Pediatric Research最新文献

{"title":"Mitochondrial DNA haplogroups and circulating cell-free mitochondrial DNA as biomarkers of bronchopulmonary dysplasia.","authors":"Sara María Fernandez-Gonzalez, Andrea Sucasas-Alonso, Vanesa Balboa-Barreiro, Ignacio Rego-Perez, Alejandro Avila-Alvarez","doi":"10.1038/s41390-025-04052-7","DOIUrl":"https://doi.org/10.1038/s41390-025-04052-7","url":null,"abstract":"<p><strong>Background: </strong>Recognizing which premature infants are at higher risk of developing BPD/death is a challenge in neonatology. The aims of our study are to identify mitochondrial haplogroups and quantify circulating cell-free mitochondrial DNA (ccf-mtDNA) levels in very preterm infants at risk of bronchopulmonary dysplasia (BPD) or death and explore the relationship between these variables and the development of BPD/death.</p><p><strong>Methods: </strong>Single-center prospective cohort study including preterm infants of ≤32 weeks gestational age (GA) and birth weight ≤1500 g. Clinical variables, mitochondrial haplogroups, and ccf-mtDNA levels were determined. Subsequently, diagnosis and staging of BPD/death were performed, and groups were compared.</p><p><strong>Results: </strong>The population consisted of 107 newborns (mean GA 28.73 ± 2 weeks; mean birth weight 1,121 ± 332 g). A total of 44 patients (41.1%) presented the outcome of BPD/death without differences in haplogroup distribution and ccf-mtDNA levels between those who survived without BPD (controls). Variables independently associated with BPD/death included GA (p < 0.001; OR = 0.36 [95%CI 0.23-0.5]), birth weight (p < 0.001; OR = 0.99 [95%CI 0.99-0.99]), maximum FiO₂ in the delivery room (p = 0.001; OR = 1.07 [95%CI 1.03-1.12]), hours on mechanical ventilation (p = 0.02; OR 1.02 [95%CI 1.00-1.02]), and postnatal corticosteroids (p < 0.001; OR = 47.12 [95%CI = 5.98-371.1]).</p><p><strong>Conclusion: </strong>This is the first study to characterize mtDNA haplogroups and ccf-mtDNA in very preterm infants at risk of BPD/death. None of the mitochondrial variables studied were associated with BPD/death. Further research is needed to elucidate the role of mtDNA in BPD.</p><p><strong>Impact statement: </strong>Despite advances in perinatal care, bronchopulmonary dysplasia continues to be the most common chronic pulmonary morbidity associated with prematurity. Prediction of BPD in early stages is crucial to improve BPD rates, but this remains a major challenge in neonatal units. Given that mitochondria play an important role in the inflammatory and oxidative stress responses, we aimed to explore the relationship between mitochondrial haplogroups, circulating cell-free mitochondrial DNA levels, and BPD. This is the first work carried out in very preterm infants where mitochondrial haplogroups and the levels ccf-mtDNA are investigated with the intention of discovering a new biomarker for BPD.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human artificial placenta technology-trials: counselling and informed consent using healthcare professionals' and parental perspectives.","authors":"Angret de Boer, André Krom, Rania Kalaai, Marieke de Vries, Marije Hogeveen, Sylvia A Obermann-Borst, Marijn Vermeulen, Juliette S van Haren, Peter Andriessen, Martine C de Vries, E J T Verweij, Rosa Geurtzen","doi":"10.1038/s41390-025-04051-8","DOIUrl":"https://doi.org/10.1038/s41390-025-04051-8","url":null,"abstract":"<p><strong>Background: </strong>The Artificial Amnion and Placenta Technology (AAPT) is developed to improve outcomes of extremely premature birth, with first in-human trials expected in the coming years. Empirical research with key stakeholders is essential for responsibly designing these trials. This study aims to discuss considerations for counselling and informed consent for the first in-human trials of the AAPT, discussing legal and ethical considerations.</p><p><strong>Methods: </strong>A qualitative study using both individual and focus group interviews with healthcare professionals (HCPs) and parents was performed. Interviews were thematically analysed.