Objective To study the relationship between uridine diphosphate glucuronic acid (UGT1A1) gene polymorphism and unexplained neonatal unconjugated hyperbilirubinemia in Jinhua.Method Full-term infants with unidentified non-binding hyperbilirubinemia were selected as hyperbilirubinemia group from January 2016 to December 2017 in the obstetrics or neonatal intensive care unit of Jinhua Central Hospital,healthy full-term neonates and those with physiological jaundice admitted during the same period were selected as control group.Whole blood DNA was extracted and UGT1A1 was sequenced and then annotated with human gene mutation database.The distribution and frequency of UGT1A1 genotype were analyzed.The correlation between different genotypes and unexplained unconjugated hyperbilirubinemia in neonates was also studied.Result Two hundred and forty cases were enrolled in the hyperbilirubinemia group,and 216 cases were enrolled in the control group.Four single nucleotide variation (SNV) sites associated with the disease were found on UGT1A1,which were c.211G＞A (Gly71Arg),c.686C＞A (Pro229Gln),c.1091C＞T (Pro364Leu) and c.1456T＞G (Tyr486Asp),accounting for 83.9％(141/168),1.8％(3/168),8.9％(15/168) and 5.4％(9/168) in the experimental group respectively.The genotype frequency and allele frequency analysis showed that the distribution of the two SNV sites of c.211G＞A and c.1456T＞G were statistically different between the experimental group and the control group (P＜0.05),whereas there was no statistical difference of the other two SNV sites of c.686C＞A and c.1091C＞T between the two groups.Binary Logistic regression analysis showed that c.211G＞A and c.1456T＞G were related to the occurrence of unexplained hyperbilirubinemia,The OR values (95％CI) were 5.412 (3.567～ 8.212) and 8.377 (1.052～66.670) respectively,but no correlation was found of the other two polymorphic loci.At the different genotypes of c.211G＞A locus,the levels of total bilirubin and non-binding bilirubin in infants with homozygous mutant (AA) were higher than those in infants with heterozygous mutant (GA) and wild type (GG),which was statistically significant (P＜0.05).Conclusion The most common mutation site of the UGT1A1 gene in Jinhua is c.211G＞A.The mutations of c.211G＞A and c.1456T＞G are risk factors forunconjugated hyperbilirubinemia in neonates.Of the different genotypes of c.211G＞A locus,the serum bilirubin level of homozygous mutant group was significantly higher than heterozygous mutant group and wild type group.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.