Neurodevelopmental Outcomes In Patients Research Articles

Congenital central hypoventilation syndrome in korea: 20years of clinical observation and evaluation of the ventilation strategy in a single center.

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder characterized by hypoventilation due to impaired breathing control by the central nervous system and other symptoms of autonomic dysfunction. Mutations in paired-like homeobox 2 B (PHOX2B) are responsible for most cases of CCHS. Patients with CCHS have various phenotypes and severities, making the diagnosis difficult. This study aimed to present a comprehensive single-center experience of patients with CCHS, including key clinical features, treatment strategies, and outcomes.A retrospective chart review was performed for patients diagnosed with CCHS between January 2001 and July 2023 at Seoul National University Children's Hospital. Finally, we selected 24 patients and collected their demographic data, genotypes, ventilation methods, and clinical features related to autonomic dysfunction. The relationship between the clinical manifestations and genotypes was also examined.All patients used home ventilators, and tracheostomy was performed in 87.5% of patients. Fifteen (62.5%) patients had constipation and nine (37.5%) were diagnosed with Hirschsprung disease. Arrhythmia, endocrine dysfunction, and subclinical hypothyroidism were present in nine (37.5%), six patients (25.0%), and two patients (16.7%), respectively. A significant number of patients exhibited neurodevelopmental delays (19 patients, 79.2%). There was a correlation between the phenotype and genotype of PHOX2B in patients with CCHS. (r = 0.71, p < 0.001). Conclusion: There was a positive correlation between paired-like homeobox 2 B mutations (especially the number of GCN repeats in the polyalanine repeat mutations sequence) and clinical manifestations. This study also demonstrated how initial treatment for hypoventilation affects neurodevelopmental outcomes in patients with CCHS. What is Known: • Congenital central hypoventilation syndrome is a rare genetic disorder characterized by hypoventilation and dysfunction of autonomic nervous system. • The disease-defining gene of CCHS is PHOX2B gene - most of the cases have heterozygous PARMs and the number of GCN triplets varies among the patients(20/24 - 20/33). What is New: • We have noted in the Korean patients with CCHS that there is a correlation between genotype (number of GCN repeats) and severity of phenotype. • National support for rare diseases allowed for a prompter diagnosis of patients with CCHS in Korean population.

Language brain responses and neurodevelopmental outcome in preschoolers with congenital heart disease: A fNIRS study

Neurodevelopmental disabilities affect up to 50% of survivors of congenital heart disease (CHD). Language difficulties are frequently identified during preschool period and can lead to academic, social, behavioral, and emotional difficulties. Structural brain alterations are associated with poorer neurodevelopmental outcomes in patients with CHD during infancy, childhood, and adolescence. However, evidence is lacking about the functional brain activity in children with CHD and its relationship with neurodevelopment. This study therefore aimed to characterize brain responses during a passive story-listening task in 3-year-old children with CHD, and to investigate the relationship between functional brain patterns of language processing and neurodevelopmental outcomes. To do so, we assessed hemodynamic concentration changes, using functional near-infrared spectroscopy (fNIRS), and neurodevelopmental outcomes, using the Wechsler Preschool and Primary Scale of Intelligence – 4th Edition (WPPSI-IV), in children with CHD (n = 19) and healthy controls (n = 23). Compared to their healthy peers, children with CHD had significantly lower scores on the Verbal comprehension index (VCI), the Vocabulary acquisition index (VAI), the General ability index (GAI), and the Information and the Picture Naming subtests of the WPPSI-IV. During the passive story-listening task, healthy controls showed significant hemodynamic brain responses in the temporal and the temporal posterior regions, with stronger activation in the temporal posterior than in the temporal regions. In contrast, children with CHD showed reduced activation in the temporal posterior regions compared to controls, with no difference of activation between regions. Reduced brain responses in the temporal posterior regions were also correlated with lower neurodevelopmental outcomes in both groups. This is the first study that reveals reduced brain functional responses in preschoolers with CHD during a receptive language task. It also suggests that the temporal posterior activation could be a potential brain marker of cognitive development. These findings provide support for the feasibility of identifying brain correlates of neurodevelopmental vulnerabilities in children with CHD.

