Effect of clofibrate in jaundiced term newborns

Objective: Clofibrate is a glucuronosyl transferase inducer that has been proposed to increase the elimination of bilirubin in neonates with hyperbilirubinemia. The aim of this study was to characterize the therapeutic effect of clofibrate in neonates born at full term and present with non-hemolytic jaundice.Methods: A clinical controlled study was performed in two groups of healthy full term neonates. Thirty neonates were treated with a single oral dose of clofibrate (100 mg/kg) plus phototherapy (clofibrate-treated group) while another 30 neonates (control group) received only phototherapy.Result: The mean plasma total bilirubin levels of 12^th, 24^th and 48^th hours were significantly lower in the clofibrate-treated group as compared with the control group (P<0.0001, P<0.0001 and P=0.004, respectively). Treatment with clofibrate also resulted in a shorter duration of jaundice and a decreased use of phototherapy (P<0.0001). No side effects were observed.Conclusion: Although other pharmacological agents such as metalloporphyrins and Sn-mesoporphyrin also seem to be effective in decreasing bilirubin production, these products are not available for routine use and cannot be used because the safety of these drugs has to be confirmed prior to their widespread use. Therefore, clofibrate is now the only available pharmacological treatment of neonatal jaundice.     

Late neurological sequelae of non-hemolytic hyperbilirubinemia of healthy term neonates

Records of the only children's hospital equipped to perform exchange transfusions in West Berlin were used to identify all 29 non-hemolytic healthy term newborns with total serum bilirubin between 20 and 30 mg/dL, 16 of whom were available for follow-up neurological examination according to Touwen. Compared to 18 case controls with bilirubin <12 mg/dL, jaundiced children scored significantly worse only on the choreiform dyskinesia scale.     

Gamma-glutamyl transferase in neonatal non-hemolytic indirect hyperbilirubinemia

Serum gamma-glutamyl transferase (GGT) activities were determined on the third day of life in healthy controls (n:15) and in infants with non-hemolytic hyperbilirubinemia (n:16). GGT activities were 39.6 +/- 28.4 units/ml and 46.6 +/- 26.7 units/ml, respectively. There was no statistical difference between both groups (p greater than 0.05).     

Brainstem auditory electrophysiology is supressed in term neonates with hyperbilirubinemia

BackgroundWhether hyperbilirubinemia suppresses electrophysiological activity of the neonatal auditory brainstem remains to be investigated.AimTo determine whether hyperbilirubinemia suppresses the brainstem auditory electrophysiology in term neonates.MethodsMaximum length sequence brainstem auditory evoked response (MLS BAER) was recorded shortly after confirming hyperbilirubinemia in 58 term neonates. Wave amplitudes of the response were analyzed in detail.ResultsCompared with age-matched term controls, the neonates with hyperbilirubinemia showed a significant reduction in the amplitudes of MLS BAER waves III and particularly V at all click rates 91–910/s. The reduction tended to be more significant at higher than lower rates. Wave I amplitude was reduced at 910/s. V/I amplitude ratio was decreased at all click rates. Therefore, the amplitudes of MLS BAER, particularly later, waves were all reduced. The amplitudes of all MLS BAER waves tended to be reduced with the increase in total serum bilirubin level. All wave amplitudes were correlated with the level of total serum bilirubin at some or most click rates.ConclusionsBrainstem auditory electrophysiology is suppressed in neonates with hyperbilirubinemia, which related to the severity of hyperbilirubinemia. Wave amplitudes are valuable BAER variables to detect functional impairment of the brainstem and auditory pathway in neonatal hyperbilirubinemia, and are recommended to be used in assessing bilirubin neurotoxicity to the neonatal brain.     

Indications of phototherapy for full term newborn infants with non-hemolytic hyperbilirubinemia: a critical analysis

Phototherapy is a common procedure in the neonatal period. However there is great controversy in the literature about when and at which serum bilirubin levels phototherapy and exchange transfusion should be indicated. The aim of this paper is to review the literature and to suggest guidelines to help pediatricians in deciding when to treat non-hemolytic jaundice in full-term newborn infants.     

Serum levels of resistin and its correlation with adiponectin and insulin in healthy full term neonates

Resistin and adiponectin are two adipokines involved in the regulation of insulin sensitivity, and have been suggested as mediators of adult metabolic syndrome.

Aim

The aim of this study was to investigate cord blood levels of resistin, and their postnatal changes in full-term appropriate for gestational age (AGA) neonates. Interrelations between resistin, adiponectin, and insulin, and between resistin and neonatal and maternal anthropometric parameters were also assessed.

Design

Blood samples were obtained from 30 full term AGA neonates at birth and on the 4th day of life. Anthropometric variables studied included birth weight, length, body mass index (BMI), neonatal weight loss, and mother's BMI. Resistin and adiponectin were determined by ELISA, and insulin by radioimmunoassay method. Data were analyzed using Wilcoxon test and Spearman's correlation coefficient.

Results

Resistin levels were high at birth and did not change on the 4th day of life. Resistin levels were not correlated to insulin, nor adiponectin levels, nor any anthropometric parameter of neonates or their mothers. Instead, adiponectin levels increased on the 4th day of life, and were correlated to insulin levels.

Conclusion

High levels of resistin in full-term AGA neonates suggest that this hormone may play a role in maintenance of metabolic neonatal homeostasis, but its physiological significance needs further investigation.     

200例新生儿高间接胆红素血症的临床分析

新生儿高间接胆红素血症（以下简称高胆）发病率较高,在部分医院依然占据新生儿住院病例的首位［１～４］。为进一步了解新生儿高胆的病因、程度分布、发病日龄、临床主要表现、治疗所需时间和预后等相互间关系,本文对我院儿科住院的２００例新生儿高胆患儿的临床资料作...     

Transcutaneous bilirubin in predicting hyperbilirubinemia in term neonates

Objective  To assess the utility of 24 and 48 hours transcutaneous bilirubin (TcB) index for predicting subsequent significant hyperbilirubinemia in healthy term neonates. Methods  TcB indices were obtained for healthy, breastfed, term AGA newborns at 24 ± 2, 48 ± 2 and subsequently at intervals of 24 hours. Neonates with illness, on treatment and positive Direct Coomb’s test were excluded. Serum bilirubin levels were obtained whenever indicated. Neonates having serum bilirubin ≥ 17 mg/dL were considered as significant hyperbilirubinemia. The 24 and 48 hour TcB indices, as risk predictors for such hyperbilirubinemia were determined. Results  Study included 461 healthy term neonates. The mean birth weight was 2949 (± 390) gm and mean gestation of 38.6 (± 1.1) weeks. Eight one (17.6%) had significant hyperbilirubinemia. Of 461, 135 (29.3%) had TcB index < 5 at 24 hours and 200 (43.3%) had index < 8 at 48 hours. None of them had later hyperbilirubinemia (100 % negative predictive value). Significant hyperbilirubinemia increased from 8.1 % to 76.4% as 24 hours TcB index raised from 5 to 9 and from 10.4 % to 83.7% as 48 hour TcB index raised from 8 to 11. Sensitivity and specificity were optimised at TcB value of 7(risk: OR=26.8, 95%Cl: 13.9–51.5) at 24 hours and 10 (risk: OR= 17.1, 95%Cl 8.9–32.9) at 48 hours. C-statistics for 24 and 48 hour measurements are 0.838 and 0.836 respectively. Conclusion  The 24 and 48 hour TcB indices are predictive for subsequent significant hyperbilirubinemia and can guide clinician in early discharge of healthy term newborns.     

Serum alpha-fetoprotein (AFP) levels in breastfed infants with prolonged indirect hyperbilirubinemia

The aim of this prospective study was to verify normal serum AFP (alpha-fetoprotein) levels in jaundiced breastfed infants with indirect hyperbilirubinemia. METHODS: The study was conducted in clinically jaundiced breastfed infants, 20, or more, days old, referred to our outpatient ambulatory. Inclusion criteria were: birth at term after a physiologic pregnancy, with an Apgar score >7 at 1 and 5 min, no evidence of congenital anomalies or diseases, direct bilirubin <1 mg/dl, normal values of alpha-1-antitrypsin, glucose-6-phosphate dehydrogenase, thyroid stimulating hormone, triiodothyronine, tyroxine, and normal growth. 30 non-jaundiced breastfed infants age-weight-matched, were used as control group. RESULTS: 98 jaundiced breastfed infants satisfied inclusion criteria. Their mean serum concentration of AFP was significantly higher than control infants (3548 vs 1095 ng/ml, p<0.001). Serum AFP levels of jaundiced infants were directly associated with serum indirect bilirubin and gamma-glutamyltranspeptidase concentrations. CONCLUSIONS: The most probable explanation of elevated AFP in jaundiced breastfed infants may be the presence in human milk of one or more factors which affect hepatocyte growth and/or function. Based on our finding we demonstrated that in jaundiced breastfed infants normal range of serum AFP levels are higher than previously published data for healthy infants. Our data can be useful for a right interpretation of AFP levels in breastfed infants with prolonged jaundiced and may be used to avoid unnecessary investigations.     

Cerebral infarcts in full term neonates

Cerebral infarcts are an important cause of neonatal convulsions. We report the etiologic factors, and clinical and neuroradiologic findings of four full term neonates who presented with neonatal convulsions and had cerebral infarct. In our patients the risk factors for the cerebral infarct were perinatal asphyxia, sepsis, dehydration and catheter application. All had convulsions as the initial sign of infarct and had cranial imaging which revealed the definitive diagnosis. The patients underwent an extensive evaluation for hereditary causes of cerebral infarct that included anticoagulant factors (Proteins C and S, antithrombin III, antiphospholipid antibodies), factor V Leiden and prothrombin gene mutations, blood and urine amino acid and urine organic acid levels. The results were found to be within normal limits. In conclusion, neonatal convulsions can be the first sign of cerebral infarct. For this reason it seems preferable to include cranial imaging by computed tomography or magnetic resonance imaging (MRI) in the work-up of cases with unexplained neonatal convulsions.     

Risk factors for hyperbilirubinemia in breastfed term neonates

Increased breastfeeding was suggested as a contributing factor to significant hyperbilirubinemia. The aim of this study was to identify the risk factors associated with jaundice in exclusively breastfed term neonates. We retrospectively reviewed all consecutively live-born neonates from August 2009 to July 2010 who had complete outpatient department (OPD) follow-up at ≤14 days old. Hyperbilirubinemia was defined as a transcutaneous bilirubin (TcB) value of ≥15 mg/dl. During the study period, there were 718 deliveries, of which 152 neonates were transferred to the special care nursery or neonatal intensive care unit; 566 neonates were discharged from the nursery, and 243 neonates were excluded: 83 did not return to the OPD, 46 were older than 14 days at OPD follow-up, 44 were <37 weeks of gestational age, and 70 had been fed formula. In total, 323 neonates were enrolled and classified into the hyperbilirubinemic (114 neonates) and non-hyperbilirubinemic groups (209 neonates). The gender, gestational age, Apgar score, age at nursery discharge, birth weight, and body weight at nursery discharge and at OPD were comparable between the two groups. TcB values at nursery discharge were positively correlated with TcB values in the OPD. Infants with hyperbilirubinemia exhibited significantly greater body weight loss from birth to the OPD follow-up and significantly less body weight gain from nursery discharge to OPD follow-up. Conclusion High TcB values at nursery discharge and a smaller body weight gain are associated with hyperbilirubinemia in term neonates who are exclusively breastfed.     

Efficacy of light-emitting diode versus other light sources for treatment of neonatal hyperbilirubinemia: a systematic review and meta-analysis

