Urinary β2‐microglobulin and bronchopulmonary dysplasia: Trends in preterm infants

Background

The developmental process of bronchopulmonary dysplasia (BPD) is not identical between very preterm infants born small for gestational age (SGA) and those born appropriate for gestational age (AGA). In this study, we compared the pattern of the inflammatory response in infants of each group, by measuring urinary β2‐microglobulin (Uβ2M) as an alternative, concise, and less‐invasive biomarker.

Methods

Uβ2M and clinical details were examined at birth and at 4 weeks of age in 146 very preterm infants.

Results

Of the 57 infants diagnosed with BPD, 18 were SGA, and 39 were AGA. Uβ2M at birth was significantly lower in SGA BPD infants than in AGA BPD infants, but it increased with time. The prevalence of chorioamnionitis (CAM) was significantly lower in SGA BPD infants than in AGA BPD infants, while that of pregnancy‐induced hypertension was the opposite.

Conclusions

Exposure to prenatal factors other than CAM may sensitize fetal lungs to become vulnerable to postnatal inflammation in very preterm SGA infants with BPD.     

Evaluation of proximal tubular function in preterm infants by urinary α1-microglobulin

α₁-Microglobulin is a low molecular weight protein that is relatively stable in urine of low pH. There have been few reports on urinary α₁-microglobulin (U-A₁M) excretion in preterm infants. This study was designed to establish the ranges for U-A₁M in clinically stable preterm infants and to investigate changes observed in sick preterm infants. We measured U-A₁M and urinary β₂-microglobulin (U-B₂M) levels at 1, 4, 7, 14, 28 and 90 days after birth in stable preterm infants (Group 1) and sick preterm infants who were depressed at birth and required immediate resuscitation (Group 2). In Group 1 infants, both parameters were high during the first 28 days and appeared to decline thereafter. U-A₁M in Group 2 infants was only significantly increased compared with Group 1 on day 1, as was U-B₂M. On each day of the study, U-A₁M had significant positive correlations with U-B₂M for all the infants studied. The changes of the two parameters observed in Group 1 probably reflect postnatal evolution of proximal tubular function in stable preterm infants. A comparison of groups 1 and 2 shows a high prevalence of acute tubular injury at birth in sick infants and also suggests that U-A₁M as well as U-B₂M may be a sensitive index for detecting acute tubular damage and for following its course in preterm infants.     

Impaired β‐cell sensitivity to glucose and maximal insulin secretory capacity in adolescents with type 2 diabetes

Elder DA, Woo JG, D’Alessio DA. Impaired β‐cell sensitivity to glucose and maximal insulin secretory capacity in adolescents with type 2 diabetes. Background: Adults with type 2 diabetes mellitus (T2DM) have broad impairments in β‐cell function, including severe attenuation of the first‐phase insulin response to glucose, and reduced β‐cell mass. In adolescents with T2DM, there is some evidence that β‐cell dysfunction may be less severe. Our objective was to determine β‐cell sensitivity to glucose and maximal insulin secretory capacity (AIR_max) in teenagers with T2DM. Methods: Fifteen adolescents with T2DM [11 F/4 M, age 18.4 ± 0.3 yr, body mass index (BMI) 39.8 ± 2.2 kg/m²] and 10 non‐diabetic control subjects (7 F/3 M, age 17.4 ± 0.5 yr, BMI 41.5 ± 2.2 kg/m²) were studied. T2DM subjects had a mean duration of diabetes of 48.8 ± 6.4 months, were treated with conventional therapies, and had good metabolic control [hemoglobin A1c (HbA1c) 6.7 ± 1.2%]. Insulin and C‐peptide were determined before and after a graded glucose infusion and after intravenous arginine at a whole blood glucose level of ≥22 mM. Results: The insulin response to increasing plasma glucose concentrations was blunted in the diabetic compared with control subjects (34.8 ± 11.9 vs. 280.5 ± 57.8 pmol/mmol; p < 0.0001), and AIR_max was also significantly reduced in the diabetic group (1868 ± 330 vs. 4445 ± 606; p = 0.0005). Conclusion: Even adolescents with well‐controlled T2DM have severe impairments of insulin secretion. These data support β‐cell dysfunction as central in the pathogenesis of T2DM in young people, and indicate that these abnormalities can develop over a period of just several years.     

β–HCG Elevation in Wilms Tumor: An Uncommon Presentation

Wilms tumor (nephroblastoma) is a readily diagnosed common abdominal tumor in children. Rarely, it may present with factors that may confound the diagnosis. We report a 6‐year‐old female child who presented with a rapidly growing and invasive abdominal mass with the histopathologic features of Wilms tumor associated with an elevated serum beta human chorionic gonadotropin, which has not been previously reported in this condition.     

