Identifying novel data-driven subgroups in congenital heart disease using multi-modal measures of brain structure.

Individuals with congenital heart disease (CHD) have an increased risk of neurodevelopmental impairments. Given the hypothesized complexity linking genomics, atypical brain structure, cardiac diagnoses and their management, and neurodevelopmental outcomes, unsupervised methods may provide unique insight into neurodevelopmental variability in CHD. Using data from the Pediatric Cardiac Genomics Consortium Brain and Genes study, we identified data-driven subgroups of individuals with CHD from measures of brain structure. Using structural magnetic resonance imaging (MRI; N = 93; cortical thickness, cortical volume, and subcortical volume), we identified subgroups that differed primarily on cardiac anatomic lesion and language ability. In contrast, using diffusion MRI (N = 88; white matter connectivity strength), we identified subgroups that were characterized by differences in associations with rare genetic variants and visual-motor function. This work provides insight into the differential impacts of cardiac lesions and genomic variation on brain growth and architecture in patients with CHD, with potentially distinct effects on neurodevelopmental outcomes.

Risk Factors for Admission Hyperthermia and Associated Outcomes in Infants Born Preterm.

Maternal, placental, and neonatal factors were compared between infants born at ≤29 weeks of gestational age with admission hyperthermia (>37.5○C) and euthermia (36.5-37.5○C). Admission hyperthermia was associated with longer duration of face-mask positive-pressure ventilation and infant's temperature ≥37.5○C in the delivery room. Infants born preterm with admission hyperthermia had greater odds of developing necrotizing enterocolitis and neurodevelopmental impairment.

Neurodevelopmental outcomes of extremely preterm infants with bronchopulmonary dysplasia (BPD) - A retrospective cohort study.

OBJECTIVE: To investigate the neurodevelopmental outcomes for preterm infants born < 29 weeks gestation with/without bronchopulmonary dysplasia (BPD). STUDY DESIGN: Preterm infants < 29 weeks' gestation born 2007-2018 in New South Wales and the Australian Capital Territory, Australia, were included. Infants who died < 36 weeks' postmenstrual age and those with major congenital anomalies were excluded. Subjects were assessed at 18-42 months corrected age using the Bayley Scales of Infant Development, 3rd edition. RESULTS: 1436 infants without BPD (non-BPD) and 1189 infants with BPD were followed. The BPD group, 69 % infants were discharged without respiratory support (BPD1), 29 % on oxygen (BPD2) and 2 % on pressure support/tracheostomy (BPD3). Moderate neurodevelopmental impairment (NDI) was evident in 5.7 % of non-BPD infants, 11 % BPD1, 15 % BPD2, 15 % BPD3 infants. Severe NDI was seen in 1.7 % non-BPD infants, 3.4 % BPD1, 7.3 % BPD2, 35 % BPD3 infants. After adjusting for confounders, infants with BPD2 (OR 2.24, 99.9 % CI 1.25 to 5.77) or BPD3 (OR 5.99, 99.9 % CI 1.27 to 46.77) were more likely to have moderate-severe NDI compared to non-BPD infants. CONCLUSION: The majority of infants with BPD were discharged home without respiratory support and had better neurocognitive outcomes in early childhood compared to those that required home-based oxygen or respiratory support.

Searching molecular biomarkers correlating with BSID-III at 24 months in infants with neonatal hypoxic-ischemic encephalopathy.

