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Impact of persistent pulmonary hypertension on cerebral oxygenation in infants with neonatal encephalopathy. 持续性肺动脉高压对新生儿脑病婴儿脑氧合的影响。
IF 3.1 3区 医学 Q1 PEDIATRICS Pub Date : 2024-11-07 DOI: 10.1038/s41390-024-03718-y
Dimitrios Rallis, Hoda El-Shibiny, Eniko Szakmar, Aisling Garvey, Helen Christou, Mohamed El-Dib

Background: Persistent pulmonary hypertension of the newborn (PPHN) affects systemic oxygenation and may worsen brain injury in infants with neonatal encephalopathy (NE). Evidence suggests that higher cerebral regional oxygenation (crSO2) indicates derangement in cerebral autoregulation, energy metabolism, and blood flow following NE. Our aim was to evaluate the impact of PPHN on crSO2, in infants with NE treated with therapeutic hypothermia (TH).

Methods: We retrospectively evaluated infants with NE and PPHN vs without PPHN, between 2018-2022. Linear regression analysis was performed to evaluate the impact of PPHN on crSO2 and total MRI score, adjusted for perinatal factors.

Results: 164 infants were analyzed, including 19(12%) with PPHN and 145(88%) without. PPHN-infants had significantly higher crSO2 during rewarming and post-rewarming compared to non-PPHN infants (87 ± 6 vs 80 ± 6, p = 0.001; 87 ± 5 vs 80 ± 7, p = 0.008, respectively), and a significantly higher total MRI score [7(2-19) vs 1(0-3), p < 0.001]. PPHN was significantly associated with higher crSO2 during rewarming (b = 6.21, 95% CI 2.37-10.04, p = 0.002) and post-rewarming (b = 8.60, 95% CI 2.28-14.91, p = 0.009), and total MRI score (b = 7.42, 95% CI 4.88-9.95, p < 0.001).

Conclusions: PPHN was associated with higher crSO2 during and after rewarming, and worse brain MRI score, indicating a significant impact of PPHN on brain injury in infants with NE undergoing TH.

Impact: Cerebral oxygenation was significantly higher in infants with neonatal encephalopathy (NE) and persistent pulmonary hypertension (PPHN) compared to infants without PPHN, during the rewarming and post-rewarming periods of therapeutic hypothermia (TH). PPHN is associated with brain injury in infants with NE undergoing TH. In infants with NE and PPHN, monitoring of cerebral oxygenation would help detect infants at higher risk of adverse outcomes.

背景:新生儿持续性肺动脉高压(PPHN)会影响全身氧合,并可能加重新生儿脑病(NE)婴儿的脑损伤。有证据表明,较高的脑区氧合(crSO2)表明新生儿脑病后脑的自动调节、能量代谢和血流发生了失调。我们的目的是评估在接受治疗性低温(TH)治疗的 NE 婴儿中 PPHN 对 crSO2 的影响:我们对2018-2022年间患有NE和PPHN与未患有PPHN的婴儿进行了回顾性评估。进行线性回归分析,评估 PPHN 对 crSO2 和 MRI 总分的影响,并对围产期因素进行调整:对164名婴儿进行了分析,其中19名(12%)患有PPHN,145名(88%)不患有PPHN。与非PPHN婴儿相比,PPHN婴儿在复温期间和复温后的crSO2明显更高(分别为87 ± 6 vs 80 ± 6,p = 0.001;87 ± 5 vs 80 ± 7,p = 0.PPHN婴儿在复温期间(b = 6.21,95% CI 2.37-10.04,p = 0.002)和复温后(b = 8.60,95% CI 2.28-14.91,p = 0.009)的MRI总评分[7(2-19) vs 1(0-3),p 2]明显更高,而MRI总评分(b = 7.42,95% CI 4.88-9.95,p 结论:PPHN与较高的crRNA相关:PPHN与复温期间和复温后较高的crSO2以及较差的脑磁共振成像评分有关,表明PPHN对接受TH治疗的NE婴儿的脑损伤有显著影响:新生儿脑病(NE)合并持续性肺动脉高压(PPHN)的婴儿在治疗性低温(TH)的复温期和复温后的脑氧饱和度明显高于无PPHN的婴儿。在接受治疗性低温的 NE 婴儿中,PPHN 与脑损伤有关。对患有 NE 和 PPHN 的婴儿进行脑氧合监测有助于发现不良后果风险较高的婴儿。
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引用次数: 0
Model-based characterization of total serum bilirubin dynamics in preterm infants. 基于模型的早产儿血清总胆红素动态表征。
IF 3.1 3区 医学 Q1 PEDIATRICS Pub Date : 2024-11-07 DOI: 10.1038/s41390-024-03644-z
Meng Chen, Alain Beuchée, Emmanuelle Levine, Laurent Storme, Geraldine Gascoin, Alfredo I Hernández