Neurocognitive function in patients with β‐thalassemia major

Background: Children with β‐thalassemia major (β‐TM) have multiple risk factors for developing cognitive impairment. The aim of the present study was to evaluate cognitive function in patients with β‐TM. Methods: Twenty children with β‐TM were enrolled into the study and were compared with a control group consisting of 21 healthy children. All participants were evaluated with neuropsychological tests and event‐related potentials (ERP). Results: All of the participants had normal IQ scores, but the patient group had significantly lower full‐scale, performance, and verbal IQs compared with the control group (P < 0.05). The number of children with visuomotor dysfunction was higher in the patient group compared with the control group (P < 0.05). In the P300 test, the patient group had significantly prolonged N1, P2 and N2 latencies at the FZ, and a prolonged N1 latency at the Cz compared with the control group (P < 0.05). The patient group also had lower N1 and P3N4 amplitudes at the Fz, and lower N1, N1P2 and P3N4 amplitudes at the Cz when compared with the control group (P < 0.05). Mismatch negativity latency and duration were longer in the patient group (P < 0.05). Conclusions: Neuropsychological tests are safe, and reliable for the diagnosis of cognitive impairment in β‐TM patients, and the use of ERP may facilitate early diagnosis. The number of β‐TM patients in the present study was limited, however, and larger numbers of patients are required in further studies.     

30 417例儿童地中海贫血基因类型分析

目的了解广西地区儿童地中海贫血基因类型及其分布。方法2011年1月至2019年12月对广西壮族自治区妇幼保健院30 417例地中海贫血筛查阳性患儿采用单管多重PCR后经琼脂糖凝胶电泳和反向点杂交技术进行常见α、β地中海贫血基因检测。对2 703例疑似罕见地中海贫血患儿进行跨越断裂点PCR检测和/或基因序列分析。结果30 417例地中海贫血筛查阳性患儿中，确诊地中海贫血23 214例（76.32%），其中α、β及α合并β地中海贫血检出率分别为47.77%、23.75%和4.80%。检出13种α地中海贫血等位基因共计18 480个，以--^SEA为主（54.98%），包括7种罕见等位基因：--^THAI（0.43%）、HKαα（0.02%）、-α³⁰（0.01%）、-α^1.0（0.01%）、-α^2.4（0.01%）、-α^21.9（0.01%）和HBA₂:C272-279 del（0.01%）；检出17种β地中海贫血等位基因共计9 168个，主要为CD41-42（47.79%），其次是CD17（25.53%），包括3种罕见等位基因：IVS-Ⅱ-5（0.02%）、IVS-I-2（0.01%）和^Gγ(^Aγδβ)⁰（0.01%）。14 531例α地中海贫血患儿中检出37种基因类型，6种主要类型为--^SEA/αα（52.20%）、-α^3.7/αα（13.24%）、α^CSα/αα（7.52%）、-α^4.2/αα（6.06%）、--^SEA/-α^3.7（5.91%）和α^WSα/αα（3.41%），共占88.34%。7 223例β地中海贫血患儿中检出49种基因类型，6种主要类型为CD41-42/β^N（45.81%）、CD17/β^N（24.30%）、IVS-Ⅱ-654/β^N（7.49%）、-28/β^N（5.62%）、CD71-72/β^N（4.42%）和CD26/β^N（3.94%），共占91.13%。1 460例α合并β地中海贫血患儿中检出137种基因类型，主要为--^SEA/αα合并CD41-42/β^N（14.17%）、CD17/β^N（8.35%）。HbH病（α⁰/α⁺）2 050例，包括合并β地中海贫血杂合子134例；巴氏水肿胎（--^SEA/--^SEA）12例；β地中海贫双重杂合子355例、纯合子128例，包括合并α地中海贫血93例。结论广西地区儿童地中海贫血基因突变多样，基因类型丰富；以α地中海贫血为主，--^SEA/αα是主要基因类型；α合并β地中海贫血比例较高，β地中海贫血双重杂合子和纯合子（中重型）患儿出生较多。     

Effect of recombinant human fibroblast growth factor‐2 on bone formation in rabbit mandibular distraction models using β‐tricalcium phosphate

This study was designed to evaluate the effect of recombinant human fibroblast growth factor‐2 (rhFGF‐2) on the amount and period of new bone formation in rabbit mandibular distraction models using β‐tricalcium phosphate (β‐TCP) as a bone graft substitute. Sixteen male Japanese White rabbits were divided into the following four experimental groups: 1, distraction alone; 2, distraction with β‐TCP granules; 3, distraction with rhFGF‐2 (25 µg/50 µL) injected into β‐TCP granules; and 4, distraction with rhFGF‐2 (100 µg/50 µL) injected into β‐TCP granules. The bones were harvested at 4 weeks after the operation and examined using soft radiography, micro‐computed tomography (micro‐CT), and peripheral quantitative computed tomography (pQCT). The dissected mandibles were stained using the Villanueva bone staining method, and the amount of new bone formed, bioresorption of β‐TCP, and new blood vessel formation were morphometrically calculated using bone histomorphometry. Radiopaque areas were observed more frequently in the distracted area of groups 3 and 4. Micro‐CT analysis revealed partial new bone formation in the central region of the distracted area in groups 3 and 4. pQCT analysis revealed increased bone mineral density in groups 3 and 4. Histomorphometric analysis revealed increased newly formed bone and blood vessel areas in groups 3 and 4. In group 4, the number of osteoclasts around the β‐TCP granules had significantly increased. The present findings suggested that the combined use of rhFGF‐2 and β‐TCP reduced the treatment period for distraction osteogenesis and accelerated the formation of a new high‐quality bone.     

