Pediatric reference values for molecular markers in hemostasis

BACKGROUND: The hemostatic system is a developing and changing process relative to age. OBJECTIVES: To distinguish the differences in hemostatic parameters between children and adults, and to establish the normal range of these parameters in children of different age groups. DESIGN/METHODS: Blood was obtained from healthy children aged 1 to 18 years (n=70) and adults (n=26). Children were categorized into 3 age groups: 1 to 5 years, 6 to 10 years, and 11 to 18 years. Several coagulation and fibrinolysis parameters were determined. RESULTS: Children in all age groups showed no significant difference in mean levels of von Willebrand factor antigen and activity, activated partial thromboplastin time, fibrinogen, activated factor VII, tissue plasminogen activator, plasminogen activator inhibitor-1, and thrombin activatable fibrinolysis inhibitor compared with adults. However, children aged 1 to 5 years had significantly higher mean values of soluble thrombomodulin (P=0.001), prothrombin time (P=0.03), tissue factor (P<0.001), thrombin-antithrombin complex (P<0.001), and D-dimer (P=0.009) whereas they had significantly lower mean levels of protein C activity (P=0.02) than did adults. CONCLUSIONS: These data indicate physiologic differences in the hemostatic system between children and adults and should serve as a useful reference guide in interpreting test results for children with suspected bleeding disorders.     

High accuracy of noninvasive tests to diagnose Helicobacter pylori infection in very young children

OBJECTIVE: To validate the (13)C-urea-breath-test (UBT) and stool antigen test (HpSA) in children aged 5 years or younger, against invasive histologic study and rapid-urease-testing or culture. STUDY DESIGN: On all consecutive children aged 5 years or younger undergoing endoscopy in 1 single center during the last 7.5 years, UBT and HpSA were performed. RESULTS: Of a total of 184 children (median age 2.2 years, range 0.2-5.5), 30 were Helicobacter pylori-positive (16.3%). Sensitivity and specificity of UBT were 93.3% (95%CI 77.9%-99.2%) and 95.5% (90.9-98.2), with a cutoff of 5 per thousand, but specificity increased to 98.1% (94.4%-99.6%) with a cutoff of 8 per thousand. Sensitivity and specificity of HpSA were 93.3% (77.9%-99.2%) and 98.7% (95.4%-99.8%). CONCLUSION: Accuracy of noninvasive tests in our single-center study were satisfactory: specificity of UBT improved with a cutoff at 8%, and sensitivity of HpSA was high when determined locally without transportation after long or inadequate storage that could impair results.     

Observations on the use of three different contrast sensitivity tests in children and young adults

Forty-one children and young adults aged 4 to 25 years (mean 14.5 +/- 6.9, SD) with normal eyes were examined with three different contrast sensitivity tests: the Vistech distance and near test, the Cambridge Low Contrast Gratings test, and the LH-5 Contrast test. In different age groups, the youngest children aged 4 to 9 years had the lowest result values. The results of the older children aged 10 to 15 years and young adults aged 16 to 25 years were close to each other. The range of the results in all tests was large in every age group. The values of contrast sensitivity could not be compared from one test to another; in the Vistech tests the values varied from 10 to 200, in the Cambridge test from 170 to 560, and in the LH-5 test from 5 to 50. Most of the children liked the LH-5 test best, while most of the young adults preferred the Vistech distance test. It is useful to examine children and adults with different contrast sensitivity tests; however, the same test should be used in follow-up examinations.     

