Effect of clofibrate in non-hemolytic indirect hyperbilirubinemia in full term neonates

Objective Jaundice is a common clinical problem in neonatal period which may result in brain damage even in healthy full term newborns, when it is severe. The aim of this study was to characterize the therapeutic effect of clofibrate in full term neonates who present with nonhemolytic jaundice. Methods A clinical controlled study was performed on 60 full term neonates who presented with non-hemolytic jaundice. 30 neonates were treated with a single oral dose of clofibrate (100 mg/Kg) plus phototherapy (case group), while 30 neonates received only phototherapy (control group). Both groups were compared in regard to post therapeutic mean total and indirect plasma bilirubin levels, admission duration and the rate of exchange transfusion. Results The reduction rate of total and indirect plasma bilirubin levels were significantly higher in the clofibrate-treated group as compared with the control group (P<0.05). The mean duration of admission was found to be reduced from 2.9 +/− 0.9 days in the control groupl to 2.2 +/− 0.6 days in clofibrate-treated group (P=0.002). The mean plasma total bilirubin level was lower in the clofibrate-treated group. No cases required phototherapy after 48 hour in clofibrate-treated group, while 9 neonates (30%) and 2 neonates (6.7%) required phototherapy after 72 hour and 96 hour respectively in the control group. There was no difference between both the groups for sex, the time of developing jaundice and the rate of exchange transfusion. Conclusion A single dose of clofibrate (100 mg/Kg) alongwith phototherapy is more effective than phototherapy alone in treating non-hemolytic hyperbilirubinemia in term healthy newborn infants.     

Randomized controlled trial of oral versus intravenous fluid supplementation on serum bilirubin level during phototherapy of term infants with severe hyperbilirubinaemia

OBJECTIVE: To compare the rates of decrease in serum bilirubin levels in severely jaundiced healthy term infants given oral or intravenous fluid supplementation during phototherapy. METHODS: A randomized controlled study was carried out in the neonatal intensive care unit (NICU) of Hospital Universiti Kebangsaan Malaysia over a 12-month period. Fifty-four healthy term infants with severe hyperbilirubinemia were randomized to receive either solely enteral feeds (n = 27) or both enteral and intravenous (n = 27) fluid during phototherapy. RESULTS: There were no significant differences in the mean birthweight, mean gestational age, ethnic distribution, gender distribution, modes of delivery and types of feeding between the two groups. Similarly, there was no significant difference in the mean indirect serum bilirubin (iSB) level at the time of admission to the NICU between the enteral (359 +/- 69 micromol/L [mean +/- SD]) and intravenous group (372 +/- 59 micromol/L; P = 0.4). The mean rates of decrease in iSB during the first 4 h of phototherapy were also not significantly different between the enteral group (10.4 +/- 4.9 micromol/L per h) and intravenous group (11.2 +/- 7.4 micromol/L per h; P = 0.6). There was no significant difference in the proportion of infants requiring exchange transfusion (P = 0.3) nor in the median duration of hospitalization (P = 0.7) between the two groups. No infant developed vomiting or abdominal distension during the study period. CONCLUSION: Severely jaundiced healthy term infants had similar rates of decrease in iSB levels during the first 4 h of intensive phototherapy, irrespective of whether they received oral or intravenous fluid supplementation. However, using the oral route avoided the need for intravenous cannulae and their attendant complications.     

