Association of maternal weight gain in early pregnancy with congenital heart disease in offspring: a China birth cohort study.

OBJECTIVES: Little study has reported the association of maternal weight gain in early pregnancy with fetal congenital heart disease (CHD). We aimed to explore the potential relationship based on a China birth cohort while adjusting by multiple factors. DESIGN: Cohort study. SETTING: China birth cohort study conducted from 2017 to 2021. PARTICIPANTS: The study finally included 114 672 singleton pregnancies in the 6-14 weeks of gestation, without missing data or outliers, loss to follow-up or abnormal conditions other than CHD. The proportion of CHD was 0.65% (749 cases). PRIMARY AND SECONDARY OUTCOME MEASURES: Association between maternal pre-pregnancy weight gain and CHD in the offspring were analysed by multivariate logistic regression, with the unadjusted, minimally adjusted and maximally adjusted methods, respectively. RESULTS: The first-trimester weight gain showed similar discrimination of fetal CHD to that period of maternal body mass index (BMI) change (DeLong tests: p=0.091). Compared with weight gain in the lowest quartile (the weight gain less than 0.0 kg), the highest quartile (over 2.0 kg) was associated with a higher risk of fetal CHD in unadjusted (OR 1.36, 95% CI: 1.08 to 1.72), minimally adjusted (adjusted OR (aOR) 1.29, 95% CI: 1.02 to 1.62) and maximally adjusted (aOR 1.29, 95% CI: 1.02 to 1.63) models. The association remains robust in pregnant women with morning sickness, normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with folic acid (FA) and/or multivitamin supplementation. CONCLUSIONS AND RELEVANCE: Although the association of maternal pre-pregnancy weight gain on fetal CHD is weak, the excessive weight gain may be a potential predictor of CHD in the offspring, especially in those with morning sickness and other conditions that are routine in the cohort, such as normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with FA and/or multivitamin supplementation.

Trisomy 21-driven metabolite alterations are linked to cellular injuries in Down syndrome.

Down syndrome (DS) arises from a genetic anomaly characterized by an extra copy of chromosome 21 (exCh21). Despite high incidence of congenital diseases among DS patients, direct impacts of exCh21 remain elusive. Here, we established a robust DS model harnessing human-induced pluripotent stem cells (hiPSCs) from mosaic DS patient. These hiPSC lines encompassed both those with standard karyotype and those carrying an extra copy of exCh21, allowing to generate isogenic cell lines with a consistent genetic background. We unraveled that exCh21 inflicted disruption upon the cellular transcriptome, ushering in alterations in metabolic processes and triggering DNA damage. The impact of exCh21 was also manifested in profound modifications in chromatin accessibility patterns. Moreover, we identified two signature metabolites, 5-oxo-ETE and Calcitriol, whose biosynthesis is affected by exCh21. Notably, supplementation with 5-oxo-ETE promoted DNA damage, in stark contrast to the protective effect elicited by Calcitriol against such damage. We also found that exCh21 disrupted cardiogenesis, and that this impairment could be mitigated through supplementation with Calcitriol. Specifically, the deleterious effects of 5-oxo-ETE unfolded in the form of DNA damage induction and the repression of cardiogenesis. On the other hand, Calcitriol emerged as a potent activator of its nuclear receptor VDR, fostering amplified binding to chromatin and subsequent facilitation of gene transcription. Our findings provide a comprehensive understanding of exCh21's metabolic implications within the context of Down syndrome, offering potential avenues for therapeutic interventions for Down syndrome treatment.

Preconception folic acid supplementation for the prevention of birth defects: a prospective, population-based cohort study in mainland China.

