A systematic review and meta-analysis of school and cognitive function domains of health-related quality of life measures for children and young adults with congenital heart disease

\ua9 2023 The Authors. Birth Defects Research published by Wiley Periodicals LLC.Background: Research on cognitive and school functioning domains of health-related quality of life (HRQOL) for children and adolescents with congenital heart disease (CHD) presents inconsistencies. Objectives: To summarize and synthesize data on school and cognitive function domains of HRQOL for children and young people (CYP) with CHD. Methods: Five electronic databases MEDLINE, Scopus, PsycINFO, EMBASE, ERI, and citations were systematically searched. We included original-research articles reporting the cognitive and school function domains of HRQOL for children and young people with CHD (child and parent reports included). Both fixed and random-effects meta-analyses were performed to estimate pooled mean test scores for cognitive and school function. A total of 34 studies met our inclusion criteria and were synthesized narratively, 17 studies were included in formal meta-analyses. Results: Self-reported cognitive function was lower for children and young people with CHD than healthy controls (SMD −0.28 (−0.42, −0.15)). Parental reports demonstrated similar results to self-reports (SMD −0.54 (−0.91, −0.18)). School function was lower in children and young people with CHD compared with healthy controls in self-reported (SMD −0.30 (−0.48, −0.13)) and parent reported HRQOL (SMD −0.49 (0.64, −0.36)). Self-reported school function domain scores were lower for young (<8 years) (SMD −0.65 (−1.32, 0.03)) and older children (8–18 years) (SMD −0.25 (−0.47, −0.03)) with CHD than their peers. Similarly, parents reported lower school function domain scores for young (<8 years) (SMD −0.68 (−1.29, −0.07)) and older (8–18 years) (SMD −0.46 (−068, −0.25)) children with CHD than typically developing peers. Conclusion: Children born with CHD may experience lower cognitive and school function HRQOL scores than healthy controls (self and proxy-report). This is consistent with a subgroup meta-analysis of young (<8 years) and older (8 years old or more) children with CHD reporting lower school function scores compared to controls

Increased Power for Detection of Parent-of-Origin Effects via the Use of Haplotype Estimation

Parent-of-origin (or imprinting) effects relate to the situation in which traits are influenced by the allele inherited from only one parent and the allele from the other parent has little or no effect. Given SNP genotype data from case-parent trios, the parent of origin of each allele in the offspring can often be deduced unambiguously; however, this is not true when all three individuals are heterozygous. Most existing methods for investigating parent-of-origin effects operate on a SNP-by-SNP basis and either perform some sort of averaging over the possible parental transmissions or else discard ambiguous trios. If the correct parent of origin at a SNP could be determined, this would provide extra information and increase the power for detecting the effects of imprinting. We propose making use of the surrounding SNP information, via haplotype estimation, to improve estimation of parent of origin at a test SNP for case-parent trios, case-mother duos, and case-father duos. This extra information is then used in a multinomial modeling approach for estimating parent-of-origin effects at the test SNP. We show through computer simulations that our approach has increased power over previous approaches, particularly when the data consist only of duos. We apply our method to two real datasets and find a decrease in significance of p values in genomic regions previously thought to possibly harbor imprinting effects, thus weakening the evidence that such effects actually exist in these regions, although some regions retain evidence of significant effects

Preoperative behavioural intervention to reduce drinking before elective orthopaedic surgery: the PRE-OP BIRDS feasibility RCT.

Background Heavy alcohol consumption is associated with an increased risk of postoperative complications and extended hospital stay. Alcohol consumption therefore represents a modifiable risk factor for surgical outcomes. Brief behavioural interventions have been shown to be effective in reducing alcohol consumption among increased risk and risky drinkers in other health-care settings and may offer a method of addressing preoperative alcohol consumption. Objectives To investigate the feasibility of introducing a screening process to assess adult preoperative drinking levels and to deliver a brief behavioural intervention adapted for the target population group. To conduct a two-arm (brief behavioural intervention plus standard preoperative care vs. standard preoperative care alone), multicentre, pilot randomised controlled trial to assess the feasibility of proceeding to a definitive trial. To conduct focus groups and a national web-based survey to establish current treatment as usual for alcohol screening and intervention in preoperative assessment. Design A single-centre, qualitative, feasibility study was followed by a multicentre, two-arm (brief behavioural intervention vs. treatment as usual), individually randomised controlled pilot trial with an embedded qualitative process evaluation. Focus groups and a quantitative survey were employed to characterise treatment as usual in preoperative assessment. Setting The feasibility study took place at a secondary care hospital in the north-east of England. The pilot trial was conducted at three large secondary care centres in the north-east of England. Participants Nine health-care professionals and 15 patients (mean age 70.5 years, 86.7% male) participated in the feasibility study. Eleven health-care professionals and 68 patients (mean age 66.2 years, 80.9% male) participated in the pilot randomised trial. An additional 19 health-care professionals were recruited to one of three focus groups, while 62 completed an electronic survey to characterise treatment as usual. Interventions The brief behavioural intervention comprised two sessions. The first session, delivered face to face in the preoperative assessment clinic, involved 5 minutes of structured brief advice followed by 15–20 minutes of behaviour change counselling, including goal-setting, problem-solving and identifying sources of social support. The second session, an optional booster, took place approximately 1 week before surgery and offered the opportunity to assess progress and boost self-efficacy. Main outcome measures Feasibility was assessed using rates of eligibility, recruitment and retention. The progression criteria for a definitive trial were recruitment of ≥ 40% of eligible patients and retention of ≥ 70% at 6-month follow-up. Acceptability was assessed using themes identified in qualitative data. Results The initial recruitment of eligible patients was low but improved with the optimisation of recruitment processes. The recruitment of eligible participants to the pilot trial (34%) fell short of the progression criteria but was mitigated by very high retention (96%) at the 6-month follow-up. Multimethod analyses identified the methods as acceptable to the patients and professionals involved and offers recommendations of ways to further improve recruitment. Conclusions The evidence supports the feasibility of a definitive trial to assess the effectiveness of brief behavioural intervention in reducing preoperative alcohol consumption and for secondary outcomes of surgical complications if recommendations for further improvements are adopted. Trial registration Current Controlled Trials ISRCTN36257982. Funding This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 12. See the National Institute for Health Research Journals Library website for further project information

