Worse Neurodevelopmental Outcomes Research Articles

Neurodevelopmental Outcomes After Multiple General Anaesthetic Exposure Before Five Years Of Age - A Cohort Study.

The GAS trial demonstrated evidence that most neurodevelopmental outcomes at 2 years and 5 years of age in infants who received a single general anaesthetic (GA) for elective inguinal herniorrhaphy were clinically equivalent when compared to infants who did not receive GA. More than 20% of the children in the trial had at least one subsequent anaesthetic exposure after their initial surgery. Using the GAS database, this study aimed to address whether multiple (2 or more) GA exposures compared to one or no GA exposure in early childhood were associated with worse neurodevelopmental outcomes at 5 years. Children with multiple GA exposures and children with one or no GA exposure were identified from the GAS database. The primary outcome was the full-scale intelligence quotient (FSIQ) on the Wechsler Preschool and Primary Scale of Intelligence third edition (WPPSI-III) at 5 years of age. Secondary outcomes included neurocognitive tests addressing all major developmental domains and caregiver-reported questionnaires assessing emotional and behavioural problems. Complete assessment was available from a total of 90 children in the multiple GA group and 141 children in the 0 or 1 GA group. Compared with children with a single or no GA exposure, multiply exposed children scored on average almost 6 points lower (mean: -5.8, 95% CI: -10.2 to -1.4, p= 0.011) in WPPSI-III FSIQ. They also demonstrated lower verbal and performance IQ scores and more emotional, behavioural, and executive function difficulties. However, significant residual confounding cannot be excluded from the results due to the observational nature of this study. Multiple GA exposure before 5 years of age was associated with reduced performance in general intelligence score and some domains of neurodevelopmental assessments. The clinical significance of our results must be cautiously interpreted in light of several sources of limitations including small sample size and unadjusted residual confounding. This study illustrates the limitations of trial data sets that may not be fit for the purpose for the secondary analysis.

Cortical Alterations Associated with Executive Function Deficits in Youth with a Congenital Heart Defect

Abstract Adolescents and young adults born with a complex congenital heart defect (CHD) are at risk for executive function (ExF) impairments, which contribute to the psychological and everyday burden of CHD. Cortical dysmaturation has been well described in fetuses and neonates with CHD and early evidence suggests that cortical alterations in thickness, surface area, and gyrification index are non-transient and can be observed in adolescents with CHD. However, cortical alterations have yet to be correlated with ExF deficits in youth with CHD. This study aims to use a data-driven approach to identify the most important cortical features associated with ExF deficits in adolescents and young adults with CHD. To do so, we combined two comparable datasets acquired at the Research Institute of the McGill University Health Centre and the University Children’s Hospital Zurich each including both youth with CHD and healthy controls. For each participant, a high-resolution T1-weighted magnetic resonance image, a self-reported ExF assessment (the Behaviour Rating Inventory of Executive Function— Adult Scale), and their clinical and demographic characteristics were available. Corticometric Iterative Vertex-Based Estimation of Thickness (CIVET) was used to extract cortical thickness, cortical surface area, and local gyrification index measures. Using orthogonal projective non-negative matrix factorization (OPNMF), we identified non-overlapping spatial components that integrate cortical thickness, cortical surface area, and local gyrification index and capture structural covariance across these features. Behavioural partial least squares correlation (bPLS) analysis was then used to compute correlations between the individual variability in the OPNMF covariance patterns and ExF outcomes for each subject. A total of 56 youth with CHD who underwent cardiopulmonary bypass surgery before three years of age and 56 age- and sex-matched healthy controls were included in our analyses. Cortical grey matter volume, cortical thickness, and cortical surface area were found to be significantly reduced in CHD patients compared to controls. OPNMF identified 12 stable cortex-wide components summarizing the inter-subject variability in cortical thickness, cortical surface area, and local gyrification index. bPLS revealed two significant latent variables (LV) accounting for a total of 82.8% of the variance in the sample, each describing distinct patterns between the brain and cognitive data. LV1 summarized a pattern of belonging to the CHD group, worse scores on most BRIEF-A scales, younger age at MRI, and female sex. This pattern was associated with increased cortical thickness, local gyrification index, and decreased cortical surface area in several OPNMF components. Finally, we identified a positive relationship between the LV1 brain-behaviour pattern and total aortic cross-clamp time in the CHD group, indicating that longer aortic cross-clamp time was associated with worse neurodevelopmental outcomes. In this study, we uncover novel multivariate relationships between ExF and alterations in cortical thickness, surface area, and local gyrification index in adolescents and young adults with CHD using a data-driven approach. Although our findings highlight the important role played by the cortex in higher order cognitive processes, future studies are needed to elucidate the individual contribution of individual and clinical attributes into the deficits observed in this population.

