Dataset Information

Transcriptomics integrated with metabolomics reveals partial molecular mechanisms of nutritional risk and neurodevelopment in children with congenital heart disease.

ABSTRACT:

Purpose

To explore molecular mechanisms affecting nutritional risk and neurodevelopment in children with congenital heart disease (CHD) by combining transcriptome and metabolome analysis.

Methods

A total of 26 blood and serum samples from 3 groups of children with CHD low nutritional risk combined with normal neurodevelopment (group A), low nutritional risk combined with neurodevelopmental disorders (group B) and high nutritional risk combined with normal neurodevelopment (group C) were analyzed by transcriptome and metabolomics to search for differentially expressed genes (DEGs) and metabolites (DEMs). Functional analysis was conducted for DEGs and DEMs. Further, the joint pathway analysis and correlation analysis of DEGs and DEMs were performed.

Results

A total of 362 and 1,351 DEGs were detected in group B and C compared to A, respectively. A total of 6 and 7 DEMs were detected in group B and C compared to A in positive mode, respectively. There were 39 and 31 DEMs in group B and C compared to A in negative mode. Transcriptomic analysis indicated that neurodevelopment may be regulated by some genes such as NSUN7, SLC6A8, CXCL1 and LCN8, nutritional risk may be regulated by SLC1A3 and LCN8. Metabolome analysis and joint pathway analysis showed that tryptophan metabolism, linoleic and metabolism and glycerophospholipid metabolism may be related to neurodevelopment, and glycerophospholipid metabolism pathway may be related to nutritional risk.

Conclusion

By integrating transcriptome and metabolome analyses, this study revealed key genes and metabolites associated with nutritional risk and neurodevelopment in children with CHD, as well as significantly altered pathways. It has important clinical translational significance.

SUBMITTER: Gao M

PROVIDER: S-EPMC11341388 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Transcriptomics integrated with metabolomics reveals partial molecular mechanisms of nutritional risk and neurodevelopment in children with congenital heart disease.

Gao Minglei M Shen Yang Y Yang Ping P Yuan Chang C Sun Yanan Y Li Zipu Z

Frontiers in cardiovascular medicine 20240809

<h4>Purpose</h4>To explore molecular mechanisms affecting nutritional risk and neurodevelopment in children with congenital heart disease (CHD) by combining transcriptome and metabolome analysis.<h4>Methods</h4>A total of 26 blood and serum samples from 3 groups of children with CHD low nutritional risk combined with normal neurodevelopment (group A), low nutritional risk combined with neurodevelopmental disorders (group B) and high nutritional risk combined with normal neurodevelopment (group C ...[more]

PMID: 39185136

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Project description:IntroductionWorldwide, congenital heart disease is the principal heart disease in children and constitutes one of the major causes of infant mortality, particularly in developing countries. Infants and children with congenital heart disease exhibit a range of delays in weight gain and growth. In some instances, the delay can be relatively mild, whereas in other cases, cause the failure to thrive.ObjectivesTo determine the nutritional status and associated factors of pediatric patients with congenital heart disease.Material and methodA cross sectional analytical study conducted over a period of 6 months (Feb to Jul 2020). A total of 228 subjects with congenital heart disease who visited the cardiac center during the study period where included until the calculated sample size attained. Data is collected from patient's card and their care giver. Data was then analyzed using Statistical Package for Social Sciences (SPSS) for windows version 25.0. Odds Ratio with 95% Confidence Interval (CI) was used to determine the effect of the independent variables on the outcome variable and P-value less than 0.05 was considered statistically significant.ResultsA total of 228 children ranging from 3month to 17yrs of age with mean age of 4.7 years (SD = 3.8 years) were included in the study. Most of the subjects had acyanotic heart disease accounting for 87.7%. The overall prevalence of wasting, underweight and stunting were 41.3%, 49.1% and 43% respectively. Children with congenital heart disease and having pulmonary hypertension, were found more likely to develop wasting compared to those without pulmonary hypertension with an odds of 1.9 (95% CI: 1.0-3.4) and also have greater chance of stunting with an odds of 1.9 (95% CI: 1.0-3.4). Children 5 to 10 years of age were 2.3 times more likely to be underweight.ConclusionMalnutrition is a major problem in pediatric patients with congenital heart disease. Pulmonary hypertension and older age are associated with increased risk of undernutrition.

