Association of Isolated Congenital Heart Disease with Fetal Brain Maturation.
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ABSTRACT: Background and purpose
Brain MRI of newborns with congenital heart disease show signs of immaturity relative to healthy controls. Our aim was to determine whether the semiquantitative fetal total maturation score can detect abnormalities in brain maturation in fetuses with congenital heart disease in the second and third trimesters.Materials and methods
We analyzed data from a prospective study of fetuses with and without congenital heart disease who underwent fetal MR imaging at 25-35 weeks' gestation. Two independent neuroradiologists blinded to the clinical data reviewed and scored all images using the fetal total maturation score. Interrater reliability was evaluated by the intraclass correlation coefficient using the individual reader scores, which were also used to calculate an average score for each subject. Comparisons of the average and individual reader scores between affected and control fetuses and relationships with clinical variables were evaluated using multivariable linear regression.Results
Data from 69 subjects (48 cardiac, 21 controls) were included. High concordance was observed between readers with an intraclass correlation coefficient of 0.98 (95% CI, 0.97-0.99). The affected group had significantly lower fetal total maturation scores than the control group (β-estimate, -0.9 [95% CI, -1.5 to -0.4], P = .002), adjusting for gestational age and sex. Averaged fetal total maturation, germinal matrix, myelination, and superior temporal sulcus scores were significantly delayed in fetuses with congenital heart disease versus controls (P < .05 for each). The fetal total maturation score was not significantly associated with any cardiac, anatomic, or physiologic variables.Conclusions
The fetal total maturation score is sensitive to differences in brain maturation between fetuses with isolated congenital heart disease and healthy controls.
SUBMITTER: Jaimes C
PROVIDER: S-EPMC7658885 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Neurodevelopmental impairments are the most common extracardiac morbidities among patients with complex congenital heart disease (CHD) across the lifespan. Robust clinical research in this area has revealed several cardiac, medical, and social factors that can contribute to neurodevelopmental outcome in the context of CHD. Studies using brain magnetic resonance imaging (MRI) have been instrumental in identifying quantitative and qualitative difference in brain structure and maturation in this patient population. Full-term newborns with complex CHD are known to have abnormal microstructural and metabolic brain development with patterns similar to those seen in premature infants at approximately 34 to 36 weeks' gestation. With the advent of fetal brain MRI, these brain abnormalities are now documented as they begin in utero, as early as the third trimester. Importantly, disturbed brain development in utero is now known to be independently associated with neurodevelopmental outcome in early childhood, making the prenatal period an important timeframe for potential interventions. Advances in fetal brain MRI provide a robust imaging tool to use in future neuroprotective clinical trials. The causes of abnormal fetal brain development are multifactorial and include cardiovascular physiology, genetic abnormalities, placental impairment, and other environmental and social factors. This review provides an overview of current knowledge of brain development in the context of CHD, common prenatal imaging tools to evaluate the developing fetal brain in CHD, and known risk factors contributing to brain immaturity.
| S-EPMC9905309 | biostudies-literature
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| S-EPMC5409515 | biostudies-literature
Project description:There is emerging evidence for delayed brain development in neonates with congenital heart disease. We hypothesize that the perioperative development of the structural brain connectome is a proxy to such delays. Therefore, we set out to quantify the alterations and longitudinal pre- to post-operative changes in the connectome in congenital heart disease neonates relative to healthy term newborns and assess factors contributing to disturbed perioperative network development. In this prospective cohort study, 114 term neonates with congenital heart disease underwent cardiac surgery at the University Children's Hospital Zurich. Forty-six healthy term newborns were included as controls. Pre- and post-operative structural connectomes were derived from mean fractional anisotropy values of fibre pathways traced using diffusion MR tractography. Graph theory parameters calculated across a proportional cost threshold range were compared between groups by multi-threshold permutation correction adjusting for confounders. Network-based statistic was calculated for edgewise network comparison. White-matter injury volume was quantified on 3D T1-weighted images. Random coefficient mixed models with interaction terms of (i) cardiac subtype and (ii) injury volume with post-menstrual age at MRI, respectively, were built to assess modifying effects on network development. Pre- and post-operatively, at the global level, efficiency, indicative of network integration, was lower in heart disease neonates than controls. In contrast, local efficiency and transitivity, indicative of network segregation, were higher compared to controls (all P < 0.025 for one-sided t-tests). Pre-operatively, these group differences were also found across multiple widespread nodes (all P < 0.025, accounting for multiple comparison), whereas post-operatively nodal differences were not evident. At the edge-level, the majority of weaker connections in heart disease neonates compared to controls involved inter-hemispheric connections (66.7% pre-operatively; 54.5% post-operatively). A trend showing a more rapid pre- to post-operative decrease in local efficiency was found in class I cardiac sub-type (biventricular defect without aortic arch obstruction) compared to controls. In congenital heart disease neonates, larger white-matter injury volume was associated with lower strength (P = 0.0026) and global efficiency (P = 0.0097). The maturation of the structural connectome is delayed in congenital heart disease neonates, with a pattern of lower structural integration and higher segregation compared to controls. Trend-level evidence indicated that normalized post-operative cardiac physiology in class I sub-types might improve structural network topology. In contrast, the burden of white-matter injury negatively impacts network strength and integration. Further research is needed to elucidate how aberrant structural network development in congenital heart disease represents neural correlates of later neurodevelopmental impairments.
