Shaping Microbiota During the First 1000 Days of Life.

Given that the host-microbe interaction is shaped by the immune system response, it is important to understand the key immune system-microbiota relationship during the period from conception to the first years of life. The present work summarizes the available evidence concerning human reproductive microbiota, and also, the microbial colonization during early life, focusing on the potential impact on infant development and health outcomes. Furthermore, we conclude that some dietary strategies including specific probiotics and other-biotics could become potentially valuable tools to modulate the maternal-neonatal microbiota during this early critical window of opportunity for targeted health outcomes throughout the entire lifespan.

Protocol and preregistration for the CODEC project: measuring, modelling and mechanistically understanding the nature of cognitive variability in early childhood.

BACKGROUND: Children's cognitive performance fluctuates across multiple timescales. However, fluctuations have often been neglected in favour of research into average cognitive performance, limiting the unique insights into cognitive abilities and development that cognitive variability may afford. Preliminary evidence suggests that greater variability is associated with increased symptoms of neurodevelopmental disorders, and differences in behavioural and neural functioning. The relative dearth of empirical work on variability, historically limited due to a lack of suitable data and quantitative methodology, has left crucial questions unanswered, which the CODEC (COgnitive Dynamics in Early Childhood) study aims to address. METHOD: The CODEC cohort is an accelerated 3-year longitudinal study which encompasses 600 7-to-10-year-old children. Each year includes a 'burst' week (3 times per day, 5 days per week) of cognitive measurements on five cognitive domains (reasoning, working memory, processing speed, vocabulary, exploration), conducted both in classrooms and at home through experience sampling assessments. We also measure academic outcomes and external factors hypothesised to predict cognitive variability, including sleep, mood, motivation and background noise. A subset of 200 children (CODEC-MRI) are invited for two deep phenotyping sessions (in year 1 and year 3 of the study), including structural and functional magnetic resonance imaging, eye-tracking, parental measurements and questionnaire-based demographic and psychosocial measures. We will quantify developmental differences and changes in variability using Dynamic Structural Equation Modelling, allowing us to simultaneously capture variability and the multilevel structure of trials nested in sessions, days, children and classrooms. DISCUSSION: CODEC's unique design allows us to measure variability across a range of different cognitive domains, ages, and temporal resolutions. The deep-phenotyping arm allows us to test hypotheses concerning variability, including the role of mind wandering, strategy exploration, mood, sleep, and brain structure. Due to CODEC's longitudinal nature, we are able to quantify which measures of variability at baseline predict long-term outcomes. In summary, the CODEC study is a unique longitudinal study combining experience sampling, an accelerated longitudinal 'burst' design, deep phenotyping, and cutting-edge statistical methodologies to better understand the nature, causes, and consequences of cognitive variability in children. TRIAL REGISTRATION: ClinicalTrials.gov - NCT06330090.

Development of full-body rhythmic synchronization in middle childhood.

Rhythmic entrainment is a fundamental aspect of musical behavior, but the skills required to accurately synchronize movement to the beat seem to develop over many years. Motion capture studies of corporeal synchronization have shown immature abilities to lock in to the beat in children before age 5, and reliable synchronization ability in adults without musical training; yet there is a lack of data on full-body synchronization skills between early childhood and adulthood. To document typical rhythmic synchronization during middle childhood, we used a wireless motion capture device to measure period- and phase-locking of full body movement to rhythm and metronome stimuli in 6 to 11 year-old children in comparison with adult data. Results show a gradual improvement with age; however children's performance did not reach adult levels by age 12, suggesting that these skills continue to develop during adolescence. Our results suggest that in the absence of specific music training, full-body rhythmic entrainment skills improve gradually during middle childhood, and provide metrics for examining the continued maturation of these skills during adolescence.

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.

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.

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.

Early-emerging combinatorial thought: Human infants flexibly combine kind and quantity concepts.

Combinatorial thought, or the ability to combine a finite set of concepts into a myriad of complex ideas and knowledge structures, is the key to the productivity of the human mind and underlies communication, science, technology, and art. Despite the importance of combinatorial thought for human cognition and culture, its developmental origins remain unknown. To address this, we tested whether 12-mo-old infants (N = 60), who cannot yet speak and only understand a handful of words, can combine quantity and kind concepts activated by verbal input. We proceeded in two steps: first, we taught infants two novel labels denoting quantity (e.g., "mize" for 1 item; "padu" for 2 items, Experiment 1). Then, we assessed whether they could combine quantity and kind concepts upon hearing complex expressions comprising their labels (e.g., "padu duck", Experiments 2-3). At test, infants viewed four different sets of objects (e.g., 1 duck, 2 ducks, 1 ball, 2 balls) while being presented with the target phrase (e.g., "padu duck") naming one of them (e.g., 2 ducks). They successfully retrieved and combined on-line the labeled concepts, as evidenced by increased looking to the named sets but not to distractor sets. Our results suggest that combinatorial processes for building complex representations are available by the end of the first year of life. The infant mind seems geared to integrate concepts in novel productive ways. This ability may be a precondition for deciphering the ambient language(s) and building abstract models of experience that enable fast and flexible learning.

