Association of congenital heart disease and neurodevelopmental disorders: an observational and Mendelian randomization study.

BACKGROUND: This study aims to thoroughly study the connection between congenital heart disease (CHD) and neurodevelopmental disorders (NDDs) through observational and Mendelian randomization (MR) designs. METHODS: This observational study uses data from the National Survey of Children's Health (2020-2021). Multivariable logistic regression and propensity score matching (PSM) were performed to analyze the association. PSM was used to minimize bias for covariates such as age, race, gender, maternal age, birth weight, concussion or brain injury, preterm birth, cerebral palsy, Down syndrome, and other inherited conditions. In MR analyses, inverse variance-weighted measures, weighted median, and MR-Egger were employed to calculate causal effects. RESULTS: A total of 85,314 children aged 0-17 were analyzed in this study. In regression analysis, CHD (p = 0.04), the current heart condition (p = 0.03), and the severity of current heart condition (p < 0.05) had a suggestive association with speech or language disorders. The severity of current heart condition (p = 0.08) has a potential statistically significant association with attention deficit hyperactivity disorder(ADHD). In PSM samples, ADHD(p = 0.003), intellectual disability(p = 0.012), and speech or language disorders(p < 0.001) were all significantly associated with CHD. The severity of current heart condition (p < 0.001) also had a significant association with autism. MR analysis did not find causality between genetically proxied congenital cardiac malformations and the risk of NDDs. CONCLUSIONS: Our study shows that children with CHD have an increased risk of developing NDDs. Heart conditions currently and severity of current heart conditions were also significantly associated with these NDDs. In the future, we need to try more methods to clarify the causal relationship between CHD and NDDs.

Relationship of interleukin-6-572C/G promoter polymorphism and serum levels to post-percutaneous coronary intervention restenosis.

BACKGROUND: It has been recently reported that inflammatory mechanisms play an important role in in-stent restenosis (ISR) processes. Inflammatory factors after percutaneous coronary intervention (PCI) for dynamic monitoring can probably predict ISR. Functional polymorphisms in the promoter region of genes coding for inflammatory factors might be important for determining the magnitude of the inflammatory response. Thus, in the present study, we aimed to investigate the serial changes in serum interleukin-6 (IL-6) levels before and after PCI and the relationship between the -572C/G polymorphism in the promoter region of the IL-6 gene and ISR. We also discussed genetic polymorphisms in the inflammatory response to PCI. METHODS: A total of 437 patients who successfully underwent bare metal stent (BMS) implantation with a follow-up angiography were divided into an ISR group (n = 166) and a non-ISR (NISR) group (n = 271). The IL-6 gene promoter polymorphism at position -572 was determined by restricted fragment length polymorphism using the polymerase chain reaction (PCR-RFLP) method. The serum IL-6 levels before and one day, five days and 180 days after PCI were determined by the radioimmunoassay method. RESULTS: ISR patients showed higher IL-6 serum levels than NISR patients before PCI ((324.42 ± 28.14) ng/L vs. (283.22 ± 47.30) ng/L, P < 0.001), and one day post-PCI IL-6 serum levels in the ISR group also showed a significantly higher level than in the NISR group (P < 0.001). Increased IL-6 after PCI persisted at a statistically significant level throughout the study in ISR patients, whereas IL-6 levels had normalized five days after the procedure in NISR patients. One day post-PCI serum IL-6 level was the most accurate marker for diagnosis of ISR, the area under the ROC curve being 0.927 (95%CI 0.878 - 0.977). The cut-off value for IL-6 to predict ISR was over 355.50 ng/L, with a sensitivity of 0.968 and a specificity of 0.865. There were no significant differences in frequencies of -572 genotype and allele between the two groups (P > 0.05). One day post-PCI IL-6 serum levels in patients with the G allele was significantly higher than in patients without the G allele ((366.99 ± 49.37) ng/L vs. (347.20 ± 55.30) ng/L, P < 0.05). In the ISR group, one day post-PCI serum levels of IL-6 in patients with the G allele was also significantly higher than that in patients without the G allele ((405.67 ± 26.56) ng/L vs. (375.69 ± 38.81) ng/L, P < 0.05). Multivariate Logistic regression analysis revealed positive correlations between male gender, one day post-PCI serum levels of IL-6, the pre-PCI degree of stenosis, the length of the target lesion stenosis, and restenosis; and there were negative correlations between the stent diameter, the diameter of the reference vessel before stent implantation and restenosis. CONCLUSIONS: IL-6 is an early post-PCI inflammatory cytokine, and one day post-PCI serum IL-6 level is an independent risk factor for restenosis. The frequencies of IL-6 gene -572 genotype and allele are not different between patients with and without ISR in a Chinese Tianjin Han population, but carrying the IL-6 -572G allele is likely to increase an individual's susceptibility to ISR by promoting serum IL-6 levels.

