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Children with heart conditions, particularly CHDs, may experience adverse neurodevelopmental and psychosocial outcomes. Our study aimed to: (1) compare national prevalence of mental, behavioural, and developmental disorders among children by heart condition status and (2) identify associated characteristics among children with heart conditions.
Methods:
Nationally representative data from the National Survey of Children’s Health (2016–2021) on U.S. children aged 6–17 years without Down syndrome were analysed. Caregivers reported whether a healthcare provider told them their child has ever had a heart condition or currently has depression, anxiety, ADHD, behavioural, or conduct problems, Tourette syndrome, autism spectrum disorder, developmental delay, intellectual disability, learning disability, or a speech or other language disorder. Logistic regression analysis compared disorder prevalence by heart condition status and, among children with heart conditions, assessed whether disorders were associated with demographic and contextual characteristics.
Results:
Among 3,440 children with heart conditions, 42% had an examined disorder, compared to 23% of 133,280 children without heart conditions (adjusted prevalence ratio = 1.8; 95% confidence interval: 1.7, 2.0). Each disorder was more prevalent among children with versus without heart conditions (adjusted prevalence ratio range: 1.9 to 5.1), with anxiety (22.1%), ADHD (20.4%), and learning disabilities (19.6%) most common. Among children with heart conditions, disorders were consistently associated with an increased number of adverse childhood experiences.
Conclusion:
These findings support clinical guidelines recommending neurodevelopmental and mental health screening and interventions for children with heart conditions and can be used as a national baseline to gauge progress of guideline implementation.
Prenatal maternal mental health and social determinants of health may influence pregnancy, child hospitalisation, and child neurodevelopmental outcomes in critical congential heart disease (CHD). We examined 189 mother–child dyads of children born with CHD who underwent neonatal cardiac surgery and completed neurodevelopmental assessment between the ages 13 and 29 months. We used latent profile analysis to identify distinct maternal groups based on prenatal maternal mental health screening scores and individual- and neighbourhood-level social determinants of health factors. We examined the association between maternal groups with their child’s gestational age, birth weight, hospital length of stay (HLOS), and neurodevelopment. Latent profile analysis identified two distinct groups: high-risk (n = 46) and low-risk (n = 143). Mothers in the high-risk group had higher mental health screening scores, lower age, higher social vulnerability, lower education, and were more likely to have Medicaid insurance and represent a minority group than mothers in the low-risk group. The high-risk group had children with lower gestational age and weight at birth, longer HLOS, and lower cognitive, language, and motor scales than children in the low-risk group (p < 0.05). Sensitivity analysis in mother–infant dyads without foetal extracardiac conditions found that significant relationships persisted in the high-risk group, with lower gestational age and lower language scale scores than the low-risk group (p < 0.05). Children of mothers with adverse prenatal maternal mental health and social determinants of health risks had significantly worse pregnancy and child outcomes. Interventions are critically needed to address maternal mental health and social determinants of health risks beginning in the prenatal period.
“Frailty” is associated with worse outcomes in adult cardiology. There is limited data on the associations between frailty and outcomes in paediatric cardiology. We aimed to define the prevalence of frailty and identify associations between frailty and neurodevelopmental and quality-of-life outcomes in high-risk paediatric cardiac populations.
Study Design:
This cross-sectional study included patients 4–18 years seen in a neurodevelopmental programme between 6/2017 and 11/2022. Demographic and clinical data were obtained from medical records. As part of the routine care, physical therapy assessment and neurocognitive, psychosocial, adaptive functioning, and quality-of-life surveys were administered. Social determinants of health were assessed by insurance status and Childhood Opportunity Index. Frailty was defined as the abnormality in 3 of 5 categories: body composition, weakness, slowness, physical activity, and exhaustion. Chi-Square, Student t, and Wilcoxon Rank Sum tests were used to assess differences between frail and non-frail groups.
Results:
Of the 270 patients, 101 (37%) met the frailty criteria. Frailty was not associated with social determinants of health, cardiac diagnosis, genetic syndrome, number of cardiac surgeries, or history of clinical complications. Frail patients were more likely to be older (p = 0.004) and have neurocognitive (p = 0.024), emotional (p = 0.003), social (p < 0.001), motor (p < 0.001), and adaptive dysfunction (p < 0.001) and lower quality of life (p = 0.029).
