The role of circadian rhythms and sleep in the aetiology of autism spectrum disorder and attention-deficit/hyperactivity disorder: New evidence from bidirectional two-sample Mendelian randomization analysis.

LAY ABSTRACT: Research shows that people with autism spectrum disorder and attention-deficit/hyperactivity disorder often have sleep issues and problems with the body's natural daily rhythms, known as circadian rhythms. By exploring the genetic variants associated with these rhythms and the conditions, this study reveals that these rhythm changes and sleep patterns are directly linked to autism spectrum disorder and attention-deficit/hyperactivity disorder. It found that the timing of one's most active hours can increase the likelihood of having both autism spectrum disorder and attention-deficit/hyperactivity disorder. Importantly, it also shows that good sleep quality might protect against autism spectrum disorder, while disturbed sleep in people with attention-deficit/hyperactivity disorder seems to be a result rather than the cause of the condition. This understanding can help doctors and researchers develop better treatment approaches that focus on the specific ways sleep and body rhythms affect those with autism spectrum disorder and attention-deficit/hyperactivity disorder, considering their unique associations with circadian rhythms and sleep patterns. Understanding these unique links can lead to more effective, personalized care for those affected by these conditions.

Sex-specific associations of adolescent motherhood with cognitive function, behavioral problems, and autistic-like traits in offspring and the mediating roles of family conflict and altered brain structure.

BACKGROUND: Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. METHODS: This study included 6952 children aged 9-11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers < 20 years at the time of birth, while the unexposed group was composed of children of mothers aged 20-35 at birth. We employed a generalized linear mixed model to investigate the associations of adolescent motherhood with cognitive, behavioral, and autistic-like traits in offspring. We applied an inverse-probability-weighted marginal structural model to examine the potential mediating factors including adverse perinatal outcomes, family conflict, and brain structure alterations. RESULTS: Our results revealed that children of adolescent mothers had significantly lower cognitive scores (ß, - 2.11, 95% CI, - 2.90 to - 1.31), increased externalizing problems in male offspring (mean ratio, 1.28, 95% CI, 1.08 to 1.52), and elevated internalizing problems (mean ratio, 1.14, 95% CI, 0.99 to 1.33) and autistic-like traits (mean ratio, 1.22, 95% CI, 1.01 to 1.47) in female. A stressful family environment mediated ~ 70% of the association with internalizing problems in females, ~ 30% with autistic-like traits in females, and ~ 20% with externalizing problems in males. Despite observable brain morphometric changes related to adolescent motherhood, these did not act as mediating factors in our analysis, after adjusting for family environment. No elevated rate of adverse perinatal outcomes was observed in the offspring of adolescent mothers in this study. CONCLUSIONS: Our results reveal distinct sex-specific neurodevelopmental outcomes impacts of being born to adolescent mothers, with a substantial mediating effect of family environment on behavioral outcomes. These findings highlight the importance of developing sex-tailored interventions and support the hypothesis that family environment significantly impacts the neurodevelopmental consequences of adolescent motherhood.

Assessing the usefulness of the Little Developmental Coordination Disorder Questionnaire-Chinese in Chinese preschoolers: a sex-and age-specific analysis.

Aim: This study evaluated the sex-and age-specific usefulness of the Little Developmental Coordination Disorder Questionnaire-Chinese (LDCDQ-CH) in Chinese preschoolers. Method: A population-based sample of 51,110 children aged 3-5 years was recruited. Internal reliability, construct validity, concurrent validity with the Ages and Stages Questionnaire-third edition (ASQ-3), and discriminant validity with the Movement Assessment Battery for Children-second edition (MABC-2) were assessed. Age and sex effects on LDCDQ-CH scores were analyzed using ANOVA and t-tests. Results: The LDCDQ-CH exhibited excellent internal consistency and reliability across ages and genders. Confirmatory factor analysis supported the 15-item model's satisfactory fit. Positive and significant correlations were observed between LDCDQ-CH and ASQ-3 scores, indicating robust concurrent validity. Significant associations were found between LDCDQ-CH and MABC-2 scores. Higher scores were observed in older children and girls, indicating age- and sex-related differences in motor functional performance. Conclusion: The LDCDQ-CH is a reliable and valid tool to support early identification of motor coordination difficulty in Chinese preschoolers, and guiding interventions. Findings support its use across ages and genders, highlighting its potential in the Chinese context. Age- and sex-specific norms are needed for enhanced clinical applicability.