Postoperative EEG abnormalities in relation to neurodevelopmental outcomes after pediatric cardiac surgery.

We had reported that postoperative EEG background including sleep-wake cycle (SWC) and discharge (seizures, spikes/sharp waves) abnormalities were significantly correlated with adverse early outcomes in children after cardiac surgery. We aimed to analyze the relations between these EEG abnormalities and neurodevelopmental outcomes at about2 years after cardiac surgery. We enrolled 121 patients undergoing cardiac surgery at 3.3 months (0.03 ~ 28 months). EEG abnormalities described above during the first postoperative 48 h were evaluated. Griffiths Mental Development Scales-Chinese was used to evaluate the quotients of overall development and 5 subscales of the child's locomotor, language, personal-social, eye-hand coordination and performance skills at 16 ~ 31 months of age. EEG background abnormalities occurred in 59/121 (48.8%) patients and 33 (55.9%) unrecovered to normal by 48 h. Abnormal SWC occurred in 15 (12.4%) patients and 7 (5.8%) unrecovered to normal by 48 h. EEG seizures occurred in 11 (9.1%) patients with frontal lobe seizures in 4. Spikes/sharp waves occurred in 100 (82.6%). EEG background abnormalities, number of spikes/sharp waves and frontal lobe seizures were significantly associated with neurodevelopmental impairment at about 1 ~ 2 year after surgery (Ps ≤ 0.05). Most parameters of EEG abnormalities were significantly associated with neurodevelopmental impairment after cardiac surgery. Neurodevelopmental impairment in children with congenital heart disease remain poorly understood. Previous studies had reported that either EEG seizures or background abnormalities were associated with worse neurodevelopmental outcomes. Our present study showed that all the EEG background and discharge abnormalities including EEG background, seizures and spikes/sharp waves in the early postoperative period were significantly associated with neurodevelopmental impairment at about 1 ~ 2 years after cardiac surgery. Comprehensive evaluation of early postoperative EEG may provide further insights about postoperative brain injury, its relation with neurodevelopmental impairment, and guide to improve clinical management.

What are the neurodevelopmental outcomes of children with asymptomatic congenital cytomegalovirus infection at birth? A systematic literature review.

Congenital cytomegalovirus (cCMV) is among the most common congenital infections globally. Of 85%-90% cCMV-infected infants without symptoms at birth, 10%-15% develop sequelae, most commonly sensorineural hearing loss (SNHL); their childhood neurodevelopmental outcomes are less well understood. Embase and MEDLINE were searched for publications from 16th September 2016 to 9th February 2024 to identify studies reporting primary data on neurodevelopmental outcomes in children with asymptomatic cCMV (AcCMV), measured using assessment tools or as evaluated by the study investigators, clinicians, educators, or parents. The Newcastle-Ottawa scale was applied to studies to assess risk of bias. Of 28 studies from 18 mostly high-income countries, there were 5-109 children with AcCMV per study and 6/28 had a mean or median age at last follow-up of ≥5years. Children with AcCMV had better neurodevelopmental outcomes than children with symptomatic cCMV in 16/19 studies. Of 9/28 studies comparing AcCMV with CMV-uninfected children, six reported similar outcomes whilst three reported differences limited to measures of full-scale intelligence and receptive vocabulary among children with AcCMV and SNHL, or more generally in motor impairment. Common limitations of studies for our question were a lack of cCMV-uninfected controls, heterogeneous definitions of AcCMV, lack of focus on neurodevelopment, selection bias and inadequate follow-up. There was little evidence of children with AcCMV having worse neurodevelopmental outcomes than CMV-uninfected children, but this conclusion is limited by study characteristics and quality; findings highlight the need for well-designed and standardised approaches to investigate long-term sequelae.

Does surgery affect the neurodevelopmental outcome of moderate laryngomalacia?

BackgroundModerate laryngomalacia lies in the grey zone where the parents and treating team might hesitate to decide the treatment plan for the child. Neurodevelopmental assessment of the child was neither assessed nor incorporated in surgical decision-making in the past. ObjectivesTo evaluate the neurodevelopmental outcome of moderate laryngomalacia treatment strategies (surgery versus conservative). MethodsWe conducted an observational multicentric cohort study. We compared two groups of patients according to their moderate laryngomalacia treatment strategy: surgical treatment and no treatment. The neurodevelopmental outcome was assessed by Griffiths-III developmental scales. ResultsA total of 150 children were diagnosed with moderate laryngomalacia of which 56 were successfully treated with surgery and 94 improved without intervention. The median Griffiths-III developmental quotients (DQs) of subscales A, B, C, E, and general development were significantly higher in the surgically treated group compared to conservatively treated ones. ConclusionUntreated moderate laryngomalacia cases have worse neurodevelopmental outcomes than surgically treated cases.

