1. Abeasi DA, Nkosi NG, Badoe E, Adjeman J. Caring by default: experiences of caregivers of children with developmental disabilities in Ghana mirrored in the context of the stress process model. BMC Nurs;2024 (Jul 15);23(1):482.

BACKGROUND: Caring for a child with developmental disabilities (DD) is associated with significant stress and burden. Caregivers’ experiences are influenced by factors such as poverty, stigma, and the lack of accessibility to services, equipment, and assistive devices. These factors are prevalent in a low-resource setting like Ghana which ultimately influences the experiences of caregivers. The aim of the study was to explore the experiences of caregivers of children with DD in the context of the Stress Process Model. METHODS: The study employed a descriptive phenomenological design Caregivers of children with DD attending the Neurodevelopmental Clinic of a Teaching Hospital were purposively sampled. Data collection involved semi-structured interviews, reaching saturation with 14 participants. The interviews were audio-recorded transcribed verbatim and analysed using thematic analysis. RESULTS: Four main themes emerged: perception of caregiving, stressors faced by caregivers, negative health outcomes and coping strategies. Perception of caregiving had two sub-themes as stressful nature of caregiving and time-consuming. Six sub-themes were linked to stressors faced by caregivers: the child’s ADL needs, communication barrier, managing challenging behaviour, child’s health needs, unmet educational needs, and economic burden. Negative health outcomes had three sub-themes: decline in physical, mental and social well-being. While some caregivers used maladaptive coping strategies like blaming, others employed adaptive coping strategies like religious coping through prayer, self-encouragement and support from other family members. CONCLUSION: The study highlights the complex interaction between caregivers’ perception of their caregiving situation, the stressors they experience, their coping resources, and the negative health outcomes associated with caregiving. These findings underscore the need for context-specific caregiver programmes to mitigate the negative impacts of caregiving.

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2. Bin Zuair HM, Baird JM, Caldwell AR. Parent-Mediated Occupational Therapy Interventions for Children with Developmental Disabilities: A Scoping Review. Phys Occup Ther Pediatr;2024 (Jul 16):1-17.

AIM: This scoping review synthesizes literature about occupational therapy parent-mediated interventions (PMIs) that target occupation-based outcomes for children with developmental disabilities (DD). METHODS: A search of PubMed, Web of Science, and CINAHL from 2010 through 2023 was performed resulting in 471 publications. Studies were included if they involved PMIs for participants with DD aged 3-12 years and were published in English. Studies were excluded if the outcomes were not occupation-based. A thematic analysis was conducted following an iterative review of charted data. RESULTS: Twelve studies met the inclusion criteria reflecting four themes across occupational therapy PMIs, including variation in terminologies, types of PMIs, key components of PMIs, and the overall impact. While the effects of PMIs are difficult to define due to the variability in the samples, interventions, and outcomes, this review suggests general positive impacts of PMIs. CONCLUSION: The emerging body of evidence supporting PMIs within the field of occupational therapy suggests they are feasible and have the potential to improve child and parent outcomes when delivered to children with DD. Further research is needed to clarify PMIs’ components, unify the identification terminology, and test the efficacy of different types of PMIs for specific populations.

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3. Efron D, Fowler J, Cull E, Noakes K, Wilkin C, Haslam R. A novel model of care for paediatric patients with developmental disabilities and associated behaviours of concern. J Paediatr Child Health;2024 (Jul 16)

AIM: Children and adolescents with autism spectrum disorder and/or intellectual disability often present to emergency departments with behaviours of concern: irritability, aggression and self-injurious behaviour. The objective of this study was to design, implement and evaluate a new model of care to support these patients and their families following presentation to reduce the need for re-presentation. METHODS: We designed and evaluated a new model of care for these patients, comprising consultations with a developmental paediatrician and a child psychiatrist, referral to a specialist behavioural service and 6 weeks of care coordination by a clinical nurse consultant. Using a quality improvement framework, iterative improvements were made to the model via a series of plan-do-study-act cycles. Re-presentation rates were compared with a control group of patients who presented with behaviours of concern but were not recruited into the study. Participating families and treating clinicians were surveyed at 2 and 6 weeks post-enrolment to gather qualitative feedback about their experience of the model. RESULTS: A total of 31 families participated in the study. Three- and 6-month re-presentation rates were 48.7% and 36.3% lower than the control group. Qualitative evaluation of the model by both families and clinicians was positive. The model was feasible and acceptable. Families reported feeling heard and understood, and that the intervention was helpful and provided a positive path forwards. CONCLUSIONS: The findings suggest that a simple model of care can be successfully implemented and provide meaningful benefits for families of children with behaviours of concern, including reduced crisis-oriented help-seeking.

