Magnetic resonance spectroscopy and auditory brain-stem response audiometry as predictors of bilirubin-induced neurologic dysfunction in full-term jaundiced neonates.

The purpose of this research was to define the functions of MRS and ABR as predictors of bilirubin-induced neurologic dysfunction (BIND) in full-term neonates who required intervention (phototherapy and/or exchange transfusion). This prospective cohort study was done at the NICU of Tanta University Hospitals over a 2-year duration. Fifty-six full-term neonates with pathological unconjugated hyperbilirubinemia were divided according to MRS and ABR findings into 2 groups: group (1) included 26 cases with mild acute bilirubin encephalopathy (BIND-M score 1-4). Group (2) included 30 cases with neonatal hyperbilirubinemia only. In addition, 20 healthy neonates with similar ages were employed as the controls. When compared to group 2 and the control group, group 1's peak-area ratios of NAA/Cr and NAA/Cho were found to be significantly reduced (P < 0.05). As compared to group 2 and the control group, group 1's Lac/Cr ratio was significantly greater (P < 0.05), but the differences were not significant for group 2 when compared to the control group. Waves III and V peak latencies, I-III, and I-V interpeak intervals were significantly prolonged in group 1 in comparison to group 2 and controls (P < 0.05) with no significant difference between group 2 and control group.   Conclusion: When the symptoms of ABE are mild and MRI does not show any evident abnormalities, MRS and ABR are helpful in differentiating individuals with ABE from patients with neonatal hyperbilirubinemia.    Trial registration:  ClinicalTrials.gov , Identifier: NCT06018012. What is Known: • MRS can be used as a diagnostic and prognostic tool for the differential diagnosis of patients with acute bilirubin encephalopathy, from patients with neonatal hyperbilirubinemia What is New: • ABR is a useful diagnostic and prognostic tool in the care and management of neonates with significantly raised bilirubin. It can be used as early predictor of acute bilirubin encephalopathy in the earliest stage of auditory damage caused by bilirubin.

Current status of neonatal jaundice management in Japan.

BACKGROUND: This nationwide survey aimed to determine the status of jaundice management in Japan. METHODS: A questionnaire about bilirubin level measurements and neonatal jaundice treatment was sent to 330 institutions providing neonatal care. The responses were analyzed according to institution level. RESULTS: Of 330 institutions, 172 responded (52.1% response rate). Total bilirubin levels were measured in the central laboratory using spectrophotometry at 134 institutions and a blood gas analyzer at 81 institutions. Unbound bilirubin (UB) levels were measured by 79 institutions, while transcutaneous bilirubin measurements were taken at 63 institutions. There was no association between institution level and UB or transcutaneous bilirubin measurement. For phototherapy criteria, the Murata-Imura criteria were adopted by 67 institutions, Nakamura criteria by 36, and Morioka criteria by 39. Light-emitting diodes (LED) were used by 160 institutions versus fluorescent lights by 31. When a blue LED was used, 119 institutions used the high mode. There is no standard for increasing light intensity. No association was found between institution level and phototherapy criteria. UB was measured in 14 of 63 institutions using the Murata-Imura criteria. CONCLUSIONS: There is a large variation in the management and treatment of neonatal jaundice among institutes in Japan.

The development and validation of a predictive model for neonatal phototherapy outcome using admission indicators.