Effect of feeding type on the efficacy of phototherapy

OBJECTIVE: The objective of this study was to assess the efficacy of phototherapy for nonhemolytic hyperbilirubinemia and rebound bilirubin levels in breast-fed newborns as compared with mixed-fed (breast milk and formula) newborns. STUDY DESIGN/SETTING: Prospective study of effects of feeding type on response to phototherapy in newborns. METHODS: The subjects were 53 full-term healthy newborns with nonhemolytic hyperbilirubinemia [defined as total serum bilirubin 12 mg/dL (205.2 micromol/L) in the first 48 hours of life or 15 mg/dl (256.5 micromol/L), on subsequent days]. Groups were formed according to type of feeding. Group 1 consisted of 28 breast-fed newborns and group 2 consisted of 25 mixed-fed newborns. Phototherapy was terminated when total serum bilirubin concentration fell to 14 mg/dL (< 239.4 micromol/L). Rebound bilirubin measurements were obtained 24 hours after phototherapy ended. RESULTS: The groups were comparable with respect to age at the start of phototherapy. The amount of weight loss (relative to birth weight) recorded at the start of phototherapy was significantly greater in group 1 than in group 2 (8.1+/- 3.9% vs. 5.4+/- 2.6% p = 0.004). The duration of phototherapy was significantly longer in group 1 than in group 2 (38.6+/- 12.6 h vs. 26.8+/- 9.4 h; P < 0.001). The 24-hour rate of decrease in bilirubin concentration in group 2 was significantly higher than that in group 1 [5.4+/- 2.2 mg/dL/d (92.3+/-37.6 micromol/L/d) vs. 4+/- 1.3 mg/dL/d (68.4+/- 22.2 micromol/L/d); p = 0.01]. The overall rate of decrease in bilirubin concentration in group 1 was significantly lower than that in group 2 [0.16+/- 0.05 mg/dL/h (2.73+/- 0.85 micromol/L/h) vs. 0.22+/- 0.09 mg/dL/h (3.76+/- 1.53 micromol/L/h); p = 0.01]. There was no significant difference between the two groups with respect to rebound bilirubin concentration (P = 0.184). Conclusion: Phototherapy effectively reduced bilirubin levels in breastfed newborns with hyperbilirubinemia, but these patients show significantly slower response to this treatment than mixed-fed newborns.     

不同方法对重症新生儿高胆红素血症的疗效观察

探讨不同治疗方法对重症新生儿高胆红素血症的治疗效果 ,将 43例重症新生儿高胆红素血症患儿 (达换血标准 )按治疗方法分为 3组。光疗组 1 5例 ,予以药物治疗及光疗直至退黄 ;丙球组 1 6例 ,药物及光疗同前组 ,另加静脉输注丙种球蛋白(简称丙球 )× 3d ;换血组 1 2例 ,予以换血 ,换血前后药物治疗及光疗同前二组。所有三组患儿分别于治疗前 ,治疗后第 1d、4d、7d测血胆红素。结果 :( 1 )血清胆红素值 :治疗第 1d换血组明显低于丙球组及光疗组 (P均 <0 0 1 ) ,但光疗组与丙球组之间无统计学意义 (P >0 0 5) ;治疗第 4d、7d三组间比较均有显著性差异 (P均 <0 0 1 ) ;( 2 )所需光疗时间及黄疸消退时间 :换血组明显低于丙球组及光疗组 (P均 <0 0 1 ) ,但光疗组与丙球组之间无统计学意义 (P >0 0 5) ;( 3)临床情况 :43例患儿黄疸均消退 ,换血组 1 2例无胆红素脑病、贫血发生 ;丙球组胆红素脑病 2例 ,明显贫血 5例 ;光疗组胆红素脑病 3例 ,明显贫血 5例 ,亦因拒绝输血而未予纠正。结论 :换血疗法仍然是治疗重症新生儿黄疸的最佳选择     

Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia - a double-blind, randomized, controlled trial