Objectives: This study aims to characterize the age-related natural dynamics of total serum bilirubin (TSB) in preterm infants through a mathematical model and to study the model parameters as potential biomarkers for detecting associated morbidities.

Methods: We proposed an exponential decay model and applied it to each infant. Patient-specific parameters were obtained by minimizing the error between measured TSB and model output. Modeling evaluation was based on root-mean-square error (RMSE). The occurrence of high-risk clinical events was analyzed based on RMSE.

Results: In a subset of the CARESS-Premi study involving 373 preterm infants (24-32 weeks' gestation), 72 patient-specific models were fitted. RMSE ranged from 1.20 to 40.25 µmol/L, with a median [IQR] of 8.74 [4.89, 14.25] µmol/L.

Conclusions: Our model effectively characterized TSB dynamics for 72 patients, providing valuable insights from model parameters and fitting errors. To our knowledge, this is the first long-term mathematical description of natural TSB decay in preterm infants. Furthermore, the model was able to estimate the occurrence of clinical events such as necrotizing enterocolitis, as reflected by the relatively high RMSE. Future implications include the development of model-based clinical decision support systems for optimizing NICU monitoring and detecting high-risk events.

Impact: The study characterizes the natural dynamics of total serum bilirubin in preterm infants (24-32 weeks' gestation) using a patient-specific exponential decay model. The model describes patient-specific patterns of TSB evolution from day three to the first weeks, providing a median [IQR] root-mean-squared error of 8.74 [4.89, 14.25] µmol/L. Complementary to previous studies focusing on the first 72-96 h, our study emphasizes the later decay course, contributing to a comprehensive long-term characterization of the natural TSB dynamics in preterm infants. The proposed model holds potential for clinical decision support systems for the optimization of NICU monitoring and high-risk event detection.

研究目的本研究旨在通过数学模型描述早产儿血清总胆红素(TSB)与年龄相关的自然动态变化,并将模型参数作为检测相关疾病的潜在生物标志物进行研究:方法:我们提出了一个指数衰减模型,并将其应用于每个婴儿。方法:我们提出了一个指数衰减模型,并将其应用到每个婴儿身上,通过最小化测量的 TSB 与模型输出之间的误差来获得特定于患者的参数。模型评估基于均方根误差(RMSE)。根据 RMSE 分析了高风险临床事件的发生率:结果:在涉及 373 名早产儿(妊娠 24-32 周)的 CARESS-Premi 研究子集中,拟合了 72 个患者特异性模型。RMSE介于1.20至40.25 µmol/L之间,中位数[IQR]为8.74 [4.89, 14.25] µmol/L:我们的模型有效地描述了 72 例患者的 TSB 动态变化,从模型参数和拟合误差中提供了有价值的见解。据我们所知,这是首个对早产儿 TSB 自然衰减的长期数学描述。此外,该模型还能估计出坏死性小肠结肠炎等临床事件的发生率,这一点从相对较高的 RMSE 可以看出。未来的意义包括开发基于模型的临床决策支持系统,以优化新生儿重症监护室的监测和检测高风险事件:该研究利用患者特异性指数衰减模型描述了早产儿(妊娠 24-32 周)血清总胆红素的自然动态特征。该模型描述了早产儿血清总胆红素从第三天到最初几周的演变规律,其中位数[IQR]均方根误差为 8.74 [4.89, 14.25] µmol/L。我们的研究与以往侧重于前 72-96 小时的研究互为补充,强调了后期的衰减过程,有助于全面长期地描述早产儿 TSB 的自然动态变化。所提出的模型有望用于临床决策支持系统,以优化新生儿重症监护室的监测和高风险事件的检测。
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引用次数: 0
Perinatal stroke and neonatal hypoxic-ischemic encephalopathy co-occur: role of intrapartum events. 围产期中风与新生儿缺氧缺血性脑病并发:产时事件的作用。
IF 3.1 3区 医学 Q1 PEDIATRICS Pub Date : 2024-11-07 DOI: 10.1038/s41390-024-03710-6
Thiviya Selvanathan, Steven P Miller
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引用次数: 0
Can pathophysiological lung function markers guide the use of postnatal corticosteroids for bronchopulmonary dysplasia? 病理生理学肺功能标志物能否指导使用产后皮质类固醇治疗支气管肺发育不良?
IF 3.1 3区 医学 Q1 PEDIATRICS Pub Date : 2024-11-07 DOI: 10.1038/s41390-024-03682-7
T'ng C Kwok, Brett J Manley, Charles C Roehr, Arun Sett
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引用次数: 0
Cerebral near-infrared spectroscopy guided neonatal intensive care management for the preterm infant. 大脑近红外光谱引导早产儿新生儿重症监护管理。
IF 3.1 3区 医学 Q1 PEDIATRICS Pub Date : 2024-11-07 DOI: 10.1038/s41390-024-03649-8
Adelina Pellicer, Willem de Boode, Eugene Dempsey, Gorm Greisen, Jonathan Mintzer, Gunnar Naulaers, Gerhard Pichler, Charles Christoph Roehr, Claudia Roll, Christoph Schwarz, Cristine Sortica da Costa, Elisabeth Kooi

