Assisted reproduction and congenital malformations: A systematic review and meta-analysis.

Prior studies have explored the links between congenital anomalies and assisted reproduction techniques, among other factors. However, it remains unclear whether a particular technique harbors an inherent risk of major congenital anomalies, either cumulatively or in an organ-specific manner. A meta-analysis was conducted using relevant studies from inception to February 2023 using six databases and two appropriate registers. Sources of heterogeneity were explored using sub-group analysis, using study weight, risk of bias and geographical location of original studies. Neonates conceived through assisted reproduction appear to have a higher risk of major congenital anomalies compared to naturally conceived neonates, OR 0.67 [95% CI 0.59, 0.76], I2 = 97%, p < 0.00001, with neonates conceived through intracytoplasmic sperm injection (ICSI) at a 9% higher chance of being affected in comparison to neonates conceived through in vitro fertilization (IVF). The increase in cardiac, gastrointestinal (GI), and neurological congenital anomalies appears to be independent of the assisted reproduction technique, while urogenital and musculoskeletal (MSK) anomalies were found to be increased in ICSI compared with IVF, OR 0.83 [95% CI 0.69, 0.98]; p = 0.03, I2 = 0%, and OR 0.65 [95% CI 0.49, 0.85]; p = 0.002, I2 = 80%, respectively. Neonates conceived using assisted reproduction techniques appear to be at higher risk of major congenital anomalies, with a higher risk attributable to conception using ICSI. The increase in cardiac, neurological, and GI congenital anomalies does not appear to be technique-specific, while the opposite held true for urogenital and MSK anomalies.

Pathophysiology and Treatment of Intraseptal-Course Left Coronary Anomaly: Surgery for All?

Intraseptal-course, ectopic coronary anomalies are not well characterized as to anatomy, function, prognosis, and treatment. Recently, a revolutionary but unsupported new theory is claiming that most patients with a Left Anomalous Coronary Artery originating from the Opposite Sinus with anomalous Intra-Septal course (L-ACAOS-IS)-even small children-have significant stenoses and require open-heart surgery to prevent acute myocardial infarction and death. This surprising view has spurred ongoing discussions among adult and pediatric cardiologists and cardiac surgeons, compelling us (the conservative party in the discussion) to offer an in-depth and comprehensive review of this anomaly, based on objective but opposite data. We and other adult cardiologists have followed numerous L-ACAOS-IS patients for many years and have observed none of the claimed catastrophes. Rather, we have consistently found that L-ACAOS-IS generally has a benign clinical prognosis. We present the general principle of coronary artery dysfunction in anatomical congenital anomalies (that only significant luminal coronary stenosis can have clinical repercussions). We then review anatomical and functional details of L-ACAOS-IS related to prognosis and treatment indications, which could explain many of the clinical presentations recently mentioned. Finally, we encourage our more liberal colleagues to recognize that, compared with normal coronary arteries, those with anomalies of origin and course are associated with frequent coronary spasm. In particular, we underscore that some of the ischemic manifestations and other results might actually be caused by pressure wire-induced artifacts (rigid wires tend to cause coronary spasm when advanced into tortuous coronary arteries).

Clinical characteristics of pediatric inpatients infected with the SARS-CoV-2 Omicron variant-a retrospective observational cohort study.