Aim: To compare the incidence of hyponatremia in full‐term neonates with severe hyperbilirubinemia, receiving intravenous fluid supplementation with 0.2% saline in 5% dextrose versus 0.9% saline in 5% dextrose, to prevent blood exchange transfusion (BET). Methods: In this double‐blind, randomized, controlled trial, full ‐ term newborns (≥37 weeks), appropriate for gestational age, with severe non‐haemolytic hyperbilirubinemia (serum bilirubin ≥ 20 mg/dL) were enrolled. Eligible neonates were randomized to receive either 0.2% saline in 5% dextrose (hypotonic fluid group) or 0.9% saline in 5% dextrose (isotonic fluid group) over 8 hrs, in addition to phototherapy. The primary outcome was proportion of neonates developing hyponatremia (serum Na < 135 mmol/L) after 8 h. Results: Forty‐two neonates were analysed in each group. Proportion of neonates developing hyponatremia after 8 h was higher in hypotonic fluid group as compared to isotonic fluid group (48.8% vs. 10.5%, p < 0.001). However, a larger proportion in isotonic fluid group developed hypernatremia (39.5% vs. 12.2%, p < 0.001). The rate of BET was similar in both groups. Conclusion: In full‐term neonates with severe hyperbilirubinemia, administration of hypotonic fluid to prevent BET was associated with a higher incidence of hyponatremia while isotonic fluid was associated with an increased incidence of hypernatremia.     

茵栀黄口服液治疗足月新生儿高间接胆红素血症的多中心随机对照研究

目的 通过大样本的前瞻性多中心随机对照试验,评价茵栀黄口服液对足月新生儿高间接胆红素血症的治疗效果及安全性。方法 2010年3月至9月期间16家医院收治的胆红素水平达到美国儿科学会指南的时龄-胆红素水平曲线第40百分位的足月儿,随机分为单纯光疗组(409例)、苯巴比妥联合光疗组（373例）和茵栀黄口服液联合光疗组（395例）。入组后立即开始药物治疗,并持续5d,一旦胆红素水平达到光疗水平则加用光疗。分别记录各组患儿的一般资料,比较治疗前、治疗72 h和治疗完成后的血清胆红素水平及胆红素水平的下降率,以及不同干预对光疗率的影响。比较各组不良反应的发生率。结果 符合人选标准患儿共计1177例,男性707例(60.1％),汉族1119例(95.1％)。治疗前血清总胆红素平均为(282.0±70.9)μmol/L,最高为626 μmol/L。其中血清总胆红素水平在342 μmol/L～427μmol/L((20 mg/dl～25 mg/dl)的重度高胆红素血症186例,占15.8％;＞427 μmol/L(25 mg/dl)的极重度高胆红素血症30例,占2.5％。3组间治疗72 h的胆红素水平下降率差异没有统计学意义（F=2.89,P=0.056）。治疗完成后茵栀黄口服液组的胆红素水平下降率明显超过其他2组（F=5.55,P=0.004）。茵栀黄口服液组未接受光疗的比例显著高于苯巴比妥组和单纯光疗组(x2=47.38,P=0.000)。30例极重度高胆红素血症患儿,经过光疗或光疗联合药物治疗,虽未经换血,但均未出现神经系统症状。茵栀黄口服液联合光疗组有25.1％的患儿每天大便次数超过5次,该比例显著高于其他两组;皮疹的发生率高于苯巴比妥组,但是和单纯光疗组并没有显著差异。结论因黄疸入院的足月儿约18％是重度或极重度高胆红素血症。茵栀黄口服液联合光疗对于足月儿高间接胆红素血症具有较好的疗效,尽早服用茵栀黄口服液可以抑制胆红素水平进一步上升,使部分患儿避免光疗。应用茵栀黄口服液除大便次数增加和皮疹以外,未观察到其他严重不良反应。     

Efficacy of oral phenobarbitone in term "at risk" neonates in decreasing neonatal hyperbilirubinemia: a randomized double-blinded, placebo controlled trial