Assessing the journey of calcium supplementation: A mendelian randomization study on the causal link between calcium levels and sleep disorders.

BACKGROUND & AIM: Sleep disorder is a growing concern, and calcium supplementation is often recommended as a potential intervention for sleep disorders. However, the causal relationship between calcium levels and the incidence of sleep disorders remains unclear. Mendelian randomization techniques utilizing genetic variants that affect calcium levels, can provide valuable insights into causality. This study aims to examine the association between calcium levels and sleep disorders in a diverse population that includes both adolescents and adults, and investigate the effects of calcium levels on sleep disorders. METHODS: Mendelian randomization analysis was conducted using data from UK Biobank and FinnGen datasets. The inverse-variance weighting (IVW) was selected as the primary method. In addition, traditional mediation analysis was performed on a subset of the NHANES data spanning from 2007 to 2018. RESULTS: Our findings provide evidence supporting a causal relationship between calcium intake and reduced risk of sleep disorders (beta = -0.079, SE = 0.0395, P = 0.0457). While not reaching statistical significance, other MR methods such as weighted median and Mr-Egger exhibited similar directional trends. Analysis of the NHANES cohort revealed a negative association between calcium levels and the prevalence of sleep disorders in male, black, and physically active populations. However, this association was not observed in other demographic groups. CONCLUSION: Our results suggested that there is no significant correlation between calcium levels and sleep disorder in non-exercise populations. This raises concerns about the long-term high-dose calcium supplementation in clinical practice, which requires further investigation.

Advances in Genetics and Epigenetics of Developmental Coordination Disorder in Children.

Developmental coordination disorder (DCD) is a developmental disorder characterized by impaired motor coordination, often co-occurring with attention deficit disorder, autism spectrum disorders, and other psychological and behavioural conditions. The aetiology of DCD is believed to involve brain changes and environmental factors, with genetics also playing a role in its pathogenesis. Recent research has identified several candidate genes and genetic factors associated with motor impairment, including deletions, copy number variations, single nucleotide polymorphisms, and epigenetic modifications. This review provides an overview of the current knowledge in genetic research on DCD, highlighting the importance of continued research into the underlying genetic mechanisms. While evidence suggests a genetic contribution to DCD, the evidence is still in its early stages, and much of the current evidence is based on studies of co-occurring conditions. Further research to better understand the genetic basis of DCD could have important implications for diagnosis, treatment, and our understanding of the condition's aetiology.

Association between screen time and suspected developmental coordination disorder in preschoolers: A national population-based study in China.

Introduction: Excessive screen exposure (ESE) is a growing global public health concern. This study aims to investigate the potential association between ESE and suspected developmental coordination disorder (DCD) in Chinese pre-schoolers, with or without siblings. Method: A retrospective cohort study was conducted, involving 126,433 children from 551 cities in China. The Little Developmental Coordination Disorder Questionnaire (LDCDQ) was employed to evaluate motor impairment in children, while parents provided information on their children's screen time in the past year. A mixed and multi-level logistic regression model was used to analyze the associations of all screen exposure measurements from the past year with LDCDQ scores and the risk of suspected DCD. Results: The prevalence of excessive screen exposure was 67.6% (>1 h per day) and 28.9% (>2 h per day) in Chinese pre-schoolers. One hour's increase in weekday daily screen time, weekend daily screen time, and screen time before sleep in the past year was associated with a decreased total score of the LDCDQ (ß were -0.690, -0.398, and -1.587, p < 0.001) and an increased risk of suspected DCD by 15.3%, 9.1%, and 46.8% when adjusting for the child, family and maternal health characteristics. Excessive screen exposure decreased the total LDCDQ scores by 1.335 (>1 vs. ≤1 h) and 1.162 (>2 vs. ≤2 h) and increased risks of suspected DCD by 44.0% (>1 vs. ≤1 h) and 31.1% (>2 vs. ≤2 h) with statistical significance (each p < 0.05). The stratified analysis showed that the association between screen time and LDCDQ score was stronger in children without siblings than in those with siblings. Conclusion: The risk of suspected DCD was highest for screen time exposure before bed compared with average weekday and weekend exposures. Parents should be advised to prevent their children from using electronic screens unsupervised, especially in one-child families.

