Hippocampal volume and cognitive performance in children with congenital heart disease

Background: Congenital heart disease (CHD) is associated with an increased risk of brain abnormalities. Studies indicate a particular vulnerability of the hippocampus to hypoxia and inflammation. Yet, information regarding the hippocampus and its relation to cognitive function in school-age children with CHD remains scarce. Methods: Children who underwent cardiopulmonary bypass surgery for CHD (N = 17) and healthy controls (N = 14) at 10 years of age underwent neurodevelopmental assessment and cerebral magnetic resonance imaging to measure IQ, working memory performance and hippocampal volume. Results: IQ was significantly lower in children with CHD compared to controls (98 vs 112, P = 0.02). Children with CHD showed worse working memory performance with significantly lower scores in the letter-number sequencing test (P = 0.02). After adjusting for total brain volume, hippocampal volume was smaller in children with CHD compared to controls (P 0.1). Conclusion: This study suggests that the hippocampus may be particularly susceptible in children with CHD thereby contributing to cognitive impairments. Further research is necessary to understand the contribution of the hippocampus to cognitive impairments in children with CHD. Impact: IQ is significantly lower in school-age children with congenital heart disease compared to controls. Working memory performance seems to be worse in children with congenital heart disease. Smaller hippocampal volume is associated with lower IQ and seems to be associated with lower working memory performance. The study adds knowledge on the etiology of cognitive impairments in school-age children with congenital heart disease

Blood Lactate Levels during Therapeutic Hypothermia and Neurodevelopmental Outcome or Death at 18–24 Months of Age in Neonates with Moderate and Severe Hypoxic-Ischemic Encephalopathy

Introduction: Blood lactate levels in neonates with hypoxic-ischemic encephalopathy (HIE) vary, and their impact on neurodevelopmental outcome is unclear. We assessed blood lactate course over time in neonates with HIE during therapeutic hypothermia (TH) and investigated if blood lactate values were associated with neurodevelopmental outcome at 2 years of age. Methods: This is a retrospective cohort study of neonates with HIE born between 2013 and 2019, treated at the University Children’s Hospital Zurich. We recorded blood lactate values over time and calculated time until lactate was ≤2 mmol/L. Neurodevelopmental outcome was assessed at 18–24 months of age using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), and categorized as favorable or unfavorable. We investigated associations between blood lactate values and outcome using logistic regression and adjusted for Sarnat stage. Results: 33/45 neonates (69%) had a favorable and 14 (31%) an unfavorable neurodevelopmental outcome. Mean initial lactate values were lower in the favorable (13.9 mmol/L, standard deviation [SD]: 2.9) versus unfavorable group (17.1 mmol/L, SD 3.2; p = 0.002). Higher initial and maximal blood lactate levels were associated with unfavorable outcome, also when adjusted for Sarnat stage (adjusted odds ratio [aOR]: 1.37, 95% CI: 1.01–1.88, p = 0.046, and aOR: 1.35, 95% CI: 1.01–1.81, p = 0.041, respectively). Conclusion: In neonates with HIE receiving TH, initial and maximal blood lactate levels were associated with neurodevelopmental outcome at 18–24 months of age, also when adjusted for Sarnat stage. Further investigations to analyze blood lactate as a biomarker for prognostic value are needed

Mortality and neurodevelopmental outcome at 1 year of age comparing hybrid and Norwood procedures