Genetic and Congenital Anomalies in Infants With Hypoxic-Ischemic Encephalopathy

BackgroundInfants with hypoxic ischemic encephalopathy (HIE) may have underlying conditions predisposing them to hypoxic-ischemic injury during labor and delivery. It is unclear how genetic and congenital anomalies impact outcomes of HIE. MethodsInfants with HIE enrolled in a phase III trial underwent genetic testing when clinically indicated. Infants with known genetic or congenital anomalies were excluded. The primary outcome, i.e., death or neurodevelopmental impairment (NDI), was determined at age two years by a standardized neurological examination, Bayley Scales of Infant Development, Third Edition (BSID-III), and the Gross Motor Function Classification Scales. Secondary outcomes included cerebral palsy and BSID-III motor, cognitive, and language scores at age two years. ResultsOf 500 infants with HIE, 24 (5%, 95% confidence interval 3% to 7%) were diagnosed with a genetic (n = 15) or congenital (n = 14) anomaly. Infants with and without genetic or congenital anomalies had similar rates of severe encephalopathy and findings on brain magnetic resonance imaging. However, infants with genetic or congenital anomalies were more likely to have death or NDI (75% vs 50%, P = 0.02). Among survivors, those with a genetic or congenital anomaly were more likely to be diagnosed with cerebral palsy (32% vs 13%, P = 0.02), and had lower BSID-III scores in all three domains than HIE survivors without such anomalies. ConclusionsAmong infants with HIE, 5% were diagnosed with a genetic or congenital anomaly. Despite similar clinical markers of HIE severity, infants with HIE and a genetic or congenital anomaly had worse neurodevelopmental outcomes than infants with HIE alone.

Abstract 14308: Perioperative Cyclohexanone Exposure During Neonatal Congenital Heart Surgery Potentiates Brain Injury

Introduction: Neurodevelopmental delay is hallmark for children with congenital heart defects. Risk factors include industrial contaminants in medical devices, such as cyclohexanone. Hypothesis: To evaluate associations between perioperative cyclohexanone and cyclohexanone metabolites with perioperative biomarkers of brain injury. Methods: From 75 neonates who underwent congenital heart surgery involving cardiopulmonary bypass (CPB), we assayed perioperative serum samples (preoperation, post-CPB, 24 hours postoperation) for cyclohexanone, two cyclohexanone metabolites (trans-1,2- and trans-1,4-cyclohexanediol), and biomarkers of brain injury: glial fibrillary acidic protein (GFAP), neurofilament light (NF-L), and Tau. We calculated the molar sum of cyclohexanone metabolites (Σmetabolites), and at each timepoint we used quantile regression to evaluate differences in median brain injury biomarker concentrations (pg/mL) per doubling in concentration of cyclohexanone or Σmetabolites (ng/mL). We adjusted associations for cyclohexanone assay batch, postnatal age at surgery (days), weight at surgery (kg), The Society of Thoracic Surgeons and The European Association for Cardio-Thoracic Surgery (STAT) mortality risk category, and total duration of CPB (min). Results: In adjusted analyses, a doubling in preoperation cyclohexanone concentration was associated with a 19 pg/mL (95% CI: 3, 35) greater median Tau concentration. Similarly, a doubling in post CPB cyclohexanone was associated with an 88 pg/mL (95% CI: 20, 156) greater median concentration of Tau and 137 pg/mL (95% CI: 54, 220) greater median concentration of NF-L. Associations with Σmetabolites were generally null, though a doubling in post-CPB concentration was associated with a 34.7 pg/mL (95% CI: -0.8, 70) greater NF-L and 54.1 pg/mL (95% CI: 15, 94) greater Tau concentration. Associations with GFAP at all timepoints were null. Conclusions: Perioperative cyclohexanone exposure is associated with worse neurodevelopmental outcomes and in this study, cyclohexanone levels were associated with NF-L and Tau which are measures of axonal damage. Interventions to reduce cyclohexanone exposure may improve long term neurodevelopment.

Neurodevelopmental outcomes of preterm neonates receiving rescue inhaled nitric oxide in the first week of age: a cohort study

ObjectiveTo assess the neurodevelopmental outcomes of preterm neonates who received inhaled nitric oxide (iNO) in the first week of age for hypoxaemic respiratory failure (HRF).MethodsIn this retrospective cohort study, we...