Delayed exchange transfusion therapy (ETT) after phototherapy failure for newborns with severe hyperbilirubinemia could lead to serious complications such as bilirubin encephalopathy (BE). In this current manuscript we developed and validated a model using admission data for early prediction of phototherapy failure. We retrospectively examined the medical records of 292 newborns with severe hyperbilirubinemia as the training cohort and another 52 neonates as the validation cohort. Logistic regression modeling was employed to create a predictive model with seven significant admission indicators, i.e., age, past medical history, presence of hemolysis, hemoglobin, neutrophil proportion, albumin (ALB), and total serum bilirubin (TSB). To validate the model, two other models with conventional indicators were created, one incorporating the admission indicators and phototherapy failure outcome and the other using TSB decrease after phototherapy failure as a variable and phototherapy outcome as an outcome indicator. The area under the curve (AUC) of the predictive model was 0.958 [95% confidence interval (CI): 0.924-0.993] and 0.961 (95% CI: 0.914-1.000) in the training and validation cohorts, respectively. Compared with the conventional models, the new model had better predictive power and greater value for clinical decision-making by providing a possibly earlier and more accurate prediction of phototherapy failure. More rapid clinical decision-making and interventions may potentially minimize occurrence of serious complications of severe neonatal hyperbilirubinemia.

Effects of lipid emulsions on unbound bilirubin and response to phototherapy in preterm infants.

OBJECTIVE: Bilirubin-induced neurotoxicity is mediated by the fraction of total serum bilirubin (TSB) not bound to albumin (Bf). Unbound free fatty acids (FFAu) generated from lipid emulsions compete with bilirubin for albumin binding, increasing Bf. Soy-based (IL) and soy-MCT-olive-fish oil-based (SMOF) lipid emulsions contain different fatty acids with distinct albumin binding affinities. IL increases Bf in preterm infants, but the effects of SMOF on Bf are not known. Our objective was to compare changes in TSB, Bf, FFAu, and response to phototherapy in preterm infants receiving SMOF and IL. We hypothesized that SMOF would be associated with lower Bf and better response to phototherapy than IL. METHODS: Very preterm and low birth weight infants (<1500 g, <32 weeks) were infused with IL (n = 20) or SMOF (n = 20) as prescribed by providers. Phototherapy was prescribed using the standard care practice. FFAu profiles and levels, TSB, and Bf were measured on 0, 1, 2, and 3 g/kg/day of lipid infusion and at the initiation and termination of phototherapy. TSB was analyzed in the clinical laboratory using the diazo technique. FFAu and Bf were measured using fluorescent probes. RESULTS: Escalating doses of IL and SMOF increased FFAu levels and Bf, but not TSB. Phototherapy did not significantly decrease Bf for infants receiving either lipid. IL-treated infants had higher levels of unbound linoleic acid, and SMOF-treated infants had higher unbound arachidonic, oleic, and docosahexaenoic acids. CONCLUSIONS: IL and SMOF both increase Bf similarly, and phototherapy does not significantly affect Bf for infants receiving them.

Bilirubin Encephalopathy.

PURPOSE OF REVIEW: Hyperbilirubinemia is commonly seen in neonates. Though hyperbilirubinemia is typically asymptomatic, severe elevation of bilirubin levels can lead to acute bilirubin encephalopathy and progress to kernicterus spectrum disorder, a chronic condition characterized by hearing loss, extrapyramidal dysfunction, ophthalmoplegia, and enamel hypoplasia. Epidemiological data show that the implementation of universal pre-discharge bilirubin screening programs has reduced the rates of hyperbilirubinemia-associated complications. However, acute bilirubin encephalopathy and kernicterus spectrum disorder are still particularly common in low- and middle-income countries. RECENT FINDINGS: The understanding of the genetic and biochemical processes that increase the susceptibility of defined anatomical areas of the central nervous system to the deleterious effects of bilirubin may facilitate the development of effective treatments for acute bilirubin encephalopathy and kernicterus spectrum disorder. Scoring systems are available for the diagnosis and severity grading of these conditions. The treatment of hyperbilirubinemia in newborns relies on the use of phototherapy and exchange transfusion. However, novel therapeutic options including deep brain stimulation, brain-computer interface, and stem cell transplantation may alleviate the heavy disease burden associated with kernicterus spectrum disorder. Despite improved screening and treatment options, the prevalence of acute bilirubin encephalopathy and kernicterus spectrum disorder remains elevated in low- and middle-income countries. The continued presence and associated long-term disability of these conditions warrant further research to improve their prevention and management.

A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia.