</p><p><strong>Results: </strong>Fifteen parents and 46 HCPs were interviewed. The results are represented into key themes reflecting participants' perspectives on: (I) the moral and legal status of the subject treated in AAPT trials, (II) the first participant: the pregnant person, and (III) the terminology used to describe the technology. Furthermore, considerations around the informed consent process and counselling, including parental hope, are described. The findings suggest these factors are interconnected, as the moral and legal context surrounding AAPT trials influences the approach to counselling and informed consent.</p><p><strong>Conclusion: </strong>Resolving key ethical and legal issues important for counselling and informed consent is essential for establishing parental right and the development of a responsible, ethically sound informed consent process.</p><p><strong>Impact: </strong>Addressing ethical and legal issues surrounding counseling and informed consent is essential to safeguard a responsible and ethically sound consent process for future human artificial amnion and placenta technology (AAPT)-trials. This is the first study exploring stakeholder perspectives on the AAPT, highlighting the complexities in counselling and informed consent, such as the moral status of participants and the rights of all parties, which must be carefully navigated before trial designs can progress. The article underscores the importance of establishing consensus and maintaining open dialogue among all stakeholders to create a robust, ethically grounded framework for informed consent in future trials.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in global mortality rates and causes of death among children under five, 2000-2021.","authors":"Changgen Li, Jingyang Li, Angela Vinturache, Guodong Ding","doi":"10.1038/s41390-025-04061-6","DOIUrl":"https://doi.org/10.1038/s41390-025-04061-6","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex dimorphism in brain cell death after hypoxia-ischemia in newborn piglets.","authors":"Daniel Alonso-Alconada, Marc Chillida, Ana Catalan, Pierre Gressens, Nicola J Robertson","doi":"10.1038/s41390-025-04046-5","DOIUrl":"https://doi.org/10.1038/s41390-025-04046-5","url":null,"abstract":"<p><strong>Background: </strong>Clinical data suggest that females might be more resistant to hypoxia than males, with male sex recognized as a risk factor for suffering life-long neurological sequelae. However, the impact of hypoxia-ischemia in certain brain regions and its association with genetic sex remains unclear.</p><p><strong>Methods: </strong>Using the piglet model of neonatal brain injury, fifteen piglets (8 females and 7 males) were subjected to a global cerebral hypoxic-ischemic insult. After 48 h, total cell death and the number of necrotic, apoptotic and cleaved-caspase-3 positive cells was quantified in five brain regions.</p><p><strong>Results: </strong>Male piglets exposed to hypoxia-ischemia were more vulnerable than females (total cell death p < 0.01), also showing a region-specific response to brain injury depending on sex, with males being more affected in both deep gray (caudate p < 0.01; THAL p < 0.0001) and white (p < 0.01) matter. Despite necrosis was the primary form of cell death for both sexes, the pattern of cell death differed: while male piglets showed more necrosis (p < 0.0001), apoptosis (p < 0.0001) and caspase-3 activation (p < 0.0001) were higher in females.</p><p><strong>Conclusion: </strong>Our results suggest that male piglets were globally and regionally more vulnerable than females after HI; further, both the pattern of cell death and the apoptotic molecular mechanisms were sexually dimorphic.</p><p><strong>Impact: </strong>Clinical data suggest that females might be more resistant to perinatal asphyxia than male newborns. The impact of hypoxia-ischemia in certain brain regions and the association of cell death patterns with sex remain unclear. Hypoxic-ischemic male piglets were more vulnerable than females, showing also increased regional vulnerability in both deep gray and white matter areas. Although necrosis was the primary form of cell death for both sexes, male piglets showed more necrosis, whereas apoptosis and caspase-3 activation were higher in females. Neonatal brain injury and therapeutic responses may be sex-dependent due to differences in cell death patterns and molecular mechanisms.