Peak Serum Bilirubin Levels Research Articles

Cochrane Review: Prophylactic phototherapy for preventing jaundice in preterm or low birth weight infants

Low birth weight and premature infants are at major risk for exaggerated hyperbilirubinaemia and jaundice that can lead to bilirubin encephalopathy. Phototherapy is the most common treatment for neonatal hyperbilirubinaemia and could be most effective in preventing the sequelae of hyperbilirubinaemia if initiated prophylactically. To evaluate the efficacy and safety of prophylactic phototherapy for preterm (< 37 weeks gestational age) or low birth weight infants (birth weight < 2500 g). We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3) on 31 March 2011, MEDLINE (1950 to 31 March 2011), EMBASE (1980 to 31 March 2011) and CINAHL (1982 to 31 March 2011). Randomised controlled trials or quasi-randomised controlled studies evaluating the effects of prophylactic phototherapy for preterm or low birth weight infants. Two authors independently obtained data from published articles. We performed fixed-effect meta-analysis for the outcomes: rate of exchange transfusion, cerebral palsy or other neurodevelopmental impairment, peak serum bilirubin level and all-cause mortality. Nine studies of 3449 participants were included. The rate of exchange transfusion was reduced in one study with liberal transfusion criteria (risk ratio (RR) 0.20; 95% confidence interval (CI) 0.13 to 0.31) but not in the other two more recent studies with stringent criteria (typical RR 0.66; 95% CI 0.19 to 2.28). There was no statistically significant difference in the rate of cerebral palsy (typical RR 0.96; 95% CI 0.50 to 1.85; two studies, 756 participants). However, one large study that reported on neurodevelopmental impairment (a composite outcome including cerebral palsy) found a slightly lower rate of neurodevelopmental impairment with prophylactic phototherapy (RR 0.85; 95% CI 0.74 to 0.99; 1804 participants). The prophylactic phototherapy group had lower peak bilirubin levels (mean difference (MD) -2.73; 95% CI -2.89 to -2.57; six studies, 2319 participants) and had fewer neonates with peak unconjugated serum bilirubin levels > 10 mg/dl (typical RR 0.27; 95% CI 0.22 to 0.33; three studies, 1090 participants) or peak unconjugated serum bilirubin levels > 15 mg/dl (typical RR 0.13; 95% CI 0.07 to 0.23; four studies, 1116 participants). There was no statistically significant difference in the rate of all-cause mortality between the two groups (typical RR 1.08; 95% CI 0.93 to 1.26; four studies, 3044 participants). Prophylactic phototherapy helps to maintain a lower serum bilirubin concentration and may have an effect on the rate of exchange transfusion and the risk of neurodevelopmental impairment. However, further well-designed studies are needed to determine the efficacy and safety of prophylactic phototherapy on long-term outcomes including neurodevelopmental outcomes.

Pattern of BAER abnormalities in neonatal hyperbilirubinemia

Article history: This study was done to determine the various abnormalities of Brain Auditory Evoked Response (BAER) in neonates with hyperbilirubinemia and to correlate the specific BAER abnormality with a particular range of bilirubin levels. Prospective study was done in 100 cases in a tertiary care hospital over a period from 2007-2008. All cases with hyperbilirubinemia were subjected to BAER test. Fifty five percent (n=44) out of 80 cases showed abnormal BAER test and 24 of them showed bilaterally in babies having peak serum bilirubin levels of more than 20mg/dL. Seventy five percent (n=33) showed prolong interpeak latency in wave III-V indicating that the conduction from superior olivary complex (wave III) to inferior collicullus (wave V) were more commonly affected with peak levels of bilirubin when compared to control which were found to be statistically significant (p<0.05). BAER is a simple and effective tool for determining the auditory functions in neonates with hyperbilirubinemia and could predict the impending encephalopathy or to identify subtle findings that could be reversed.

