IntroductionBehavioral outcomes may be suboptimal in school-age children and adolescents with congenital heart disease (CHD). However, little is known about the behavioral outcomes of preschool children with CHD. This study aimed to compare behavioural outcomes in preschool children with CHD and controls, and to investigate the impact of a cognitively stimulating home environment on these outcomes.MethodsCross-sectional case-control study based on parent-rated questionnaires assessing child behavior and cognitively stimulating opportunities in the home environment in 56 preschool children (4–6 years) with CHD and 215 control participants. Validated questionnaires were used to assess temperament (Child Behavior Questionnaire), autism traits (Social Communication Questionnaire), ADHD symptoms (ADHD-Rating Scale-IV), empathy (EmQue), and behavioral difficulties (Strengths and Difficulties Questionnaire). Higher scores on these measures indicate more severe difficulties. The Cognitively Stimulating Parenting Scale was used to assess the presence of cognitive stimulating opportunities in the home environment.ResultsUnivariate robust regression analyses showed that children with CHD compared to controls had higher levels of age-adjusted hyperactivity/impulsivity (B = −0.339, p = 0.032), hyperactivity/inattention (B = −0.390, p = 0.032) and peer relationship problems (B = −0.298, p = 0.045), after controlling for gestational age at birth, sex and neighborhood deprivation, with results surviving false discovery rate correction. We did not find any differences between children with CHD and controls in the other behavioral measures assessed. Group (CHD or control) significantly moderated the relationship between cognitively stimulating opportunities at home and selective behavioral outcomes: hyperactivity/impulsivity, inattention and peer problems. More cognitively stimulating opportunities at home were associated with more favorable behavioral outcomes in children with CHD (hyperactivity/impulsivity: B = −0.092, p < 0.001; hyperactivity/inattention: B = −0.088, p < 0.001; peer problems: B = −0.124, p < 0.001) but not in controls (hyperactivity/impulsivity: B = −0.005, p = 0.727; hyperactivity/inattention: B = −0.019, p = 0.225; peer problems: B = −0.002, p = 0.911).ConclusionsCompared to controls, and after adjusting for potential confounders, preschool children with CHD have more hyperactivity/impulsivity, inattention and peer relationship problems. Fewer behavioral problems were associated with a more cognitively stimulating home environment, highlighting this modifiable factor as a promising target for future longitudinal research.

BACKGROUND:The relationship between fetal aortic valvuloplasty procedural volume and outcomes is crucial to understand whether regionalization should be advised worldwide. This study utilizes the International Fetal Cardiac Intervention Registry to examine the relationship between center volume for fetal aortic valvuloplasty and outcome metrics including procedure success, complications, and fetal death. METHODS:Data were included from institutions performing ≥3 procedures (2001-2018). The primary outcome was technical success, defined as ≥1 balloon inflation across the aortic valve, with increased antegrade flow across the valve, new aortic regurgitation, or both. Secondary end points were procedural complications and fetal periprocedural death (within 48 hours). Univariable and Classification and Regression Tree analyses were performed. RESULTS:Eleven centers, with volumes ranging from 6 to 31 cases, performed 162 fetal aortic valvuloplasties with a technical success rate of 80.2%. Higher volume was not associated with better technical success or fewer complications but was associated with fewer periprocedural fetal deaths. Employing Classification and Regression Tree modeling, the largest drivers of improved outcomes for all measures were greater estimated fetal weight and gestational age. A single cardiac puncture was associated with greater technical success and fewer procedural complications after accounting for fetal estimated fetal weight and gestational age. CONCLUSIONS:In this registry cohort, higher-volume centers did not have greater fetal aortic valvuloplasty technical success or fewer complications but did have fewer periprocedural fetal deaths. Fetal gestational age and number of cardiac punctures influenced outcomes, suggesting that unmeasured fetal selection criteria, such as different referral patterns, and technical expertise, indicative of overall center/team experience, may influence fetal survival.

