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Response to Letter "Therapeutic Hypothermia for Neonatal Encephalopathy in Low-Resource Settings: Methodological Inaccuracies and Inconsistencies in the Latest Systematic Review". 对“低资源环境下治疗性低温治疗新生儿脑病:最新系统综述中方法的不准确和不一致”的回复。
IF 2.5 3区 医学 Q1 PEDIATRICS Pub Date : 2023-01-01 DOI: 10.1159/000527970
Ioannis Bellos, Aakash Pandita
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引用次数: 0
Magnetic Resonance Biomarkers and Neurological Outcome of Infants with Mild Hypoxic-Ischaemic Encephalopathy Who Progress to Moderate Hypoxic-Ischaemic Encephalopathy. 从轻度缺氧缺血性脑病发展为中度缺氧缺血性脑病的婴儿的磁共振生物标志物和神经预后
IF 2.5 3区 医学 Q1 PEDIATRICS Pub Date : 2023-01-01 DOI: 10.1159/000527871
Paolo Montaldo, Simona Puzone, Elisabetta Caredda, Francesca Galdo, Umberto Pugliese, Anna Maietta, Serena Ascione, Mario Diplomatico, Ferdinando Spagnuolo, Vincenzina Roma, Massimiliano De Vivo, Mauro Carpentieri, Sabino Moschella, Lucio Giordano, Alessandra D'Amico, Carlo Capristo, Laura Travan, Giovanni Chello, Emanuele Miraglia Del Giudice, Mario Cirillo

Background: There is increasing concern that infants with mild hypoxic-ischaemic encephalopathy (HIE) may develop seizures and progress to moderate HIE beyond the therapeutic window for cooling.

Objective: The aim of this study was to examine the effect of therapeutic hypothermia on magnetic resonance imaging (MRI) biomarkers and neurological outcomes in infants with mild HIE and seizures within 24 h after birth.

Methods: This study shows an observational cohort study on 366 (near)-term infants with mild HIE and normal amplitude-integrated electroencephalography background.

Results: Forty-one infants showed progression (11.2%); 29/41 (70.7%) were cooled. Infants with progression showed cerebral metabolite perturbations and higher white matter injury scores compared to those without in both cooled and non-cooled groups (p = 0.001, p = 0.02). Abnormal outcomes were seen in 5/12 (42%) non-cooled and 7/29 (24%) cooled infants with progression (p = 0.26).

Conclusions: Early biomarkers are needed to identify infants with mild HIE at risk of progression. Mild HIE infants with progression showed a higher incidence of brain injury and abnormal outcomes.

背景:越来越多的人担心,患有轻度缺氧缺血性脑病(HIE)的婴儿可能会发生癫痫发作,并在冷却治疗窗口后发展为中度HIE。目的:本研究的目的是研究治疗性低温对出生后24小时内患有轻度HIE和癫痫发作的婴儿的磁共振成像(MRI)生物标志物和神经学预后的影响。方法:本研究对366例(近)足月婴儿进行了观察性队列研究,这些婴儿患有轻度HIE,且振幅综合脑电图背景正常。结果:41例患儿出现进展(11.2%);29/41(70.7%)被冷却。在冷却组和非冷却组中,有进展的婴儿表现出脑代谢物紊乱和更高的白质损伤评分(p = 0.001, p = 0.02)。5/12(42%)未降温婴儿和7/29(24%)降温婴儿出现异常结局(p = 0.26)。结论:需要早期的生物标志物来识别有进展风险的轻度HIE婴儿。进展的轻度HIE婴儿表现出更高的脑损伤发生率和异常结局。
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引用次数: 1
Effect of Early Erythropoietin on Retinopathy of Prematurity: A Stratified Meta-Analysis. 早期红细胞生成素对早产视网膜病变的影响:分层荟萃分析。
IF 2.5 3区 医学 Q1 PEDIATRICS Pub Date : 2023-01-01 Epub Date: 2023-06-27 DOI: 10.1159/000530126
Hendrik S Fischer, Nora J Reibel, Christoph Bührer, Christof Dame

Background: Recombinant human erythropoietin (rhEPO) lost its role in minimizing red blood cell transfusion in very preterm infants after it had been associated with severe retinopathy of prematurity (ROP). Previous systematic reviews did not stratify ROP by gestation and birth weight (BW).