BACKGROUND: Folic acid supplementation is recommended for reducing the risk of birth defects. We aimed to assess the protective association of periconception folic acid supplements with birth defects in real-world setting. METHODS: This prospective, population-based cohort study utilized national preconception registered data of married Chinese couples planning a pregnancy within 6 months between 2010 and 2012 in Mainland China. Participated women are freely provided folic acid starting 3 months before conception till 3 months after conception. Birth defects were self-reported at 42 days postpartumn followup. R software (v4.0.2) was applied for statistical analyses. RESULTS: Complete data of 567,547 couples with pregnancy outcomes and folic acid supplementation were extracted for final analysis. A total of 74.7% women were with folic acid supplementation, and 599 birth defects were self-reported. The odd of birth defects was lower among women taking folic acid compared to their counterparts not taking (0.102% vs 0.116%, P < 0.001). In the multiple logistic regression analyses, the odd of birth defects was lower among couples with maternal folic acid supplementation (OR = 0.78, 95%CI: 0.66-0.95, P = 0.011), especially decreased odd of neural tube defects (NTDs) (OR = 0.56, 95%CI: 0.39-0.82, P = 0.003). This association was confirmed by 1:4 and 1:10 case control analysis. Odds of birth defects were significantly lower among women with folic acid supplementation more than 3 months before pregnancy (P < 0.001), and moreover, the odds of cleft (P = 0.007) and NTDs (P = 0.007) were of notable decrease. CONCLUSION: This retrospective case cohort study provides programmatic evidence for public health strategy-making to for reducing the risk of NTDs and clefts.

Maternal exposure to folate antagonists and susceptibility to congenital heart disease in offspring: A systematic review and meta-analysis.

AIMS: The objective of this meta-analysis was to determine whether maternal exposure to folate antagonists is associated with increased rates of congenital heart disease in offspring. METHODS: A comprehensive search for articles in the MEDLINE (PubMed) and EMBASE databases published up to 21 August 2023 was performed. The search strategy was not limited by study design but only for articles in the English language. RESULTS: Analysis of 6 cohort studies and 5 cross-sectional studies, published between 1976 and 2020, showed significant increase in rate of congenital heart disease (odds ratio 1.55, 95% confidence interval, 1.28-1.87) when exposed to folate antagonists compared with the control. Further subgroup analysis showed the increased rate for exposure to both dihydrofolate reductase inhibitors and antiepileptic drugs separately. No differences were observed when analyses were stratified by timing of study. CONCLUSION: Administration of folate antagonists within the 12-week period preceding conception and throughout the second and third months of gestation exhibited a statistically significant elevation in the susceptibility to congenital heart diseases. Notably, the protective effect of folic acid supplementation was reported in cases of congenital heart disease linked to dihydrofolate reductase inhibitors but not that associated with antiepileptic drugs.

Exploring the healthcare needs and experiences of pregnant women with congenital heart disease: A qualitative study.

PROBLEM: Little is known regarding the healthcare needs and experiences of pregnant women with congenital heart disease (CHD) during pregnancy. BACKGROUND: Congenital heart diseases are the most common birth anomalies, and they embrace a wide range of defects ranging from mild to complex and life-threatening defects. Pregnancy carries many physiological and psychological changes that affect pregnant woman with CHD and need special attention and consideration. AIM: To explore the healthcare needs and experiences of Jordanian women with CHD during pregnancy. METHODS: A descriptive phenomenological design was used. Utilising purposive sampling, 15 participants were recruited. Data was collected using individualised semi-structured interviews. Interviews were recorded and transcribed verbatim. Data were analyzed using Colaizzi's method. FINDINGS: Three themes were identified: a) A broad spectrum of health needs during pregnancy, b) not being cared for, c) and the healthcare journey: Challenges and recommendations. Findings revealed that pregnancy in women with CHD is associated with many challenges and needs, and the lived healthcare experiences are mostly negative. DISCUSSION: This study addresses the healthcare needs and experiences of pregnant women with CHD during pregnancy. Our findings shed light on healthcare needs explored hidden aspects of the experiences of this vulnerable population and gave them the chance to make their voices heard. CONCLUSION: The study concluded that pregnant women with CHD experience hardship associated with negative challenges and personal suffering. The findings highlight the importance of the basic values and the need for a holistic approach and effective teamwork to minimise suffering among pregnant women with CHD.

Analysis of the hospitalization costs of surgical patients with congenital heart disease in the plateau region of western China, 2010-2019.

