Effects of a Nonwearable Digital Therapeutic Intervention on Preschoolers With Autism Spectrum Disorder in China: Open-Label Randomized Controlled Trial.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause difficulty with communication and social interactions as well as complicated family dynamics. Digital health interventions can reduce treatment costs and promote healthy lifestyle changes. These therapies can be adjunctive or replace traditional treatments. However, issues with cooperation and compliance prevent preschool patients with ASD from applying these tools. In this open-label, randomized controlled trial, we developed a nonwearable digital therapy called virtual reality-incorporated cognitive behavioral therapy (VR-CBT). OBJECTIVE: The aim of this study was to assess the adjunctive function of VR-CBT by comparing the effects of VR-CBT plus learning style profile (LSP) intervention with those of LSP-only intervention in preschool children with ASD. METHODS: This trial was performed in China on 78 preschool children (age 3-6 years, IQ>70) diagnosed with ASD who were randomized to receive a 20-week VR-CBT plus LSP intervention (intervention group, 39/78, 50%) or LSP intervention only (control group, 39/78, 50%). The primary outcome was the change of scores from baseline to week 20, assessed by using the parent-rated Autism Behavior Checklist (ABC). Secondary outcomes included the Childhood Autism Rating Scale (CARS), Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV), and behavioral performance data (accuracy and reaction time) in go/no-go tasks. All primary and secondary outcomes were analyzed in the intention-to-treat population. RESULTS: After the intervention, there was an intervention effect on total ABC (ß=-5.528; P<.001) and CARS scores (ß=-1.365; P=.02). A similar trend was observed in the ABC subscales: sensory (ß=-1.133; P=.047), relating (ß=-1.512; P=.03), body and object use (ß=-1.211; P=.03), and social and self-help (ß=-1.593; P=.03). The intervention also showed statistically significant effects in improving behavioral performance (go/no-go task, accuracy, ß=2.923; P=.04). Moreover, a significant improvement of ADHD hyperactivity-impulsivity symptoms was observed in 53 children with comorbid ADHD based on ADHD-RS-IV (ß=-1.269; P=.02). No statistically significant intervention effect was detected in the language subscale of ABC (ß=-.080; P=.83). Intervention group girls had larger improvements in ABC subscales, that is, sensory and body and object use and in the CARS score and accuracy of go/no-go task (all P<.05) than the control group girls. Statistically significant intervention effects could be observed in hyperactivity-impulsivity symptoms in the intervention group boys with comorbid ADHD compared with those in the control group boys (ß=-1.333; P=.03). CONCLUSIONS: We found potentially positive effects of nonwearable digital therapy plus LSP on core symptoms associated with ASD, leading to a modest improvement in the function of sensory, motor, and response inhibition, while reducing impulsivity and hyperactivity in preschoolers with both ASD and ADHD. VR-CBT was found to be an effective and feasible adjunctive digital tool. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100053165; http://www.chictr.org.cn/showproj.aspx?proj=137016.

A nested case-control study of prenatal vanadium exposure and low birthweight.

