World Journal of Pediatrics最新文献

{"title":"Asparaginase methylation and childhood obesity: cross-tissue patterns and parent-child concordance in a prospective cohort.","authors":"Maria Niubó-Pallàs, Ariadna Gómez-Vilarrubla, Júlia Mollà-Martínez, Berta Mas-Pares, Alexandra Bonmatí-Santané, José-María Martínez-Calcerrada, Francis de Zegher, Lourdes Ibáñez, Abel López-Bermejo, Judit Bassols","doi":"10.1007/s12519-026-01071-0","DOIUrl":"10.1007/s12519-026-01071-0","url":null,"abstract":"<p><strong>Background: </strong>Early-life epigenetic mechanisms may contribute to the developmental programming of childhood obesity. We aimed to examine whether placental asparaginase (ASPG) DNA methylation (DNAm) is associated with adiposity at 6 years of age and to explore its cross-tissue patterns and parent-child concordance.</p><p><strong>Methods: </strong>In a prospective birth cohort, placental ASPG DNAm was quantified by pyrosequencing and related to anthropometric and cardiometabolic outcomes in children at 6 years (n = 180). DNAm was also measured in child peripheral blood (n = 127) and in maternal and paternal blood samples during pregnancy (n = 44).</p><p><strong>Results: </strong>Increased placental ASPG DNAm was associated with increased adiposity and cardiometabolic markers at 6 years and increased odds of overweight/obesity [odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.01-1.11, P = 0.01]. Similar associations were observed for child blood (OR = 1.19, 95% CI = 1.04-1.36, P = 0.01), although these analyses were cross-sectional. Placental and child DNAm levels were positively correlated (r = 0.40, P < 0.01), and maternal-child DNAm was concordant (r = 0.48, P < 0.01), although the parental analyses were exploratory and based on a limited sample size (n = 44).</p><p><strong>Conclusions: </strong>ASPG DNAm is associated with childhood adiposity and shows cross-tissue and parent-child concordance, suggesting its potential role as an early-life epigenetic marker associated with metabolic risk. Given the modest effect sizes and exploratory nature of some analyses, these findings warrant cautious interpretation and require replication in independent cohorts.</p>","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"899-909"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging challenges and call to action for adolescent health in China.","authors":"Jian-Rong He, Wan-Qing Xiao, Wen-Hao Zhou, Xiu Qiu","doi":"10.1007/s12519-026-01074-x","DOIUrl":"10.1007/s12519-026-01074-x","url":null,"abstract":"","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"849-851"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct peripheral B-cell immunophenotypes define clinical heterogeneity in childhood-onset systemic lupus erythematosus.","authors":"Li-Yun Xu, Hui Chen, Yong-Zhen Li, Lan Luo, Ming Yang, Xiao-Chuan Wu","doi":"10.1007/s12519-026-01082-x","DOIUrl":"10.1007/s12519-026-01082-x","url":null,"abstract":"<p><strong>Background: </strong>B-cell dysregulation is central to the pathogenesis of childhood-onset systemic lupus erythematosus (cSLE), yet the B-cell immunophenotypes across disease states remain incompletely defined. This study aimed to investigate the mechanistic basis and clinical relevance of B-cell-mediated immune dysregulation in cSLE.</p><p><strong>Methods: </strong>Peripheral blood samples from 64 cSLE patients and 40 age- and sex-matched healthy controls (HCs) were analyzed using flow cytometry. The subsets were compared across disease states, including lupus low disease activity state (LLDAS), active disease, and clinical flare. Diagnostic performance was evaluated using logistic regression and receiver operating characteristic analyses.</p><p><strong>Results: </strong>Compared with HCs, patients with cSLE exhibited reduced unswitched memory B cells and expanded pathogenic subsets, including double-negative (DN) B cells, age-associated B cells (ABCs), short-lived plasma cells (SLPCs), and long-lived plasma cells (LLPCs) (all P < 0.05). LLPCs showed the strongest disease association [area under the curve (AUC) = 0.855] and a combined model further improved discrimination (AUC = 0.936). Active disease was characterized by expanded DN B cells, ABCs, SLPCs, and LLPCs (all P < 0.05). Clinical flare involved selective enrichment of ABCs, DN B cells, and plasma cells without further increase in total B cells. Of note, LLPCs remained elevated in LLDAS compared with HCs (P < 0.01). ABCs were negatively correlated with complement C3 levels (r =  - 0.26, P = 0.04).