Congenital heart disease (CHD) is associated with impaired early brain development and an increased risk of adverse neurodevelopmental outcomes. Previous studies have reported smaller hippocampal volumes in infants, children and adolescents with CHD. However, it is unclear whether specific subfields are differentially sensitive as hippocampal subfield morphometry has not been assessed in this population. The aims of this study were to test the hypothesis that infants with CHD deviate from typical hippocampal morphometry, using a normative modelling approach with reference data from 217 typically developing infants, and characterize the relationship between hippocampal morphometric measures and both cerebral oxygen delivery and neurodevelopmental outcomes in infants with CHD. Infants with CHD [60 preoperative and 29 postoperative, gestational age at birth median (range) 38.43 (36.71-40.57) weeks, postmenstrual age at scan 39.86 (37.14-45.71) weeks] and typically developing infants underwent brain MRI on a 3T scanner, and T2-weighted and inversion recovery T1-weighted imaging were acquired. Phase-contrast angiography was acquired in 53 infants with CHD before surgery, and cerebral oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 52) using the Bayley Scales of Infant and Toddler Development-Third Edition. Volumes of the whole hippocampus, subiculum, cornu ammonis 1-4, dentate gyrus, and stratum radiatum lacunosum and moleculare were obtained by segmenting T1-weighted MRI data using a U-net model trained on infant data using HippUnfold. Normative curves were generated from the typically developing infants using two models: one for relative hippocampal volumes and one for hippocampal gyrification. Models accounted for the infant's postmenstrual age at scan, postnatal age at scan and sex. The hippocampal gyrification model also accounted for hippocampal subfield volume. Z-scores representing the degree of positive or negative deviation from the normative mean were generated for infants with CHD. Relative volume z-scores were reduced for the bilateral cornu ammonis 4 and dentate gyrus (median Z-scores -0.45 to -0.82) and were increased for the left subiculum (mean Z-scores: preoperative 0.44; postoperative 0.51) in infants with CHD. Hippocampal gyrification was reduced in the bilateral subiculum, cornu ammonis 1-4 and dentate gyrus both pre- and postoperatively (mean Z-scores, -0.50 to -1.33). There was no significant relationship between preoperative hippocampal morphometric Z-scores and cerebral oxygen delivery or neurodevelopmental outcomes. Our findings suggest that hippocampal morphometry is altered in infants with CHD; however these effects are not uniform across the hippocampus.

Abstract Children with congenital heart disease (CHD) are at increased risk of altered early brain development and neurodevelopmental impairments. Although environmental factors are known to influence neurodevelopmental outcomes, the interplay between neonatal brain structure and the home environment in shaping behavioural outcomes remains unclear. We investigated associations between neonatal structural covariance networks (SCNs), cognitively stimulating parenting, and behavioural outcomes at 4–6 years in 44 preschool children with CHD and 117 controls. Principal component analysis of 19 parent-reported questionnaires identified distinct components of childhood behaviour. Parents completed the cognitively stimulating parenting scale (CSPS) to assess cognitive stimulation at home. Forty SCNs were extracted from Jacobian determinants of neonatal T2-weighted MRI using independent component analysis. In children with CHD, anterior thalamus and cingulum morphometry was associated with empathy in childhood. Higher CSPS scores were associated with fewer neurodevelopmental difficulties in CHD, but not controls. In both groups, CSPS moderated the relationship between superior temporal gyrus morphometry and empathy while, in CHD only, CSPS moderated the relationship between inferior temporal gyrus morphometry and empathy. These findings identify early neurobiological and environmental determinants of behavioural outcomes in children with CHD and highlight the home environment as a modifiable factor in supporting neurodevelopment in this population.

BACKGROUND:Brain development is altered in neonates with congenital heart disease (CHD), with well-characterised reductions in regional brain volumes and enlargement of CSF spaces. However, perioperative morphological changes remain incompletely understood. PURPOSE:To identify brain regions showing spatial patterns of coordinated expansion and contraction that differ between neonates with CHD after cardiac intervention and controls, assess perioperative changes and effects of perioperative risk factors, using Structural Covariance Component (SCC) analysis. STUDY TYPE:Prospective. POPULATION:Forty-one neonates with CHD (male = 20) who underwent cardiac surgery or catheterization and 359 healthy neonates (male = 185). FIELD STRENGTH AND SEQUENCE:3T T2-weighted turbo-spin-echo sequence. ASSESSMENT:Images were motion-corrected and reconstructed using a neonatal algorithm. Jacobian determinants calculated from non-linear image registration to a template were input into an Independent Component Analysis to identify SCCs (N = 40). SCC weightings were extracted, reflecting the degree to which the covariance pattern is expressed per neonate. STATISTICAL TESTS:Postoperative SCC weightings were compared to those of controls using a general linear model or robust regression. Perioperative change was assessed using a linear mixed effects model, and associations between perioperative differences and age at surgery, cardiopulmonary bypass duration, and postoperative pediatric intensive care unit stay were assessed using partial Spearman's rank correlation. Analyses were adjusted for covariates and corrected for multiple comparisons using False Discovery Rate, significant at p < 0.05. RESULTS:Sixteen of the 40 SCCs showed significant differences between neonates with CHD after surgery and controls, including white matter, cortical- and deep gray matter, brainstem, and CSF (f2 partial = 0.02-0.04), with seven also showing significant perioperative change (f2 partial < 0.01-0.27). An additional nine SCCs only showed significant perioperative change (f2 partial < 0.01-0.14). Perioperative risk factors were not associated with perioperative change (p > 0.463). DATA CONCLUSION:This work highlights region-specific postoperative alterations and perioperative changes in brain morphology of neonates with CHD. EVIDENCE LEVEL:1. TECHNICAL EFFICACY:Stage 3.