Project description:BackgroundNeurodevelopmental impairment is common in children with congenital heart disease (CHD), but postnatal variables explain only 30% of the variance in outcomes. To explore whether the antecedents for neurodevelopmental disabilities might begin in utero, we analyzed whether fetal brain volume predicted subsequent neurodevelopmental outcome in children with CHD.MethodsFetuses with isolated CHD and sociodemographically comparable healthy control fetuses underwent fetal brain magnetic resonance imaging and 2-year neurodevelopmental evaluation with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) and the Adaptive Behavior Assessment System, Third Edition (ABAS-3). Hierarchical regression evaluated potential predictors of Bayley-III and ABAS-3 outcomes in the CHD group, including fetal total brain volume adjusted for gestational age and sex, sociodemographic characteristics, birth measures, and medical history.ResultsThe CHD group (n=52) had lower Bayley-III cognitive, language, and motor scores than the control group (n=26), but fetal brain volumes were similar. Within the CHD group, larger fetal total brain volume correlated with higher Bayley-III cognitive, language, and motor scores and ABAS-3 adaptive functioning scores (r=0.32-0.47; all P<0.05), but this was not noted in the control group. Fetal brain volume predicted 10% to 21% of the variance in neurodevelopmental outcome measures in univariate analyses. Multivariable models that also included social class and postnatal factors explained 18% to 45% of the variance in outcome, depending on developmental domain. Moreover, in final multivariable models, fetal brain volume was the most consistent predictor of neurodevelopmental outcome across domains.ConclusionsSmall fetal brain volume is a strong independent predictor of 2-year neurodevelopmental outcomes and may be an important imaging biomarker of future neurodevelopmental risk in CHD. Future studies are needed to support this hypothesis. Our findings support inclusion of fetal brain volume in risk stratification models and as a possible outcome in fetal neuroprotective intervention studies.

Project description:To determine whether children who underwent resection of a congenital lung abnormality (CLA) are at higher risk for neurodevelopmental impairments than peers in the general population. The study population consisted of children born between 1999-2018 who underwent resection of a symptomatic CLA. Neurocognitive development (intelligence, memory, attention, visuospatial processing, executive functioning) and motor function of this population are monitored through our structured, prospective longitudinal follow-up program at the ages of 30 months, 5, 8, and 12 years. We compared study population scores with Dutch norm values using one-sample t-tests and one-sample binominal proportion tests. Forty-seven children were analyzed. The 8-year-olds showed significant impairments in sustained attention through the Dot Cancellation Test (mean z-scores -2.4; [-4.1; -0.8], p = 0.006 and -7.1; [-12.8; -1.4], p = 0.02 for execution speed and fluctuations respectively). Visuospatial memory was impaired at 8 years, though only in 1 out of 3 assessment tools (Rey Complex Figure Test z-scores (-1.0; [-1.5; -0.5], p < 0.001). Further neurocognitive outcomes were unimpaired at all tested ages. Regarding motor function outcomes, mean z-scores of total motor functioning were unimpaired across assessed ages. However, at 8 years, significantly more children than expected had definite motor problems (18% vs 5%, 95% CI [0.052; 0.403], p = 0.022). Conclusion: This evaluation reveals impairment in some subtests of sustained attention, visuospatial memory and motor development. However, globally, normal neurodevelopmental outcomes were found throughout childhood. We recommend testing for neurodevelopmental impairments in children who underwent surgery for CLA only if associated morbidities are present or if caregivers express doubts about their daily functioning. What is Known: • In general, surgically managed CLA cases seldom suffer from long-term surgery-related morbidity and show favorable lung function. What is New: • Long-term neurocognitive and motor function outcome appear unimpaired within surgically managed CLA cases. We recommend testing for neurodevelopmental impairments in children who underwent surgery for CLA only if associated morbidities are present or if caregivers express doubts about their daily functioning.

Dataset Information

Transcriptomics integrated with metabolomics reveals partial molecular mechanisms of nutritional risk and neurodevelopment in children with congenital heart disease.

Purpose

Methods

Results

Conclusion

Publications

Transcriptomics integrated with metabolomics reveals partial molecular mechanisms of nutritional risk and neurodevelopment in children with congenital heart disease.

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