Artificial Neural Network Modeling to Predict Neonatal Metabolic Bone Disease in the Prenatal and Postnatal Periods.

Importance: Early recognition of metabolic bone disease (MBD) in infants is necessary but difficult; an appropriate tool to screen infants at risk of developing MBD is needed. Objectives: To develop a predictive model for neonates at risk for MBD in the prenatal and postnatal periods and detect the pivotal exposed factors in each period. Design, Setting, and Participants: A diagnostic study was conducted from January 1, 2012, to December 31, 2021, in Shanghai, China. A total of 10 801 pregnant women (singleton pregnancy, followed up until 1 month after parturition) and their infants (n = 10 801) were included. An artificial neural network (ANN) framework was used to build 5 predictive models with different exposures from prenatal to postnatal periods. The receiver operating characteristic curve was used to evaluate the model performance. The importance of each feature was examined and ranked. Results: Of the 10 801 Chinese women who participated in the study (mean [SD] age, 29.7 [3.9] years), 7104 (65.8%) were local residents, 1001 (9.3%) had uterine scarring, and 138 (1.3%) gave birth to an infant with MBD. Among the 5 ANN models, model 1 (significant prenatal and postnatal factors) showed the highest AUC of 0.981 (95% CI, 0.970-0.992), followed by model 5 (postnatal factors; AUC, 0.977; 95% CI, 0.966-0.988), model 4 (all prenatal factors; AUC, 0.850; 95% CI, 0.785-0.915), model 3 (gestational complications or comorbidities and medication use; AUC, 0.808; 95% CI, 0.726-0.891), and model 2 (maternal nutritional conditions; AUC, 0.647; 95% CI, 0.571-0.723). Birth weight, maternal age at pregnancy, and neonatal disorders (anemia, respiratory distress syndrome, and septicemia) were the most important model 1 characteristics for predicting infants at risk of MBD; among these characteristics, extremely low birth weight (importance, 50.5%) was the most powerful factor. The use of magnesium sulfate during pregnancy (model 4: importance, 21.2%) was the most significant predictor of MBD risk in the prenatal period. Conclusions and Relevance: In this diagnostic study, ANN appeared to be a simple and efficient tool for identifying neonates at risk for MBD. Combining prenatal and postnatal factors or using postnatal exposures alone provided the most precise prediction. Extremely low birth weight was the most significant predictive factor, whereas magnesium sulfate use during pregnancy could be an important bellwether for MBD before delivery.

Associations of preterm and early-term birth with suspected developmental coordination disorder: a national retrospective cohort study in children aged 3-10 years.

BACKGROUND: This study analyzed the motor development and suspected developmental coordination disorder of very and moderately preterm (< 34+0 gestational age), late preterm (34+0-36+6 gestational week), and early-term (37+0-38+6 gestational week) children compared to their full-term peers with a national population-based sample in China. METHODS: A total of 1673 children (799 girls, 874 boys) aged 3-10 years old were individually assessed with the Movement Assessment Battery for Children-second edition (MABC-2). The association between gestational age and motor performance of children was analyzed using a multilevel regression model. RESULTS: The global motor performance [ß = - 5.111, 95% confidence interval (CI) = - 9.200 to - 1.022; P = 0.015] and balance (ß = - 5.182, 95% CI = - 5.055 to - 1.158; P = 0.003) for very and moderately preterm children aged 3-6 years old were significantly lower than their full-term peers when adjusting for confounders. Late preterm and early-term children showed no difference. Moreover, very and moderately preterm children aged 3-6 years had a higher risk of suspected developmental coordination disorder (DCD) (≤ 5 percentile of MABC-2 score) when adjusting for potential confounders [odds ratio (OR) = 2.931, 95% CI = 1.067-8.054; P = 0.038]. Late preterm and early-term children showed no difference in motor performance from their full-term peers (each P > 0.05). CONCLUSIONS: Our findings have important implications for understanding motor impairment in children born at different gestational ages. Very and moderately preterm preschoolers have an increased risk of DCD, and long-term follow-up should be provided for early detection and intervention.