Prevalence of congenital heart defects in Europe, 2008-2015: A registry‐based study

Background: The total prevalence of congenital heart defects (CHDs) varies by populations and over time. Studies that examine trends in the prevalence of CHD in different regions may shed light on our understanding of the occurrence of CHD and the impact of different risk factors. Objectives: To examine trends in total and live birth prevalence of nonsyndromic CHD in Europe between the years 2008 and 2015 and to investigate if the decreasing trend reported by previous studies is continuing. Methods: Cases of CHD delivered between January 1, 2008 and December 31, 2015 notified to 25 population-based EUROCAT (European Surveillance of Congenital Anomalies) registries in 14 countries, formed the population-based case-series. Prevalence (total/live) rates and 95% confidence intervals were calculated as the number of cases per 10,000 births (live and stillbirths). Time trends in prevalence of all nonsyndromic CHDs and for three CHD severity groups (very severe, severe, and less severe) were plotted using a Poisson regression multilevel approach. Results: The total prevalence of nonsyndromic CHD was 57.1 per 10,000 births (live births and stillbirths) for the 8-year period and remained stable across the three CHD severity groups while the live birth prevalence was 60.2 per 10,000 births. There was considerable variation in the reported total CHD prevalence and the direction of trends by registry. A decreasing prevalence ofCHD was observed for the Norway and England/Wales registries, whereas the CHD prevalence increased for registries in Italy and Croatia. Conclusions: The total prevalence of CHD in Europe between the years 2008 and 2015 remained stable for all CHD and across the three CHD severity groups. The decreasing trend reported by previous studies has not continued. However, we found significant differences in the total and live birth prevalence by registry.info:eu-repo/semantics/publishedVersio

Maternal age and the prevalence of congenital heart defects in Europe, 1995-2015:A register-based study

BACKGROUND: Evidence on the direction and strength of association between maternal age and the prevalence of congenital heart defects (CHD) in different age group categories is conflicting. Some studies have illustrated different trends with an increase in prevalence in younger and older age groups while other studies have reported a linear relationship. Given the increase in maternal age over recent years, it is important to study the CHD prevalence by maternal age.OBJECTIVES: To examine the association between maternal age and the prevalence of CHD in Europe between 1995 and 2015 using population-based data from 24 registries belonging to the European Surveillance of Congenital Anomalies (EUROCAT) network.METHODS: Associations over time of all nonsyndromic CHD according to maternal age category and for three CHD severity groupings (severity group I: very severe; severity group II: severe; severity group III: less severe) were examined using Bayesian multilevel Poisson regression modeling. Further subgroup analyses were undertaken within four maternal age-bands: ≤24, 25-29, 30-34 and 35-44 years. Descriptive summaries are also presented.RESULTS: There were 51,608 nonsyndromic CHD cases in Europe over the 20-year study period. Total prevalence for all CHD combined was increased for younger mothers (≤24 years) and for mothers 35-44 years of age when compared with mothers aged 25-29 years (reference group) (IRR: 1.05, 95% CI: 1.02, 1.07). The total prevalence was increased for severity group I (very severe) only for younger mothers compared to those aged 25-29 years (IRR: 1.14, 95% CI: 1.04, 1.23). We found an increased prevalence of the following CHD subtypes: double outlet right ventricle (IRR:1.33, 95% CI: 1.09, 1.60), hypoplastic left heart syndrome (IRR: 1.18, 95% CI: 1.05, 1.32), hypoplastic right heart syndrome (IRR: 1.41, 95% CI: 1.05, 1.84), atrioventricular septal defect (IRR: 1.15, 95% CI: 1.01, 1.32), coarctation of aorta (IRR: 1.15, 95% CI: 1.03, 1.28) and atrial septal defect (IRR: 1.08, 95% CI: 1.02, 1.13). For older mothers (35-44 years) compared to the reference category, we observed an increased risk in the prevalence for severity group II (IRR: 1.09, 95% CI: 1.03, 1.14), severity group III (IRR: 1.05, 95% CI: 1.01, 1.08) and an increased prevalence of the CHD subtypes: Pulmonary valve stenosis (IRR: 1.22, 95% CI: 1.09, 1.34), ASD (IRR: 1.07, 95% CI: 1.02, 1.13), CoA (IRR: 1.18, 95% CI: 1.06, 1.32) and Tetralogy of Fallot (IRR: 1.14, 95% CI: 1.01, 1.28). Finally, for all age categories compared to the reference category, different associations of ASD and an increased prevalence of CoA was also observed.CONCLUSIONS: Based on data for cases of CHD from 24 European population-based registries, evidence of a positive association between maternal age and the total prevalence of CHD for younger (≤24 years old) and older (35-44 years old) mothers was observed. The results suggest that young maternal age (≤24 years old) is a factor associated with severe CHD phenotypes while a positive association between advanced maternal age (35-44 years old) and mild CHD phenotypes was observed.</p

