sensitivity, physical examination. Results: A total of 419 articles were found, from which 69 were selected based on their titles and abstracts. After quality assessment, five articles were chosen for extraction of data according to inclusion criteria; data were analyzed on a sample of 404,735 newborns in the five included studies. The following values were found, corresponding to the operational characteristics of oximetry in combination with the physical examination: sensitivity: 0.92 (CI 95%, 0.87-0.95), specificity: 0.98 (CI 95%, 0.89-1.00), for physical examination alone sensitivity: 0.53 (CI 95%, 0.28-0.78) and specificity: 0.99 (CI 95%, 0.97-1.00). Conclusions: Evidence found in different articles suggests that pulse oximetry in addition to neonatal physical examination presents optimal operative characteristics that make it an adequate screening test for detection of CCHD in newborns, above all this is essential in low and middle-income settings where technology medical support is not entirely available.

Mechanisms of in utero cortisol effects on the newborn heart revealed by transcriptomic modeling.

We have identified effects of elevated maternal cortisol (induced by maternal infusion 1 mg·kg-1·day-1) on fetal cardiac maturation and function using an ovine model. Whereas short-term exposure (115-130-day gestation) increased myocyte proliferation and Purkinje fiber apoptosis, infusions until birth caused bradycardia with increased incidence of arrhythmias at birth and increased perinatal death, despite normal fetal cortisol concentrations from 130 days to birth. Statistical modeling of the transcriptomic changes in hearts at 130 and 140 days suggested that maternal cortisol excess disrupts cardiac metabolism. In the current study, we modeled pathways in the left ventricle (LV) and interventricular septum (IVS) of newborn lambs after maternal cortisol infusion from 115 days to birth. In both LV and IVS the transcriptomic model indicated over-representation of cell cycle genes and suggested disruption of cell cycle progression. Pathways in the LV involved in cardiac architecture, including SMAD and bone morphogenetic protein ( BMP) were altered, and collagen deposition was increased. Pathways in IVS related to metabolism, calcium signaling, and the actin cytoskeleton were altered. Comparison of the effects of maternal cortisol excess to the effects of normal maturation from day 140 to birth revealed that only 20% of the genes changed in the LV were consistent with normal maturation, indicating that chronic elevation of maternal cortisol alters normal maturation of the fetal myocardium. These effects of maternal cortisol on the cardiac transcriptome, which may be secondary to metabolic effects, are consistent with cardiac remodeling and likely contribute to the adverse impact of maternal stress on perinatal cardiac function.

Chronic maternal cortisol excess during late gestation leads to metabolic alterations in the newborn heart.

Our laboratory has previously shown in an ovine model of pregnancy that abnormal elevations in maternal cortisol during late gestation lead to increased fetal cardiac arrhythmias and mortality during peripartum. Furthermore, transcriptomic analysis of the fetal heart suggested alterations in TCA cycle intermediates and lipid metabolites in animals exposed to excess cortisol in utero. Therefore, we utilized a sheep model of pregnancy to determine how chronic increases in maternal cortisol alter maternal and fetal serum before birth and neonatal cardiac metabolites and lipids at term. Ewes were either infused with 1 mg·kg-1·day-1 of cortisol starting at gestational day 115 ( n = 9) or untreated ( n = 6). Serum was collected from the mother and fetus (gestational day 125), and hearts were collected following birth. Proton nuclear magnetic resonance (1H-NMR) spectroscopy was conducted to measure metabolic profiles of newborn heart specimens as well as fetal and maternal serum specimens. Mass spectrometry was conducted to measure lipid profiles of newborn heart specimens. We observed alterations in amino acid and TCA cycle metabolism as well as lipid and glycerophospholipid metabolism in newborn hearts after excess maternal cortisol in late gestation. In addition, we observed alterations in amino acid and TCA cycle metabolites in fetal but not in maternal serum during late gestation. These results suggest that fetal exposure to excess maternal cortisol alters placental and fetal metabolism before birth and limits normal cardiac metabolic maturation, which may contribute to increased risk of peripartum cardiac arrhythmias observed in these animals or later life cardiomyopathies.