Multi-informant evaluation of Cognitive Disengagement Syndrome (formerly Slow Cognitive Tempo). Children's self-reported measures in relation to parents / Evaluación multi-informante del Síndrome de Desconexión Cognitiva (anteriormente Tempo Cognitivo Lento). Medidas autoinformadas de los niños con relación a padres

El objetivo fue examinar, desde una aproximación multi-informante, las medidas del Síndrome de Desconexión Cognitiva (SDC) de padres/madres e hijos/as y su relación con síntomas internalizantes y externalizantes. 279 niños/as (9-13 años), y sus padres/madres completaron las evaluaciones sobre SDC, la inatención del trastorno por déficit de atención e hiperactividad (TDAH) y otras medidas internalizadas y externalizadas. Los ítems de las tres medidas de SDC convergieron razonablemente bien en el factor SDC. Se aportaron pruebas discriminantes de la validez de las relaciones entre las puntuaciones de las pruebas y las medidas de los tres constructos diferentes (SDC, soledad y preferencia por la soledad). La asociación más estrecha estuvo entre la evaluación parental de las medidas de SDC con ansiedad y depresión, y entre inatención con hiperactividad/impulsividad y trastorno negativista desafiante. Se observó capacidad predictiva de la medida de SDC sobre la soledad y preferencia por estar solo autoinformadas. Se encontró una posible asociación entre la medida del SDC evaluado por padres/madres y sexo y edad de los niños. En conclusión, los datos apoyan la inclusión de medidas autoinformadas en la evaluación del SDC. Las medidas del SDC en niños se vinculan con medidas internalizantes y, la inatención con las externalizantes.(AU)

[Research progress on the effects of exposure to major persistent organic pollutants during pregnancy on the functional development of nervous system in children].

Persistent Organic Pollutants (POPs) have the characteristics of resistance to environmental degradation, bioaccumulation and long-distance migration potential. Maternal exposure to POPs during pregnancy can enter the fetal blood circulation through the placental barrier, and have a potential impact on the functional development of the nervous system of the offspring. This in turn leads to the occurrence and development of neurological defects and diseases in adulthood. The purpose of this paper is to elucidate the effects of exposure to three major POPs (organochlorine compounds, perfluoroalkyl and polyfluoroalkyl substances, and polybrominated diphenyl ethers) during pregnancy on the functional development of the nervous system (social emotions, cognition, language, exercise, and adaptability) in children, and to provide reference for subsequent studies.

Interventions to improve executive functions in children aged 3 years and under: A systematic review.

BACKGROUND: Early executive functioning (EF) skills are foundational capabilities that predict school readiness, academic development and psychiatric risk. Early interventions enhancing these capabilities could have critical import in improving outcomes. However, to develop interventions, it is necessary to identify specific EF skills that will vary with child age. Thus, we aimed to examine the characteristics and efficacy of interventions targeting EF in infancy and early childhood up to age 3. METHODS: A comprehensive search of PubMed, Embase, CINAHL and APA PsycINFO databases was performed for studies published before December 2022. Randomized and non-randomized studies of interventions designed to improve at least one EF skill in children ≤3 years were included. EF skills included attentional control, inhibition/self-regulation, activity initiation, working memory, cognitive flexibility, planning ability, problem-solving and performance monitoring. We independently extracted data, used the revised Cochrane Risk-of-Bias tool to assess the quality of the evidence and conducted Synthesis Without Meta-analysis (SWiM). The overall quality of the evidence and the strength of recommendations was determined using elements of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Thirty-five studies met inclusion criteria (original n = 7467). Studies were highly variable in the EF skill targeted, target subject (i.e., child, parent and teacher), nature and dosage of the intervention, and timing of outcome assessment. Most interventions focused on improving impulse control and self-regulation. The overall quality of evidence was low to moderate with a high risk of bias, though six studies had low risk of bias but yielded mixed findings of efficacy. CONCLUSIONS: The relatively small number of early EF intervention studies uses such variable methods that there is currently no converging evidence of efficacy to recommend a specific intervention. Thus, findings support the need for a more systematic, targeted approach to the design and implementation of early EF interventions for target populations.

