Prenatal Parental Exposure to Metals and Birth Defects: A Prospective Birth Cohort Study.

While maternal exposure to high metal levels during pregnancy is an established risk factor for birth defects, the role of paternal exposure remains largely unknown. We aimed to assess the associations of prenatal paternal and maternal metal exposure and parental coexposure with birth defects in singletons. This study conducted within the Jiangsu Birth Cohort recruited couples in early pregnancy. We measured their urinary concentrations for 25 metals. A total of 1675 parent-offspring trios were included. The prevalence of any birth defects among infants by one year of age was 7.82%. Paternal-specific gravity-corrected urinary concentrations of titanium, vanadium, chromium, manganese, cobalt, nickel, copper, and selenium and maternal vanadium, chromium, nickel, copper, selenium, and antimony were associated with a 21-91% increased risk of birth defects after adjusting for covariates. These effects persisted after mutual adjustment for the spouse's exposure. Notably, when assessing the parental mixture effect by Bayesian kernel machine regression, paternal and maternal chromium exposure ranked the highest in relative importance. Parental coexposure to metal mixture showed a pronounced joint effect on the risk of overall birth defects, as well as for some specific subtypes. Our findings suggested a couple-based prevention strategy for metal exposure to reduce birth defects in offspring.

Association between neural prosody discrimination and language abilities in toddlers: a functional near-infrared spectroscopy study.

BACKGROUND: Language delay affects near- and long-term social communication and learning in toddlers, and, an increasing number of experts pay attention to it. The development of prosody discrimination is one of the earliest stages of language development in which key skills for later stages are mastered. Therefore, analyzing the relationship between brain discrimination of speech prosody and language abilities may provide an objective basis for the diagnosis and intervention of language delay. METHODS: In this study, all cases(n = 241) were enrolled from a tertiary women's hospital, from 2021 to 2022. We used functional near-infrared spectroscopy (fNIRS) to assess children's neural prosody discrimination abilities, and a Chinese communicative development inventory (CCDI) were used to evaluate their language abilities. RESULTS: Ninety-eight full-term and 108 preterm toddlers were included in the final analysis in phase I and II studies, respectively. The total CCDI screening abnormality rate was 9.2% for full-term and 34.3% for preterm toddlers. Full-term toddlers showed prosody discrimination ability in all channels except channel 5, while preterm toddlers showed prosody discrimination ability in channel 6 only. Multifactorial logistic regression analyses showed that prosody discrimination of the right angular gyrus (channel 3) had a statistically significant effect on language delay (odd ratio = 0.301, P < 0.05) in full-term toddlers. Random forest (RF) regression model presented that prosody discrimination reflected by channels and brain regions based on fNIRS data was an important parameter for predicting language delay in preterm toddlers, among which the prosody discrimination reflected by the right angular gyrus (channel 4) was the most important parameter. The area under the model Receiver operating characteristic (ROC) curve was 0.687. CONCLUSIONS: Neural prosody discrimination ability is positively associated with language development, assessment of brain prosody discrimination abilities through fNIRS could be used as an objective indicator for early identification of children with language delay in the future clinical application.

Characteristics of Speech Auditory Brainstem Response in Preschool Children With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: This study aimed to investigate the characteristics of auditory processing (AP) in preschool children with attention-deficit/hyperactivity disorder (ADHD) using the speech auditory brainstem response (speech-ABR), which provides insights into the AP of speech signals in the central auditory nervous system (CANS). METHOD: A total of 84 preschool children diagnosed with ADHD, aged 4-6 years, were matched with 84 typically developing (TD) children based on gender and age. All children underwent speech-ABR testing, cognitive assessment using the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition or the Wechsler Intelligence Scale for Children-Fourth Edition, and a continuous performance test. RESULTS: Children with ADHD exhibited significantly longer latencies of speech-ABR waveforms V, A, and D compared to TD children. Multiple linear regression analysis showed that the latencies of speech-ABR waves V, A, and D were affected by the presence of ADHD, but not by the full-scale intelligence quotient. CONCLUSIONS: This study revealed that preschool children with ADHD exhibited abnormal AP of speech signals in their CANS. The findings suggest that speech-ABR can be utilized as a reliable measure to evaluate AP ability in this population, as it remains unaffected by cognitive or attentional factors. The transient response (V, A) of speech-ABR was found to be a significant predictor of ADHD in a clinical setting. Early assessment of AP abnormalities via speech-ABR is recommended in preschool-age children to develop targeted interventions for ADHD. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26376502.

