Peak Serum Bilirubin Concentration Research Articles

Potential protective effects of bilirubin following the treatment of neonatal hypoxic-ischemic encephalopathy with hypothermia therapy.

Background: Therapeutic hypothermia (TH) is the standard therapy for hypoxic-ischemic encephalopathy (HIE) and is associated with a wide range of physiological changes. Objective: We re-evaluated the effects of HIE and TH on bilirubin measurements following HIE in a center involved in the China cooling randomized controlled trial (RCT). Methods: Serial serum bilirubin concentrations measured during the first week of life were compared among the HIE + NT (normothermia) group, HIE + TH treatment group and control group (without HIE). Survivors of HIE were followed and assessed at approximately 2 years of age, and the results were correlated with peak bilirubin levels during the first week of life. Results: One hundred and thirty-eight infants were available for analysis. Significantly lower bilirubin levels were recorded in the HIE + NT group than in the controls (P<0.05). Significant differences were not observed among the patients in the HIE + NT group (mild to severe) or between the HIE + TH group and the HIE + NT group at any time point (P>0.05). The peak serum bilirubin concentrations recorded at 96 h of age showed a good correlation with the results of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III) (P=0.02). Conclusion: Bilirubin potentially exerts a neuroprotective effect during the first week of life, and low temperature does not affect the possible antioxidant function of bilirubin during TH following HIE.

Contribution of UGT1A1 variations to chemotherapy-induced unconjugated hyperbilirubinemia in pediatric leukemia patients.

Chemotherapy for malignant neoplasms sometimes induces unconjugated hyperbilirubinemia, resulting in the early cessation of treatment. We evaluated the role of variations in the bilirubin uridine-5-diphosphate (UDP)-glucuronosyltransferase gene (UGT1A1) in unconjugated hyperbilirubinemia development during chemotherapy in pediatric patients with leukemia. UGT1A1 allelic variations were evaluated in 25 Japanese pediatric leukemia patients with hyperbilirubinemia (peak serum bilirubin concentration 3.57 ± 1.02 mg/dl) and 25 control patients without hyperbilirubinemia (0.92 ± 0.32 mg/dl) by PCR-direct sequencing. In the hyperbilirubinemic group, 22 of 25 patients showed biallelic variations of UGT1A1. Nine (36%) patients were homozygous for UGT1A1*6 and eight (32%) were compound heterozygous for UGT1A1*6 and UGT1A1*28. Three (12%) patients were homozygous for UGT1A1*28. There were no biallelic variations in UGT1A1 in the non-hyperbilirubinemic group. The allelic frequencies of UGT1A1*6 in the hyperbilirubinemic group (0.58) was significantly higher than those of the non-hyperbilirubinemic group (0.1) (χ(2) = 25.7, P < 0.05). The high frequency of biallelic variations of UGT1A1 in the hyperbilirubinemic group suggests an association with Gilbert syndrome. Therefore, it is not necessary to cease chemotherapy in patients with these mutations who develop unconjugated hyperbilirubinemia without associated liver dysfunction.

Prophylactic Versus Therapeutic Phototherapy in Very Low Birth Weight Infants

Background: Preterm and very low birth weight (VLBW) infants are at great risk of hyperbilirubinemia and bilirubin-associated brain damage. Objectives: The aim of this study was to compare the efficacy of prophylactic versus therapeutic phototherapy in VLBW infants. Patients and Methods: Fifty VLBW infants were randomly assigned to receive either phototherapy from the first day of life regardless of their serum bilirubin level for up to five days (prophylactic group) or phototherapy when their bilirubin level reached half the exchange transfusion level (therapeutic group). All data, including gestational age, gender, birth weight, serum bilirubin level on the first day, peak serum bilirubin concentration, the age at which the peak serum bilirubin level was reached, duration of phototherapy, and the number of exchange transfusions, were studied and analyzed. Results: The mean bilirubin level on the first day in both groups exhibited no significant difference. The peak serum bilirubin was 7.7 ± 1.4 and 8.5 ± 2.1 mg/dL in the prophylactic and therapeutic group, respectively, and there was no significant difference in the age at which the peak serum bilirubin levels were reached in both groups (2.4 ± 1.2 vs. 2.1 ± 1 days in the prophylactic and the therapeutic group, respectively). The mean duration of phototherapy in the prophylactic group was 84 ± 43 hours, while for the therapeutic group it was 72 ± 39 hours, and hence the difference was not significant. The need for an exchange transfusion was lower in the prophylactic group compared to the therapeutic group (33% vs. 7%), although the difference was not statistically meaningful (P < 0.112). Conclusions: According to our study, phototherapy should not be used as prophylactic therapy for all VLBW infants, but rather it should be individualized in order to maintain low bilirubin levels.