Infant formula supplemented with milk fat globule membrane compared with standard infant formula for the cognitive development of healthy term-born formula-fed infants: protocol for a randomised controlled trial.

INTRODUCTION: Milk fat globule membrane (MFGM) is a complex lipid-protein structure in mammalian milk and human milk that is largely absent from breastmilk substitutes. The objective of this trial is to investigate whether providing infant formula enriched with MFGM versus standard infant formula improves cognitive development at 12 months of age in exclusively formula-fed full-term infants. METHODS AND ANALYSIS: This is a randomised, controlled, clinician-blinded, researcher-blinded and participant-blinded trial of two parallel formula-fed groups and a breastfed reference group that were recruited in the suburban Adelaide (Australia) community by a single study centre (a medical research institute). Healthy, exclusively formula-fed, singleton, term-born infants under 8 weeks of age were randomised to either an MFGM-supplemented formula (intervention) or standard infant formula (control) from enrolment until 12 months of age. The reference group was not provided with formula. The primary outcome is the Cognitive Scale of the Bayley Scales of Infant Development, Fourth Edition (Bayley-IV) at 12 months. Secondary outcomes are the Bayley-IV Cognitive Scale at 24 months, other Bayley-IV domains (language, motor, emotional and behavioural development) at 12 and 24 months of age, infant attention at 4 and 9 months of age, parent-rated language at 12 and 24 months of age, parent-rated development at 6 and 18 months of age as well as growth, tolerance and safety of the study formula. To ensure at least 80% power to detect a 5-point difference in the mean Bayley-IV cognitive score, >200 infants were recruited in each group. ETHICS AND DISSEMINATION: The Women's and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/19/WCHN/140). Caregivers gave written informed consent prior to enrolling in the trial. Findings of this study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12620000552987; Australian and New Zealand Clinical Trial Registry: anzctr.org.au.

Endogenous Control and Reward-based Mechanisms Shape Infants' Attention Biases to Caregiver Faces.

Infants rely on developing attention skills to identify relevant stimuli in their environments. Although caregivers are socially rewarding and a critical source of information, they are also one of many stimuli that compete for infants' attention. Young infants preferentially hold attention on caregiver faces, but it is unknown whether they also preferentially orient to caregivers and the extent to which these attention biases reflect reward-based attention mechanisms. To address these questions, we measured 4- to 10-month-old infants' (N = 64) frequency of orienting and duration of looking to caregiver and stranger faces within multi-item arrays. We also assessed whether infants' attention to these faces related to individual differences in Surgency, an indirect index of reward sensitivity. Although infants did not show biased attention to caregiver versus stranger faces at the group level, infants were increasingly biased to orient to stranger faces with age and infants with higher Surgency scores showed more robust attention orienting and attention holding biases to caregiver faces. These effects varied based on the selective attention demands of the task, suggesting that infants' attention biases to caregiver faces may reflect both developing attention control skills and reward-based attention mechanisms.

Analyzing Children's Weight Growth Variations and Associated Factors in Ethiopia, India, Peru, and Vietnam: Using Fractional Polynomial Mixed-Effects Model.

Background: Children's growth is increasingly considered a key mediator of later life outcomes. When examining weight growth, the correlation between repeated observations on the same subject must be regarded as well-modelled. This study aimed to analyze children's weight growth variations and associated factors in Ethiopia, India, Peru, and Vietnam using a fractional polynomial mixed-effects model. Methods: This study used longitudinal data from the Young Lives Cohort Study conducted from 2002 to 2016 in Ethiopia, India, Peru, and Vietnam. The study included 7,140 children of 1 to 15 years old A fractional polynomial mixed-effects model was used to analyze the data. Results: Ethiopian, Peruvian, and Vietnamese children had significantly higher average body weights than children in India (1.426, P<0.001; 1.992, P<0.001; 1.334, P<0.001, respectively). Girl children's average body weight was significantly 0.15 times less than that of boys (-0.148; P=0.027). The average weight of rural children was significantly 0.671 times less than that of urban children (0.671, P<0.001). Children from Peru and Vietnam had higher rates of weight change than those from India. However, the rate of weight change was lower in Ethiopian children than in Indian children. Children from urban areas had a significantly higher rate of weight gain than those from rural areas. Conclusion: Country, sex, residence, parental education, household size, wealth, good drinking water, and reliable power affected children's longitudinal weight growth. Therefore, WHO and the nation's health ministry should monitor children's weight growth status and these associated factors to plan future action.