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4. Forsen E, Marrus N, Joyce J, Zhang Y, Constantino JN. Mate selection and current trends in the prevalence of autism. Mol Autism;2024 (Jul 16);15(1):29.

BACKGROUND: According to the most recent U.S. CDC surveillance data, the rise in prevalence of childhood autism spectrum disorder among minority children has begun to outpace that of non-Hispanic white children. Since prior research has identified possible differences in the extent of mate selection for autistic traits across families of different ethnicity, this study examined variation in autism related traits in contemporaneous, epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white populations. The purpose was to determine whether discrepancies by ethnicity could contribute to differential increases in prevalence in the current generation of young children. METHODS: Birth records were used to identify all twin pairs born between 2011 and 2013 in California and Missouri. Families were selected at random from pools of English-speaking Hispanic families in California and Non-Hispanic White families in Missouri. Autistic trait data of parents was obtained using the Adult Report Form of the Social Responsiveness Scale (SRS-2). RESULTS: We did not identify a statistically significant difference in the degree of mate selection for autism related traits between Hispanic and non-Hispanic white spousal pairs. However, the degree of spousal correlation observed in this recent cohort was pronounced (on the order of ICC 0.45) and exceeded that typically reported in prior research (on the order of 0.30), surpassing also widely reported estimates for sibling correlation (also on the order of 0.30). LIMITATIONS: The sample did not allow for a direct appraisal of change in the magnitude of spousal correlation over time and the ascertainments of trait burden were derived from spouse report. CONCLUSION: Across two epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white families across two U.S. states (respectively, California and Missouri), the extent of autism-related trait co-variation for parents of the current generation of young children is substantial and exceeds correlations typically observed for siblings. Given the heritability of these traits and their relation to autism risk, societal trends in the degree of mate selection for these traits should be considered as possible contributors to subtle increases in the incidence of autism over time and across generations.

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5. Hsu TT, Huang TN, Wang CY, Hsueh YP. Deep brain stimulation of the Tbr1-deficient mouse model of autism spectrum disorder at the basolateral amygdala alters amygdalar connectivity, whole-brain synchronization, and social behaviors. PLoS Biol;2024 (Jul 16);22(7):e3002646.

Autism spectrum disorders (ASDs) are considered neural dysconnectivity syndromes. To better understand ASD and uncover potential treatments, it is imperative to know and dissect the connectivity deficits under conditions of autism. Here, we apply a whole-brain immunostaining and quantification platform to demonstrate impaired structural and functional connectivity and aberrant whole-brain synchronization in a Tbr1+/-autism mouse model. We express a channelrhodopsin variant oChIEF fused with Citrine at the basolateral amygdala (BLA) to outline the axonal projections of BLA neurons. By activating the BLA under blue light theta-burst stimulation (TBS), we then evaluate the effect of BLA activation on C-FOS expression at a whole brain level to represent neural activity. We show that Tbr1 haploinsufficiency almost completely disrupts contralateral BLA axonal projections and results in mistargeting in both ipsilateral and contralateral hemispheres, thereby globally altering BLA functional connectivity. Based on correlated C-FOS expression among brain regions, we further show that Tbr1 deficiency severely disrupts whole-brain synchronization in the absence of salient stimulation. Tbr1+/-and wild-type (WT) mice exhibit opposing responses to TBS-induced amygdalar activation, reducing synchronization in WT mice but enhancing it in Tbr1+/-mice. Whole-brain modular organization and intermodule connectivity are also affected by Tbr1 deficiency and amygdalar activation. Following BLA activation by TBS, the synchronizations of the whole brain and the default mode network, a specific subnetwork highly relevant to ASD, are enhanced in Tbr1+/-mice, implying a potential ameliorating effect of amygdalar stimulation on brain function. Indeed, TBS-mediated BLA activation increases nose-to-nose social interactions of Tbr1+/-mice, strengthening evidence for the role of amygdalar connectivity in social behaviors. Our high-resolution analytical platform reveals the inter- and intrahemispheric connectopathies arising from ASD. Our study emphasizes the defective synchronization at a whole-brain scale caused by Tbr1 deficiency and implies a potential beneficial effect of deep brain stimulation at the amygdala for TBR1-linked autism.