Background: Phototherapy is a recommended method for the treatment of neonatal hyperbilirubinemia. However, biomarkers for predicting the more effective duration of phototherapy prior to treatment are lacking. Therefore, we aimed to determine novel predictors for the timing of phototherapy from the perspective of metabolomics. Methods: A total of 12 newborns with neonatal hyperbilirubinemia were recruited on the day of admission. The infants were divided into a short-duration (<30 hours) phototherapy group and a long-duration (≥30 hours) phototherapy group based on the length of phototherapy treatment. Metabolites in serum samples were then explored using an untargeted metabolomics strategy. Results: In total, 59 of 1,073 significantly different metabolites were identified between the short-duration and long-duration phototherapy groups, including 18 upregulated and 41 downregulated metabolites. The results of metabolomic analysis showed that the differentially expressed metabolites were enriched in glycerophospholipid metabolism, which is closely associated with the excretion of bilirubin. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the metabolites were also enriched in alpha-Linolenic acid metabolism and fatty acid elongation. Spearman correlation hierarchical clustering analysis demonstrated that 9 metabolites were negatively correlated with the duration of phototherapy. Metabolites, especially phosphatidylethanolamine (PE) (22:1(13Z)/15:0), phosphatidylcholine (PC) (18:1(9Z)/18:1(9Z)), phosphatidylserine (PS) (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)), had better predictability for the duration of phototherapy [area under curve (AUC): 1; 95% confidence interval (CI): 1-1] than total serum total bilirubin and direct bilirubin (AUC: 0.806; 95% CI: 0.55-1), as revealed by receiver operating characteristic analysis. Conclusions: Our research found that the differential metabolites were associated with the duration of neonatal jaundice and that glycerophospholipid metabolism might have played a role in this biological process. Moreover, metabolites such as PE (22:1(13Z)/15:0), PC (18:1(9Z)/18:1(9Z)), PS (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)) could be used as predictors for phototherapy duration in neonatal hyperbilirubinemia and assist with decision-making.

High levels of unbound bilirubin are associated with acute bilirubin encephalopathy in post-exchange transfusion neonates.

BACKGROUND: Although it is known that unbound bilirubin can enter the brain, there is little evidence of its association with the development of acute bilirubin encephalopathy. Here, we investigated this potential relationship in neonates who had undergone exchange transfusion. METHODS: Data from 46 newborns who underwent exchange transfusion between 2016 and 1-1 to 2018-12-31 at the First People's Hospital of Changde City in China were analyzed. The unbound bilirubin level was taken as the independent variable and the development of the acute bilirubin encephalopathy as the dependent variable. The covariates were age, birth weight, sex, red blood cell count, blood glucose, hemolytic disease, and whether the infant had received phototherapy. RESULTS: The mean age and gestational age of the neonates were 146.5 ± 86.9 h and 38.6 ± 1.3 weeks [38.7(34.6-41.1) weeks] old, respectively; 52.17% were male. Binary logistic regression analysis after adjustment for covariates showed a positive association between the levels of unbound bilirubin and the development of acute bilirubin encephalopathy (odds ratio = 1.41, 95% confidence intervals 1.05-1.91, P = < 0.05). CONCLUSION: There is a significant association between unbound bilirubin levels and the development of acute bilirubin encephalopathy in neonates. Further investigations are required to explore the mechanisms.

Usefulness of the unbound serum bilirubin for predicting neonatal bilirubin encephalopathy / 国际儿科学杂志