Model to Predict Hyperbilirubinemia in Healthy Term and Near-Term Newborns with Exclusive Breast Feeding

The aim of this study was to identify high-risk newborns who will subsequently develop significant hyperbilirubinemia Days 4 to 10 of life by using the clinical data from the first three days of life. We retrospectively collected exclusively breastfeeding healthy term and near-term newborns born in our nursery between May 1, 2002, to June 30, 2005. Clinical data, including serum bilirubin were collected and the significant predictors were identified. Bilirubin level ≥15mg/dL during Days 4 to 10 of life was defined as significant hyperbilirubinemia. A prediction model to predict subsequent hyperbilirubinemia was established. This model was externally validated in another group of newborns who were enrolled by the same criteria to test its discrimination capability. Totally, 1979 neonates were collected and 1208 cases were excluded by our exclusion criteria. Finally, 771 newborns were enrolled and 182 (23.6%) cases developed significant hyperbilirubinemia during Days 4 to 10 of life. In the logistic regression analysis, gestational age, maximal body weight loss percentage, and peak bilirubin level during the first 72 hours of life were significantly associated with subsequent hyperbilirubinemia. A prediction model was derived with the area under receiver operating characteristic (AUROC) curve of 0.788. Model validation in the separate study (N = 209) showed similar discrimination capability (AUROC = 0.8340). Gestational age, maximal body weight loss percentage, and peak serum bilirubin level during the first 3 days of life have highest predictive value of subsequent significant hyperbilirubinemia. We provide a good model to predict the risk of subsequent significant hyperbilirubinemia.

Outcome and cost analysis of implementing selective Coombs testing in the newborn nursery

(1) To determine whether infants born to O+ mothers who had selective cord-blood testing would have higher rates of clinically significant hyperbilirubinemia compared with those newborns who had routine cord-blood testing. (2) To determine the amount of cost savings by implementing a policy of selective cord-blood testing in newborns born to O+ mothers. We conducted a retrospective pre/post intervention chart review on all infants in the normal newborn nursery at Loyola, born to blood type O+ women between 1 April 2008 and 1 April 2009. The pre-intervention group (routine testing) included infants born within 6 months before implementation of a new policy. The post-intervention group (selective testing) included infants born within 6 months following the implementation of a new policy. Data were collected for each of these groups regarding clinically significant hyperbilirubinemia. All 250 of the infants in the routine testing group had a cord-blood type and Coombs done, whereas 42 of 164 (25%) infants in the selective group had testing done. By the end of the 6 months following the policy change, only 8% of infants were undergoing cord testing. When comparing routine vs selective testing, there was no statistically significant difference in the 24-h serum bilirubin, rate of phototherapy during the birth hospitalization, rate of readmission for hyperbilirubinemia or peak serum bilirubin level at readmission. The 92% reduction of cord-blood typing and Coombs testing would lead to a cost saving of $4100 per year to our hospital and $18 900 per year to our patients, and 95 h per year of technician time to perform these tests. When extrapolated to Illinois births in 2008, this would lead to an annual cost saving of almost $800 000 to Illinois hospitals and about $3.6 million to patients. Selective newborn cord testing of infants born to O+ mothers can decrease the use of resources and costs without increasing the risk of clinically significant hyperbilirubinemia.

International Perspectives

After completing this article, readers should be able to: 1. Describe the unique characteristics of neonatal jaundice in Chinese infants. 2. Describe the major findings from a recent epidemiological survey of bilirubin encephalopathy or kernicterus in China. 3. Understand the primary causes and current problems for decreasing the incidence of bilirubin encephalopathy or kernicterus in China. 4. Outline future directions for obtaining population based data on bilirubin encephalopathy or kernicterus and formulating optimal management of neonatal jaundice. Hyperbilirubinemia is the number one reason for neonatal admission in most Chinese neonatal units. Early severe neonatal hyperbilirubinemia, resulting in bilirubin encephalopathy, may cause kernicterus, with residual hearing loss, cerebral palsy, neurodevelopmental disabilities, and other complications. It inflicts a heavy burden on both families and society. With the use of phototherapy, exchange transfusion, and other treatment technologies, kernicterus became less common, but an upward trend in incidence has been observed in recent years. China's large population, the very uneven distribution of medical resources between regions, and Asians being at high risk for hyperbilirubinemia suggest that the incidence of bilirubin encephalopathy and kernicterus should be higher than that in Western countries. Because of the lack of large-sample epidemiological surveys and population-based disease reporting systems, the specific incidence is not clear. In 1998, Yeung (1) summarized the characteristics of neonatal jaundice in China: 1) high unconjugated hyperbilirubinemia causing neonatal jaundice is particularly prevalent in South China; 2) he believes there is a “Chinese nonspecific neonatal jaundice” characterized by the clinical jaundice being more severe and longer lasting and having a delayed peak that occurs after the fourth day; 3) hemolytic disease of the newborn due to ABO incompatibility is the most common form of hemolytic jaundice; 4) in neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency, an acute bilirubin encephalopathy can appear late in the neonatal period; and 5) resolution of …