Conclusion:
Frailty is common in school-aged patients with cardiac disease and is associated with adverse neurocognitive, psychosocial, motor, and adaptive outcomes and worse quality of life. Risk stratification for frailty may be a critical evaluation and screening element of high-risk cardiac patients in neurodevelopmental programmes.
This chapter explores adolescent involvement in cults. Adolescence is a time in which many individuals engage in group-like activity. However, this chapter defines cult-like behavior as beyond the range of normal group-like activity expected during the transitional time of adolescence. The biological, social, and psychological factors of adolescent development increase their susceptibility to peer pressure, predispose them to self-exploration, and contribute to characteristics that attract adolescents to cults. This chapter describes the characteristics of normal adolescent life that predispose adolescents to cult recruitment, characteristics of adolescents who are likely to join cults, and characteristics of the leaders of cults that attract adolescents. Important regarding adolescents in particular, the increased access to technology, the internet, and social media is redefining adolescent membership in cults and future considerations may offer an updated lens through which to define and consider adolescent involvement in cults.
Lamotrigine is beneficial in bipolar disorder and is often prescribed to patients during their period of reproductive potential. We summarise aspects of the pharmacology of lamotrigine, highlight its uses in psychiatric practice, drawing attention to recent findings relating to potential hazards arising from lamotrigine exposure in utero, and make some suggestions for clinical management.
This study aimed to assess the impact of hypertensive disorders of pregnancy on infant neurodevelopment by comparing 6-month and 2-year psychomotor development outcomes of infants exposed to gestational hypertension (GH) or preeclampsia (PE) versus normotensive pregnancy (NTP). Participating infants were children of women enrolled in the Postpartum Physiology, Psychology and Paediatric (P4) cohort study who had NTPs, GH or PE. 6-month and 2-year Ages and Stages Questionnaires (ASQ-3) scores were categorised as passes or fails according to domain-specific values. For the 2-year Bayley Scales of Infant and Toddler Development (BSID-III) assessment, scores > 2 standard deviations below the mean in a domain were defined as developmental delay. Infants (n = 369, male = 190) exposed to PE (n = 75) versus GH (n = 20) and NTP (n = 274) were more likely to be born small for gestational age and premature. After adjustment, at 2 years, prematurity status was significantly associated with failing any domain of the ASQ-3 (p = 0.015), and maternal tertiary education with increased cognitive scores on the BSID-III (p = 0.013). However, PE and GH exposure were not associated with clinically significant risks of delayed infant neurodevelopment in this study. Larger, multicentre studies are required to further clarify early childhood neurodevelopmental outcomes following hypertensive pregnancies.
Antenatal steroids (ANS) are one of the most widely prescribed medications in pregnancy, being administered to women at risk of preterm delivery. In the setting of preterm delivery at or below 35 weeks’ gestation, systematic review data show ANS reduce perinatal morbidity and mortality, primarily by promoting fetal lung maturation. However, with the expanding use of this intervention has come a growing appreciation for the potential off-target, adverse effects of ANS therapy on wider fetal development. We undertook a narrative literature review of the animal and clinical literature to assess current evidence for adverse effects of ANS exposure and fetal development. This review presents a summary of the evidence relating to the potential for wide-ranging, off-target, adverse effects of ANS therapy on fetal development and programming. We highlight an urgent need for further animal and clinical studies investigating the effects of ANS on the fetal immune, cardiovascular, renal and hepatic systems given a current sparsity of evidence. We also strongly suggest an emphasis on open disclosure, discussion and education of clinicians and patients with regard to the potential benefits and risks of ANS therapy, particularly in late preterm and term gestations where infants derive relatively few benefits from these drugs. We also propose further studies on the optimisation of ANS therapy through improved patient selection and improved dosing regimens based on a pharmacokinetic-pharmacodynamic informed understanding of ANS action on the fetal lung.