Objectives: The aim of this study was to investigate the effect of early prophylactic rhEPO on ROP in a stratified meta-analysis of randomized controlled trials (RCTs).

Methods: The databases EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched in January 2022 and complemented by citation searching. RCTs comparing early rhEPO treatment with no treatment or placebo were selected if they were published in a peer-reviewed journal and reported ROP outcomes. Previously unpublished data were requested from the study authors to allow stratified analyses by gestational age (GA) and BW. Data were extracted and analyzed using the standard methods of the Cochrane Neonatal Review Group. Pre-specified outcomes were "ROP stage ≥3" (primary outcome) and "any ROP."

Results: Fourteen RCTs, comprising 2,040 infants of <29 weeks of GA, were included for meta-analysis. Data syntheses showed no effects of rhEPO on ROP stage ≥3 or on any ROP, neither in infants of <29 weeks GA, nor in infants of <1,000 g BW, nor in any GA strata. The risk ratio (95% confidence interval) for ROP stage ≥3 in infants of <29 weeks of GA was 1.13 (0.84, 1.53), p = 0.41 (quality of evidence: moderate).

Conclusions: The present meta-analysis detected no effects of early rhEPO on ROP in any comparison, but most stratified analyses were limited by low statistical power.

背景:重组人红细胞生成素(rhEPO)在与严重的早产儿视网膜病变(ROP)相关后,在极早产儿中失去了最大限度减少红细胞输注的作用。先前的系统综述没有根据妊娠和出生体重(BW)对ROP进行分层。目的:本研究的目的是在随机对照试验(RCTs)的分层荟萃分析中研究早期预防性rhEPO对ROP的影响。方法:数据库EMBASE、MEDLINE、,2022年1月检索了Cochrane对照试验中央登记册,并辅以引文检索。如果在同行评审期刊上发表并报告了ROP结果,则选择比较早期rhEPO治疗与未治疗或安慰剂的随机对照试验。研究作者要求提供以前未发表的数据,以便按胎龄(GA)和体重进行分层分析。数据采用Cochrane新生儿审查小组的标准方法进行提取和分析。预先指定的结果为“ROP≥3期”(主要结果)和“任何ROP”。结果:14项随机对照试验,包括2040名<;29周的GA纳入荟萃分析。数据综合显示,rhEPO对ROP≥3期或任何ROP均无影响,<;29周GA,<;1000g BW,也不存在于任何GA地层中。<;29周的GA为1.13(0.84,1.53),p=0.41(证据质量:中等)。结论:本荟萃分析在任何比较中都没有发现早期rhEPO对ROP的影响,但大多数分层分析都受到低统计能力的限制。
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引用次数: 1
Associations between Early Thyroid-Stimulating Hormone Levels and Morbidities in Extremely Preterm Neonates. 极早产儿早期促甲状腺激素水平与发病率的关系。
IF 2.5 3区 医学 Q1 PEDIATRICS Pub Date : 2023-01-01 DOI: 10.1159/000528817
Li-Wen Chen, Chi-Hsiang Chu, Yung-Chieh Lin, Hsiao-Jan Chen, Shu-Min Kao, Chao-Ching Huang

Introduction: High-end cutoffs of thyroid-stimulating hormone (TSH) have been emphasized for hypothyroidism therapy in extremely preterm infants, but the significance of low TSH levels remains unknown. This study hypothesized that the spectrum of TSH levels by newborn screening after birth signifies specific morbidities in extremely preterm neonates.

Methods: The multicenter population cohort analyzed 434 extremely preterm neonates receiving TSH screening at 24-96 h of age in 2008-2019. Neonates were categorized by blood TSH levels into group 1: TSH <0.5 µU/mL, group 2: 0.5 ≤ TSH <2 µU/mL, group 3: 2 ≤ TSH <4 µU/mL, and group 4: TSH ≥4 µU/mL. Neonatal morbidities were categorized using the modified Neonatal Therapeutic Intervention Scoring System.