深圳地区学龄前儿童用力肺活量测定的可行性及正常预计值公式

目的探讨学龄前儿童用力肺活量测定的可行性,并建立儿童常规用力肺活量的正常参考值。方法对深圳地区3~6岁正常儿童343例(男性184例,女性159例),采用意大利COSMED公司生产的COSMED流量传感仪,参考美国胸科协会可接受曲线标准,测定用力肺活量(FVC)、0.5 s用力呼气容积(FEV0.5)、0.75 s用力呼气容积(FEV0.75)、1 s用力呼气容积(FEV1)、0.5s用力呼气容积占用力肺活量比值(FEV0.5/FVC)、0.75 s用力呼气容积占用力肺活量比值(FEV0.75/FVC)、1 s用力呼气容积占用力肺活量比值(FEV1/FVC)、最大呼气中段流量(FEF25%~75%)、最高呼气流量(PEF)、最高吸气流量(PIF)、呼气时间(FET100%)等11个指标,并对各实测指标作多元逐步线性回归及曲线回归,得出回归方程式。比较本方程与国外Nystad方程对指定身高、体重、年龄的儿童的差异。结果所有儿童测试的总成功率为81.3%,其中3~岁、4~岁、5~岁、6~岁各年龄段测试的成功率分别为69.9%、70.8%、92.3%、91.6%;217例(77.7%)可以完成至少2条可接受的曲线。FVC、FEV0.5、FEV0.75、FEV1、FEF25%~75%、PEF、PIF在各年龄组间差异均有统计学意义(P均<0.01);大多数肺功能指标与身高、体重和年龄均呈密切正相关,男性儿童的大多数肺功能指标与身高的关系最为密切,而女性儿童的大多数肺功能指标则与年龄的关系最为密切。所有儿童的呼气时间为(1.61±0.52)s(x-±s),5百分位数为0.9 s,受试儿童中有18例(6.5%)呼气时间<1 s。建立了各肺功能指标的多元回归方程。结论利用儿童心理特点,通过形象比喻、竞赛游戏的方法进行用力肺活量的测定在中国的学龄前儿童中也是可行的。男性儿童肺功能指标受身高变化影响大于体重和年龄变化;女性儿童肺功能指标受年龄变化影响大于身高和体重变化;首次建立了中国深圳地区学龄前儿童用力肺活量正常值及其回归方程式。     

Blood-pressures in Offspring of Hypertensive Parents

ABSTRACT. The blood-pressures in a material of 59 children aged 6–17 years and 49 adults aged 18–37 years, all of whom had one parent with essential hypertension were compared with control materials. Despite the facts that all of these had one parent with essential hypertension and 2/3 had, in addition, at least one grandparent with essential hypertension, the blood-pressures in the age-group 6–17 years did not differ from the control population. This held true also for the pulse, obesity index, weight and HDL/total cholesterol. In the age-group 18–37 years, 22 % had diastolic blood-pressures of over the 95 % control percentile. In the group of men as a whole, the diastolic blood-pressure (phase 4) was significantly higher ( p <0.01) than in the control population while no difference in the systolic blood-pressure was found. It is concluded that it does not appear to be necessary to control the blood-pressure in children under the age of 18 years with one hypertensive parent more frequently than in other children, while there may be good reasons for controlling the blood-pressure in young adults over 18 years if one of the parents has hypertension.     

Blood-pressures in offspring of hypertensive parents

The blood-pressures in a material of 59 children aged 6-17 years and 49 adults aged 18-37 years, all of whom had one parent with essential hypertension were compared with control materials. Despite the facts that all of these had one parent with essential hypertension and 2/3 had, in addition, at least one grandparent with essential hypertension, the blood-pressures in the age-group 6-17 years did not differ from the control population. This held true also for the pulse, obesity index, weight and HDL/total cholesterol. In the age-group 18-37 years, 22% had diastolic blood-pressures of over the 95% control percentile. In the group of men as a whole, the diastolic blood-pressure (phase 4) was significantly higher (p less than 0.01) than in the control population while no difference in the systolic blood-pressure was found. It is concluded that it does not appear to be necessary to control the blood-pressure in children under the age of 18 years with one hypertensive parent more frequently than in other children, while there may be good reasons for controlling the blood-pressure in young adults over 18 years if one of the parents has hypertension.     

