早期早产儿血浆N末端脑钠肽参考值范围

目的 制定早期早产儿血浆N末端脑钠肽(NT-proBNP)参考值范围.方法 1.研究对象按下列标准纳入:(1) 2009年10月至2012年8月出生后24 h内入住郑州大学第一附属医院新生儿病房的早产儿;(2)母亲孕期健康;(3)家属签署知情同意书者;(4)出生当天血气分析、电解质、肝肾功能、心肌酶、血常规及传染病4项(乙肝、丙肝、梅毒及艾滋病)等实验室辅助检查无异常者.2.用电化学发光免疫法于出生后1d、3d、7d检测血浆NT-proBNP水平.变量资料选用Shapiro-Wilk检验法进行正态性检验,呈正态分布者用x-±s表示.不同时间点早产儿NT-proBNP水平比较采用重复测量资料的方差分析;NT-proBNP表达的影响因素分析采用多重线性回归模型,参考值区间:包含95％的参考总体的参考值范围.双侧正态(均数法):x-±1.96 s.检验水准均为α=0.05.结果 1.共入选因早产和(或)出生体质量较低要求寄养的早产儿204例.男104例,女100例;胎龄27+1～36+6周(中位数33周);出生体质量700 ～ 3050 g(中位数1590 g);阴道分娩78例,剖宫产126例;血清胆红素水平(56.6±23.1) μmol/L;母亲年龄为(30.6±5.3)岁;不同性别之间各项参数差异无统计学意义(P＞0.05).2.出生后1d血浆NT-proBNP水平作为因变量,将性别、分娩方式、胎龄、出生体质量、营养方式、血清胆红素及母亲年龄作为潜在的影响因素,行多重线性回归分析,Enter法全部强迫引入,结果 显示,以α =0.05为检验水准,均与NT-proBNP水平无相关性.3.早产儿204例血浆NT-proBNP水平出生后1d、3d、7d数据经Shapiro-Wilk正态检验均呈正态分布.经重复测量资料的方差分析:不同日龄血浆NT-proBNP水平差异有统计学意义(F =443.824,P=0.000);出生后1d最高,之后随出生后日龄增加而降低,二者呈负相关(r=-0.476,P=0.000).不同日龄组间NT-proBNP水平两两比较,差异均有统计学意义(t1d与3d =4.358,t1d与7 d=14.743,t3d与7d =11.105,P均=0.000).出生后1d、3d、7d早产儿血浆NT-proBNP水平分别为(1875 ±686) ng/L、(1615±574) ng/L、(1118 ±380) ng/L;均数95％置信区间分别为530～3220 ng/L、490～2740 ng/L、373～ 1863 ng/L.结论 早产儿血浆NT-proBNP水平出生第1天达高峰,之后随日龄增加而下降,二者呈负相关;血浆NT-proBNP水平不受胎龄、性别、出生体质量、分娩方式及营养方式的影响.     

Reference ranges for sonographic renal dimensions in preterm infants

Background

Ultrasonographic measurement of kidney dimensions is important in evaluation of renal disease in preterm infants who have multiple comorbidities that affect renal function.

Objective

The purpose of this study was to determine the reference ranges of kidney dimensions in preterm newborns and to provide a chart to use easily in daily practice.

Materials and methods

We evaluated renal dimensions in 498 preterm infants with a gestational age of <37 weeks using sonography within the first week of life. We statistically analyzed the relationships between all dimensions and gender, gestational age (based on the last menstrual period), height and weight. Minimum and maximum values of dimensions were defined.

Results

All dimensions of the kidneys were statistically different in boys and girls (P?<?0.05). Both longitudinal and anteroposterior dimensions of the right and left kidneys showed high correlation with gestational age, weight and height in girls and boys. Weight correlated best with dimensions.

Conclusion

Nomograms from these data can be used to determine an abnormality in kidneys of preterm newborns.     

Establishing a reference range for triiodothyronine levels in preterm infants

Objectives

Thyroid dysfunction affects clinical complications in preterm infants and older children. However, thyroid hormone replacement in preterm infants has no proven benefits, possibly owing to the lack of an appropriate reference range for thyroid hormone levels. We aimed to establish a reference range for triiodothyronine (T3) levels at 1-month postnatal age (PNA) in preterm infants.

Methods

This retrospective study included preterm infants born at a tertiary referral neonatal center at gestational age (GA) < 35 weeks with no apparent thyroid dysfunction, for 6 consecutive years, with follow-up from PNA 2 weeks to 16 weeks. Using thyroid function tests (TFT), the relationships between T3 levels and thyrotropin (TSH) and free thyroxine (fT4) levels, birth weight, GA, postmenstrual age (PMA), and PNA were examined. The conversion trend for fT4 to T3 was analyzed using the T3/fT4 ratio.