</p><p><strong>Conclusions: </strong>cSLE is characterized by distinct peripheral B-cell immunophenotypes across different clinical states, marked by expansion of ABCs and plasma-cell populations. Persistent LLPC enrichment during clinical quiescence suggests incomplete immunological restoration and may contribute to disease heterogeneity and relapse susceptibility.</p>","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"910-921"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of growth markers and patterns of growth on children's cardiometabolic health: a life course perspective.","authors":"Ling Luo, Juan Tong, Xing Wang, Qi-Zheng Huang, Yong-Kang Liu, Ping Lv, Jie Wang, Cong Geng, Hui Gao, Hong Gan, Meng-Long Geng, Bei-Bei Zhu, Shu-Man Tao, Xiao-Yan Wu, Kun Huang, Shuang-Qin Yan, Fang-Biao Tao","doi":"10.1007/s12519-026-01072-z","DOIUrl":"10.1007/s12519-026-01072-z","url":null,"abstract":"<p><strong>Background: </strong>Growth and development in children are known to be closely associated with cardiometabolic health. However, there is a lack of systematic assessments of associations between growth markers and growth patterns across different developmental stages and pediatric cardiometabolic health in prospective birth cohorts. This study aimed to identify critical developmental windows and growth characteristics that may be relevant to cardiometabolic health that could inform future prevention strategies.</p><p><strong>Methods: </strong>We utilized the Ma'anshan birth cohort and obtained repeated measurements of body length/height and weight from birth through school age at each follow-up visit to examine childhood body mass index (BMI) growth curves. During school age, additional measurements were taken for cardiometabolic risk factors (CMRFs) including waist circumference, blood pressure, blood glucose, and blood lipids. Linear mixed modeling was used to fit childhood BMI growth curves and calculate 11 growth markers: adiposity peak (AP)-age, AP-BMI, adiposity rebound (AR)-age, AR-BMI, infancy slope, toddlerhood slope, preschool/school-age slope, infancy area under the curve (AUC), toddlerhood AUC, preschool age AUC, and school-age AUC. Different growth patterns were classified using k-means clustering.</p><p><strong>Results: </strong>Among the 1786 children included, significant differences existed between boys and girls in growth markers (t-tests) and patterns (chi-square tests) (P < 0.05). With the exception of AP-age, the remaining 10 growth markers showed significant associations with clustered CMRFs in both boys and girls (P < 0.05). Compared to low-risk patterns, children with high-risk patterns had significantly increased risks of clustered CMRFs in both boys [relative risk (RR) = 6.75, 95% confidence interval (CI) = 3.81-12.92, P < 0.05] and girls (RR = 8.34, 95% CI = 4.15-18.69, P < 0.05). In stratified analyses by obesity status, these associations remained significant.</p><p><strong>Conclusions: </strong>Childhood growth patterns and markers during different parts of the life course were closely associated with cardiometabolic health; AP-age association was sex-specific. These findings support the importance of monitoring childhood growth trajectories from infancy onward for early identification of cardiometabolic risk.</p>","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"873-885"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GRIN-related epilepsy in Chinese pediatric patients: a retrospective study of clinical, genetic, and mutant protein structural features in a tertiary center cohort.","authors":"Si-Jia Wen, Hao Wang, Shi-Jia Ouyang, Jun-Jiao Zhang, Quan-Zhen Tan, Shang-Ru Li, Yue-Hua Zhang, Ye Wu, Yu-Wu Jiang","doi":"10.1007/s12519-026-01083-w","DOIUrl":"10.1007/s12519-026-01083-w","url":null,"abstract":"<p><strong>Background: </strong>N-methyl-D-aspartate receptors (NMDARs) play a pivotal role in neurodevelopment. While pathogenic variants in GRIN genes cause a broad spectrum of epileptic and developmental disorders, the precise molecular determinants that drive specific neurodevelopmental courses remain poorly understood. This study aims to utilize high-resolution structural modeling to identify associations between localized conformational alterations in NMDARs and distinct clinical phenotypes.