An early prediction of outcomes of neonatal hypoxic-ischemic encephalopathy (NE) is of key importance in reducing neonatal mortality and morbidity. The objectives were (i) to analyze the characteristics of miRNA expression and metabolic patterns of neonates with NE and (ii) to assess their predictive performance for neurodevelopmental outcomes. Plasma samples from moderate/severe NE patients (N = 92) of the HYPOTOP study were collected before, during, and after therapeutic hypothermia (TH) and compared to a control group (healthy term infants). The expression of miRNAs and concentrations of metabolites (hypoxia-related and energy, steroid, and tryptophan metabolisms) were analyzed. Neurodevelopmental outcomes were evaluated at 24 months postnatal age using Bayley Scales of Infant Development, ed. III, BSID-III. Differences in miRNA and metabolic profiles were found between NE vs. control infants, abnormal (i.e., mildly and moderately abnormal and severe) vs. normal, and severe vs. non-severe (i.e., normal and mildly and moderately abnormal) BSID-III. 4-Androstene-3,17-dione, testosterone, betaine, xanthine, and lactate were suitable for BSID-III outcome prediction (receiver operating characteristic areas under the curve (AUCs) ≥ 0.6), as well as 68 miRNAs (AUCs of 0.5-0.9). Significant partial correlations of xanthine and betaine levels and the expression of several miRNAs with BSID-III sub-scales were found. Conclusion: We have identified metabolites/miRNAs that might be useful to support the prediction of middle-term neurodevelopmental outcomes of NE. What is known and what is new: • The early prediction of outcomes of neonatal hypoxic-ischemic encephalopathy (NE) is of key importance in reducing neonatal mortality and morbidity. • Alterations of the metabolome and miRNAs had been observed in NE. • We performed miRNA sequencing and quantified selected metabolites (i.e., lactate, pyruvate, ketone bodies, Krebs cycle intermediates, tryptophan pathway, hypoxia-related metabolites, and steroids) by GC- and LC-MS. • Specific miRNAs and metabolites that allow prediction of middle-term neurodevelopmental outcomes of newborns with NE undergoing hypothermia treatment were identified.

Associations between the social environment and early childhood developmental outcomes of Puerto Rican children with prenatal Zika virus exposure: a cross-sectional study.

BACKGROUND: Prenatal exposure to the Zika virus can lead to microcephaly and adverse developmental outcomes, even in children without evident birth defects. The social environment plays a crucial role in infant health and developmental trajectories, especially during periods of heightened brain plasticity. The study aimed to assess socioenvironmental factors as predictors of developmental outcomes of 36-month-old children exposed to Zika virus prenatally. STUDY DESIGN: This cross-sectional study included 53 mothers and 55 children enrolled in the Pediatric Outcomes of Prenatal Zika Exposure cohort study in Puerto Rico. The study performs follow-up developmental assessments of children born to mothers with confirmed and probable Zika virus infection during pregnancy. Mothers completed socioenvironmental questionnaires (e.g., Perceived Neighborhood Scale and US Household Food Insecurity Survey). Children's developmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development: Third Edition, the Ages and Stages Questionnaires: Third Edition, the Ages and Stages Questionnaire-Socioemotional: Second Edition, and the Child Adjustment and Parent Efficacy Scale. RESULTS: Linear regression models, adjusting for a child's sex and age and maternal education, revealed that early life exposure to food insecurity and maternal pregnancy stressors were significantly associated with poorer developmental outcomes in Zika virus-exposed children at 36 months of age. Maternal resilience representation of adaptive ability was associated with the preservation of adequate developmental outcomes in children. CONCLUSIONS: Pregnancy and early childhood are critical life periods for ensuring optimal brain development in children. While the mechanisms in the interaction of children with their environment are complex, the risk and protective factors identified in the study are modifiable through public policy and preventive initiatives. Implementation of comprehensive strategies that improve access to social support programs, educational and nutritional interventions, and mental health services during pregnancy and early childhood can enhance the developmental potential of vulnerable children.

Association between maternal antidepressant use during pregnancy and the risk of autism spectrum disorder and attention deficit hyperactivity disorder in offspring.

Prenatal antidepressant exposure has been reported to be associated with adverse neurodevelopmental outcomes, yet studies considering confounding factors in Asian populations are lacking. This study utilized a nationwide data base in Taiwan, enrolling all liveborn children registered in the National Health Insurance system between 2004 and 2016. Subjects were divided into two groups: antidepressant-exposed (n = 55,707)) and antidepressant-unexposed group (n = 2,245,689). The effect of antidepressant exposure during different trimesters on autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) was examined. Sibling controls and parallel comparisons by paternal exposure status were treated as negative controls. Additional sensitivity analyses were conducted to examine the effects of antidepressant exposure before and after pregnancy. Prenatal antidepressant exposure was associated with increased risks of ASD and ADHD in population-wide and adjusted analysis. However when comparing antidepressant-exposed children with their unexposed siblings, no differences were found for ASD (Hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.76-1.42 in first trimester; HR: 0.96, 95% CI 0.62-1.50 in second trimester; HR: 0.69, 95% CI 0.32-1.48 in third trimester) and ADHD (HR: 0.98, 95%CI 0.84-1.15 in first trimester; HR: 0.91, 95% CI 0.73-1.14 in second trimester; HR: 0.79, 95% CI 0.54-1.16 in third trimester). Increased risks for ASD and ADHD were also noted in paternal control, before and after pregnancy analyses. These results imply that the association between prenatal antidepressant exposure and ASD and ADHD is not contributed to by an intrauterine medication effect but more likely to be accounted for by maternal depression, genetic, and potential environmental factors.