[Myocardial injury and inflammatory response after interventional therapy in children with congenital heart disease].

OBJECTIVE: To study myocardial injury and inflammatory response within 7 days after interventional therapy in children with congenital heart disease (CHD). METHODS: A total of 77 children with CHD, including 12 cases of ventricular septal defect (VSD), 14 cases of atrial septal defect (ASD), 14 cases of pulmonary stenosis (PS) and 37 cases of patent ductus arteriosus (PDA), were enrolled. The levels of myocardial enzyme (AST, CK and CKMB), cardiac troponin I (cTnI) and CRP in serum were measured before operation, immediately after operation, and 6 hrs, 24 hrs, 72 hrs and 7 days after operation. RESULTS: Serum AST levels in the VSD group were significantly higher than the other CHD groups immediately after operation, and 6 hrs and 24 hrs after operation (P<0.05). There were significant differences in serum CK and CKMB levels among the four CHD groups immediately and 6 hrs after operation (P<0.05), and the highest serum CK and CKMB levels were found in the VSD group. Serum CRP levels in the PDA group were significantly higher than the other CHD groups 72 hrs and 7 days after operation (P<0.05). Compared with before operation, serum AST levels increased significantly in all four CHD groups 6 and 24 hrs after operation groups (P<0.05). Serum CK and CKMB levels increased significantly in the VSD group immediately and 6 hrs after operation (P<0.05). Serum cTnI levels increased significantly in the VSD, PDA and PS groups immediately and 6 hrs after operation (P<0.05). The PDA group showed increased CRP levels 24 hrs, 72 hrs and 7 days after operation (P<0.05). CONCLUSIONS: Minor myocardial injury can be noted within 7 days after interventional therapy in children with CHD and mainly occurs between immediately and 24 hrs after operation. The injury is more significant in VSD cases. The interventional therapy does not cause significant inflammation.

[Relationship of interleukin-10 gene polymorphism with restenosis after percutaneous coronary intervention in Chinese].

OBJECTIVE: To investigate the relationship of interleukin-10 gene (IL-10) polymorphism and the serum IL-10 level with restenosis after percutaneous coronary intervention (PCI) in Tianjin Chinese Han population and study the effect of IL-10 gene polymorphism on serum IL-10 level. METHODS: Four hundred and thirty-seven patients who successfully underwent PCI with a follow-up angiography were divided into a restenosis group (n = 166) and non-restenosis group (n = 271). The IL-10 gene promoter polymorphism at position -592 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Meanwhile their serum IL-10 level before and 24 h after PCI was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: (1) There was no significant difference in frequencies of -592 genotypes and alleles between the two groups (P > 0.05); (2) The 24 h post-PCI IL-10 serum level of restenosis group was significantly lower than that of the non-restenosis group [(82.67 ± 35.02) ng/L vs. (95.08 ± 32.26) ng/L, P < 0.05]; (3) The serum level of the A allele carriers (AA+AC) was significantly lower than that of the CC carriers [(86.13 ± 34.77) ng/L vs. (102.50 ± 27.52) ng/L, P < 0.05]; (4) In the restenosis group, the 24 h post-PCI serum level of IL-10 in the A allele carriers was also significantly lower than that in those without the A allele [(78.51 ± 34.09) ng/L vs. (102.19 ± 33.66) ng/L, P < 0.05]; (5) Logistic regression analysis revealed positive correlations between acute coronary syndrome patients, pre-PCI degree of stenosis, length of target stenosis lesion and restenosis (OR = 5.90, 1.86, 2.83 respectively); and there were negative correlations between 24 h post-PCI serum level of IL-10, the stent diameter, the diameter of reference vessel before stent implantation and restenosis(OR = 0.99, 0.70, 0.46 respectively). CONCLUSION: (1) The IL-10 gene -592 C/A polymorphism was not associated with restenosis in the Tianjin Chinese Han population; (2) IL-10 is an early post-PCI inflammatory cytokine, 24 h post-PCI serum IL-10 level was an independent predictive factor for restenosis, the IL-10 A allele carriers may have increased incidence of in-stent restenosis (ISR) by reducing the serum IL-10 levels.