Infants requiring admission to the neonatal intensive care unit (NICU) are particularly vulnerable to developing brain injury. The severity of the underlying clinical conditions and the complexity of care call for continuous, cot-side, non-invasive monitoring tools. Near-infrared spectroscopy (NIRS) measures the regional tissue oxygen saturation of hemoglobin (rStO2) and provides continuous information on the net-result of several factors. Cerebral rStO2 correlates with echocardiography-derived measures of blood flow. Cerebral fractional tissue oxygen extraction provides information on the balance between oxygen supply and demand and can be continuously derived from the combined use of cerebral rStO2 and arterial oxygen saturation. Information on cerebral blood flow autoregulatory capacity can be obtained from combining cerebral rStO2 and invasive blood pressure monitoring by appropriate software. Cerebral rStO2 provides real-time, end-organ information on perfusion-oxygenation, and when interpreted in the clinical context based on pathophysiological principles may be used as a help to guide interventions in the NICU. In this review we will discuss how to optimize NIRS monitoring for application in the NICU, with a particular focus on the preterm infant. IMPACT: Near-infrared spectroscopy (NIRS) provides cot-side, real-time information on blood and oxygen supply to the brain. Therefore, it is a valuable tool to better understand the pathophysiology underlaying disease processes. Current evidence suggests that NIRS-guided treatment in extremely preterm infants during transitional circulation does not improve clinical outcomes. Specific training is needed to maximize potential performance. Pathophysiological interpretation of cerebral NIRS data in the given clinical context may help in decision-making. Appropriate use of this monitoring technique, interpreted concurrently with other routine parameters, is a potential clinical tool to guide interventions in the NICU setting.

需要入住新生儿重症监护室(NICU)的婴儿特别容易发生脑损伤。由于潜在临床症状的严重性和护理的复杂性,需要在婴儿床边使用连续、无创的监测工具。近红外光谱(NIRS)可测量区域组织血红蛋白氧饱和度(rStO2),并提供有关多种因素净结果的连续信息。大脑 rStO2 与超声心动图得出的血流测量值相关。脑组织氧萃取分数可提供氧气供需平衡的信息,并可通过结合使用脑 rStO2 和动脉血氧饱和度持续得出。通过适当的软件将大脑 rStO2 和有创血压监测相结合,可以获得脑血流自动调节能力的信息。脑 rStO2 可提供有关灌注-氧合的实时末梢器官信息,如果根据病理生理学原理在临床环境中进行解释,则有助于指导新生儿重症监护室的干预措施。在本综述中,我们将讨论如何优化 NIRS 监测在新生儿重症监护室中的应用,并特别关注早产儿。影响:近红外光谱(NIRS)可在婴儿床边提供有关大脑供血和供氧的实时信息。因此,它是更好地了解疾病过程的病理生理学的宝贵工具。目前的证据表明,在过渡循环期间对极早产儿进行 NIRS 指导治疗并不能改善临床预后。需要进行专门的培训,以最大限度地发挥潜在的性能。在特定的临床背景下,对脑近红外成像数据进行病理生理学解释有助于做出决策。适当使用这种监测技术,并与其他常规参数同时解读,是指导新生儿重症监护室干预的潜在临床工具。
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引用次数: 0
Wearable biosensors for pediatric hospitals: a scoping review. 用于儿科医院的可穿戴生物传感器:范围综述。
IF 3.1 3区 医学 Q1 PEDIATRICS Pub Date : 2024-11-07 DOI: 10.1038/s41390-024-03693-4
Areum Hyun, Mari Takashima, Stephanie Hall, Leonard Lee, Mitchell Dufficy, Halley Ruppel, Amanda Ullman