Reduced inhibition control ability in children with ADHD due to coexisting learning disorders: an fNIRS study.

Introduction: Inhibition control, as the core component of executive function, might play a crucial role in the understanding of attention deficit/hyperactivity disorder (ADHD) and specific learning disorders (SLD). Inhibition control deficits have been observed in children with ADHD or SLD. This study sought to test in a multi-modal fashion (i.e., behavior and plus brain imaging) whether inhibition control abilities would be further deteriorated in the ADHD children due to the comorbidity of SLD. Method: A total number of 90 children (aged 6-12 years) were recruited, including 30 ADHD, 30 ADHD+SLD (children with the comorbidity of ADHD and SLD), and 30 typically developing (TD) children. For each participant, a 44-channel functional near infrared spectroscopy (fNIRS) equipment was first adopted to capture behavioral and cortical hemodynamic responses during a two-choice Oddball task (a relatively new inhibition control paradigm). Then, 50 metrics were extracted, including 6 behavioral metrics (i.e., OddballACC, baselineACC, totalACC, OddballRT, baselineRT, and totalRT) and 44 beta values in 44 channels based on general linear model. Finally, differences in those 50 metrics among the TD, ADHD, and ADHD+SLD children were analyzed. Results: Findings showed that: (1) OddballACC (i.e., the response accuracy in deviant stimuli) is the most sensitive metric in identifying the differences between the ADHD and ADHD+SLD children; and (2) The ADHD+SLD children exhibited decreased behavioral response accuracy and brain activation level in some channels (e.g., channel CH35) than both the ADHD and TD children. Discussion: Findings seem to support that inhibition control abilities would be further decreased in the ADHD children due to the comorbidity of SLD.

The dairy-derived peptide Miltin exerts anti-obesity effects by increasing adipocyte thermogenesis.

Growing research has highlighted that the consumption of dairy products improves the metabolic health in obese individuals by functioning as regulatory modulators. However, the molecular basis of this effect remains largely unknown. Herein, we report a dairy-derived peptide, which we named Miltin, that activates the thermogenesis of brown adipocytes and increases white adipocyte browning. Previously, Miltin was merely identified for its antioxidant capacity, although it is commonly present in different dairy products. In this study, we revealed the effect of Miltin in modulating adipose thermogenesis and further explored its potential in treating obesity through in vivo and in vitro strategies. The administration of Miltin in mice fed with a high-fat diet resulted in enhanced thermogenesis, improved glucose homeostasis, and reduced body mass and lipid accumulation, indicating the anti-obesity effect of Miltin. Genomic analysis revealed that Miltin modulates thermogenesis by inducing the activation of the MAPK signaling pathway by preferentially interacting with GADD45γ to promote its stability. Together, our findings indicate that Miltin's role in initiating the thermogenesis of adipocytes makes it a potential anti-obesity therapy for future development.

[Association between auditory processing and problem behaviors in preschool children: the mediating role of executive function]. / å¬å¤„ç†ä¸Žå­¦é¾„å‰å„¿ç«¥é—®é¢˜è¡Œä¸ºçš„å ³ç³»ï¼šæ‰§è¡ŒåŠŸèƒ½çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To investigate the association between auditory processing and problem behaviors in preschool children, as well as the mediating role of executive function. METHODS: A total of 2 342 preschool children were selected from 7 kindergartens in Nanjing, China from June to August 2021. They were evaluated using Preschool Auditory Processing Assessment Scale, Conners Parent Symptom Questionnaire, and Behavior Rating Inventory of Executive Functioning-Preschool version. Children with different demographic features were compared in the scores and the abnormality rates of auditory processing, problem behaviors, and executive function. The influencing factors of the total scores of auditory processing, problem behaviors, and executive function were evaluated using multiple linear regression analysis. Whether executive function was a mediating factor between auditory processing and executive function was examined. RESULTS: Sex and grade were the main influencing factors for the total score of auditory processing (P<0.05), and sex, grade, parental education level, and family economic status were the main influencing factors for the total scores of problem behaviors and executive function (P<0.05). The auditory processing score (rs=0.458, P<0.05) and problem behavior score (rs=0.185, P<0.05) were significantly positively correlated with the executive function score, and the auditory processing score was significantly positively correlated with the problem behavior score (rs=0.423, P<0.05). Executive function played a partial mediating role between auditory processing and problem behaviors, and the mediating effect accounted for 33.44% of the total effect. CONCLUSIONS: Auditory processing can directly affect the problem behaviors of preschool children and indirectly affect problem behaviors through executive function.