Childhood obsessive-compulsive disorder (OCD) stems from a bunch of restricted and repetitive behaviors, which are part of normal behavioral repertoire up to the age of 7. The persistence of compulsive-like behaviors after that age is often associated with unique comorbidity patterns, which are age-at-onset dependent and reflect different developmental stages. In particular, OCD synchronically co-occurs with a broad constellation of neurodevelopmental disorders, whereas diachronically it is related to an increased risk of major adult psychoses. Moreover, OCD is associated with trait-like sensory phenomena, suggesting a common disrupted sensorimotor grounding.
The present study is aimed at exploring the hypothesis that this specific temporal and comorbidity OCD profile may be due to a developmental heterochronic mechanism of delay in attenuation of ontogenetically early behavioral patterns. The developmental shift of highly evolutionarily conserved behavioral phenotypes might be regulated by epigenetic changes induced by different conditions of sensory unbalance. This evolutionary and developmental model allows capturing childhood OCD in light of the ultimate causes of ritual behavior throughout phylogeny, namely its “homeostatic” function over conditions of unpredictability. Moreover, it may have important clinical implications, as OCD symptoms could represent putative biomarkers of early divergent developmental trajectories, with a pathoplastic effect on course and outcome.
Children with CHD are at increased risk for neurodevelopmental disabilities and neuropsychological impairments throughout their life span. The purpose of this report is to share our experience building a sustainable, novel, inpatient, interdisciplinary Neurocardiac Critical Care Program to mitigate risks and optimize outcomes during the ICU stay.
Material and methods:
A descriptive review was chosen to identify meaningful characteristics, challenges and lessons learned related to the establishment, expansion of and sustainability of Neurocardiac Critical Care Program in a 26-bed pediatric cardiac ICU.
Results:
We successfully launched, expanded, and sustained an interdisciplinary Neurocardiac Critical Care Program. Here, we share the foundation, framework, challenges, and lessons learned as we established and sustained the Neurocardiac Critical Care Program. The key elements of our program are (1) consistent engagement by pediatric neurologists in the cardiac ICU, (2) comprehensive education initiatives, (3) evidence-based clinical practice changes, and (4) quality improvement and research projects.
Discussion:
The development of a pediatric Neurocardiac Critical Care Program is feasible and sustainable. This program was informed by recent research related to perioperative and psychosocial risk factors that impact brain development and neurodevelopmental outcomes in this vulnerable population. By aligning our efforts, our multidisciplinary team is helping shift the paradigm in pediatric cardiac critical care to actively manage complex heart disease, while simultaneously and proactively mitigating risks to the developing brain and family unit.
Mentalizing—our ability to make inferences about the mental states of others—is impaired across psychiatric disorders and robustly associated with functional outcomes. Mentalizing deficits have been prominently linked to aberrant activity in cortical regions considered to be part of the “social brain network” (e.g., dorsomedial prefrontal cortex, temporoparietal junction), yet emerging evidence also suggests the importance of cerebellar dysfunction. In the present study—using a transdiagnostic, clinical psychiatric sample spanning the psychosis-autism-social anxiety spectrums—we examined the role of the cerebellum in mentalizing and its unique contributions to broader social functioning.
Methods
Sixty-two participants (38 with significant social dysfunction secondary to psychiatric illness and 24 nonclinical controls without social dysfunction) completed a mentalizing task during functional magnetic resonance imaging. General linear model analysis, latent variable modeling, and regression analyses were used to examine the contribution of cerebellum activation to the prediction of group status and social functioning.
Results
Mentalizing activated a broad set of social cognitive brain regions, including cerebral mentalizing network (MN) nodes and posterior cerebellum. Higher posterior cerebellum activation significantly predicted clinical status (i.e., individuals with psychiatric disorders versus nonclinical controls). Finally, cerebellar activation accounted for significant variance in social functioning independent of all other cerebral MN brain regions identified in a whole-brain analysis.
Conclusions
Findings add to an accumulating body of evidence establishing the unique role of the posterior cerebellum in mentalizing deficits and social dysfunction across psychiatric illnesses. Collectively, our results suggest that the posterior cerebellum should be considered – alongside established cerebral regions – as part of the mentalizing network.