Various light-emitting diode (LED) phototherapy devices have been trialled on the assumption of a more effective spectral distribution of the light emitted. We reviewed the current literature to determine whether LED is more effective than other types of phototherapy. Eligible studies were randomized controlled trials of LED versus other phototherapies. Studies were found to be of medium quality based on a components approach. Data were statistically aggregated within a very homogeneous population (term or late preterm neonates). Results appeared robust at sensitivity analysis. Five hundred and eleven neonates were included in the meta-analysis. LED and other phototherapy devices appeared to be equally effective in reducing total serum bilirubin (TSB) in term or late preterm neonates. The pooled mean TSB rate of decrease was 3.269 μmol/L/h (0.191 mg/dL/h) and 3.074 μmol/L/h (0.18 mg/dL/h) in the LED and conventional arms, respectively [average difference in TSB rate of decrease = 0.194 μmol/L/h (0.011 mg/dL/h) in favour of LED phototherapy; p = 0.378]. CONCLUSION: No significant difference in TSB rate of decrease was detected between LED and other types of phototherapy. Further randomized controlled trials are needed to ascertain whether LED phototherapy may be more effective when increasing the spectral power, or in certain selected subpopulations.     

健康新生儿经皮小时胆红素百分位列线图预测高胆红素血症的价值

目的 绘制健康新生儿小时经皮胆红素(TCB)百分位列线图,评价其在预测高胆红素血症发生风险中的价值。方法 选取5 250 名足月儿或晚期早产儿(胎龄≥ 35 周,出生体重≥ 2 000 g),连续记录生后168 h TCB 值。将生后24~48 h、49~72 h 和73~96 h 内对应最高危区TCB 值作为预测指标,采用小时TCB 列线图结合受试者工作特征曲线(ROC 曲线)评价小时TCB 列线图对高胆红素血症的预测价值。结果 小时TCB百分位列线图显示,生后16~72 h TCB 快速上升明显,72 h 后至144 h 上升逐渐减缓,144 h 后维持一个平稳高值,其中第95 百分位(P₉₅)小时胆红素在96 h 已趋于稳定。P₄₀、P₇₅、P₉₅ 小时TCB 高峰值分别为173、217、248 μmol/L。生后24~48 h、49~72 h 和73~96 h 内TCB 水平预测高胆红素血症ROC 曲线下面积(AUC)分别为0.77、0.85 和0.87。24~48 h、49~72 h 和73~96 h 内高危区预测新生儿高胆红素血症患病率分别为35.03%、43.35% 和79.95%,阳性似然比分别为3.35、4.75 和22.70。结论 小 时TCB 百分位列线图结合TCB 值危险区的划分可较好预测新生儿高胆红素血症的发生。73~96 h 内小时胆红素若处于高危区,73~96 h 后有较大可能发生高胆红素血症。     

足月新生儿不同程度黄疸听性脑干反应特点分析

目的 探讨不同程度黄疸足月新生儿的听性脑干反应（ABR）特点。方法 对2010年7月至2011年4月入住我院新生儿科的黄疸（以间接胆红素增高为主）足月新生儿（除外合并缺氧缺血性脑病、颅内出血、颅内感染,机械辅助通气者）进行ABR检测,分别测定Ⅰ、Ⅲ、Ⅴ各波的潜伏期（PL）、波间期（IPL）与振幅（AMP）。并根据性别分为男、女婴两组;根据胆红素水平分为3组：轻度组≤250μmol/L,中度组251~299μmol/L,重度组≥300μmol/L。比较不同性别及不同程度黄疸新生儿的ABR特点。结果 共入选足月黄疸新生儿442例,其中男婴筛查异常率46.2%,女婴筛查异常率29.8%,差异有统计学意义（P〈0.01）。男、女婴左耳平均阈值分别为39.6 dBnHL和32.2 dBnHL,右耳平均阈值分别为38.7 dBnHL和34.3 dBnHL,男婴均高于女婴,差异有统计学意义（P〈0.01）。重度组ABR筛查异常率（40.8%）明显高于轻度组（25.0%）,差异有统计学意义（P〈0.001）,重度组与中度组（37.9%）之间、中度组与轻度组之间差异均无统计学意义（P〉0.05）;重度组双耳Ⅰ波潜伏期、Ⅴ波潜伏期和Ⅰ~Ⅴ波间期均较轻度组和中度组延长,差异有统计学意义（P〈0.01）,轻度组与中度组差异无统计学意义（P〉0.05）。结论 黄疸足月儿中男婴听力损失发生率高于女婴。胆红素影响听力不仅表现在阈值升高,同时还存在波潜伏期及波间期延长、振幅降低。随着黄疸程度加重即胆红素水平的升高,ABR波形潜伏期也逐渐延长,达一定水平后影响中枢听觉神经。     