Background: Congenital heart disease (CHD) is one of the most common birth defects and consumes a substantial amount of health care resources. CHD leads to heavy economic burdens for families. However, there are limited data regarding the utilization of healthcare resources for CHD. The objectives of this study were to evaluate the composition, changing trends, and factors affecting hospitalization costs for patients with CHD in the western highlands area of China over a 10-year period. Methods: We conducted a study using the International Quality Improvement Collaborative for Congenital Heart Surgery (IQIC) database and information management system of The First Hospital of Lanzhou University between January 2010 and December 2019. Results: Among 3,087 patients hospitalized for CHD surgery, annual CHD hospitalization costs saw an increasing trend over the 10-year period, with an average growth rate of 4.6% per year. The major contributors to the hospitalization costs were surgery, surgical material, and drug costs. Length of stay (ß=0.203; 0.379; 0.474, P<0.01), age at hospitalization (ß=0.293, P<0.01), proportion of surgery (ß=0.090; -0.102; -0.122; -0.110, P<0.01) and drug costs (ß=-0.114; -0.147; -0.069, P<0.01), and use of traditional Chinese medicine (ß=0.141, P<0.01) were independent factors affecting average hospitalization costs. Conclusions: The financial burden of patients with CHD in the Chinese western highland region is high. Independent of inflation, CHD hospitalization costs are increasing. Measures taken by medical institutions to control the increase in drug costs, and to shorten the length of stay may be expected to have positive effects on reducing the financial burden of individuals with CHD and their families.

Recommendations for centers performing pediatric heart surgery in the United States.

Care and outcomes for the more than 40,000 patients undergoing pediatric and congenital heart surgery in the United States annually are known to vary widely. While consensus recommendations have been published across numerous fields as one mechanism to promote a high level of care delivery across centers, it has been more than two decades since the last pediatric heart surgery recommendations were published in the United States. More recent guidance is lacking, and collaborative efforts involving the many disciplines engaged in caring for these children have not been undertaken to date. The present initiative brings together professional societies spanning numerous care domains and congenital cardiac surgeons, pediatric cardiologists, nursing, and other healthcare professionals from diverse programs around the country to develop consensus recommendations for United States centers. The focus of this initial work is on pediatric heart surgery, and it is recommended that future efforts focus in detail on the adult congenital population. We describe the background, rationale, and methodology related to this collaborative effort, and recommendations put forth for Essential Care Centers (essential services necessary for any program), and Comprehensive Care Centers (services to optimize comprehensive and high-complexity care), encompassing structure, process, and outcome metrics across 14 domains.

Relationships between Maternal Folic Acid Supplementation and GATA4 Gene Polymorphisms in Patients with Non-Chromosomal Congenital Heart Disease: A Hospital-Based Case-Control Study in China.

This study aimed to investigate the relationships between maternal FA supplementation and nine single-nucleotide variants of the GATA4 gene in non-chromosomal CHD and further explore the gene-environment interactions associated with CHD. A total of 585 CHD patients and 600 controls were recruited in the case-control study. Maternal FA (FA-containing multivitamin) supplementation information and nine polymorphisms of the GATA4 gene were collected in this study. Adjusted ORs (aOR) and their 95% confidence intervals (CIs) were calculated using proper statistical methods to analyze the relationships between the two main exposures of interest with respect to CHD. After adjusting the suspicious confounding factors, a significantly increased risk for CHD in offspring was found with non-FA supplementation before/during the pregnancy to CHD in offspring (aOR = 1.58, 95% CI: 1.01-2.48). We suggested taking FA supplementation before/during the pregnancy to prevent CHD in offspring, especially in the preconception period (aOR = 0.53, 95% CI: 0.32-0.90). The genetic results showed that the polymorphisms of rs4841588, rs12458, and rs904018 under specific genotypes and genetic models were significantly related to CHD. The gene-environment interaction between rs10108052 and FA supplementation before/during pregnancy could increase the risk of CHD (aOR = 5.38, 95% CI: 1.67-17.09, Pinteraction = 0.004). Relationships between maternal FA supplementation and specific polymorphisms of the GATA4 gene, as well as the gene-environment interaction, were significantly associated with CHD in offspring.

A Parent-child yoga intervention for reducing attention deficits in children with congenital heart disease: the Yoga for Little Hearts Feasibility Study Protocol.