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6. Kurumada C, Rivera R, Allen P, Bennetto L. Perception and adaptation of receptive prosody in autistic adolescents. Sci Rep;2024 (Jul 16);14(1):16409.

A fundamental aspect of language processing is inferring others’ minds from subtle variations in speech. The same word or sentence can often convey different meanings depending on its tempo, timing, and intonation-features often referred to as prosody. Although autistic children and adults are known to experience difficulty in making such inferences, the science remains unclear as to why. We hypothesize that detail-oriented perception in autism may interfere with the inference process if it lacks the adaptivity required to cope with the variability ubiquitous in human speech. Using a novel prosodic continuum that shifts the sentence meaning gradiently from a statement (e.g., « It’s raining ») to a question (e.g., « It’s raining? »), we have investigated the perception and adaptation of receptive prosody in autistic adolescents and two groups of non-autistic controls. Autistic adolescents showed attenuated adaptivity in categorizing prosody, whereas they were equivalent to controls in terms of discrimination accuracy. Combined with recent findings in segmental (e.g., phoneme) recognition, the current results provide the basis for an emerging research framework for attenuated flexibility and reduced influence of contextual feedback as a possible source of deficits that hinder linguistic and social communication in autism.

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7. Li YX, Tan ZN, Li XH, Ma B, Adu Nti F, Lv XQ, Tian ZJ, Yan R, Man HY, Ma XM. Correction: Increased gene dosage of RFWD2 causes autistic-like behaviors and aberrant synaptic formation and function in mice. Mol Psychiatry;2024 (Jul 16)

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8. Lyvers M, Luarca A, Priestly G, Thorberg FA. Adult symptoms of ASD in relation to excessive internet use: The roles of ADHD symptoms and negative mood. Int J Psychol;2024 (Jul 15)

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) have been reportedly associated with excessive internet use, also known as internet addiction. As ADHD is the most common comorbidity in ASD, the present study examined the possibility that ADHD symptoms, and/or trait and mood factors linked to ASD, ADHD and internet addiction, could account for the association of ASD with internet addiction symptoms. A nonclinical young adult sample of 248 internet using men and women completed self-report measures of ASD and ADHD symptoms, alexithymia, impulsivity, negative moods and internet addiction symptoms. Scores on the ASD and ADHD symptom measures were normally distributed, consistent with the notion that the corresponding disorders represent extreme, impairing ends of population distributions of their symptoms. Hierarchical regression followed by path analysis indicated that the relationship between ASD and internet addiction symptoms was fully mediated by ADHD symptoms and negative moods. Further, the relationship between ADHD and internet addiction symptoms was partially mediated by impulsivity and negative moods. Present findings point to the mediating roles of ADHD symptoms and negative moods in the association of ASD with internet addiction symptoms.

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9. Massaguer-Bardaji B, Grau-Touriño A, Gómez-Hinojosa T. [Differences in self-harm among adolescents and young adults with autism spectrum disorder: a gender-based approach]. Rev Neurol;2024 (Jul 16);79(2):35-40.

INTRODUCTION: Self-harm in children and young people with autism spectrum disorder (ASD) poses risks to their physical well-being, negatively impacts their quality of life and that of their families, and presents challenges to their integration into school and social environments. This study aimed to investigate possible differences in terms of gender between adolescents and young adults with autism admitted to the neurodevelopmental unit of ITA Argentona due to non-suicidal self-harming behaviour. PATIENTS AND METHODS: A sample of 50 patients with ASD, whose ages ranged from 14 to 27 years, who were treated in the ITA Argentona neurodevelopmental unit. The methodology adopted consisted of a non-causal correlational cross-sectional study, for which the Autism Diagnostic Observation Schedule, second edition, and the Autism Diagnostic Interview-Revised were administered, as well as the Inventory of Statements About Self-injury. RESULTS: The results obtained revealed significant and positive correlations between sex and certain types of self-harm (burning, pulling hair and carving) and the motivations or functions that the participants report for engaging in non-suicidal self-harm. CONCLUSIONS: Although the study concluded that there is no substantially greater likelihood of one sex in particular engaging non-suicidal self-harm, significant differences were identified in terms of the specific types of self-harm, and the motivations or functions associated with these non-suicidal self-harming behaviours.