Background: The children infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at risk of progressing to severe disease. Clinical characteristics treatment measures and prognosis of these special age group of patients have not been completely understood which necessitate more researches. This study sought to analyze the clinical characteristics of children infected with the Omicron variant to provide evidences for the prevention, diagnosis and treatment of the Omicron variant infection in children. Methods: The subjects of this study included children hospitalized for the Omicron variant at Tianjin Binhai Hospital in November 2022. The data were collected from the electronic medical record system, and the clinical characteristics of the children were analyzed. The primary endpoints included the clinical presentation, laboratory tests, virological characteristics, treatment regimen, and clinical prognosis of the patients. Results: A total of 49 patients were enrolled, of whom 32 (65.3%) were male. The patients had a median age of 10 (interquartile range, 6-11) years, and 34.7% of the patients received 2 or more coronavirus disease 2019 (COVID-19) vaccines. The main clinical manifestations of the patients were fever (79.6%) and cough (24.5%), with a maximum temperature of 42 ℃ and a median temperature of 39 (interquartile range, 38.4-39) ℃. The proportions of neutrophils and C-reactive protein were elevated by 50.0% and 25.0%, respectively. The total percentages of white blood cells and thrombocytopenia were 12.5% and 6.3%, respectively. D-dimer was examined in 6 cases, and was elevated to 1.77 µg/mL in 1 case (16.7%), and normal in 5 cases. The liver function, kidney function, and coagulation of 9 (100%) patients were all normal. After the anti-virus, anti-inflammatory response, antipyretic, and traditional Chinese medicine treatments, all the children were cured and discharged from the hospital. There were no severe cases. Conclusions: The main manifestations of children infected with the SARS-CoV-2 Omicron variant were fever and cough. Some children had a high fever, nasal congestion, runny nose, gastrointestinal symptoms, and rash. A proportion of 12.5% of patients have a white blood cell count less than 4×109/L, and 6.3% have thrombocytopenia. The prognosis of the child was favorable after treatment with antiviral, antipyretic, and traditional Chinese medicine.

Narrative review of single ventricle: where are we after 40 years?

Background and Objective: Key medical and surgical advances have been made in the longitudinal management of patients with "functionally" single ventricle physiology, with the principles of Fontan circulation applied to other complex congenital heart defects. The purpose of this article is to review all of the innovations, starting from fetal life, that led to a change of strategy for single ventricle. Methods: Our literature review included all full articles published in English language on the Cochrane, MedLine, and Embase with references to "single ventricle" and "univentricular hearts", including the initial history of the treatments for this congenital heart defects as well as the innovations reported within the last decades. Key Content and Findings: All innovations introduced have been analyzed, including: (I) fetal diagnosis and interventions, in particular to prevent or reduce brain damages; (II) neonatal care; (III) post-natal diagnosis; (IV) interventional cardiology procedures; (V) surgical procedures, including neonatal palliations, hybrid procedures, bidirectional Glenn and variations, Fontan completion, biventricular repair; (VI) peri-operative management; (VII) Fontan failure, with Fontan take-down and conversion, and mechanical circulatory support; (VIII) transplantation, including heart, heart and lung, heart and liver; (IX) exercise; (X) pregnancy; (XI) adolescents and adults without Fontan completion; (XII) future studies, including experimental studies on animals, computational studies, genetics, stem cells and bioengineering. Conclusions: These last 40 years have certainly changed the course of natural history for children born with any form of "functionally" single ventricle, thanks to the improvement in diagnostic and treatment techniques, and particularly to the increased knowledge of the morphology and function of these complex hearts, from fetal to adult life. There is still much left unexplored and room for improvement, and all efforts should be concentrated in collaborations among different institutions and specialties, focused on the same matter.

Aortic valve leaflets are asymmetric and correlated with the origin of coronary arteries.