3022例儿童乙型肝炎表面抗体检测结果分析

目的：观察儿童乙型肝炎表面抗体（HBsAb）阳性率情况。方法对2009~2011年3022例在门诊行健康体检的儿童采用酶联免疫法进行乙肝血清学检测,分析HBsAb阳性率。结果HBsAb阳性率随年龄增高而降低（P0.05),但1岁~组男孩HBsAb阳性率低于女孩(P<0.01),而3~＜4岁组男孩HBsAb阳性率高于女孩(P<0.01)。男孩组中HBsAb阳性率随年龄增高而降低,2岁~组男孩HBsAb阳性率低于1岁~组（P<0.01）;女孩组中HBsAb阳性率亦随年龄增高而降低,且各年龄组之间两两比较差异均有统计学意义（均P<0.01）。结论HBsAb阳性率随儿童年龄增高而降低,且低龄儿童是感染乙型肝炎的高危人群,需要加强乙肝血清学监测。     

Developmental profile of mitochondrial glycine N -acyltransferase in human liver

Objective: To study the developmental profile of glycine N -acyltransferase (GAT) in the livers of children of various ages and to compare the total and specific GAT activity with that of the adult control subjects.Methods: We measured the specific and the total mitochondrial activity of GAT in liver samples taken from 13 children 4 hours to 11 years of age. The samples were compared with those of control adults aged 24 to 40 years. Samples, either from liver-transplant donors or from autopsy, from those who died of a disorder not related to the liver, were obtained between 6 and 36 hours after death.Results: At 4 hours after birth, very low specific activity and the total liver mitochondrial activity were observed (0.19 μmol/min per milligram protein and 210 mmol/min), with a steady increase up to age 7 months (2.51 μmol/min per milligram protein and 812 mmol/min). The mean specific and total GAT activity in children (n = 5) aged 18 months to 11 years was 6.38 ± 0.13 and 1389 ± 43 and in control adults aged 24 to 40 years (n = 3) was 6.5 ± 0.3 and 1461 ± 71 μmol/min per milligram protein and μmol/min, respectively. These specific and total GAT activity values from children aged 18 months to 11 years were not statistically significant (by analysis of variance and Mann-Whitney test) in comparison with the corresponding activity values from the adult control subjects.Conclusions: Our results indicate that up to age 7 months, children have only 5% to 40% of liver GAT-specific activity, whereas the peak activity is achieved at 18 months and remains constant until age 40 years. The delayed development of GAT in children may thus compromise the detoxification of various drugs and xenobiotics. (J Pediatr 1997;130:1003-7)     

北京地区3~12岁920名儿童心率变异性分层随机抽样调查分析

摘要 目的 测定920名3～12岁儿童心率变异性（HRV）时域指标值范围；明确HRV与年龄、性别的相关性；研究无症状期前收缩和QT延长儿童HRV的变化。方法 920名3～12岁儿童分为学龄前期组（3～6岁，274名)、学龄期组（～10岁，365名)、青春前期组（～12岁，281名)，行24 h HRV时域分析；进行各年龄组、性别HRV的方差分析；室性期前收缩按照Lown分级法分成4组，QT延长以QTc>450 ms为界分成正常和延长2组，分别进行组间HRV的方差分析。结果 ①HRV各时域指标值随年龄增长而增高，各年龄组均数间差异有统计学意义（P<0.01）。②按性别分组比较HRV 5项时域指标值，男性高于女性，总体标准差（SDNN）、均值标准差（SDANN）和标准差均值（SDNNINX）3项指标均数差异有统计学意义（P<0.05），学龄期和青春前期组SDNN、SDANN均数的男、女间差异有统计学意义（P<0.01），差值均方的平方根（RMSSD）和差值>50 ms的百分比（PNN50）均数差异无统计学意义（P>0.05）。③无期前收缩组与无症状偶发期前收缩组、频发期前收缩组和病理性期前收缩组HRV时域指标值差异无统计学意义（P>0.05）。④QT间期正常组和延长组HRV时域指标值差异无统计学意义（P>0.05）。结论 ①儿童HRV存在年龄差异。HRV的时域指标值随年龄增长而增加，提示儿童心脏自主神经系统发育尚不成熟，交感神经和迷走神经随年龄的增长发育渐趋完善和平衡。②学龄前期至青春前期，HRV男性高于女性。提示心脏自主神经总张力男性高于女性，男性心交感神经张力较女性相对增高；而心迷走神经张力男、女间差异无统计学意义，男、女心脏迷走神经功能发育可能较一致。青春期前，男、女间HRV的差异最为显著。可能提示此年龄段男、女间心脏自主神经发育的不一致性。③无症状期前收缩及QT间期延长儿童的HRV与其他儿童HRV相比无明显变化。     