STUDY QUESTION: Is prenatal vanadium exposure associated with adverse birth outcomes? SUMMARY ANSWER: The odds of low birthweight (LBW) are increased 2.23-fold in mothers with a urinary vanadium of ≥2.91 µg/g creatinine compared with that in mothers with a urinary vanadium of ≤1.42 µg/g creatinine. WHAT IS KNOWN ALREADY: Human exposure to vanadium occurs through intake of food, water and polluted air. Vanadium has been suggested to have fetotoxicity and developmental toxicity in animal studies, and epidemiological studies have reported an association between a decrease in birthweight and vanadium exposure estimated from particulate matter. STUDY DESIGN, SIZE, DURATION: A nested case-control study involving 816 study participants (204 LBW cases and 612 matched controls) was conducted with data from the prospective Healthy Baby Cohort between 2012 and 2014 in the province of Hubei, China. PARTICIPANTS/MATERIALS, SETTING, METHODS: Vanadium concentrations in 816 maternal urine samples collected before delivery [the median gestational age was 39 weeks (range 27-42 weeks)] were measured by inductively coupled plasma mass spectrometry. Information on the infants' birth outcomes was obtained from medical records. Conditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). MAIN RESULTS AND THE ROLE OF CHANCE: The median urinary vanadium concentration of the cases was much higher than that of the controls (3.04 µg/g creatinine versus 1.93 µg/g creatinine). The results revealed a significant positive trend between the odds of LBW and level of maternal urinary vanadium [relative to the lowest tertile; adjusted OR = 1.69 (95% CI: 0.92, 3.10) for the medium tertile; adjusted OR = 2.23 (95% CI: 1.23, 4.05) for the highest tertile; P-trend = 0.02]. Additionally, the association was not modified by maternal age (P for heterogeneity = 0.70) or infant gender (P for heterogeneity = 0.21). LIMITATIONS, REASONS FOR CAUTION: The maternal urine sample was collected before labor, and the maternal urinary vanadium levels measured at one point in time may not accurately reflect the vanadium burden during the entire pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study can enrich the biological monitoring data on urinary vanadium in pregnant women; and may be evidence that vanadium may affect fetal development. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Natural Science Foundation of China (21437002, 81372959 and 81402649), the R&D Special Fund for Public Welfare Industry (Environment) (201309048) and the Fundamental Research Funds for the Central Universities, HUST (2016YXZD043). The authors have no conflicts of interest to declare.

Automating General Movements Assessment with quantitative deep learning to facilitate early screening of cerebral palsy.

The Prechtl General Movements Assessment (GMA) is increasingly recognized for its role in evaluating the integrity of the developing nervous system and predicting motor dysfunctions, particularly in conditions such as cerebral palsy (CP). However, the necessity for highly trained professionals has hindered the adoption of GMA as an early screening tool in some countries. In this study, we propose a deep learning-based motor assessment model (MAM) that combines infant videos and basic characteristics, with the aim of automating GMA at the fidgety movements (FMs) stage. MAM demonstrates strong performance, achieving an Area Under the Curve (AUC) of 0.967 during external validation. Importantly, it adheres closely to the principles of GMA and exhibits robust interpretability, as it can accurately identify FMs within videos, showing substantial agreement with expert assessments. Leveraging the predicted FMs frequency, a quantitative GMA method is introduced, which achieves an AUC of 0.956 and enhances the diagnostic accuracy of GMA beginners by 11.0%. The development of MAM holds the potential to significantly streamline early CP screening and revolutionize the field of video-based quantitative medical diagnostics.

Mental health problems of preschool children during the COVID-19 home quarantine: A cross-sectional study in Shanghai, China.

Objective: As the coronavirus disease 2019 (COVID-19) pandemic spread across Shanghai, China, in late February 2022 and protective measures to mitigate its impact were enacted, this study aimed to estimate how home quarantine affected the mental health of preschool children in Shanghai, China and explore the association between lifestyle factors and mental health during this special period. Methods: A cross-sectional online survey of 2,110 preschool students from Shanghai, China, was conducted during May 20-25,2022. Preschooler' mental health (Strengths and Difficulties Questionnaire, SDQ) and daily activities were reported by parents. Results: The sample involved 2,110 children with a mean age of 4.65 years [standard deviation (SD): 0.91, range: 3-6 years]. Boys and children whose mother's education level were college and high school had higher rate of mental health problems. Boys had significantly higher rates of peer problems and prosocial behaviors than girls. The 3-year-old group had significantly higher rates of prosocial behaviors than other groups. As compared to the Shanghai norm and the SDQ results of preschool children in Shanghai in 2019 (SH2019), there were a significant decrease in emotional symptoms score, as well as a significant increase in conduct problems score. Additionally, peer problems score significantly increased compared to SH2019. Decreased time spent on daily sleep was associated with the increased risk for preschoolers' mental health problems. Conclusion: There was an increase in the frequency of emotional and behavioral problems, especially regarding conduct problems and peer problems, in preschool children during the COVID-19 home quarantine in Shanghai, China. Boys, younger preschool children and children whose mother's education level were college and high school may be especially vulnerable to emotional and behavioral problems. It was also found that decreased time spent on sleep may aggravate preschool children's mental health problems. It may be beneficial to differentiate and focus on conducting psychoeducation and implementing psycho-behavioral interventions to solve these issues.