Background: Asymmetry of the aortic valve leaflets has been known since Leonardo Da Vinci, but the relationship between size and shape and origin of the coronary arteries has never been examined. Our aim was to evaluate this anatomy in a population of pediatric patients using a cross-sectional study design. Methods: Consecutive pediatric patients with trans-esophageal echocardiography (TEE), with or without trans-thoracic echocardiography (TTE), were included in our study. Exclusion criteria: (I) bicuspid aortic valve; (II) aortic valve stenosis; (III) hypoplasia of aortic valve annulus, or aortic root; (IV) truncal valve; (V) coronary artery atresia; (VI) previous surgery on aortic valve and/or coronary arteries. In pre-operative TTE and intra-operative TEE inter-commissural distance and length of aortic valve leaflets were measured in short axis view in the isovolumic phase of systole. Echocardiography investigations, anonymized and randomly coded, were independently reviewed by at least two readers. Echocardiography, angiography, cardiac computed tomography (CT) scan and magnetic resonance imaging (MRI), and operative notes were reviewed to identify origin of coronary arteries. Results: Two hundred sixty-one pediatric patients were identified, 93 excluded per our criteria, leaving 168 patients, age 2.6±4.3 years, weight 12.87±17.34 kg, 128 (76%) with normal and 40 (24%) with abnormal coronary arteries. In TTE and TEE measurements the non-coronary leaflet had larger area (P<0.001), while the right and left had equal areas, but different shape, with the left leaflet longer (P<0.001) and narrower (P=0.005) than the right. With the major source of blood flow from the right coronary sinus, the non-coronary leaflet was still the longest. However, there was no statically significant difference between the size and shape previously observed between the right and left leaflets. Conclusions: Our study showed asymmetry of size and shape among aortic valve leaflets, and a relationship with coronary artery origin. The complex aortic root anatomy must be approximated to optimize function of any surgical repair. These findings also may prove useful in the pre-operative definition of coronary artery anatomy and in the recognition of coronary artery anomalies.

Impact on clinical outcomes from transcatheter closure of the Fontan fenestration: A systematic review and meta-analysis.

Background: Meta-analysis of the impact on clinical outcome from transcatheter closure of Fontan fenestration. Methods: Cochrane, Embase, MEDLINE, and Open-Gray were searched. Parameters such as changes in oxygen saturation, cavo-pulmonary pressure, maximum heart rate during exercise, exercise duration, and oxygen saturation after fenestration closure were pooled and statistical analysis performed. Results: Among 922 publications, 12 retrospective observational studies were included. The included studies involved 610 patients, of which 552 patients (90.5%) had a fenestration. Of those patients, 505 patients (91.5%) underwent attempt at trans-catheter closure. When it could be estimated, the pooled overall mean age at trans-catheter fenestration closure was 6.6 ± 7.4 years, and the mean follow-up time was 34.4 ± 10.7 months. There were 32 minor (6.3%) and 20 major (4.0%) complications during or after trans-catheter Fontan fenestration closure. The forest plots demonstrate that following fenestration closure, there was a significant increase in the mean arterial oxygen saturation of 7.9% (95% CI 6.4-9.4%, p < 0.01). There was also a significant increase in the mean cavo-pulmonary pressure of 1.4 mmHg (95% CI 1.0-1.8 mmHg, p < 0.01) following fenestration closure. The exercise parameters reported in 3 studies also favored closing the fenestration as well, yet the exercise duration increase of 1.7 min (95% CI 0.7-2.8 min, p < 0.01) after fenestration closure is probably clinically insignificant. Conclusion: Late closure of a Fontan fenestration has the impact of improving resting oxygen saturation, exercise oxygen saturation, and a modest improvement of exercise duration. These clinical benefits, however, may be at the expense of tolerating slightly higher cavo-pulmonary mean pressures.

Anesthesia for Echocardiography and Magnetic Resonance Imaging in the African Clawed Frog (Xenopus laevis).