Results

Overall, 464 TFTs from 266 infants were analyzed, after excluding 65 infants with thyroid dysfunction. T3 levels increased with fT4 levels, birth weight, GA, PMA, and PNA but not with TSH levels. The T3/fT4 ratio also increased with GA, PNA, and PMA. The average T3 level at 1 month PNA was 72.56 ± 27.83 ng/dL, with significant stratifications by GA.

Conclusions

Relatively low T3 and fT4 levels in preterm infants were considered normal, with T3 levels and conversion trends increasing with GA, PMA, and PNA. Further studies are required to confirm the role of the present reference range in thyroid hormone replacement therapy.     

Timing of peak serum cortisol values in preterm infants in low-dose and the standard ACTH tests

The low-dose ACTH test seems to reveal mild cases of adrenal insufficiency and is beginning to be preferred over the standard ACTH test in the evaluation of adrenal suppression both in infants and in adults. The concentration-time profile of plasma cortisol in infants after a low ACTH dose is obscure. In this crossover study, we compared timing of the peak values in the low-dose and the standard ACTH stimulation tests in preterm and full-term infants. We performed the standard ACTH tests (250 microg/1.73 m2) and the low-dose ACTH tests (1 microg/1.73 m2) on 10 infants (26-40 wk gestational age) and measured serum cortisol concentration at 0, 30, 40, 60, and 120 min by RIA. Nine of the infants had received postnatal glucocorticoid treatment, and most of them had also been treated with dexamethasone antenatally. In the low-dose test, the peak values occurred at 30 or 40 min in 9/10 patients. In the standard-dose test, the peak values occurred at 60 or 120 min in 8/10 patients. These results are comparable with those from adults. According to this study, blood samples for the low-dose ACTH test in infants should be taken before dosing and between 30 and 40 min after dosing.     

Salivary cortisol in preterm infants: Validation of a simple method for collecting saliva for cortisol determination

BACKGROUND AND AIMS: The increased use of salivary cortisol as a biomarker of stress and/or diurnal rhythms has facilitated research of Hypothalamic-pituitary-adrenocortical (HPA)function. Saliva collection remains problematic with preterm infants. The twofold purpose of this study is to 1) establish validity of the filter paper method for saliva collection and 2) apply the filter paper method for saliva collection to preterm infants. DESIGN AND MEASURES: Whole saliva was collected from six normal adult subjects to create a pool. Validation measures included comparison of levels obtained from whole saliva and filter paper, an evaluation of storage effects, assessing spiking recovery, and measurement of linearity of dilution. In the application study, saliva was collected every three hours, before feedings for three consecutive days from 26 hospitalized preterm infants. Diurnal variation in cortisol was examined using hierarchical linear modeling and individual calculation of diurnal pattern using an accepted technique. RESULTS: Validation studies revealed acceptable recovery of whole saliva from filters, no effect of room temperature storage of filters for up to six months, and acceptable linearity of dilution up to 4. Saliva from preterm infants was easily collected. Only 2% of the samples were lost due to inadequate wetting of the filters. An inverse association was found between postconceptional age and one-minute APGAR scores and infant cortisol levels. Variable daily cortisol patterns and no discernable rhythm were found for this sample; however, four infants appeared to show atypical diurnal pattern. CONCLUSIONS: The filter paper method is a valid method of saliva collection that is feasible to use with preterm infants.     

Correlation between plasma and salivary cortisol levels in preterm infants

We sought to determine correlations between plasma and salivary cortisol levels in preterm infants in the basal state and after adrenocorticotropic hormone (ACTH) stimulation during the first week of life. Infants (n = 48) were given ACTH or saline solution; each injection was separated by 24 hours. Salivary and plasma cortisol levels correlated at baseline (r = 0.67, P <.0001) and 1 hour after ACTH stimulation (r = 0.40, P =.0047). ACTH increased cortisol levels in plasma from 12.3 +/- 6.4 to 30.3 +/- 13.2 microg/dL (P <.0001) and in saliva from 1.0 +/- 0.8 to 2.6 +/- 1.0 microg/dL (P <.0001). The adrenal response to ACTH can be detected in the saliva of premature newborns during the first week of life.     