OBJECTIVES Neonates with hypoplastic left heart syndrome (HLHS) are at risk of high mortality and neurodevelopmental morbidity. As an alternative to Norwood-type stage I palliation, the hybrid procedure has been developed. It consists of bilateral pulmonary artery banding, catheter-based stenting of the arterial duct and balloon atrioseptostomy and delays open-heart surgery. Thus, it may be associated with a better outcome. The aim of this study was to determine the mortality and neurodevelopmental outcome in patients with HLHS and other univentricular heart (UVH) defects treated with hybrid or Norwood procedures. METHODS Thirty-one children (18 males) with HLHS and other UVH defects undergoing Norwood or hybrid procedure between 2004 and 2008 were consecutively enrolled. Mortality and neurodevelopmental outcome at 1 year of age were determined. RESULTS One-year mortality was 36% (31% in the hybrid vs. 39% in the Norwood group, P=0.71). Predictors of mortality were lower birth weight (P=0.02), older age at first procedure (P=0.02) and smaller size of ascending aorta (P=0.05). Overall, median psychomotor development index (PDI) and mental development index (MDI) of the Bayley Scales of Infant Development II were lower than the norm of 100 [PDI 57 (49-99), P<0.001; MDI 91 (65-109), P=0.002]. No effect of surgical treatment on neurodevelopmental outcome was found. Predictors of impaired motor outcome were length of hospital stay (LOHS) (P=0.01), lower body weight at second procedure (P=0.004) and female sex (P=0.01). Predictors of impaired cognitive outcome were longer mechanical ventilation time (P=0.03), intensive care unit stay (P=0.04) and LOHS (P<0.001), respectively. CONCLUSIONS Mortality at 1 year of age is comparable between patients undergoing hybrid and Norwood procedures. Early neurodevelopmental outcome is significantly impaired in patients with both HLHS and other UVH defects. Multicentre randomized studies are needed to determine the long-term neurodevelopmental outcome of children treated with the hybrid procedur

Placental findings are not associated with neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy - an 11-year single-center experience

OBJECTIVES: Although neonates with moderate to severe hypoxic ischemic encephalopathy (HIE) receive therapeutic hypothermia (TH), 40-50% die or have significant neurological disability. The aim of this study is to analyse the association of placental pathology and neurodevelopmental outcome in cooled neonates with HIE at 18-24 months of age. METHODS: Retrospective analysis of prospectively collected data on 120 neonates registered in the Swiss National Asphyxia and Cooling Register born between 2007 and 2017. This descriptive study examines the frequency and range of pathologic findings in placentas of neonates with HIE. Placenta pathology was available of 69/120 neonates, whose results are summarized as placental findings. As neonates with HIE staged Sarnat score 1 (21/69) did not routinely undergo follow-up assessments and of six neonates staged Sarnat Score 2/3 no follow-up assessments were available, 42/48 (88%) neonates remain to assess the association between placental findings and outcome. RESULTS: Of the 42/48 (88%) neonates with available follow up 29% (12/42) neonates died. Major placenta abnormalities occurred in 48% (20/42). Major placenta abnormality was neither associated with outcome at 18-24 months of age (OR 1.75 [95% CI 0.50-6.36, p=0.381]), nor with death by 2 years of age (OR 1.96 [95% CI 0.53-7.78, p=0.320]). CONCLUSIONS: In this study cohort there could not be shown an association between the placenta findings and the neurodevelopmental outcome at 18-24 months of age

Cerebral lesions on magnetic resonance imaging correlate with preoperative neurological status in neonates undergoing cardiopulmonary bypass surgery

OBJECTIVES To determine the prevalence, spectrum and course of cerebral lesions in neonates with congenital heart disease (CHD) undergoing full flow cardiopulmonary bypass (CPB) surgery using magnetic resonance imaging (MRI) and to examine the correlation between cerebral lesions and clinical neurological abnormalities. METHODS Prospective cohort study of neonates with d-transposition of the great arteries (n = 22), univentricular heart malformation with hypoplastic aortic arch (n = 6) and aortic arch obstructions (n = 2) undergoing CPB. Neonates underwent cerebral MRI and blinded standardized neurological examination before (median day 6) and after surgery (day 13). The MRI findings were compared with those of 20 healthy controls. RESULTS Preoperative cerebral lesions were present in 7 of 30 patients (23%) with isolated mild or moderate white matter injury (WMI) (n = 4), isolated small cerebral stroke (n = 1) and combined WMI and stroke (n = 2). None of the healthy controls had cerebral lesions on MRI. CHD neonates with preoperative cerebral lesions had more neurological abnormalities (P = 0.01) than neonates without cerebral lesions. Low arterial oxygen saturation (P = 0.03) was a risk factor for preoperative cerebral lesions, while balloon atrioseptostomy (P = 0.19) was not. After surgery, preoperative cerebral lesions persisted in 5 of 7 neonates, and 2 neonates (7%) showed signs of additional WMI in their postoperative MRI. CONCLUSIONS In neonates with severe CHD, WMI was the predominant preoperative finding, while cerebral strokes were less frequent. New postoperative lesions were rare. Preoperative neurological abnormalities correlated with the presence of cerebral lesions on MR