OBJECTIVE: To evaluate the efficacy of oral phenobarbitone in "at risk " term neonates (with high cord bilirubin) in decreasing hyperbilirubinemia. DESIGN: Double blind, placebo-control, randomized trial. SETTING: Tertiary level neonatal unit. OUTCOME: Primary-hyperbilirubinemia defined as total serum bilirubin (TSB) greater than 13 mg/dL. Secondary-TSB at 72 +/- 12 hr, need for phototherapy or exchange transfusion and side effects of phenobarbitone therapy. METHODS: All consecutively born term healthy neonates with cord bilirubin > or = 2.5 mg/dL were randomly assigned to receive either phenobarbitone (n = 37) or placebo (n = 38) after obtaining informed consent. Phenobarbitone was administered orally (5 mg/kg/day) for 3 days starting within 12 hours of birth. The neonates were followed up till seven days of life. TSB was estimated in neonates who developed jaundice with clinically assessed level of 8-10 mg/dL and at 72 +/-12 hours of age in 55 neonates. RESULTS: The baseline characteristics were similar in two groups. There was no significant reduction in incidence of hyperbilirubinemia in phenobarbitone group compared to in placebo group (6/37 (16.2%) versus 13/38 (34.3%); RR 0.47, 95% confidence interval: 0.20-1.11; risk difference: -18.1%, 95% confidence interval: -39.5 to 3.3%). However TSB at 72 +/-12 hours in phenobarbitone group (mean +/- S.D: 10.0 +/- 3.7 mg/dL) was significantly lesser than in placebo group (mean +/- S.D: 12.3 +/- 3.3 mg/dL) (difference of means: -2.3 mg/dL, 95% confidence interval: -3.9 to -0.7 mg/dl, P = 0.018). No significant difference with respect to need for treatment was observed in two groups. No significant adverse effects of phenobarbitone were noted. CONCLUSIONS: Prophylactic phenobarbitone is not helpful in reducing the incidence of hyper-bilirubinemia in "at risk" term neonates.     

新生儿血型不合溶血病丙种球蛋白治疗安全性和有效性的Meta分析

目的 新生儿母婴血型不合溶血病仍是新生儿早期高胆红素血症的主要病因,严重者需要光照及交换输血治疗.早期静脉使用丙种球蛋白可以在一定程度上阻断溶血.本研究通过Meta分析评价静脉滴注丙种球蛋白对新生儿血型不合溶血病的治疗作用及安全性.方法 使用相关检索词检索MEDLINE、Cochrane Library、EMBASE、CNKI及CBM数据库,获得关于静脉滴注丙种球蛋白治疗新生儿Rh及ABO血型不合溶血病的临床随机对照试验,采用Review Manager 4.2统计软件对数据进行Meta分析.结果 共纳入6篇文献、456例溶血病新生儿.其中4篇文献纳入Rh血型不合溶血病患儿,共109例;4篇文献纳入ABO血型不合溶血病患儿,共347例.各研究中丙种球蛋白治疗组和对照组新生儿的胎龄、体重及性别等均无统计学差异.静脉滴注丙种球蛋白联合光疗组新生儿相对于单纯光疗组新生儿,平均光疗时间缩短(加权均数差-15.42,95%可信区间-29.00～-1.85),换血人数比率明显减少(相对危险度0.25,95%可信区间0.17～0.39),平均住院时间缩短(加权均数差-25.44,95%可信区间-36.93～-13.94),但是对降低血清最高胆红素值的效果不明显(加权均数差-29.91,95%可信区间-78.24～18.42),对晚期贫血的发生也无明显作用.没有研究发现静脉应用丙种球蛋白有明显的不良反应.结论 Meta分析支持静脉滴注丙种球蛋白对新生儿血型不合溶血病有一定治疗效果,可缩短光疗时间,减少换血次数,但还需要更严格设计的大样本双盲随机对照试验,并应进行较长期的随访研究.     

Comparison of the effectiveness of phototherapy and exchange transfusion in the management of nonhemolytic neonatal hyperbilirubinemia.