Occurrence of thyroid papillary carcinoma in young patients. A Chernobyl connection?

The risk of thyroid papillary carcinoma is increased by external radiation particularly in children under 15 years of age as shown by a marked increase in those exposed to radiation after Chernobyl. We were recently confronted in Belgium over a short period with four patients (3 F, 1 M) with papillary thyroid carcinoma who were aged 10 years, 2 months, 2 years and 6 years when the Chernobyl accident occurred. We thus raise the question of a possible relationship. The patients were aged 17, 11, 10, 19 years at presentation. They all presented fortuitously over 3 years which was a very unusual increase in our extensive experience in thyroid surgery (62 cases of thyroid cancer among 1014 thyroidectomies in adults vs 4 cases in 18 children since the Chernobyl accident in 1986). Two out of the four patients had psammoma bodies (identifiable on CT scanning and ultrasound) and thyroglobulin autoantibodies (TgAb). The first patient had positive lymph nodes at the time of surgery. The incidence of thyroid cancers in Belarus and Ukraine rose just 4 years after the Chernobyl disaster; because radioactive clouds passed over Belgium, we wonder whether the occurrence of thyroid cancer in our patients could be related to this irradiation. The mechanism of increased incidence of radiation-induced thyroid cancer is thought to be due to rearrangement of the tyrosine kinase domains of the RET and TTK genes. The other important similarities in our patients are the presence of psammoma bodies that can be visualized on radiological examination and the presence of TgAb that are more frequent in differentiated thyroid cancers. Whether or not these cases reflect an increased incidence in the population as a whole, clinicians must remain vigilant for this rare but curable cancer in young patients, especially if suggestive radiological features or TgAb are present.     

Seroprevalence of mumps, varicella and rubella antibodies in children 1-16 years of age in eastern Turkey

In this study, seroprevalence of mumps, varicella and rubella was investigated in 803 unvaccinated children in eastern Turkey whose ages ranged between 1 and 16 years. Mumps IgG, varicella IgG and rubella IgG antibody levels in all children were studied by enzyme-linked immunosorbent assay (ELISA) method. Information regarding socioeconomic characteristics, number of siblings and disease history was gathered for each participant. No significant difference in seropositivity was detected between girls and boys. Seroprevalence of mumps increased with age, with a seropositivity rate of 29.9% in children aged 1-4 years and of 88.8% in those aged 13-16 years. Seroprevalence of varicella increased with age, with a seropositivity rate of 26.8% in children aged 1-4 years and of 90.3% in those aged 13-16 years. Seroprevalence of rubella also increased with age, with a seropositivity rate of 47.3% in the children aged 1-4 years and of 89.2% in those aged 13-16 years. There was a statistically significant increase in the rate of seropositivity with advancing age through the group of 13-16 years old (p < 0.05). In conclusion, in order to avoid mumps, varicella and rubella diseases and their possible complications, children should be vaccinated against these three diseases before the age of two, since seroprevalence increases with age.     

Investigation of age‐related developmental differences of button ability

Background: There is little standardized information on simple and easy‐to‐use evaluation of fine motor skills in disabled children. The purpose of the present study was to determine the relationship between unbuttoning and buttoning ability and age and sex difference. Methods: One hundred and forty‐four children (63 boys and 81 girls; age range, 36–83 months) and 14 young adults took part in the present study. The children were categorized into four groups according to age. Every subject went to nursery school and/or kindergarten. On the basis of Montessori education system, unbuttoning and buttoning were performed. The time from beginning to end was measured individually. All the participants were instructed to do the task in the same way. Results: The mean time required for unbuttoning activity was decreased until 4 years old, while that for buttoning was also reduced until 5 years old, respectively. There were no significant differences between boys and girls except in unbuttoning activity at the age of 3 years. Conclusion: More attention should be paid to unbuttoning and buttoning activities in children. It might be a simple and easy‐to‐use evaluation method in the clinical setting.     