Total serum bilirubin levels during cyclooxygenase inhibitor treatment for patent ductus arteriosus in preterm infants

To determine whether ibuprofen use in VLBW infants is associated with increased serum bilirubin levels and impaired neurodevelopmental outcome at 2 years of age compared to indomethacin. We retrospectively evaluated bilirubin data and outcome parameters of 178 VLBW infants treated with COX inhibitors for a haemodynamically relevant patent ductus arteriosus (PDA) between 1998 and 2003 in a single institution. In our department ibuprofen replaced indomethacin for PDA treatment in 2001, while clinical and echocardiographic criteria for the indication of PDA invention have remained unchanged. Ibuprofen and indomethacin therapy groups did not differ in their baseline clinical profile. Peak serum bilirubin concentration was 10.2 mg/dL in the ibuprofen group and 8.6 mg/dL in the indomethacin group (p < 0.01), while phototherapy duration did not differ. At 2 years of age neurodevelopmental outcome was similar in both groups. In a single case analysis, four cases of adverse neurodevelopmental outcome despite inconspicuous clinical course were identified in the ibuprofen group. In VLBW infants with PDA, ibuprofen treatment was associated with higher bilirubin levels than indomethacin.

Outcomes of extremely premature infants related to their peak serum bilirubin concentrations and exposure to phototherapy.

To analyze, in extremely low birth weight infants, associations between peak bilirubin concentration and evidence of brain damage, and between peak bilirubin concentration and blindness attributable to retinopathy of prematurity. Retrospective study of 128 infants of </=800 g birth weight and </=27 weeks gestation born between 1980 and 1989 and discharged from a tertiary neonatal intensive care unit. After screening analyses, multivariable analyses were conducted to identify associations between blindness and peak bilirubin concentration (dichotomized at different levels to create 3 binary variables), and between severe adverse neurodevelopmental outcome at 18 months postterm age and peak bilirubin levels. Of 128 18-month survivors, 15 had severe visual loss attributable to retinopathy of prematurity, 21 had neurodevelopmental deficit, and 5 were deaf. Visual loss was significantly associated with low-peak serum bilirubin concentration (<9.4 mg/dL (<160 micromol/L) versus >/=9.4 mg/dL (odds ratio [OR] confidence interval [CI] 4.48 [1.15-17.43])), low gestational age (OR [CI] per week 1.95 [1.05-3.63]), and longer duration of phototherapy (OR [CI] per 10 hours 1.17 [1.02-1.33]). The association of neurodevelopmental impairment with grades 3 and 4 intraventricular hemorrhage was statistically significant (OR 5.39 [1.83-15.84]), but with high-peak serum bilirubin concentration >/=11.7 mg/dL (>/=200 micromol/L), was not significant (OR 2.89 [0. 87-9.53]). In these infants, prolonged phototherapy and low-peak serum bilirubin concentrations were associated with severe visual loss attributable to retinopathy of prematurity. The findings should be interpreted with caution until the evidence is reinforced in other patient populations.

Semiautomated sequence-specific mutation detection of the human K-ras oncogene using "cold" SSCP analysis

Stepwise multiple regression affirmed that cAFP and cBIL contributed to the variation in the peak serum bilirubin concentration, r = 0.504, P <0.0001. In this study they were the only cord blood substances found to associate with postnatal serum bilirubin concentrations. However, no significant correlation existed between them. The incidence of idiopathic NNJ in a local Chinese population reported in 1986 was 23.8% [3]. Assuming the same incidence today, the positive predictive value and the efficiency of using a combination of cAFP (at a cutoff concentration of 100 000 j.tg/L) and cBIL (at a cutoff concentration of 29 j.molIL) would be 52.3% and 77.7%, respectively. We conclude that a combination of cAFP and cBIL can be used as a predictive marker for the development of idiopathic NNJ. Our results also indicated that both liver immaturity and increased bilirubin production were associated with the development of hyperbilirubinemia in newborn infants.