The relative effectiveness of phototherapy and exchange transfusion for nonhemolytic neonatal hyperbilirubinemia was compared in two closely matched groups of infants. Although the exchange transfusion achieved an immediate reduction of bilirubin level, the "rebound" was rapid and tended to offset this reduction. The more gradual and steady effect of phototherapy resulted in a significantly lower serum bilirubin level at 1, 2, and 3 days after commencement of therapy; the rebound after phototherapy was small. Phototherapy was demonstrated to be more effective than exchange transfusion in achieving prolonged reduction of bilirubin levels for nonhemolytic hyperbilirubinemia. With more efficient lamps delivering more energy in the desired spectrum, it would seem feasible to treat hyperbilirubinemia of whatever etiology with this safer and more convenient form of therapy, though sometimes only as in adjunct therapy.     

脐血胆红素预测新生儿黄疸的意义

目的研究脐带血胆红素水平预测足月健康新生儿后续黄疸程度的价值。方法523例足月健康新生儿,测定脐血胆红素、白蛋白水平,监测每日经皮胆红素值（TCB）。对时龄0—24hTCB≥18;-48hTCB≥21;-72hTCB≥25;〉72h≥25者,送检静脉血血清胆红素值（TSB）,考虑是否需要光疗。将新生儿按脐血胆红素水平分为〈30μmol／L;≥30μmoL／L;≥36μmol／L;≥42μmoL／L,共4组。比较4组新生儿TCB≥25、TSB〉205μmol／L、TSB〉257μmoL／L及需要光疗的发生率。对脐血胆红素水平预告新生儿黄疸进行分析。比较黄疸组新生儿和非黄疸组新生儿临床特征。结果脐血胆红素水平升高,各组新生儿TCB≥25、TSB〉205μmol／L、TSB〉257μmoL／L和需要光疗的发生率增加。脐血胆红素水平用于预测新生儿黄疸发生有统计学意义（P〈0．001）。黄疸组新生儿脐血胆红素值显著高于非黄疸组（t=10．96,P〈0．001）。而脐血清白蛋白值（t=2．38,P〉0．05）、妊娠周数（t=-0．90,P〉0．05）、出生体重（t=0．10,P〉0．05）比较,两组均无统计学差异。结论脐血胆红素水平用于预测足月健康新生儿后续黄疸的程度是一种有效的方法。     

Neonatal hyperbilirubinemia associated with glucose-6-phosphate dehydrogenase deficiency in Sephardic-Jewish neonates: incidence, severity, and the effect of phototherapy.

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is frequently associated with neonatal hyperbilirubinemia, and sometimes kernicterus, often in the absence of any identifiable trigger or hematological evidence of hemolysis. The aim of this study was to compare the incidence and severity of, and the effect of phototherapy on, jaundice in G 6-PD-deficient vs G-6-PD-normal neonates in the Sephardic-Jewish community. Healthy term newborns, born to mothers of families stemming from geographic areas known to be "at risk" for G-6-PD deficiency, were screened for the condition and surveyed for hyperbilirubinemia. Seventy-five G-6-PD-deficient neonates formed the study group, while 266 neonates with normal levels of the enzyme formed the control group. Neonates with any other identifiable cause for jaundice were excluded. Phototherapy was commenced when the serum bilirubin levels reached 16 mg/dL (274 mumol/L) or more, and it was discontinued at 12 mg/dL (205 mumol/L) or less. Hyperbilirubinemia developed in 27 (36%) of the deficient neonates (serum total bilirubin greater than 13.9 mg/dL [238 mumol/L]), compared with 50 (18.8%) of control neonates (P = .002), while 20 (26.7%) of the study group required phototherapy, compared with 31 (11.7%) of control neonates (P = .002). Two neonates in the study group required exchange transfusion (serum bilirubin greater than 20 mg/dL [342 mumol/L]), vs 0 in the control group (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)     

A new device for phototherapy of neonatal jaundice]

