World Journal of Pediatrics最新文献

Background: Preschooling is a critical time for intervention in children with autism spectrum disorder (ASD); thus, we analyzed brain tissue component volumes (BTCVs) and clinical indicators in preschool children with ASD to identify new biomarkers for early screening.

Methods: Eighty preschool children (3-6 years) with ASD were retrospectively included. The whole-brain myelin content (MyC), white matter (WM), gray matter (GM), cerebrospinal fluid (CSF), and non-WM/GM/MyC/CSF brain component volumes were obtained using synthetic magnetic resonance imaging (SyMRI). Clinical data, such as intelligence scores, autism diagnostic observation schedule-calibrated severity scores, age at first production of single words (AFSW), age at first production of phrases (AFP), and age at walking onset (AWO), were also collected. The correlation between the BTCV and clinical data was evaluated, and the effect of BTCVs on clinical data was assessed by a regression model.

Results: WM and GM volumes were positively correlated with intelligence scores (both P < 0.001), but WM and GM did not affect intelligence scores (P = 0.116, P = 0.290). AWO was positively correlated with AFSW and AFP (both P < 0.001). The multivariate linear regression analysis revealed that MyC, AFSW, AFP, and AWO were significantly different (P = 0.005, P < 0.001, P < 0.001).

Conclusions: This study revealed positive correlations between WM and GM volumes and intelligence scores. Whole-brain MyC affected AFSW, AFP, and AWO in preschool children with ASD. Noninvasive quantification of BTCVs via SyMRI revealed a new visualizable and quantifiable biomarker (abnormal MyC) for early ASD screening in preschool children.

Introduction: Methylmalonic acidemia (MMA) is a disorder of autosomal recessive inheritance, with an estimated prevalence of 1:50,000. First-tier clinical diagnostic tests often return many false positives [five false positive (FP): one true positive (TP)]. In this work, our goal was to refine a classification model that can minimize the number of false positives, currently an unmet need in the upstream diagnostics of MMA.

Methods: We developed machine learning multivariable screening models for MMA with utility as a secondary-tier tool for false positives reduction. We utilized mass spectrometry-based features consisting of 11 amino acids and 31 carnitines derived from dried blood samples of neonatal patients, followed by additional ratio feature construction. Feature selection strategies (selection by filter, recursive feature elimination, and learned vector quantization) were used to determine the input set for evaluating the performance of 14 classification models to identify a candidate model set for an ensemble model development.

Results: Our work identified computational models that explore metabolic analytes to reduce the number of false positives without compromising sensitivity. The best results [area under the receiver operating characteristic curve (AUROC) of 97%, sensitivity of 92%, and specificity of 95%] were obtained utilizing an ensemble of the algorithms random forest, C5.0, sparse linear discriminant analysis, and autoencoder deep neural network stacked with the algorithm stochastic gradient boosting as the supervisor. The model achieved a good performance trade-off for a screening application with 6% false-positive rate (FPR) at 95% sensitivity, 35% FPR at 99% sensitivity, and 39% FPR at 100% sensitivity.

Conclusions: The classification results and approach of this research can be utilized by clinicians globally, to improve the overall discovery of MMA in pediatric patients. The improved method, when adjusted to 100% precision, can be used to further inform the diagnostic process journey of MMA and help reduce the burden for patients and their families.

Background: Autism spectrum disorder (ASD) is a complex group of neurodevelopmental disorders. Research has highlighted a close association between the retinoic acid (RA) signaling pathway and ASD. This study investigates alterations in the vitamin A (VA, retinol) to RA metabolic pathway in children with ASD and speculates on the underlying reasons for these changes. We propose a subtype characterized by downregulated RA signaling in ASD, laying the groundwork for precise diagnosis and treatment research.

Methods: We included 489 children with ASD and 280 typically developing (TD) children. Those with ASD underwent evaluations of core symptoms and neuro-developmental levels, which were conducted by professional developmental behavior physicians using assessment scales. Serum VA and all-trans RA (atRA) levels were determined by high-performance liquid chromatography and ultra-high-performance liquid chromatography-tandem mass spectrometry. The expression levels and concentrations of enzyme molecules such as retinol dehydrogenase 10 were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay.

Results: Children with ASD exhibited reduced serum atRA, accompanied by a downregulation of atRA synthesis enzymes. The reduction in serum atRA levels was linked not only to VA levels but also to the aberrant expression of metabolic enzymes responsible for atRA. Furthermore, the serum atRA levels in children with ASD were more strongly correlated with core symptoms and neurodevelopmental levels than VA levels.

Conclusion: Children with ASD exhibited a dual regulation of reduced serum atRA levels, influenced by both VA levels and abnormal expression of atRA metabolic enzymes.

Background: The coronavirus disease 2019 (COVID-19) pandemic, a global health crisis, profoundly impacted all aspects of daily life. Adolescence, a pivotal stage of psychological and social development, is heavily influenced by the psychosocial and socio-cultural context. Hence, it is imperative to thoroughly understand the psychosocial changes adolescents experienced during the pandemic and implement effective management initiatives.