Bilirubin encephalopathy is still one of the challenges for neonatal society.In recent years,the incidence in Europe and North America is 1/100 000 ～ 1/40 000,while it is 1.13‰ in China.The current guideline for neonatal hyperbilirubinemia is based on total serum bilirubin (TSB),combined with gestational age,birth weight,age and risk factors.TSB is used as a main index for phototherapy and exchange transfusion.However,only unbound serum bilirubin (UB) can cross blood brain barrier and neuron membrane to cause neurotoxicity,so it is important to monitor UB.In view of the difficulties to measure UB directly,it has been proposed to measure serum albumin (SA),the TSB/SA ratio,TSB/SA molar ratio and the affinity of SA for TSB in addition to monitor TSB,but their clinical practice value is limited.Previously,the methods for direct detection of UB such as oxidase method,modified peroxidase method and photometric method have not been accepted nor routinely used.Recently Martelanc has piloted to use high performance liquid chromatography to directly measure UB with precision up to pmol/L.This recent progress offers reference for measuring UB in neonates,but the threshold of UB predicting bilirubin encephalopathy needs to be further studied.This article will review the important role of UB in predicting bilirubin encephalopathy,predicting experimental parameters of neonatal bilirubin encephalopathy,current methodologies for direct detection of UB.

A clinical study on the effects of exchange transfusion and intensive phototherapy on neurodevelopment in neonates with severe hyperbilirubinemia / 中国新生儿科杂志

Objective To study the effects of exchange transfusion(ET) and intensive phototherapy (IPT) on neurodevelopment in neonates with severe hyperbilirubinemia reaching ET criteria.Method From January 2015 to March 2016,neonates with severe hyperbilirubinemia reaching ET criteria with gestational age ≥35 weeks,and hospitalized in the Department of Neonatology of our hospital were enrolled in the study.The parents were informed of the risks of acute bilirubin encephalopathy (ABE) and both the advantages and disadvantages of IPT and ET.Based on the different choices of their parents,the neonates were assigned into the ET group and the IPT group.General conditions,treatment effects,the incidences of ABE and the prognosis were recorded and analyzed.Result A total of 335 patients were included in this study,147 in the ET group and 188 in the IPT group.Before intervention,the peak of total serum bilirubin (TSB) in ET group (475.8± 100.6 μmol/L) was higher than IPT group (398.3±39.8 μmol/L) (the difference of TSB between two groups was 77.4 μmol/L,P＜0.001),and the incidences of high risk factors such as blood incompatibilities,sepsis,cranial hematoma and intracranial hemorrhage in ET group were higher than IPT group (P＜0.05).Compared with at admission,the incidence of ABE in the ET group increased from 32.0％ to 34.0％ at discharge,mainly due to moderate and severe ABE (the ratio of moderate ABE increased from 2.7％ to 10.2％,and severe ABE increase from 2.7％ to 4.8％).Statistically significant differences existed in the proportion of ABE with different severity at admission and discharge in ET group (P＜0.05),while that in IPT group wasn't statistically significant.241 patients were followed up (follow-up rate 71.9％),with the age ranging from 20 to 36 months.6 cases (5.7％,6/106) in the ET group showed hearing disorder while none (0％,0/135) in the IPT group (P＜0.05).The incidences of neuromotor dyskinesia,language development disorder and spasm in ET group were higher than IPT group(7.5％ vs.3.7％,3.8％ vs.1.5％,4.7％ vs.4.4％,respectively),but the differences weren't statistically significant(P＞ 0.05).No deaths were observed in both groups.Conclusion In neonates with severe hyperbilirubinemia whose TSB exceeding the upper limit of current ET criteria (and within upper limit+5 mg/dl),if the neonates have no risk factors nor clinical symptoms of moderate or severe ABE,only IPT and without ET does not increase the incidence of unfavourable prognosis of central nervous system.

Hyperbilirubinemia in preterm infants in Japan: New treatment criteria.