Neurodevelopmental Outcomes in Infants Screened for Retinopathy of Prematurity

Preterm infants screened for retinopathy of prematurity (ROP) are at risk for heterogenous neurodevelopment outcomes that are difficult to predict. To characterize the potential association between socioeconomic and clinical risk factors and neurodevelopmental outcomes in a diverse, multicenter cohort of premature neonates screened for ROP. This was a retrospective cohort study using electronic medical records and US Census Bureau income data. This study was performed at academic (University of California, Los Angeles [UCLA] Mattel Children's Hospital and UCLA Santa Monica Hospital), community (Cedars-Sinai Medical Center), and LA county (Harbor-UCLA Medical Center) neonatal intensive care units. Participants included infants who met American Academy of Pediatrics guidelines for ROP screening and had records from at least 1 Bayley Scales of Infant and Toddler Development (BSID) neurodevelopment assessment between 0 and 36 months of adjusted age. Data analyses were conducted from January 1, 2011, to September 1, 2022. Demographic and clinical information, proxy household income, and health insurance type were collected as risk factors. Neurodevelopmental outcomes in the cognitive, language, and motor domains measured via BSID were the primary outcomes. A total of 706 infants (mean [SD] age, 28.6 [2.4] weeks; 375 male [53.1%]) met inclusion criteria. In a multivariable model, which included adjustments for birth weight, sex, insurance type, intraventricular hemorrhage (IVH), and age at assessment, public health insurance was associated with a 4-fold increased risk of moderate to severe neurodevelopmental impairment (NDI) in cognitive and language domains (cognitive, odds ratio [OR], 3.65; 95% CI, 2.28-5.86; P = 8.1 × 10-8; language, OR, 3.96; 95% CI, 2.61-6.02; P = 1.0 × 10-10) and a 3-fold increased risk in the motor domain (motor, OR, 2.60; 95% CI, 1.59-4.24; P = 1.4 × 10-4). In this adjusted model, clinical factors that were associated with an increased risk of moderate to severe NDI included lower birth weight, diagnosis of IVH, male sex, and older age at time of Bayley assessment. In unadjusted analyses, infants who received either laser or anti-VEGF treatment, compared with infants without treatment-requiring ROP, had lower BSID scores in multiple domains at 0 to 12 months, 12 to 24 months, and 24 to 36 months (DATA). In the multivariable model, treatment type was no longer associated with worse neurodevelopmental outcomes in any domain. Study results suggest an association between public insurance type and NDI in a diverse population screened for ROP, indicating the complexities of neurodevelopment. This study also supports the early neurodevelopmental safety of anti-VEGF treatment, as anti-VEGF therapy was not found to be independently associated with worse NDI in any domain.

Fetal insular measurements in pregnancy with estimated fetal weight

A growing body of evidence suggests that fetal growth restriction is associated with changes in brain structures as a result of chronic hypoxia. However, less is known about the effects of growth restriction on the fetal insula, particularly in less severely affected late-onset growth-restricted fetuses. This study aimed to (1) compare sonographic insular measurements between fetal-growth restricted, small-for-gestational-age, and appropriate-for-gestational-age control fetuses; and (2) evaluate the association of sonographic insular measurements with perinatal and neurodevelopmental outcomes in fetuses categorized as fetal-growth restricted or small-for-gestational-age. This was a cohort study of singleton nonanomalous pregnancies with an estimated fetal weight <10th centile. Using data from the last examination before delivery, fetal insular depth, Sylvian fissure depth, hypoechoic insular zone thickness, circumference, and area were measured. All measurements were adjusted for by head circumference. Neurodevelopmental outcomes were evaluated at 2 to 3 years of age using the Bayley-III scales. Kruskal-Wallis H tests were performed to compare insular measurements between groups. Paired t tests were used to compare insular measurements between appropriate-for-gestational-age fetuses and gestational age-matched growth-restricted fetuses. Insular measurements for patients with and without an adverse perinatal outcome were compared using independent-samples t-tests. Spearman correlations were performed to evaluate the relationship of insular measurements to the percentile scores for each of the 5 Bayley-III subscales and to a summative percentile of these subscales. A total of 89 pregnancies were included in the study; 68 of these pregnancies had an estimated fetal weight <10th percentile (fetal-growth restricted: n=39; small-for-gestational-age: n=29). The appropriate-for-gestational-age cohort consisted of 21 pregnancies. The gestational age at measurement was similar between fetal-growth restricted and small-for-gestational-age groups, but lower in the appropriate-for-gestational-age group. Differences between groups were noted in normalized insular depth, Sylvian fissure depth, and hypoechoic insular zone (P<.01). Normalized insular depth and hypoechoic insular zone circumference were larger in the growth-restricted cohort (P<.01). Normalized Sylvian fissure depth was smaller in the growth-restricted cohort (P<.01). There were no significant differences in insular measurements between pregnancies with and without an adverse perinatal outcome. Bayley-III results were available in 32 of the growth-restricted cases. Of all insular measurements, hypoechoic insular zone circumference was inversely correlated with the adaptive behavior Bayley-III score. In our cohort, fetuses with estimated fetal weight <10th percentile had smaller Sylvian fissure depths and larger insular depths and hypoechoic insular zone circumferences than normally grown controls. A larger hypoechoic insular zone circumference was substantially correlated with worse neurodevelopmental outcomes in early childhood. We speculate that enlargement of this region may be an indication of accelerated neuronal maturation in growth-restricted fetuses with mild hypoxia.