Neurodevelopmental outcomes in congenital heart disease: usefulness of biomarkers of brain injury

IntroductionAt present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. MethodsProspective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: 1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; 2) clinical and laboratory data from the immediate postnatal and perioperative periods; 3) treatments and complications; 4) neurodevelopment (Bayley-III scale) at age 2 years. Resultsthe study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. Conclusionschildren with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer followups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.

Neurodesarrollo a los 2 años en cardiopatía congénita: utilidad pronóstica de los marcadores de daño cerebral

IntroductionAt present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. MethodsProspective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. ResultsThe study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. ConclusionsChildren with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer followups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.

Brain injury and neurodevelopmental outcomes in children undergoing surgery for congenital heart disease

ObjectivesBrain injury is commonly seen on magnetic resonance imaging in infants with complex congenital heart disease. The impact of perioperative brain injury on neurodevelopmental outcomes is not well understood. We evaluate the association of brain injury and other markers on neurodevelopmental outcomes in patients undergoing surgery for congenital heart surgery during infancy. MethodsTerm newborns with infant cardiac surgery performed between 2008 and 2019 at a single tertiary center, and both preoperative and postoperative brain magnetic resonance imaging were included. Those with underlying genetic conditions were excluded. Brain injury was characterized using an magnetic resonance imaging scoring system. Neurodevelopmental outcomes were assigned using the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. Independent risk factors for poor neurodevelopmental outcomes were determined by multivariable Cox regression. ResultsA total of 122 patients were included. New or progressive postoperative brain injury was noted in 69 patients (57%). A total of 101 patients (83%) had at least 1 neurodevelopmental assessment (median age 36 months) with an early assessment (5-24 months) performed in 95 children. Multivariable Cox regression analysis of early neurodevelopmental outcomes identified new stroke on postoperative magnetic resonance imaging to be an independent predictor of poor neurodevelopmental outcome. Postoperative peak lactate was an independent predictor of poor outcome assessed by the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. ConclusionsOur study reveals that evidence of new stroke on magnetic resonance imaging after infant congenital heart surgery is a predictor of poor neurodevelopmental outcomes in early childhood. Postoperative lactic acidosis is associated with poor neurodevelopmental outcome and may be a surrogate biomarker for ischemic brain injury.

The association of placental pathology and neurodevelopmental outcomes in patients with neonatal encephalopathy.

Studies conflict on how acute versus chronic placental pathology impacts outcomes after neonatal encephalopathy from presumed hypoxic-ischemic encephalopathy (HIE). We examine how outcomes after presumed HIE vary by placental pathology categories. We performed retrospective chart review for neonates with presumed HIE, regardless of severity, focusing on 50 triads for whom placental specimens were available for re-review. Placentas were categorized as having only acute, any chronic, or no lesions. Primary outcomes included in-hospital morbidity/mortality and long-term neurodevelopmental symptoms. Secondary outcomes assessed neonatal MRI and EEG. Demographics did not differ between groups. Forty-seven neonates were treated with therapeutic hypothermia. Placental acuity category was not associated with primary or secondary outcomes, but clinical and/or histopathological chorioamnionitis was associated with abnormal EEG background and post-neonatal epilepsy (16.7%, n = 3 with chorioamnionitis versus 0%, n = 0 without chorioamnionitis, p = 0.04). When grouped by acute, chronic, or absent placental lesions, we observed no association with in-hospital, neurodevelopmental, MRI, or EEG outcomes. When reanalyzed by the presence of chorioamnionitis, we found that chorioamnionitis appeared to be associated with a higher risk of EEG alterations and post-neonatal epilepsy. Despite our limited sample size, our results emphasize the critical role of placental examination for neuroprognostication in presumed HIE. Neonatal encephalopathy presumed to result from impaired fetal cerebral oxygenation or blood flow is called hypoxic ischemic encephalopathy (HIE). Prior studies link placental pathology to various outcomes after HIE but disagree on the impact of acute versus chronic pathology. Our study determines that neurodevelopmental outcomes, in-hospital outcomes, injury on MRI, and EEG findings in patients with HIE are not differentially associated with acute versus chronic placental pathology. Chorioamnionitis is associated with an increased risk of abnormal EEG patterns and post-neonatal epilepsy. Histopathologic chorioamnionitis without clinical symptoms is common in HIE, emphasizing the crucial role of placental pathology for neuroprognostication.