In 1992, Kobe University proposed treatment criteria for hyperbilirubinemia in newborns using total serum bilirubin and serum unbound bilirubin reference values. In the last decade, chronic bilirubin encephalopathy has been found to develop in preterm infants in Japan because it can now be clinically diagnosed based on an abnormal signal of the globus pallidus on T2-weighted magnetic resonance imaging and abnormal auditory brainstem response with or without apparent hearing loss, along with physical findings of kinetic disorders with athetosis. We therefore revised the Kobe University treatment criteria for preterm hyperbilirubinemic infants in 2017. The three revised points are as follows: (i) newborns are classified under gestational age at birth or corrected gestational age, not birthweight; (ii) three treatment options were created: standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion; and (iii) initiation of standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion is decided based on the total serum bilirubin and serum unbound bilirubin reference values for gestational weeks at birth at <7 days of age, and on the reference values for corrected gestational age at ≥7 days of age. Studies are needed to establish whether chronic bilirubin encephalopathy can be prevented using the 2017 revised Kobe University treatment criteria for preterm infants in Japan.

Turkish Neonatal Society guideline to the approach, follow-up, and treatment of neonatal jaundice.

Jaundice is one of the most common problems in the newborn. It is generally accepted as a physiologic condition; most cases are benign and transient. However, in a small portion of jaundiced newborn infants, serum bilirubin concentrations increase to a level at which irreversible brain damage can occur. The timely diagnosis and management of severe hyperbilirubinemia is essential to prevent acute bilirubin encephalopathy and kernicterus. Kernicterus still occurs although it is almost always preventable. The focus of this guideline is to reduce the incidence of severe hyperbilirubinemia and bilirubin encephalopathy. Therefore, a system-based approach using the recommendations of this guideline should be implemented in all birthing facilities and continued in ambulatory care of the newborn infants.

The effects of LED blue light tube phototherapy in the treatment of acute bilirubin encephalopathy / 中国新生儿科杂志

Objective To study the clinical efficacy of LED blue light tube phototherapy in severe hyperbilirubinemia with acute bilirubin encephalopathy (ABE).Method Clinical data of newborns admitted to neonatal department of our hospital between Dec.2013 and Dec.2016 were retrospectively reviewed.Infants with gestational age ≥ 35 weeks who were diagnosed with severe hyperbilirubinemia and ABE were collected and analyzed.From Dec.2013 to Nov.2014,infants treated with common blue light tube were assigned into traditional blue light group (traditional group).From Dec.2014 to Dec.2016,infants treated with LED blue light tube were assigned to LED blue light group (LED group).Total serum bilirubin (TSB) levels and bilirubin induced neurological dysfunction (BIND) scores were analyzed between the two groups.Neuron specific enolase (NSE) levels before and after phototherapy were also compared.Follow-up data for three months after discharge were analyzed.Result Fifty-one infants with severe hyperbilirubinemia and ABE were included,with 24 cases in traditional group and 27 cases in LED group.There were no significant differences in TSB levels and BIND scores between the two groups before phototherapy (P ＞ 0.05).TSB levels at 4 h,24 h and 48 h after phototherapy in LED group were significantly lower than traditional group respectively [(331.3 ±21.8) μmol/L vs.(372.1 ±25.2) μmol/L,(233.6 ± 20.4) μmol/L vs.(269.4 ± 19.8) μmol/L,(184.5 ± 15.2) μmol/L vs.(226.3 ± 22.7) μmol/L,P ＜ 0.05].However,there was no significant difference in TSB levels at 12 h after phototherapy between the two groups (P ＞ 0.05).BIND scores at 4 h after phototherapy in LED group were significantly lower than traditional group [(4.0 ± 0.6) vs.(4.7 ± 0.8),P ＜ 0.05].There were no significant differences in BIND scores at other time points after phototherapy between the two groups (P ＞ 0.05).In both groups,serum NSE levels after phototherapy were lower than before phototherapy.Serum NSE level after phototherapy in the LED group was significantly lower than the traditional group (P ＜ 0.05).Total phototherapy duration of the LED group was significantly shorter than the traditional group (P ＜ 0.05).The incidence of exchange transfusion in LED group was significantly lower than traditional group.The incidence of abnormal brainstem auditory evoked potential in LED group were significantly lower than traditional group at 1 month and 3 months after birth (P ＜ 0.05).The proportion of abnormal cranial MRI between the two groups showed no statistical differences (P ＞ 0.05).Conclusion TSB levels and brain injury indicators should be closely monitored and evaluated in infants with severe hyperbilirubinemia and ABE.Active LED blue light phototherapy can rapidly reduce TSB levels,effectively control the progress of ABE,and reduce the ratio of exchange transfusion.Adverse reactions of LED blue light phototherapy are not observed in this study.