Assessment of Neurodevelopment and Growth in Congenital Hypothyroidism: Serial 6-Year Follow-up Study of 408 Patients.

The link between congenital hypothyroidism (CH) and neurodevelopment is suggested, yet studies applying quantifiable measures are lacking. Moreover, socioeconomic disparities and subtle variation in timing of approach make the relationship difficult to detect. To evaluate associations between CH and abnormalities in neurodevelopment and growth and determine the critical period for intervention. We utilized a nationwide database to conduct a longitudinal analysis of 919 707 children. Exposure to CH was identified using claims-based data. The primary outcome of interest was suspected neurodevelopmental disorder, as measured using the Korean Ages & Stages Questionnaires (K-ASQ) administered annually from 9 to 72 months of age. Secondary outcomes were height and BMI z-scores. After randomly matching cases and controls at a 1:10 ratio, we employed inverse probability of treatment weighting and generalized estimating equation models for our analyses. We conducted subgroup analysis based on the age of treatment initiation. The prevalence of CH in our population was 0.05% (n = 408). Relative to the control group, the CH group had higher risk of suspected neurodevelopmental disorders (propensity score-weighted odds ratio: 4.52; 95% CI: 2.91, 7.02), and significantly increased risk in each of the 5 K-ASQ domains. No time interactions were noted at any rounds for the outcomes according to when the neurodevelopmental assessment was conducted (all P for interaction >.05). The CH group also had higher risk for low height-for-age z-score, but not for elevated BMI-for-age z-score. In subgroup analysis, delayed medication for CH correlated with worse neurodevelopmental outcomes. The CH group had worse neurodevelopmental outcomes and reduced height-for-age z-score. Outcomes were worse when onset of treatment was increasingly delayed.

Early brain magnetic resonance imaging findings and neurodevelopmental outcome in children with congenital heart disease: A systematic review.

To investigate the association between early brain magnetic resonance imaging (MRI) findings and neurodevelopmental outcome (NDO) in children with congenital heart disease (CHD). A search for studies was conducted in Embase, Medline, Web of Science, Cochrane Central, PsycINFO, and Google Scholar. Observational and interventional studies were included, in which patients with CHD underwent surgery before 2 months of age, a brain MRI scan in the first year of life, and neurodevelopmental assessment beyond the age of 1 year. Eighteen studies were included. Thirteen found an association between either quantitative or qualitative brain metrics and NDO: 5 out of 7 studies showed decreased brain volume was significantly associated with worse NDO, as did 7 out of 10 studies on brain injury. Scanning protocols and neurodevelopmental tests varied strongly. Reduced brain volume and brain injury in patients with CHD can be associated with impaired NDO, yet standardized scanning protocols and neurodevelopmental assessment are needed to further unravel trajectories of impaired brain development and its effects on outcome.

EBNEO commentary: Early amino acids in extremely preterm infants and neurodisability at 2 years.