INTRODUCTION: Preschoolers and school-aged children with congenital heart disease (CHD) are at higher risk of attention deficit hyperactivity disorder (ADHD) compared with the general population. To this day, no randomised controlled trial (RCT) aiming to improve attention has been conducted in young children with CHD. There is emerging evidence indicating that parent-child yoga interventions improve attention and reduce ADHD symptoms in both typically developing and clinical populations. METHODS AND ANALYSIS: This is a single-blind, two-centre, two-arm trial during which 24 children with CHD and their parents will be randomly assigned to (1) a parent-child yoga intervention in addition to standard clinical care or (2) standard clinical care alone. All participants will undergo standardised assessments: (1) at baseline, (2) immediately post-treatment and (3) 6 months post-treatment. Descriptive statistics will be used to estimate the feasibility and neurodevelopmental outcomes. This feasibility study will evaluate: (1) recruitment capacity; (2) retention, drop-out and withdrawal rates during the yoga programme and at the 6-month follow-up; (3) adherence to the intervention; (4) acceptability of the randomisation process by families; (5) heterogeneity in the delivery of the intervention between instructors and use of home-based exercises between participants; (6) proportion of missing data in the neurodevelopmental assessments and (7) SD of primary outcomes of the full RCT in order to determine the future appropriate sample size. ETHICS AND DISSEMINATION: Ethical approval has been obtained by the Research Ethics Board of the Sainte-Justine University Hospital. The findings will be disseminated in peer-reviewed journals and conferences and presented to the Canadian paediatric grand round meetings. TRIAL REGISTRATION NUMBER: NCT05997680.

Recommendations for Centers Performing Pediatric Heart Surgery in the United States.

Care and outcomes for the more than 40,000 patients undergoing pediatric and congenital heart surgery in the United States annually are known to vary widely. While consensus recommendations have been published across numerous fields as one mechanism to promote a high level of care delivery across centers, it has been more than two decades since the last pediatric heart surgery recommendations were published in the United States. More recent guidance is lacking, and collaborative efforts involving the many disciplines engaged in caring for these children have not been undertaken to date. The present initiative brings together professional societies spanning numerous care domains and congenital cardiac surgeons, pediatric cardiologists, nursing, and other healthcare professionals from diverse programs around the country to develop consensus recommendations for United States centers. The focus of this initial work is on pediatric heart surgery, and it is recommended that future efforts focus in detail on the adult congenital population. We describe the background, rationale, and methodology related to this collaborative effort, and recommendations put forth for Essential Care Centers (essential services necessary for any program), and Comprehensive Care Centers (services to optimize comprehensive and high-complexity care), encompassing structure, process, and outcome metrics across 14 domains.

Health related quality of life in adults after late repair of tetralogy of fallot: experience from a low-middle income country.

PURPOSE: Without neonatal screening in low middle-income countries like Pakistan, Tetralogy of Fallot (TOF) is a congenital heart disease which frequently remains untreated beyond infancy. The purpose of this study is to determine and assess outcomes and health related quality of life (HRQOL) in patients who undergo complete repair of TOF as adults. METHODS: 56 patients who underwent complete TOF repair after 16 years of age were included. Patient data was collected via retrospective chart review, and a semi structured interview along with Short-Form 36 (SF-36) questionnaire were used to assess HRQOL. RESULTS: 66.1% of patients were male with the mean age at surgery of 22.3 ± 6.00. All patients had a post-operative NYHA Classification of I or II, 94.6% had an ejection fraction of ≥ 50% and 28.6% showed small residual lesions in follow-up echocardiograms. 32.1% of patients suffered post-operative morbidity. For the quantitative assessment using SF-36 scores, patients showed good scores of median 95 (65-100). A major cause of delay to treatment was lack of consensus between treatments offered by doctors in different parts of Pakistan. There was a pattern of 'inability to fit in' among patients who had had late TOF repair, despite self- reported improved HRQOL. CONCLUSION: Our results indicate that even with a delayed diagnosis, surgical repair of TOF produces good functional results. However, these patients face significant psychosocial issues. While early diagnosis remains the ultimate goal, patients undergoing late repair should be managed in more holistic manner with attention to psychological impact of the disease as well.