</p><p><strong>Methods: </strong>We retrospectively evaluated a cohort of 31 Chinese pediatric patients with GRIN-related epilepsy (GRIN1, n = 3; GRIN2A, n = 14; GRIN2B, n = 11; GRIN2D, n = 3) using detailed electroclinical and neurodevelopmental phenotyping. Concurrently, three-dimensional structural models for 23 missense variants were generated using AlphaFold2. Domain-specific root-mean-square deviation (RMSD) and Euclidean displacements of transmembrane helices were quantified.</p><p><strong>Results: </strong>Patients in this cohort predominantly presented with early-onset epilepsy, multiple seizure types, and significant pharmaco-resistance, with 41.9% achieving seizure freedom after treatment. GRIN2B variants were primarily associated with developmental and epileptic encephalopathy (DEE) (63.6%, 7/11), whereas GRIN2A variants tended to be related with the epileptic encephalopathy (EE) course (71.4%, 10/14). Pathogenic variants were significantly clustered within the ligand-binding domain (LBD) and transmembrane domain (TMD). In silico structural analysis suggested that spatial displacement at the extracellular end of the M1 helix (M1 Top) might be associated with electrical status epilepticus during sleep (ESES) (median RMSD 0.54 Å vs. 0.37 Å, P = 0.038). Furthermore, a potential divergent structure-phenotype correlation was noted within the LBD: conformational alterations in the LBD-S1 region appeared more frequent in the developmental encephalopathy (DE) phenotype than in the EE group (median RMSD: 0.45 Å vs. 0.36 Å, adjusted P = 0.017), whereas LBD-S2 alterations were more prominent in the EE group than in the DEE group (median RMSD: 1.30 Å vs. 0.64 Å, adjusted P = 0.017).</p><p><strong>Conclusions: </strong>Localized conformational alterations within specific NMDAR micro-domains provide insights into pathogenic clinical phenotypes. However, the observed divergence suggests that geometric deviations alone may not account for clinical severity in a linear fashion. Our findings highlight the potential for in silico modeling to complement clinical phenotyping, but emphasize that precision medicine requires a multimodal framework combining structural predictions with functional validation.</p>","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"922-938"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning model for intravenous immunoglobulin resistance in Kawasaki disease: model development and validation study.","authors":"Jia-Ying Zhang, Ting-Jiao You, Jing Li, Jin-Feng Dong, Lei Xu, Xuan Li, Jun-Long Hu, Yun-Jia Tang, Miao Hou, Ying Liu, Zhen-Xing Xu, Hai-Tao Lv, Hong-Biao Huang","doi":"10.1007/s12519-026-01075-w","DOIUrl":"10.1007/s12519-026-01075-w","url":null,"abstract":"<p><strong>Background: </strong>Intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) increases coronary artery risk. Early prediction is crucial for improving outcomes. This study aimed to develop and validate a machine learning (ML) model for predicting IVIG resistance in children with KD.</p><p><strong>Methods: </strong>A retrospective cohort of patients with KD was used for model development, with external validation cohorts from Fuzhou and Yangzhou, and a prospective validation cohort. Clinical and laboratory variables were extracted from electronic medical records. We evaluated 12 algorithms and support vector machine (SVM) was selected for optimal performance. SHapley Additive exPlanations (SHAP) values assessed feature importance, followed by stepwise feature elimination. Model performance was evaluated using area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). A web-based calculator was developed.