Risk factors of acute bilirubin encephalopathy in neonates with severe hyperbilirubinemia / 中国新生儿科杂志

Objective To study the risk factors of acute bilirubin encephalopathy (ABE) in neonates with severe hyperbilirubinemia (total serum bilirubin ≥ 427.5 μmol/L).Method Clinical information of neonates with severe hyperbilirubinemia admitted to the Neonatal Department of Baoan Maternal and Child Health Hospital in Shenzhen from December 2013 to October 2017 were collected.The enrolled cases were grouped as ABE and the control group (without ABE).The risk factors for ABE were compared between the two groups and the Logistic regression analysis was used to evaluate the independent risk factor.Result A total of 104 neonates were recruited.There were 32 cases in the ABE group and 72 cases in the control group.The level of total serum bilirubin and indirect bilirubin,the ratio of total bilirubin/albumin,the incidence of glucose-6-phosphate dehydrogenase deficiency and metabolic acidosis and sepsis,the rate of using traditional Chinese medicine and the failure of treatment in other hospitals and non-resident population were all significantly higher in the ABE group than the control (P ＜ 0.05).Logistic regression analysis showed that total serum bilirubin (OR =1.013,95％ CI 1.007 ～ 1.020) and sepsis (OR =6.343,95％ CI 1.801 ～22.338) were the independent risk factors for ABE.Conclusion The severe hyperbilirubinemia infants,particularly with sepsis,are at higher risk of developing acute bilirubin encephalopathy.

Newborn Bilirubin Screening for Preventing Severe Hyperbilirubinemia and Bilirubin Encephalopathy: A Rapid Review.

According to the 2004 American Academy of Pediatrics guideline on the management of hyperbilirubinemia, every newborn should be assessed for the risk of developing severe hyperbilirubinemia with the help of predischarge total serum bilirubin or transcutaneous bilirubin measurements and/or assessments of clinical risk factors. The aim of this rapid review is 1) to review the evidence for 1) predicting and preventing severe hyperbilirubinemia and bilirubin encephalopathy, 2) determining the efficacy of home/community treatments (home phototherapy) in the prevention of severe hyperbilirubinemia, and 3) non-invasive/transcutaneous methods for estimating serum bilirubin level. METHODS: In this rapid review, studies were identified through the Medline database. The main outcomes of interest were severe hyperbilirubinemia and encephalopathy. A subset of articles was double screened and all articles were critically appraised using the SIGN and AMSTAR checklists. This review investigated if systems approach is likely to reduce the occurrence of severe hyperbilirubinemia. RESULTS: Fifty-two studies met the inclusion criteria. Included studies assessed the association between bilirubin measurement early in neonatal life and the subsequent development of severe hyperbilirubinemia and chronic bilirubin encephalopathy/kernicterus. It was observed that, highest priority should be given to (i) universal bilirubin screening programs; (ii) implementation of community and midwife practice; (iii) outreach to communities for education of prospective parents; and (iv) development of clinical pathways to monitor, evaluate and track infants with severe hyperbilirubinemia. CONCLUSIONS: We found substantial observational evidence that severe hyperbilirubinemia can be accurately predicted and prevented through universal bilirubin screening. So far, there is no evidence of any harm.

Facility-based constraints to exchange transfusions for neonatal hyperbilirubinemia in resource-limited settings.