Theoretically derived scaling laws capture the nonlinear relationships between rapidly expanding brain volume and cortical gyrification across mammalian species and in adult humans. However, the preservation of these laws has not been comprehensively assessed in typical or pathological brain development. Here, we assessed the scaling laws governing cortical thickness (CT), surface area (SA), and cortical folding in the neonatal brain. We also assessed multivariate morphological terms that capture brain size, shape, and folding processes. The sample consisted of 345 typically developing infants, 73 preterm infants, and 107 infants with congenital heart disease (CHD) who underwent brain MRI. Our results show that typically developing neonates and those with CHD follow the cortical folding scaling law obtained from mammalian brains, children, and adults which captures the relationship between exposed SA, total SA, and CT. Cortical folding scaling was not affected by gestational age at birth, postmenstrual age at scan, sex, or multiple birth in these populations. CHD was characterized by a unique reduction in the multivariate morphological term capturing size, suggesting that CHD affects cortical growth overall but not cortical folding processes. In contrast, preterm birth was characterized by altered cortical folding scaling and altered shape, suggesting that the developmentally programmed processes of cortical folding are disrupted in this population. The degree of altered shape was associated with cognitive abilities in early childhood in preterm infants.

ABSTRACT Objective To use artificial intelligence (AI) to automatically extract video clips of the fetal heart from a stream of ultrasound video, and to assess the performance of these when used for remote second review. Methods Using a dataset from a previous clinical trial of AI to assist in fetal ultrasound scanning, AI was used to automatically extract video clips of the fetal heart from ultrasound scans of 48 fetuses in which the diagnosis was known: 24 normal and 24 with congenital heart disease (CHD). These, and manually still saved images, were shown in a random order to expert clinicians, who were asked to detect cardiac abnormalities. Results The initial manual scan had a sensitivity of 0.792 and specificity of 0.917 for detecting CHD in this cohort. The addition of second review improved the sensitivity to 0.975 using video clips, which was significantly higher than using still images (0.892, p = 0.002). There was a significant drop in specificity to 0.767 and 0.833 ( p < 0.001) for the video and still method, respectively, which were statistically similar to each other ( p = 0.117). The median review time was 1.0 min (IQR 0.71) for the still images, and 3.75 min (IQR 3.12) for the AI‐generated video clips. Conclusion AI can be used to automatically extract fetal cardiac video clips, and these can be used for remote second review to improve detection rates. Video clips are superior to still images, but both methods result in a significant drop in specificity.

BACKGROUND:Newborns with transposition of the great arteries (TGA) are at risk of severe hypoxia from inadequate atrial mixing, closure of the arterial duct, and/or persistent pulmonary hypertension of the newborn (PPHN). Acute maternal hyperoxygenation (AMH) might assist in identifying at-risk fetuses. We report pulmonary vasoreactivity to AMH in TGA fetuses and its relationship to early postnatal hypoxia and requirement for emergency balloon atrial septostomy (e-BAS). METHODS:Standard fetal echocardiographic (FE) assessment of the foramen ovale (FO): to total septal length and morphology of flap valve of the FO were used to predict the need for e-BAS. Following prospective recruitment, additional assessments were performed in fetuses with TGA at baseline and repeated after 10 minutes of 10 L/min of 100% oxygen delivered via non-rebreather mask to the pregnant mother. Analysis included measurement of atrial septal excursion, branch pulmonary artery pulsatility index (PA PI), middle cerebral artery (MCA) PI, and cardiac output. Delivery and newborn status were reviewed. Hypoxia was defined as preductal oxygen saturations <75% and e-BAS when undertaken within 2 hours of birth. Area under receiver operating characteristics curves were calculated. RESULTS:Thirty cases underwent FE at 34.6 weeks' gestation (interquartile range, 34.6-35.6). All 7 predicted to require e-BAS based on standard FE were correctly identified prenatally. Three of 30 were hypoxic without FO restriction and treated with nitric oxide (PPHN). Change in PA PI ≤ 15% was associated with PPHN (P = .001) but not with e-BAS. The MCA PI response to AMH varied according to newborn condition, a mean reduction occurred in the non-hypoxic newborns (-7.8 ± 18.3, P = .05). Increase in MCA PI Z score (area under receiver operating characteristics curves; 0.837; 95% CI, 0.663-1.00, P = .01), reduction in right ventricular cardiac output (0.811; 95% CI, 0.623-0.998, P = .04), and reduction in combined cardiac output (0.851; 95% CI, 0.699-1.0, P = .01) were moderately associated with e-BAS. Changes in atrial septal excursion and FO flow direction with AMH did not correlate with newborn condition. CONCLUSIONS:A PA PI change ≤15% to AMH was associated with postnatal hypoxia due to PPHN. Increase in right and combined cardiac output and reduced MCA resistance with AMH are seen in those who do not require e-BAS.