</p><p><strong>Results: </strong>A total of 2371 patients with KD involved in the retrospective development cohort, 443 in Fuzhou cohort, 198 in Yangzhou cohort, and 253 in prospective validation cohort. The SVM model achieved AUCs of 0.782 in internal validation, 0.746 and 0.759 in the external validation cohorts from Fuzhou and Yangzhou, respectively, and 0.799 in prospective validation. The final model incorporated eight predictors, with SHAP analysis providing both global and local explanations of feature contributions. The model also demonstrated good calibration and favorable net benefit across clinically relevant thresholds in DCA.</p><p><strong>Conclusions: </strong>The SVM-based ML model using routine clinical data shows potential for predicting IVIG resistance in KD and may support early risk stratification.</p>","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"939-954"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma transfusion in neonatal sepsis.","authors":"Fang-Rui Ding, Xiao-Yan Li","doi":"10.1007/s12519-026-01095-6","DOIUrl":"10.1007/s12519-026-01095-6","url":null,"abstract":"","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"839-848"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial heterogeneity in area-level environmental context of hospital-based congenital structural anomaly burden in Southwest China: a retrospective study from a provincial pediatric referral center.","authors":"Cheng-Hao Zhanghuang, Yong-Yu Ma, Chun-Li Zheng, Xi Hu, Ming-Xiang Zhang, Yun-Peng Gao, Jun-Ru Chen, Shi-Wu Yang, Hong Zhang, Ru-Tao Dai, Xi-Chen Zhang, Jin Shen, Bing Yan, Jun Wu","doi":"10.1007/s12519-026-01059-w","DOIUrl":"10.1007/s12519-026-01059-w","url":null,"abstract":"<p><strong>Background: </strong>Congenital structural anomalies constitute a major source of pediatric morbidity and surgical burden. However, evidence regarding the spatial epidemiology of congenital structural anomalies and their area-level environmental context remains limited, particularly in geographically and socioeconomically heterogeneous regions. This study aimed to investigate the spatial heterogeneity of area-level environmental contextual associations with hospital-based congenital anomaly burden.</p><p><strong>Methods: </strong>We conducted a retrospective hospital-based study including pediatric inpatients with congenital structural anomalies admitted to the largest provincial pediatric referral center in Yunnan Province between 2014 and 2024. Descriptive epidemiological analyses were performed to summarize demographic characteristics, temporal trends, and system-level distributions. High-frequency congenital anomalies were selected to construct stable county-level datasets for spatial analysis. Ordinary least squares (OLS) and geographically weighted regression (GWR) models were applied to examine spatially varying, area-level contextual associations between environmental factors and anomaly burden across five congenital anomaly systems (circulatory, digestive, urogenital, musculoskeletal, and other structural anomalies).</p><p><strong>Results: </strong>A total of 56,434 pediatric inpatients with congenital structural anomalies were identified. Among pediatric inpatients, boys accounted for the majority (67.68%), and admissions were predominantly concentrated in early childhood. Digestive (29.63%) and urogenital (23.30%) anomalies accounted for the largest proportions of pediatric inpatients. Among 41,531 pediatric inpatients included in spatial modeling, GWR consistently demonstrated better performance than global OLS models across five congenital anomaly systems. Area-level environmental associations with referral-weighted institutional burden showed substantial spatial heterogeneity. Carbon monoxide demonstrated predominantly positive associations across anomaly systems, whereas sulfur dioxide showed pronounced spatial heterogeneity. Vegetation coverage showed consistent negative associations, while population density displayed geographically varying associations.</p><p><strong>Conclusions: </strong>Hospital-based congenital structural anomaly burden showed a substantial spatial heterogeneity in its area-level environmental context within a provincial pediatric referral center dataset. Spatially explicit approaches such as GWR may help characterize referral-weighted, area-level patterns of institutional burden beyond global models. These findings are descriptive and hypothesis-generating and require validation using population-based or multi-center studies.