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10. Ozonoff S, Young GS, Bradshaw J, Charman T, Chawarska K, Iverson JM, Klaiman C, Landa RJ, McDonald N, Messinger D, Schmidt RJ, Wilkinson CL, Zwaigenbaum L. Familial Recurrence of Autism: Updates From the Baby Siblings Research Consortium. Pediatrics;2024 (Jul 16)

OBJECTIVES: Autism spectrum disorder (ASD) is estimated to be ∼10 times higher in children with versus without an autistic sibling in population-based studies. Prospective studies of infant siblings have revealed even higher familial recurrence rates. In the current prospective longitudinal study, we provide updated estimates of familial ASD recurrence using a multinational database of infants with older autistic siblings. METHODS: Data were collated across 18 sites of the Baby Siblings Research Consortium, an international network studying the earliest manifestations of ASD. A total of 1605 infants with an older autistic sibling were followed from early in life to 3 years, when they were classified as ASD or non-ASD. Hierarchical generalized linear modeling, with site as a random effect, was used to examine predictors of recurrence in families and calculate likelihood ratios. RESULTS: A total of 20.2% of siblings developed ASD, which is not significantly higher than the previously reported rate of 18.7%. Male infant sex and >1 older affected sibling were significant predictors of familial recurrence. Proband sex also influenced recurrence rates, with siblings of female probands significantly more likely to develop ASD than siblings of male probands. Race and maternal education were also associated with recurrence in families. CONCLUSIONS: The familial recurrence rate of ASD, as measured in infant sibling studies, has not changed appreciably since previous estimates were made in 2011. Younger siblings of autistic children, particularly those who are male, have an affected female sibling, multiple affected siblings, or are impacted by social inequities, should be closely monitored and promptly referred for diagnostic evaluation.

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11. Öztürk D, Aydoğan S, Kök İ, Akın Bülbül I, Özdemir S, Özdemir S, Akay D. Linguistic summarization of visual attention and developmental functioning of young children with autism spectrum disorder. Health Inf Sci Syst;2024 (Dec);12(1):39.

Diagnosing autism spectrum disorder (ASD) in children poses significant challenges due to its complex nature and impact on social communication development. While numerous data analytics techniques have been proposed for ASD evaluation, the process remains time-consuming and lacks clarity. Eye tracking (ET) data has emerged as a valuable resource for ASD risk assessment, yet existing literature predominantly focuses on predictive methods rather than descriptive techniques that offer human-friendly insights. Interpretation of ET data and Bayley scales, a widely used assessment tool, is challenging for ASD assessment of children. It should be understood clearly to perform better analytic tasks on ASD screening. Therefore, this study addresses this gap by employing linguistic summarization techniques to generate easily understandable summaries from raw ET data and Bayley scales. By integrating ET data and Bayley scores, the study aims to improve the identification of children with ASD from typically developing children (TD). Notably, this research represents one of the pioneering efforts to linguistically summarize ET data alongside Bayley scales, presenting comparative results between children with ASD and TD. Through linguistic summarization, this study facilitates the creation of simple, natural language statements, offering a first and unique approach to enhance ASD screening and contribute to our understanding of neurodevelopmental disorders.

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12. Percy AK, Neul JL, Benke TA, Berry-Kravis EM, Glaze DG, Marsh ED, Barrett AM, An D, Bishop KM, Youakim JM. Trofinetide for the treatment of Rett syndrome: Long-term safety and efficacy results of the 32-month, open-label LILAC-2 study. Med;2024 (Jul 16)