Newborn genetic screening for Fabry disease: Insights from a retrospective analysis in Nanjing, China.

Fabry disease (FD), an X-linked disorder resulting from dysfunction of α-galactosidase A, can result in significant complications. Early intervention yields better outcomes, but misdiagnosis or delayed diagnosis is common, impacting prognosis. Thus, early detection is crucial in the clinical diagnosis and treatment of FD. While newborn screening for FD has been implemented in certain regions, challenges persist in enzyme activity detection techniques, particularly for female and late-onset patients. Further exploration of improved screening strategies is warranted. This study retrospectively analyzed genetic screening results for pathogenic GLA variants in 17,171 newborns. The results indicated an estimated incidence of FD in the Nanjing region of China of approximately 1 in 1321. The most prevalent pathogenic variant among potential FD patients was c.640-801G > A (46.15 %). Furthermore, the residual enzyme activity of the pathogenic variant c.911G > C was marginally higher than that of other variants, and suggesting that genetic screening may be more effective in identifying potential female and late-onset patients compared to enzyme activity testing. This research offers initial insights into the effectiveness of GLA genetic screening and serves as a reference for early diagnosis, treatment, and genetic counseling in FD.

Vitamin A ameliorates valproic acid-induced autism-like symptoms in developing zebrafish larvae by attenuating oxidative stress and apoptosis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive/stereotyped behaviors. Prenatal exposure to valproic acid (VPA) has been reported to induce ASD-like symptoms in human and rodents. However, the etiology and pathogenesis of ASD have not been well elucidated. This study aimed to explore the mechanisms underlying VPA-induced ASD-like behaviors using zebrafish model and investigated whether vitamin A could prevent VPA-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 25 and 50 µM VPA from 4 to 96 h post fertilization (hpf) and the neurotoxicity was assessed. Our results showed that VPA affected the normal development of zebrafish larvae and induced ASD-like behaviors, including reduced locomotor activity, decreased distance near conspecifics, impaired social interaction and repetitive swimming behaviors. Exposure to VPA decreased the GFP signal in transgenic HuC:egfp zebrafish according to the negative effect of VPA on the expression of neurodevelopmental genes. In addition, VPA enhanced oxidative stress by promoting the production of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) and inhibiting the activity of superoxide dismutase, then triggered apoptosis by upregulation of apoptotic genes. These adverse outcomes were mitigated by vitamin A, suggesting that vitamin A rescued VPA-induced ASD-like symptoms by inhibiting oxidative stress and apoptosis. Overall, this study identified vitamin A as a promising strategy for future therapeutic regulator of VPA-induced ASD-like behaviors.

Association of Breastfeeding and Neonatal Jaundice With Infant Neurodevelopment.