Prophylactic phototherapy for preventing jaundice in preterm or low birth weight infants

Low birth weight and premature infants are at major risk for exaggerated hyperbilirubinaemia and jaundice that can lead to bilirubin encephalopathy. Phototherapy is the most common treatment for neonatal hyperbilirubinaemia and could be most effective in preventing the sequelae of hyperbilirubinaemia if initiated prophylactically. To evaluate the efficacy and safety of prophylactic phototherapy for preterm (< 37 weeks gestational age) or low birth weight infants (birth weight < 2500 g). We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3) on 31 March 2011,MEDLINE (1950 to 31 March 2011), EMBASE (1980 to 31 March 2011) and CINAHL (1982 to 31 March 2011). Randomised controlled trials or quasi-randomised controlled studiesevaluating the effects of prophylactic phototherapy for preterm or low birth weight infants. Two authors independently obtained data from published articles. We performed fixed-effect meta-analysis for the outcomes: rate of exchange transfusion, cerebral palsy or other neurodevelopmental impairment, peak serum bilirubin level and all-cause mortality. Nine studies of 3449 participants were included. The rate of exchange transfusion was reduced in one study with liberal transfusion criteria (risk ratio (RR) 0.20; 95% confidence interval (CI) 0.13 to 0.31) but not in the other two more recent studies with stringent criteria (typical RR 0.66; 95% CI 0.19 to 2.28). There was no statistically significant difference in the rate of cerebral palsy (typical RR 0.96; 95% CI 0.50 to 1.85; two studies, 756 participants). However, one large study that reported on neurodevelopmental impairment (a composite outcome including cerebral palsy) found a slightly lower rate of neurodevelopmental impairment with prophylactic phototherapy (RR 0.85; 95% CI 0.74 to 0.99; 1804 participants). The prophylactic phototherapy group had lower peak bilirubin levels (mean difference (MD) -2.73; 95% CI -2.89 to -2.57; six studies, 2319 participants) and had fewer neonates with peak unconjugated serum bilirubin levels > 10 mg/dl (typical RR 0.27; 95% CI 0.22 to 0.33; three studies, 1090 participants) or peak unconjugated serum bilirubin levels > 15 mg/dl (typical RR 0.13; 95% CI 0.07 to 0.23; four studies, 1116 participants). There was no statistically significant difference in the rate of all-cause mortality between the two groups (typical RR 1.08; 95% CI 0.93 to 1.26; four studies, 3044 participants). Prophylactic phototherapy helps to maintain a lower serum bilirubin concentration and may have an effect on the rate of exchange transfusion and the risk of neurodevelopmental impairment. However, further well-designed studies are needed to determine the efficacy and safety of prophylactic phototherapy on long-term outcomes including neurodevelopmental outcomes.

Changing picture of central nervous system complications in liver transplant recipients

Central nervous system (CNS) complications are common after liver transplantation (LT). According to the literature, the most common causes are infections and the neurotoxicity of immunosuppressive drugs (cyclosporine and tacrolimus). The aim of this study was to evaluate the incidence, clinical presentations, etiologies, and outcomes of CNS complications in a series of 395 consecutive LT recipients whose immunosuppression regimen was designed for low tacrolimus blood levels. An analysis of the 12-hour trough concentrations of tacrolimus in the study population showed that the target drug levels, which were designed to maintain minimal immunosuppression, were usually achieved. In all, 64 patients (16.2%) developed major neurological symptoms (37 within 30 days of LT). None of the observed CNS complications were caused by infections (viral, bacterial, or fungal), and only 3 of the 395 patients (0.8%) received a diagnosis of tacrolimus-related leukoencephalopathy. Cerebrovascular disease was identified in 15 patients (3.8%; 8 had cerebral hemorrhages, 5 had ischemic strokes, and 2 had subdural hemorrhages). Pontine myelinolysis was found in 2 patients (0.5%). Notably, no clear cause was identified for the remaining 44 cases (11.1%): brain imaging was negative for 22 cases, and diffuse hypoxic changes were present for the other 22. CNS complications were significantly associated with a reduction in 3-month patient survival (88.8% versus 95.4%) and 5-year patient survival (57.3% versus 84.1%). Among the pretransplant variables that were analyzed, the incidence of portosystemic encephalopathy, the peak serum bilirubin levels, and the lowest serum total cholesterol levels were significantly different between the 64-patient group with CNS complications and the asymptomatic group of 331 patients.