This report describes an anesthesia technique that we used to study cardiovascular anatomy and physiology with echocardiography and cardiac magnetic resonance (CMR) in 46 African clawed frogs (Xenopus laevis) (n = 24 for electrocardiography and n = 22 for CMR). For administration of anesthesia, 3 holding tanks, one each for transportation, sedation, and recovery, were filled with filtered water, with 0.05% buffered tricaine methasulfonate solution (MS-222) added into the sedation tank. Fifteen minutes after the frog was placed in the sedation tank, a paper towel was soaked in MS-222 solution, and the frog was placed in a supine position and rolled 3 to 4 times in the soaked paper with the head and legs exposed. Vital signs were monitored and recorded throughout the procedure. After imagining, frogs were unrolled from the paper towel, placed in the recovery tank, and later returned to their home tank. Monitoring was discontinued when the frogs resumed typical activity. No mortality or complications were observed in frogs that underwent this procedure. Mean duration ±1 SD of anesthesia induction was 12 ± 5 min in the echocardiography group and 14 ± 6 min in the CMR group. The mean duration of anesthesia maintenance was 60 ± 18 min in the echocardiography group and 118 ± 37 min in the CMR group. An additional dose of anesthesia was necessary during maintenance for 9 of 24 (37%) frogs in the echocardiography group and 6 of 22 (27%) frogs in the CMR group. At the end of the procedure, the mean oxygen saturation was 66 ± 9% in the echocardiography group and 85 ± 6% in the CMR group, and heart rate was 48 ± 13 beats/min in the echocardiography group and 42 ± 7 beats/min in the CMR group. We conclude that the anesthesia technique of immersion in MS-222 is suitable for performing echocardiography and CMR imaging in this species without complications.

Ebstein's Anomaly: From Fetus to Adult-Literature Review and Pathway for Patient Care.

Ebstein's anomaly, first described in 1866 by Dr William Ebstein, accounts for 0.3-0.5% of congenital heart defects and represents 40% of congenital tricuspid valve abnormalities. Ebstein's anomaly affects the development of the tricuspid valve with widely varying morphology and, therefore, clinical presentation. Associated congenital cardiac lesions tend to be found more often in younger patients and may even be the reason for presentation. Presentation can vary from the most extreme form in fetal life, to asymptomatic diagnosis late in adult life. The most symptomatic patients need intensive care support in the neonatal period. This article summarizes and analyzes the literature on Ebstein's anomaly and provides a framework for the investigation, management, and follow-up of these patients, whether they present via fetal detection or late in adult life. For each age group, the clinical presentation, required diagnostic investigations, natural history, and management are described. The surgical options available for patients with Ebstein's anomaly are detailed and analyzed, starting from the initial mono-leaflet repairs to the most recent cone repair and its modifications. The review also assesses the effects of pregnancy on the Ebstein's circulation, and vice versa, the effects of Ebstein's on pregnancy outcomes. Finally, two attached appendices are provided for a structured echocardiogram protocol and key information useful for comprehensive Multi-Disciplinary Team discussion.

Essential role of cardiac computed tomography for surgical decision making in children with total anomalous pulmonary venous connection and single ventricle.

BACKGROUND: Total anomalous pulmonary venous connection (TAPVC) is a major risk factor in infants with single ventricle (SV). Exact definition of TAPVC anatomy is crucial for surgical planning. AIM: To evaluate the role of cardiac computed tomography (CT) in this setting. METHODS: Retrospective review of 13 infants who underwent TAPVC repair associated with SV from May 2016 to October 2021. Anatomy, incidence, and mechanisms of pulmonary venous obstruction (PVO) were described. Cardiac CT diagnostic yield was compared to echocardiography (echo). RESULTS: Of 13 infants, median age and weight were 24 days (range 2-303 days) and 3.2 (range 2.6-9.1) kg, 8 (62%) were male, 4 (31%) premature, and 11 (85%) had heterotaxy syndrome. All infants had pre- and postoperative echo; 13 had preoperative and 8 (62%) had postoperative cardiac CT. Type of TAPVC: six (46%) supracardiac, two (15%) intracardiac, one (8%) infracardiac, and four (31%) mixed, with pulmonary veins draining in >1 confluence in nine (69%). PVO was present in 6/13 (46%) preoperatively and 5/13 (31%) postoperatively. Mechanisms of PVO: 9/11 (82%) stenosis, 1/9 (9%) membrane formation, and 1/9 (9%) external compression. The sensitivity to diagnose PVO was 45.5% for echo and 100% for cardiac CT, the specificity was 100% for both. No discrepancy was found between cardiac CT and intraoperative findings, but echo had a complete preoperative diagnosis in 1/13 (8%) (p < .00001, Fisher exact test). CONCLUSIONS: Cardiac CT is essential to evaluate pre- and postoperative TAPVC in SV for surgical decision making and long term follow up.