Association of developmental coordination disorder with early-life exposure to fine particulate matter in Chinese preschoolers.

Although fine particulate matter (PM2.5) is a neurotoxicant, little is known about whether early-life PM2.5 exposure is associated with an increased risk of developmental coordination disorder (DCD). We conducted a cohort study of 109 731 children aged 3-5 years from 551 county-level cities in China between April 2018 and December 2019. Residential PM2.5 exposure was estimated using a hybrid satellite-based exposure model. Children's motor performance was assessed using the Little DCD Questionnaire (LDCDQ). Linear mixed-effect models and generalized linear mixed models with a binomial distribution were used to examine the associations of PM2.5 exposure with LDCDQ scores and risk of DCD, respectively. Both prenatal and postnatal exposure to a higher level of PM2.5 was significantly associated with reduced total LDCDQ score, and the impacts were evident on subscales of control during movement and general coordination function but not fine motor function. For example, an interquartile range increase in PM2.5 exposure in ages 0-3 was associated with a 0.19 (95% confidence interval [CI]: 0.05, 0.33) decrement in the total score. Additionally, higher PM2.5 exposure was associated with increased risk of DCD, and the adjusted odds ratios were 1.06 (95% CI: 1.01, 1.10) and 1.06 (95% CI: 1.01, 1.13) for each interquartile range increase in PM2.5 exposure during the first trimester and the first 3 years, respectively. Children who were from rural areas, had neonatal intensive care unit admission, or were exclusively breastfed for less than 6 months appeared to be more susceptible to PM2.5 exposure than their counterparts. Our findings provide robust evidence that early-life PM2.5 exposure contributes to an elevated risk of DCD.

Early-Life Exposure to PM2.5 and Sleep Disturbances in Preschoolers from 551 Cities of China.

Rationale: Air pollution has been linked with sleep disturbance in adults, but the association in children remains unclear. Objectives: To examine the associations of prenatal and postnatal exposure to fine particulate matter (particulate matter ⩽2.5 µm in aerodynamic diameter; PM2.5) with sleep quality and sleep disturbances among children in 551 Chinese cities. Methods: A total of 1,15,023 children aged 3-7 years from the Chinese National Cohort of Motor Development were included. Sleep quality was measured using the Children's Sleep Habits Questionnaire (CSHQ). PM2.5 exposure was estimated using a satellite-based model. Generalized additive mixed models with Gaussian and binomial distributions were used to examine the associations of PM2.5 exposure with CSHQ scores and risk of sleep disturbance, respectively, adjusting for demographic characteristics and temporal trends. Measurements and Main Results: Early-life PM2.5 exposure was associated with higher total CSHQ score, and the association was stronger for exposure at age 0-3 years (change of CSHQ score per interquartile range increase of PM2.5 = 0.46; 95% confidence interval [CI], 0.29-0.63) than during pregnancy (0.22; 95% CI, 0.12-0.32). The associations were more evident in sleep-disordered breathing and daytime sleepiness. Postnatal PM2.5 exposure was associated with increased risk of sleep disturbance (adjusted odds ratio for per-interquartile range increase of PM2.5 exposure at age 0-3 years, 1.10; 95% CI, 1.04-1.15), but no associations were found for prenatal exposure. Children who were exclusively breastfed for <6 months and had neonatal ICU admission may be more vulnerable to sleep disturbance related to PM2.5 exposure. Conclusions: PM2.5 exposure can impair sleep quality in preschool children.

Maternal exposure to PM2.5 induces cognitive impairment in offspring via cerebellar neuroinflammation and oxidative stress.