Results: The four groups differed in gestational age, birth weight, and the postnatal age at blood sampling so did the proportions of mechanical ventilation usage (p = 0.01), hypoxic respiratory failure (p = 0.005), high-grade intraventricular hemorrhage (p = 0.007), and periventricular leukomalacia (p = 0.048). Group 1 had higher severity scores for respiratory distress syndrome (RDS; effect size 0.39 [95% confidence interval [CI]: 0.18-0.59]) and brain injury (0.36 [0.15-0.57]) than group 2, which remained significant after adjusting for gestational age, birth weight, dopamine usage, and the postnatal age at TSH screening (RDS: mean + 0.45 points [95% CI: 0.11-0.79]; brain injury: +0.32 [0.11-0.54]).

Conclusions: Low TSH levels in extremely preterm neonates are associated with severe RDS and brain injuries. Studies recruiting more neonates with complete thyroid function data are necessary to understand central-peripheral interactions of the hypothalamic-pituitary-thyroid axis.

高端促甲状腺激素(TSH)被强调用于极早产儿甲状腺功能减退的治疗,但低TSH水平的意义尚不清楚。本研究假设,出生后新生儿筛查的TSH水平谱表明极早产儿的特定发病率。方法:对2008-2019年接受TSH筛查的434例24-96小时极度早产儿进行多中心人群队列分析。结果:四组在胎龄、出生体重、产后采血年龄、机械通气使用比例(p = 0.01)、缺氧性呼吸衰竭(p = 0.005)、重度脑室内出血(p = 0.007)、脑室周围白质软化(p = 0.048)等方面存在差异。1组呼吸窘迫综合征(RDS)严重程度评分较高;效应值为0.39[95%可信区间[CI]: 0.18-0.59])和脑损伤(0.36[0.15-0.57]),在调整胎龄、出生体重、多巴胺使用和TSH筛查时的出生后年龄(RDS:平均+ 0.45点[95% CI: 0.11-0.79])后仍然显著;脑损伤:+0.32[0.11-0.54])。结论:极早产儿低TSH水平与严重RDS和脑损伤有关。为了了解下丘脑-垂体-甲状腺轴的中枢-外周相互作用,有必要进行更多具有完整甲状腺功能数据的新生儿的研究。
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引用次数: 0
Patterns of Respiratory Support by Gestational Age in Very Preterm Infants. 极早产儿不同胎龄的呼吸支持模式。
IF 2.5 3区 医学 Q1 PEDIATRICS Pub Date : 2023-01-01 DOI: 10.1159/000527641
Mikael Norman, Baldvin Jonsson, Jonas Söderling, Lars J Björklund, Stellan Håkansson

Introduction: A detailed understanding of respiratory support patterns in preterm infants is lacking. The aim was to explore and visualize this practice in Sweden.

Methods: Preterm infants with gestational ages of 22-31 weeks, admitted to neonatal units reporting daily to the Swedish Neonatal Quality Register and discharged alive in November 2015-April 2022, were included in this descriptive cohort study. Proportions receiving mechanical ventilation, noninvasive support, or supplemental oxygen were calculated and graphically displayed for each gestational week and postnatal day (range 0-97) up to hospital discharge or 36 weeks of postmenstrual age.

Results: Respiratory support in 148,515 days of care (3,368 infants; 54% males; median [interquartile range] birthweight = 1,215 [900-1,525] g) was evaluated. Trajectories showed distinct nonlinear patterns for each category of respiratory support, but differences in respiratory support over the gestational age range were linear: the proportion of infants on mechanical ventilation decreased by -11.7 to -7.3% (variability in estimates related to the postnatal day chosen for regression analysis) for each week higher gestational age (r = -0.99 to -0.87, p ≤ 0.001). The corresponding proportions of infants with supplemental oxygen decreased by -12.4% to -4.5% for each week higher gestational age (r = -0.98 to -0.94, p < 0.001). At 36 weeks of postmenstrual age, dependencies on mechanical ventilation, noninvasive support, and supplemental oxygen varied from 3%, 84%, and 94% at 22 weeks to 0%, 3%, and 5% at 31 weeks of gestational age, respectively.

Conclusions: Respiratory support patterns in very preterm infants follow nonlinear, gestational age-specific postnatal trajectories in a dose-response-related fashion.