Preterm infants require nutritional support immediately after birth to prevent catabolism and support normal growth, often in the setting of increased energy requirements due to postnatal environmental conditions and critical illness. Observational studies in preterm infants have shown that there is a positive association between protein intake in the first month of life, short-term growth outcomes at NICU discharge1 and long-term neurodevelopmental outcomes.2, 3 However, a meta-analysis of randomised controlled trials found that preterm infants with higher intake of parenteral amino acids demonstrated improved postnatal growth but did not show improvement in neurodevelopmental outcomes compared with infants who received lower intake of amino acids.4 Despite evidence for the benefit of early protein delivery on growth in the preterm infant, there are still many questions about the optimal dosing regimen of parenteral amino acids, including starting dose, maximal intake dose, timing and speed of increase in delivery. For example, there have been small, randomised controlled trials that have raised concerns for adverse effects from high-dose (>3 g/kg/day) parenteral amino acids advanced rapidly in the first week of life, including smaller head circumference at NICU discharge5, 6 and reduced growth through the first 2 years of life.7 In this multicenter, double-blind, randomised control trial, extremely low-birth-weight infants who received higher parenteral amino acid intake in the first 5 days of life (3.4 ± 0.6 vs 2.6 ± 0.6 g/kg/day) did not have improved survival without neurodevelopmental impairment at 2 years of corrected gestational age. In fact, higher amino acid intake was associated with higher rates of moderate-to-severe neurodisability than neonates who received lower amino acid intake. Although increased protein intake was associated with improved growth in the first month of life, there were no differences in growth at 2 years old. This study was adequately powered and is the largest study to date to test for differences in neurodevelopmental outcome as a result of amino acid dose in the first week of life. The investigators provided a difference of 0.8 g/kg per day of protein between groups, thus isolating its effect over other components of parenteral nutrition. Limitations included that additional amino acids were only administered for 5 days; it is unclear whether prolonged supplementation would change outcomes. Outcomes at 2 years old weakly predict outcomes in school-aged children. Plasma amino acid concentrations were not reported, but are critical to determine whether current paediatric amino acid solutions are adequate for preterm infants. In summary, increasing parenteral amino acid intake via the umbilical arterial catheter for 5 days after birth does not improve neurodevelopmental outcomes or growth at 2 years in preterm infants; higher protein intake may be associated with worse neurodevelopmental outcomes. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition recommends that preterm infants should not receive more than 3.5 g/kg/day of parenteral amino acids unless administered in a clinical trial.8 This study supports that recommendation; clinicians should be cautious of excessive parenteral protein administration to preterm infants especially in the first 5 days of life. URL LINK: https://ebneo.org/ebneo-commentary-early-amino-acids-and-nd-outcomes/ None. None.

Critical congenital heart disease beyond HLHS and TGA: neonatal brain injury and early neurodevelopment.

Characterization of brain injury and neurodevelopmental (ND) outcomes in critical congenital heart disease (cCHD) has primarily focused on hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA). This study reports brain injury and ND outcomes among patients with heterogeneous cCHD diagnoses beyond HLHS and TGA. This prospective cohort study included infants with HLHS, TGA, or heterogenous "Other cCHD" including left- or right-sided obstructive lesions, anomalous pulmonary venous return, and truncus arteriosus. Brain injury on perioperative brain MRI and ND outcomes on the Bayley-II at 30 months were compared. A total of 218 participants were included (HLHS = 60; TGA = 118; "Other cCHD" = 40, including 8 with genetic syndromes). Pre-operative (n = 209) and post-operative (n = 189) MRI showed similarly high brain injury rates across groups, regardless of cardiopulmonary bypass exposure. At 30 months, participants with "Other cCHD" had lower cognitive scores (p = 0.035) compared to those with HLHS and TGA, though worse ND outcome in this group was driven by those with genetic disorders. Frequency of brain injury and neurodevelopmental delay among patients with "Other cCHD" is similar to those with HLHS or TGA. Patients with all cCHD lesions are at risk for impaired outcomes; developmental and genetic screening is indicated. This study adds to literature on risk of brain injury in patients with critical congenital heart disease (cCHD) diagnoses other than hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA), a heterogenous cohort of patients that has often been excluded from imaging studies. Children with cCHD beyond HLHS and TGA have similarly high rates of acquired brain injury. The high rate of neurodevelopmental impairment in this heterogenous group of cCHD diagnoses beyond HLHS and TGA is primarily driven by patients with comorbid genetic syndromes such as 22q11.2 deletion syndrome.

Feeding and developmental outcomes after neonatal seizures-A prospective observational study.

Among neonates with acute symptomatic seizures, we evaluated whether inability to take full feeds at time of hospital discharge from neonatal seizure admission is associated with worse neurodevelopmental outcomes, after adjusting for relevant clinical variables. This prospective, 9-center study of the Neonatal Seizure Registry (NSR) assessed characteristics of infants with seizures including: evidence of brainstem injury on MRI, mode of feeding upon discharge, and developmental outcomes at 12, 18, and 24 months. Inability to take oral feeds was identified through review of medical records. Brainstem injury was identified through central review of neonatal MRIs. Developmental outcomes were assessed with the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) at 12, 18, and 24 months corrected age. Among 276 infants, inability to achieve full oral feeds was associated with lower total WIDEA-FS scores (160.2±25.5 for full oral feeds vs. 121.8±42.9 for some/no oral feeds at 24 months, p<0.001). At 12 months, a G-tube was required for 23 of the 49 (47%) infants who did not achieve full oral feeds, compared with 2 of the 221 (1%) who took full feeds at discharge (p<0.001). Inability to take full oral feeds upon hospital discharge is an objective clinical sign that can identify infants with acute symptomatic neonatal seizures who are at high risk for impaired development at 24 months.

Syndromic and non-syndromic etiologies causing neonatal hypocalcemic seizures.