BACKGROUND: Trofinetide was approved for the treatment of Rett syndrome (RTT) in patients aged ≥2 years based on the results of the 12-week, randomized, phase 3 LAVENDER study. In LILAC, a 40-week, open-label extension study of LAVENDER, trofinetide continued to improve the symptoms of RTT, with a similar safety profile as LAVENDER. Here, we report long-term safety and efficacy results of LILAC-2, a 32-month, open-label extension study. METHODS: Females aged 5-22 years who completed LILAC were eligible to enter LILAC-2. Safety and tolerability were assessed with the incidence of adverse events (AEs). Efficacy was assessed with Rett Syndrome Behaviour Questionnaire (RSBQ) and Clinical Global Impression-Improvement (CGI-I) scores. Caregiver interviews explored the patient’s experience with RTT and the efficacy of trofinetide during study participation. FINDINGS: In total, 77 participants were enrolled in LILAC-2. The most common AEs were diarrhea (53.2%), COVID-19 (27.3%), and vomiting (19.5%). The mean (standard error [SE]) change in RSBQ score from LAVENDER baseline to week 104 of LILAC-2 was -11.8 (2.45). The mean (SE) CGI-I score from LILAC baseline to week 12 of LILAC-2 was 3.1 (0.10). Most caregivers (96%; n = 24/25) were satisfied or very satisfied with the benefits of trofinetide. CONCLUSIONS: Long-term treatment with trofinetide continued to improve RTT symptoms, without new safety concerns. Caregivers reported satisfaction with trofinetide related to improvements that were meaningful for their child and themselves. FUNDING: The study was supported by Acadia Pharmaceuticals (San Diego, CA, USA). This study was registered at ClinicalTrials.gov: NCT04776746.

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13. Peterson T, Dodson J, Sherwin R, Strale F, Jr. Comparative Analysis of Gender-Based Differences in Behavioral Mastery, Goals, and Characteristics in Autistic Individuals: An Applied Behavior Analysis Study. Cureus;2024 (Jun);16(6):e62427.

Introduction It is widely recognized that the prevalence and diagnosis of autism spectrum disorder (ASD) are more common in males than in females. Despite this, there is a significant gap in the body of autism research that investigates gender differences for treatment effects of applied behavior analysis (ABA) across a variety of measured variables. This research aims to comprehensively evaluate gender distinctions concerning target behavioral objectives, goals, and deficit variables. Materials and methods This study analyzed retrospective data from 100 participants, including 89 juveniles and four adults, with seven cases lacking age documentation, who underwent a three-month ABA program from March 19 to June 11, 2023. The ABA program included various methodologies such as functional analysis, discrete trial training, mass trials, and naturalistic training. Data on outcome measures, including target behavioral proficiency, age, average trials to proficiency, average teaching days to proficiency, open behavioral objectives, and target trends, were collected using the « Catalyst » software (Catalyst Software Corporation, New York, NY). Participant demographics were summarized using statistical analyses for categorical (gender and race/ethnicity) and continuous variables (percentage of mastered behavioral objectives, age, average trials, average teaching days, open objectives, percentage of failed objectives during maintenance, percentage of objectives with upward, downward, and flat trends). These statistics included mean, standard deviation, median, and range and were analyzed inferentially using nine separate two-sample independent t-tests and corresponding effect sizes using Cohen’s d. Results There were no statistically significant disparities based on gender (p > 0.05) across all nine variables examined: Percentage of Targets Mastered, Age, Average Trials to Mastery, Average Teaching Days to Mastery, Open Targets, Percentage of Targets Failed in Maintenance, Percentage of Targets Trending Up, Percentage of Targets Trending Down, and Percentage of Targets Trending Flat, and wide confidence intervals were detected. Conclusions Non-significant gender differences in response to ABA treatments regarding these nine behavioral goals, mastery, and deficit variables may be relevant. They suggest that ABA treatments could be equally beneficial for both male and female autistic individuals. These results should be interpreted cautiously. The general pattern observed, characterized by broad confidence intervals, carries a degree of statistical uncertainty, which may suggest substantial gender differences. These results might question the prevailing beliefs about the variation in treatment response based on gender. This could profoundly impact clinical practices, implying that healthcare professionals should not favor one gender over another when suggesting ABA therapies. Instead, the treatment advice should be tailored to each child’s unique requirements and traits, regardless of gender. The investigators expect these results to encourage additional research in this field. Comprehending the elements that affect treatment response is vital for improving treatment results and customizing care.

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14. Tost A, Bachiller A, Medina-Rivera I, Romero S, Serna LY, Rojas-Martínez M, García-Cazorla Á, Mañanas M. Repetitive active and passive cognitive stimulations induce EEG changes in patients with Rett syndrome. Pediatr Res;2024 (Jul 16)