前言:缺乏对早产儿呼吸支持模式的详细了解。目的是探索和可视化瑞典的这种做法。方法:2015年11月至2022年4月期间,每日向瑞典新生儿质量登记处(Swedish neonatal Quality Register)报告的22-31周的新生儿入住新生儿病房并存活出院的早产儿纳入了这项描述性队列研究。计算每个妊娠周和产后(范围0-97)至出院或经后36周接受机械通气、无创支持或补充氧气的比例,并以图形显示。结果:在148,515天的护理中获得呼吸支持(3,368名婴儿;男性54%;评估出生体重中位数[四分位数间距]= 1,215 [900-1,525]g)。每种呼吸支持类别的轨迹显示出明显的非线性模式,但在胎龄范围内呼吸支持的差异是线性的:胎龄每高一周,机械通气婴儿的比例下降- 11.7%至-7.3%(与选择用于回归分析的出生后天数相关的变异性)(r = -0.99至-0.87,p≤0.001)。每高胎龄一周,补充氧气的婴儿相应比例下降-12.4% ~ -4.5% (r = -0.98 ~ -0.94, p < 0.001)。经后36周时,对机械通气、无创支持和补充氧的依赖分别从22周时的3%、84%和94%到31周时的0%、3%和5%。结论:极早产儿的呼吸支持模式遵循非线性的、胎龄特异性的产后轨迹,以剂量反应相关的方式。
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引用次数: 0
Neonatal Thrombocytopenia as a Presenting Finding in de novo Pyruvate Kinase Deficiency. 新生儿血小板减少是丙酮酸激酶缺乏症的一个表现。
IF 2.6 3区 医学 Q1 PEDIATRICS Pub Date : 2023-01-01 Epub Date: 2023-07-20 DOI: 10.1159/000531242
Brian M Dulmovits, K Taylor Wild, John Flibotte, Michele P Lambert, Janet Kwiatkowski, Christopher S Thom

Thrombocytopenia is a common laboratory abnormality encountered in critically ill neonates. The broad differential for thrombocytopenia, and its association with potentially severe neonatal pathology, often presents a diagnostic dilemma prompting extensive evaluation. Hemolysis due to red cell enzymopathies is a rare cause of neonatal thrombocytopenia that is typically brief and self-limiting. Here, we present a case of thrombocytopenia, refractory to transfusion, associated with anemia and hyperbilirubinemia in a neonate with pyruvate kinase deficiency (PKD) arising from compound heterozygous PKLR mutations. The nature of the thrombocytopenia in this patient created considerable diagnostic uncertainty, which was ultimately resolved by whole-exome sequencing. This case emphasizes that inherited red cell defects, such as PKD, are important to consider in cases of neonatal thrombocytopenia.

血小板减少症是危重新生儿常见的实验室异常。血小板减少症的广泛差异及其与潜在的严重新生儿病理学的相关性,往往会导致诊断困境,需要进行广泛的评估。红细胞酶病引起的溶血是新生儿血小板减少症的一种罕见原因,通常是短暂的和自限性的。在此,我们报告了一例血小板减少症,输血难治,与复合杂合PKLR突变引起的丙酮酸激酶缺乏症(PKD)新生儿贫血和高胆红素血症相关。该患者血小板减少症的性质造成了相当大的诊断不确定性,最终通过全外显子组测序解决了这一问题。该病例强调,在新生儿血小板减少症的病例中,遗传性红细胞缺陷,如PKD,是重要的考虑因素。
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引用次数: 0
Microstructural Brain Development and Neurodevelopmental Outcome of Very Preterm Infants of Mothers with Gestational Diabetes Mellitus. 妊娠期糖尿病母亲的极早产儿脑微结构发育和神经发育结局。
IF 4.6 3区 医学 Q1 PEDIATRICS Pub Date : 2023-01-01 Epub Date: 2023-08-29 DOI: 10.1159/000533335
Maria Sappler, Nina Volleritsch, Marlene Hammerl, Yasmin Pellkofer, Elke Griesmaier, Elke Ruth Gizewski, Susanne Kaser, Ursula Kiechl-Kohlendorfer, Vera Neubauer

Introduction: There are data linking gestational diabetes mellitus (GDM) with adverse neurodevelopmental outcome in the offspring. We investigated the effect of GDM on microstructural brain development and neurodevelopmental outcome of very preterm infants.