INTRODUCTION: Exclusive breastfeeding is advantageous for infant neurodevelopment. Nevertheless, insufficient human milk supply in exclusively breastfed infants may elevate the risk of neonatal jaundice, which can potentially result in neurological harm. Whether mothers should adhere to exclusive breastfeeding in infants with neonatal jaundice remains unclear. METHODS: Data comes from the Jiangsu Birth Cohort (JBC), a prospective and longitudinal birth cohort study in China. A total of 2,577 infants born from November 2017 to March 2021 were included in the analysis. Multivariate linear regression models were used to analyze the associations between breastfeeding status, neonatal jaundice, and their interaction with infant neurodevelopment. Analysis was performed in 2022. RESULTS: Compared with "exclusive breastfeeding," fine motor scores of infants were lower for "mixed feeding" (ßadj, -0.16; 95% CI, -0.29 to -0.03; p=0.016) and "no breastfeeding" (ßadj, -0.41; 95% CI, -0.79 to -0.03; p=0.034). Compared with "no neonatal jaundice," infants with "severe neonatal jaundice" had lower scores for cognition (ßadj, -0.44; 95% CI, -0.66 to -0.23; p<0.001) and fine motor (ßadj, -0.19; 95% CI, -0.35 to -0.03; p=0.024). In infants with severe neonatal jaundice, the termination of exclusive breastfeeding before 6 months was associated with worse cognition (ßadj, -0.28; 95% CI, -0.57 to 0.01), while this association was not observed in those without neonatal jaundice (ßadj, 0.09; 95% CI, -0.26 to 0.43). CONCLUSIONS: Exclusive breastfeeding for the first 6 months is beneficial to the neurodevelopment of infants, especially in those with severe neonatal jaundice.

Improving Accuracy of ADHD Diagnosis with the Combination of Brain Imaging and Behavioral Measures.

Neuropsychological measures may improve Attention-deficit/hyperactivity disorder (ADHD) diagnostic accuracy and enhance treatment response detection. Highquality evaluation indicators are necessary for accurate diagnosis of ADHD. Due to the high complexity of the pathogenesis of ADHD, it may not be possible to accurately diagnose ADHD only by relying on behavioral assessment or brain imaging examination. Therefore, the authors propose a comprehensive index that combines brain imaging behavioral and measures. The results showed that the classification performance of the composite index was better than that of the single behavior or brain image index.Clinical Relevance- The results of this study help to remind practicing clinicians to consider the results of multiple clinical examinations when clinically diagnosing ADHD patients.

Using machine learning to explore the characteristics of eye movement patterns and relationship with cognition ability of Chinese children aged 1-6 years.

Researchers have begun to investigate the relationship between eye movement characteristics of gaze patterns and cognitive abilities, and have attempted to use eye-tracking technology as a new method to evaluate cognitive abilities. Traditional eye movement analysis methods typically separate spatial and temporal information of eye movements, mostly analyze averaged data, and consider individual differences as noise. In addition, current eye movement studies on gaze patterns mostly involve adults, while research on infants and toddlers is limited with small sample sizes and narrow age ranges. It is still unknown whether the conclusions drawn from adult-based research can be applied to children. Consequently, eye movement research on gaze patterns in children is necessary. To address the concerns stated above, this study used the Hidden Markov machine learning method to model gaze patterns of 330 children aged 1-6 years while observing faces freely, and analyzed characteristics of eye movement gaze patterns. Additionally, we analyzed the correlation between gaze patterns of 31 toddlers aged 1-3 years and 37 preschoolers aged 4-6 years, and the different dimensions of cognitive abilities. The findings indicated that children exhibited holistic and analytic gaze patterns while observing different faces freely. More children adopted a holistic gaze pattern, and there were age-specific gaze pattern characteristics and regularities. Gaze patterns of toddlers may be correlated with their adaptive abilities and gaze patterns of preschoolers may be correlated with their visual space abilities. Specifically, toddlers aged 1-3 years showed a moderate negative correlation between the H-A scale and the adaptive dimension, while preschoolers aged 4-6 years showed a low negative correlation between the H-A scale and the visual space dimension. This study may provide new insights into the characteristics of children's eye-movement gaze patterns during face observation, and potentially offer objective evidence for future research aimed at promoting the use of eye-tracking technology in the assessment of toddlers' adaptive abilities and preschoolers' visual space abilities in the field of face perception.