Umbilical Cord Clamping and Preterm Infants: A Randomised Trial

OBJECTIVE--To investigate the clinical effects of regulating umbilical cord clamping in preterm infants. DESIGN--A prospective randomised study. SETTING--The Queen Mother's Hospital, Glasgow. SUBJECTS--36 vaginally delivered infants over 27 and under 33 weeks' gestation. INTERVENTION--Holding the infant 20 cm below the introitus for 30 seconds before clamping the umbilical cord group, 17 patients), or conventional management (random group, 19 patients). MAIN OUTCOME MEASURES--Initial packed cell volume, peak serum bilirubin concentrations, red cell transfusion requirements, and respiratory impairment (assessed by ventilatory requirements, arterial-alveolar oxygen tension ratio over the first day in ventilated infants, and duration of dependence on supplemental oxygen). RESULTS--There were statistically significant differences between the two groups in mean initial packed cell volume (regulated group 0.564, random group 0.509) and median red cell transfusion requirements (regulated group zero, random group 23 ml/kg). 13 infants from each group underwent mechanical ventilation and showed significant differences in mean minimum arterial-alveolar oxygen tension ratio on the first day (regulated group 0.42, random group 0.22) and in median duration of dependence on supplemental oxygen (regulated group three days, random group 10 days). Differences in final outcome measures such as duration of supplemental oxygen dependence and red cell transfusion requirements were mediated primarily through arterial-alveolar oxygen tension ratio and also packed cell volume. CONCLUSIONS--This intervention at preterm deliveries produces clinical and economic benefits.

Umbilical cord clamping and preterm infants: a randomised trial.

To investigate the clinical effects of regulating umbilical cord clamping in preterm infants. A prospective randomised study. The Queen Mother's Hospital, Glasgow. 36 vaginally delivered infants over 27 and under 33 weeks' gestation. Holding the infant 20 cm below the introitus for 30 seconds before clamping the umbilical cord ("regulated" group, 17 patients), or conventional management ("random" group, 19 patients). Initial packed cell volume, peak serum bilirubin concentrations, red cell transfusion requirements, and respiratory impairment (assessed by ventilatory requirements, arterial-alveolar oxygen tension ratio over the first day in ventilated infants, and duration of dependence on supplemental oxygen). There were statistically significant differences between the two groups in mean initial packed cell volume (regulated group 0.564, random group 0.509) and median red cell transfusion requirements (regulated group zero, random group 23 ml/kg). 13 infants from each group underwent mechanical ventilation and showed significant differences in mean minimum arterial-alveolar oxygen tension ratio on the first day (regulated group 0.42, random group 0.22) and in median duration of dependence on supplemental oxygen (regulated group three days, random group 10 days). Differences in final outcome measures such as duration of supplemental oxygen dependence and red cell transfusion requirements were mediated primarily through arterial-alveolar oxygen tension ratio and also packed cell volume. This intervention at preterm deliveries produces clinical and economic benefits.

Predictive inability of cord zinc, magnesium and copper levels on the development of benign hyperbilirubinemia in the newborn.

Cord serum concentrations of zinc, magnesium and copper were determined in 90 healthy term infants. The infants were divided by peak bilirubin values into an icteric group (peak bilirubin > 136 mumol/l) (n = 21) and a control group (peak bilirubin < or = 136 mumol/) (n = 69). Mean cord serum zinc, magnesium and copper concentrations in the icteric group did not differ from those of the control group. Furthermore, no significant correlation was found between peak serum bilirubin concentrations and cord serum concentrations of these three elements. We conclude that cord serum concentrations of zinc, magnesium or copper are not useful in predicting which neonates will develop hyperbilirubinemia.

NEONATAL SENSORINEURAL HEARING LOSS ASSOCIATED WITH FUROSEMIDE: A CASE‐CONTROL STUDY

Thirty-five neonates with sensorineural hearing loss (SNHL), identified by brainstem auditory evoked response (BAER), and 70 matched controls with normal BAERs were studied. All infants had had BAERs before discharge from hospital as part of a screening program for high-risk neonates. Infants with SNHL showed no response to a 60dBnHL click stimulus and all had these results confirmed on at least one occasion after hospital discharge. Based on the screening program results, over-all prevalence of non-hereditary hearing loss was estimated to be 0.93 per 1000 live births, and in neonates weighing less than 2000g at birth to be 15.54 per 1000 live births. Several factors, including seizures, exposure to anticonvulsant drugs, furosemide and kanamycin were associated with SNHL, but after multivariate analysis, only exposure to furosemide remained significant. Peak serum bilirubin concentration and benzyl alcohol exposure did not appear to be related to hearing loss.