The Secrets of the Frogs Heart.

The heart of the African clawed frog has a double-inlet and single-outlet ventricle supporting systemic and pulmonary circulations via a truncus, and a lifespan of 25-30 years. We sought to understand the unique cardiac anatomic and physiologic characteristics, with balanced circulation and low metabolic rate, by comparing the basic anatomy structures with focused echocardiography and cardiac magnetic resonance imaging. Twenty-four adult female African clawed frogs were randomly subjected to anatomic dissection (n = 4), echocardiography (n = 10), and cardiac magnetic resonance (n = 10). All anatomical features were confirmed and compared with echocardiography and cardiac magnetic resonance imaging. The main characteristics of the cardiovascular circulation in frogs are the following: Intact interatrial septum, with two separate atrio-ventricular valves, preventing atrial mixing of oxygenated and desaturated blood. Single spongiform ventricular cavity, non-conducive for homogeneous mixing. Single outlet with a valve-like mobile spiral structure, actively streaming into systemic and pulmonary arteries. Intact interatrial septum, spongiform ventricle, and valve-like spiral in the conus arteriosus are likely responsible for balanced systemic and pulmonary circulation in frogs, in spite of double-inlet and single-outlet ventricle.

Absorbable sutures for cardiopulmonary bypass purse strings in pediatric heart surgery.

BACKGROUND: Absorbable sutures, commonly used in general surgery, are not routinely used as purse strings for arterial and venous cannulation for cardiopulmonary bypass in pediatric heart surgery. The general concern is absorbable sutures could predispose to immediate postoperative bleeding; this safety concern has been evaluated in this retrospective study. MATERIALS AND METHODS: A single center, retrospective study, was conducted with criteria for inclusion patient <18 years of age, operation on with cardiopulmonary bypass for heart surgery from July 1, 2018 to June 30, 2020, with purse strings for cannulation performed with absorbable sutures. Data collection included demographics at the time of surgery, site of arterial and venous cannulation with absorbable purse strings, bleeding, required reoperation, related hospital mortality, and complications. RESULTS: One hundred and ninety-eight patients, mean ± standard deviation (SD) age of 1597 ± 3021 days, mean ± SD body weight of 15.9 ± 18.8 kg, were operated on using absorbable sutures for purse strings for arterial and venous cannulation: No bleeding was reported, either intraoperative or in the immediate postoperative period, related to the type of sutures used for purse strings for cannulation. No hospital deaths or complications related to the type of sutures were observed. CONCLUSIONS: Based on the results of our analysis, we can conclude that the utilization of purse strings absorbable sutures for arterial and venous cannulation for cardio-pulmonary bypass in children is safe in relationship to the intraoperative and immediate postoperative period. No complications related to the use of absorbable sutures have been observed in a large pediatric patient population.

Congenital heart defects and copy number variants associated with neurodevelopmental impairment.

A genetic etiology is identifiable in 20%-30% of patients with congenital heart defects (CHD). Chromosomal microarray analysis (CMA) can detect copy number variants (CNV) associated with CHD. In previous studies, the diagnostic yield of postnatal CMA testing ranged from 4% to 28% in CHD patients. However, incidental pathogenic CNV and variants of unknown significance are often discovered without any known association with CHD. The study objective was to describe the rate of pathogenic CNV associated with neurodevelopmental impairment (NDI) and compare clinical findings in CHD neonates with genetic results. A single-center retrospective review was performed on all consecutive newborns with CHD admitted to a tertiary neonatal intensive care unit from January 2013 to March 2019 (n = 525). CHD phenotypes were classified as per the National Birth Defect Prevention Study. CMA detected pathogenic CNV in 21.3% (61/287) of neonates, and karyotype or fluorescence in situ hybridization detected aneuploidies in an additional 11% of the overall cohort (58/525). Atrioventricular septal defects and conotruncal defects showed the highest diagnostic yield by CMA (28.6% and 27.2%, respectively). Among neonates with pathogenic CNV on CMA, 78.7% (48/61) were associated with NDI. Neonates with pathogenic CNV were smaller in length at birth compared to those with benign CNV or variants of unknown significance (p = 0.005) and were more likely to be discharged with an enteral feeding tube (p = 0.027). CMA can discover genetic variants associated with NDI and are common in neonates with CHD. Genetic testing in the neonatal period can heighten awareness of genetic risk for NDI.