A prospective study of prenatal ventriculomegaly: natural course, survival, and neurodevelopmental status.

Prenatal ventriculomegaly (VM) is classified as mild, moderate, or severe on the basis of the diameter of the atrium. Neurodevelopmental status in prenatal VM is associated with various factors such as the course of VM, VM type, progression, and associated anomalies. In this study, the authors aimed to evaluate neurodevelopmental outcome in patients with prenatal VM and to detect possible associated risk factors. In this study, 73 pregnancies with VM who were referred to Children's Medical Center, Tehran, Iran, between 2019 and 2021 were prospectively followed. They were followed up every 2-4 weeks with ultrasonography (US) before delivery and were then observed for an average time of 14.6 months. The authors collected demographic and ultrasound information, associated abnormalities, pregnancy outcomes, and developmental status according to Centers for Disease Control criteria. The mean gestational age at the time of diagnosis was 28.1 weeks, and 46.6% of fetuses were female. According to the first US, 46.6% had mild, 21.9% had moderate, and 31.5% had severe VM. Serial US scans showed that VM had regressed in 20.5% of patients, remained stable in 35.6%, and progressed in 43.8%. Other cranial abnormalities were detected in 38.4% of fetuses. During follow-up, 62.5% of cases had normal developmental status, 26.6% had mild delay, and 10.9% had severe neurodevelopmental delay. Pregnancy was terminated in 9 (12.3%) cases. Normal neurodevelopment was reported in 75.8% of patients with mild VM versus 50% of those with severe VM (p = 0.19). Neurodevelopmental status was normal in 72.5% of cases without other cranial abnormalities (p = 0.018) and in 86.7% of cases with regression of VM (p = 0.028). Despite analysis of different factors in prenatal VM, only progression of VM and associated cranial abnormalities had significant relationships with neurodevelopmental prognosis.

A guide to prenatal counseling regarding neurodevelopment in congenital heart disease.

Advances in cardiac surgical techniques taking place over the past 50years have resulted in the vast majority of children born with congenital cardiac malformations now surviving into adulthood. As the focus shifts from survival to the functional outcomes of our patients, it is increasingly being recognized that a significant proportion of patients undergoing infant cardiac repair experience adverse neurodevelopmental (ND) outcomes. The etiology of abnormal brain development in the setting of congenital heart disease is poorly understood, complex, and likely multifactorial. Furthermore, the efficacy of therapies available for the learning disabilities, attention deficit, and hyperactivity disorders and other ND deficits complicating congenital heart disease is currently uncertain. This situation presents a challenge for prenatal counseling as current antenatal testing does not usually provide prognostic information regarding the likely ND trajectories of individual patients. However, we believe it is important for parents to be informed about potential issues with child development when a new diagnosis of congenital heart disease is disclosed. Parents deserve a comprehensive and thoughtful approach to this subject, which conveys the uncertainties involved in predicting the severity of any developmental disorders encountered, while emphasizing the improvements in outcomes that have already been achieved in infants with congenital heart disease. A balanced approach to counseling should also discuss what local arrangements are in place for ND follow-up. This review presents an up-to-date overview of ND outcomes in patients with congenital heart disease, providing possible approaches to communicating this information to parents during prenatal counseling in a sensitive and accurate manner.