Data sources: We examined the incidence rates of depressive and anxiety disorders among adolescents aged 10-19 years globally and regionally. We utilized data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 to compare pre-pandemic (2018-2019) and pandemic (2020-2021) periods. Our investigation covered 204 countries and territories across the six World Health Organization regions. We conducted a comprehensive literature search using databases including PubMed/MEDLINE, Scopus, and Google Scholar, employing search terms such as "psychosocial", "adolescent", "youth", "risk factors", "COVID-19 pandemic", "prevention", and "intervention".

Results: During the pandemic, the mental health outcomes of adolescents deteriorated, particularly in terms of depressive and anxiety disorders. According to GBD 2021, the incidence rate of anxiety disorders increased from 720.26 [95% uncertainty intervals (UI) = 548.90-929.19] before the COVID-19 pandemic (2018-2019) to 880.87 per 100,000 people (95% UI = 670.43-1132.58) during the COVID-19 pandemic (2020-2021). Similarly, the incidence rate of major depressive disorder increased from 2333.91 (95% UI = 1626.92-3138.55) before the COVID-19 pandemic to 3030.49 per 100,000 people (95% UI = 2096.73-4077.73) during the COVID-19 pandemic. This worsening was notably pronounced in high-income countries (HICs). Rapid environmental changes, including heightened social anxiety, school closures, economic crises, and exacerbated racism, have been shown to adversely affect the mental well-being of adolescents.

Conclusions: The abrupt shift to remote learning and the absence of in-person social interactions heightened feelings of loneliness, anxiety, sadness, and stress among adolescents. This change magnified existing socioeconomic disparities, posing additional challenges. These complexities profoundly impact adolescents' well-being, especially vulnerable groups like those from HICs, females, and minorities. Acknowledging the underreporting bias in low- to middle-income countries highlights the importance of addressing these mental health alterations in assessments and interventions within these regions as well. Urgent interventions are crucial as the pandemic-induced mental stress may have lasting effects on adolescents' mental health.

Background: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care.

Methods: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children.

Results: Convulsion rates (97.5% vs. 4.3%, $P$ < 0.001) and frequencies (median: 2.0 vs. 1.6, $P$ < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both $P$ < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( $P$ < 0.001), while not in the three non-Omicron-subgroups $(P$ = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, $P$ < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( $P$ < 0.001). Fifteen of the 112 severe Omicron cases had brain damage.

Conclusions: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

Background: Button battery (BB) exposures are common in children and can have devastating consequences. We reviewed current evidence on the complications associated with BB exposure and identified predictors of outcomes using individual patient-level data.

Data sources: We carried out a systematic review and pooled analysis by searching MEDLINE, Embase, and Scopus up to May 19, 2023. Included studies describe complications following BB exposures in children (aged < 18 years). Odds ratios (ORs) were calculated using binary logistic regression to measure associations between predictive factors and different outcomes.

Results: Two-hundred seventeen studies (439 children) were included. The median age at presentation was 1.75 [interquartile range (IQR) 1.00-3.00] years and 399 (90.9%) exposures were ingestions. Of the 380 cases reporting sex, 162 (42.6%) were female. Feeding (192, 48.1%) and respiratory difficulties (138, 34.6%) were common presenting features for ingestions, while symptomatology was site-specific for insertions. Common complications included oesophageal mucosal damage alone (105, 26.3%) and tracheooesophageal fistula (93, 23.3%) for ingestions, and nasal septal perforation (22, 55.0%) and mucosal damage alone (13, 32.5%) for insertions. Intestinal perforation occurred in 2.5% of ingestion cases, including perforation of Meckel's diverticulum, peritonitis, and jejunocolic fistula. Vascular complications were common among children who died. Age (≤ 2 years), battery exposure duration (> 6 hours), and battery diameter (≥ 20 mm) were associated with common and severe complications of ingestions.

Conclusion: BB injuries are time-critical, with severe sequelae predominantly affecting young children. Diagnosis is challenging. Preventative work through regulation and safer battery design are required to eliminate this problem.

Background

Congenital malformations of the female genital tract (CM-FGT) are characterized by abnormal development of the fallopian tubes, uterus, and vagina, often accompanied by malformations in the urinary system, bones and hearing. However, no definitive pathogenic genes and molecular genetic causes have been identified.

Methods

We present the largest whole-genome sequencing study of CM-FGT to date, analyzing 590 individuals in China: 95 patients, 442 case–controls, and 53 familial controls.

Results

Among the patients, 5.3% carried known CM-FGT-related variants. Pedigree and case–control analyses in two dimensions of coding and non-coding regulatory regions revealed seven novel de novo copy number variations, 12 rare single-nucleotide variations, and 10 rare 3' untranslated region (UTR) mutations in genes related to CM-FGT, particularly highlighting ASH1L as a pathogenic gene. Single-cell sequencing data showed that the majority of CM-FGT-related risk genes are spatiotemporally specifically expressed early in uterus development.

Conclusions

In conclusion, this study identified novel variants related to CM-FGT, particularly highlighting ASH1L as a pathogenic gene. The findings provide insights into the genetic variants underlying CM-FGT, with single-cell sequencing data revealing spatiotemporal specific expression patterns of key risk genes early in uterine development. This study significantly advances the understanding of CM-FGT etiology and genetic landscape, offering new opportunities for prenatal screening.

Graphical abstract