Association between Peak Serum Bilirubin and Neurodevelopmental Outcomes in Term Babies with Hyperbilirubinemia

To find the association between neonatal Peak serum bilirubin (PSB) levels and the neurodevelopmental outcomes at 6 months in term infants with neonatal hyperbilirubinemia. Term neonates who developed jaundice with atleast one PSB value of above 15 mg/dl within first wk of life were included. Babies with any condition affecting the neurodevelopment, like prematurity, convulsions or asphyxia were excluded from the study. This prospective cohort study included 66 term babies out of the 6548 newborns delivered during the study period. The incidence of abnormal developmental quotient gradually increased with increase in the level of PSB. Based on univariate analysis, a PSB ≥ 22 mg/dl (the cut off obtained based on Receiver operating characteristic curve), Rh incompatibility and occurrence of jaundice within 2 days of life were found to be significant risk factors for abnormal developmental quotient. These three risk factors were also independently associated with abnormal development by multivariate logistic regression analysis. PSB level of ≥ 22 mg/dl, Rh incompatibility and occurrence of jaundice within 2 days of life are independent predictors of abnormal development in babies with neonatal jaundice.

211 G to A Variation of UDP-Glucuronosyl Transferase 1A1 Gene and Neonatal Breastfeeding Jaundice

Breastfeeding jaundice is a common problem in neonates who were exclusively breastfed, but its pathogenesis is still unclear. The uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphism was shown to contribute to the development of neonatal hyperbilirubinemia. We hypothesize that the variation of UGT1A1 gene may contribute to neonatal breastfeeding jaundice. We prospectively enrolled 688 near-term and term infants who were exclusively breastfed (BF group) or were supplemented by infant formula partially (SF group) before onset of hyperbilirubinemia. Genotyping of the promoter and exon1 of UGT1A1 was performed in all neonates. Neonates in BF group had a significantly higher maximal body weight loss ratio, peak bilirubin level, and a greater incidence of hyperbilirubinemia than those in SF group. Neonates with nucleotide 211 GA or AA variation in UGT1A1 genotypes had higher peak serum bilirubin levels and higher incidence of hyperbilirubinemia than WTs (GG). This phenomenon was only seen in BF group but not in SF group when subset analysis was performed. This suggests that neonates who carry the nucleotide 211 GA or AA variation within coding region in UGT1A1 gene are more susceptible to develop early-onset neonatal breastfeeding jaundice.

327 Excessively High Bilirubin and Exchange Transfusion in Very Low Birth Weight Infants

Objective: To evaluate the distribution of peak serum bilirubin levels in very low birth weight (VLBW) infants and the performance of exchange transfusion in infants with excessively high bilirubin levels. Methods: A population based observational study using data collected by the Israel National VLBW Infant Database. The study sample comprised 13,499 infants of 24 to 33 weeks gestation. Two definitions of excessively high peak bilirubin levels which might be considered as threshold levels for performance of exchange transfusion were used. Firstly, a bilirubin level of ≥ 15 mg/dL for all infants (PSB-15), and secondly, incremental bilirubin levels ranging from 12-17 mg/dL according to gestational age (PSB-GA). Multivariable logistic regression analyses were performed to examine the factors associated with performance of exchange transfusion. Results: Four hundreds sixty eight (3.5%) and 1035 infants (7.7%) infants in the PSB-15 and in the PSB-GA groups respectively had peak serum bilirubin levels above thresholds for exchange transfusion. Exchange transfusion's were performed in only 66 (14.1%) of these infants in the PSB-15 group and 91 (8.8%) in the PSB-GA group. In both groups performance of exchange transfusion was significantly associated with peak serum bilirubin levels, with an odds ratio of 1.38 for each mg/dL increase above the threshold level. Conclusion: Exchange transfusion was performed in only 9-14% of VLBW infants with excessively high bilirubin levels. This may be related to an absence of definitive guidelines or the possible belief that the risks of exchange transfusion outweigh the potential risk of bilirubin induced neurological injuries.

