Early neurodevelopmental problems and risk for avoidant/restrictive food intake disorder (ARFID) in the general child population: a Japanese birth cohort study

Background: An overrepresentation of neurodevelopmental disorders (NDDs) has been observed in individuals with avoidant/restrictive food intake disorder (ARFID). Previous studies on the association between ARFID and NDDs are limited to cross-sectional data from clinical samples of small size. This study aimed to extend previous research by using prospectively collected data in children from a general population sample. We examined the occurrence and predictive power of early neurodevelopmental problems in 4-7-year-old children with suspected ARFID. Methods: Data were collected via parent-report in 3,728 children born between 2011 and 2014 in Kochi prefecture, a sub-sample of the Japan Environment and Children's Study (JECS). Neurodevelopmental problems were assessed with several instruments at different time points between 0.5 and 3 years of age as part of the JECS. In an add-on study, ARFID was identified cross-sectionally (between 4 and 7 years of age) using a newly developed screening tool. Results: Circa 3% of children at high risk for NDDs in preschool age screened positive for ARFID between age 4 and 7 years, reflecting a three times increased risk of suspected ARFID. A fifth (20.8%) of children with suspected ARFID had likely NDDs, compared to 8.6% of children without suspected ARFID. Developmental delay trajectories of children with and without suspected ARFID started to divert after the age of 6 months. Only 2.2% of children with early feeding problems later screened positive for ARFID. The inclusion of neurodevelopmental problems improved the prediction of later ARFID. Conclusions: The results mirror the previously observed overrepresentation of NDDs in ARFID populations, although to a weaker extent. In non-clinical populations, early feeding problems are common and rarely develop into ARFID, however, our findings imply that they should be monitored closely in children with high neurodevelopmental risk in order to prevent ARFID.

Bedtime to the brain: How infants sleep habits intertwine with sleep neurophysiology

Adequate sleep is critical for development and facilitates the maturation of the neurophysiological circuitries at the basis of cognitive and behavioral function. Observational research has associated sleep problems in early life with worse later cognitive, psychosocial, and somatic health outcomes. Yet, the extent to which day-to-day sleep habits in early life relate to neurophysiology - acutely and long-term - remains to be explored. Here, we report that sleep habits in 32 healthy 6-month-olds assessed with actimetry are linked to fundamental aspects of their neurophysiology measured with high-density electroencephalography (hdEEG). Our study reveals four key findings: First, daytime sleep habits are linked to EEG slow wave activity (SWA). Second, habits of nighttime movement and awakenings from sleep are connected with spindle density. Third, habitual sleep timing is linked to neurophysiological connectivity quantified as Delta-coherence. And lastly, Delta-coherence at age 6 months predicts nighttime sleep duration at age 12 months. These novel findings widen our understanding that infants' sleep habits are closely intertwined with three particular levels of neurophysiology: sleep pressure (determined by SWA), the maturation of the thalamocortical system (spindles), and the maturation of cortical connectivity (coherence). Our companion paper complements this insight in the perspective of later developmental outcomes: early thalamocortical connectivity (spindle density) at age 6 months predicts later behavioural status at 12 and 24 months. The crucial next step is to extend this concept to clinical groups to objectively characterize infants' sleep habits "at risk" that foster later neurodevelopmental problems.

Association Between Sleep Disturbances With Neurodevelopmental Problems and Decreased Health‐Related Quality of Life in Children With Fontan Circulation

Background Children with Fontan circulation are known to be at increased risk for neurodevelopmental problems and decreased health‐related quality of life (HRQOL), but many factors that may contribute to this risk are unknown. Sleep disturbances may be one previously unidentified factor that contributes to this risk. Methods and Results We analyzed data from the Pediatric Heart Network Fontan cross‐sectional study to evaluate associations between a parent or child report of sleep disturbance with reported neurodevelopmental concerns and HRQOL in 558 children with Fontan circulation. Parent‐reported sleep disturbance was present in 11% of participants and child‐reported sleep disturbance was present in 15%. Parent‐reported sleep disturbance was associated with a significantly higher risk of attention problems, anxiety, depression, behavioral problems, and developmental delay ( P <0.001 for all). Similarly, parent‐reported disturbance was associated with decreased HRQOL on both parent and child‐reported HRQOL ( P <0.001 for most domains). Child‐reported sleep disturbances were associated with increased odds of anxiety, depression, and attention problems as well as worse HRQOL. These associations were present even after adjustment for cardiac, demographic, and socioeconomic factors that may affect HRQOL and neurodevelopmental status. Conclusions Sleep disturbances in children with Fontan circulation are associated with an increased risk of neurodevelopmental problems as well as reduced HRQOL compared with those without sleep disturbance. Better understanding of sleep disturbances is needed in children with Fontan circulation, as sleep disturbances may represent a reversible cause of neurodevelopmental problems and decreased HRQOL in this population.