Early childhood development strategy for the world's children with disabilities.

Early childhood is foundational for optimal and inclusive lifelong learning, health and well-being. Young children with disabilities face substantial risks of sub-optimal early childhood development (ECD), requiring targeted support to ensure equitable access to lifelong learning opportunities, especially in low- and middle-income countries. Although the Sustainable Development Goals, 2015-2030 (SDGs) emphasise inclusive education for children under 5 years with disabilities, there is no global strategy for achieving this goal since the launch of the SDGs. This paper explores a global ECD framework for children with disabilities based on a review of national ECD programmes from different world regions and relevant global ECD reports published since 2015. Available evidence suggests that any ECD strategy for young children with disabilities should consists of a twin-track approach, strong legislative support, guidelines for early intervention, family involvement, designated coordinating agencies, performance indicators, workforce recruitment and training, as well as explicit funding mechanisms and monitoring systems. This approach reinforces parental rights and liberty to choose appropriate support pathway for their children. We conclude that without a global disability-focussed ECD strategy that incorporates these key features under a dedicated global leadership, the SDGs vision and commitment for the world's children with disabilities are unlikely to be realised.

Developmental outcomes in abusive head trauma.

Abusive head trauma (AHT) is associated with high mortality and poorer outcomes compared to accidental head injuries. The short and long-term developmental outcomes for AHT are not well identified. Variability in outcome measures, small sample sizes, difficulty in measuring domain-specific developmental skills, co-existence of comorbidities, genetic and environmental factors and high attrition rates all contribute to the challenges on providing data in this area. The objective of this article is to review the scientific literature on the developmental outcomes of AHT, highlighting factors that affect outcomes, the available assessment tools, and short and long-term developmental outcomes, recommended follow up, societal costs, and future opportunities for research. Authors searched OVID Medline and PubMed for articles published between 2013 and 2023 using the terms "abuse", "craniocerebral trauma" and "development". Fifty-five records were included for this review. The data shows that injuries sustained from AHT result in a spectrum of outcomes ranging from normal development to death. There are more than 100 outcome assessment tools limiting the ability to compare studies. More than half of patients are left with disabilities post discharge. Gross motor and cognition/academics are the 2 most common domains studied. Advancement in surgical and neurocritical care management has influenced AHT outcomes. Close long-term follow up is recommended to maximize each child's developmental potential, irrespective of the presence of disability at discharge. We suggest that future research should focus on adopting a consistent diagnostic and assessment approach and explore the social environmental factors that can affect recovery.

Effects of a staff-led multicomponent physical activity intervention on preschooler's fundamental motor skills and physical fitness: The ACTNOW cluster-randomized controlled trial.