Early gut microbiome development may impact brain and behavioral development. Using a nonhuman primate model (Macaca mulatta), we investigated the association between social environments and the gut microbiome on infant neurodevelopment and cognitive function. Infant rhesus monkeys (n = 33) were either mother-peer-reared (MPR) or nursery-reared (NR). Neurodevelopmental outcomes, namely emotional responsivity, visual orientation, and motor maturity, were assessed with the Primate Neonatal Neurobehavioral Assessment (PNNA) at 14–30 days. Cognitive development was assessed through tasks evaluating infant reward association, cognitive flexibility, and impulsivity at 6–8 months. The fecal microbiome was quantified from rectal swabs via 16S rRNA sequencing. Factor analysis was used to identify “co-abundance factors” describing patterns of microbial composition. We used multiple linear regressions with AIC Model Selection and differential abundance analysis (MaAsLin2) to evaluate relationships between co-abundance factors, microbiome diversity, and neuro-/cognitive development outcomes. At 30 days of age, a gut microbiome co-abundance factor, or pattern, with high Prevotella and Lactobacillus (β = −0.88, p = 0.04, AIC Weight = 68%) and gut microbiome alpha diversity as measured by Shannon diversity (β = −1.33, p = 0.02, AIC Weight = 80%) were both negatively associated with infant emotional responsivity. At 30 days of age, being NR was also associated with lower emotional responsivity (Factor 1 model: β = −3.13, p < 0.01; Shannon diversity model: β = −3.77, p < 0.01). The infant gut microbiome, along with early-rearing environments, may shape domains of neuro-/cognitive development related to temperament.
The literature regarding breastfeeding and effects of anti-seizure medication (ASM) exposure via breastmilk has evolved over the past two decades, with mounting evidence that supports breastfeeding for women with epilepsy (WWE) taking ASMs. In this chapter, we provide an overview of the current evidence that supports breastfeeding in infants of mothers taking ASM; safety profile of each ASM and reported adverse effects for various ASMs. Lastly, we review rates and patterns, as well as potential barriers to breastfeeding in WWE and potential intervention to improve breastfeeding practices in WWE.
Children born growth-restricted are well recognized to be at an increased risk of poor neurodevelopmental outcomes. This prospective study examined the influence of chest-to-head circumference ratio at birth on neurodevelopment in the first three years among children enrolled in the Japan Environment and Children’s Study. We analyzed information of 84,311 children (43,217 boys, 41,094 girls). Children were divided into low, normal, and high chest-to-head circumference ratio groups. Neurodevelopment was assessed every six months (from 6 months to 3 years) using the Ages and Stages Questionnaire (Japanese translation), with delays defined as scores below 2 standard deviations from the mean. Additionally, we evaluated the contributions of chest and head circumference to the observed association. Linear mixed-effect regression revealed increased risk of delays in communication, gross motor, fine motor, problem-solving, and personal-social skills in the low-ratio group compared to the normal-ratio group. Adjusted risk ratios were in the range of 1.14 – 1.39 in boys and 1.16 – 1.37 in girls, with no such increase observed in the high-ratio group. The heightened risk in the low-ratio group was likely associated with a relatively narrow chest rather than a large head. The area under the ROC curves in predicting any developmental delay at three years for newborn measurements ranged from 0.513 to 0.526 in boys and 0.509 to 0.531 in girls. These findings suggest that a low chest-to-head circumference ratio may indicate children who are at risk for neurodevelopmental deficits. However, the ability to predict poor neurodevelopmental outcomes at three years of age is limited.
The prenatal and early-life periods pose a crucial neurodevelopmental window whereby disruptions to the intestinal microbiota and the developing brain may have adverse impacts. As antibiotics affect the human intestinal microbiome, it follows that early-life antibiotic exposure may be associated with later-life psychiatric or neurocognitive outcomes.
Aims
To explore the association between early-life (in utero and early childhood (age 0–2 years)) antibiotic exposure and the subsequent risk of psychiatric and neurocognitive outcomes.
Method
A search was conducted using Medline, PsychINFO and Excerpta Medica databases on 20 November 2023. Risk of bias was assessed using the Newcastle-Ottawa scale, and certainty was assessed using the grading of recommendations, assessment, development and evaluation (GRADE) certainty assessment.
