Causes Of Neonatal Hyperbilirubinemia Investigations And Related Genetic Research

Part One:A Multicenter Survey About The Etiology of Neonatal Hyperbilirubinemia[Abstracts] Objectives:To understand the current situation of the etiology of neonatal hyperbilirubinemia in China, and compare the difference between different areas. Methods:Three tertiary neonatal wards with NICU from three provinces were selected. The data of all neonatal hyperbilirubinemia cases including new admission and inpatients with the gestational age from 34 weeks to term were collected by using a survey form during the period from Aug,2010 to July,2011. All data were analyzed after they had been rechecked by one medical staff to confirm the diagnosis of etiology for hyperbilirubinemia. Results:There were 1103 cases in total from all three areas, the separate number of the cases from different areas were 534,238 and 331. All the cases were classified as different etiologic categories, the percentage of each showed as 249/1103 (22.57%), unknown reasons 220/1103 (19.95%) combined reasons 149/1103 (13.51%), other reasons (such as prterm, LGA, infants of GDM, et al) 128/1103 (11.6%), infection diseases 110/1103 (9.97%), breast feeding related jaundice or excessive weight loss or insufficient intake 92 (8.34%), breast milk jaundice 91(8.25%), haemorrhage 37(3.35%),polycythemia 9(0.82%), delay of meconium 9例(0.82%), thyroid function disorder 9 (0.82%)。The first three single etiological causes are hemolysis, unknown reason, and infection. The clinical features of three groups were different in BW, admission age, admission weight, onset time of jaundice, feeding pattern, feeding starting time, TB, DB, Hb, and Ret,.P<0.05～0.001. The most significant difference was between the south area and the other two areas. Conclusions:This multi-center survey showed the major causes of neonatal hyperbilirubinemia in China were hemolysis, unknown reason and infection. But some of the causes may work together as combined cause. There were about 20% of neonatal hyperbilirubinemia cases having unknown reason, which is interested to us for further investigation. The differences of clinical features between centers may also because of the etiologic difference. Part Two:A Multicenter Study About UGT1A1 Gene In The Neonates With Unknown Reason Hyperbilirubinemia[Abstracts] Objectives:To investigate the mutation of UGT1A1 in the neonates with unknown-reason hyperbilirubinemia. The DNA sequences of UGT1A1 were tested and analyzed. Methods:There were four different places in China involved in the study. The neonatal hyperbilirubinemia cases who have unknown causes were selected following the criteria of including and excluding.50 term babies without pathological jaundice during newborn period were enrolled as control group. The clinical history and venous blood sample were collected. The whole five exons sequences of UGT1A1 were tested and analyzed for all the individuals. Results: There were total of 145 cases enrolled, but only 118 cases were confirmed as unknown reason group, the rest 27 cases were separated as the group of hyperbilirubnemia with clear reason after history review by one single medical staff after all the data collected. The patients from two places were combined as one group because of the cases numbers, so three groups from east, south and north of China were defined. There were totally eight different site of mutations found, and the only one spot showing the statistical difference between all groups was G71R, P<0.001. The frequencies of allele G71R showed increasing from south to north area in China, the difference between north and south area was significant, P<0.01. The clinical features of the onset time, feeding starting time, the TB and DB level showed the differences between three groups, P<0.05～0.001. The statistical analysis between G71R mutation and time of jaundice presence and severity of hyperbilirubinemia showed the correlation between G71R mutation and the jaundice present time, P=0.0094 and P=0.0499. Conclusions:The mutation of UGT1A1 on G71R probably is the potential etiology of unknown-reason hyperbilirubinemia in part areas of China. The differences of G71R mutation between three areas may be related to the clinical features of cases from different areas. The time of jaundice presenting is related to the status of with or without G71R mutation in these patients. Part Three:The Etiology and Clinical Features of Cholestasis in Neonates[Abstracts] Objectives:To explore the etiology and clinical features of cholestasis in neonates, and find the difference between preterm and term infants.Methods:A retrospective study was conducted for the cases of cholestasis during neonatal periods. A total of 176 cases from January 2004 to December 2010 were identified by the etiology as PNAC, infection, biliary tract disorders, congenital abnormalities and chromosomal disorders, metabolic diseases, others (prenatal hypoxia, post unconjugated hyperbilirubinemia, neonatal lupus, and congenital chylothorax) and unknown reason. They were also classified to term and preterm groups according to gestational age, the relative factors, such as feeding patterns, using of PN, infection and hypoxia history, and the clinical features, such as cholestasis onset age, bilirubin level, liver function, and outcome were compared between these two groups. Results:The etiology of 35 term infants was summarized as infection 11/35(31.4%), biliary tract disorders 4/35(11.4%), congenital abnormalities and chromosomal disorders 7/35(20.0%), metabolic diseases 3/35(8.6%), others 7/35(20.0%), unknown reason 3/35(8.6%). There were 97/141(68.8%) of PNAC in preterm infants, the average gestational age was 30+4 (25+3～36+2) weeks. And etiology of the rest 44 preterm cases without PNAC was infection 21/141(14.9%), biliary tract disorders 3/141(2.1%), metabolic diseases 2/141(1.4%), others 5/141(3.6%),unknown reason 13/141(9.2%).The time of fasting, the age of starting feeding, the age of reaching to full feeding was longer than in preterm than term group (P<0.001). The preterm group had more PN and infection cases, and overall PN time was longer in this group (P<0.05～0.001). The term group presented cholestasis and liver function damage was earlier than preterm (P<0.05～0.001). Conclusions:The etiology of neonatal cholestasis is various, it may more complicated in term and non PNAC preterm infants. It is important to screen cholestasis in neonatal inpatients. Investigation of the basic etiology and long term follow up is necessary for the positive cases.