The diagnosis of neonatal hypocalcemic seizures (HS) in newborns is made based on clinical signs and serum calcium level. Their etiology is broad and diverse, and timely detection and initiation of treatment is essential. We retrospectively reviewed 1029 patients admitted to the neonatal intensive care unit. Neonatal HS were diagnosed in 16 patients, and we compared etiologies and clinical outcomes, including clinical seizures and neurodevelopment at least over 1 year old. The etiologies can be broadly categorized into 5 syndromic and 11 non-syndromic neonatal HS. Syndromic neonatal HS included 3 Digeorge syndrome, 1 Kleefstra syndrome and 1 Alström syndrome. Non-syndromic neonatal HS included 8 vitamin D deficiency, 1 hypoparathyroidism, and 2 hypoxic-ischemic encephalopathy. Patients with syndromic neonatal HS were found to have worse clinical outcomes than those with nonsyndromic HS. In eight patients with vitamin D deficiency, neurodevelopment was normal. Five of five patients (100%) with syndromic HS used two or more antiseizure drugs. However, among patients with non-syndromic neonatal HS, only one of 11 (9.1%) used more than one drug (p = 0.001). This finding highlighted that syndromic hypocalcemic seizures in newborns have worse neurodevelopmental outcomes and are more often difficult to manage, and would benefit from a genetic diagnostic approach.

Impact of tight glycemic control and hypoglycemia after pediatric cardiac surgery on neurodevelopmental outcomes at three years of age: Findings from a randomized clinical trial

BackgroundStudies examining the impact of randomization As per standard instruction, city is required for affiliations; however, this information is missing in affiliation 6. Please check if the provided city is correct and amend if necessary. to tight glycemic control (TGC) and resultant hypoglycemia on later neurodevelopmental outcomes have produced mixed results. Our study examined this association in children undergoing cardiac surgery.MethodsParticipants who were enrolled in the Safe Pediatric Euglycemia after Cardiac Surgery (SPECS) trial returned for neurodevelopmental (ND) follow-up between 30 to 42.5 months of age. ND outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. ND scores were compared between the TGC and standard care treatment groups and between patients with moderate to severe and no to mild hypoglycemia. As a secondary analysis, to increase sample size and power, we combined the three-year-old assessments with previously collected assessments done at < 30 months of age to further examine differences between groups longitudinally.ResultsAmong the 269 participants who completed neurodevelopmental evaluation (in-person testing or questionnaires) at three years of age (follow-up rate, 31%), there were no statistically significant differences in ND outcomes according to treatment group or hypoglycemia status. In the combined analysis of all evaluations (from 9 to 42.5 months of age), we found no treatment group differences. However, in these longitudinal analyses, children who experienced moderate to severe hypoglycemia had lower scores on the Bayley-III cognitive and motor domains compared to children with no to mild hypoglycemia.ConclusionsFor infants undergoing cardiac surgery, there was no impact of tight glycemic control on neurodevelopmental outcomes. Moderate to severe hypoglycemia was associated with worse ND outcomes in longitudinal analyses.Trial registrationClinicalTrials.gov NCT00443599. Registered: November 2016.

Sleep disturbances in infants and young children following an acquired brain injury.

Sleep disturbances impact over half of older children and teens with acquired brain injury (ABI) following critical care hospitalization but are underevaluated in infants and young children. Given the importance of sleep in brain development and healing after injury, we hypothesized sleep disturbances would be associated with worse neurodevelopmental outcomes in infants with ABI. We performed a retrospective cohort study of 68 children aged 2-32 months following critical care hospitalization for ABI. The Brief Infant Sleep Questionnaire assessed sleep disturbances. Bayley Scales of Infant and Toddler Development, third edition and Adaptive Behavior Assessment System, third edition assessed developmental and adaptive functioning outcomes, respectively. t tests compared sleep characteristics in infants with ABI to historical healthy controls. Spearman's correlation evaluated relationships among sleep and outcomes. Multiple linear regression investigated relationships controlling for demographic and ABI characteristics. Compared to healthy controls, children with ABI had shorter nighttime sleep duration (P = .01), longer daytime sleep duration (P < .001), and longer duration of nighttime awakenings (P < .001). Duration of night awakenings negatively correlated with Bayley Cognitive scores (Spearman's correlation = -.40). Night awakenings negatively correlated with worse Adaptive Behavior Assessment System, third edition General Adaptive Composite scores (Spearman's correlation = -.42). When controlling for demographic and ABI characteristics, ≥ 3 awakenings was significantly associated with worse Adaptive Behavior Assessment System, third edition General Adaptive Composite (β = -11.3; 95% confidence interval = -19.2, -3.5). Sleep disturbances are associated with poorer outcomes in infants and toddlers after ABI. Sleep is vital to recovery and a potentially modifiable target to improve outcomes. Klapp JM, Hall TA, Riley AR, Williams CN. Sleep disturbances in infants and young children following an acquired brain injury. J Clin Sleep Med. 2022;18(10):2387-2395.