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.

Relationship Between Prone Skills and Motor-Based Problem-Solving Abilities in Full-Term and Preterm Infants During the First 6 Months of Life.

Motor experiences shape cognitive development in infancy, with the prone position being one such crucial motor experience in the first 6 months of life. Although the motor benefits of the prone position are well-documented, its influence on early cognitive abilities remains insufficiently explored. This study quantified the relationship between prone motor skills and motor-based problem-solving abilities in 48 full-term and preterm infants aged 3-6 months. Prone skills were assessed using the Alberta Infant Motor Scale's prone domain. The Assessment of Problem-Solving in Play was utilized to measure motor-based problem-solving by observing how motor actions were used to solve toys. Advanced prone motor skills were correlated with an increase in sophisticated exploration skills and a concurrent decline in lower order exploration skills in all infants, with correlations being stronger in preterm infants. Notably, a 1-point increase in prone skills was associated with a 1.3-point increase in total motor-based problem-solving abilities in all infants. Our findings provide preliminary evidence for the contribution of prone play to cognitive development in infants, prompting considerations for assessment and intervention strategies. Further research is needed to ascertain if the delayed acquisition of prone motor skills is indicative of poor early problem-solving abilities in preterm infants.

Toddlers strategically adapt their information search.

Adaptive information seeking is essential for humans to effectively navigate complex and dynamic environments. Here, we developed a gaze-contingent eye-tracking paradigm to examine the early emergence of adaptive information-seeking. Toddlers (N = 60, 18-36 months) and adults (N = 42) either learnt that an animal was equally likely to be found in any of four available locations, or that it was most likely to be found in one particular location. Afterwards, they were given control of a torchlight, which they could move with their eyes to explore the otherwise pitch-black task environment. Eye-movement data and Markov models show that, from 24 months of age, toddlers become more exploratory than adults, and start adapting their exploratory strategies to the information structure of the task. These results show that toddlers' search strategies are more sophisticated than previously thought, and identify the unique features that distinguish their information search from adults'.

Preeclampsia, Fetal Growth Restriction, and 24-Month Neurodevelopment in Very Preterm Infants.

Importance: Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized. Objective: To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants. Design, Setting, and Participants: In this cohort study, infants in the prospective Neonatal Neurobehavior and Outcomes in Very Preterm Infants study were enrolled between April 2014 and June 2016 from 9 US university-affiliated neonatal intensive care units (NICUs). Eligible infants were born before 30 weeks' gestation. Infants were excluded for any major congenital anomalies and for maternal age younger than 18 years or cognitive impairment impacting the ability to provide informed consent. Data analysis was performed from November 2023 to January 2024. Exposure: Maternal preeclampsia and FGR in very preterm infants. Main Outcomes and Measures: The Bayley-III cognition, motor, and language scores less than 85 (-1 SD) indicated developmental delay. Child Behavior Checklist/Preschool 1.5-5 T-scores greater than or equal to 64 for internalizing, externalizing, or total problems indicated clinical importance. Results: Of 704 infants enrolled, 529 (mean [SD] gestational age, 27.0 [1.9] weeks; 287 male [54.3%]) were studied at 24-month follow-up. A total of 94 infants' mothers had preeclampsia (23.2%), and 46 infants (8.7%) had FGR. In adjusted models, preeclampsia was not associated with Bayley-III (cognitive, B = 3.43 [95% CI, -0.19 to 6.66]; language, B = 3.92 [95% CI, 0.44 to 7.39]; motor, B = 1.86 [95% CI, -1.74 to 5.47]) or Child Behavior Checklist/Preschool 1.5-5 (internalizing, B = -0.08 [95% CI, -2.58 to 2.73]; externalizing, B = 0.69 [95% CI, -1.76 to 3.15]; total, B = 0.21 [95% CI, -2.48 to 2.91]) outcomes. FGR was associated with significantly lower Bayley-III scores (cognitive, B = -8.61 [95% CI, -13.33 to -3.89]; language, B = -8.29 [95% CI, -12.95 to -3.63]; motor, B = -7.60 [95% CI, -12.40 to -2.66]), regardless of preeclampsia status. Conclusions and Relevance: In this cohort study of preterm infants, preeclampsia was not associated with developmental and/or behavioral outcomes, but infants with FGR may be prone to developmental delays. These findings suggest future areas of research for understanding the roles of preeclampsia and FGR separately and together in early child development for preterm infants.

Reaching While Learning to Sit: Capturing the Kinematics of Co-Developing Skills at Home.