[Relationship between home literacy environment and emotional regulation in children: the mediating effect of the parent-child relationship]. / å®¶åº­é˜ è¯»çŽ¯å¢ƒä¸Žå„¿ç«¥æƒ ç»ªè°ƒèŠ‚èƒ½åŠ›çš„å ³ç³»ï¼šäº²å­å ³ç³»çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To study the impact of the home literacy environment on children's emotional regulation skills and the mediating role of the parent-child relationship between them. METHODS: A stratified cluster sampling approach was employed to select 1 626 preschool children from five kindergartens in Nanjing. Questionnaires were used to collect detailed information on the home literacy environment, children's emotional regulation skills, and the parent-child relationship. A mediation model was established using the Process program in SPSS macro, and the significance of the mediation effect was tested using the Bootstrap method. RESULTS: The findings revealed a positive correlation between the home literacy environment and children's emotional regulation skills (r=0.217, P<0.001), as well as parent-child intimacy (r=0.065, P<0.01). Conversely, a negative correlation was found between the home literacy environment and parent-child conflict (r=-0.129, P<0.001). Additionally, parent-child conflict demonstrated a negative correlation with children's emotional regulation skills (r=-0.443, P<0.001), while parent-child intimacy exhibited a positive correlation (r=0.247, P<0.001). The home literacy environment exerted a significant direct effect on children's emotional regulation skills (ß=0.162, P<0.001), and the mediating effect of the parent-child relationship accounted for 25.54% of the total effect. CONCLUSIONS: The home literacy environment significantly influences children's emotional regulation skills, with the parent-child relationship partially mediating this relationship.

[Application of Preschool Auditory Processing Assessment Scale in children with attention deficit hyperactivity disorder]. / å­¦é¾„å‰å„¿ç«¥å¬å¤„ç†è¯„ä¼°é‡è¡¨åœ¨æ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢å„¿ç«¥ä¸­çš„åº”ç”¨ç ”ç©¶.

OBJECTIVES: To investigate the characteristics of auditory processing (AP) in preschool children with attention deficit hyperactivity disorder (ADHD) using Preschool Auditory Processing Assessment Scale (hereafter referred to as "auditory processing scale"). METHODS: A total of 41 children with ADHD and 41 typically developing (TD) children were assessed using the auditory processing scale, SNAP-IV rating scale, and Conners' Kiddie Continuous Performance Test (K-CPT). The auditory processing scale score was compared between the TD and ADHD groups. The correlations of the score with SNAP-IV and K-CPT scores were assessed. RESULTS: Compared with the TD group, the ADHD group had significantly higher total score of the auditory processing scale and scores of all dimensions except visual attention (P<0.05). In the children with ADHD, the attention deficit dimension score of the SNAP-IV rating scale was positively correlated with the total score of the auditory processing scale (rs30=0.531, P<0.05; rs27=0.627, P<0.05) as well as the scores of its subdimensions, including auditory decoding (rs=0.628, P<0.05), auditory attention (rs=0.492, P<0.05), and communication (rs=0.399, P<0.05). The hyperactivity-impulsivity dimension score of the SNAP-IV rating scale was positively correlated with the hyperactivity-impulsivity dimension score of the auditory processing scale (rs=0.429, P<0.05). In the children with ADHD, the attention deficit dimension score of the K-CPT was positively correlated with the total score (rs30=0.574, P<0.05; rs27=0.485, P<0.05) and the hyperactivity-impulsivity dimension score (rs=0.602, P<0.05) of the auditory processing scale. CONCLUSIONS: Preschool children with ADHD have the risk of AP abnormalities, and the auditory processing scale should be used early for the screening and evaluation of AP abnormalities in children.

NRXN1 depletion in the medial prefrontal cortex induces anxiety-like behaviors and abnormal social phenotypes along with impaired neurite outgrowth in rat.

BACKGROUND: Neurodevelopmental disorders (NDDs) are a group of disorders induced by abnormal brain developmental processes. The prefrontal cortex (PFC) plays an essential role in executive function, and its role in NDDs has been reported. NDDs are associated with high-risk gene mutations and share partially overlapping genetic abnormalities. METHODS: Neurexins (NRXNs) are related to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). NRXN1, an essential susceptibility gene for NDDs, has been reported to be associated with NDDs. However, little is known about its key role in NDDs. RESULTS: NRXN1 downregulation in the medial PFC induced anxiety-like behaviors and abnormal social phenotypes with impaired neurite outgrowth in Sh-NRXN1 in prefrontal neurons. Moreover, tandem mass tag (TMT)-based proteomic analysis of rat brain samples showed that NRXN1 downregulation led to significant proteome alterations, including pathways related to the extracellular matrix, cell membrane, and morphologic change. Furthermore, full-automatic immunoblotting analysis verified the differently expressed proteins related to cell morphology and membrane structure. CONCLUSIONS: Our results confirmed the association of NRXN1 with abnormal behaviors in NDDs and provided richer insights into specific prefrontal knockdown in adolescence, potentially expanding the NRXN1 interactome and contributing to human health.

Nano-TiO2 aggravates bioaccumulation and developmental neurotoxicity of difenoconazole in zebrafish larvae via oxidative stress and apoptosis: Protective role of vitamin C.

Titanium dioxide nanoparticles (n-TiO2) could enhance the bioavailability and toxicity of coexisting organic contaminants in the aquatic environment. This study attempted to investigate the combined effects of n-TiO2 and difenoconazole (DIF) on the neurodevelopment of zebrafish and the underlying mechanisms. In this study, zebrafish embryos were exposed to n-TiO2 (100 µg/L), DIF (0, 0.1 and 0.5 mg/L) and their mixtures from 4 to 96 h post fertilization (hpf) and neurotoxicity was evaluated. Our results indicated that n-TiO2 adsorbed DIF into the brain of zebrafish and significantly enhanced the bioaccumulation of DIF and n-TiO2 in the 0.5 mg/L co-exposure group. 100 µg/L n-TiO2 was not developmentally toxic to the zebrafish larvae, but it exacerbated DIF-induced neurobehavioral alterations in the zebrafish larvae. n-TiO2 also aggravated DIF-induced suppression of central nervous system (CNS) neurogenesis in Tg (HuC:egfp) zebrafish, motor neuron axon length in Tg (hb9:egfp) zebrafish, and downregulation of neurodevelopmental genes (elavl3, ngn1, gap43, gfap and mbp). In addition, DIF elevated oxidative stress by accumulation of reactive oxygen species (ROS) and inhibition of antioxidant enzymes, and triggered apoptosis by upregulation of p53, bax, bcl-2 and caspase-3, which were markedly intensified in the presence of n-TiO2. Moreover, vitamin C (VC) ameliorated n-TiO2/DIF-induced abnormal locomotor behaviors and neurotoxicity by inhibiting oxidative stress and apoptosis, indicating that oxidative stress and apoptosis are involved in n-TiO2/DIF-induced neurotoxicity. Taken together, our data indicated that n-TiO2 enhanced the accumulation of DIF and heightened oxidative stress and apoptosis, thereby inducing neurotoxicity. This study exemplifies the importance of the toxicity assessment of chemical mixtures and novel insights to mitigate their combined toxicity.

Human milk-derived extracellular vesicles alleviate high fat diet-induced non-alcoholic fatty liver disease in mice.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), characterized by excessive hepatic lipid accumulation, imposes serious challenges on public health worldwide. Breastfeeding has been reported to reduce the risk of NAFLD. Extracellular vesicles (EVs) are bilayer membrane vesicles released from various cells into the extracellular space, participating in multiple life processes. Whether EVs from human milk exert metabolic benefits against NAFLD is worth investigating. METHODS AND RESULTS: In this study, the EVs were isolated from human milk collected from healthy mothers and quantified. Functional analyses were performed using the NAFLD mouse model and free fatty acid (FFA)-stimulated mouse primary hepatocytes. The results showed that human milk-derived EVs could effectively alleviate high fat diet-induced hepatic steatosis and insulin resistance in mice with NAFLD via inhibiting lipogenesis and increasing lipolysis. The FFA-induced lipid accumulation was also inhibited in hepatocytes after treatment with human milk-derived EVs. Mechanistically, the human milk derived-EVs cargo (proteins and miRNAs), which linked to lipid metabolism, may be responsible for these beneficial effects. CONCLUSION: The findings of this study highlighted the therapeutic benefits of human milk-derived EVs and provided a new strategy for NAFLD treatment.

Development, Reliability, and Validity of the Preschool Learning Skills Scale: A Tool for Early Identification of Preschoolers at Risk of Learning Disorder in Mainland China.