Plasma cortisol, cortisone and urinary glucocorticoid metabolites in preterm infants

OBJECTIVE AND METHODS: In the fetal circulation, there is a low cortisol:cortisone (F:E) ratio ( approximately 0.3) suggesting high activity of 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2). The circulating F:E ratio rises after birth in term infants, but little is known about infants born prematurely. Our hypothesis was that the low fetal plasma F:E ratio would persist in infants born prematurely, due to persistently high tissue 11betaHSD2 activity. To test this hypothesis, a longitudinal observational study of plasma F, E levels and urinary F and E metabolites was performed in 22 preterm infants of 24-31 weeks gestation. RESULTS: Median plasma F was 234-380 nmol l(-1), median 124-177 nmol l(-1) from 1 to 14 days age. Plasma F fell with increasing postnatal and postconceptional age. The F:E ratio was 3 in the first week of life, and thereafter was 1-2, falling with postnatal age. Urinary glucocorticoid metabolites were low in quantity ( approximately 48-120 microg kg(-1) day(-1)), consisted of E metabolites until term, and did not reflect the plasma F:E ratio. CONCLUSIONS: The fetal plasma F:E ratio did not persist in these preterm infants, due to tenfold higher levels of F. The F:E ratios were similar to those reported in term infants. These data suggest that the low F:E ratio in utero is due to low fetal production of cortisol, and effective placental inactivation of maternal F by 11betaHSD2.     

The relationship of salivary and cord blood cortisol in preterm infants

Recent studies reveal that salivary cortisol measurements accurately reflect blood cortisol levels in older children and adults; yet, the relationship between the two values in premature infants has not been established. This study explores the use of salivary cortisol as an accurate measure of adrenal steroid concentrations in premature infants to provide a reliable and less invasive tool for investigating hormonal stress response. Premature infants (n=51) were recruited, with saliva and blood collected immediately after birth, and cortisol levels measured by radioimmunoassay. A linear relationship emerged between cord plasma and salivary cortisol values in the 102 paired samples [(salivary cortisol) = 0.546 +/- 0.192 x (plasma cortisol), r = 0.481 and p = 0.0003]. Findings demonstrated that salivary and plasma cortisol levels were correlated in premature infants. This information will be useful in future studies that assess use of salivary cortisol to evaluate neonatal stress axis function.     

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??Oxygen therapy plays an important role in the management of preterm infants??but inappropriate oxygen therapy will cause adverse neurodevelopmental outcome in preterm infants. Monitoring of oxygen saturation is essential in oxygen therapy. However?? optimal range of oxygen saturation for preterm infants still remain controversial. In order to solve the clinical dilemma??many prospective multi-center randomized trials about optimal range of oxygen saturation for preterm infants has been completed. Lower target of oxygen saturation??85-89%?? may result in a lower incidence of retinopathy of prematurity but higher rate of death than higher oxygen saturation target in preterm infants.     

Umbilical cord cortisol and prolactin levels in preterm infants. Relation to labor and delivery

The influence of labor and route of delivery upon the umbilical cord serum levels of cortisol and prolactin in ninety-nine preterm infants not exposed prenatally to corticosteroids was studied. Vaginally born infants (group A) presented a higher mean cord cortisol concentration than those delivered by cesarean section (group B); mean prolactin values, however, were not different between both groups. Although there was no difference in cortisol and prolactin levels between infants delivered by cesarean section after spontaneous onset of labor (group B-I) and those without labor (group B-II), the mean cortisol concentration was significantly higher in group A than in group B-I. The mean prolactin levels did not differ among all the studied groups. It is concluded that there is no association between presence of labor or route of delivery and cord serum levels of prolactin, there is no association between spontaneous preterm labor and cord cortisol values and there is an association between vaginal delivery and high cord cortisol levels in preterm infants. It is suggested that the increase in serum cortisol levels does not precede the initiation of preterm parturition but it is secondary to the stress caused by vaginal delivery.     

Reference ranges for sonographic dimensions of the liver and spleen in preterm infants

Background

Preterm infants usually have multiple comorbidities that affect spleen and liver. Ultrasonographic measurement of organ sizes is an important and reliable parameter in evaluation of spleen and liver pathology in preterm newborns.

Objective

The purpose of this study was to determine reference values of ultrasonographic measurements of the liver and spleen in preterm newborns.

Materials and methods

We prospectively performed sonography on 498 preterm newborns in the first week of life. We measured spleen and liver dimensions and statistically analyzed relationships between the dimensions and gender, gestational age (based on mother’s last menstrual period), height and weight. Reference ranges of dimensions were defined.

Results

Longitudinal and anteroposterior dimensions of the liver and spleen were statistically significantly different between the boys and girls (P?<?0.05) and showed high correlation with the gestational age, weight and height. Weight was the parameter best correlated with the dimensions.

Conclusion

Nomograms from these data are useful for sonographic evaluation of the liver and spleen in preterm newborns.     