Maternal age and the prevalence of congenital heart defects in Europe, 1995–2015: A register‐based study

Background: Evidence on the direction and strength of association between maternal age and the prevalence of congenital heart defects (CHD) in different age group categories is conflicting. Some studies have illustrated different trends with an increase in prevalence in younger and older age groups while other studies have reported a linear relationship. Given the increase in maternal age over recent years, it is important to study the CHD prevalence by maternal age. Objectives: To examine the association between maternal age and the prevalence of CHD in Europe between 1995 and 2015 using population-based data from 24 registries belonging to the European Surveillance of Congenital Anomalies (EUROCAT) network. Methods: Associations over time of all nonsyndromic CHD according to maternal age category and for three CHD severity groupings (severity group I: very severe; severity group II: severe; severity group III: less severe) were examined using Bayesian multilevel Poisson regression modeling. Further subgroup analyses were undertaken within four maternal age-bands: ≤24, 25–29, 30–34 and 35–44 years. Descriptive summaries are also presented. Results: There were 51,608 nonsyndromic CHD cases in Europe over the 20-year study period. Total prevalence for all CHD combined was increased for younger mothers (≤24 years) and for mothers 35–44 years of age when compared with mothers aged 25–29 years (reference group) (IRR: 1.05, 95% CI: 1.02, 1.07). The total prevalence was increased for severity group I (very severe) only for younger mothers compared to those aged 25–29 years (IRR: 1.14, 95% CI: 1.04, 1.23). We found an increased prevalence of the following CHD subtypes: double outlet right ventricle (IRR:1.33, 95% CI: 1.09, 1.60), hypoplastic left heart syndrome (IRR: 1.18, 95% CI: 1.05, 1.32), hypoplastic right heart syndrome (IRR: 1.41, 95% CI: 1.05, 1.84), atrioventricular septal defect (IRR: 1.15, 95% CI: 1.01, 1.32), coarctation of aorta (IRR: 1.15, 95% CI: 1.03, 1.28) and atrial septal defect (IRR: 1.08, 95% CI: 1.02, 1.13). For older mothers (35–44 years) compared to the reference category, we observed an increased risk in the prevalence for severity group II (IRR: 1.09, 95% CI: 1.03, 1.14), severity group III (IRR: 1.05, 95% CI: 1.01, 1.08) and an increased prevalence of the CHD subtypes: Pulmonary valve stenosis (IRR: 1.22, 95% CI: 1.09, 1.34), ASD (IRR: 1.07, 95% CI: 1.02, 1.13), CoA (IRR: 1.18, 95% CI: 1.06, 1.32) and Tetralogy of Fallot (IRR: 1.14, 95% CI: 1.01, 1.28). Finally, for all age categories compared to the reference category, different associations of ASD and an increased prevalence of CoA was also observed. Conclusions: Based on data for cases of CHD from 24 European populationbased registries, evidence of a positive association between maternal age and the total prevalence of CHD for younger (≤24 years old) and older (35–44 years old) mothers was observed. The results suggest that young maternal age (≤24 years old) is a factor associated with severe CHD phenotypes while a positive association between advanced maternal age (35–44 years old) and mild CHD phenotypes was observed.info:eu-repo/semantics/publishedVersio

Genome-wide association study identifies loci on 12q24 and 13q32 associated with Tetralogy of Fallot

We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot (TOF), using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (P = 1.4 × 10−7) and replicated convincingly (P = 3.9 × 10−5) in 798 cases and 2931 controls [per allele odds ratio (OR) = 1.27 in replication cohort, P = 7.7 × 10−11 in combined populations]. Single nucleotide polymorphisms in the glypican 5 gene on chromosome 13q32 were also associated (P = 1.7 × 10−7) and replicated convincingly (P = 1.2 × 10−5) in 789 cases and 2927 controls (per allele OR = 1.31 in replication cohort, P = 3.03 × 10−11 in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of TO

Genome-Wide Analysis in Over 1 Million Individuals of European Ancestry Yields Improved Polygenic Risk Scores for Blood Pressure Traits

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P \u3c 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits