新生儿高胆红素血症光疗的副作用

自上世纪50年代以后,蓝光被广泛使用于新生儿高胆红素血症的治疗中。新生儿光疗可有效降低血清未结合胆红素,预防胆红素脑病的发生,极大地降低了交换输血疗法的使用频率。普遍认为光疗副作用轻微并且容易控制。但是最近研究提供了光疗副作用的新证据。光疗近期副作用包括影响母婴互动、体温失衡和水分丢失、电解质紊乱、生理节律紊乱和青铜症等。此外,光疗可能与黑素痣和皮肤癌、动脉导管未闭、视网膜损伤及成年生殖能力受损等远期副作用相关。因此,需要制定完善的循证指南,发展包括光导纤维光毯和发光二极管在内的新设备,以及光疗替代制剂,并在此基础上探讨个体化治疗,以最大程度减少光疗副作用。     

强光疗治疗新生儿高胆红素血症的疗效及安全性

目的 探讨采用强光疗治疗新生儿高胆红素血症的疗效及安全性。方法 对144 例新生儿高胆红素血症患儿进行前瞻性随机分组,其中强光疗组和传统光疗组各72 例,对两组疗效及并发症等情况进行比较。结果 光疗后12 h 内强光疗组患儿血总胆红素水平明显低于传统光疗组(P<0.05),且胆红素下降幅度明显高于传统光疗组(P<0.05)。强光疗组患儿总光疗时间明显短于传统光疗组(P<0.05)。两组患儿光疗后发热、腹泻、皮疹、低钙血症发生率及光疗后血钙水平和血红蛋白下降水平等比较差异均无统计学意义。结论 强光疗在光疗开始初期可迅速有效降低高胆红素血症患儿血中胆红素水平,缩短总光疗时间,且不增加不良反应的发生率,是一种优于传统光疗的治疗措施。     

Phototherapy for neonatal hyperbilirubinemia

Approximately 60 years ago in England, phototherapy for neonatal hyperbilirubinemia was used in clinical practice. It was introduced in Japan approximately 50 years ago. At that time, the mechanism underlying the serum bilirubin concentration decrease by phototherapy was still unknown. The mechanism was identified by chemists, biochemists, and pediatricians. Clarification started with the report that unconjugated bilirubin was excreted into bile after photoirradiation in Gunn rats. After confirmation of the molecular structure of bilirubin on X‐ray analysis, the mechanism for bile excretion of unconjugated bilirubin was verified based on geometric configurational photoisomers in the Gunn rat. Finally, the reaction and excretion of structural bilirubin photoisomers was proved to be the main mechanism for the decrease in serum bilirubin during phototherapy for neonatal hyperbilirubinemia, which differs from the mechanism in the Gunn rat. The most effective and safest light source and the optimal method to evaluate phototherapy, however, remain unknown. Moreover, as for bronze baby syndrome, which is a well‐known adverse reaction to phototherapy, the etiology is unclear. Hence, we review phototherapy for hyperbilirubinemia including a fundamental understanding of the bilirubin photochemical reactions, and discuss the subclinical carcinogenic risk of phototherapy and the increased mortality rate of extremely low‐birthweight infants due to aggressive phototherapy, which is becoming an increasing problem.     

新生儿高胆红素血症对机体的损伤

新生儿高胆红素血症是新生儿住院的主要原因之一,是常见于新生儿早期的以皮肤巩膜黄染为主要表现的病症.患儿血清总胆红素及未结合胆红素水平大幅度升高,如不及时干预可能对新生儿脑功能、肾功能、听力及心功能产生损伤,严重者可致死亡.研究证实,高胆红素血症对新生儿的脑神经、听力、肾脏及心脏均可造成损伤,且靶器官的受损程度与血中胆红素水平呈正相关.该文就高胆红素血症对新生儿的不良影响作一综述.     

新生儿黄疸的光疗干预指征及相关问题

新生儿黄疸或新生儿高胆红素血症是新生儿的一种常见现象,多数情况下是一个良性过程.多种因素造成胆红素的产生和清除失衡即可引起高胆红素血症,部分患儿可发展成重度高胆红素血症,可能会导致永久性的神经系统后遗症(核黄疸).光疗是新生儿黄疸常见的治疗方法,应根据本地区、民族等不同因素的流行病学特点,确定日龄或时龄相对应黄疸的干预值,并结合高危因素的评估,给予适时干预,同时避免过度治疗.     

Inhibitory effect of pooled human immunoglobulin on cytokine production in peripheral blood mononuclear cells

Human intravenous immunoglobulins (IVIG) are widely used as immunomodulators because of their ability to modify the course of various immune-mediated diseases. We investigated the mechanisms responsible for the regulatory effects of IVIG on in vitro human peripheral blood mononuclear cell (PBMC) cytokine production. Pre-incubation of PBMCs with IVIG inhibited lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA)/ionomycin stimulated cytokine secretion. Pre-incubation of PBMCs with IVIG induced a significant inhibition of LPS-stimulated (IL-6) secretion (p = 0.045); the effect on tumor necrosis factor-alpha (TNF-alpha) secretion was not significant (p = 0.234). Pre-incubation of PBMCs with IVIG inhibited IL-6 secretion (p = 0.033) stimulated with anti-CD14 antibody cross-linking but had no significant effect on TNF-alpha secretion (p = 0.125). PBMC pre-incubation with anti-CD14-blocking antibody induced a significant reduction (p = 0.042) in LPS-stimulated TNF-alpha secretion in comparison with a non-significant reduction (p =0.256) noted with IVIG pre-treatment. In contrast, pre-incubation of PBMCs with anti-CD14 antibody did not induce a significant reduction in LPS-stimulated IL-6 secretion (p = 0.166) in comparison with a significant reduction (p = 0.001) induced with IVIG pre-treatment. Our data suggest that the immunoregulatory properties of IVIG may rely on several mechanisms, some of which may be independent of CD14. Our data also showed that cross-linking cell membrane-bound IVIG with anti-human kappa- and lambda-chain antibodies resulted in cytokine secretion levels similar to those elicited by LPS. In addition, intracellular DNA staining results did not support the involvement of apoptosis in the regulatory mechanisms of IVIG. This data may further our understanding of the immunoregulatory effects exerted by IVIG on the production of inflammatory-response mediators.     

Ibuprofen affects pro- and anti-inflammatory cytokine production by mononuclear cells of preterm newborns

The in vitro effect of ibuprofen (IB) on the production of the proinflammatory cytokines interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) and the anti-inflammatory cytokine IL-10 by cord blood mononuclear cells from preterm newborns was compared to that of peripheral blood mononuclear cells of adults. Mononuclear cells were incubated without or with lipopolysaccharide in the absence or presence of various concentrations of IB. The levels of IL-1beta, IL-6, TNF-alpha, and IL-10 in the supernatants were tested by ELISA. The mononuclear cells from the two groups responded to IB by an increased secretion of IL-6 and TNF-alpha and by a reduced production of IL-10. The pattern of response to the drug was similar following stimulation with lipopolysaccharide. The IL-1beta production was mostly unaffected by IB. It is suggested that in preterm newborns the differences observed in the in vitro proinflammatory cytokine production in response to IB, as observed in the present study, or to indomethacin, as reported previously, may affect various clinical outcomes using these two drugs.     

同型血外周动静脉同步换血对不同病因高胆红素血症的疗效对比研究

目的探讨同型血外周动静脉同步换血对不同病因所致高胆红素血症的疗效。方法对不同病因高胆红素血症患儿均采用同型血外周动静脉同步换血,换血前后行血常规、生化、胆红素、血培养等检查。结果不同病因的高胆红素血症患儿换血前后胆红素对比均有显著降低（Ｐ＜００１）,总胆红素换出率分别是３７８２％、４５５２％和４８４１％,平均换出率是４２６２％。在体重、输入量和换出量无显著差异（Ｐ＞００５）的情况下,各组间总胆红素和间接胆红素换出率无显著差异（Ｐ＞００５）。结论采用同型血对不同病因所致的高胆红素血症换血效果相近;外周动静脉同步换血是简单、实用的方法,值得推广。     

新生儿外周血单个核细胞乙型肝炎病毒DNA检测的临床意义

目的探讨HBsAg阳性产妇新生儿外周血单个核细胞(PBMC)乙型肝炎病毒(HBV)感染率、影响因素及检测的临床意义。方法50例HBsAg阳性产妇和其新生儿为研究组,另18例血清乙肝标志物均阴性者为对照组。采用套式聚合酶链反应(n-PCR)法分别检测产妇、新生儿血清及PBMCHBV-DNA。结果HBsAg阳性母亲血清及PBMCHBV-DNA检出率分别为60·0%和40·0%;其新生儿血清及PBMCHBV-DNA阳性率分别为46·0%及30·0%;其中仅血清阳性10例,仅PBMC阳性2例,血清和PBMC均阳性13例。对照组母儿血清及PBMC中未检出HBV-DNA。新生儿PBMCHBV-DNA阳性率在母血清HBeAg、HBV-DNA阳性组高于阴性组(P<0·05,P<0·01);母PBMCHBV-DNA阳性组高于阴性组(P<0·01);母血清和PBMCHBV-DNA均阳性组高于仅血清阳性组(P<0·01);新生儿血清HBV-DNA阳性组高于阴性组(P<0·05)。结论HBsAg阳性母亲新生儿HBV-DNA感染率为30·0%;其感染率与母、儿血清病毒血症水平及孕妇PBMCHBV-DNA状态有关,检测出新生儿PBMCHBV-DNA具有重要临床意义。     

Adverse events associated with neonatal exchange transfusion for hyperbilirubinemia

To estimate the incidence of blood exchange and determine causes and complication of blood exchange and identify strategies for risk reduction of Kernicterus in newborn with jaundice. From march 2004 to march 2006 in neonatal Department in children hospital, medical center Tehran, Iran,346 neonates were admitted as neinatal jaundice without sign and symptoms of infections. We identified causes and complications of exchange. Of 346 infants with jaundice who received phototherapy. 50, 14.45 percent cases underwent exchange transfusion with mean age 9.38+5.75 days. The mean total Serum billirubin level was 29.39+6.13mg/dl. ABO incompatibility was the most common cause for hyperbillirubinemia.the incidence of apnea was 12% there was no direct death from exchange transfusion. To make payment women aware to cbserve jaundice regularly after birth of their child and short breast feeding to control dehydretion.     

A randomized trial of aggressive versus conservative phototherapy for hyperbilirubinemia in infants weighing less than 1500 g: Short- and long-term outcomes

OBJECTIVE

Treatment regimens for hyperbilirubinemia vary for very low birth weight infants. The present study seeks to determine whether the initiation of conservative phototherapy is as effective as aggressive phototherapy in reducing peak bilirubin levels without increasing adverse effects.

STUDY DESIGN

The present randomized, controlled study included infants with birth weights between 500 g and 1500 g, stratified into two birth weight groups. In one group, aggressive phototherapy was commenced by 12 h of age, while in the other group, conservative phototherapy was commenced if serum bilirubin levels exceeded 150 μmol/L. The primary outcome variables were peak serum bilirubin levels and hours of phototherapy. Secondary outcomes were age at peak bilirubin levels, number of infants with rebound hyperbilirubinemia, and number of adverse short- and long-term outcomes.

RESULTS

Of 174 eligible infants, 95 consented to participate −49 in the conservative arm and 46 in the aggressive arm. Ninety-two infants completed the study. There was no significant difference in peak bilirubin levels except in infants who weighed less than 1000 g −171.2±26 μmol/L (conservative) versus 139.2±46 μmol/L (aggressive); P<0.02. There was no difference in duration of phototherapy or rebound hyperbilirubinemia. There were no differences in short-term adverse outcomes. Of the 87 infants who survived until hospital discharge, 82 (94%) had some follow-up and 75 (86%) attended follow-up until 18 months corrected age. The incidence of cerebral palsy, abnormal mental developmental index at 18 months corrected age, or combined outcome of cerebral palsy and death did not significantly differ between the two groups.

CONCLUSIONS

In infants weighing less than 1000 g, peak bilirubin levels were significantly higher using conservative phototherapy regimens and there was a tendency for poor neurodevelopmental outcome.     

Erythropoietin inhibits cytokine production of neonatal and adult leukocytes

BACKGROUND: Erythropoietin (Epo) was originally defined as a hematopoietic growth factor, but also has potent tissue-protective properties. The cytokine-modulating actions of Epo have received scant attention. We hypothesized that Epo significantly influences the in vitro cytokine production in both neonates and adults. METHODS: The effects of Epo were investigated using a standardized in vitro whole blood assay. Production of various cytokines was assessed by means of intracellular cytokine detection (IL-2, -6, -8, IFN-gamma and TNF-alpha) in preterm infants, term neonates and adults. Furthermore, synthesis of IL-4, -5 and -10 in adults was investigated via cytometric bead array. RESULTS: Epo significantly inhibits the production of various cytokines in preterm infants, term neonates and adults. In CD3+ lymphocytes, Epo predominantly decreases the number of IL-2-positive cells in all age groups. Similarly, in CD14+ cells, Epo significantly diminishes the number of IL-6- and TNF-alpha-producing cells. Furthermore, Epo significantly inhibits the synthesis of IL-4, IL-5 and IL-10 in adults. CONCLUSION: rhEpo has significant inhibitory potential on the production of various cytokines by leukocytes in preterm and term infants as well as in adults. The described effect likely contributes to the tissue protective properties of Epo.     

外周动静脉同步换血治疗新生儿高胆红素血症临床研究

新生儿高胆红素血症是新生儿期常见的疾病,重度高胆红素血症常导敛新生儿死亡或留下严重的后遗症和脑损伤。换血可快速清除血中游离的胆红素、致敏红细胞、细菌及炎症介质等,是治疗新生儿重度高胆红素血症的急救措施之一。传统的换血疗法多采用脐静脉换血,要求较高,潜在危险及并发症较多,难以普及。近儿年国内文献报道多采用外周动静脉同步换血治疗,效果好,无明显并发症。我科自2005年3月至2006年6月对37例达到换血指征的新生儿高胆红素血症患儿采用外周动静脉同步换血疗法,治疗效果满意,总结报告如下。     

应用蓝光发光二极管治疗新生儿高胆红素血症的研究

目的探讨蓝光发光二极管（lightemittingdiodes,LEDs）对新生儿高胆红素血症的光疗效应。方法将LEDs与普通蓝光灯分成四组LEDs组、单面蓝光组、LEDs+单面蓝光组、双面蓝光组。四组光源照射黄疸早产儿,然后应用高效液相色谱仪（HPLC）测定血、尿中胆红素光异构体的变化,同时观察皮疹、体温、大便性状等改变情况,评价LEDs的效应。结果黄疸早产儿分别在四组光源照射6h后,血清胆红素构象异构体（14Z,15E-bilirubinⅨα,ZE）和胆红素结构异构体（lumirubin,LR）的含量LEDs组［（13.0±1.9）、（3.9±1.0）μmol/L］与单面蓝光组［（13.4±2.2）、（4.3±1.2）μmol/L］比较差异无显著性（P＞0.05）;LEDs+单面蓝光组［（21.9±2.3）、（7.2±1.4）μmol/L］与双面蓝光组［（23.1±3.3）、（7.5±1.4）μmol/L］比较差异无显著性（P＞0.05）;而LEDs+单面蓝光组、双面蓝光组均大于LEDs组和单面蓝光组（P＜0.05）。在光照12h后血清ZE的量及12h内尿LR的总排出量四组比较;LEDs+单面蓝光组、双面蓝光组均明显大于LEDs组、单面蓝光组(P＜0.01)。光组12h后血清LR的量,四组比较差异无显著性（P＞0.05）。LEDs光照新生儿未发现皮疹、腹泻及发热,而普通蓝光光照新生儿有个别出现发热和腹泻。结论HPLC测定光照前后血和尿胆红素光异构体的变化,可作为评价光疗效应的指标,而定量测定尿液光异构体LR的量,既可靠、又无创伤性。LEDs能起到普通单面蓝光一样的光疗效果,且副作用并无增多。     

Interferon-gamma pretreatment of peripheral blood mononuclear cells partially restores defective cytokine production in children with atopic dermatitis

Interferon-gamma (IFN-γ) is considered an important determinant of the balance between T-helper type 1 and 2 cytokines and has been used experimentally for the treatment of atopic dermatitis. However, contrasting results have been reported relative to the Th-UTh-2 cytokine profile in atopic patients. In this study, we examined cytokine production by polyclonally activated peripheral blood mononuclear cells (PBMC) from children with atopic dermatitis, and assessed the influence of in vitro IFN-γ pretreatment on these cells. A fraction of PBMC isolated from children with severe atopic dermatitis, as well as from age-matched controls, was initially exposed to IFN-γ. After washing, both treated and untreated cells were then put into culture either alone or with the addition of phytohemagglutinin (PHA) or phorbol myristate acetate (PMA) plus ionomycin. IL-4, IL-5, IL-10 and IFN-γ production were measured in the supernatants using commercially available ELISAs. PBMC from atopic patients produced more IL-4 (P = 0.04) and IL-10 (P = 0.03) and less IFN-γ (P = 0.01) than controls, when stimulated with PHA. Interestingly, in PMA + ionomycin stimulated cultures, the atopic cytokine profile was different with more IL-5 (P = 0.0068) and less IFN-γ production (P = 0.00046) than the control group. When cells were pretreated with IFN-γ, there were no significant differences between patients and controls. PBMC from children with atopic dermatitis show alterations in cytokine production, compatible in general terms with the Th-l/ Th-2 model. Exposure of PBMC to IFN-γ before activation results in a reduction of these differences, so that cytokine production becomes similar in the atopic and normal groups.     