Background: Early identification of children at risk of learning disorders (LD) may mitigate the adverse effects of delayed intervention by guiding children to receive preventive services at an earlier age. However, there is no assessment tool for the early identification of children at risk of LD in Mainland China. Therefore, this study aimed to create a Chinese version of the Preschool Learning Skills Scale and investigate its validity and reliability. Methods: Firstly, a pilot scale was designed based on literature review and expert review. Secondly, a pre-survey of the pilot scale was conducted. In phase 3, a formal survey was carried out to test the reliability and validity of the scale by involving 2,677 preschool children from 7 kindergartens. Data were collected using a checklist for demographic characteristics, the preschool learning skills scale, the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P), and Conners' Rating Scales. Results: The final scale included 38 items under seven factors. The reliability and validity tests confirmed that the Cronbach's alpha, split-half reliability, and test-retest reliability coefficients of the scale were 0.946, 0.888, and 0.941, respectively. The Spearman correlations of factor-total score ranged from 0.685 to 0.876. The results of criterion-related validity showed a direct and significant association between the preschool learning skills scale with the BRIEF-P (r = 0.641, P < 0.001) and the cognitive problems factor of Conners' Rating Scales (r = 0.564, P < 0.001). The model had a good fit (χ 2 /df = 3.489, RMSEA = 0.047, RMR = 0.024, CFI = 0.912, TLI = 0.900, and IFI = 0.912). Multigroup confirmatory factor analysis supported the structural and measurement invariance on the preschool learning skills scale across gender and grade. Conclusions: The developed preschool learning skills scale has good reliability and validity, indicating that the scale can be used to identify preschool children at risk of LD and can be recommended for use in clinical research and practice.

Association of Maternal Mild Hypothyroidism With Offspring Neurodevelopment in TPOAb-Negative Women: A Prospective Cohort Study.

Objectives: Adequate maternal thyroid hormone availability is crucial for fetal neurodevelopment, but the role of maternal mild hypothyroidism is not clear. We aim to investigate the association of maternal mild hypothyroidism with neurodevelopment in infants at 1 year of age among TPOAb-negative women. Methods: The present study was conducted within the Jiangsu Birth Cohort. A total of 793 mother-infant pairs were eligible for the present study. Maternal thyroid function was assessed by measuring serum thyroid-stimulating hormone, free thyroxine, and thyroid peroxidase antibodies. Neurodevelopment of infants was assessed by using the Bayley Scales of Infant and Toddler Development third edition screening test (Bayley-III screening test). Results: In the multivariate adjusted linear regression analyses, infants of women with subclinical hypothyroidism and isolated hypothyroxinemia were associated with decreased receptive communication scores (ß = -0.68, p = 0.034) and decreased gross motor scores (ß = -0.83, p = 0.008), respectively. Moreover, infants of women with high-normal TSH concentrations (3.0-4.0 mIU/L) and low FT4 concentrations were significantly associated with lower gross motor scores (ß = -1.19, p = 0.032), while no differences were observed in infants when the mothers had a high-normal TSH concentration and normal FT4 levels. Conclusions: Maternal subclinical hypothyroidism is associated with decreased receptive communication scores in infants at 1 year of age. In addition, maternal TSH concentration greater than 4.0 mIU/L and maternal isolated hypothyroxinemia are associated with impaired gross motor ability of infants, especially in infants of women with high-normal TSH concentrations (3.0-4.0 mIU/L).

Development and Evaluation of Orthographic Knowledge Awareness Scale for Children Aged 6-12 Years.