BACKGROUND: Fundamental motor skills (FMS) and physical fitness (FIT) play important roles in child development and provide a foundation for lifelong participation in physical activity (PA). Unfortunately, many children have suboptimal levels of PA, FMS, and FIT. The Active Learning Norwegian Preschool(er)s (ACTNOW) study investigated the effects of a staff-led PA intervention on FMS, FIT, and PA in 3-5-year-old children. METHODS: Preschools in Western Norway having ≥ six 3-4-year-old children were invited (n = 56). Of these, 46 agreed to participate and were cluster-randomized into an intervention (n = 23 preschools [381 children, 3.8 yrs., 55% boys]) or a control group (n = 23 [438, 3.7 yrs., 52% boys]). Intervention preschools participated in an 18-month PA intervention involving a 7-month staff professional development between 2019 and 2022, amounting to 50 h, including face-to-face seminars, webinars, and digital lectures. Primary outcomes in ACTNOW were cognition variables, whereas this study investigated effects on secondary outcomes. FMS was measured through 9 items covering locomotor, object control, and balance skills. FIT was assessed as motor fitness (4 × 10 shuttle-run test) and upper and lower muscular strength (handgrip and standing long jump). PA was measured with accelerometers (ActiGraph GT3X +). All measures took place at baseline, 7-, and 18-month follow-up. Effects were analysed using a repeated measures linear mixed model with child and preschool as random effects and with adjustment for baseline scores. RESULTS: Participants in the intervention preschools showed positive, significant effects for object control skills at 7 months (standardized effect size (ES) = 0.17) and locomotor skills at 18 months (ES = 0.21) relative to controls. A negative effect was found for handgrip strength (ES = -0.16) at 7 months. No effects were found for balance skills, standing long jump, or motor fitness. During preschool hours, sedentary time decreased (ES = -0.18), and light (ES = 0.14) and moderate-to-vigorous PA (ES = 0.16) increased at 7 months, whereas light PA decreased at 18 months (ES = -0.15), for intervention vs control. No effects were found for other intensities or full day PA. CONCLUSIONS: The ACTNOW intervention improved some FMS outcomes and increased PA short-term. Further research is needed to investigate how to improve effectiveness of staff-led PA interventions and achieve sustainable improvements in children's PA, FMS, and FIT. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT04048967 , registered August 7, 2019. FUNDING: ACTNOW was supported by the Research Council of Norway (grant number 287903), the County Governor of Sogn og Fjordane, the Sparebanken Sogn og Fjordane Foundation, and the Western Norway University of Applied Sciences.

Cohort differences between preschool development of in vitro fertilization and naturally conceived infants.

To explore the differential cohort situation between preschool development of in vitro fertilization (IVF) and naturally conceived infants. From April 2014 to June 2022, 60 preschool IVFs were selected as the research subjects for follow-up at the pediatric health clinic of hospital's prevention and health department. They were set as the experimental group (Group S), and 60 naturally conceived infants of the same age were selected as the control group (Group Z). Data from both groups were collected through telephone follow-up and other methods. No significant difference showed between the 2 groups in age specific height, age specific weight, Gesell developmental score, Denver developmental screening test screening results, intellectual development index, and motor development index (P > .05). The influence of birth environment factors such as family background and maternal education level on children's height and weight was not significant (P > .05), while maternal education level had a significant impact on children's intellectual development index (P < .05). No significant difference showed in the development of preschool children in IVF compared to naturally conceived children, and the level of parental education has a significant impact on children's mental and motor development.

"The Early Years are Like a Foundation for the Future" Perspectives, Facilitators, and Challenges of Anganwadi Workers in Supporting Early Child Development Interventions in Hyderabad, India: Qualitative Findings from a Scalable Program Incorporating Early Child Development Interventions.

BACKGROUND: Integrated Child Development Services (ICDS) scheme, a large public health program, addresses the needs of young children with Anganwadi Workers (AWWs) as frontline agents of delivery. A scalable program incorporating early child development interventions (ASPIRE) has been developed to complement the program and address some of its gaps. OBJECTIVES: This paper describes formative work done with AWWs, as part of ASPIRE to assess their understanding of early childhood development (ECD) and acceptability of a novel ECD intervention using digital technology. MATERIALS AND METHODS: Six focus group discussions (FGDs) were conducted with 31 AWWs, using a semi-structured guide. RESULTS: Framework analysis of their responses from FGDs led to the identification of three themes: (1) time use, (2) understanding of ECD, and (3) delivering messages using videos. The findings suggest that AWWs tight schedules often leave them feeling overburdened with work. They are aware of factors that can aid as well as hinder child growth and development, but their understanding of play is limited to games played by older children. They expressed acceptability in using a video intervention, specifying features that would increase relevance for families. CONCLUSION: Integration of novel ECD interventions delivered by frontline workers needs to take into account their existing work schedules and associated challenges. Training on ECD interventions will need to broaden AWWs understanding of the critical foundational experiences which responsive caregiving and early child stimulation can provide.

A longitudinal multi-centric cohort study assessing infant neurodevelopment delay among women with persistent postpartum depression in Nepal.