Nivel de conocimientos de enfermeros sobre medicina natural y tradicional para la rehabilitación de operados de cardiopatías congénitas

Introducción: la medicina natural y tradicional puede integrarse a la rehabilitación de los pacientes operados de cardiopatías congénitas, por lo que se requieren profesionales de enfermería con preparación para realizar las intervenciones específicas útiles en estos pacientes. Objetivo: identificar el nivel de conocimientos que posee el personal de enfermería sobre medicina natural y tradicional para la rehabilitación de las personas operadas de cardiopatía congénita. Materiales y métodos: se realizó un estudio descriptivo, transversal, en el Cardiocentro Pediátrico William Soler, de La Habana, durante el período junio-noviembre de 2019. Se aplicó una encuesta diseñada por los investigadores y validada por criterio de expertos. El universo lo constituyeron 100 enfermeras involucradas en el proceso de rehabilitación en práctica diaria, de las cuales se seleccionaron 60 mediante muestreo aleatorio simple. Para procesar la información se utilizó el software estadístico IMB SPSS Statistics. Resultados: se identificó el bajo nivel de conocimientos sobre las intervenciones de enfermería en medicina natural y tradicional para la rehabilitación de personas operadas de cardiopatías congénitas, resultado esperado por la insuficiente investigación en ese campo. Conclusiones: el estudio posibilitó identificar las debilidades relacionadas con el objeto de estudio, y propuso el diseño de un programa para la integración de la medicina natural y tradicional en las intervenciones de enfermería para la rehabilitación de personas operadas de cardiopatías congénitas.

Introduction: natural and traditional medicine can be integrated into the rehabilitation of patients operated of congenital heart diseases, so nursing professionals are required with training to perform the specific interventions that are useful in these patients. Objective: to identify the level of knowledge that the nursing staff have on natural and traditional medicine for the rehabilitation of patients operated of congenital heart disease. Materials and methods: across-sectional, descriptive study was carried out in the Pediatric Cardio Center William Soler, in Havana, during the period from June to November 2019. A survey, designed by the researchers and validated by expert criteria, was applied. The universe were 100 nurses involved in the rehabilitation process in their daily practice, of whom 60 were selected by simple random sampling. IMB SPSS Statistics software was used to process the information. Results: the low level of knowledge on nursing interventions in natural and traditional medicine for the rehabilitation of patients operated of congenital heart diseases was identified, an expected result due to insufficient research in this field. Conclusions: the study made it possible to identify weaknesses related to the object of study, and proposed the design of a program to integrate natural and traditional medicine into nursing interventions for the rehabilitation of patients operated of congenital heart diseases.

Association of maternal methionine synthase reductase gene polymorphisms with the risk of congenital heart disease in offspring: a hospital-based case-control study.

BACKGROUND: Evidence suggests that periconceptional folic acid supplementation may prevent congenital heart disease (CHD). Methionine synthase reductase (MTRR) is one of the key regulatory enzymes in the folate metabolic pathway. This study aimed to comprehensively evaluate the association of single nucleotide polymorphisms (SNPs) in the maternal MTRR gene with CHD risk in offspring. METHODS: A hospital-based case-control study involving 740 mothers of CHD cases and 683 health controls was conducted. RESULTS: The study showed that maternal MTRR gene polymorphisms at rs1532268 (C/T vs. C/C: aOR = 1.524; T/T vs. C/C: aOR = 3.178), rs1802059 (G/A vs. G/G: aOR = 1.410; A/A vs. G/G: aOR = 3.953), rs2287779 (G/A vs. G/G: aOR = 0.540), rs16879334 (C/G vs. C/C: aOR = 0.454), and rs2303080 (T/A vs. T/T: aOR = 0.546) were associated with the risk of CHD. And seven haplotypes were observed to be associated with the risk of CHD, T-G-A haplotype (OR = 1.298), C-A-C-C (OR = 4.824) and A-G haplotype (OR = 1.751) were associated with increased risk of CHD in offspring; A-A-A (OR = 0.773), T-A-A (OR = 0.557), G-A-C-C (OR = 0.598) and G-C (OR = 0.740) were associated with decreased risk of CHD in offspring. CONCLUSIONS: Maternal MTRR gene polymorphisms were associated with CHD in offspring, and its haplotypes have affected the occurrence of CHD. Furthermore, given the complexity and heterogeneity of CHD, the mechanisms by which these factors influence offspring cardiac development remain unknown, and studies in larger samples in an ethnically diverse population are needed.

Comparing the impact of comprehensive care with conventional care in children with congenital heart disease: a systematic review and meta-analysis.