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Necrotizing enterocolitis: diagnosis with plasma IgG anti-tissue transglutaminase antibodies.","authors":"Hua Li, Chaoting Lan, Shuo Chen, Chun Yan, Shuchen Huangfu, Bowen Tian, Lin Li, Yide Mu, Shenwei Huang, Jiemei Liang, Liqiong Zhu, Junjian Lv, Yufeng Liu, Yan Tian","doi":"10.1038/s41390-025-04040-x","DOIUrl":"https://doi.org/10.1038/s41390-025-04040-x","url":null,"abstract":"<p><strong>Background: </strong>Necrotizing enterocolitis (NEC) is a severe inflammatory gastrointestinal disease in neonates. We aimed to evaluate the potential of IgG anti-tissue transglutaminase antibodies (IgG tTG) as early biomarkers for NEC.</p><p><strong>Method: </strong>We conducted a prospective observational study, collecting plasma from 60 neonates with abdominal distension (AD), which were divided into the NEC (n = 30) and the controls (n = 30) according to the follow-up results, and used the autoantigen microarray to identify for NEC-associated autoantibodies. An Enzyme-linked immunosorbent assay (ELISA) was utilized to measure plasma IgG tTG levels in a validation study (NEC n = 43, controls n = 20).</p><p><strong>Results: </strong>Microarray analysis indicated significantly elevated IgG tTG levels in neonates with NEC compared to controls (P < 0.001). ELISA further confirmed the significant elevation of IgG tTG in neonates with NEC (P < 0.001). IgG tTG effectively distinguished neonates with NEC from the controls, with an area under the curve (AUC) of 0.8674 (sensitivity of 72.09% and specificity of 95%). Encouragingly, IgG tTG levels were significantly higher in neonates with NEC I than in controls (P < 0.001). Additionally, as clinical conditions of neonates with NEC improved, the IgG tTG levels declined (P = 0.0159).</p><p><strong>Conclusion: </strong>IgG tTG has potential as a biomarker for early diagnosis of NEC and predicting its prognosis after treatment.</p><p><strong>Impact: </strong>Our results demonstrate that IgG anti-tissue transglutaminase antibodies possess significant diagnostic value for NEC. IgG anti-tissue transglutaminase antibodies can serve as a biomarker for early diagnosis NEC and its prognosis of treatment. The relationship between IgG anti-tissue transglutaminase antibodies and immune diseases may shed light on the pathogenesis of NEC, potentially opening new therapeutic avenues for preventing and treating neonates with NEC.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental and genetic risk factors for preterm birth: interplays with stressful events during pregnancy.","authors":"Silvina L Heisecke, María R Santos, Mercedes Negri Malbrán, Hugo Kupitzki, Susana M Mosca, María L Ribeiro, Gustavo Leguizamon, Jorge S López Camelo, Lucas G Gimenez","doi":"10.1038/s41390-025-04047-4","DOIUrl":"https://doi.org/10.1038/s41390-025-04047-4","url":null,"abstract":"<p><strong>Background: </strong>Preterm birth (PTB) etiology remains poorly understood. Our aim was to investigate the relation of environmental factors and specific gene polymorphisms involved in PTB in the context of stressful life events during pregnancy.</p><p><strong>Methods: </strong>Parental sociodemographic and obstetric data as well as genetic variants of 1263 preterm newborns were analyzed. Logistic regressions were used to identify shared environmental and genetic risk factors for PTB and stressful life events. A Lasso Ridge logistic regression with cross-validation was used to select the best predictors of maternal stress. Associations were evidenced through Bayesian networks.</p><p><strong>Results: </strong>Starting from a great number of variables, our model was processed and reduced until it allowed to visualize only two environmental factors (alcohol intake and chronic hypertension) along with three SNPs rs66911171 (CR1), rs854552 (PON1), rs4966038 (IGF1R) and two interactions rs854552 x rs4966038 (PON1xIGFR1) and rs5742612 x rs1942386 (IGF1xPGR) related to PTB and maternal stress.</p><p><strong>Conclusion: </strong>Machine learning techniques allow us to identify two environmental factors, three genetic markers, and two interactions related to PTB in the context of stressful life events. Findings of this exploratory study contribute to the understanding of the complex pathways relating maternal stress and PTB.</p><p><strong>Impact: </strong>An analysis of environmental factors and preterm birth specific gene polymorphisms in the context of stressful life events during pregnancy is presented. Alcohol intake and chronic hypertension along with SNPs of CR1, PON1, IGF1R and two interactions PON1xIGFR1 and IGF1xPGR are shown as related to preterm birth in the context of stressful life events. This research could help in developing targeted interventions and preventive strategies for at-risk populations. The study emphasizes the potential of machine learning to interpret biological and social interactions affecting health outcomes.