</p>","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"955-967"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward resilient and efficient pediatric critical care provision amid falling birth rates.","authors":"Gang Liu, Quan Wang, Su-Yun Qian","doi":"10.1007/s12519-026-01087-6","DOIUrl":"10.1007/s12519-026-01087-6","url":null,"abstract":"","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"852-858"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between prenatal exposure to acid-suppressive medications and subsequent risk of autoimmune diseases in offspring: a nationwide birth cohort study in South Korea.","authors":"Yoon Lee, Kyeongmin Lee, Yeona Jo, Seohyun Hong, Sooji Lee, Hyesu Jo, Selin Woo, Yerin Hwang, Sunyoung Kim, Hyeon Seok Hwang, Jinseok Lee, Jaeyu Park, Hayeon Lee, Dong Keon Yon","doi":"10.1007/s12519-026-01077-8","DOIUrl":"10.1007/s12519-026-01077-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Although acid-suppressive medications are commonly used during pregnancy and may influence immune development in offspring, studies examining their association with pediatric autoimmune diseases remain limited. Therefore, we aimed to investigate the association between prenatal exposure to acid-suppressive medications and the risk of autoimmune diseases in offspring, using a nationwide birth cohort from South Korea.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This large-scale, nationwide mother-child cohort study in South Korea was conducted from January 1, 2009, to December 31, 2023, using data from the National Health Insurance Service of Korea. We evaluated the risk of autoimmune diseases in offspring following prenatal exposure to acid-suppressive medications, including histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs). The outcome was defined as the occurrence of systemic autoimmune diseases, autoimmune endocrine diseases, autoimmune thyroid diseases, autoimmune hepatitis, and other autoimmune conditions, classified according to International Classification of Diseases, 10th Revision codes (ICD-10). After applying propensity score-based overlap weighting, we used Cox proportional hazards models to estimate the risk, presenting adjusted hazard ratios (aHRs) with 95% confidence intervals (95% CIs). Sensitivity analyses were conducted by medication type, pregnancy trimester of exposure, time-dependent risk, and through various stratifications. In addition, we accounted for within-family clustering in the sibling comparison analysis with each mother treated as a separate stratum.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among the 3,012,992 mother-child pairs initially identified, a total of 2,777,119 children met the inclusion criteria. Of these, 507,845 pairs were exposed to prenatal acid-suppressive medications, and the mean follow-up duration was 9.6 years [standard deviation (SD): 2.4]. In the overlap-weighted cohort (404,550 pairs exposed and 404,551 pairs unexposed), prenatal exposure to acid-suppressive medications was modestly associated with increased risks of systemic autoimmune diseases (aHR: 1.11, 95% CI 1.01-1.21) and other autoimmune diseases (aHR: 1.09, 95% CI 1.05-1.12), such as lupus erythematosus, psoriasis, and rheumatoid arthritis. However, the high numbers needed to harm (37,716 and 6102 per year, respectively) indicate that the absolute excess risks were small, with insignificant sibling-comparison findings (aHR: 0.89, 95% CI 0.77-1.03, and aHR: 0.97, 95% CI 0.92-1.02, respectively). For any autoimmune disease, first-trimester exposure was associated with a slightly elevated risk (aHR: 1.09, 95% CI 1.06-1.13).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Modest associations were observed between prenatal exposure to acid-suppressive medications and pediatric autoimmune diseases; however, the low absolute excess risks and null findings from the sibling comparison analysis, which provides stronger c","PeriodicalId":23883,"journal":{"name":"World Journal of Pediatrics","volume":" ","pages":"859-872"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}