399The causal effect of BMI on neurodevelopment: a within family Mendelian randomization study using MoBa

Background Higher BMI in childhood predicts subsequent neurodevelopmental and emotional problems, but it is unclear if associations are causal. Observational studies are vulnerable to reverse causation and confounding. Mendelian randomization (MR) studies with unrelated individuals can also suffer from familial biases, such as dynastic effects (“genetic nurture”). Methods We apply within-family MR (WFMR) to overcome these biases. We used genetic information from 26,370 family trios in the Norwegian Mother, Father and Child Cohort Study (MoBa) to construct BMI polygenic scores in children and both parents. By using all three polygenic scores to instrument BMI, we avoided familial biases affecting previous studies. Results Multivariable-adjusted and conventional MR models implied an impact of children’s BMI on depressive, ADHD, and autism symptoms. In conventional MR models, a 5kg/m2 increase in BMI corresponded to depressive symptoms 0.49 SD higher (95%CI: 0.24-0.73), and ADHD symptoms 0.49 SD higher (95%CI: 0.28-0.70). WFMR estimates were less precise but gave little evidence of causal impacts of children’s BMI. Maternal BMI was positively associated with children’s depressive (0.16 SD per 5kg/m2, 95%CI: 0.04-0.28) and autism symptoms, and paternal BMI with children’s ADHD symptoms. Conclusions Compared to conventional MR models, MR models accounting for parental genotype found less evidence of causal effects of children’s own BMI on emotional and neurodevelopmental symptoms. The discrepancy may suggest an influence of family or population-level effects. Key messages The influence of children’s own BMI on emotional and neurodevelopmental problems may have been overstated. Parental BMI, familial or population level effects may influence these outcomes.

Congenital Diaphragmatic Hernia: More than Just a Lung Problem

Congenital Diaphragmatic Hernia (CDH) is a rare congenital anomaly characterized by a defect in the diaphragm, which permits abdominal organs to herniate into the thorax. This causes lung hypoplasia and at birth, children with CDH experience respiratory distress and pulmonary hypertension. Despite optimal neonatal treatment, CDH is still associated with a high mortality and morbidity. In severe cases, Fetal Intervention (FETO) may alter the natural course of this disease. Herein we describe the rationale, action mechanism and technique to perform this intervention. Despite hope giving results, this technique remains investigational for left sided CDH. However, an increased survival may come at the cost of increased morbidity. Children born with CDH are at increased risk for long and short-term morbidity, including neurodevelopmental problems. Until now, there are still uncertainties about the severity and prevalence of neurologic morbidity. Furthermore, it remains uncertain if these problems are already present prenatally and if a prenatal intervention influence this.

Infant–Father Attachment in Infants Born Preterm - A Brief Report

This study examines the infant–father attachment in infants born preterm (< 1500 g at birth and/or < 37 weeks gestation) in comparison to full-term infants. The infant–father attachment was assessed using the Strange Situation Procedure at a (corrected) age of 15 months. We found at least half of preterm and full-term infants (50.0% and 56.5 % respectively) securely attached to their fathers, and no significant overall difference was observed concerning the distribution of attachment quality comparing the two groups. In light of the fact that preterm infants tend to have numerous neurodevelopmental problems, it is encouraging that significant differences were not found in the distribution of the attachment quality among the groups. Therefore, from the perspective of attachment research, it would be highly beneficial to include fathers in the care of their preterm infants.

Protocol for a randomized pilot study (FIRST STEPS): implementation of the Incredible Years-ASLD® program in Spanish children with autism and preterm children with communication and/or socialization difficulties

Having access to parenting interventions in the early years is key to improve the developmental outcomes of children with neurodevelopmental problems. The Incredible Years® (IY) Parent Program is a group intervention that has demonstrated efficacy in terms of reducing stress in parents, as well as improving behavioral, emotional, and social outcomes in children. The program has been recently adapted for families of children with autism or language delays (IY-ASLD®). This intervention has not yet been implemented in the Spanish Public Health System, where there is a scarcity of evidence-based interventions being offered to families with young children presenting neurodevelopmental problems. The main aims of this study are to determine the feasibility of implementing the IY-ASLD® program within Spanish Child Mental Health Services and to examine parents’ acceptability and satisfaction with the intervention. As a secondary objective, we aim to evaluate its preliminary effectiveness in terms of reducing parental stress and behavioral difficulties in their children. The FIRST STEPS study is a multicenter, pilot randomized controlled trial comparing the IY-ASLD® program with a treatment-as-usual (TAU) condition. Approximately 70 families of children with autism spectrum disorder (ASD) and preterm children with communication and/or socialization difficulties (aged 2–5 years) will be recruited. Families will be assessed prior to randomization and after the intervention. Due to the COVID-19 pandemic, the intervention will consist of 22 weekly online sessions (approximately 6 months). The FIRST STEPS pilot trial will demonstrate the feasibility and acceptability of reliably implementing the IY-ASLD® program within the Spanish Public Health System. The results of this study could represent the first step to inform policymakers in Spain when designing evidence-based healthcare pathways for families of children presenting ASD symptoms or neurodevelopmental difficulties at early stages. Trial registration ClinicalTrials.gov NCT04358484. Registered on 04 April 2020