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Project description:ObjectiveTo test the hypothesis that delayed brain development in fetuses with d-transposition of the great arteries or hypoplastic left heart syndrome heightens their postnatal susceptibility to acquired white matter injury.MethodsThis is a cohort study across 3 sites. Subjects underwent fetal (third trimester) and neonatal preoperative magnetic resonance imaging of the brain to measure total brain volume as a measure of brain maturity and the presence of acquired white matter injury after birth. White matter injury was categorized as no-mild or moderate-severe based on validated grading criteria. Comparisons were made between the injury groups.ResultsA total of 63 subjects were enrolled (d-transposition of the great arteries: 37; hypoplastic left heart syndrome: 26). White matter injury was present in 32.4% (n = 12) of d-transposition of the great arteries and 34.6% (n = 8) of those with hypoplastic left heart syndrome. Overall total brain volume (taking into account fetal and neonatal scan) was significantly lower in those with postnatal moderate-severe white matter injury compared with no-mild white matter injury after adjusting for age at scan and site in d-transposition of the great arteries (coefficient: 14.8 mL, 95% confidence interval, -28.8 to -0.73, P = .04). The rate of change in total brain volume from fetal to postnatal life did not differ by injury group. In hypoplastic left heart syndrome, no association was noted between overall total brain volume and change in total brain volume with postnatal white matter injury.ConclusionsLower total brain volume beginning in late gestation is associated with increased risk of postnatal moderate-severe white matter injury in d-transposition of the great arteries but not hypoplastic left heart syndrome. Rate of brain growth was not a risk factor for white matter injury. The underlying fetal and perinatal physiology has different implications for postnatal risk of white matter injury.
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Project description:BackgroundChildren with congenital heart disease are at risk for impaired neurodevelopment (ND). We investigated the association of fetal cerebrovascular resistance with ND in patients with single ventricle lesions.MethodsIn the Single Ventricle Reconstruction (SVR) and Infant Single Ventricle trials, 14-month ND was assessed using the Bayley Scales of Infant Development II. We investigated associations between ND scores and fetal middle cerebral artery pulsatility index (MCA-PI) z-scores, a Doppler-derived estimate of cerebrovascular resistance in a subset of those infants.ResultsNeurodevelopment assessments were performed at age 14.3 ± 1 months in 170 (74%) of 230 Infant Single Ventricle and 321 (58%) of 555 SVR subjects. Fetal echocardiographic data were available in 119 subjects, 72 (61%) of which had ND testing. Mean Psychomotor Development Index (PDI) (76 ± 20) and Mental Development Index (MDI) (89 ± 17) scores were lower than normative means (100 ± 15, P < .001). Mean MCA-PI z-score was -0.95 ± 1.52. Middle cerebral artery pulsatility index z-score correlated negatively with PDI (r = -0.27, P = .02) but was not associated with MDI. When MCA-PI z-score was added to a multivariable model controlling for factors identified in the SVR trial to predict PDI, the percentage of explained variation increased from 23% to 30%, and MCA-PI z-score remained an independent predictor (r = -3.864, P = .03). Middle cerebral artery pulsatility index z-score was not an independent predictor in a model adjusting for site.ConclusionsAmong fetuses with single ventricle anomalies, lower cerebrovascular resistance was associated with higher ND scores. This relationship is opposite to that observed with advanced intrauterine growth retardation and may represent a unique ability of these congenital heart disease fetuses to compensate for diminished cerebral oxygen delivery.