Influencing factors of the neurodevelopment of high-risk infants.

BACKGROUND: High-risk infants refer to newborns exposed to high-risk factors in the prenatal, natal or postnatal period. High-risk infants are at high risk of developmental retardation, and early identification of developmental abnormalities plays a vital role in improving high-risk infants' quality of life. AIMS: To describe the neurodevelopment of high-risk infants aged less than 1 year old, and to analyse the incidences and influencing factors of neurodevelopmental abnormalities in order to provide a basis for neurodevelopment monitoring and management of high-risk infants. METHODS: High-risk infants born between January 2016 and December 2016 in the maternity and infant health hospitals of three districts in Shanghai were followed up. The Gesell Developmental Scale was used to assess the neurodevelopmental level at the time of recruitment (0-2 months) and at 9 months. Univariate and multivariate analyses of the influencing factors were conducted. RESULTS: 484 high-risk infants (male 51%, female 49%) with an average gestation age of 36.5±2.2 weeks were recruited. At the time of recruitment, the average age was 2.1 (0.8) months, and the developmental quotient (DQ) scores of full-term high-risk infants in motor (t=3.542, p=0.001), cognitive (t=3.125, p=0.002), language (t=3.189, p=0.002) and social (t=3.316, p=0.001) areas were higher than those of preterm infants. The incidences of developmental abnormalities of full-term high-risk infants in motor (χ2 =9.452, p=0.002), cognitive (χ 2 =6.258, p=0.012), language (χ 2 =12.319, p =0.001) and social (χ 2 =6.811, p=0.009) areas were lower than the preterm infants. At 9 months, there was no difference in the DQ scores and incidences of developmental abnormalities in four areas between full-term and preterm high-risk infants, and the incidence of developmental abnormalities was around 10%. CONCLUSION: The incidence of neurodevelopmental abnormalities in high-risk infants aged less than 1 year old is high. Preterm birth and parental bad habits are significant factors affecting the neurodevelopment. Monitoring and early interventions help to improve high-risk infants' neurodevelopment.

Prenatal chromium exposure and risk of preterm birth: a cohort study in Hubei, China.

Few studies have investigated the association of environmental chromium exposure and preterm birth in general population. This study was designed to investigate whether maternal chromium exposure during pregnancy is associated with reduced gestational age or risk of preterm birth using the data from Healthy Baby Cohort study conducted in Hubei, China between 2012 and 2014 (n = 7290). Chromium concentrations in maternal urine samples collected at delivery were measured with inductively coupled plasma mass spectrometry. Tertiles of chromium concentrations was negatively associated with gestational age in multivariable linear regression analyses [ß (95% CI): low = reference; middle = -0.67 days (-1.14, -0.20); high = -2.30 days (-2.93, -1.67); p trend <0.01]. Logistic regression analyses also indicated that higher maternal chromium [adjusted odds ratio (OR) (95% CI): 1.55(0.99, 2.42) for the medium tertile; 1.89(1.13, 3.18) for the highest tertile; p trend <0.01] was associated with increased risk of preterm birth. The associations appeared to be more pronounced in male infants (adjusted OR (95% CI): 2.54 (1.29, 4.95) for the medium tertile; 2.92 (1.37, 6.19) for the highest tertile; p trend <0.01). Our findings suggest maternal exposure to higher chromium levels during pregnancy may potentially increase the risk of delivering preterm infants, particularly for male infants.

Association of adverse birth outcomes with prenatal exposure to vanadium: a population-based cohort study.