Correlation of cytomegalovirus viral load between whole blood and plasma of congenital cytomegalovirus infection under valganciclovir treatment

BackgroundCongenital cytomegalovirus (CMV) infection (cCMV) can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Oral valganciclovir (VGCV) therapy has been reported to improve long-term audiological and neurodevelopmental outcomes in patients with cCMV. The levels of CMV DNA in whole blood have been monitored in previous studies. However, quantitative methods using whole blood have not been standardized. Recently, the plasma viral load has been standardized and widely used in CMV-associated diseases.MethodsCMV viral loads in whole blood and plasma were serially measured in 24 patients with a confirmatory diagnosis of cCMV during oral VGCV therapy using an in-house real-time PCR assay. Plasma samples were assayed using the Cobas 6800 system (Roche Diagnostics) in addition to an in-house assay.ResultsPlasma CMV viral loads were remarkably decreased at the end of therapy compared to before therapy. A significant correlation of CMV levels between whole blood and plasma was observed (Spearman’s ρ = 0.566). The levels of CMV DNA before therapy were significantly correlated with the period of decreasing the viral loads to below the detection limit, not only in whole blood (Spearman’s ρ = 0.901) but also in plasma (Spearman, ρ = 0.804). Finally, CMV viral loads between the in-house assay and commercially available standardized assay in 75 plasma samples with positive PCR results for CMV were compared; a significant correlation was observed between the results of both assays.ConclusionsThere was a significant correlation between the two assays (Spearman, ρ = 0.882), suggesting that CMV plasma viral loads measured by the standardized assay are widely used to monitor the levels of CMV DNA in patients with cCMV during oral VGCV therapy.

Neurodevelopmental and functional outcome in hypoplastic left heart syndrome after Hybrid procedure as stage I.

Patients with hypoplastic left heart syndrome (HLHS) undergoing staged palliation until Fontan procedure are at risk for impaired neurodevelopmental (ND) outcome. The Hybrid procedure with bilateral pulmonary artery banding, ductal stenting, and balloon atrioseptostomy may offer a less invasive stage I procedure compared to the Norwood stage I procedure avoiding early neonatal cardiopulmonary bypass (CPB) surgery. Despite altered fetal cerebral hemodynamics, the type of stage I procedure may be a covariate influencing ND outcome and functional outcome may also be altered due to postponing neonatal CPB surgery. Within this review, we analyzed ND outcome as well as functional outcome after Hybrid procedure as stage I procedure. The review analyzed original publications (OPs) published before March 15, 2022, identified by Cochrane, EMBASE, OVID, Scopus, and Web of science. An OP was included if short-to-long-term neurodevelopment outcome, brain development, somatic, and cardiac outcome in patients for HLHS and variants treated by Hybrid procedure were analyzed. In addition to database searches, we reviewed all references of the analyzed OP to obtain a comprehensive list of available studies. The author, year of publication, demographic characteristics of study population, study design (prospective or retrospective), study assessment, and main findings were summarized. Twenty-one OPs were included with data of patients with ND outcome and functional cardiac outcome. Overall, there is an impaired mid-term ND outcome in patients with Hybrid procedure as stage I for HLHS. Only slight differences between stage I procedures (Hybrid vs. Norwood) in two comparing studies have been determined affecting right ventricular remodeling, short- and mid-term ND outcome, reduced brain growth until two years of age, sufficient quality of life, and altered hemodynamics influencing brain volumes and cerebral perfusion pattern. Despite some minor differences regarding the mid-term follow-up in patients with HLHS comparing Hybrid vs. Norwood procedure, its impact on ND outcome seems rather low. This may be explained by the large number of covariates as well as the small study populations and the different selection criteria for patients undergoing Hybrid or Norwood procedure as stage I.

Postnatal surgery for myelomeningocele in neonates: neurodevelopmental outcomes.