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of BCL-2 and Laminin in Rectosigmoid Hirschsprung Disease: Correlations with Hirschsprung-Associated Enterocolitis.","authors":"Merve Dede, Fatih Celik, Ebrucan Bulut, Rumeysa Fatma Balaban, Nuseybe Huriyet, Ufuk Unal, Nesrin Ugras, Gulsah Cecener, Irfan Kiristioglu","doi":"10.1038/s41390-025-03994-2","DOIUrl":"https://doi.org/10.1038/s41390-025-03994-2","url":null,"abstract":"<p><strong>Background: </strong>Hirschsprung disease (HD) involves aganglionosis of the intestinal segment, with unclear etiology and challenging histopathological identification. The etiology of Hirschsprung-associated enterocolitis (HAEC) remains elusive. This study aims to explore the potential roles of Laminin and BCL-2 in the etiology of HD and HAEC by examining their expression levels.</p><p><strong>Methods: </strong>Tissues from 20 Rectosigmoid Hirschsprung patients (10 with and 10 without postoperative HAEC) and 10 controls were analyzed retrospectively. Protein expression was analyzed using immunohistochemistry, mRNA levels were measured using Real-Time PCR, and DNA mutations were found using Sanger Sequencing.</p><p><strong>Results: </strong>BCL-2 immunohistochemistry indicated decreased expression in HD patients' aganglionic tissues compared to ganglionic tissues (p ≤ 0.001). BCL-2 mRNA expression was significantly lower in HD patients' tissues than in controls (p < 0.0001). Laminin immunohistochemistry revealed significant positive staining in ganglionic tissues, with most aganglionic tissues negative and some mildly positive (p < 0.016). There was no significant association between BCL-2, Laminin, and HAEC (p > 0.05). DNA sequencing discovered a novel BCL-2 gene mutation in HD patients.</p><p><strong>Conclusion: </strong>BCL-2 and Laminin immunohistochemistry can differentiate ganglionic and aganglionic tissues. Reduced BCL-2 mRNA expression in HD patients indicates a disease that affects the whole gut. More research is needed on the new BCL-2 gene mutations.</p><p><strong>Impact statement: </strong>This is the first study to examine the correlation between BCL-2 and Laminin expression changes and enterocolitis developing in HD. It is a previously unreported contribution to the literature that BCL-2 mRNA expression was lower than expected in all intestinal tissues of HD patients, including the intestinal tissues considered to be healthy. Mutagenic changes have been detected in the BCL-2 gene of some HD patients. A definitive novel mutation, which has not been reported in the literature before, was detected in one patient.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Science, faith and belief in pediatric animal models.","authors":"Per T Sangild","doi":"10.1038/s41390-025-04036-7","DOIUrl":"https://doi.org/10.1038/s41390-025-04036-7","url":null,"abstract":"<p><strong>Impact statement: </strong>Antibiotic treatment may affect gut microbiota development with adverse effects on immune responses in the gut and other internal organs, like the lung. Animal models help to uncover mechanisms and consequences of antibiotic treatment, but direct translation of animal results to infants and children is often difficult. Objective scientific knowledge from both animal and human studies may need to be combined with more subjective faith convictions, to reach the commonly agreed beliefs that inform clinical practice.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A scoping review of adult NCD-relevant phenotypes measured in today's large child cohort studies.","authors":"Katie McBain, Dorothea Dumuid, Ashleigh Shipton, Susan A Clifford, Timothy Olds, Melissa Wake","doi":"10.1038/s41390-025-04056-3","DOIUrl":"https://doi.org/10.1038/s41390-025-04056-3","url":null,"abstract":"<p><strong>Background: </strong>Child cohort studies are important resources that can inform strategies to prevent adult noncommunicable diseases (NCDs). Technological advances now enable direct measurement of NCD-relevant phenotypes at large scale. Across contemporary large child cohorts, we aimed to provide the first comprehensive map of NCD-relevant phenotype measurement and gaps.