Chemotactic and random movement of human newborn monocytes

Boyden's method was used to assess the chemotactic and random mobility of monocytes from healthy newborns, children aged 3–8 years, and adults aged 20–28. Monocyte chemotaxis in the newborn was decreased in comparison with that of control groups. No difference was observed in random cell mobility in the groups examined. Monocyte chemotactic activity in infants over 3 years of age was the same as in adults. According to our results, the leading-front and lower-surface evaluation methods, in newborns at least, do not give the same information on chemotaxis.     

Pancreatitis in children. A study in the North of England.

Cases of pancreatitis in children in the Newcastle Regional Board area were studied over approximately 6 years. There were 9 cases aged between 6 weeks and 15 years. In 5 children (all under 7 years of age) likely aetiological factors were found (2 cases of mumps and 1 case wach due to trauma, measles, and hereditary pancreatitis). In 4 children all over 13 years of age no likely aetiological factor was found. It is speculated that they may represent one end of the age spectrum of idiopathic pancreatitis as it occurs in adults. Hereditary pancreatis was definitely found in only one child and possibly in one other. Therefore, it probably does not represent the major cause of pancreatitis in children as has been previously thought. One child died, but all the other children have thrived since their illness.     

重庆市一社区0~4 岁儿童便秘患病率和排便情况横断面调查

目的 基于社区调查0~4岁儿童便秘患病率和排便情况。方法 采取整群抽样方法,以在重庆市渝中区大溪沟社区卫生服务中心（调查现场）出生后建立儿童健康体检卡的全部0~4岁儿童家长为问卷调查对象,2013年10~12月对来调查现场的儿童家长指导填写儿童生长发育和营养状况调查问卷;对未来调查现场的儿童家长通过电话指导完成问卷调查,家长按Bristol图确定儿童大便形状。以罗马Ⅲ便秘诊断标准作为本文诊断便秘标准,获得社区儿童便秘患病率;以Bristol大便形状1~3型分别与本文便秘诊断标准主要倚重项目组合,计算敏感度、特异度、阳性似然比和阴性似然比。结果 所在社区建立儿童健康体检卡的0~4岁儿童共1 206名,进入分析972份有效问卷中男535名,女437名;符合本文便秘诊断标准55例,所在社区0~4岁儿童便秘患病率为5.6%。符合本文便秘诊断标准的55例均为Bristol大便形状的1~3型; 0~4和~6月龄组以6型便为主,8月龄以上组以4型便为主。Bristol大便形状1~3型分别与本文便秘诊断标准倚重项目“每周排便2次及以下”和“排便疼痛或排便困难史”组合后诊断便秘的敏感度均为100%,特异度96.8%以上,前者阳性似然比高于后者（142.9 vs 31.3）。结论 0~4岁儿童便秘患病率为5.6%,Bristol大便形状1～3型是儿童发生便秘的警示指标。     

Diagnostic significance of hemoglobin F and A2 levels in homo- and heterozygous beta-thalassemia during infancy

For diagnosis of beta- and beta delta-thalassemia in the first year of life the physiological changes of hemoglobin F and A2 levels occurring in this age group have to be considered. The analysis of the hemoglobin pattern in 29 cases of thalassemia major and 285 cases of thalassemia trait, 47 of them aged less than one year, showed that all cases of homozygous beta-thalassemia aged less than one year could be diagnosed by definitely increased hemoglobin F levels exceeding the normal range for the appropriate age. In children older than ten years and in adults with heterozygous beta-thalassemia, the diagnosis could be made accurately by increased hemoglobin A2 levels in 97 percent. In children between one and ten years only 77 percent and in infants aged less than one year only 55 percent of the cases showed increases hemoglobin A2 levels. In contrast to adults, the hemoglobin F level seems to be helpful for the diagnosis of thalassemia trait. The younger the patient the more is the hemoglobin F level increased above the normal range for the appropriate age. It appears impossible to differentiate between beta- and beta delta-thalassemia trait when hemoglobin A2 is normal or low.     