BACKGROUND: Infant neurodevelopment in the first years after birth is determined by multiple factors, including parental care and maternal mental wellbeing. In this study, we aim to assess the impact of persistent maternal depressive symptoms during the first 3 months postpartum on infant neurodevelopment at 6 months. METHODS: Using a longitudinal cohort design, 1253 mother-infant pairs were followed up at 7, 45, and 90 days to assess postpartum depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS); infants were followed up at 6 months to assess neuro-developmental status using the WHO's Infant and Young Child Development (IYCD) tool. A generalized linear regression model was used to assess the association between persistent postpartum depressive symptoms and infant neurodevelopmental delay at 6 months. A generalized linear mixed model (GLMM) with a hospital as a random intercept was used to assess the persistent postpartum depressive symptoms with an IYCD score. Linear regression was used to compare the IYCD scores between exposure groups. RESULTS: In the study population, 7.5% of mothers had persistent depressive symptoms, and 7.5% of infants had neurodevelopmental delay. Infants born to mothers with persistent depressive symptoms had a higher proportion of neurodevelopmental delay than infants born to women without persistent symptoms (48.6% vs 5.1%; p < 0.001). In the adjusted regression model, infants whose mothers had persistent depressive symptoms at 7, 45, and 90 days had a 5.21-fold increased risk of neurodevelopmental delay (aRR, 5.21; 95% CI, 3.17, 8.55). Mean scores in the motor domain (12.7 vs 15.2; p < 0.001) and language domain (6.4 vs 8.5; p < 0.001) were significant when a mother had persistent depression vs. no depression. Mean scores in the general behavioral domain (5.9 vs 10.4, p < 0.001) and the socio-emotional domain (15.4 vs 17.7; p < 0.001) were significantly different when a mother had persistent depression vs no persistent depression. CONCLUSIONS: Our results suggest that 6-month-old infants are at higher risk for neurodevelopment delays if their mother reports persistent symptoms of depression from 7 to 90 days postpartum. The neurodevelopmental delay can be observed in all functional domains. Preventive intervention to reduce maternal postpartum depression may reduce the impact on infant developmental delay.

The varied perspectives of organisational effectiveness: What's at stake for early childhood development programmes in Rwanda?

Within global health and development, dissatisfaction with nongovernmental organisations' effectiveness (NGOs) is an increasingly pervasive aspect of programming. Today, the international community no longer accepts that NGOs are doing what they claim. This change in expectations has emphasised the importance of measuring organisational effectiveness for improved health and development impact. Using New Institutionalism as a theoretical framework, we investigated how institutional norms and expectations influence the adoption of structures and processes by NGOs, and Early Childhood Development (ECD) programming effectiveness in Rwanda - since little research connects these concepts. We employed qualitative methods: 45 in-depth interviews and 6 focus group discussions. Findings revealed a misalignment of 'organizational effectiveness' across scales, from global to local. Findings stress that, effectiveness, though an expectation of the institutional environment, may not be a valid construct for NGOs, generating implications for ECD programming. Findings also indicate measurement of global health interventions generally and the notion of effectiveness specifically can yield adverse implications for ECD programming. These findings are relevant for researchers and practitioners trying to better understand organisational effectiveness for ECD programmes because they suggest that effectiveness is socially constructed and measured differently across the different scales.

Cumulative sucrose exposure for repeated procedural pain in preterm neonates and neurodevelopment at 18 months of corrected age: a prospective observational longitudinal study.

INTRODUCTION: Oral sucrose is repeatedly administered to neonates in the neonatal intensive care unit (NICU) to treat pain from commonly performed procedures; however, there is limited evidence on its long-term cumulative effect on neurodevelopment. We examined the association between total sucrose volumes administered to preterm neonates for pain mitigation in the NICU and their neurodevelopment at 18 months of corrected age (CA). METHODS: A prospective longitudinal single-arm observational study that enrolled hospitalised preterm neonates <32 weeks of gestational age at birth and <10 days of life was conducted in four level III NICUs in Canada. Neonates received 0.1 mL of 24% sucrose 2 min prior to all commonly performed painful procedures during their NICU stay. Neurodevelopment was assessed at 18 months of CA using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Multiple neonatal and maternal factors known to affect development were adjusted for in the generalised linear model analysis. RESULTS: 172 preterm neonates were enrolled and 118 were included in the analysis at 18 months of CA. The total mean sucrose volume administered/neonate/NICU stay was 5.96 (±5.6) mL, and the mean Bayley-III composite scores were: cognitive 91 (±17), language 86 (±18) and motor 88 (±18). There was no association between Bayley-III scores and the total sucrose volume: cognitive (p=0.57), language (p=0.42) and motor (p=0.70). CONCLUSION: Cumulative sucrose exposure for repeated procedural pain in preterm neonates was neither associated with a delay in neurodevelopment nor neuroprotective effects at 18 months of CA. If sucrose is used, we suggest the minimally effective dose combined with other non-pharmacological interventions with demonstrated effectiveness such as skin-to-skin contact, non-nutritive sucking, facilitated tucking and swaddling. TRIAL REGISTRATION NUMBER: NCT02725814.