胰岛素样生长因子-1在新生儿高胆红素血症中的变化及意义

目的：胰岛素样生长因子-1(IGF-1)是神经系统必需的调节因子,目前少有报道其与高胆红素血症之间的关系。该文主要通过测定高胆红素血症（高胆）新生儿血清中IGF-1水平及新生儿神经行为评分(NBNA)来探讨IGF-1与高胆的关系及其临床意义。方法：应用电化学发光分析法检测57例高胆新生儿和 25例正常新生儿血清中IGF-1 浓度,同步测定血清总胆红素(TSB)、未结合胆红素(USB)及白蛋白(ALB)含量,计算USB与ALB比值(B/A),并行新生儿 NBNA 评分。高胆组按血清TSB值221~256 μmol/L,257~342 μmol/L,＞342 μmol/L分为轻、中、重三组;对照组TSB ＜85 μmol/L。结果：轻、中、重高胆患儿血清IGF-1浓度均值分别为39.38±8.42,30.77±4.65,26.34±2.05 ng/L,较对照组50.16±15.73 ng/ L明显降低,在轻、中、重高胆组间IGF-1浓度差异存在显著性(P＜0.01),其值随着胆红素的升高而降低;轻、中、重高胆组NBNA评分均值分别为35.01±2.26,32.45±2.74,26.77±5.02,明显低于对照组38.24±0.78(P＜0.01),高胆各组间差异也有显著性(P＜0.01);血清IGF-1 浓度与NBNA评分呈正相关(r=0.603, P＜0.01),与B/A值呈负相关(r=-0.483, P＜0.01)。结论：高胆患儿血清IGF-1浓度显著降低,降低程度与血清胆红素水平有关;IGF-1可能与新生儿胆红素脑损伤密切相关。［中国当代儿科杂志,2009,11（5）：357-360］     

The Effect of Clofibrate on Decreasing Serum Bilirubin in Healthy Term Neonates under Home Phototherapy

Objective

This study was designed to determine the effect of clofibrate on neonatal uncomplicated jaundice treated with home phototherapy.

Methods

This clinical trial study was performed on 60 newborns with jaundice that received home phototherapy. Inclusion criteria were body weight between 2500 to 4000 gr, breastfed, total serum bilirubin (TSB) between 14 to 20 mg/dl, aged over 72 hours. The neonates were randomly divided into two groups. All received home phototherapy. Group I received a single dose of 50 mg/kg clofibrate and the other group served as control group. Total serum bilirubin level was measured every 24 hours.

Findings

Two groups were matched regarding weight, sex, age and first TSB. At 24 and 48 hours of treatment, the mean values of TSB in the clofibrate group were 13.72 (1.56), 9.5 (0.56) and in the control group 15.30 (1.44), 12.6 (1.44). The results show that TSB was significantly decreased after 24 and 48 hours in clofibrate group (P<0.001). The mean duration of phototherapy in group I was 72(0.0) hours and in the control group 76.80 (±9.76) hours. The duration of phototherapy was significantly shorter in clofibrate group (P<0.001).

Conclusion

Clofibrate is effective for outpatients with neonatal hyperbilirubinemia who are under home phototherapy. Of course, further studies are needed for approved routine use of this drug in the treatment of neonatal jaundice.     

选择性剖宫产对新生儿近远期的影响

剖宫产手术技术的日臻完善、临床上对剖宫产手术指征的放宽以及对剖宫产术对新生儿不利影响的认识不足,都在一定程度上促使了剖宫产率的大幅上升.该文围绕选择性剖宫产手术对新生儿近期及远期的影响,分析其与新生儿呼吸系统疾病、医源性早产、免疫系统建立以及特异反应性疾病等之间的联系.目前认为,剖宫产手术虽不能作为独立危险因素存在,但可与其他因素产生协同作用,增加新生儿的病死率.所以,临床上应严格掌握手术指征,降低无手术指征的选择性剖宫产率.