Materials and methods: Preterm infants <32 gestational weeks of mothers with GDM obtained cerebral magnetic resonance imaging (MRI) including diffusion-tensor imaging at term-equivalent age. For every infant, two gestational age-, sex-, and MRI scanner type-matched controls were included. Brain injury was assessed and fractional anisotropy (FA) and apparent diffusion coefficient (ADC) measured in 14 defined cerebral regions. Neurodevelopmental outcome was quantified at the corrected age of 24 months using the Bayley Scales of Infant Development.

Results: We included 47 infants of mothers with GDM and 94 controls. There were no differences in neonatal morbidity between the groups, nor in any type of brain injury. The GDM group showed significantly higher FA values in the centrum semiovale, the posterior limb of the internal capsule and the pons bilaterally, in the corpus callosum and the right occipital white matter, as well as lower ADC values in the right centrum semiovale, the right occipital white matter and the corpus callosum. Neurodevelopmental outcome did not differ between the groups.

Conclusion: We found no impairment of brain development in GDM-exposed infants compared to matched controls, but differences in white matter microstructure in specific regions indicating an enhanced maturation. However, neurodevelopmental outcome was equal in both groups. Further studies are needed to better understand brain maturation in preterm infants exposed to GDM.

有资料表明妊娠期糖尿病(GDM)与后代的不良神经发育结局有关。我们研究了GDM对极早产儿脑微结构发育和神经发育结局的影响。材料与方法:孕32周的早产儿GDM母亲在足月等龄行脑磁共振成像(MRI),包括弥散张量成像。对于每个婴儿,包括两个胎龄,性别和MRI扫描仪类型匹配的对照。评估脑损伤,并测量14个脑区分数各向异性(FA)和表观扩散系数(ADC)。使用Bayley婴儿发育量表在校正年龄24个月时对神经发育结果进行量化。结果:我们纳入了47名患有GDM的母亲和94名对照组。两组之间的新生儿发病率没有差异,也没有任何类型的脑损伤。GDM组半瓣中央、内囊后肢和双侧桥、胼胝体和右侧枕白质FA值显著升高,右侧半瓣中央、右侧枕白质和胼胝体ADC值显著降低。两组之间的神经发育结果没有差异。结论:我们发现,与对照组相比,gdm暴露婴儿的大脑发育没有损伤,但特定区域白质微观结构的差异表明成熟程度增强。然而,两组的神经发育结果是相同的。需要进一步的研究来更好地了解暴露于GDM的早产儿的大脑成熟。
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引用次数: 0
Author's Response. 作者回复
IF 2.6 3区 医学 Q1 PEDIATRICS Pub Date : 2023-01-01 Epub Date: 2023-04-26 DOI: 10.1159/000529999
Anna Lavizzari, Chiara Veneroni
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引用次数: 0
Reply to "Oxygen Saturation Index: A Trigger for Neonatal Transfer?" 回复“氧饱和度指数:新生儿转移的触发因素?”
IF 2.5 3区 医学 Q1 PEDIATRICS Pub Date : 2023-01-01 DOI: 10.1159/000529641
Emily J J Horn-Oudshoorn, Irwin K M Reiss, Philip L J DeKoninck
Dear Editor, We appreciate the interest of Dr. Gopal and Dr. Fernandes in our studies on the use of the oxygen saturation index (OSI) as an early predictor of clinical deterioration in infants with a congenital diaphragmatic hernia (CDH). The authors propose an alternative usage of the OSI by incorporating it into assessment algorithms designed to facilitate timely transfer to higher level centers with extracorporeal membrane oxygenation (ECMO) therapy. This is an interesting suggestion, and we fully acknowledge the promising potential of OSI within such an approach, but underscore that this is particularly useful in health care systems where management of CDH infants is not centralized. Contrary to what is suggested by the authors, this is not the case for the Dutch setting, as all CDH infants are managed in two national expertise ECMO centers. Yet, in other conditions associated with hypoxic-respiratory failure, such as meconium aspiration, this indeed may be a very helpful strategy to expedite early transfer [1]. It is certainly true that most CDH infants will have arterial access, and thus OSI will not entirely replace the oxygenation index (OI), but we do want to emphasize that, in our opinion, also tertiary-care centers could profit from incorporating OSI into their management. For instance, in cases where preductal arterial blood sampling is not possible, OSI provides an interesting alternative. Also, OSI can be measured continuously and can thus potentially identify signs of clinical deterioration earlier than OI, given that the latter is a snapshot measurement that is often determined ad hoc when the clinical picture is already changing. In addition, automated analysis theoretically gives an opportunity to perform trend analysis. On the other hand, we agree that the predictive value of OSI after clinical interventions triggered by worsening or improving OSI values remains to be investigated.
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引用次数: 0
Olfactomedin-4-Positive Neutrophils in Neonates: Link to Systemic Inflammation and Bronchopulmonary Dysplasia. 新生儿中Olfactomedin-4阳性中性粒细胞:与全身炎症和支气管肺发育不良的联系
IF 2.5 3区 医学 Q1 PEDIATRICS Pub Date : 2023-01-01 Epub Date: 2022-12-22 DOI: 10.1159/000527902
Faris N Al Gharaibeh, Kristalynn M Kempton, Matthew N Alder