Prenatal exposure to PM2.5 and childhood body mass index growth trajectories from birth to 6 years old.

This study aimed to determine the relationships between prenatal PM2.5 exposure and childhood growth trajectories during the first 6 years of life. A total of 47,625 pairs of mothers and children were recruited from a prospective birth cohort conducted between 2011 and 2013 in Wuhan, China, and followed for 6 years. We used the group-based trajectory models to classify the population into three trajectory groups: slow growth (n = 13,671, 28.7%), normal growth (n = 29,736, 62.4%), and rapid growth (n = 4218, 8.9%). Multinomial logistic regression models were used to determine the associations of prenatal PM2.5 exposure and childhood growth trajectories. Compared to normal growth trajectory, increased PM2.5 exposure in trimester 1, trimester 2 and the entire pregnancy showed significant associations with an increased risk of the slow growth trajectory but reduced the risk for the rapid growth trajectory, significant association of prenatal PM2.5 exposure with rapid growth trajectory was only observed in the trimester 3. Stratified analyses displayed relatively stronger associations among those mothers with maternal age over 35 years, pre-pregnancy BMI ≥ 25 kg/m2, and previous delivery experience. Prenatal exposure to PM2.5, particularly during the midpoint period of pregnancy, was more likely to have a slow growth trajectory and a lower risk of rapid growth trajectory. Maternal age, pre-pregnancy BMI, and previous delivery experience might modify these associations.

Large-scale analysis of structural brain asymmetries during neurodevelopment: Associations with age and sex in 4265 children and adolescents.

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.

Parental prenatal representations of the child are related to 18-month-old children's social-emotional competence.

Parental representations of the child are linked to positive developmental outcomes in children, but the impact of prenatal representations on early social-emotional development, particularly from fathers, is less understood. This study explores how fathers' and mothers' prenatal representations within two-parent families are associated with early social-emotional development. Prenatal representations of fathers (n = 88) and mothers (n = 92) were assessed between 28 and 32 weeks of gestation using the Working Model of the Child Interview, categorizing them as balanced or nonbalanced. The children's (n = 97; 49.5% girls) social-emotional and behavioral problems and competencies were measured at 18 months using the Brief Infant-Toddler Social and Emotional Assessment. Balanced prenatal representations of both parents were related to higher social-emotional competence in toddlers. However, prenatal representations were not related to social-emotional and behavioral problems. The results highlight the benefits of balanced prenatal representations in promoting early social-emotional competence in children.

Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-up.

INTRODUCTION: Currently, the majority of women worldwide with threatened preterm birth are treated with tocolytics. Although tocolytics can effectively delay birth for 48 hours, no tocolytic drug has convincingly been shown to improve neonatal outcomes and effects on long-term child development are unknown. The aim of this follow-up study of a placebo controlled randomised trial is to investigate the long-term effects of atosiban administration in case of threatened preterm birth on child's neurodevelopment and behaviour development, overall health and mortality. METHODS AND ANALYSIS: This protocol concerns a follow-up study of the multicentre randomised double-blind placebo controlled APOSTEL 8 trial (NL61439.018.17, EudraCT-number 2017-001007-72). In this trial, women with threatened preterm birth (between 30 and 34 weeks of gestation) defined as uterine contractions with (1) a cervical length of <15 mm or (2) a cervical length of 15-30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or Actim-Partus test or (4) ruptured membranes, are randomised to atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Children born to mothers who participated in the APOSTEL 8 study (n=760) will be eligible for follow-up at 4 years of corrected age and assessed using four parent-reported questionnaires. Primary outcomes are neurodevelopment and behaviour problems. Secondary outcomes are on child growth and general health. All outcomes will be compared between the atosiban and placebo group with OR and corresponding 95% CI. Analyses will be performed using the intention-to-treat approach. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee from Amsterdam UMC confirmed that de Medical Research Involving Human Subjects Act (Dutch WMO-law) did not apply to our study (W21_386 # 21.431). Results will be published in a peer-reviewed journal and shared with stakeholders and participants. This protocol is published before analysis of the results.