Results
Thirty studies were included (n = 7 047 853 participants). Associations were observed between in utero antibiotic exposure and later development of autism spectrum disorder (ASD) (odds ratio 1.09, 95% CI: 1.02–1.16) and attention-deficit hyperactivity disorder (ADHD) (odds ratio 1.19, 95% CI: 1.11–1.27) and early-childhood exposure and later development of ASD (odds ratio 1.19, 95% CI: 1.01–1.40), ADHD (odds ratio 1.33, 95% CI: 1.20–1.48) and major depressive disorder (MDD) (odds ratio 1.29, 95% CI: 1.04–1.60). However, studies that used sibling control groups showed no significant association between early-life exposure and ASD or ADHD. No studies in MDD used sibling controls. Using the GRADE certainty assessment, all meta-analyses but one were rated very low certainty, largely owing to methodological and statistical heterogeneity.
Conclusions
While there was weak evidence for associations between antibiotic use in early-life and later neurodevelopmental outcomes, these were attenuated in sibling-controlled subgroup analyses. Thus, associations may be explained by genetic and familial confounding, and studies failing to utilise sibling-control groups must be interpreted with caution. PROSPERO ID: CRD42022304128
Several organizations including the Environmental Protection Agency, World Health Organization and American Academy of Pediatrics recommend that hospital sound levels not exceed 45 decibels. Yet, several studies across multiple age groups have observed higher than recommended levels in the intensive care setting. Elevated sound levels in hospitals have been associated with disturbances in sleep, patient discomfort, delayed recovery, and delirium.
Methods:
We measured sound levels in a pediatric cardiac intensive care unit and collected vital signs data, sedation dosing and delirium scores. During a 5-week study period, sound levels for 68 patients in 22 private and 4 semi-private rooms were monitored.
Results:
Sound levels were consistently above stated recommendations with an average daytime level of 50.6 decibels (maximum, 76.9 decibels) and an average nighttime level of 49.5 decibels (maximum, 69.6 decibels). An increase in average and maximum sound levels increased the probability of sedation administration the following hour (p-value < 0.001 and 0.01, respectively) and was predictive of an increase in heart rate and blood pressure (p-value < 0.001).
Conclusion:
Sound levels in the CICU were consistently higher than recommended. An increase in heart rate, blood pressure and sedation utilization may suggest a stress response to persistent and sudden loud sounds. Given known negative impacts of excessive noise on stress, sleep, and brain development, as well as the similar adverse effects from the related use of sedative medications, reducing excessive and sudden noise may provide an opportunity to improve short- and long-term hemodynamic and neurodevelopmental outcomes in the pediatric cardiac intensive care unit.
Associations between childhood trauma, neurodevelopment, alcohol use disorder (AUD), and posttraumatic stress disorder (PTSD) are understudied during adolescence.
Methods
Using 1652 participants (51.75% female, baseline Mage = 14.3) from the Collaborative Study of the Genetics of Alcoholism, we employed latent growth curve models to (1) examine associations of childhood physical, sexual, and non-assaultive trauma (CPAT, CSAT, and CNAT) with repeated measures of alpha band EEG coherence (EEGc), and (2) assess whether EEGc trajectories were associated with AUD and PTSD symptoms. Sex-specific models accommodated sex differences in trauma exposure, AUD prevalence, and neural development.
Results
In females, CSAT was associated with higher mean levels of EEGc in left frontocentral (LFC, ß = 0.13, p = 0.01) and interhemispheric prefrontal (PFI, ß = 0.16, p < 0.01) regions, but diminished growth in LFC (ß = −0.07, p = 0.02) and PFI (ß = −0.07, p = 0.02). In males, CPAT was associated with lower mean levels (ß = −0.17, p = 0.01) and increased growth (ß = 0.11, p = 0.01) of LFC EEGc. Slope of LFC EEGc was inversely associated with AUD symptoms in females (ß = −1.81, p = 0.01). Intercept of right frontocentral and PFI EEGc were associated with AUD symptoms in males, but in opposite directions. Significant associations between EEGc and PTSD symptoms were also observed in trauma-exposed individuals.