BACKGROUND: Despite being considered a rare disease, Rett syndrome is a leading cause of profound cognitive impairment in females. This study explores game-based cognitive stimulation to enhance attention during learning tasks, offering an alternative treatment perspective. METHODS: Fifteen diagnosed Rett syndrome girls participated in four 24-minute sessions, including a 5-minute initial resting state recording. Primary indicators for analysis included relative power and spectral entropy. RESULTS: Significant findings indicated variations among conditions (resting state, active task, passive task) in response to stimulation. Notably, over four days, evolution occurred, characterized by decreasing delta power and increasing theta and beta power. Topographic maps confirmed these shifts, highlighting affected brain areas. Linear regression emphasized the most significant impact on the first day, with subsequent shifts towards higher frequencies, particularly during the resting state. By the fourth day, resting-state patterns resembled those during cognitive activities. CONCLUSION: Findings suggest cognitive stimulation induces substantial EEG spectral changes, potentially linked to cognitive enhancements in Rett syndrome. The shift towards higher frequency bands and increased spectral entropy align with enhanced brain activation during cognitive sessions, underscoring the potential of cognitive stimulation therapies and calling for further research to optimize abilities in individuals with Rett syndrome. IMPACT: Game-based cognitive stimulation induces substantial EEG changes in individuals with Rett syndrome, enhancing cognitive functions, notably attention during learning. This study conducts a distinctive examination, assessing the habituation paradigm through the combination of game-based cognitive stimulation and learning, providing valuable insights into enhancing attention in Rett syndrome. Impacting understanding of cognitive processes in Rett syndrome, this research reveals significant EEG variations during tasks, emphasizing the potential of cognitive stimulation for attention enhancement and the need for further research in tailored interventions.

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15. Verpeut JL. Restoring cerebellar-dependent learning. Elife;2024 (Jul 16);13

Behavioral and pharmaceutical interventions reverse defects associated with increased cerebellar long-term depression in a mouse model of Fragile X syndrome.

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16. Yin H, Zhang J, Chen Y, Guo J, Li Q, Dinnyes A, Sun Q, Liu X, He G, Zhu B, Liu Y, Xu P, Xu W, Xie J. Placenta-specific CYP11A1 overexpression lead to autism-like symptom in offspring with altered steroid hormone biosynthesis in the placenta-brain axis and rescued by vitamin D intervention. Brain Behav Immun;2024 (Jul 16);121:13-25.

Alterations in steroid hormone regulation have been implicated in the etiology and progression of autism spectrum disorders (ASD), with the enzyme cytochrome P450 family 11 subfamily A member 1 (CYP11A1)-a key catalyst in cholesterol side-chain cleavage, prominently expressed in the adrenal glands, ovaries, testes, and placenta-standing at the forefront of these investigations. The potential link between aberrations in placental Cyp11a1 expression and the resultant neurodevelopmental disorders, along with the mechanisms underpinning such associations, remains inadequately delineated. In this study, we employed a placental trophoblast-specific Cyp11a1 Hipp11 (H11) knock-in murine model to dissect the phenotypic manifestations within the placenta and progeny, thereby elucidating the underlying mechanistic pathways. Behavioral analyses revealed a diminution in social interaction capabilities alongside an augmented anxiety phenotype, as evidenced by open field and elevated plus maze assessments; both phenotypes were ameliorated after vitamin D3 supplementation. Electrophysiological assays underscored the augmented inhibition of paired-pulse facilitation, indicating impaired neuroplasticity in Cyp11a1 H11-modified mice. An elevation in progesterone concentrations was noted, alongside a significant upregulation of Th1-related cytokines (IL-6 and TNFα) across the plasma, placental, and frontal cortex-a pathological state mitigable through vitamin D3 intervention. Western blotting revealed a vitamin D-mediated rectification of vitamin D receptor and PGC-1α expression dysregulations. Immunofluorescence assays revealed microglial activation in the knock-in model, which was reversible upon vitamin D3 treatment. In conclusion, Cyp11a1 overexpression in the placenta recapitulated an autism-like phenotype in murine models, and vitamin D3 administration effectively ameliorated the resultant neurobehavioral and neuroinflammatory derangements. This study substantiates the application of Cyp11a1 as a biomarker in prenatal diagnostics and posits that prenatal vitamin D3 supplementation is a viable prophylactic measure against perturbations in steroid hormone metabolism associated with ASD pathogenesis.

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17. Yu WH, Chu CH, Chen LW, Lin YC, Koh CL, Huang CC. The developmental phenotype of motor delay in extremely preterm infants following early-life respiratory adversity is influenced by brain dysmaturation in the parietal lobe. J Neurodev Disord;2024 (Jul 15);16(1):38.

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 cm(3), 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.

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