Neurodevelopmental outcomes at 18 months of children diagnosed with CHD compared to children born very preterm.

OBJECTIVE: To compare neurodevelopmental outcomes and parent behaviour ratings of children born term with CHD to children born very preterm. METHODS: A clinical research sample of 181 children (CHD [n = 81]; very preterm [≤32 weeks; n = 100]) was assessed at 18 months. RESULTS: Children with CHD and born very preterm did not differ on Bayley-III cognitive, language, or motor composite scores, or on expressive or receptive language, or on fine motor scaled scores. Children with CHD had lower ross motor scaled scores compared to children born very preterm (p = 0.047). More children with CHD had impaired scores (<70 SS) on language composite (17%), expressive language (16%), and gross motor (14%) indices compared to children born very preterm (6%; 7%; 3%; ps < 0.05). No group differences were found on behaviours rated by parents on the Child Behaviour Checklist (1.5-5 years) or the proportion of children with scores above the clinical cutoff. English as a first language was associated with higher cognitive (p = 0.004) and language composite scores (p < 0.001). Lower median household income and English as a second language were associated with higher total behaviour problems (ps < 0.05). CONCLUSIONS: Children with CHD were more likely to display language and motor impairment compared to children born very preterm at 18 months. Outcomes were associated with language spoken in the home and household income.

Factors affecting neurodevelopmental outcome following surgical necrotising enterocolitis: a systematic review.

Surgically treated necrotising enterocolitis (sNEC) is associated with significantly worse neurodevelopmental outcomes than that seen in premature infants without NEC. We aim to review the association between factors involved in the surgical treatment of NEC and subsequent neurodevelopmental outcomes to identify potential areas for improvement. The PubMed and Embase databases were interrogated for articles reporting neurodevelopmental outcomes in babies treated surgically for NEC using key terms including: "Infant", "Necrotising enterocolitis", "Surgical", "Neurodevelopmental" and "Outcomes". The search strategy yielded 1170 articles and after applying inclusion and exclusion criteria 22 studies remained and formed the review. A diverse range of neurodevelopmental outcomes were reported. Extreme prematurity and lower birth weight were associated with worse neurodevelopmental outcomes. The use of peritoneal drains and enterostomies were associated with worse outcomes. Modifications to surgical strategies in NEC may improve neurodevelopmental outcomes but the effect of confounding factors remains unclear. Further large scale studies are required to define the optimum strategies for treating NEC surgically and to develop a core outcome set for research into NEC.

Comorbid ADHD and Pediatric Sickle Cell Disease: Prevalence and Risk Factors.

Sickle cell disease (SCD) is a genetic blood condition that places youth at increased risk for deficits in complex attention suggestive of increased risk for Attention-Deficit/Hyperactivity Disorder (ADHD). We used systematic screening to assess the prevalence of ADHD in a clinic-based sample of youth with SCD and explored factors related to ADHD. Caregivers of 107 children with SCD (ages 7-11 years) completed routine psychosocial screening which included inattentive symptoms of ADHD. Follow-up diagnostic procedures were completed for patients with elevated inattentive symptoms to assess for ADHD diagnoses. Biomedical and social-environmental variables were examined from the screening and medical records. Twenty-six percent of patients showed elevated inattentive symptoms with 13% meeting diagnostic criteria for ADHD diagnoses. Most children (75%) who met criteria for ADHD had not been previously diagnosed. Disease severity did not predict inattentive symptoms or ADHD diagnoses, though a measure of chronic inflammation was associated with ADHD. Family functioning was related to elevated inattentive symptoms but not ADHD diagnoses. Children with SCD show relatively high rates of ADHD with many cases not detected through routine care. Screening for ADHD as part of hematology care may be a feasible strategy to improve identification and access to intervention.

Neurodevelopmental Outcomes at Two Years' Corrected Age of Very Preterm Infants after Implementation of a Post-Discharge Responsive Parenting Intervention Program (TOP Program).