Available evidence suggest that exposure to PM2.5 during pregnancy is associated with reduced cognitive function in offspring. This study aimed to investigate the effects of maternal exposure to PM2.5 on offspring cognitive function and to elucidate the underlying mechanisms. In this work, pregnant C57BL/6 female mice were exposed to concentrated ambient PM2.5 or filtered air from day 0.5 (=vaginal plug) to day 15.5 in the Shanghai Meteorological and Environmental Animal Exposure System, and offspring cerebellar tissues were collected on embryonic day 15.5, as well as postnatal days 0, 10 and 42. The mean PM2.5 concentrations exposed to the pregnant mice were 73.06 ± 4.90 µg/m3 and 11.15 ± 2.71 µg/m3 in the concentrated ambient PM2.5 and filtered air chambers, respectively. Maternal concentrated PM2.5 exposure was negatively correlated with offspring spatial memory significantly as assessed by the Morris water maze. Compared with the filtered air group, PM2.5-exposed offspring mice had reduced cerebellar microglia. Both RNA and protein levels of IL-8 and TNF-α were elevated in the concentrated ambient PM2.5 group. PM2.5 exposure increased the level of 8-OHG in miRNA of microglia and Purkinje cells in 6-week-old offspring. The level of prostaglandin F2α (8-iso-PGF2Aα) in the cerebellum was increased at different growing stages of offspring after gestational exposure of PM2.5. These results suggested that maternal air pollution exposure might cause inflammatory damage and oxidative stress to the cerebellum, contributing to reduced cognitive performance in mice offspring.

Prevalence of Sleep Disorder in Chinese Preschoolers: A National Population-Based Study.

Study Objectives: This study provides data on the prevalence of clinical sleep disorders in Chinese preschoolers aged 3-5 years old and examined their sleep behaviours and problems with a nationally representative sample. Methods: A national population-based cohort study was conducted with 114,311 children aged 3-5 years old from 551 cities in China. Children's daily sleep hours and pediatric sleep disorders defined by the Children's Sleep Habits Questionnaire (CSHQ) were reported by parents. Results: The estimated sleep disorder prevalence was 76.78% (95% CI:76.54%, 77.03%). Rates of specific disorders were as follows: Bedtime resistance (97.00%, 95% CI:96.90%, 97.10%), Daytime sleepiness (77.68%,95% CI:77.43%, 77.92%), Sleep duration (70.24%,95% CI:69.97%, 70.50%), Parasomnia (58.52%,95% CI:58.23%, 58.80%), Sleep anxiety (55.53%,95% CI:55.24%, 55.81%), Sleep onset delay (51.99%,95% CI:51.70%, 52.28%) Night wakings (30.37%,95% CI:30.10%, 30.63%) and Sleep-disordered breathing (21.86%, 95% CI: 21.62%, 22.09%). The prevalence of sleep disorder, daily sleep hours and rates of specific disorder varied across children of different sex and ages. Conclusion: A high prevalence of sleep disorder was found in Chinese preschoolers, and the specific sleep problems of Chinese preschoolers vary from other cultures. A local standard may be required when using the CSHQ to define sleep disorders in children in China. An in-depth investigation into the reasons for the high sleep disorder prevalence should be conducted and supportive intervention should be provided to preschoolers in China.

The sibling effect on neurodevelopment of preschoolers under China's newly relaxed child policy: A national retrospective cohort study.