</p><p><strong>Methods: </strong>We included cohorts with >8000 child participants that were recruiting in whole or part after 2010 and measuring phenotypes relevant to ten high-burden NCDs. Our database and gray literature search identified 15 cohort studies for inclusion. Details on phenotype measurement (methods, age, location) are presented in an online, searchable inventory.</p><p><strong>Results: </strong>All 15 cohorts measure body size or composition. Most cohorts measure aspects of cardiovascular health (n = 10) and neurocognition (n = 9). Fewer measure musculoskeletal phenotypes (n = 6), pulmonary function (n = 6), vision (n = 6) and glucose (n = 4). Only two cohorts measure hearing or kidney function.</p><p><strong>Conclusions: </strong>Today's childhood cohorts are not measuring some phenotypes important to global burden of disease, notably kidney function and hearing. Given the rarity of very large contemporary child cohorts, cross-cohort coordination will be required if all major NCD precursors are to be adequately represented for future benefit.</p><p><strong>Impact: </strong>This scoping review provides a comprehensive overview of NCD-relevant phenotype measurement across large, modern child cohort studies. This review has identified measurement gaps in important areas that may obviate steps to prevent and detect NCDs with high global disease burden. Findings may inform planning of collaborative projects and future data collection to address measurement gaps for greatest future benefit.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive, motor, and behavioral outcomes in preterm infants exposed to opioids.","authors":"Philipp Steinbauer, Julia Kühnl, Karin Pichler, Sophie Stummer, Katrin Klebermass-Schrehof, Philipp Deindl, Claudia Lindtner, Monika Olischar, Sophia Brandstetter, Renate Fuiko, Angelika Berger, Vito Giordano","doi":"10.1038/s41390-025-04048-3","DOIUrl":"https://doi.org/10.1038/s41390-025-04048-3","url":null,"abstract":"<p><strong>Background: </strong>Preterm infants undergo multiple painful procedures, which may negatively affect neurodevelopment. Proper pain management, including opioid use, is essential. This study aimed to determine the impact of opioid administration in very and extremely preterm infants on cognitive, motor, and behavioral outcomes at the corrected age of 3 years.</p><p><strong>Methods: </strong>This retrospective, single-center study included preterm infants born between 23 and 32 weeks of gestation, admitted to the Medical University of Vienna between 2011 and 2017. Follow-up data were collected at 3 years corrected age. Primary outcomes included behavioral outcomes assessed by the Child Behavior Checklist (CBCL) and cognitive and motor outcomes using the Bayley Scales of Infant Development (BSID).</p><p><strong>Results: </strong>A total of 333 preterm infants were included, with 214 in the non-opioid group (no exposure to opioids) and 119 in the opioid-group (exposure to opioids). Significant differences in cognitive and motor scores were observed between the groups (92.5 (85.5-98.5) vs 88 (79-94) and 85 (76-96) vs 76 (67-85), both p = 0.001). Behavioral outcomes were within the normal range in both groups, although higher depressive scores were noted in the opioid group.</p><p><strong>Conclusions: </strong>Cumulative opioid exposure in neonatal care may negatively impact cognitive and motor development but did not significantly affect overall behavioral outcomes.</p><p><strong>Impact: </strong>Our findings suggest that cumulative opioid exposure in the NICU does not significantly influence overall behavioral problems at the age of 3 years. However, it poses a risk for altered cognitive and motor development. This study highlights the distinct effects of opioid exposure on motor development and cognitive outcomes, while offering a nuanced perspective on behavioral outcomes, filling gaps in understanding the long-term neurodevelopmental consequences in preterm infants. The findings emphasize the need for careful management of opioid administration in NICU settings, balancing pain relief with potential long-term neurodevelopmental risks, while also underscoring the role of confounding factors such as IVH in shaping developmental trajectories.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}