The effectiveness of a new device for phototherapy in the treatment of nonhemolytic hyperbilirubinemia (Wallaby Phototherapy System) was evaluated. 46 healthy term infants, appropriate for gestational age and with serum bilirubin > 12 mg/dl in the first 3 days of life or > 15 mg/dl after 3rd day were randomly assigned to a treatment group (24 hours of light exposure with Wallaby Phototherapy System) and to a control group (any treatment for hyperbilirubinemia). Body temperature, weight, feeding and hydration were recorded during the study period. Serum bilirubin and haematocrit were done every 12 hours in all babies. In the treated group we found a decrease of 5.1% and of 7.8% at 12 and 24 hours, while an increase of 3.37% and of 2.9% at 12 and 24 hours was found in the control group. After 24 hours the serum bilirubin level was significantly lower in the treated group than in the control group (p < 0.05). No newborn of the treated group needed conventional phototherapy versus 4 control infants (17.4%). The conclusion of our study is that the Wallaby System is useful in the treatment of neonatal nonhemolytic hyperbilirubinemia even if its effectiveness for higher bilirubin levels has still to be tested.     

Phototherapy for neonatal hyperbilirubinemia: six-year follow-up of the National Institute of Child Health and Human Development clinical trial

The National Institute of Child Health and Human Development Randomized, Controlled Trial of Phototherapy for Neonatal Hyperbilirubinemia was conducted to determine whether phototherapy used to control serum bilirubin is safe and is as effective in preventing brain injury as exchange transfusion. The study, conducted at six neonatal care centers, randomly assigned 1339 newborn infants to phototherapy or control groups by the following subgroups: (1) birth weight less than 2000 g; (2) birth weight 2000 to 2499 g and bilirubin level greater than 171 mumol/L (10 mg/dL); or (3) birth weight greater than or equal to 2500 g and bilirubin level greater than 222 mumol/L (13 mg/dL). Phototherapy was administered for 96 hours, and exchange transfusion was used to control hyperbilirubinemia at the same predetermined levels in both groups. Neurological and developmental examinations were conducted at 1 and 6 years of age, with follow-up rates of 83% and 62%, respectively. The two groups did not differ in mortality or diagnosed medical conditions. The phototherapy and control groups had similar rates of cerebral palsy (5.8% vs 5.9%), other motor abnormalities including clumsiness and hypotonia (11.1% vs 11.4%), and sensorineural hearing loss (1.8% vs 1.9%). The Wechsler Intelligence Scale for Children-Revised scores overall were not significantly different for the two groups (Verbal, 96.8 vs 94.8; Performance, 95.8 vs 95.1 for phototherapy and control groups, respectively). Phototherapy effectively controlled neonatal hyperbilirubinemia without evidence of adverse outcome at 6 years of age and was at least as effective as management with exchange transfusion alone.     

Clofibrate as an Adjunct to Phototherapy for Unconjugated Hyperbilirubinemia in Term Neonates

Objective

To evaluate the efficacy of oral clofibrate as an adjunct to phototherapy for unconjugated hyperbilirubinemia in term neonates.

Methods

This randomized controlled trial was done in the level III neonatal intensive care unit (NICU) of a tertiary care hospital. Ninety term neonates with unconjugated hyperbilirubinemia with serum bilirubin 15–25 mg/dl were randomized to either intervention group (single dose of clofibrate in a dose of 50 mg/kg prior to starting phototherapy) or standard care group (only phototherapy). Primary outcome was absolute fall in bilirubin by 48 h. Secondary outcomes were duration of phototherapy, absolute fall in bilirubin levels at 12, 24, 36, 48 h, need for exchange transfusion and incidence of side-effects.

Results

After 48 h of intervention, significantly lower bilirubin levels were noted in the intervention group compared to standard care group with a mean difference of 7 mg/dl (95% CI 6.7 mg/dl to 7.2 mg/dl). Duration of phototherapy required was less in the intervention group compared to standard care group with mean difference of 23.82 h (95% CI 30.46 h to 17.18 h). Exchange transfusion was needed for 4 neonates in the standard care group and none in the intervention group. No side-effects were noted with clofibrate.