Excessively high bilirubin and exchange transfusion in very low birth weight infants

To evaluate the performance of exchange transfusion in very low birth weight (VLBW) infants with excessively high serum bilirubin levels. A population-based observational study using data collected by the Israel National VLBW Infant Database. The study sample comprised 13,499 infants. Two definitions of excessively high-peak bilirubin levels that might be considered as threshold levels for performance of exchange transfusion were used. First, a bilirubin level of ≥15 mg/dL for all infants (PSB-15), and second, incremental bilirubin levels ranging from 12 to 17 mg/dL according to gestational age (PSB-GA). Four hundreds sixty-eight (3.5%) and 1035 infants (7.7%) infants in the PSB-15 and in the PSB-GA groups respectively had peak serum bilirubin levels above thresholds for exchange transfusion. Exchange transfusions were performed in 66 (14.1%) of these infants in the PSB-15 group and 91 (8.8%) in the PSB-GA group. Using logistic regression analysis, peak serum bilirubin was found as an independent factor for performing exchange transfusion. Exchange transfusion was performed in only 9-14% of VLBW infants with excessively high bilirubin levels. We speculate that this may be a result of an absence of definitive guidelines or the possible belief that the risks of exchange transfusion outweigh the potential risk of bilirubin-induced neurological injuries.

Clinical Characteristics of G6PD Deficiency in Infants With Marked Hyperbilirubinemia

This study analyzes the clinical features of glucose-6-phosphate dehydrogenase (G6PD) deficiency in infants with marked hyperbilirubinemia. We retrospectively assessed a cohort of 413 infants with peak total serum bilirubin (TSB) level >or=20 mg/dL from 1995 to 2007. The prevalence of G6PD deficiency was proportional to the level of peak TSB: 21.1% (81/383) in 20 mg/dL to 29.9 mg/dL, 45.5% (10/22) in 30 mg/dL to 39.9 mg/dL, and 100% (8/8) in >or=40 mg/dL. Male sex was more common in G6PD deficiency (75.8%). When compared with G6PD-normal infants, those with G6PD deficiency tended to have extreme hyperbilirubinemia (peak TSB level >or=25 mg/dL) and hemoglobin value<13 g/dL (P<0.001). Furthermore, mortality rate was significantly higher in G6PD-deficient infants (3.0%) than in the G6PD-normal counterparts (0.0%). Among 58 of the G6PD-deficient infants who were followed for more than 12 months, 4 developed the classic neurologic manifestations of kernicterus (6.6%). These findings show that G6PD deficiency is an important risk factor of extreme hyperbilirubinemia, death, and kernicterus.