Objective: This study primarily aimed to develop an orthographic knowledge awareness scale in Mandarin for children aged 6-12 years. Related factors affecting orthographic knowledge awareness in children were analyzed, and a basis for individualized intervention was provided to improve reading and writing. Methods: A conceptual framework for orthographic knowledge awareness in children aged 6-12 years was determined through a detailed reading of the literature on Chinese character orthography, combined with qualitative interviews of the target population and consultation with experts. The orthographic knowledge awareness scale initially consisted of three versions: for grades 1-2 (210 items), grades 3-4 (207 items), and grades 5-6 (220 items), accumulating a total of 637 items. The initial scale was then used for the study involving children aged 6-12 years in Maanshan City, Jiangsu Province. Various approaches to screening items were comprehensively used to determine the formal version of the orthographic knowledge awareness scale. The official scale was ultimately used to conduct the third round of surveys among 1,354 children aged 6-12 years in ordinary primary schools located in 5 cities in Jiangsu Province, namely, Changzhou, Lianyungang, Nantong, Xuzhou, and Yangzhou. The reliability, validity, and discriminating power of the formal scale were evaluated. Results: A total of 360 items were included in the formal version of the orthographic knowledge awareness scale. The formal scale was divided into three versions for grades 1-2, 3-4, and 5-6. Each grade version consisted of 120 items. The scale was composed of the stroke awareness test, radical awareness test, and left-right reversal test. The cumulative variance contribution rates of grades 1-2, 3-4, and 5-6 were 82.47, 61.71, and 64.19%, respectively. The Cronbach's α coefficients of the three-grade version of the scale were 0.989, 0.946, and 0.938; the split-half reliability coefficients were 0.925, 0.766, and 0.847; and the test-retest reliability coefficients were 0.847, 0.895, and 0.8928, respectively. Conclusion: The proposed orthographic knowledge awareness scale for children aged 6-12 years exhibits good reliability and validity. The formal scale consisted of two dimensions: identification of left-right reversal at the stroke and radical levels and the left-right reversal at the whole character level. The two dimensions can more comprehensively reflect the ability of children to discriminate orthographic structures.

Associations between antenatal corticosteroid exposure and neurodevelopment in infants.

BACKGROUND: It has been well recognized that antenatal administration of dexamethasone to pregnant women at risk of preterm delivery may markedly accelerate fetal maturation and reduce the risk of adverse perinatal outcomes in their preterm infants, particularly for births before 34 weeks of gestation. Since 2015, antenatal corticosteroid administration has been extended beyond 34 weeks of gestation by clinical guidelines, as it might have beneficial effects on fetal maturation and perinatal outcomes. However, concerns regarding the potential influence of antenatal corticosteroid treatment on offspring neurodevelopment have been raised. OBJECTIVE: This study aimed to investigate whether maternal antenatal corticosteroid administration was associated with neurodevelopment in infants at 1 year of age. STUDY DESIGN: In this prospective and longitudinal birth cohort study, women were followed up throughout gestation, and their infants underwent a Bayley Scales of Infant and Toddler Development, Third Edition, screening test at 1 year of age between December 2018 and September 2020. Finally, 1609 pregnant women and 1759 infants were included in the current study. Using a generalized linear mixed model, we examined the association between antenatal corticosteroid exposure and infant neurodevelopment in cognitive, receptive communication, expressive communication, fine motor, and gross motor functions. RESULTS: Of the 1759 infants eligible for this study, 1453 (82.6%) were singletons. A total of 710 infants were exposed to antenatal corticosteroids, among whom 415 were dexamethasone exposed and 483 were prednisone exposed. Dexamethasone was prescribed most often in late pregnancy, whereas prednisone was often used before 8 weeks of gestation among women who conceived through assisted reproductive technology. Compared with those who had no exposure, antenatal corticosteroid exposure was associated with an increased risk of infants being noncompetent in the cognitive development domain after adjusting for conventional risk factors (adjusted risk ratio, 1.53; 95% confidence interval, 1.08-2.18; P=.017). For medication-specific exposure, those exposed vs not exposed to antenatal dexamethasone were 1.62-fold (95% confidence interval, 1.10-2.38; P=.014) more likely to be noncompetent in the cognitive development domain at 1 year. The association did not vary markedly between preterm and term infants, singletons and twins, or assisted reproductive technology-conceived and spontaneously conceived infants (all P>.05 for heterogeneity). In contrast, a null association was observed for the risk of being noncompetent in any domain of neurodevelopment with antenatal prednisone exposure at early pregnancy. CONCLUSION: Here, antenatal corticosteroid, particularly dexamethasone exposure, was markedly associated with an increased risk of infants being noncompetent in the cognitive development domain at 1 year of age. These findings may provide new information when weighing the benefits and potential risks of maternal antenatal corticosteroid administration.