Clinical Features Of Bilirubin Encephalopathy In Near Term And Term Newborns

Clinical jaundice is present in the majority of the newborns. Although most jaundice is benign, there are still some infants suffering from bilirubin encephalopathy due to the extremely high serum bilirubin level and the development of bilirubin-induced neurologic injury. Bilirubin encephalopathy was reported worldwide. It can be classified as acute bilirubin encephalopathy (ABE) and chronic bilirubin encephalopathy. Although we have paid more attention to the disease and the medical techniques are constantly improved, bilirubin encephalopathy still occurs frequently.The prediction and diagnosis of ABE are dependent on the assessment of clinical symptoms, total serum bilirubin (TSB), bilirubin to albumin ratio (B/A), auditory brainstem responses (ABR), and magnetic resonance imaging (MRI). In China, some people used the neonatal behavioral neurological assessment (NBNA) to assess the clinical symptoms, but it was complex and less specific in predicting bilirubin encephalopathy. Bilirubin-induced neurological dysfunction (BIND) score was easy to operate and have been used by many international researchers. TSB and B/A were the most commonly used laboratory examinations to predict ABE, but their usefulness is controversies. Until now, none of these methods can be a perfect prediction for ABE, and the clinical management relies on the comprehensive assessment of clinical symptoms and the laboratory or imaging examinations.The epidemiological study can provide basis for clinical management. There have been many years since the last multicenter epidemiological study in China. Whether the recent epidemiological characteristics are different from the past is still unknown, and more researches are needed.We conducted this study to summarize the recent epidemiological characteristics of bilirubin encephalopathy. We also evaluated the role some methods played in the prediction of bilirubin encephalopathy.Part OneEpidemiological characteristics of bilirubin encephalopathy in near term and term newbornsObjective1. To summarize the recent epidemiological characteristics of bilirubin encephalopathy.2. To compare the recent epidemiological characteristics with those in the past multicenter epidemiologic study.Methods1. The study was conducted in the neonatal intensive care unit (NICU) and neonatal ward in Children’s Hospital of Zhejiang University. Clinical information of all newborns whose gestational age≥35weeks and was diagnosed bilirubin encephalopathy at discharge between January 1,2011 and December 31,2015 was retrospectively collected.2. Analysis the data of basic information, concomitant diseases, examinations, treatment and short-term outcomes at discharge.3. Compare our data with a recent multicenter epidemiological study in China.Results1. Basic information:In the past five years, there were 32063 newborns admitted to the NICU and neonatal ward, with 112 of them were diagnosed bilirubin encephalopathy. Among the 112 cases,107(95.5%) cases were Han ethnicity,84(75.0%) cases came from Zhejiang Province,81(72.3%) cases were male, and the ratio of male to female was 2.61:1,55(49.1%) cases were primiparae,72(64.3%) cases were natural labor,87(78.4%) cases were exclusive breast feeding or mixed feeding. The mean gestational age was 38.5±1.6weeks,97(86.6%) cases had a gestational age≥37weeks. The mean birth weight was 3174.8±493.3grams,6(5.4%) cases were low birth weight infants,8(7.1%) cases were small for gestational age infants. The age the jaundice appears was 2.3(2.0-3.0) days, the age at admission was 6.0(4.0～8.4) days.2. Concomitant diseases:94 (83.9%) case had concomitant diseases,49 (43.8%) cases had more than one concomitant disease. The most common concomitant diseases were sepsis or infection (42.9%), ABO incompatibility (31.2%), G6PD deficiency (25.0%), birth trauma (24.1%).3. Examinations:The mean peak TSB level after admission was 516.0±144.7 μmol/L,11(13.4%) cases had a peak TSB level less than 342.0μmol/L. The mean B/A level was 7.9±2.5mg/g, the mean albumin level was 36.9±3.6g/L. The abnormal rate of ABR and AABR was 74.4%. The classical changes of ABE in MRI