Early treatment for children with mental health problems and genetic conditions through a parenting intervention (The GAP): study protocol for a pragmatic randomized controlled trial.

BACKGROUND: Children with genetic conditions are at increased risk for mental health and neurodevelopmental problems, often accompanied by significant parental distress. Genetic and family factors can impact children and parents' mental health. Early parenting interventions, like the Incredible Years® programs, have demonstrated to improve parental distress and children's mental health. The recent version for young children with language delays or autism spectrum disorder (IY-ASLD®) has shown to be feasible and effective to support parents in their children's developmental trajectories. The effectiveness of treatments for children with genetic conditions and neurodevelopmental problems is largely unexplored, leaving significant gaps in evidence-based options. Clinicians lack guidance, especially when patients exhibit language or social communication impairments but do not meet diagnostic criteria for a full-blown autism spectrum disorder (ASD). We aim to fill this gap, providing evidence on the feasibility and effectiveness of the IY-ASLD® intervention for such patients. METHODS: We designed a prospective multicenter pragmatic randomized controlled trial including approximately 68 children aged 3 to 7 years, recruited from three tertiary care reference hospitals. Inclusion criteria will necessitate genetic confirmation of a neurodevelopmental disorder along with language, communication, or socialization difficulties. Individuals with an ASD diagnosis will be excluded. All subjects are included in a territorial register for rare conditions (ReMin, Registre de Malalties Minoritàries de Catalunya). Families will randomly be assigned to the intervention or the control group. The intervention will be held online by clinical psychologists and child and adolescent psychiatrists. DISCUSSION: Our group has recently piloted the online implementation of the IY-ASLD® intervention for the first time in Spain, for parents of children with language delays, socialization difficulties, or ASD, but not genetically determined. Our multicenter research consortium is well-positioned to recruit patients with rare conditions and implement efficient treatment pathways within the National Health System. Given the geographical dispersion of families affected by rare conditions, the online format offers logistical advantages and improved therapy access, enhancing homogeneity across all patients. The results of this study will inform clinicians and policymakers about evidence-based treatment options for this vulnerable and overlooked group of young children. TRIAL REGISTRATION: ClinicalTrials.gov NCT06125093 . Date of registration: first submitted 2023-10-23; first posted 2023-11-09. URL of trial registry record.

Introduction of Solid Foods in Preterm Infants and Its Impact on Growth in the First Year of Life-A Prospective Observational Study.

The aim of this study was to investigate whether age at introduction of solid foods in preterm infants influences growth in the first year of life. This was a prospective observational study in very low birth weight infants stratified to an early (<17 weeks corrected age) or a late (≥17 weeks corrected age) feeding group according to the individual timing of weaning. In total, 115 infants were assigned to the early group, and 82 were assigned to the late group. Mean birth weight and gestational age were comparable between groups (early: 926 g, 26 + 6 weeks; late: 881 g, 26 + 5 weeks). Mean age at weaning was 13.2 weeks corrected age in the early group and 20.4 weeks corrected age in the late group. At 12 months corrected age, anthropometric parameters showed no significant differences between groups (early vs. late, mean length 75.0 vs. 74.1 cm, weight 9.2 vs. 8.9 kg, head circumference 45.5 vs. 45.0 cm). A machine learning model showed no effect of age at weaning on length and length z-scores at 12 months corrected age. Infants with comorbidities had significantly lower anthropometric z-scores compared to infants without comorbidities. Therefore, regardless of growth considerations, we recommend weaning preterm infants according to their neurological abilities.