OBJECTIVE: To compare neurodevelopmental outcomes at 2 years corrected age (CA) between infants born very preterm (VP) who did or did not receive a postdischarge responsive parenting intervention (Transmural developmental support for very preterm infants and their parents [TOP program]) between discharge home and 12 months' CA. STUDY DESIGN: The Systemic Hydrocortisone to Prevent Bronchopulmonary Dysplasia (SToP-BPD) study showed no differences between treatment groups in motor and cognitive development using the Dutch Bayley Scales of Infant Development and behavior using the Child Behavior Checklist at 2 years' CA. During its study period, the TOP program was gradually scaled up nationwide in the same population, providing an opportunity to evaluate the effect of this program on neurodevelopmental outcome, after adjusting for baseline differences. RESULTS: Among 262 surviving VP infants in the SToP-BPD study, 35% received the TOP program. Infants in the TOP group had a significantly lower incidence of a cognitive score <85 (20.3% vs 35.2%; adjusted absolute risk reduction: -14.1% [95% CI: -27.2 to -1.1]; P = .03), and a significantly higher mean cognitive score (96.7 ± 13.8), compared with the non-TOP group (92.0 ± 17.5; crude mean difference: 4.7 [95% CI: 0.3 to 9.2]; P = .03). No significant differences were found on motor scores. For behavior problems, a small but statistically significant effect for anxious/depressive problems was found in the TOP group (50.5 vs 51.2; P = .02). CONCLUSIONS: VP infants supported by the TOP program from discharge until 12 months' CA had better cognitive function at 2 years' CA. This study demonstrates a sustained positive effect of the TOP program in VP infants.

Neonatal herpes simplex virus infection: From the maternal infection to the child outcome.

This review examines the recent literature on the management of herpes simplex virus (HSV) infections in neonates. We summarized the three clinical categories of maternal HSV infection during pregnancy (primary first episode, nonprimary first episode, or recurrent episode) and the mechanisms of fetal damage. Considering when the transmission of the infection from the mother to the fetus/newborn occurs, three types of neonatal infection can be distinguished: intrauterine infection (5% of cases), postnatal infection (10% of cases), and perinatal infections (85% of cases). Neonatal presentation could range from a limited disease with skin, eye, and mouth disease to central nervous system disease or disseminated disease: the treatment with acyclovir should be tailored according to symptoms and signs of infection, and virological tests. These children need a multidisciplinary follow-up, to timely intercept any deviation from normal neurodevelopmental milestones. Prevention strategies remain a challenge, in the absence of an available vaccine against HSV.

Zika Virus affects neurobehavioral development, and causes oxidative stress associated to blood-brain barrier disruption in a rat model of congenital infection.

Zika virus (ZIKV) is a mosquito-borne flavivirus associated with several neurodevelopmental outcomes after in utero infection. Here, we studied a congenital ZIKV infection model with immunocompetent Wistar rats, able to predict disabilities and that could pave the way for proposing new effective therapies. We identified neurodevelopmental milestones disabilities in congenital ZIKV animals. Also, on 22nd postnatal day (PND), blood-brain barrier (BBB) proteins disturbances were detected in the hippocampus with immunocontent reduction of ß_Catenin, Occludin and Conexin-43. Besides, oxidative stress imbalance on hippocampus and cortex were identified, without neuronal reduction in these structures. In conclusion, even without pups' microcephaly-like phenotype, congenital ZIKV infection resulted in neurobehavioral dysfunction associated with BBB and oxidative stress disturbances in young rats. Therefore, our findings highlighted the multiple impact of the congenital ZIKV infection on the neurodevelopment, which reinforces the continuity of studies to understand the spectrum of this impairment and to provide support to future treatment development for patients affected by congenital ZIKV.

Long-term adverse neurodevelopmental outcomes of discordant twins delivered at term: A nationwide population-based study.