Congenital heart disease (CHD) and prematurity are leading causes of infant mortality and morbidity. Both groups of infants share certain common neurological sequalae, such as increased risk of neonatal brain injury and neurodevelopmental impairments later in life, leading to hypotheses that there may be shared underlying structural differences in the infant brain. However, there is no empirical evidence to support this, and our objective with this study was to compare and contrast neonatal brain structure between at-risk infant groups, then analyse their relationship with neurodevelopmental outcome. We carried out a retrospective, longitudinal, case-control analysis of 602 T2-weighted infant brain MRIs, acquired between 37 and 44 weeks postmenstrual age (PMA). The cohort comprised early preterm (n = 60), late preterm (n = 67), infants with congenital heart disease (CHD; n = 116), and term-born controls from the Developing Human Connectome Project (n = 360). We analyse structural covariance networks, a data-driven extraction of co-maturing neuroanatomical structures, capturing the variation in brain morphometry for each infant. We found distinct structural profiles in CHD and preterm infants, with minimal overlap observed between groups. A subset (n = 428) returned for neurodevelopmental follow-up at 18-24 months, and we explored the association with Bayley-III cognitive and motor scores. We found that variation in neonatal brain morphology is a significant predictor of toddler neurodevelopment in preterm infants and controls, but this association is absent in CHD. These findings suggest divergent neurobiological pathways may underlie adverse outcomes in these high-risk infants.

BACKGROUND:Relationship between blood pressure (BP) control and left ventricular (LV) diastolic function in children with chronic kidney disease (CKD) is uncertain. The aim of this study is to investigate whether achieving lower BP yields a favourable impact on diastolic function. METHODS:We performed an exploratory analysis in the HOT-KID, a parallel group, open-label, multicentre, randomised, controlled trial (ISRCTN25006406). Children with CKD were randomised to standard (50th-75th percentile) or intensive (<40th percentile) standardised office systolic BP targets. Echocardiograms were performed at baseline and at follow-up visits. Diastolic function was assessed by early (E) and late mitral inflow (A) E/A ratio, mitral annular motion of myocardial relaxation (e') and atrial contraction (a') velocity, LV compliance of E/e' and e'/a' ratio, and left atrial volume index (LAVi) by a blinded observer. FINDINGS:There was a difference in the average annual rate of change in E/A ratio (difference in means -0·07 per year, 95% CI: -0·14 to -0·01), septal e' (difference in means -0·003 m/s per year, 95% CI: -0·005 to 0·001), and LAVi (difference in means 0·82 ml/m2 per year, 95% CI: 0·22-1·42) in the standard (n = 60) compared to the intensive treatment arm (n = 64). However, the average annual changes in all other diastolic function measures were similar between standard and intensive treatment groups. There was no difference for overall adverse events or serious adverse events between the two treatment groups. INTERPRETATION:Our exploratory analysis in a small, open label RCT suggests that achieving lower blood pressure may favourably impact some measures of LV diastolic function in children with CKD. FUNDING:British Heart Foundation (PG/11/90/28,994); The authors MDS, PJC acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre and Clinical Research Facilities awards to Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. There are no relationships with industry.

Fetal two-dimensional speckle tracking echocardiography (2D-STE) is a novel technique that provides information on fetal heart function by measuring global longitudinal strain (GLS) and global longitudinal strain rate (GLSR). These features assess the longitudinal deformity of the fetal cardiac wall. 2D-STE is shown to be of prognostic value in children and adults with congenital heart disease (CHD). Therefore, its importance in fetal life should also be considered. This systematic review and meta-analysis provides an overview of the literature on 2D-STE (GLS/GLSR) in fetuses with CHD, focusing on the left and right ventricles (LV/RV). Findings indicated that LV-GLS was significantly lower in fetuses with coarctation of the aorta (CoA) and Tetralogy of Fallot (ToF) compared to controls. Conversely, fetuses with a single left ventricle exhibited higher LV-GLS. RV-GLS was significantly lower in fetuses with hypoplastic left heart syndrome (HLHS) and ToF compared to controls. LV-GLSR was significantly lower in fetuses with CoA. Overall, considerable heterogeneity was observed, possibly due to differences in study design. More prospective longitudinal studies on 2D-STE in fetuses with CHD, considering heterogeneity parameters, could offer better insights into this promising technique.