Modern advances regarding interatrial communication in congenital heart defects.

BACKGROUND: The interatrial communication, one of the most frequent congenital heart defects, represents an important intracardiac shunt between systemic and pulmonary circulations. Direction and magnitude of the interatrial shunting depends upon several features, including defect size, shape and location, pressure difference between right and left atrium, and difference in right and left ventricular compliance. METHODS: In this review article, the presence or absence of interatrial communication, and its role, have been analyzed, as they can have a critical impact on the cardiovascular physiopathology, and the interatrial communication can prove to be either clinically harmful, useful or indispensable. Accordingly, the utility and role of the interatrial communication in modern congenital, pediatric and adult, disease has evolved, with modification of the indications to close, maintain patency, or create an interatrial communication. RESULTS: The interatrial communication and shunting can be manipulated to maximize the oxygen delivery to the tissues, accordingly with the underlying congenital heart defect. While not always relevant to patients with bi-ventricular circulations, this becomes extremely important in children and adults with complex congenital heart defects. CONCLUSIONS: With improving long-term survival for the vast majority of congenital heart patients, an advanced understanding of the role and utility of the interatrial communication, and of all the possibilities of its manipulation, is essential to improve the patient outcomes.

Can Erythropoietin Reduce Hypoxemic Neurological Damages in Neonates With Congenital Heart Defects?

Congenital heart defects (CHD), the most common cause of birth defects with increasing birth prevalence, affect nearly 1% of live births worldwide. Cyanotic CHD are characterized by hypoxemia, with subsequent reduced oxygen delivery to the brain, especially critical during brain development, beginning in the fetus and continuing through the neonatal period. Therefore, neonates with CHD carry a high risk for neurological comorbidities, even more frequently when there are associated underlying genetic disorders. We review the currently available knowledge on potential prevention strategies to reduce brain damage induced by hypoxemia during fetal development and immediately after birth, and the role of erythropoietin (EPO) as a potential adjunctive treatment. Maternal hyper-oxygenation had been studied as a potential therapeutic to improve fetal oxygenation. Despite demonstrating some effectiveness, maternal hyper-oxygenation has proven to be impractical for extensive clinical application, thus prompting the investigation of specific pathways for pharmacological intervention. Among those, the role of antioxidant pathways and Hypoxia Inducible Factors (HIF) have been studied for their involvement in the protective response to hypoxic injury. One of the proteins induced by HIF, EPO, has properties of being anti-apoptotic, antioxidant, and protective for neurons, astrocytes, and oligodendrocytes. In human trials, EPO administration in neonates with hypoxic ischemic encephalopathy (HIE) significantly reduced the neurological hypoxemic damages in several reported studies. Currently, it is unknown if the mechanisms of pathophysiology of cyanotic CHD are like HIE. Neonates with cyanotic CHD are exposed to both chronic hypoxemia and episodes of acute ischemia-reperfusion injury when undergo cardiopulmonary bypass surgery requiring aortic cross-clamp and general anesthesia. Our review supports future trials to evaluate the potential efficiency of EPO in reducing the hypoxemic neurologic damages in neonates with CHD. Furthermore, it suggests the need to identify early biomarkers of hypoxia-induced neurological damage, which must be sensitive to the neuroprotective effects of EPO.