OBJECTIVE: To evaluate long-term adverse neurodevelopmental outcomes of discordant twins delivered at term. DESIGN: Retrospective cohort study. SETTING: Nationwide (Republic of Korea). POPULATION: All twin children delivered at term between 2007 and 2010. METHODS: The study population was divided into two groups according to inter-twin birthweight discordancy: the 'concordant twin group', twin pairs with inter-twin birthweight discordancy less than 20%; and the 'discordant twin group', twin pairs with inter-twin birthweight discordancy of 20% or more. The risk of long-term adverse neurodevelopmental outcomes was compared between the concordant twin group and the discordant twin group. Long-term adverse neurodevelopmental outcomes between smaller and larger twin children within twin pairs were further analysed. The composite adverse neurodevelopmental outcome was defined as the presence of at least one of the following: motor developmental delay, cognitive developmental delay, autism spectrum disorders/attention deficit hyperactivity disorders, tics/stereotypical behaviour or epileptic/febrile seizure. MAIN OUTCOME MEASURES: Long-term adverse neurodevelopmental outcome. RESULTS: Of 22 468 twin children (11 234 pairs) included, 3412 (15.19%) twin children were discordant. The risk of composite adverse neurodevelopmental outcome was higher in the discordant twin group than in the concordant twin group (adjusted hazard ratio [HR] 1.13, 95% CI 1.03-1.24). The long-term adverse neurodevelopmental outcomes were not significantly different between smaller and larger twin children in discordant twin pairs (adjusted HR 1.01, 95% CI 0.81-1.28). CONCLUSION: In twin pairs delivered at term, an inter-twin birthweight discordancy of 20% or greater was associated with long-term adverse neurodevelopmental outcomes; and long-term adverse neurodevelopmental outcomes were not significantly different in smaller or larger twin children in discordant twin pairs.

Umbilical cord blood acid-base analysis at birth and long-term neurodevelopmental outcomes in children: a systematic review and meta-analysis.

BACKGROUND: Umbilical cord blood acid-base sampling is routinely performed at many hospitals. Recent studies have questioned this practice and the association of acidosis with cerebral palsy. OBJECTIVE: To investigate the associations between the results of umbilical cord blood acid-base analysis at birth and long-term neurodevelopmental outcomes and mortality in children. SEARCH STRATEGY: We searched six databases using the search strategy: umbilical cord AND outcomes. SELECTION CRITERIA: Randomised controlled trials, cohorts and case-control studies from high-income countries that investigated the association between umbilical cord blood analysis and neurodevelopmental outcomes and mortality from 1 year after birth in children born at term. DATA COLLECTION AND ANALYSIS: We critically assessed the included studies, extracted data and conducted meta-analyses comparing adverse outcomes between children with and without acidosis, and the mean proportions of adverse outcomes. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. MAIN RESULTS: We have very low confidence in the following findings: acidosis was associated with higher cognitive development scores compared with non-acidosis (mean difference 5.18, 95% CI 0.84-9.52; n = two studies). Children with acidosis also showed a tendency towards higher risk of death (relative risk [RR] 5.72, 95% CI 0.90-36.27; n = four studies) and CP (RR 3.40, 95% CI 0.86-13.39; n = four studies), although this was not statistically significant. The proportion of children with CP was 2.39/1000 across the studies, assessed as high certainty evidence. CONCLUSION: Due to low certainty of evidence, the associations between umbilical cord blood gas analysis at delivery and long-term neurodevelopmental outcomes in children remains unclear.

Paracetamol use in pregnancy: Not as safe as we may think?

Paracetamol is used by more than 50% of women worldwide during pregnancy; headache representing the most frequent indication. Several studies report that long-term exposure to paracetamol in utero is associated with adverse neurodevelopmental outcomes in children, indicating a dose-response effect. However, less or no risk is found to be associated with short-term exposure. Paracetamol most likely crosses the placenta through passive diffusion, and there are several possible mechanisms for how paracetamol might affect fetal brain development. Although the literature suggests an association between prenatal paracetamol exposure and neurodevelopmental outcomes, the role of confounders cannot be ruled out. Consequently, as a precaution, we believe that pregnant women should be recommended ideally to only use paracetamol to treat conditions that might harm the fetus, such as severe pain or a high fever. This Comment aims to put focus on the potential fetal risks of paracetamol exposure in utero.

Effects of 1.5-T versus 3-T magnetic resonance imaging in fetuses: is there a difference in postnatal neurodevelopmental outcome? Evaluation in a fetal population with left-sided congenital diaphragmatic hernia.