Does ABO incompatibility matter?

The incidence and severity (peak serum bilirubin concentration) of clinically detectable jaundice was determined retrospectively in 110 elution positive cases of ABO incompatibility. Neither the incidence nor the severity of jaundice in the study group differed significantly from a control group. In the individual case Coombs positivity and/or a strongly positive elution test may be a helpful predictor of jaundice occurring but not of its severity.

Relationship between peri-intraventricular hemorrhage and neonatal hyperbilirubinemia in very low-birthweight infants.

The incidence of hyperbilirubinemia (serum bilirubin values greater than 205 mumol/l) in two groups of preterm infants (birthweight less than 1500 gm) with and without peri-intraventricular hemorrhage (PIVH) was studied. In the first 10 days of life, 16 (39%) of the 41 infants with PIVH vs. 22 (46.8%) of those without PIVH (n = 47) had high bilirubin levels. No difference in peak serum bilirubin concentrations nor a need for phototherapy was noted between the two groups (P greater than 0.07). Forty-one infants had PIVH: 30 had PIVH grade I or II and 11 had grade III or IV. No statistically significant correlation was found between degree of PIVH and hyperbilirubinemia. Moreover, at 12 months corrected age, major and minor handicaps were equally distributed between the two groups. The neurologic outcome appeared to relate, in largest part, to the severity of the PIVH, and to not be influenced by the hyperbilirubinemia. We conclude that there is no positive relationship between incidence and extension of PIVH, plasma bilirubin levels, and outcome in very low-birth weight infants.

Neonatal jaundice: its prevalence in Chinese babies and associating factors.

A prospective study of 1238 full-term Chinese newborn infants was conducted to determine the incidence of neonatal jaundice and associated factors. A significantly more severe degree of hyperbilirubinaemia was present in infants whose ABO blood group was incompatible with that of their mothers and those who were deficient in the enzyme glucose-6-phosphate dehydrogenase (G6PD). Among the remainder, clinical jaundice was present in 87% and 23.9% had a peak serum bilirubin (SB) concentration greater than 204 mumol/l. Factors that were found to have an association with a higher peak SB concentration included: male infants; elder siblings who had a history of neonatal jaundice; and breast-fed infants with or without supplementation with formula feed. Factors that were found to have no significant association with the peak SB concentration were: gestational age; birthweight; the mode of delivery of the infants; maternal consumption of Chinese herbs and syntocinon induction or augmentation of labour.

Randomized trial of prophylactic phototherapy in the infant with very low birth weight

Twenty-two preterm infants (birth weight 850 +/- 220 gm) were randomly assigned to receive phototherapy either soon after birth or after the serum bilirubin concentration reached 5 mg/dl. Infants receiving prophylactic phototherapy were placed under lights at a significantly earlier age and lower serum bilirubin concentration than infants in the routine group (P less than 0.001). There was no significant difference between groups in peak serum bilirubin concentration, age at which it peaked, rate of rise in serum bilirubin concentration, or serum bilirubin concentration at any time during the study. Infants assigned to the prophylactic phototherapy group were under lights for a significantly longer time than those in the routine group (P less than 0.05). There was a significant rise in both configurational and structural photo-isomers (P less than 0.005) independent of serum bilirubin concentration after phototherapy in all patients. These data suggest that the clinical course of hyperbilirubinemia is not altered in infants with very low birth weight receiving prophylactic phototherapy compared with infants with phototherapy begun at a bilirubin concentration of 5 mg/dl.

420 THE COURSE OF HYPERBILIRUBINEMIA IN THE VERY LOW BIRTHWEIGHT INFANT TREATED WITH PHENOBARBITAL

We examined the effect of early phenobarbital therapy on the course of jaundice in 58 infants below 1500g. The study group of 28 infants (BW 1149+/-251g, GA 29.5+7-2.7wks), was treated with a phenobarbital loading dose of 20mg/kg/day at 4.2+/7-3.6 hrs of age, followed by a maintenance dose of 5mg/kg/day for one week. Thirty infants served as controls. Seventeen study and 20 control infants suffered from intraventricular hemorrhage. The results of the comparison showed that treated infants had lower peak serum bilirubin concentrations (7.9+/-1.7 vs 8.6+/7-2.2mg/dl), reached peak SBC levels earlier (92.5+/-50.7 vs 138.0+7-101.1 hrs) and spent less time on phototherapy (5.5+7-2.9 vs 7.5+/-3.S days). In the study group, although peak SBC was similar to that of no IVH infants, the IVH subgroup reached peak SBC later (112.8+/-53.0 vs 61.2+7-25.6 hrs) and spent more time on phototherapy (6.9+7-2.3 vs 3.2+/-2.4 days). Control IVH infants showed similar results with an age at peak of 150.0+7-100.3 vs 114.1+/-101.4 hrs and a duration of phototherapy of 8.8+7-3.7 vs 4.8+7-2.5 days when compared to control infants without IVH. In this group of infants P was effective in reducing the severity of hyperbilirubinemia as indicated by the decreased need for therapy. In addition, the presence of IVH contributed to the hyperbilirubinemia in both treated and control infants.