The study aims to evaluate the neurodevelopmental outcomes of neonates with myelomeningocele (MMC) operated in the postnatal period. This is a prospective follow-up study in a tertiary neonatal intensive care unit. Neurodevelopmental outcomes of term neonates operated for MMC and healthy term newborns were compared with the Bayley Scales of Infant and Toddler Development -Third Edition (BSID III) at 12-18 months. A total of 57 cases were included in the study (patient group = 27; control group = 30). Demographic data between the groups were similar. Cognitive, linguistic, and motor composite scores of the patient group were lower than those of the control group (p < 0.001). In the patient group, those who underwent ventriculoperitoneal shunt had lower cognitive, language and motor scores than those without shunt (p < 0.05). The cognitive, linguistic, and motor composite scores in the patient group who underwent surgery before 72 h were better than those who underwent surgery after 72 h. In our study, it was found that the neurodevelopmental prognosis of MMC cases requiring ventriculoperitoneal shunt in the postnatal period was significantly worse than those without shunt. It is the first study in which the neurodevelopment of patients with MMC who were operated in the postnatal period was evaluated with BSID III evaluated and delays in all areas were shown in cases with MMC compared to normal cases. Better neurodevelopmental outcomes in patients operated in the first 72 h suggest that early surgery will improve neurodevelopmental outcomes in patients with MMC.

Association between placental syndrome and 2-year neurodevelopmental outcome in patients with primary maternal CMV infection

Association between placental syndrome and 2-year neurodevelopmental outcome in patients with primary maternal CMV infection

The Relationship Between Placental Pathology and Neurodevelopmental Outcomes in Complex Congenital Heart Disease.

Complex congenital heart disease (CCHD) is associated with impaired neurodevelopmental outcomes. Peri- and post-operative factors are known contributors while the impact of the prenatal environment is not yet delineated. Variations in fetal circulation, seen in transposition of the great arteries (TGA) and single ventricular physiology (SVP), are associated with placenta abnormalities. These abnormalities may be associated with placental insufficiency, a risk factor for poor neurodevelopmental outcomes. We hypothesized there is a correlation between placental pathology and impaired neurodevelopmental outcomes in patients with CCHD. We performed a single center retrospective cohort study with patients with TGA and SVP from 2010 to 2017 at Children's Wisconsin. Patient variables were obtained from the medical record. Bayley Scales of Infant Development Third Edition standard scores for cognitive, motor, and language performance were collected from neurodevelopmental visits. Placenta pathology reports were reviewed with tabulation of predetermined anatomical and pathological characteristics. We identified 79 patients in our cohort and 61 (77.2%) had abnormal placentas. There was no significant difference between the two groups in any demographic or clinical variables. For cognitive and motor performance, without adjusting for the covariates, infants with placental abnormalities had significantly lower scores compared to infants without (p = 0.026, p = 0.045 respectively). Conversely, there was no significant difference in language scores between the two groups (p = 0.12). Placenta abnormalities are common in patients with CCHD, and placenta abnormalities are associated with impaired neurodevelopmental outcomes. These results underscore the complex causal pathways of neurodevelopmental impairment in infants with CCHD and offer opportunities for targeted postnatal developmental interventions after discharge.

Clinical Characteristics and Neurologic Outcomes of X-Linked Myotubular Myopathy

Purpose: X-linked myotubular myopathy (XLMTM) is a rare condition of centronuclear myopathy caused by myotubularin 1 (MTM1) mutations. Patients with XLMTM show different neurodevelopmental outcomes after the neonatal period depending on age and acquired hypoxic damage. We aim to evaluate the clinical characteristics and neurodevelopmental outcomes of patients with XLMTM who were followed up at a single center. It is essential to understand the volume and conditions to prepare for being a candidate for new therapeutic strategies. Methods: Patients diagnosed with centronuclear myopathy by muscle pathology and MTM1 mutation analysis were included. We retrospectively investigated motor milestones, communication skills, and bulbar and respiratory function in the patients. The patients were categorized into two groups: with and without hypoxic insults (HI). Results: All 13 patients were severely affected by neonatal hypotonia and required respiratory support and a feeding tube during the neonatal period. The follow-up duration was 4.4 years (range, 0.3 to 8.9). In the non-HI group, developmental milestones were delayed but were slowly achieved. Some patients underwent training in oral feeding with thickened foods and weaning from ventilation. Patients with HI showed poor motor function catch-up and communication skills. Three deaths were associated with acute respiratory failure.Conclusion: Patients with XLMTM without HI can survive long-term with the slow achievement of motor milestones and bulbar and respiratory function. However, hypoxic brain damage following acute respiratory failure negatively influences their developmental potential or even lead to death. Therefore, parental education for proper respiratory management is necessary, especially for young children.