Effects of single and combined exposure to lead and stress during pregnancy on offspring neurodevelopment

ObjectiveTo assess associations of single and combined exposures to lead and stress during different stages of pregnancy with offspring neurodevelopment. MethodsWe measured prenatal lead (maternal blood-lead in early-pregnancy and umbilical-cord-blood-lead) and maternal stress levels in Shanghai-Birth-Cohort from 2013 to 2016. Maternal stress was assessed using Center-for-Epidemiological-Studies-Depression-Scale and Self-Rating-Anxiety-Scale during mid-pregnancy. The Ages-Stages-Questionnaires-3 (at 6/12-months-of-age) and Bayley-III (at 24-months-of-age) were both used to assess neurodevelopment. ResultsA total of 2132 mother-child pairs with both prenatal lead and stress measurements were included. The geometric-means of blood-lead in early-pregnancy and cord-blood-lead were 1.46 μg/dL and 1.33 μg/dL, respectively. Among the study women, 1.89 % and 0.14 % were screened positive for depression and anxiety. Adjusting for related confounders, the combined exposures had stronger adverse associations with offspring social-emotional skills than single exposures; and the combined exposure in early-pregnancy was associated with greater neurodevelopmental differences than combined exposure around-birth, especially in social-emotion at 24 months-of-age [β (95 %CI): − 10.48(−17.42, −3.54) vs. − 5.95(−11.53, −0.36)]. ConclusionsBoth single and combined prenatal exposures to lead/stress impaired infant neuro-development, and the effects of combined exposure may be more profound than single exposures. Combined exposure in early-pregnancy may be associated with worse neurodevelopmental outcomes than combined exposure around-birth, especially in social-emotional development.

Dexamethasone, Prednisolone, and Methylprednisolone Use and 2-Year Neurodevelopmental Outcomes in Extremely Preterm Infants

Practice variability exists in the use of corticosteroids to treat or prevent bronchopulmonary dysplasia in extremely preterm infants, but there is limited information on longer-term impacts. To describe the use of corticosteroids in extremely preterm infants and evaluate the association with neurodevelopmental outcomes. This cohort study was a secondary analysis of data from the Preterm Erythropoietin Neuroprotection (PENUT) randomized clinical trial, conducted at 19 participating sites and 30 neonatal intensive care units (NICUs) in the US. Inborn infants born between 24 0/7 and 27 6/7 weeks gestational age between December 2013 and September 2016 were included in analysis. Data analysis was conducted between February 2021 and January 2022. Cumulative dose of dexamethasone and duration of therapy for dexamethasone and prednisolone or methyl prednisolone were evaluated. Demographic and clinical characteristics were described in infants who did or did not receive corticosteroids of interest and survived to discharge. Neurodevelopmental outcomes at 2 years of age were evaluated using the Bayley Scales of Infant Development-Third Edition (BSID-III) at corrected age 2 years. A total of 828 extremely preterm infants (403 [49%] girls; median [IQR] gestational age, 26 [25-27] weeks) born at 19 sites who survived to discharge were included in this analysis, and 312 infants (38%) were exposed to at least 1 corticosteroid of interest during their NICU stay, including 279 exposed to dexamethasone, 137 exposed to prednisolone or methylprednisolone, and 79 exposed to both. Exposed infants, compared with nonexposed infants, had a lower birth weight (mean [SD], 718 [168] g vs 868 [180] g) and were born earlier (mean [SD] gestational age, 25 [1] weeks vs 26 [1] weeks). The median (IQR) start day was 29 (20-44) days for dexamethasone and 53 (30-90) days for prednisolone or methylprednisolone. The median (IQR) total days of exposure was 10 (5-15) days for dexamethasone and 13 (6-25) days for prednisolone or methylprednisolone. The median (IQR) cumulative dose of dexamethasone was 1.3 (0.9-2.8) mg/kg. After adjusting for potential confounders, treatment with dexamethasone for longer than 14 days was associated with worse neurodevelopmental outcomes, with mean scores in BSID-III 7.4 (95% CI, -12.3 to -2.5) points lower in the motor domain (P = .003) and 5.8 (95% CI, -10.9 to -0.6) points lower in the language domain (P = .03), compared with unexposed infants. These findings suggest that long duration and higher cumulative dose of dexamethasone were associated with worse neurodevelopmental scores at corrected age 2 years. Potential unmeasured differences in the clinical conditions of exposed vs unexposed infants may contribute to these findings. Improved standardization of treatment and documentation of indications would facilitate replication studies.