Introduction: The change in Chinese fertility policy brings new challenges and considerations for children's health outcomes; however, very little is known about the interaction between siblings, family socioeconomic status (SES), and neurodevelopment in the Chinese preschool-age population. Therefore, this study aimed to develop a new explanatory pathway from sibling effect to early childhood development and explored the mediation effect of family SES in the pathway. Methods: From April 2018 to December 2019, we conducted a national retrospective cohort study in 551 cities in China, and a total of 115,915 preschool-aged children were selected for the final analysis. Children's neurodevelopment, including Communication, Gross motor, Fine motor, Problem-solving, and Personal-social, was assessed with the Ages & Stages Questionnaires, Third Edition (ASQ-3). Hypothesis tests and multilevel regression models were used to assess the associations and their strength between sibling effect and neurodevelopmental delay. Pathway analysis was used to verify the mediation effect of SES. Results: The results showed that there were significant risk effects of a sibling on preschoolers' overall neurodevelopment including communication, gross motor, fine motor, and problem-solving delay. The adjustment of family SES, however, brought a reversal of this association. The results of the mediation model illustrated a direct, protective effect of one-sibling status (ßASQ-delay = -0.09; ßASQ-scores = 0.07; p < 0.001), and an indirect, risk effect from one-sibling status through family SES to neurodevelopment outcomes (ßASQ-delay =0.12; ßASQ-scores = -0.12; p < 0.001). The total sibling effect was weakened but remained negative (ßASQ-delay =0.03; ßASQ-scores = -0.05; p < 0.001). Discussion: This study concluded that family SES mediated the negative effects of one sibling on early child development. To enhance the positive influence of sibling addition, we suggested providing more resources and instructions to the families with less educated and poorer employed parents under the coming multi-child era.

Prenatal second-hand smoke exposure and the risk of suspected developmental coordination disorder in preschoolers: A nationwide retrospective cohort study in China.

Prenatal exposure to second-hand smoke (SHS) is associated with increased neurodevelopmental problems in children, however, its impact on the risk of developmental coordination disorder (DCD) in preschoolers have not been studied thoroughly. Herein, we probed this association based on a nationwide retrospective cohort study of 149,005 preschoolers in China. We divided the objects into the prenatal SHS-exposed group or the no prenatal smoke exposed group (NS-exposed group). Preschoolers were assessed for motor proficiency by the Chinese version of Little Developmental Coordination Disorder Questionnaire (LDCDQ). Multivariable logistic regression was used to evaluate the associations. The prevalence of prenatal SHS exposure was 23.89%. Generally, the prevalence of suspected DCD was significantly higher in prenatal SHS-exposed group (16.38% VS. 14.19%, P < 0.001). With the increase of age, the mean total scores of LDCDQ of both boys and girls increased gradually; and the prevalence of suspected DCD in girls was higher than that in boys in the same age group. After adjusting for covariates, prenatal SHS exposure had the negative association with the total score of LDCDQ and increased the risk of suspected DCD. Our results suggest a need for interventions designed to reduce maternal SHS exposure during pregnancy, early screen for DCD and increase targeted movement and coordination skill training for vulnerable children.

Associations between gestational age and childhood sleep: a national retrospective cohort study.

BACKGROUND: Both sleep quality and quantity are essential for normal brain development throughout childhood; however, the association between preterm birth and sleep problems in preschoolers is not yet clear, and the effects of gestational age across the full range from preterm to post-term have not been examined. Our study investigated the sleep outcomes of children born at very-preterm (<31 weeks), moderate-preterm (32-33 weeks), late-preterm (34-36 weeks), early-term (37-38 weeks), full-term (39-40 weeks), late-term (41 weeks) and post-term (>41 weeks). METHODS: A national retrospective cohort study was conducted with 114,311 children aged 3-5 years old in China. Children's daily sleep hours and pediatric sleep disorders defined by the Children's Sleep Habits Questionnaire (CSHQ) were reported by parents. Linear regressions and logistic regression models were applied to examine gestational age at birth with the sleep outcomes of children. RESULTS: Compared with full-term children, a significantly higher CSHQ score, and hence worse sleep, was observed in very-preterm (ß = 1.827), moderate-preterm (ß = 1.409), late-preterm (ß = 0.832), early-term (ß = 0.233) and post-term (ß = 0.831) children, all p<0.001. The association of pediatric sleep disorder (i.e. CSHQ scores>41) was also seen in very-preterm (adjusted odds ratio [AOR] = 1.287 95% confidence interval [CI] (1.157, 1.433)), moderate-preterm (AOR = 1.249 95% CI (1.110, 1.405)), late-preterm (AOR = 1.111 95% CI (1.052, 1.174)) and post-term (AOR = 1.139 95% CI (1.061, 1.222)), all p<0.001. Shorter sleep duration was also found in very-preterm (ß = -0.303), moderate-preterm (ß = -0.282), late-preterm (ß = -0.201), early-term (ß = -0.068) and post-term (ß = -0.110) compared with full-term children, all p<0.01. Preterm and post-term-born children had different sleep profiles as suggested by subscales of the CSHQ. CONCLUSIONS: Every degree of premature, early-term and post-term birth, compared to full-term, has an association with sleep disorders and shortened daily sleep duration. Preterm, early-term, and post-term should therefore all be monitored with an increased threat of sleep disorder that requires long-term monitoring for adverse sleep outcomes in preschoolers.