Cerebral desaturation during neonatal congenital heart surgery is associated with perioperative brain structure alterations but not with neurodevelopmental outcome at 1 year.

The significance of intraoperative cerebral desaturation (CD) measured by near-infrared spectroscopy (NIRS) to predict neurological outcome after congenital heart surgery is uncertain. The goal of this study was to compare brain structure changes and neurodevelopmental outcome in patients with severe congenital heart disease with and without intraoperative CD. Neonates requiring congenital heart surgery were enrolled in a cohort study. NIRS data from their first cardiac operation were collected. Pre- and postoperative brain magnetic resonance imaging results and Bayley-III scores at 1 year were compared between patients with and without CD, defined by 2 NIRS thresholds: regional cerebral oxygen saturation (rSO2) of 45% (45%rSO2) and rSO2 below 20% of baseline value (20%BLrSO2). Thirty-two patients (72% male) with d-transposition of the great arteries (n = 24, 75%) and other complex types of congenital heart diseases (n = 8, 25%) were analysed. Perioperative relative lateral ventricle volume change was increased in patients with versus without intraoperative CD (P = 0.003 for 45%rSO2, P = 0.008 for 20%BLrSO2). For 45%rSO2, the effect of CD remained significant after adjusting for age at postoperative scan, time between scans and cardiac diagnosis (P = 0.019). New intracranial lesions occurred predominantly in CD groups (6/6 patients for 45%rSO2, 5/6 patients for 20%BLrSO2). Neurodevelopmental outcome at 1 year was not associated with intraoperative CD. This study demonstrates the clinical relevance of NIRS monitoring during congenital heart surgery. The occurrence of intraoperative CD is associated with perioperative lateral ventricle volume change and new intracranial lesions.

363 School-age Morphological And Neurodevelopmental Outcomes In Patients With Sagittal Craniosynos

OBJECTIVES/GOALS: Several studies compare perioperative parameters and postoperative morphology of open cranial vault remodeling (CVR) and endoscopic-assisted craniectomy (EAC) in the treatment of sagittal craniosynostosis. However, data on neurodevelopmental outcomes comparing these techniques is lacking. METHODS/STUDY POPULATION: Patients with repaired sagittal synostosis were enrolled from a single tertiary care center between five and fifteen years of age. Patients with any craniofacial syndrome (e.g., 22q11.2 deletion) or other medical conditions that could affect neurodevelopment were excluded. Neurodevelopment was measured using the Differential Ability Scale-II (DAS-II). The General Cognitive Ability (GCA) score was the primary outcome measure, describing overall intellectual ability. Secondary outcome measures were measurements of cephalic index (CI) from pre- and postoperative imaging studies. Family socioeconomic status (SES) was estimated using the Hollingshead index (total score, continuous). RESULTS/ANTICIPATED RESULTS: 26 patients [10 CVR (2 Female:8 Male), 16 EAC (6 F:10 M)] were studied. Mean age at repair was greater with CVR than EAC (15.5 ± 8.5 months vs 3.5 ± 1.3 months, respectively, p &lt; 0.001). Mean age at DAS-II testing was 9.0 ± 2.2 years. Patients GCA scores were within the average range relative to test norms (CVR 95.7 ± 15.4 vs EAC 102.6 ± 17.4). After adjusting for SES and preoperative CI, group differences in GCA were modest and statistically nonsignificant (p = 0.646). GCA scores were associated with SES (p = 0.054) but not preop CI (p = 0.479). Differences between CVR and EAC were not statistically significant for any of the imaging parameters (pre and postop CI, pre to postop change in CI, or age at postop imaging; 0.131 &lt;= p &lt;= 0.867). None of the independent variables were significantly associated with postop CI (0.140 &lt;= p &lt;= 0.689). DISCUSSION/SIGNIFICANCE: Interim analysis of the preliminary data suggests no association between surgical procedure and cognitive and morphological outcomes at school-age in patients with sagittal craniosynostosis who underwent CVR versus EAC. Collection of data continues, with the goal to enroll 50 participants in each group by 2022.