新生儿小时胆红素百分位曲线图预测高胆红素血症的研究进展

新生儿高胆红素血症是新生儿期的常见病,约8％～11％的新生儿发生严重的高胆红素血症.严重高胆红素血症如果没有得到及时控制和治疗,可发展为胆红素脑病,导致神经损害和功能残疾.利用小时胆红素百分位曲线图对新生儿进行出院的风险预测、干预及随访,降低胆红素脑病的发生,是国内外儿科医生关注的焦点.该文就各国制备的小时胆红素百分位曲线预测出院后高胆红素血症发生风险的研究进展作一综述,以便于小时胆红素百分位曲线更好地指导临床诊疗.     

High-intensity phototherapy for the treatment of severe nonhaemolytic neonatal hyperbilirubinemia

Aim: To describe the clinical approach to term and near‐term newborn infants with severe hyperbilirubinaemia and to analyse the effect of high‐intensity phototherapy on total serum bilirubin (TSB) levels. Methods: We analysed a cohort of 116 newborn infants with severe nonhaemolytic hyperbilirubinaemia (TSB ≥ 20 mg/dL/342 μmol/L). All patients were treated with high‐intensity phototherapy. The main outcomes were reduction in TSB levels in the first 24 h of phototherapy, incidence of exchange transfusion, pathological brainstem auditory evoked responses and pathological findings on neurological examination at discharge. Results: The mean birth weight and gestational age were 3161 ± 466 g and 37.8 ± 1.6 weeks. Mean initial TSB concentration was 22.4 ± 2.4 mg/dL. Per cent decreases in TSB after 2, 4, 6, 12, 18 and 24 h of phototherapy were 9.4%, 16%, 23%, 40%, 44% and 50%, respectively. No infant was treated with exchange transfusion. Brainstem evoked response audiometry (BAER) was performed in 100% of the patients, and in three of them, this examination was altered. However, when repeated 3 months later, these BAER examinations were normal. Neurological examination was normal in all patients. Conclusions: High‐intensity phototherapy significantly reduces TSB in nonhaemolytic severe hyperbilirubinaemia and decreases the need for exchange transfusion.     

Cord blood bilirubin and prediction of neonatal hyperbilirubinemia and perinatal infection in newborns at risk of hemolysis

ObjectiveTo assess the accuracy of umbilical cord bilirubin values to predict jaundice in the first 48 h of life and neonatal infection.MethodNewborn infants treated at a regional well-baby nursery born at ≥36 weeks of gestation were included in this retrospective cohort study. All infants born in a 3-year period from mothers with O blood type and/or Rh-negative were included and had the umbilical cord bilirubin levels measured. Hyperbilirubinemia in the first 48 h was defined as bilirubin levels above the phototherapy threshold. Neonatal infection was defined as any antibiotic treatment before discharge.ResultsA total of 1360 newborn infants were included. Two hundred and three (14.9%) newborn infants developed hyperbilirubinemia in the first 48 h of life. Hyperbilirubinemic infants had smaller birth weight, higher levels of umbilical cord bilirubin, a higher rate of infection and were more often direct antiglobulin test positive. Umbilical cord bilirubin had a sensitivity of 76.85% and a specificity of 69.58% in detecting hyperbilirubinemia in the first 48 h, with the cut-off value at 34 μmol/L. The area under the receiver operating characteristic curve was 0.80 (95% CI: 0.78–0.82). Umbilical cord bilirubin had a sensitivity of 27.03% and specificity of 91.31% in detecting perinatal infection. The area under the receiver operating characteristic (ROC) curve was 0.59 (95% CI: 0.57–0.63).ConclusionsA positive correlation was found between umbilical cord bilirubin and hyperbilirubinemia in the first 48 h of life. Umbilical cord bilirubin is a poor marker for predicting neonatal infection.