As wearable biosensors are increasingly used in healthcare settings, this review aimed to identify the types of wearable biosensors used for neonate and pediatric patients and how these biosensors were clinically evaluated. A literature search was conducted using PubMed, CINAHL, Embase, Web of Science, and Cochrane. The studies published between January 2010 and February 2024 were included. Descriptive statistics were used to present counts and percentages of types, locations, clinical evaluation methods, and their results. Seventy-nine studies were included. 104 wearable sensors and 40 devices were identified. The most common type of biosensor was optoelectrical sensors (n = 40, 38.5%), and used to measure heart rate (n = 22, 19.0%). The clinical evaluation was tested by a combination of validity (n = 68, 86.1%) and reliability (n = 14, 17.7%). Only two-thirds of the wearable devices were validated or reported acceptable reliability. The majority of the biosensor studies (n = 51, 64.5%) did not report any complications related to wearable biosensors. The current literature has gaps regarding clinical evaluation and safety of wearable biosensor devices with interchangeable use of validity and reliability terms. There is a lack of comprehensive reporting on complications, highlighting the need for standardized guidelines in the clinical evaluation of biosensor medical devices. IMPACT: The most common types of biosensors in pediatric settings were optoelectrical sensors and electrical sensors. Only two-thirds of the wearable devices were validated or reported acceptable reliability, and more than half of the biosensor studies did not report whether they assessed any complications related to wearable biosensors. This review discovered significant gaps in safety and clinical validation reporting, emphasizing the need for standardized guidelines. The findings advocate for improved reporting clinical validation processes to enhance the safety of wearable biosensors in pediatric care.

随着可穿戴生物传感器越来越多地应用于医疗机构,本综述旨在确定用于新生儿和儿科患者的可穿戴生物传感器的类型,以及如何对这些生物传感器进行临床评估。我们使用 PubMed、CINAHL、Embase、Web of Science 和 Cochrane 进行了文献检索。纳入的研究发表于 2010 年 1 月至 2024 年 2 月。研究采用描述性统计方法来显示类型、地点、临床评估方法及其结果的计数和百分比。共纳入 79 项研究。确定了 104 种可穿戴传感器和 40 种设备。最常见的生物传感器类型是光电传感器(40 个,占 38.5%)和用于测量心率的传感器(22 个,占 19.0%)。临床评估由有效性(68 人,占 86.1%)和可靠性(14 人,占 17.7%)两部分组成。只有三分之二的可穿戴设备通过了验证或报告了可接受的可靠性。大多数生物传感器研究(n = 51,64.5%)未报告任何与可穿戴生物传感器相关的并发症。目前的文献在可穿戴生物传感器设备的临床评估和安全性方面存在空白,有效性和可靠性的术语可以互换使用。目前缺乏有关并发症的全面报告,这凸显了在生物传感器医疗设备的临床评估方面制定标准化指南的必要性。影响:儿科环境中最常见的生物传感器类型是光电传感器和电传感器。只有三分之二的可穿戴设备经过验证或报告了可接受的可靠性,超过一半的生物传感器研究没有报告是否评估了与可穿戴生物传感器相关的并发症。本次综述发现了安全性和临床验证报告方面的重大差距,强调了制定标准化指南的必要性。研究结果提倡改进临床验证报告流程,以提高可穿戴生物传感器在儿科护理中的安全性。
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引用次数: 0
Physician perspectives on communication quality in pediatric care. 医生对儿科护理中沟通质量的看法。
IF 3.1 3区 医学 Q1 PEDIATRICS Pub Date : 2024-11-07 DOI: 10.1038/s41390-024-03715-1
Katherine F Guttmann, Gabriella Raviv, Andrea S Weintraub

Background: We aimed to explore physician perspectives on communication quality across pediatric contexts.