Factors associated with neurodevelopmental impairment in preterm infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a common and serious complication in preterm infants with very low birth weight and is known to lead to poor neurodevelopmental outcomes. This study aimed to identify factors associated with neurodevelopmental impairment (NDI) in patients with moderate to severe BPD. A total of 83 preterm infants born between 24- and 29-weeks' gestation who were admitted to the neonatal intensive care unit and developed moderate/severe BPD between 2013 and 2017 were retrospectively evaluated. Developmental assessment was performed at 18 to 24 months of corrected age using the Bayley Scales of Infant Development II (BSID-II). Patients with NDI (n=41) and without NDI (n=42) were compared. BSID-II Mental Development Index and Psychomotor Development Index scores were 87±11 and 83±8 in the non-NDI group and 57±12 and 52±8 in the NDI group, respectively (p<0.001). The NDI group had significantly lower birth weight (847±174 vs. 1012±192 g) and gestational age (26.1±1.3 and 27.6±1.6 weeks) compared to the non-NDI group (p<0.001). Intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, exposure to steroids, duration of respiratory support, and length of hospital stay were significantly higher in the NDI group (p<0.001). Many of the conditions in this study were found to be associated with poor neurodevelopmental outcomes in patients with BPD, such as prolonged respiratory support, prolonged hospitalization, intraventricular hemorrhage, retinopathy, and steroid therapy, can be avoided or prevented with strict protocols and prevention strategies. Appropriate management of comorbid risk factors may help prevent poor neurodevelopmental outcomes.

Impact of fetal haemodynamics on surgical and neurodevelopmental outcomes in patients with Ebstein anomaly and tricuspid valve dysplasia.

To evaluate the impact of fetal haemodynamics on surgical and neurodevelopmental outcomes in severe Ebstein anomaly and tricuspid valve dysplasia. Thirty-four fetuses with Ebstein anomaly/tricuspid valve dysplasia were referred from 2013 to 2019 for fetal echocardiography and clinical management. Nineteen fetuses with Ebstein anomaly/tricuspid valve dysplasia and 30 controls underwent cardiovascular magnetic resonance to quantify the fetal blood flow and to calculate cerebral oxygen delivery (cDO2) and consumption (cVO2). The 3D steady-state free precession acquisition was used to measure fetal brain volume. Surgical outcome, brain MRI, and neurodevelopmental follow-up were reviewed. Twenty-six fetuses were live born (76%) and survival (65%) at a mean follow-up of 4 years. Nine fetuses had a brain MRI before discharge, and all had clinically silent injuries and volume loss. At 18 months, five single-ventricle patients had a neurodevelopmental delay in cognition and language (mean percentile: 11th), with gross-motor skills more affected than fine-motor skills (mean percentiles: 4th and 34th). Fetuses with Ebstein anomaly/tricuspid valve dysplasia had smaller brains, lower combined ventricular output, ascending aorta, superior caval vien and umbilical vein flows, lower oxygen saturation in ascending aorta and superior caval vien, lower cDO2 and cVO2 (p < 0.05). Superior caval vien/combined ventricular output and descending aorta/combined ventricular output ratios were lower in fetuses with circular shunt (p < 0.05). Fetuses requiring the Starnes procedure tended to have smaller brains, lower combined ventricular output, superior caval vien, descending aorta, and umbilical vein flows. All patients with Ebstein anomaly/tricuspid valve dysplasia are at high risk of neurodevelopmental delay and warrant follow-up. Fetal cardiovascular magnetic resonance revealed impaired brain growth with diminished cerebral blood flow and cDO2, the extenting dependent on the severity of the haemodynamic compromise.