Conclusions

Single dose clofibrate prior to starting phototherapy in term neonates with uncomplicated unconjugated hyperbilirubinemia reduces the duration of phototherapy significantly.

     

Rebound in serum bilirubin level following intensive phototherapy

OBJECTIVES: To document the need for repeated phototherapy (as an index of significant rebound in serum bilirubin levels) following the discontinuation of intensive phototherapy and to compare the use of repeated phototherapy in infants who first received phototherapy during their birth hospitalization with the use of first-time phototherapy on readmission after infants were discharged from their birth hospitalization. DESIGN: A retrospective review of the medical records of 303 term and near-term newborns treated between January 1996 and December 1998, who received phototherapy in our well-baby nursery during their birth hospitalization (group 1, n = 158) or who had been discharged from the nursery and were readmitted for phototherapy (group 2, n = 144). All infants received intensive phototherapy but were managed by individual attending pediatricians. Rebound measurements were included if a bilirubin level was obtained between 4 and 48 hours after discontinuing phototherapy. SETTING: Newborn nursery and pediatric ward of a large community hospital. MAIN OUTCOME MEASURES: The number of infants who received repeated phototherapy and the magnitude of the bilirubin-level rebound. RESULTS: Thirteen (8.2%) of 158 (95% confidence interval [CI], 3.9-12.4) infants treated with phototherapy before discharge from the nursery (group 1) and only 1 (0.7%) of 144 (95% CI, 0-2.0) infants who first received phototherapy on readmission (group 2) received repeated phototherapy (P =.002). Phototherapy was discontinued when mean +/- SD total serum bilirubin levels were, 10.4 +/- 1.8 mg/dL (178 +/- 31 micromol/L) in group 1 and 12.3 +/- 1.3 mg/dL (210 +/- 22 micromol/L) in group 2. The mean +/- SD increase in the total serum bilirubin levels following rebound was 1.3 +/- 2.0 mg/dL (22 +/- 34 micromol/L) in group 1 and 0.27 +/- 1.46 mg/dL (4.6 +/- 25 micromol/L) in group 2 (P<.001). CONCLUSIONS: It is not necessary to keep infants in the hospital to check for rebound. However, for infants who require phototherapy during their birth hospitalization and for those with significant hemolytic disease, we recommend obtaining a follow-up bilirubin level 24 hours after discharge. This is probably not necessary in those who are readmitted for phototherapy but, because rare instances of significant rebound have occurred in these infants, additional clinical follow-up is appropriate, particularly if phototherapy is discontinued at higher total serum bilirubin levels than used in this study.     

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.     

Carboxyhemoglobin Measurements in the Diagnosis of ABO Hemolytic Disease

To assess hemolysis in hyperbilirubinemic infants with ABO isoimmunization, we measured the carboxyhemoglobin (HbCO) concentrations in full-term infants with ABO isoimmunization during the first week of life. Two groups of infants, ABO compatible (n=34) and ABO incompatible (n=30), were further divided into two groups with and without hyperbilirubi-nemia. All the infants from ABO incompatible pregnancies showed a positive indirect Coombs' test. The groups with hyperbilirubinemia included infants with maximum serum total bilirubin levels about 15 mg/dL and infants treated by phototherapy or exchange transfusion. In the ABO incompatible infants, the HbCO levels in those with hyperbilirubinemia were significantly higher than in infants without hyperbilirubinemia during the first week after birth (p < 0.01 at 24, 72, 120 hours after birth, respectively). The levels of HbCO in the ABO incompatible infants with hyperbilirubinemia were significantly higher compared with the levels in the ABO compatible infants with hyperbilirubinemia (p < 0.05 at 24 hours, p < 0.01 at 72 and 120 hours after birth, respectively). HbCO measurement may facilitate the early diagnosis of hemolytic disease and the prediction of jaundice caused by ABO isoimmunization.     