Methods: We conducted semi-structured interviews over a 4-month period. Purposive sampling was conducted to ensure a broad sampling of pediatricians from multiple subspecialties and practice settings. Interviews were conducted until thematic saturation was reached. An interview guide was created based on existing literature. Interviews were transcribed and analyzed for key themes.

Results: Eleven pediatricians enrolled in our study. Following thematic analysis, results were organized into four primary themes: Communication Education, High Quality Communication; Low Quality Communication; and Communication Factors and Barriers. Participants prioritized information transfer as a key aspect of communication quality. They identified communication quality as having wellness implications for clinicians.

Conclusion: Participants prioritize information transfer and state that clinicians often neglect bidirectional information exchange. Participants often lacked formal communication skills training which may make it difficult to navigate common barriers such as language and cultural differences, lack of time, and interprofessional dysfunction. Formal communication skills training may help overcome challenges and may enhance physician wellness while improving patient care.

Impact: While the importance of clinician-parent communication in pediatric settings has been established, little is known about provider perceptions of communication quality. Participants identified information transfer as a key aspect of communication quality, often neglecting bidirectional information exchange. Participants often lacked formal communication skills training which may make it difficult to navigate common barriers such as language and cultural differences, lack of time, and interprofessional dysfunction. Formal communication skills training may help with these challenges and may enhance physician wellness while improving patient care. More work is needed to explore the impact of communication skills training on each of these factors.

背景:我们的目的是探讨医生对不同儿科环境下沟通质量的看法:我们进行了为期 4 个月的半结构化访谈。我们进行了有目的的抽样,以确保从多个亚专科和实践环境中广泛抽取儿科医生。访谈一直进行到主题饱和为止。根据现有文献编制了访谈指南。对访谈内容进行转录并分析关键主题:11 名儿科医生参加了我们的研究。经过专题分析,研究结果被归纳为四个主要专题:交流教育、高质量交流、低质量交流以及交流因素和障碍。参与者认为信息传递是沟通质量的一个重要方面。他们认为沟通质量对临床医生的健康有影响:与会者将信息传递放在首位,并指出临床医生经常忽视双向信息交流。参与者通常缺乏正规的沟通技能培训,这可能会导致他们难以克服语言和文化差异、时间不足以及跨专业功能障碍等常见障碍。正规的沟通技能培训有助于克服这些挑战,并在改善患者护理的同时提高医生的健康水平:虽然儿科临床医生与家长沟通的重要性已经得到证实,但人们对提供者对沟通质量的看法却知之甚少。参与者认为信息传递是沟通质量的一个重要方面,但往往忽视了双向信息交流。参与者往往缺乏正规的沟通技巧培训,这可能会使他们难以克服语言和文化差异、时间不足和跨专业功能障碍等常见障碍。正规的沟通技巧培训可能有助于应对这些挑战,并在改善患者护理的同时提高医生的健康水平。还需要做更多的工作来探索沟通技巧培训对上述各项因素的影响。
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引用次数: 0
Oxytocin receptor epigenetics: from biomarker to potential therapeutic target. 催产素受体表观遗传学:从生物标志物到潜在治疗靶点。
IF 3.1 3区 医学 Q1 PEDIATRICS Pub Date : 2024-11-07 DOI: 10.1038/s41390-024-03686-3
Heather H Burris, Lauren K White, Rebecca Waller, Barbara H Chaiyachati
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引用次数: 0
Dietary intake and sleep in late childhood - do shorter children have distinct patterns? 儿童后期的饮食摄入和睡眠--身材矮小的儿童是否有独特的模式?
IF 3.1 3区 医学 Q1 PEDIATRICS Pub Date : 2024-11-06 DOI: 10.1038/s41390-024-03678-3
Naama Fisch-Shvalb, Maya Zur, Liora Lazar, Raanan Shamir, Moshe Phillip, Michal Yackobovitch-Gavan

Background: The exceptional growth rate during adolescence demands increased dietary intake. We aimed to compare diet and lifestyle of pre-adolescents with height and weight below the 10th percentile, with those of pre-adolescents of higher height and weight.

Methods: This case-control study included healthy pre-pubertal girls (≥9 years) and boys (≥10 years). The case groups included 31 girls and 32 boys with height and weight <10th percentile, and weight percentile ≤height percentile. The control groups comprised 24 girls and 24 boys, with height ≥25th percentile, BMI 5th-85th percentiles. Participants completed 3-day food diaries and lifestyle-related questionnaires.