Several clinical guidelines for the management of infants with severe neonatal hyperbilirubinemia recommend immediate exchange transfusion (ET) when the risk or presence of acute bilirubin encephalopathy is established in order to prevent chronic bilirubin encephalopathy or kernicterus. However, the literature is sparse concerning the interval between the time the decision for ET is made and the actual initiation of ET, especially in low- and middle-income countries (LMICs) with significant resource constraints but high rates of ET. This paper explores the various stages and potential delays during this interval in complying with the requirement for immediate ET for the affected infants, based on the available evidence from LMICs. The vital role of intensive phototherapy, efficient laboratory and logistical support, and clinical expertise for ET are highlighted. The challenges in securing informed parental consent, especially on religious grounds, and meeting the financial burden of this emergency procedure to facilitate timely ET are examined. Secondary delays arising from post-treatment bilirubin rebound with intensive phototherapy or ET are also discussed. These potential delays can compromise the effectiveness of ET and should provide additional impetus to curtail avoidable ET in LMICs.

Risk factors for acute bilirubin encephalopathy on admission to two Myanmar national paediatric hospitals.

BACKGROUND: Jaundice is the commonest neonatal ailment requiring treatment. Untreated, it can lead to acute bilirubin encephalopathy (ABE), chronic bilirubin encephalopathy (CBE) or death. ABE and CBE have been largely eliminated in industrialised countries, but remain a problem of largely undocumented scale in low resource settings. As part of a quality-improvement intervention in the Neonatal Care Units of two paediatric referral hospitals in Myanmar, hospitals collected de-identified data on each neonate treated on new phototherapy machines over 13-20 months. The information collected included: diagnosis of ABE at hospital presentation; general characteristics such as place of birth, source of referral, and sex; and a selection of suspected causes of jaundice including prematurity, infection, G6PD status, ABO and Rh incompatibility. This information was analysed to identify risk factors for hospital presentation with ABE, using multiple logistic regression. RESULTS: Data on 251 neonates was recorded over 20 months in Hospital A, and 339 neonates over 13 months in Hospital B; the number of outborn neonates presenting with ABE was 32 (12.7 %) and 72 (21.2 %) respectively. In the merged dataset the final multivariate model identified the following independent risk and protective factors: home birth, ORadj = 2.3 (95 % CI: 1.04-5.4); self-referral, ORadj = 2.6 (95 % CI: 1.2-6.0); prematurity, ORadj = 0.40 (95 % CI: 0.18-0.85); and a significant interaction between hospital and screening status because screening positive for G6PD deficiency was a strong and significant risk factor at Hospital B (ORadj = 5.9; 95 % CI: 3.0-11.6), but not Hospital A (ORadj = 1.1; 95 % CI: 0.5-2.5). CONCLUSION: The study identifies home birth, self-referral and G6PD screening status as important risk factors for presentation with ABE; prematurity was protective, but this is interpreted as an artefact of the study design. As operational research, there is likely to be substantial measurement error in the risk factor data, suggesting that the identified risk factor estimates are robust. Additional interventions are required to ensure prompt referral of jaundiced neonates to treatment facilities, with particular focus on home births and communities with high rates of G6PD deficiency.

Effect of simple phototherapy or phototherapy combined with albumin therapy on severe jaundice in full-term neonates / 中国病理生理杂志

AIM:To analyze the effect of non-exchange transfusion therapy, including simple phototherapy or phototherapy combined with albumin therapy, on severe jaundice in full-term neonates.METHODS: The full-term neo-nates (n=110) with serum total bilirubin (TBIL) level over 342 μmol/L recewed simple phototherapy or phototherapy combined with albumin therapy.The changes of serum bilirubin levels and neurological signs of these neonates were ob-served.RESULTS:Serum TBIL and indirect bilirubin ( IBIL) levels in the 2 groups of hospitalized cases significantly re-duced after the first day of treatment and at discharged (P<0.01).The reduced degrees of TBIL and IBIL levels in the neonates given phototherapy combined with albumin therapy were higher than those in the neonates given simple photothera-py.All these neonates did not have bilirubin encephalopathy on admission or at discharged.CONCLUSION:Both simple phototherapy and phototherapy combined with albumin therapy treat severe jaundice effectively and prevent acute bilirubin encephalopathy in full-term neonates.