Stress Markers, Executive Functioning, and Resilience Among Early Adolescents With Complex Congenital Heart Disease

Importance: Infants with complex congenital heart disease (cCHD) may experience prolonged and severe stress when undergoing open heart surgery. However, little is known about long-term stress and its role in neurodevelopmental impairments in this population. Objective: To investigate potential differences between early adolescents aged 10 to 15 years with cCHD and healthy controls in physiological stress markers by hair analysis, executive function (EF) performance, and resilience. Design, Setting, and Participants: This single-center, population-based case-control study was conducted at the University Children’s Hospital Zurich, Switzerland. Patients with different types of cCHD who underwent cardiopulmonary bypass surgery during the first year of life and who did not have a genetic disorder were included in a prospective cohort study between 2004 and 2012. A total of 178 patients were eligible for assessment at ages 10 to 15 years. A control group of healthy term-born individuals was cross-sectionally recruited. Data assessment was between 2019 and 2021. Statistical analysis was performed from January to April 2023.ExposurePatients with cCHD who underwent infant open heart surgery. Main Outcomes and Measures: Physiological stress markers were quantified by summing cortisol and cortisone concentrations measured with liquid chromatography with tandem mass spectrometry in a 3-centimeter hair strand. EFs were assessed with a neuropsychological test battery to produce an age-adjusted EF summary score. Resilience was assessed with a standardized self-report questionnaire. Results: The study included 100 patients with cCHD and 104 controls between 10 and 15 years of age (mean [SD] age, 13.3 [1.3] years); 110 (53.9%) were male and 94 (46.1%) were female. When adjusting for age, sex, and parental education, patients had significantly higher sums of hair cortisol and cortisone concentrations (β, 0.28 [95% CI, 0.12 to 0.43]; P &amp;lt; .001) and lower EF scores (β, −0.36 [95% CI, −0.49 to −0.23]; P &amp;lt; .001) than controls. There was no group difference in self-reported resilience (β, −0.04 [95% CI, −0.23 to 0.12]; P = .63). A significant interaction effect between stress markers and EFs was found, indicating a stronger negative association in patients than controls (β, −0.65 [95% CI, −1.15 to −0.15]; P = .01). The contrast effects were not significant in patients (β, −0.21 [95% CI, −0.43 to −0.00]; P = .06) and controls (β, 0.09 [95% CI, −0.11 to 0.30]; P = .38). Conclusions and Relevance: This case-control study provides evidence for altered physiological stress levels in adolescents with cCHD and an association with poorer EF. These results suggest that future studies are needed to better understand the neurobiological mechanisms and timing of alterations in the stress system and its role in neurodevelopment

Growth and Intellectual Abilities of Six-Year-Old Children with Congenital Heart Disease

OBJECTIVE To determine growth and its relationship to IQ in children with congenital heart disease (CHD) undergoing cardiopulmonary bypass surgery within the first year of life. STUDY DESIGN Prospective single-center cohort study on 143 children (91 males) with different types of CHD (29 univentricular). Children with recognized genetic disorders were excluded. Growth (weight, height, and head circumference [HC]) was assessed at birth, before surgery, and at 1, 4, and 6 years and compared with Swiss growth charts. IQ was assessed at 6 years using standardized tests. Univariate and multivariable linear regressions were performed to determine predictors of HC and IQ at 6 years. RESULTS HC at birth was in the low average range (33rd percentile, P = .03), and weight (49th percentile, P = .23) and length (47th percentile, P = .06) were normal. All growth measures declined until the first surgery, with a catch-up growth until 6 years for height (44th percentile, P = .07) but not for weight (39th percentile, P = .003) or for HC (23rd percentile, P < .001). Children undergoing univentricular palliation showed poorer height growth than other types of CHD (P = .01). Median IQ at 6 years was 95 (range 50-135). Lower IQ at 6 years was independently predicted by lower HC at birth, lower socioeconomic status, older age at first bypass surgery, and longer length of intensive care unit stay. CONCLUSIONS Smaller HC at birth and postnatal factors are predictive of impaired intellectual abilities at school age. Early identification should alert clinicians to provide early childhood interventions to optimize developmental potential