This study examined the co-development of infant reaching and postural control across the transition to arms-free sitting at home. We observed infants with typical likelihood (TL; n = 24) and elevated likelihood (EL; n = 20) for autism at four biweekly sessions spanning the transition to arms-free sitting (infant age = 4.5-8 months at first session). At each session, infants sat on a pressure-sensitive mat with external support or independently, wore magneto-inertial sensors on both wrists, and reached for toys presented at midline. Analyses focused on characterizing and comparing control of sitting during reaching actions and standard kinematic metrics of reaching during Supported versus Independent Sitting. Although EL infants achieved arms-free sitting later than TL peers, there were no group differences on any measures. Across sessions, infants' control of the sitting posture during concurrent reaching movements improved in both contexts, though they were less stable as they reached when sitting independently compared to when sitting with support. A similar effect was apparent in the kinematics of reaches, with overall improvement over time, but evidence of poorer control in Independent relative to Supported Sitting. Taken together, these findings underscore the mutually influential and dynamic relations between emerging skills and well-established behaviors.

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.

Intrinsic Infant Hippocampal Function Supports Inhibitory Processing.

Impaired cerebral inhibition is commonly observed in neurodevelopmental disorders and may represent a vulnerability factor for their development. The hippocampus plays a key role in inhibition among adults and undergoes significant and rapid changes during early brain development. Therefore, the structure represents an important candidate region for early identification of pathology that is relevant to inhibitory dysfunction. To determine whether hippocampal function corresponds to inhibition in the early postnatal period, the present study evaluated relationships between hippocampal activity and sensory gating in infants 4-20 weeks of age (N = 18). Resting-state functional magnetic resonance imaging was used to measure hippocampal activity, including the amplitude of low-frequency fluctuations (ALFFs) and fractional ALFF. Electroencephalography during a paired-stimulus paradigm was used to measure sensory gating (P50). Higher activity of the right hippocampus was associated with better sensory gating (P50 ratio), driven by a reduction in response to the second stimulus. These findings suggest that meaningful effects of hippocampal function can be detected early in infancy. Specifically, higher intrinsic hippocampal activity in the early postnatal period may support effective inhibitory processing. Future work will benefit from longitudinal analysis to clarify the trajectory of hippocampal function, alterations of which may contribute to the risk of neurodevelopmental disorders and represent an intervention target.

Forever young: The end of history illusion in children.

The "end of history" illusion in adults (Quoidbach et al., 2013) is an asymmetrical pattern in which people accept that they've changed in the past but don't believe they will change in the future. We explore here whether the same psychological forces that cause the illusion in adults exist in the minds of children. Two studies with 4- to 11-year-olds (N = 256) suggest that they do, even in a within-subject design where the same child is asked questions about the past and the future. A third study (N = 83) finds that this illusion does not persist when children are asked about other people. These studies suggest that even young children believe that although they used to be different in the past, from this point on, they will remain forever young.

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.

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.

The developmental phenotype of motor delay in extremely preterm infants following early-life respiratory adversity is influenced by brain dysmaturation in the parietal lobe.

BACKGROUND: Research indicates that preterm infants requiring prolonged mechanical ventilation often exhibit suboptimal neurodevelopment at follow-up, coupled with altered brain development as detected by magnetic resonance imaging (MRI) at term-equivalent age (TEA). However, specific regions of brain dysmaturation and the subsequent neurodevelopmental phenotype following early-life adverse respiratory exposures remain unclear. Additionally, it is uncertain whether brain dysmaturation mediates neurodevelopmental outcomes after respiratory adversity. This study aims to investigate the relationship between early-life adverse respiratory exposures, brain dysmaturation at TEA, and the developmental phenotype observed during follow-up in extremely preterm infants. METHODS: 89 infants born < 29 weeks' gestation from 2019 to 2021 received MRI examinations at TEA for structural and lobe brain volumes, which were adjusted with sex-and-postmenstrual-age expected volumes for volume residuals. Assisted ventilation patterns in the first 8 postnatal weeks were analyzed using kmlShape analyses. Patterns for motor, cognition, and language development were evaluated from corrected age 6 to 12 months using Bayley Scales of Infant Development, third edition. Mediation effects of brain volumes between early-life respiratory exposures and neurodevelopmental phenotypes were adjusted for sex, gestational age, maternal education, and severe brain injury. RESULTS: Two distinct respiratory trajectories with varying severity were identified: improving (n = 35, 39%) and delayed improvement (n = 54, 61%). Compared with the improving group, the delayed improvement group exhibited selectively reduced brain volume residuals in the parietal lobe (mean - 4.9 cm3, 95% confidence interval - 9.4 to - 0.3) at TEA and lower motor composite scores (- 8.7, - 14.2 to - 3.1) at corrected age 12 months. The association between delayed respiratory improvement and inferior motor performance (total effect - 8.7, - 14.8 to - 3.3) was partially mediated through reduced parietal lobe volume (natural indirect effect - 1.8, - 4.9 to - 0.01), suggesting a mediating effect of 20%. CONCLUSIONS: Early-life adverse respiratory exposure is specifically linked to the parietal lobe dysmaturation and neurodevelopmental phenotype of motor delay at follow-up. Dysmaturation of the parietal lobe serves as a mediator in the connection between respiratory adversity and compromised motor development. Optimizing respiratory critical care may emerge as a potential avenue to mitigate the consequences of altered brain growth and motor developmental delay in this extremely preterm population.

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.