were found in 48.3% infants.4. Treatment and outcomes:The treatment included phototherapy (100%), intravenous albumin (83.0%), exchange transfusion (49.1%), intravenous immunoglobulin (31.3%), and other oral medicine (69.6%). The use of antibiotics was common (86.6%), and most of them was prophylactic, but it decreased year by year.7 cases died in hospital with 3 of them were low birth weight infants, and 3 cases died soon after against-advise discharge. Among 105 survival cases at discharge,38.1% of them had dystonia.5. Compare with a multicenter epidemiological study:The basic information was similar, including gestational age, gender, birth weight, feeding pattern, the age at admission and so on. The percentage of cases with concomitant diseases was higher in our study, but two of the most common concomitant diseases were the same. The peak TSB level and abnormal rate of auditory function were higher in our study, but the B/A level and abnormal rate of MRI were similar. In both studies, Phototherapy was the most common treatment technique, followed by the albumin and exchange transfusion.Conclusion1. The number of patients with bilirubin encephalopathy admitted in hospital was not decreased in the past five years.2. The epidemiological characteristics of bilirubin encephalopathy in the past five years were similar to the multicenter epidemiological study in China.3. Bilirubin encephalopathy can occur in a wide range of TSB level, the cases suffering from bilirubin encephalopathy with a low TSB level are not rare.4. Phototherapy was the most common treatment technique. The use of prophylactic antibiotics was common, but it decreased year by year.Part TwoMethods for predicting the development of acute bilirubin encephalopathy and its outcomesObjectiveTo evaluate the role TSB, B/A and BIND score played in the prediction of acute bilirubin encephalopathy and its outcomes.MethodsThe data came from the cases in Part One.1. Compare the TSB and B/A levels in cases with different risk factors.2. Evaluate the usefulness of TSB and B/A to predict the abnormal auditory function by using receiver operating characteristic curves and find the best cutoff.3. Compare the examination data and short-term outcomes in different BIND score groups.4. Compare the basic information, concomitant diseases, TSB and B/A in newborns died from ABE with those survivals.Results1. There were no differences in TSB and B/A levels between the near term infants and term infants, or between the low birth weight infants with the normal birth weight infants. Without hyperbilirubinemia neurotoxicity risk factors, the TSB level ranged from 248.0～695.0μmol/L, with a mean level of 501.1±142.2μmol/L; The B/A level ranged from 3.6-11.9mg/g, with a mean level of 7.7±2.7mg/g. When G6PD deficiency was present, the mean TSB level (654.8±36.3μmol/L, P=0.001) and B/A level(9.9±1.0 mg/g, P=0.014) were higher. When isoimmune hemolytic disease was present, the mean TSB level (384.1±100μmol/L, P=0.024) and B/A level (5.7±1.5mg/g, P=0.025) were lower. When sepsis or infection was present, the TSB threshold (219.0μmol/L) was lower.2. To predict the abnormal auditory function:The area under the curve for TSB was 0.698, and the best cutoff was 524.5μmol/L. The area under the curve for B/A was 0.676, and the best cutoff was 6.6mg/g.3. While the BIND score increased, the percentage of cases with G6PD deficiency (P=0.003) and sepsis or infection (P=0.002), the TSB (P=0.001) and B/A level (P=0.000), the mortality at discharge (P=0.000) and the percentage of survival cases with dystonia (P=0.000) were higher.4. There were no differences in basic information, the percentage of cases with risk factors, the TSB and B/A level between the dead infants and the survival infantsConclusion1. Using TSB or B/A alone could not predict acute bilirubin encephalopathy and its outcomes well.2. TSB and B/A could predict the abnormal auditory function in a moderate accuracy.3. B/A was not superior to TSB in the prediction of acute bilirubin encephalopathy and its outcomes.4. BIND score was closely related to the laboratory examinations and had a good prediction of the short-term outcomes of acute bilirubin encephalopathy.