Calculated free bilirubin levels and neurotoxicity

Although most bilirubin in the circulation is bound to albumin, a relatively small fraction remains unbound. The concentration of this 'free' bilirubin (B(F)) is believed to dictate the biologic effects of bilirubin in jaundiced newborns, including its neurotoxicity. The threshold at which B(F) produces changes in cellular function culminating in permanent cell injury and cell death has been the subject of considerable debate. The objective of this study was to compare calculated central nervous system (CNS) B(F) levels in Gunn rat pups during (i) peak postnatal hyperbilirubinemia and (ii) sulfadimethoxine-induced acute bilirubin encephalopathy (ABE) previously reported from our laboratory with those predicted in human neonates with peak total serum bilirubin (TSB) levels of 35 mg per 100 ml (599 micromol l(-1)), a clinical cohort that often evidence moderate-to-severe adverse post-icteric neurodevelopmental sequelae. Homozygous j/j Gunn rat pups with neonatal hyperbilirubinemia due to a deficiency of the bilirubin conjugating enzyme uridine-diphosphate-glucuronosyl transferase 1A1 were studied along with non-jaundiced littermate heterozygous J/j controls. Sulfadimethoxine was used to displace bilirubin from albumin in hyperbilirubinemic j/j Gunn rat pups to increase their brain bilirubin content and induce ABE. Calculated Gunn rat CNS B(F) levels were determined as a function of genotype, sulfadimethoxine exposure and albumin-bilirubin binding constant. These data were compared with the human CNS B(F) predicted from the calculated serum B(F) in human neonates with a TSB of 35 mg per 100 ml as a function of albumin-bilirubin binding constant, albumin concentration and the assumption that at this hazardous bilirubin level there may be rapid equilibration of B(F) between serum and brain. There was a large gap between the upper limit of the calculated CNS B(F) 95% confidence interval (CI) range in non-jaundiced J/j pups (for example, 112 nM at k=9.2 l micromol(-1)) and the lower limit seen in the saline-treated hyperbilirubinemic j/j pups (556 nM at k=9.2 l micromol(-1)) as well as between the upper limit in saline-treated hyperbilirubinemic j/j pups (1110 nM at k=9.2 l micromol(-1)) and the lower limit seen in sulfadimethoxine-treated jaundiced j/j littermates (3461 nM at k=9.2 l micromol(-1)). There was considerable overlap and remarkable similarity between the predicted human CNS B(F) values at a TSB of 35 mg per 100 ml for a range of reported human serum bilirubin-albumin binding constants and albumin concentrations, and those calculated for saline-treated hyperbilirubinemic j/j Gunn rat pups. This exercise yielded strikingly similar apparent calculated neurotoxic B(F) levels for Gunn rat pups and human neonates rather than orders of magnitude differences that might have been predicted at the outset and add to a growing literature aimed at defining clinically germane neurotoxic B(F) thresholds.Journal of Perinatology (2009) 29, S14-S19; doi:10.1038/jp.2008.218.

Assessment of hepatosplanchnic pathophysiology during thoracoabdominal aortic aneurysm repair using visceral perfusion and shunt☆

Despite the recognition of importance to avoid visceral ischemia during thoracoabdominal aortic aneurysm (TAAA) repair, the methodology of visceral perfusion seems still controversial and its pathophysiology has not been clearly understood. We investigated hepatosplanchnic metabolism during visceral perfusion/shunt in TAAA repair. Seventeen patients (10 male, 64+/-15 years old) who underwent elective TAAA repair using visceral perfusion/shunt under mild hypothermic distal aortic perfusion were retrospectively enrolled. Their aneurysm extension was type I and II in eight patients. In seven patients, four visceral arteries were perfused through a side-arm of distal aortic perfusion, while they were perfused by an independent pump in another five patients. In four of these 12 (two in each technique), visceral perfusion was converted into selective shunt after completion of aortic anastomosis. In the remaining five patients, four branches were initially perfused through a side-arm of distal aortic perfusion, and aortic perfusion was subsequently stopped after completion of aortic anastomosis. Hepatic venous oxygen saturation (ShO(2)), oxygen and lactate extraction ratio (OER, LER), and arterial ketone body ratio (AKBR) were measured at six time points. There was no mortality, liver/renal dysfunction, or spinal cord injury. Two patients required re-exploration for bleeding. Fourteen patients were extubated within 24h postoperatively. Mean intensive care unit stay was 2.3+/-1.7 days. During visceral perfusion, OER raised (31+/-13% to 68+/-21%, p=0.0012) and ShO(2) decreased (67+/-12% to 34+/-24%, p=0.0026) significantly. They recovered to baseline at skin closure. During the same period, LER (41+/-22% to -1+/-34%, p=0.0035) and AKBR (0.47+/-0.13 to 0.20+/-0.08, p=0.0012) significantly decreased. AKBR recovered to baseline at skin closure, but LER did not. ShO(2) (R(2)=0.483, p=0.0257) and LER (R(2)=0.774, p=0.0018) at skin closure and LER after initiation of partial cardiopulmonary bypass (R(2)=0.427, p=0.0211) had significant correlation with postoperative peak serum bilirubin level. AKBR after initiation of partial cardiopulmonary bypass had significant correlation with postoperative peak serum alanine aminotransferase level (R(2)=0.289, p=0.0476). Visceral perfusion/shunt in TAAA repair may avoid critical irreversible hepatosplanchnic ischemia but provide unphysiological blood flow to the liver and thus should be shortened.