Introduction: Little is known about the interplay between neutrophil heterogeneity in neonates in health and disease states. Olfactomedin-4 (OLFM4) marks a subset of neutrophils that have been described in adults and pediatric patients but not neonates, and this subset is thought to play a role in modulating the host inflammatory response.

Methods: This is a prospective cohort of neonates who were born between June 2020 and December 2021 at the University of Cincinnati Medical Center NICU. Olfactomedin-4-positive (OLFM4+) neutrophils were identified in the peripheral blood using flow cytometry.

Results: OLFM4+ neutrophil percentage was not correlated with gestational age or developmental age. Neonates with sepsis had a higher percentage than those without the condition, 66.9% (IQR 24.3-76.9%) versus 21.5% (IQR 10.6-34.7%), respectively, p = 0.0003. At birth, a high percentage of OLFM4+ neutrophils was associated with severe chorioamnionitis at 49.1% (IQR 28.2-61.5%) compared to those without it at 13.7% (IQR 7.7-26.3%), p < 0.0001. Among neonates without sepsis, the percentages of OLFM4+ neutrophils were lower in the BPD/early death group compared to those without BPD, 11.8% (IQR 6.3-29.0%) versus 32.5% (IQR 18.5-46.1%), p = 0.003, and this retained significance in a multiple logistic regression model that included gestational age, birthweight, and race.

Conclusion: This is the first study describing OLFM4+ neutrophils in neonates and it shows that this neutrophil subpopulation is not influenced by gestational age but is elevated in inflammatory conditions such as sepsis and severe chorioamnionitis, and lower percentage at birth is associated with developing bronchopulmonary dysplasia.

导言:人们对新生儿在健康和疾病状态下中性粒细胞异质性之间的相互作用知之甚少。Olfactomedin-4 (OLFM4)标志着中性粒细胞的一个亚群,该亚群已在成人和儿科患者中被描述过,但在新生儿中还没有被描述过,该亚群被认为在调节宿主炎症反应中发挥作用:这是一个前瞻性队列,对象是 2020 年 6 月至 2021 年 12 月期间在辛辛那提大学医学中心新生儿重症监护室出生的新生儿。使用流式细胞术鉴定外周血中的寡聚腺苷-4 阳性(OLFM4+)中性粒细胞:结果:OLFM4+ 中性粒细胞百分比与胎龄或发育年龄无关。患有败血症的新生儿比未患有败血症的新生儿的OLFM4+中性粒细胞比例更高,分别为66.9%(IQR 24.3-76.9%)和21.5%(IQR 10.6-34.7%),P = 0.0003。出生时,OLFM4+中性粒细胞比例高与重度绒毛膜羊膜炎相关,为49.1%(IQR 28.2-61.5%),而无绒毛膜羊膜炎者为13.7%(IQR 7.7-26.3%),p < 0.0001。在无败血症的新生儿中,BPD/早死组与无BPD组相比,OLFM4+中性粒细胞的百分比较低,分别为11.8%(IQR 6.3-29.0%)对32.5%(IQR 18.5-46.1%),p = 0.003:这是第一项描述新生儿中OLFM4+中性粒细胞的研究,它表明该中性粒细胞亚群不受胎龄影响,但在败血症和严重绒毛膜羊膜炎等炎症情况下会升高,出生时较低的百分比与支气管肺发育不良有关。
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引用次数: 0
期刊
Neonatology
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