Association of Gestational Age at Birth With Subsequent Neurodevelopment in Early Childhood: A National Retrospective Cohort Study in China.

Background: The association between preterm birth and neurodevelopmental delays have been well examined, however, reliable estimates for the full range of gestational age (GA) are limited, and few studies explored the impact of post-term birth on child development. Objective: This study aimed to examine the long-term neuropsychological outcomes of children born in a full range of GA with a national representative sample in China. Methods: In this retrospective population-based cohort study, a total of 137,530 preschoolers aged 3-5 years old (65,295/47.5% females and 72,235/52.5% males) were included in the final analysis. The Ages and Stages Questionnaires-Third Edition (ASQ-3) was completed by parents to evaluate children's neurodevelopment. The associations between GA and neurodevelopment were analyzed by a generalized additive mixed model with thin plate regression splines. Logistic regression was also conducted to examine the differences in children's development with different GAs. Results: There was a non-linear relationship between GA and children's neurodevelopmental outcomes with the highest scores at 40 weeks gestational age. The adjusted risks of GAs (very and moderately preterm, late-preterm, early-term, and post-term groups) on suspected developmental delays were observed in communication (OR were 1.83, 1.28, 1.13, and 1.21 respectively, each p < 0.05), gross motor skill (OR were 1.67, 1.38, 1.10, and 1.05 respectively, each p < 0.05), and personal social behavior (OR were 1.01, 1.36, 1.12, and 1.18 respectively, each p < 0.05). The adjusted OR of very and moderately preterm, late-preterm, and early-term were observed in fine motor skills (OR were 1.53, 1.22, and 1.09 respectively, each p < 0.05) and problem-solving (OR were 1.33, 1.12, and 1.06 respectively, each p < 0.05). Conclusion: GAs is a risk factor for neurodevelopmental delays in preschoolers after controlling for a wide range of covariates, and 40-41 weeks may be the ideal delivery GA for optimal neurodevelopmental outcomes. Close observation and monitoring should be considered for early- and post-term born children as well as pre-term children.

Association of the Onset of Self-Feeding With Subsequent Suspected Developmental Coordination Disorder: A Prospective Cohort Study in China.

Background: Successful self-feeding reflects the readiness of early motor development and environmental impacts, and the onset of self-feeding as a developmental milestone might be a predictor of subsequent motor development in children. In this study, we explored the association between the onset of self-feeding and childhood risk of Developmental Coordination Disorder in children from one-child and two-child families. Methods: We conducted a data-linkage prospective cohort study from 38 kindergartens in 6 cities in China. A total of 11,727 preschoolers aged 3-6 years old were included in the final analysis and were assessed with the Movement Assessment Battery for Children-second edition (MABC-2) Test. The information on early self-feeding onset was obtained from parents. The mixed and multi-level logistic models utilizing a random intercept were used to investigate the associations between the onset time of self-feeding and subsequent motor performance. Results: The results showed that, compared with those beginning self-feeding at or younger than 12 months of age, children starting self-feeding at 13-24, 25-36, and later than 36 months, showed a decrease in their total MABC-2 scores of 2.181, 3.026, and 3.874, respectively; and had an increased risk of suspected DCD by 36.0, 101.6, 102.6%, respectively; they also had 30.2, 46.6, 71.2% increased prevalence of at risk of suspected DCD, when adjusting for both child and family characteristics (each p < 0.05). Significant associations were observed in fine motor, gross motor, and balance subtests (each p < 0.05) in groups with a delayed onset of self-feeding. However, the strength of the associations was mitigated in the fine motor and balance subtests in children with a sibling. Conclusion: The delayed onset time of self-feeding acts as an early behavioral marker for later childhood motor impairment. Moreover, children with a sibling may benefit from additional interaction and their motor developmental pattern may be affected by the presence of a sibling.