Content of β‐casomorphins in milk of women with a history of allergy

The prevalence of food allergies increased over the past decade. Most symptoms of food allergy appear during the first 2 yr of life. The aim of this study was to determine the β‐casomorphin‐5 and ‐7 (BCMs) in colostrum and milk of 12 breast‐feeding women with a history and clinical manifestation of food allergy. The results were compared with the data obtained from a control group of healthy age‐matched breast‐feeding women. The level of BCM in women with food allergy was constant during lactation, whereas the highest level of opioid peptides was found in colostrums of healthy women with a subsequent rapid decrease in mature milk. These differences in BCMs profile between allergic and healthy breast‐feeding women suggest that BCM content in the human milk may be an indicator of allergic conditions.     

糖尿病母亲婴儿的神经发育结局

随着孕前糖尿病及妊娠糖尿病发生率的增高，糖尿病母亲婴儿（infants of diabetic mothers，IDMs）也呈逐年增多的趋势，IDMs易发生不良围生期结局，并可能对IDMs神经发育造成负面影响，但目前关于IDMs神经发育结局的研究还相对较少。该文查阅相关文献，从感知觉、运动、语言、智力发育、神经精神疾病、神经学检查和药物影响等方面，对IDMs的神经发育结局予以总结，为临床工作提供参考。 引用格式:     

Citrin缺陷病患儿体格和神经心理发育状况

目的探讨Citrin缺陷病（Citrin deficiency，CD）患儿的体格和神经心理发育情况。方法选择2010年8月至2015年8月于暨南大学附属第一医院就诊，经SLC25A13基因分析确诊的93例CD患儿（年龄：1.9~59.8个月）为研究对象，对其出生情况、体格生长及神经心理发育指标进行回顾性分析。其中7例患儿1岁内及1岁后各做过1次体格测量及神经心理发育评估，故共纳入100例次进行分析。结果93例患儿中，生长发育落后发生率为25%（23例），小于胎龄儿比例为47%（44例）。生长迟缓、低体重、消瘦、超重及小头畸形发生率分别为23%（23例次）、14%（14例次）、4%（4例次）、8%（8例次）、9%（9例次）。神经心理发育迟缓率为25%（25例次），适应性、大运动、精细动作、语言、个人社交5个能区发育迟缓率分别为7%（7例次）、15%（15例次）、7%（7例次）、9%（9例次）、7%（7例次）。结论CD患儿存在体格及神经心理发育落后，建议对其体格及神经心理发育进行定期评估。     

儿童轻度缺铁性贫血间歇补铁疗法的有效性研究

目的研究间歇性补铁疗法治疗儿童轻度缺铁性贫血的临床疗效。方法前瞻性选取147例轻度缺铁性贫血患儿分为间歇补铁组（n=83）和常规补铁组（n=64），检测两组患儿治疗前、治疗1个月后和治疗3个月后血红蛋白水平，对两组的治疗有效率及不良反应发生率进行统计分析。结果经过补铁治疗后，常规补铁组和间歇补铁组血红蛋白水平均较治疗前升高（P<0.05）。治疗1个月后，常规补铁组治疗有效率（61%）高于间歇补铁组（42%）（P<0.05）。治疗3个月后，常规补铁组治疗有效率（86%）与间歇补铁组（78%）比较差异无统计学意义（P>0.05）。常规补铁组的不良反应发生率（25%）高于间歇补铁组（8%）（P<0.05）。结论虽然间歇补铁法对轻度缺铁性贫血患儿的短期疗效不及常规补铁法，但是长期疗效无差异；而且相对于常规补铁法，间歇补铁法可降低不良反应发生率，减轻家庭经济负担，提高患儿治疗依从性，值得临床推广应用。     

Trends in the off‐label use of β‐blockers in pediatric patients

The use of US Food and Drug Administration (FDA)‐approved drugs for the treatment of an unapproved indication or in an unapproved age group, or at doses or route of administration not indicated on the label is known as off‐label use. Off‐label use may be beneficial in circumstances when the standard‐of‐care treatment has failed, and/or no other FDA‐approved medications are available for a particular condition. In pediatric patients, off‐label use may increase the risk of adverse events as pharmacokinetic and pharmacodynamic data are limited in children. Approximately 73% of off‐label drugs currently prescribed for various conditions do not have sufficient scientific evidence for safety and efficacy. For example, β‐blockers are a class of drugs with FDA‐approval for very few indications in pediatrics but are commonly used for various off‐label indications. Interestingly, the proportion of off‐label use of β‐blockers in adults is at about 52% (66.2 million) of the total number of β‐blockers prescribed. The frequency of off‐label use of β‐blockers in children is also high with limited data on the indications as well as safety and efficacy. We present trends in off‐label use of β‐blockers in children to discuss drug safety and efficacy and include recommendations for pediatric providers.