Conclusions
Childhood assaultive trauma is associated with changes in frontal alpha EEGc and subsequent AUD and PTSD symptoms, though patterns differ by sex and trauma type. EEGc findings may inform emerging treatments for PTSD and AUD.
To evaluate the motor proficiency, identify risk factors for abnormal motor scores, and examine the relationship between motor proficiency and health-related quality of life in school-aged patients with CHD.
Study design:
Patients ≥ 4 years old referred to the cardiac neurodevelopmental program between June 2017 and April 2020 were included. Motor skills were evaluated by therapist-administered Bruininks-Oseretsky Test of Motor Proficiency Second-Edition Short Form and parent-reported Adaptive Behavior Assessment System and Patient-Reported Outcomes Measurement Inventory System Physical Functioning questionnaires. Neuropsychological status and health-related quality of life were assessed using a battery of validated questionnaires. Demographic, clinical, and educational variables were collected from electronic medical records. General linear modelling was used for multivariable analysis.
Results:
The median motor proficiency score was the 10th percentile, and the cohort (n = 272; mean age: 9.1 years) scored well below normative values on all administered neuropsychological questionnaires. In the final multivariable model, worse motor proficiency score was associated with family income, presence of a genetic syndrome, developmental delay recognised in infancy, abnormal neuroimaging, history of heart transplant, and executive dysfunction, and presence of an individualised education plan (p < 0.03 for all predictors). Worse motor proficiency correlated with reduced health-related quality of life. Parent-reported adaptive behaviour (p < 0.001) and physical functioning (p < 0.001) had a strong association with motor proficiency scores.
Conclusion:
This study highlights the need for continued motor screening for school-aged patients with CHD. Clinical factors, neuropsychological screening results, and health-related quality of life were associated with worse motor proficiency.
Twins lag behind singletons in their early psychomotor development, but little is known about how chorionicity affects this difference. We compared early psychomotor development in singletons, monochorionic (MC) twins and dichorionic (DC) twins. Our longitudinal data from the Japan Environment and Children’s Study (JECS; see Appendix) included 98,042 singletons, 577 MC twins and 1051 DC twins representing the general Japanese population. Chorionicity was evaluated by ultrasound images and complemented by postnatal pathological examinations. Five domains of psychomotor development were evaluated at 6 time points from 6 months to 3 years of age using the Ages and Stages Questionnaires (ASQ-3). The data were analyzed using linear regression models. Twins lagged behind singletons in all areas of psychomotor development during infancy. This gap decreased over time but was still noticeable at 3 years of age. More than half of this difference was attributed to twins having lower birth weight and being born earlier in gestation. MC twins showed slightly delayed development compared to DC twins, but this difference was minor compared to the overall gap between twins and singletons. Twins delay singletons in their early psychomotor development, and this delay is not specific to MC twinning.
CHD predisposes children to neurodevelopmental delays. Frequent, prolonged hospitalisations during infancy prevent children with heart disease from participating in recommended language and cognitive development programmes, such as outpatient early childhood literacy programmes, and contribute to caregiver stress, a risk factor for adverse developmental outcomes. This study aims to describe the implementation of a single-centre inpatient early childhood literacy programme for hospitalised infants with heart disease and assess its impact on reading practices and patient–family hospital experience.
Methods:
Admitted infants ≤1 year old receive books, a calendar to track reading frequency, and reading guidance at regular intervals. Voluntary feedback is solicited from caregivers using an anonymous, QR-code survey on books. A prospective survey also assessed programme impact on hospital experience.
Results:
From February 2021 to November 2023, the Books@Heart programme provided 1,293 books to families of 840 infants, of whom 110 voluntarily submitted feedback. Caregivers reported a significant improvement in access to books (p < 0.001) and increased reading frequency after learning about Books@Heart (p = 0.003), with the proportion reading to their child daily increasing from 27% to 62%. Among 40 prospective survey responses, caregivers reported feeling a sense of personal fulfillment (60%), self-confidence (30%), connection (98%), and personal well-being (40%) while reading to their child.
Conclusion:
An inpatient early childhood literacy programme is a well-received intervention for infants with heart disease that promotes development, improves book access, increases reading exposure, and engages families. Further studies are needed to assess its impact on sustained reading practices and neurodevelopmental outcomes.