BACKGROUND: The utilization of 3-T magnetic field strength in obstetric imaging is increasingly common. It is important to ensure that magnetic resonance (MR) imaging with higher magnetic field strength is safe for the fetus. Comparison of neurodevelopmental outcome in neonates undergoing prenatal MR imaging with 1.5-T versus 3-T is of interest but has not yet been examined. OBJECTIVE: We hypothesized no clinically meaningful difference in neurodevelopmental outcome between fetuses undergoing 1.5-T versus 3-T fetal MR imaging. As imaging a normal fetus for research purposes is illegal in Pennsylvania, this study was conducted in a population of fetuses with left congenital diaphragmatic hernia (left-CDH). MATERIALS AND METHODS: A retrospective review of neurodevelopmental outcome of fetuses with left-CDH scanned at 1.5-T (n=75) versus 3-T (n=25) magnetic field strength between July of 2012 and December of 2019 was performed. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant Development, 3rd Edition (BSID-III). RESULTS: There were no statistical differences in median age of assessment (1.5-T: 18 [12, 25] versus 3-T: 21 [11, 26], P=0.79), in mean BSID-III cognitive (1.5-T: 91 ± 14 versus 3-T: 90 ± 16, P=0.82), language (1.5-T: 92 ± 20 versus 3-T: 91 ± 20, P=0.91), and motor composite (1.5-T: 89 ± 15 versus 3-T: 87 ± 18, P=0.59) scores, subscales scores (for all, P>0.50), or in risk of abnormal neuromuscular exam (P=0.29) between neonates with left-CDH undergoing a 1.5-T versus 3-T MR imaging during fetal life. Additionally, the distribution of patients with average, mildly delayed, and severely delayed BSID-III scores was similar between the two groups (for all, P>0.50). The overall distribution of the composite scores in this CDH population was similar to the general population independent of exposure to 1.5-T or 3-T fetal MR imaging. Two 3-T patients (8%) and five 1.5-T patients (7%) scored within the significant delayed range for all BSID-III domains. Subjects with lower observed-to-expected fetal lung volume (O/E FLV) and postnatal need for ECMO had lower cognitive, language, motor, and subscales scores (for all, P<0.03) regardless of being imaged at 1.5-T versus 3-T. CONCLUSION: This preliminary study suggests that, compared to 1.5-T MR imaging, fetal exposure to 3-T MR imaging does not increase the risk of neurodevelopmental impairment in fetuses with left-CDH. Additional MR imaging studies in larger CDH cohorts and other fetal populations are needed to replicate and extend the present findings.

Abnormal infant neurobehavior and later neurodevelopmental delays in children with critical CHD.

Infants with critical CHD have abnormal neurobehavior assessed by the Neonatal ICU Network Neurobehavioral Scales. This retrospective cohort study hypothesized associations between abnormal infant neurobehavior in the first month of life and later neurodevelopmental outcomes at 1-2 years of age. Associations between abnormal infant attention (orienting to and tracking stimuli) on the Neonatal ICU Network Neurobehavioral Scales and later motor, cognitive, and language neurodevelopmental outcomes on the Bayley Scales of Infant Development-III at follow-up were examined with descriptive statistics and univariable and multivariable regression. Multiple imputation was used to account for missing outcome data. 189 infants with critical CHD were included, and 69% had abnormal neurobehavioral attention scores. 58 (31%) returned as toddlers for neurodevelopmental follow-up, of which 23% had motor delay. Abnormal infant attention had high sensitivity (92%, 95% CI 60-100%) but low specificity (36%, 95% CI 23-52%) for later motor delay. Higher infant attention scores were associated with higher later motor scores in univariable analysis (coefficient 3.49, 95% CI 0.52,6.46, p = 0.025), but not in multivariable analyses. Neither cognitive nor language scores were associated with infant attention scores. Lower birth weight and male sex were significantly associated with lower motor scores in multivariable analysis (p = 0.048, 0.007). Although impaired infant attention is interdependent with other clinical and demographic risk factors, it may be a sensitive clinical marker of risk for later motor delay. In children with critical CHD, impaired infant attention may be capturing early signs of abnormal visual-motor neurodevelopment.

Paediatric cardiologist adherence to American Heart Association neurodevelopmental recommendations for CHD patients.