An outbreak of typhoid fever resistant to chloramphenicol and other drugs in Gharbeya Governorate in Egypt.

An outbreak of Typhoid fever (TF) occurred in Gharbeya Governorate in Egypt during November and December 1990. Ninety children with mean age of 9.64 +/- 3.67 years and 43 adults with mean age 22.51 +/- 5.36 years were treated in Tanta fever hospital (TFH) during this outbreak. Resistance of TF during the outbreak to the usual antibiotics given in TFH was the main feature of the outbreak, including resistance to chloramphenicol, co-trimoxazole, ampicillin, tetracycline, and gentamycin. Such resistance was detected in vitro as well as in vivo. Sensitivity was present in vitro and in vivo to ofloxacin (OF) and cefotaxime. The clinical response of OF was 96 per cent in children and 82 per cent in adults. No significant difference in side effects was detected in children treated with OF and those treated with other drugs after 6 months follow up.     

A disappearing urban/rural blood pressure difference in Nigerian children: an evaluation of possible determining factors.

Urban Nigerian school children are reported to have a higher systolic blood pressure and diastolic blood pressure than rural community school children until the age of 11-12 years when this difference tends to disappear. We evaluated 874 urban day-school children and 674 rural community school children aged 5-16 (mean 11.9) years in south-eastern Nigeria to confirm this changing pattern, and to assess the contributions of some known factors to the differences as well as the changing pattern. This study confirmed the changing pattern of urban/rural blood pressure of school children. Differences in weight, height and Body Mass Index (BMI), though important, appeared insufficient to explain this pressure difference and the changing pattern. Urban children aged 12-14 years were found to excrete more sodium and (unexpectedly) more potassium in their 24-h urine samples. The observed urban/rural blood pressure difference appears to be sustained by a multiplicity of factors, including differences in weight, BMI, height, electrolytes (especially sodium) consumption, and increased exposure to Western-type education.     

Serum levels of IgG subclasses in the normal child. Evaluation by an immunoenzymatic method using monoclonal antibodies

Serum IgG subclass levels were measured by an immunoenzymatic assay with monoclonal antibodies in 225 normal children aged 1 to 17 years. Adult concentrations of IgG1 and IgG3 were reached early (2 to 3 years of age), with mean IgG1 level slightly higher in children than in adults, whereas IgG2 and IgG4 showed a slow increase. Mean IgG2 levels in children aged 13 to 17 were still significantly lower than in adults. The distribution of IgG4 levels in every age group was very heterogeneous, with a fair incidence of subthreshold concentrations especially before 5 years of age. These data must be taken into account when defining IgG subclass deficiencies in children.     

EFFECT OF AGE ON HUMAN ADIPOSE TISSUE METABOLISM AND HORMONAL RESPONSIVENESS

Abstract. The effects of age and fat cell size on the metabolism of white human adipose tissue were analysed independently. Abdominal subcutaneous adipose tissue specimens were obtained from children varying in age from 0–15 years and from adults (mean age±S.D.; 38.2±14.1 years). The basal rates of lipolysis and glucose incorporation into lipids were considerably higher in children than in adults even when differences in fat cell size had been taken into account. Lipolysis in response to a maximal concentration of noradrenalin was higher in fat cells from children. However, on a percentage basis the responsiveness to this agent was similar in children and adults. Irrespective of age, glucagon did not elicit a lipolytic response. Thus, it does not seem that the increased lipolysis known to occur in vivo in the neonatal period is due to a direct effect of glucagon on white adipose tissue. However, the overall lipolytic capacity is increased in fat cells from children.