Association of Ongoing Cerebral Oxygen Extraction During Deep Hypothermic Circulatory Arrest With Postoperative Brain Injury

Cardiac surgery utilizing circulatory arrest is most commonly performed under deep hypothermia (∼18°C) to suppress tissue oxygen demand and provide neuroprotection during operative circulatory arrest. Studies investigating the effects of deep hypothermic circulatory arrest (DHCA) on neurodevelopmental outcomes of patients with congenital heart disease give conflicting results. Here, we address these issues by quantifying changes in cerebral oxygen saturation, blood flow, and oxygen metabolism in neonates during DHCA and investigating the association of these changes with postoperative brain injury. Neonates with critical congenital heart disease undergoing DHCA were recruited for continuous intraoperative monitoring of cerebral oxygen saturation (ScO2) and an index of cerebral blood flow (CBFi) using 2 noninvasive optical techniques, diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS). Pre- and postoperative brain magnetic resonance imaging (MRI) was performed to detect white matter injury (WMI). Fifteen neonates were studied, and 11/15 underwent brain MRI. During DHCA, ScO2 decreased exponentially in time with a median decay rate of -0.04 min-1. This decay rate was highly variable between subjects. Subjects who had larger decreases in ScO2 during DHCA were more likely to have postoperative WMI (P=0.02). Cerebral oxygen extraction persists during DHCA and varies widely from patient-to-patient. Patients with a higher degree of oxygen extraction during DHCA were more likely to show new WMI in postoperative MRI. These findings suggest cerebral oxygen extraction should be monitored during DHCA to identify patients at risk for hypoxic-ischemic injury, and that current commercial cerebral oximeters may underestimate cerebral oxygen extraction.

Long-term efficacy and safety of sapropterin in patients who initiated sapropterin at

BackgroundDuring the initial 26-week SPARK (Safety Paediatric efficAcy phaRmacokinetic with Kuvan®) study, addition of sapropterin dihydrochloride (Kuvan®; a synthetic formulation of the natural cofactor for phenylalanine hydroxylase, tetrahydrobiopterin; BH4), to a phenylalanine (Phe)-restricted diet, led to a significant improvement in Phe tolerance versus a Phe-restricted diet alone in patients aged 0–4 years with BH4-responsive phenylketonuria (PKU) or mild hyperphenylalaninaemia (HPA). Based on these results, the approved indication for sapropterin in Europe was expanded to include patients < 4 years of age. Herein, we present results of the SPARK extension study (NCT01376908), evaluating the long-term safety, dietary Phe tolerance, blood Phe concentrations and neurodevelopmental outcomes in patients < 4 years of age at randomisation, over an additional 36 months of treatment with sapropterin.ResultsAll 51 patients who completed the 26-week SPARK study period entered the extension period. Patients who were previously treated with a Phe-restricted diet only (‘sapropterin extension’ group; n = 26), were initiated on sapropterin at 10 mg/kg/day, which could be increased up to 20 mg/kg/day. Patients previously treated with sapropterin plus Phe-restricted diet, remained on this regimen in the extension period (‘sapropterin continuous’ group; n = 25). Dietary Phe tolerance increased significantly at the end of the study versus baseline (week 0), by 38.7 mg/kg/day in the ‘sapropterin continuous’ group (95% CI 28.9, 48.6; p < 0.0001). In the ‘sapropterin extension’ group, a less pronounced effect was observed, with significant differences versus baseline (week 27) only observed between months 9 and 21; dietary Phe tolerance at the end of study increased by 5.5 mg/kg/day versus baseline (95% CI − 2.8, 13.8; p = 0.1929). Patients in both groups had normal neuromotor development and growth parameters.ConclusionsLong-term treatment with sapropterin plus a Phe-restricted diet in patients who initiated sapropterin at < 4 years of age with BH4-responsive PKU or mild HPA maintained improvements in dietary Phe tolerance over 3.5 years. These results continue to support the favourable risk/benefit profile for sapropterin in paediatric patients (< 4 years of age) with BH4-responsive PKU. Frequent monitoring of blood Phe levels and careful titration of dietary Phe intake to ensure adequate levels of protein intake is necessary to optimise the benefits of sapropterin treatment.Trial registration ClinicalTrials.gov, NCT01376908. Registered 17 June 2011, https://clinicaltrials.gov/ct2/show/NCT01376908.