A 2012 American Heart Association statement concluded that children with CHD are at an increased risk for neurodevelopmental delays. Routine surveillance and evaluation throughout childhood are recommended. To assess paediatric cardiologist compliance with American Heart Association guidelines and developmental referral practices, a survey was distributed to paediatric cardiologists nationwide (n = 129). The majority of participants (69%) stated they were somewhat familiar or not familiar with the American Heart Association statement and were concerned about patients not being properly referred to specialists for developmental evaluation. Forty paediatric cardiologists (31%) indicated that their institution did not have a neurodevelopmental cardiology programme. Of these, 25% indicated they generally did not refer CHD patients for neurodevelopmental evaluation, 45% performed surveillance and referred if warranted, and 30% generally referred all patients for surveillance. Lastly, 43% of paediatric cardiologists did not feel responsible for developmental surveillance, and 11% did not feel responsible for referrals. To ensure all children with CHD are appropriately screened and referred, paediatricians and cardiologists must work together to address differing impressions of accountability for surveillance and screening of children with CHD.

A complicated Glenn procedure: risk factors and association with adverse long-term neurodevelopmental and functional outcomes.

OBJECTIVES: To determine potentially modifiable risk factors for a complicated Glenn procedure (cGP) and whether a cGP predicted adverse neurodevelopmental and functional outcomes. A cGP was defined as post-operative death, heart transplant, extracorporeal life support, Glenn takedown, or prolonged ventilation. METHODS: All 169 patients having a Glenn procedure from 2012 to 2017 were included. Neurodevelopmental assessments were performed at age 2 years in consenting survivors (n = 156/159 survivors). The Bayley Scales of Infant and Toddler Development-3rd Edition (Bayley-III) and the Adaptive Behavior Assessment System-2nd Edition (ABAS-II) were administered. Adaptive functional outcomes were determined by the General Adaptive Composite (GAC) score from the ABAS-II. Predictors of outcomes were determined using univariate and multiple variable linear or Cox regressions. RESULTS: Of patients who had a Glenn procedure, 10/169 (6%) died by 2 years of age and 27/169 (16%) had a cGP. Variables statistically significantly associated with a cGP were the inotrope score on post-operative day 1 (HR 1.04, 95%CI 1.01, 1.06; p = 0.010) and use of inhaled nitric oxide post-operatively (HR 7.31, 95%CI 3.19, 16.76; p < 0.001). A cGP was independently statistically significantly associated with adverse Bayley-III Cognitive (ES -10.60, 95%CI -17.09, -4.11; p = 0.002) and Language (ES -11.43, 95%CI -19.25, -3.60; p = 0.004) scores and adverse GAC score (ES -14.89, 95%CI -22.86, -6.92; p < 0.001). CONCLUSIONS: Higher inotrope score and inhaled nitric oxide used post-operatively were associated with a cGP. A cGP was independently associated with adverse 2-year neurodevelopmental and functional outcomes. Whether early recognition and intervention for risk of a cGP can prevent adverse outcomes warrants study.

South Indian Children's Neurodevelopmental Outcomes After Group B Streptococcus Invasive Disease: A Matched-Cohort Study.

BACKGROUND: This study is part of a multicountry matched-cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI) of children exposed to invasive group B Streptococcus (iGBS). The specific objective of this paper is to compare NDI across domains of iGBS survivors with a matched non iGBS group in our population. METHODS: Survivors of iGBS in a South Indian hospital were identified and recruited between January 2020 and April 2021. Cases were compared with age- and gender-matched non iGBS children. Participants were assessed using Bayley Scales of Infant and Toddler Development-3rd edition (BSID-III), Wechsler Preschool and Primary Scale of Intelligence-4th edition (WPPSI-IV), Wechsler Intelligence Scale for Children-5th edition (WISC-V), Child Behavior Checklist (CBCL), and Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition (BOT-2), depending on age. RESULTS: Our cohort comprised 35 GBS-exposed and 65 matched non iGBS children, aged 1-14 years. The iGBS-exposed group had 17 (48.6%) children with impairment in ≥1 domain compared to 25 (38%) in the non iGBS group (unadjusted OR, 1.51; 95% CI, .65-3.46), 9 (26%) children with "multi-domain impairment" compared to 10 (15.4%) in the non iGBS group (unadjusted OR, 1.90; 95% CI, .69-5.24), and 1 (2.9%) child with moderate to severe impairment compared to 3 (4.6%) in the non iGBS group (unadjusted OR, .60; 95% CI, .06-6.07). In the iGBS group, more children had motor impairments compared with the non iGBS group (unadjusted OR, 10.7; 95% CI, 1.19-95.69; P = .034). CONCLUSIONS: Children with iGBS seem at higher risk of developing motor impairments compared with a non iGBS group.