早产儿血清总胆汁酸升高的危险因素分析

目的 探讨早产儿血清总胆汁酸（TBA）升高的危险因素。方法 回顾性分析入住新生儿重症监护病房的216例早产儿的临床资料。以是否发生TBA升高（TBA > 24.8 μmol/L）,将早产儿分为TBA升高组（53例）和非TBA升高组（163例）。对可能导致TBA升高的影响因素进行单因素分析和非条件多因素logistic回归分析。结果 单因素分析显示,TBA升高和非TBA升高两组出生胎龄、出生体重、小于胎龄儿比例、呼吸机辅助通气比例、禁食时间、静脉营养时间以及新生儿呼吸衰竭、新生儿败血症的发生率的比较差异有统计学意义（P < 0.05）。非条件多因素logistic回归分析显示,低出生体重（OR=3.84,95% CI：1.53~9.64）、新生儿败血症（OR=2.56,95% CI：1.01~6.47）是早产儿TBA升高的独立危险因素。结论 低出生体重及新生儿败血症可导致TBA升高。     

Nasopharyngeal suctioning does not produce a salivary cortisol reaction in preterm infants

Aim: To investigate whether nasopharyngeal suctioning produces a physiological and behavioural stress reaction in preterm infants and if a possible reaction can be dampened by sweet solution. Methods: Eleven preterm infants were randomly assigned to receive either 30% oral glucose or nothing prior to morning nasopharyngeal suctioning; the procedure was reversed in the afternoon. The study included a total of 44 samples from preterm infants evaluated with salivary cortisol, pain score (Visual Analogue Scale), heart rate, oxygen saturation and recovery time through the Newborn Individualized Developmental Care and Assessment Program. For reference, 44 samples from eleven full-term infants were evaluated for salivary cortisol. Results: Regardless of whether or not preterm infants received glucose before nasopharyngeal suctioning, no statistically significant difference was found in salivary cortisol reactivity, pain score, heart rate, oxygen saturation or recovery time. Nor were any statistically significant differences between salivary cortisol baseline and response values found in full-term infants after nasopharyngeal suctioning. Conclusion: In the present setting, nasopharyngeal suctioning was not stressful enough to increase salivary cortisol or pain score. Oral glucose did not alter salivary cortisol levels.     

高氧暴露下早产大鼠血清皮质醇变化的动态研究

目的研究高氧暴露下,早产大鼠皮质醇(GC)动态变化,探讨其与支气管肺发育不良(BPD)发生之间的关系.方法妊娠21 d剖宫产娩出的早产大鼠随机分为实验组和对照组,实验组大鼠持续吸入＞90%O2,对照组大鼠呼吸空气.于生后1 d,3 d,7 d,14 d,和21 d取肺组织行HE染色.于生后3 d,7 d和14 d,从两组中随机选取仔鼠断头取血,应用放射免疫法测定血清皮质醇浓度.结果对照组早产大鼠血清皮质醇浓度在检测的各时间点无显著性改变,实验组大鼠的血清皮质醇浓度在生后3 d时与对照组比较无显著性差异(n=25,P=0.56),在生后7 d时显著高于对照组(n=25,P=0.04),在生后14 d时显著低于对照组(n=21,P=0.0018).高氧组早产鼠肺脏表现出BPD样病理改变,各时间点高氧组辐射状肺泡计数明显低于对照组(P＜0.05),生后3 d,7 d,14 d和21 d时,高氧组肺纤维化评分明显高于对照组(P＜0.05).结论高氧暴露可以导致早产大鼠肺纤维化,影响肺发育.早产大鼠的血清皮质醇浓度在高氧暴露时有明显改变,可能参与肺损伤的发生过程,影响糖皮质激素的疗效.     

高氧暴露下早产大鼠血清皮质醇变化的动态研究

目的研究高氧暴露下,早产大鼠皮质醇(GC)动态变化,探讨其与支气管肺发育不良(BPD)发生之间的关系。方法妊娠21d剖宫产娩出的早产大鼠随机分为实验组和对照组,实验组大鼠持续吸入>90%O2,对照组大鼠呼吸空气。于生后1d,3d,7d,14d,和21d取肺组织行HE染色。于生后3d,7d和14d,从两组中随机选取仔鼠断头取血,应用放射免疫法测定血清皮质醇浓度。结果对照组早产大鼠血清皮质醇浓度在检测的各时间点无显著性改变,实验组大鼠的血清皮质醇浓度在生后3d时与对照组比较无显著性差异(n=25,P=0.56),在生后7d时显著高于对照组(n=25,P=0.04),在生后14d时显著低于对照组(n=21,P=0.0018)。高氧组早产鼠肺脏表现出BPD样病理改变,各时间点高氧组辐射状肺泡计数明显低于对照组(P<0.05),生后3d,7d,14d和21d时,高氧组肺纤维化评分明显高于对照组(P<0.05)。结论高氧暴露可以导致早产大鼠肺纤维化,影响肺发育。早产大鼠的血清皮质醇浓度在高氧暴露时有明显改变,可能参与肺损伤的发生过程,影响糖皮质激素的疗效。