Background: This study compares the impact of comprehensive care and conventional care on interventional therapy in children with congenital heart disease and to provide a reference basis for clinical care. Methods: Clinical randomized controlled trials (RCTs) examining care during interventional therapy in children with congenital heart disease were identified in the PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases using a combination of subject terms and free terms. The retrieval time was from the establishment of the database to November 27th, 2022. The control group was given conventional care and the experimental group was given comprehensive care on the basis of conventional care. The outcome indicators included one or more of postoperative complications (number of cases), puncture time (minutes), pain score (points), surgical operation time (minutes), X-ray exposure time (minutes) and length of hospital stay (days). Meta-analysis was performed using Stata 14.0 software. The publication bias test was conducted using Harbor's test. Results: A total of 24 RCTs were eventually included, and a total of 2,028 study subjects were enrolled, including 1,025 in the test group and 1,003 in the control group. Meta-analysis showed that comprehensive care resulted in a lower risk of complications [risk ratio (RR) =0.27; 95% confidence interval (CI): 0.21 to 0.34]. Furthermore, subjects who received comprehensive care had lower puncture time [standardized mean difference (SMD) =-2.50; 95% CI: -3.23 to -1.77], lower operating time [SMD (95% CI): -2.50 (-3.31, -1.68)], lower X-ray exposition time [SMD (95% CI): -1.29 (-2.51, -0.07)], shorter length of hospital stay [SMD (95% CI): -1.57 (-2.04, -1.09)], and lower pain scores [SMD (95% CI): -2.43 (-3.20, -1.65)]. Conclusions: Comprehensive care has higher clinical utility, which is worthy of clinical application and popularization.

How do Adults With Congenital Heart Disease Evaluate Their Clinical Care?

BACKGROUND: Almost 90% of patients with congenital heart disease (CHD) now reach adulthood. How do they evaluate the care they received? METHODS: Adults with CHD (ACHD) recruited for an international multi-center study (APPROACH-IS II) were posed 3 additional "questions" to determine their perceptions of the positive, negative, and areas for improvement of their clinical care. The findings underwent a thematic analysis. RESULTS: Of the 210 recruited, 183 completed the questionnaire, 147 answered the 3 "questions." Most appreciated open communication and support, a holistic approach, continuity of and readily accessible care conducted by experts, and with good outcomes. Less than half reported negative concerns which included loss of autonomy, distress from multiple and/or painful investigations, restricted lifestyles, medication side-effects, and anxiety about their CHD. Others found their reviews time-consuming with long travel times. Some complained of limited support, poor accessibility to services in rural areas, shortage of ACHD specialists, absence of tailored rehabilitation programs, and at times their own as well as their clinicians' limited understanding of their CHD. Suggestions for improvement included better communication, further education about their CHD, availability of simplified written information, mental health and support services, support groups, seamless transition to adult care and providing better prognostications, financial assistance, flexible appointments, telehealth reviews, and greater access to rural specialist care. CONCLUSIONS: In addition to providing optimal medical and surgical care for ACHD, clinicians need to be cognizant of their patients' concerns and proactive in addressing them.

Gestational palmitic acid suppresses embryonic GATA-binding protein 4 signaling and causes congenital heart disease.

Dysregulated maternal fatty acid metabolism increases the risk of congenital heart disease (CHD) in offspring with an unknown mechanism, and the effect of folic acid fortification in preventing CHD is controversial. Using gas chromatography coupled to either a flame ionization detector or mass spectrometer (GC-FID/MS) analysis, we find that the palmitic acid (PA) concentration increases significantly in serum samples of pregnant women bearing children with CHD. Feeding pregnant mice with PA increased CHD risk in offspring and cannot be rescued by folic acid supplementation. We further find that PA promotes methionyl-tRNA synthetase (MARS) expression and protein lysine homocysteinylation (K-Hcy) of GATA4 and results in GATA4 inhibition and abnormal heart development. Targeting K-Hcy modification by either genetic ablation of Mars or using N-acetyl-L-cysteine (NAC) decreases CHD onset in high-PA-diet-fed mice. In summary, our work links maternal malnutrition and MARS/K-Hcy with the onset of CHD and provides a potential strategy in preventing CHD by targeting K-Hcy other than folic acid supplementation.

Triiodothyronine Supplementation in Infants Undergoing Cardiopulmonary Bypass: A Randomized Controlled Trial.