Glucose-6-phosphate dehydrogenase deficiency in neonatal indirect hyperbilirubinemia

The aim of this article is to investigate the prevalence of Glucose-6-phosphate dehydrogenase (G6PD) deficiency in neonatal hyperbilirubinemia and to compare the clinical presentation and course of G6PD-deficient and normal patients. This study included a total of 624 term neonates with indirect hyperbilirubinemia from March 2001 to September 2004. Birth weight, sex, weight at admission, serum bilirubin at admission, maximum bilirubin, phototherapy duration, duration of hospitalization and the need for exchange transfusion were recorded. Laboratory evaluations included blood group typing of mother and newborn, complete blood count, peripheral blood smear, serum total and direct bilirubin, direct coombs test, reticulocyte count, serum-free T4 and TSH, urine analysis, urinary reducing substance and erythrocyte G6PD level. The analysis of the results indicated that 24 neonates with indirect hyperbilirubinemia were G6PD-deficient. No statistically significant difference was detected between G6PD-deficient and normal groups in relation to the time of onset of jaundice, reticulocyte count, hematocrit level, phototherapy duration and duration of hospitalization. Serum bilirubin at admission, maximum serum bilirubin level and the need for exchange transfusion were higher in G6PD-deficient group. From this study our conclusion is that the G6PD deficiency is a common enzyme defect causing severe indirect hyperbilirubinemia which may result in kernicterus. Early neonatal screening programmes should be instituted in countries where the deficiency is prevalent.     

Systematic review of intravenous immunoglobulin in haemolytic disease of the newborn

OBJECTIVES: To assess the effectiveness of high dose intravenous immunoglobulin (HDIVIG) in reducing the need for exchange transfusion in neonates with proven haemolytic disease due to Rh and/or ABO incompatibility. To assess the effectiveness of HDIVIG in reducing the duration of phototherapy and hospital stay. DESIGN: Systematic review of randomised and quasi-randomised controlled trials comparing HDIVIG and phototherapy with phototherapy alone in neonates with Rh and/or ABO incompatibility. RESULTS: Significantly fewer infants required exchange transfusion in the HDIVIG group (relative risk (RR) 0.28 (95% confidence interval (CI) 0.17 to 0.47); number needed to treat 2.7 (95% CI 2.0 to 3.8)). Also hospital stay and duration of phototherapy were significantly reduced. CONCLUSION: HDIVIG is an effective treatment.     

Current validity of the exchange transfusion intervention by the classic indication. Our 15 years' experience

In this paper the Authors report their personal experience of the use of exchange transfusion, secondary to classic indication, in the treatment of neonatal hyperbilirubinemia, in order to: 1) determine the trend over the past wears in the number of exchange transfused neonates, both from a global point of view and in relation to indications; 2) critically assess the risks, in terms of complications and mortality, correlated to exchange transfusion. Four hundred and eighty-eight neonates, who were subjected to 693 exchange transfusions in the Pediatric Clinic and Neonatal Division of the Policlinico Gemelli in Roma, were studied over a period of 15 years (1972-1986), according to the following indications: 214 cases of neonatal hyperbilirubinemia with MEN-Rh, 106 cases of neonatal hyperbilirubinemia with MEN-ABO and 168 cases of idiopathic hyperbilirubinemia. The total number of exchange transfused neonates decreased drastically from 304 in the period 1972-76 to 65 in the period 1982-86. The frequency of exchange transfused neonates because of idiopathic hyperbilirubinemia decreased significantly (p greater than 0.001), booth in comparison to the number of live births and in comparison to the number of exchange transfused neonates, probably due to the gradual introduction of phototherapy. The frequency of exchange transfused neonates with iso-Rh and iso-ABO decreased or remained stationary on account of the confirmed relative lesser efficacy of phototherapy on hemolytic jaundice. With regard to mortality and morbidity, 27 out of 488 neonates died during the neonatal period, but only 4 within six hours of exchange transfusion; the majority of those who died had a reduced gestational age and low birthweight, and were affected by a severe associated pathology.