Hyperbilirubinemia and Language Delay in Premature Infants

Our goal was to evaluate whether language delay at 3 years in premature infants is associated with previous exposure to hyperbilirubinemia during the first 2 weeks after birth. We performed a retrospective case-control study of infants admitted to the NICU between January and October 2003. Inclusion criteria included a birth weight of < or =1500 g and follow-up to age 3 years. Exclusion criteria included genetic disorders and hearing loss or recurrent ear infections. Peak total serum bilirubin levels during the first 2 weeks and duration of hyperbilirubinemia (days with total serum bilirubin level at >8 mg/dL) were determined. Infants with language delay and who were receiving speech therapy by 3 years were identified through developmental clinic charts and a tracking program and compared with infants who had normal language development. A total of 125 infants with birth weight of < or =1500 g were admitted to the NICU between January and October 2003. Fifteen infants died, and 110 were discharged from the hospital. A total of 102 (93%) of 110 infants had follow-up to the age of 3 years. Four infants were excluded (1 genetic disorder, 3 delayed hearing loss or recurrent ear infections). Twenty-four infants had a language delay and received speech therapy, whereas 74 infants had normal language development. There was no significant difference in peak total serum bilirubin level and duration of hyperbilirubinemia between the 2 groups. On logistic regression, only bronchopulmonary dysplasia was associated with language delay. Hyperbilirubinemia, defined as peak total serum bilirubin level or duration of elevated bilirubin in days, is not associated with language delay in premature infants. However, this issue deserves investigation, because other measures of bilirubin, such as unbound bilirubin, may be associated with language delay.

Outcomes in a Population of Healthy Term and Near-Term Infants With Serum Bilirubin Levels of ≥325 μmol/L (≥19 mg/dL) Who Were Born in Nova Scotia, Canada, Between 1994 and 2000

The goal was to study the incidence of kernicterus, developmental delay, autism, cerebral palsy, and hearing loss in infants with peak total serum bilirubin levels of >or=325 micromol/L (>or=19 mg/dL), compared with infants with less-severe or no hyperbilirubinemia, in a population of healthy term and late preterm infants. Prospectively gathered, standardized, maternal and neonatal data for infants at >or=35 weeks of gestation who were born between January 1, 1994, and December 31, 2000, were extracted from the Nova Scotia Atlee Perinatal Database. Infants with Rh factor isoimmunization, significant congenital or chromosomal abnormalities, or severe peripartum asphyxia were excluded. Comparisons were made on the basis of peak total serum bilirubin levels. Diagnoses were obtained through data linkage with the Medical Services Insurance Database for office visits and the Canadian Institute for Health Information Database for hospital admissions. The registration file provided information allowing calculation of follow-up times, which were determined for each separate outcome. Follow-up periods ranged from 2 to 9 years, with the end point being the first time the diagnostic code was encountered in either database. Cox proportional-hazards regression analyses were used to examine the relationships between outcomes and total serum bilirubin levels. Of 61238 infants included in the study cohort, 4010 (6.7%) did not have linkage data, which left 56019 infants for analysis. There were no cases of kernicterus and no significant differences in rates of cerebral palsy, deafness, developmental delay, or visual abnormalities between the groups. There were suggestions of associations with attention-deficit disorder in the severe hyperbilirubinemia group and with autism in the combined moderate and severe hyperbilirubinemia group. There was no increase in adverse effects reported previously to be associated with bilirubin toxicity. Associations with developmental delay, attention-deficit disorder, and autism were observed.

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

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. 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 mumol/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. 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 mumol/L (conservative) versus 139.2+/-46 mumol/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. 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.