Cardiopulmonary bypass (CPB) profoundly suppresses circulating thyroid hormone levels in infants. We performed a multicenter randomized placebo controlled trial to determine if triiodothyronine (T3) supplementation improves reduces time to extubation (TTE) in infants after CPB. Infants (n = 220) undergoing cardiac surgery with CPB and stratified into 2 age cohorts: ≤30 days and >30 days to <152 days were randomization to receive either intravenous triiodothyronine or placebo bolus followed by study drug infusion until extubated or at 48 hours, whichever preceded. T3 did not significantly alter the primary endpoint, TTE (hazard ratio for chance of extubation (1.08, 95% CI: 0.82-1.43, P = 0.575) in the entire randomized population with censoring at 21 days. T3 showed no significant effect on TTE (HR 0.82, 95% CI:0.55-1.23, P = 0.341) in the younger subgroup or in the older (HR 1.38, 95% CI:0.95-2.2, P = 0.095). T3 also did not significantly impact TTE during the first 48 hours while T3 levels were maintained (HR 1.371, 95% CI:0.942-1.95, P = 0.099) No significant differences occurred for arrhythmias or other sentinel adverse events in the entire cohort or in the subgroups. This trial showed no significant benefit on TTE in the entire cohort. T3 supplementation appears safe as it did not cause an increase in adverse events. The study implementation and analysis were complicated by marked variability in surgical risk, although risk categories were balanced between treatment groups.

Correlation of maternal drug use and cytochrome P450 geneticpolymorphisms with congenital heart disease in offspring / 西安交通大学学报(医学版)

【Objective】 To investigate the association of maternal medication during early pregnancy and cytochrome P450 (CYP450) genetic polymorphisms with the risk of congenital heart disease (CHD) in offspring. 【Methods】 We selected 127 pregnant women with CHD fetuses as the observation group and 132 pregnant women with non-CHD fetuses as the control group. Their characteristics and medication history were investigated, and CYP450 polymorphisms were detected. Logistic regression analysis was used to assess the association between maternal medication, CYP450 gene variations, and offspring CHD risk. 【Results】 The risk of CHD in offspring was higher in the observation group with maternal use of ovulation induction drugs, antihypertensive drugs, antibiotics, antidepressants, miscarriage prevention drugs, and traditional Chinese medicine (P<0.05). The A/T and T/T genotypes in rs1065852 and the C/G and G/G genotypes in rs16947 increased the risk of CHD in offspring compared to their respective genotypes. The risk of CHDs in offspring increased with the presence of risk genotypes (A/T or T/T) at the rs1065852 locus of the maternal CYP450 gene and early pregnancy medication use (P<0.05); the same was observed for risk genotypes (C/G or G/G) at the rs16947 locus (P<0.05). 【Conclusion】 Maternal medication during early pregnancy may be associated with offspring CHD, and the rs1065852 and rs16947 loci of CYP450 are significantly related to the risk of CHD in offspring.

Evaluation of Cardiovascular Toxicity of Folic Acid and 6S-5-Methyltetrahydrofolate-Calcium in Early Embryonic Development.

Folic acid (FA) is a synthetic and highly stable version of folate, while 6S-5-methyltetrahydrofolate is the predominant form of dietary folate in circulation and is used as a crystalline form of calcium salt (MTHF-Ca). The current study aims to evaluate the toxicity and safety of FA and MTHF-Ca on embryonic development, with a focus on cardiovascular defects. We began to analyze the toxicity of FA and MTHF-Ca in zebrafish from four to seventy-two hours postfertilization and assessed the efficacy of FA and MTHF-Ca in a zebrafish angiogenesis model. We then analyzed the differently expressed genes in in vitro fertilized murine blastocysts cultured with FA and MTHF-Ca. By using gene-expression profiling, we identified a novel gene in mice that encodes an essential eukaryotic translation initiation factor (Eif1ad7). We further applied the morpholino-mediated gene-knockdown approach to explore whether the FA inhibition of this gene (eif1axb in zebrafish) caused cardiac development disorders, which we confirmed with qRT-PCR. We found that FA, but not MTHF-Ca, could inhibit angiogenesis in zebrafish and result in abnormal cardiovascular development, leading to embryonic death owing to the downregulation of eif1axb. MTHF-Ca, however, had no such cardiotoxicity, unlike FA. The current study thereby provides experimental evidence that FA, rather than MTHF-Ca, has cardiovascular toxicity in early embryonic development and suggests that excessive supplementation of FA in perinatal women may be related to the potential risk of cardiovascular disorders, such as congenital heart disease.