BACKGROUND: Vanadium, an important pollutant produced from anthropogenic activities, has been suggested to be embryotoxic and fetotoxic in animal studies. However, little is known about its effects on humans. We aimed to assess the association of prenatal exposure to vanadium with the risk of adverse birth outcomes in babies born to women in China. METHODS: For this population-based cohort study, the Healthy Baby Cohort, women were recruited from three cities in Hubei Province, China. Women included in this analysis were recruited from Wuhan Women and Children Medical Care Center, Wuhan. We measured urinary concentrations of vanadium and other metals simultaneously using inductively coupled plasma mass spectrometry. We used multivariable logistic regressions, with adjustment for potential confounders, to estimate the associations of natural logarithm transformed creatinine-corrected urinary vanadium (Ln-vanadium) concentrations as continuous variables and categorised into quartiles (Q; Q1: ≤0·84 µg/g creatinine, Q2: 0·84-1·40 µg/g creatinine, Q3: 1·40-2·96 µg/g creatinine, Q4: >2·96 µg/g creatinine, with the lowest quartile set as reference) with preterm delivery, early-term delivery, low birthweight, and being small for gestational age. We applied restricted cubic spline models to evaluate the dose-response relationships. FINDINGS: Data from 7297 women recruited between Sept 22, 2012, and Oct 22, 2014, were included in this study. Urinary Ln-vanadium concentrations showed non-linear dose-response relationships with risk of preterm delivery (S-shaped, p<0·0001) and low birthweight (J-shaped, p=0·0001); the adjusted odds ratios (ORs) for increasing quartiles of urinary vanadium were 1·76 (95% CI 1·05-2·95) for Q2, 3·17 (1·96-5·14) for Q3, and 8·86 (5·66-13·86) for Q4 for preterm delivery, and 2·29 (95% CI 1·08-4·84) for Q2, 3·22 (1·58-6·58) for Q3, and 3·56 (1·79-7·10) for Q4 for low birthweight. Ln-vanadium concentrations were linearly associated with the risk of early-term delivery (linear, p<0·0001) and being small for gestational age (linear, p=0·0027), with adjusted ORs of 1·15 (95% CI 1·10-1·21) for early-term delivery and 1·12 (1·04-1·21) for being small for gestational age per unit increase in Ln-vanadium concentrations. INTERPRETATION: Our findings reveal a relationship between prenatal exposure to higher levels of vanadium and increased risk of adverse birth outcomes, suggesting that vanadium might be a potential toxic metal for human beings. Further studies are needed to replicate the observed associations and investigate the interaction effects of prenatal exposure to different metals on adverse birth outcomes. FUNDING: National Key R&D Plan of China, National Natural Science Foundation of China, and Fundamental Research Funds for the Central Universities, Key Laboratory of Environment and Health.

Free and total urinary phthalate metabolite concentrations among pregnant women from the Healthy Baby Cohort (HBC), China.

Total urinary phthalate metabolites (the free plus glucuronidated forms) have been frequently measured in the general population. However, data are limited on the free forms which may be more bioactive, especially for sensitive population such as pregnant women. Here the data gap was addressed by measuring concentrations of free and total forms of six phthalate metabolites in 293 urine samples from pregnant women at delivery, who were randomly selected from the prospective Healthy Baby Cohort (HBC), China. We observed detectable concentrations of the total amount of phthalate metabolites in all urine samples. The geometric mean (GM) urinary concentrations of free and total mono-butyl phthalate (MBP) (5.20, 54.49ng/mL) were the highest, followed by mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) (4.52, 7.27ng/mL). For most of phthalate metabolites, urinary concentrations were significantly higher in women who were nulliparous. Significantly higher concentrations of mono-ethyl phthalate (MEP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) were found in women who had higher educational level. To our knowledge, this is the first study to report the free and total forms of phthalate metabolites among pregnant women in China. The results suggest that exposure characteristics may be related to parity and education.