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| S-EPMC9738149 | biostudies-literature
Project description:Heart development is a complex process requiring dynamic transcriptional regulation. Disturbance of this process will lead to severe developmental defects such as congenital heart disease/defect (CHD). CHD is a group of complex disorder with high genetic heterogeneity, common pathways associated with CHD remains largely unknown. In the manuscript, we focused on the tissue specific genes in human fetal heart samples to explore such pathways. We used the RNA microarray dataset of human fetal tissues from ENCODE project to identify genes with heart tissue specific expression. A transcriptional network was constructed for these genes based on the Pearson correlation coefficients of their expression levels. Function, selective constraints and disease associations of these genes were then examined. Our analysis identified a network consisted of 316 genes with human fetal heart specific expression. The network was highly co-regulated and showed evolutionary conserved tissue expression pattern in tetrapod. Genes in this network are enriched in CHD specific genes and disease mutations. Using the transcriptomic data, we discovered a highly concerted gene network that might reflect a common pathway associated with the etiology of CHD. Such analysis should be helpful for disease associated gene identification in clinical studies.
| S-EPMC5402266 | biostudies-literature
Project description:BackgroundCongenital heart disease (CHD) is one of the most important and common group of congenital malformations in humans. Concurrent development and close functional links between the fetal heart and placenta emphasise the importance of understanding placental function and its influence in pregnancy outcomes. The aim of this study was to evaluate placental oxygenation by relaxometry (T2*) to assess differences in placental phenotype and function in CHD.MethodsIn this prospective cross-sectional observational study, 69 women with a fetus affected with CHD and 37 controls, whole placental T2* was acquired using a 1.5-Tesla MRI scanner. Gaussian Process Regression was used to assess differences in placental phenotype in CHD cohorts compared to our controls.ResultsPlacental T2* maps demonstrated significant differences in CHD compared to controls at equivalent gestational age. Mean T2* values over the entire placental volume were lowest compared to predicted normal in right sided obstructive lesions (RSOL) (Z-Score 2.30). This cohort also showed highest lacunarity indices (Z-score -1.7), as a marker of lobule size. Distribution patterns of T2* values over the entire placental volume were positively skewed in RSOL (Z-score -4.69) and suspected, not confirmed coarctation of the aorta (CoA-) (Z-score -3.83). Deviations were also reflected in positive kurtosis in RSOL (Z-score -3.47) and CoA- (Z-score -2.86).ConclusionPlacental structure and function appear to deviate from normal development in pregnancies with fetal CHD. Specific patterns of altered placental function assessed by T2* deliver crucial complementary information to antenatal assessments in the presence of fetal CHD.
| S-EPMC7611398 | biostudies-literature
Project description:ObjectiveFetal intelligent navigation echocardiography (FINE) is a novel method that automatically generates and displays 9 standard fetal echocardiographic views in normal hearts by applying intelligent navigation technology to spatiotemporal image correlation (STIC) volume data sets. The main objective was to determine the sensitivity and specificity of FINE in the prenatal detection of congenital heart disease (CHD).MethodsA case-control study was conducted in 50 fetuses with a broad spectrum of CHD (cases) and 100 fetuses with normal hearts (controls) in the second and third trimesters. Using 4-dimensional ultrasound with STIC technology, volume data sets were acquired. After all identifying information was removed, the data sets were randomly distributed to a different investigator for analysis using FINE. The sensitivity and specificity for the prenatal detection of CHD, as well as positive and negative likelihood ratios were determined.ResultsThe diagnostic performance of FINE for the prenatal detection of CHD was: sensitivity of 98% (49 of 50), specificity of 93% (93 of 100), positive likelihood ratio of 14, and negative likelihood ratio of 0.02. Among cases with confirmed CHD, the diagnosis with use of FINE completely matched the final diagnosis in 74% (37 of 50); minor discrepancies were seen in 12% (6 of 50), and major discrepancies were seen in 14% (7 of 50).ConclusionsThis is the first time the sensitivity and specificity of the FINE method in fetuses with normal hearts and CHD in the second and third trimesters has been reported. Because FINE identifies a broad spectrum of CHD with 98% sensitivity, this method could be used prenatally to screen for and diagnose CHD.
| S-EPMC6165712 | biostudies-literature