Results: Energy intake/estimated-requirement and protein/body-weight were comparable in the case and control groups, both in boys and girls. In boys, fat (P = 0.050) and carbohydrate (P ≤ 0.001) intakes/body-weight were higher in the case group versus controls; and iron (P < 0.001), zinc (P = 0.005), vitamin A (P < 0.001), calcium (P = 0.005), and vitamin C (P = 0.034) consumption were lower. In girls, carbohydrate/body-weight was higher in the case group compared to controls (P = 0.007); micronutrient intake was comparable, and lower than recommended. Compared to controls, short and thin boys reported less sleep during weekdays (P < 0.001).

Conclusions: Relatively short, thin pre-adolescents may have distinct dietary intake and sleeping patterns compared to taller peers, especially boys.

Impact: Nutrition is a key environmental determinant of childhood growth. Not much is known about late nutritional impact on growth in children whose anthropometric indices are below the 10th percentile. We compared food diaries and lifestyle questionnaires of pre-pubertal pre-adolescents with height <10th percentiles and weight≤height for age and sex, with those of peers with indices in higher percentiles. We found distinct differences in micronutrient intakes and sleep duration in the shorter boys, but no energy deficit in either sex. We suggest that diet and lifestyle parameters should be evaluated in children with relatively low anthropometric indices, to ensure optimal growth.

背景:青春期的生长速度非常快,需要增加饮食摄入量。我们旨在比较身高和体重低于第 10 百分位数的青春期前儿童与身高和体重较高的青春期前儿童的饮食和生活方式:这项病例对照研究包括青春期前的健康女孩(≥9 岁)和男孩(≥10 岁)。病例组包括 31 名女孩和 32 名男孩,他们的身高和体重均有结果:在病例组和对照组中,男孩和女孩的能量摄入量/估计需要量和蛋白质/体重相当。在男孩中,病例组的脂肪摄入量(P = 0.050)和碳水化合物摄入量(P ≤ 0.001)/体重高于对照组;铁的摄入量(P = 0.001)和碳水化合物摄入量(P ≤ 0.001)/体重高于对照组:与身材高大的同龄人(尤其是男孩)相比,相对矮小、瘦弱的青春期前儿童可能有不同的饮食摄入和睡眠模式:影响:营养是决定儿童生长的关键环境因素。对于人体测量指数低于第 10 百分位数的儿童,人们对其后期营养对生长的影响知之甚少。我们比较了青春期前青少年的食物日记和生活方式调查问卷,结果显示,身高低于第 10 百分位数的青少年的食物日记和生活方式调查问卷均高于身高低于第 10 百分位数的青少年。
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引用次数: 0
Mutation spectrum and genotype-phenotype correlation of pediatric patients with methylmalonic acidemia. 甲基丙二酸血症儿科患者的突变谱和基因型与表型的相关性。
IF 3.1 3区 医学 Q1 PEDIATRICS Pub Date : 2024-11-05 DOI: 10.1038/s41390-024-03687-2
Fengying Lu, Bin Zhang, Yuqi Yang, Ye Shi, Fangxiu Zheng, Qin Zhou, Yingping Chen, Lingna Zhou, Bin Yu

Background: MMA incidence is significantly greater in China than in the rest of the world, but the mutation spectrum of MMA in China has not yet been mapped.

Methods: We summarized published MMA-related articles and conducted a systematic meta-analysis of the literature.

Results: We analyzed the gene variants information of 926 pediatric MMA patients in China; 517 were children with combined MMA, and 409 were children with isolated MMA. Almost all combined MMA cases were caused by MMACHC gene mutations (cblC-type). The c.609G>A variation was the most common in cblC-type children, accounting for 43.01%, followed by c.658_660delAAG, c.482G>A, c.80A>G, and c.394C>T variations. Mut-type MMA patients accounted for 98.8% (404/409) of all isolated MMA cases. The variant MMUT c.729_730insTT accounted for 10.30% (80/802) of all variants and was the most common variant in mut-type children, followed by c.323G>A and c.1106G>A.

Conclusions: Our study summarized and characterized the mutation spectrum of Chinese pediatric patients with MMACHC and MMUT variants, and we also analyzed the relationships between common variants, onset time, and clinical phenotype. These findings will contribute to understanding the phenotypic characteristics and overall pathogenesis of MMA patients, supporting the goal of gene therapy.