Postoperative hyperbilirubinemia and graft outcome in living donor liver transplantation

Little information is available on the characteristics and clinical significance of serum bilirubin level early after liver transplantation. The aim of this study was to clarify the risk factors for early graft loss and to assess the significance of postoperative hyperbilirubinemia as a predictor of graft outcome in living donor liver transplantation (LDLT). We retrospectively analyzed perioperative parameters in 68 patients who underwent LDLT. Graft loss within 1 year post-LDLT was confirmed in 9 patients (13.4%). Univariate analysis of risk factors showed that preoperative Model for End-Stage Liver Disease score, donor age, postoperative peak serum bilirubin level (p-BIL) within 28 days after LDLT, and surgical complications were significant determinants of early graft loss (<1 year post-transplant). Multivariate analysis identified p-BIL (odds ratio = 1.170, 95% confidence interval = 1.030-1.329, P = 0.016) as the only independent predictor of early graft loss. The incidence of such loss was high in patients with p-BIL over 27.0 mg/dL (area under the receiver operating characteristic curve = 0.988). In conclusion, serum bilirubin level is a useful predictor of short-term (<1 year) graft outcome and for considering retransplantation in a timely fashion.

Identification of Ultrastructural Changes in Liver Allografts of Patients Experiencing Primary Nonfunction

Background Primary nonfunction (PNF) after liver transplantation is fatal without timely retransplantation. PNF has been associated with many risk factors, but the etiology remains unknown in most cases. Using electron microscopy, we examined the hepatic ultrastructure of donor allografts in patients experiencing PNF and compared the findings with a well-matched group of other donor allografts. Materials and Methods Archival paraffin-embedded pre- and post-reperfusion donor liver biopsies were examined by electron microscopy in 10 patients with PNF and in 10 controls, matched by donor age ± 5 years, gender, cold ischemic time ± 1 hour, and donor cause of death. Mitochondria, endoplasmic reticulum, sinusoidal endothelial cells, and the glycogen content of the cells were assessed. The donors’ serum peak transaminases, bilirubin and sodium levels, as well as the recipient age and serum creatinine were compared. Results There were no significant differences in recipient age at the time of transplantation, peak recipient serum creatinine, donor peak serum transaminase, sodium or bilirubin levels. In all cases, the endoplasmic reticulum and sinusoidal endothelial cells were ultrastructurally normal. Hepatocytes had variable degrees of glycogen pooling. Hepatic steatosis and intramitochondrial inclusions cells were present in 5/10 PNF compared to 0/10 controls patients on preperfusion liver biopsy ( P = .17). Conclusion Liver allografts from patients suffering from PNF can have mitochondrial ultrastructural changes on preperfusion biopsies.

240 Delayed Cord Clamping in Very Low Birthweight Infants Reduces the Incidence of Intraventricular Hemorrhage and Late Onset Sepsis

Background: The current prevailing obstetrical practice at birth in the USA is that the umbilical cord of the very low birth weight (VLBW) infant is immediately clamped. The aim of this study was to compare the effects of immediate (ICC) and delayed (DCC) cord clamping on infants born between 24 and 31.6 weeks on two primary outcome variables: bronchopulmonary dysplasia (BPD) and suspected necrotizing enterocolitis (NEC). Secondary outcome variables were blood pressure, hematocrit, late onset sepsis (LOS), and intraventricular hemorrhage (IVH). The hypothesis was that DCC would result in less BPD and suspected NEC.Methods: This was an unmasked randomized controlled trial in which women in labor with infants between 24 and 31 weeks were randomized to ICC (cord clamped at 5 to 10 seconds) or DCC (30 to 45 seconds) groups. DCC infants were held 20–30 cm. below the introitus as possible. The exact time of cord clamping was measured. All neonatal care was at the discretion of the attending physicians.Results: Intention-to-treat analyses revealed no differences in maternal variables, birth weights, gestational age, Apgar scores, initial temperature, and peak serum bilirubin levels. There were no signficant differences in the incidence of BPD (25% vs 22%, p = .78) or suspected NEC (55% vs. 39%, p = .16). Significant differences in IVH (13 vs. 5, p = .03, OR 2.6, 955 CI, 1,6.5) and LOS (8 vs. 1, p = .01) were found between the ICC and DCC groups. In the ICC group, 12 had a grade I-2 IVH compared to 5 in the DCC group. One ICC infant had a grade 4 IVH.Conclusions: Delayed cord clamping appears to protect very low birth weight infants from IVH and sepsis. DCC is an easy to implement intervention.