Early Motor Milestones in Infancy and Later Motor Impairments: A Population-Based Data Linkage Study.

BACKGROUND: Developmental Coordination Disorder (DCD) is a neurodevelopmental condition with high prevalence. Early motor milestones are important markers to identify DCD. The current study aims to evaluate the association between the onset of crawling and independent walking and their transition pattern during infancy and later motor impairments. METHODS: A total of 8,395 children aged 3-6 years old in China were included in the final analysis. A parent questionnaire was used to collect early milestone onset data. Children's motor performance was measured using the Movement Assessment Battery for Children-2nd edition (MABC-2). The association between motor milestones and motor impairment was analyzed using a multilevel regression model. RESULTS: The result showed that a 1-month delay in crawling onset increased the risk of significant overall motor impairment by 5.3, and 14.0% when adjusting for child and family characteristics. A 1-month delay in walking onset increased the risk of significant overall motor, fine, gross, and balance impairment by 21.7, 8.3, 13.3, and 17.8%. A 1 month increase in the transition time from crawling to independent walking increased the risk of significant overall motor and gross motor impairment by 7.7 and 6.6%. These results were inconsistent across different age bands (each p < 0.05). CONCLUSIONS: Our study indicates that even a mild delay in crawling and walking onsets in infancy increase the risk for subsequent motor impairments in childhood, and children with motor impairments revealed a different transition pattern from crawling to walking. The motor abilities of children with motor impairments can be observed to diverge from typically developing children as early as 6-8 months old. The findings can facilitate the early identification of motor impairments in children, and provide early signs to initiate intervention.

Association of Gestational Age at Birth With Subsequent Suspected Developmental Coordination Disorder in Early Childhood in China.

Importance: It remains unknown whether children born at different degrees of prematurity, early term, and post term might have a higher risk of developmental coordination disorder (DCD) compared with completely full-term children (39-40 gestational weeks). Objective: To differentiate between suspected DCD in children with different gestational ages based on a national representative sample in China. Design, Setting, and Participants: A retrospective cohort study was conducted in China from April 1, 2018, to December 31, 2019. A total of 152 433 children aged 3 to 5 years from 2403 public kindergartens in 551 cities of China were included in the final analysis. A multilevel regression model was developed to determine the strength of association for different gestational ages associated with suspected DCD when considering kindergartens as clusters. Main Outcomes and Measures: Children's motor performance was assessed using the Little Developmental Coordination Disorder Questionnaire, completed by their parents. Gestational age was determined according to the mother's medical records and divided into 7 categories: completely full term (39 to 40 weeks' gestation), very preterm (<32 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), late term (41 weeks), and post term (>41 weeks). Results: A total of 152 433 children aged 3 to 5 years (mean [SD] age, 4.5 [0.8] years), including 80 370 boys (52.7%) and 72 063 girls (47.3%), were included in the study. There were 45 052 children (29.6%) aged 3 years, 59 796 (39.2%) aged 4 years, and 47 585 (31.2%) aged 5 years. Children who were born very preterm (odds ratio [OR], 1.35; 95% CI, 1.23-1.48), moderately preterm (OR, 1.18; 95% CI, 1.02-1.36), late preterm (OR, 1.24; 95% CI, 1.16-1.32), early term (OR, 1.11; 95% CI, 1.06-1.16), and post term (OR, 1.17; 95% CI, 1.07-1.27) were more likely to be classified in the suspected DCD category on the Little Developmental Coordination Disorder Questionnaire than completely full-term children after adjusting for the same characteristics. Additionally, there was no association with suspected DCD in younger (aged 3 years) early-term and postterm children by stratified analyses. Conclusions and Relevance: In this cohort study, every degree of prematurity at birth, early-term birth, and postterm birth were associated with suspected DCD when compared with full-term birth. These findings have important implications for understanding motor development in children born at different gestational ages. Long-term follow-up and rehabilitation interventions should be considered for children born early and post term.