Addressing the burden of neonatal hyperbilirubinaemia in countries with significant glucose-6-phosphate dehydrogenase deficiency.

UNLABELLED: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an established worldwide risk factor for severe hyperbilirubinaemia. This literature review examined the pattern and management of severe hyperbilirubinaemia in low- and middle-income countries (LMICs) where G6PD deficiency was 10% or more and found that it was frequently associated with neonatal mortality and, or, neurodevelopmental disorders. CONCLUSION: Low- and middle-income countries need to pay urgent attention to G6PD deficiency to curtail the preventable burden of jaundice-related morbidity, mortality and disability.

Cost-benefit analysis of exchange transfusion for acute bilirubin encephalopathy / 重庆医学

Objective To assess the cost-benefit of exchange transfusion(ET ) in the treatment of different severity of acute bili-rubin encephalopathy(ABE) .Methods Retrospective analysis was carried out on the clinical data of 137 ABE from January 2009 to December 2010 .The enrolled neonates were divided into four groups by ABE severity and interventions :40 neonates in Group SE (Subtle ABE with ET ) ,29 in Group SNE (Subtle ABE without ET ) ,49 in Group ME (Moderate to advanced ABE with ET ) ,and 19 in Group MNE (Moderate to advanced ABE without ET ) .Results The Total Serum Bilirubin (TSB) levels ,the ratio of TSB and plasma albumin (B/A) ,the proportion of neonatal hemolysis disease and the hospitalization costs per capita in Group SE were significantly higher than those in Group SNE (P0 .05) .Morbidity of the severe adverse events associated with ET in Group ME ,12 .2% was 2 .4 times to that of Group SE ,5 .0% .Conclusion ET is worth of the first-line approach rescuing subtle ABE .However ,ET is needed to be weighted the advantages and disadvantages before performed on moderate or advanced ABE .It is necessary to implement phototherapy among neonates with pathologic jaundice ,which is crucial for diminishing mortality and mor-bidity of ABE and lowering medical resource consumption .

The Clinical Characteristics According to the Risk Factors of Idiopathic Nonhemolytic Hyperbilirubinemia

PURPOSE: Hospital readmissions have recently increased due to early hospital discharge and increased trends in breast-feeding. Neonatal hyperbilirubinemia can lead to fatal permanent neurological sequelae without appropriate management. Early detection and intervention are critical. We evaluated the clinical features, risk factors, and brain MRI findings of Korean newborns with idiopathic nonhemolytic hyperbilirubinemia to determine the optimal management policy. METHODS: A retrospective review of the medical records of 79 newborns with idiopathic nonhemolytic hyperbilirubinemia was performed at the NICU of the Kyungpook National University Hospital from January 2006 to September 2009. All patients were 35 or more weeks of gestation, and their peak level of serum total bilirubin was more than 20 mg/dL. RESULTS: The mean gestational age was 38(+3)+/-1(+4) weeks, and the mean age on admission was 8.8+/-4.0 days. The mean body weight (3,105+/-479 g) was decreased by 2.8+/-6.4 percent compared to the mean birth weight (3,174+/-406 g). There were no statistically significant differences for the peak serum bilirubin level or the duration and effects of phototherapy between the patients with and without risk factors, which included: breastfeeding, cephalohematoma, subdural hemorrhage, and/or ABO incompatibility. Patients were grouped according to change of body weight. Group I consisted of patients that gained weight compared to birth weight, and group II of patients that lost weight compared to birth weight. There were significant differences in the peak serum total bilirubin level between the two groups. Thirty nine patients had brain MRI evaluation; 21 patients had bilateral symmetric signal intensity increases in the globus pallidus compared to adjacent corticospinal tract and putamen on T1-weighted images. CONCLUSION: Bilirubin encephalopathy is preventable with early screening and proper management. Parents require instruction on feeding practices and follow-up to prevent complications from idiopathic nonhemolytic hyperbilirubinemia.