Impact: The incidence of methylmalonic academia (MMA) in China is significantly greater than that in the rest of the world, but the mutation spectrum of MMA in China has not yet been mapped. In this paper, for the first time, we investigated hot-spot gene variants in MMA patients in China and comprehensively described the MMA gene mutation spectrum of the Chinese population. We explored the relationship between MMA genotype and clinical phenotype in patients, providing a basis for family genetic counseling, prenatal diagnosis, and newborn screening.

背景:中国的 MMA 发病率明显高于世界其他地区,但中国的 MMA 基因突变谱尚未绘制:中国的MMA发病率明显高于世界其他地区,但中国的MMA突变谱尚未绘制:方法:我们总结了已发表的MMA相关文章,并对文献进行了系统的荟萃分析:我们分析了中国926例小儿MMA患者的基因变异信息,其中517例为合并型MMA患儿,409例为孤立型MMA患儿。几乎所有合并型MMA病例都是由MMACHC基因突变(cblC型)引起的。c.609G>A变异在cblC型儿童中最常见,占43.01%,其次是c.658_660delAAG、c.482G>A、c.80A>G和c.394C>T变异。变异型 MMA 患者占所有孤立 MMA 病例的 98.8%(404/409)。变异MMUT c.729_730insTT占所有变异的10.30%(80/802),是突变型儿童中最常见的变异,其次是c.323G>A和c.1106G>A:我们的研究总结并描述了中国儿童MMACHC和MMUT变异患者的变异谱,还分析了常见变异、发病时间和临床表型之间的关系。这些发现将有助于了解甲基丙二酸盐病患者的表型特征和整体发病机制,支持基因治疗的目标:影响:中国甲基丙二酸血症(MMA)的发病率明显高于世界其他地区,但中国MMA的变异谱尚未绘制。本文首次研究了中国 MMA 患者的热点基因变异,全面描述了中国人群的 MMA 基因突变谱。我们探讨了MMA基因型与患者临床表型之间的关系,为家庭遗传咨询、产前诊断和新生儿筛查提供了依据。
{"title":"Mutation spectrum and genotype-phenotype correlation of pediatric patients with methylmalonic acidemia.","authors":"Fengying Lu, Bin Zhang, Yuqi Yang, Ye Shi, Fangxiu Zheng, Qin Zhou, Yingping Chen, Lingna Zhou, Bin Yu","doi":"10.1038/s41390-024-03687-2","DOIUrl":"https://doi.org/10.1038/s41390-024-03687-2","url":null,"abstract":"<p><strong>Background: </strong>MMA incidence is significantly greater in China than in the rest of the world, but the mutation spectrum of MMA in China has not yet been mapped.</p><p><strong>Methods: </strong>We summarized published MMA-related articles and conducted a systematic meta-analysis of the literature.</p><p><strong>Results: </strong>We analyzed the gene variants information of 926 pediatric MMA patients in China; 517 were children with combined MMA, and 409 were children with isolated MMA. Almost all combined MMA cases were caused by MMACHC gene mutations (cblC-type). The c.609G>A variation was the most common in cblC-type children, accounting for 43.01%, followed by c.658_660delAAG, c.482G>A, c.80A>G, and c.394C>T variations. Mut-type MMA patients accounted for 98.8% (404/409) of all isolated MMA cases. The variant MMUT c.729_730insTT accounted for 10.30% (80/802) of all variants and was the most common variant in mut-type children, followed by c.323G>A and c.1106G>A.</p><p><strong>Conclusions: </strong>Our study summarized and characterized the mutation spectrum of Chinese pediatric patients with MMACHC and MMUT variants, and we also analyzed the relationships between common variants, onset time, and clinical phenotype. These findings will contribute to understanding the phenotypic characteristics and overall pathogenesis of MMA patients, supporting the goal of gene therapy.</p><p><strong>Impact: </strong>The incidence of methylmalonic academia (MMA) in China is significantly greater than that in the rest of the world, but the mutation spectrum of MMA in China has not yet been mapped. In this paper, for the first time, we investigated hot-spot gene variants in MMA patients in China and comprehensively described the MMA gene mutation spectrum of the Chinese population. We explored the relationship between MMA genotype and clinical phenotype in patients, providing a basis for family genetic counseling, prenatal diagnosis, and newborn screening.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583845","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}
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Pediatric Research
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