Hyperbilirubinemia in Infants of Diabetic Mothers

Large for gestational age (LGA) infants of insulin-dependent diabetic mothers (IDM), appropriate for gestational age (AGA) IDM, and infants of nondiabetic mothers were compared for the incidence of neonatal hyperbilirubinemia and related etiologic factors. At 60 hours of age, LGA IDM had significantly higher serum bilirubin concentrations (12.3 +/- 2.1 mg/100 ml) than AGA IDM (7.6 +/- 3.9 mg/100 ml) or control infants (7.8 +/- 2.8 mg/100 ml) (P < .001). Peak serum bilirubin concentrations were also significantly higher in LGA IDM (14.4 +/- 2.1 mg/100 ml) than in AGA IDM (8.4 +/- 3.7 mg/100ml) or control infants (8.6 +/- 3.3 mg/100 ml) (P < .001). Mean percent of carboxyhemoglobin was used as an indicator of hemolysis and showed a significant elevation in LGA IDM (1.51 +/- 0.19) when compared to AGA IDM (1.10 +/- 0.27) and control infants (1.19 +/- 0.33) (P < .05). No significant differences were found among the three groups with respect to mode of delivery, frequency of pitocin administration, 5-minute Apgar scores, incidence of isoimmunization, incidence of enclosed hemorrhage, hemoglobin concentration, bilirubin concentrations at 12 hours, and percent of weight loss. Our data suggest that only LGA IDM are at increased risk for hyperbilirubinemia and that increased heme turnover is a significant factor in the pathogenesis.

Absence of Kernicterus in Low-Birth-Weight Infants From 1971 Through 1976: Comparison With Findings in 1966 and 1967

A review of 34 autopsied infants weighing 2,250 gm or less who died on the third to seventh days of life during the six-year period from 1971 through 1976 failed to reveal any cases of kernicterus. This contrasts with an incidence of 64% in low-birth-weight infants selected in the same manner from the same neonatal intensive care unit-premature center during the period 1966 and 1967. The 34 infants in the 1971-1976 series were not significantly different with regard to their birth weights, Apgar scores, perinatal complications, or pathologic findings, other than their lack of kernicterus, from the 14 infants in the 1966-1967 series. The only significant difference between these two groups of infants was a lower mean peak serum bilirubin concentration in the 1971-1976 series, corresponding with the establishment in 1970 of a more aggressive policy of exchange transfusion and phototherapy. The prevention of excessive hyperbilirubinemia along with the development of more sophisticated intensive care of the neonate in recent years may be responsible for the elimination of kernicterus in the 1971-1976 series of infants.

1007 ABSENCE OF KERNICTERUS IN LOW-BIRTH-WEIGHT INFANTS 1971–1976: COMPARISON WITH 1966–1967

A review of all autopsied infants weighing less than 2251 grams (34 cases) who expired on the third to seventh days of life during the six year period from 1971 to 1976 failed to reveal any cases of kernicterus. This contrasts with an incidence of 64% (9 of 14) in low-birth-weight infants from the same neonatal intensive care unit during the period 1966-67 (Pediatrics 45:906, 1970). The infants in the two series were not significantly different with regard to their birth weights, Apgar scores, perinatal complications, or non-neurologic postmortem findings. The only significant difference between these two groups of infants was a lower mean peak serum bilirubin concentration in the 1971-76 series (11.1±4.0 mg/dl vs. 8.7±3.4 mg/dl), resulting from the use since 1970 of lower serum bilirubin concentrations as criteria for exchange transfusion and the use of phototherapy since 1974. The prevention of excessive hyper-bilirubinemia as well as the development of more sophisticated intensive care of the neonate in recent years may be responsible for the elimination of kernicterus in the 1971-76 series of infants weighing less than 2251 grams.