The Role of Environmental Factors, Reactive Oxygen Species and Gene Polymorphism in Neonatal Hyperbilirubinemia and Its Clinical Implication
Date Issued
2014
Date
2014
Author(s)
Chou, Hung-Chieh
Abstract
Neonatal hyperbilirubinemia is a common problem with the incidence around 60~70%. The peak serum levels of unconjugated bilirubin in full-term Asian and American Indian neonates are almost double as those in Caucasian and black populations. The finding suggests that genetic factors are involved in the development of neonatal hyperbilirubinemia.
Breastfeeding jaundice is common in exclusively breastfed neonates, 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.
211 G to A Variation of UDP-Glucuronosyl Transferase 1A1 Gene and Neonatal Breastfeeding Jaundice
We prospectively enrolled 688 near term & term infants who were exclusively breast-fed (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 wild types (GG). This phenomenon was only seen in BF group but not in SF group when we do subset analysis. 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.
Prediction of Severe Neonatal Hyperbilirubinemia Using Cord Blood Hydrogen Peroxide: A Prospective Study
Given the relationship between bilirubin and hydrogen peroxide, which is one of reactive oxygen species, we hypothesized that cord blood hydrogen peroxide could be utilized to predict the severity of neonatal hyperbilirubinemia. We prospectively enrolled 158 term or near-term healthy neonates. Cord blood and capillary blood at three and five days of age were measured for hydrogen peroxide and bilirubin concentrations. Newborns were divided into severe or less severe hyperbilirubinemic groups. The rising patterns were similar among bilirubin concentrations and hydrogen peroxide levels during the first few days of life. There was a strong positive correlation between bilirubin concentrations and hydrogen peroxide levels after correlation analysis. It revealed that a cord blood hydrogen peroxide signal level of 2500 counts/10 seconds was an appropriate cut-off for predicting severe hyperbilirubinemia. Sensitivity and the negative predictive value were 76.2% and 93.3%, respectively. Our findings confirm that hydrogen peroxide levels and bilirubin concentrations in cord and neonatal blood are closely related. A cord blood hydrogen peroxide level above 2500 counts/10 seconds associated with a high predictive value for severe hyperbilirubinemia.
Other factors associated with neonatal hyperbilirubinemia
To evaluate the impact of breast-feeding promotion on the incidence of hyperbilirubinemia, on peak bilirubin level and on mean days of hospitalization. Total 1273 healthy full-term newborns born before and after the Baby Friendly Hospital Initiative Program was launched in July 2000.
There was a significant association between monthly rates of breast-feeding and the incidence of hyperbilirubinemia, BW loss ratio, the bilirubin level on the third or fourth day, the peak bilirubin level, the mean hospital days, the mean days of phototherapy, as well as the frequencies of urination and defecation.
A total of 874 neonates were exclusively breastfed and subsequently enrolled in this study. We analyzed the association between weight loss percentage and hyperbilirubinemia and investigated the best weight loss percentage cut-off value for prediction of subsequent hyperbilirubinemia before two weeks of age.
Neonates with lower gestational age (GA) and greater weight loss percentage were associated with hyperbilirubinemia. By using weight loss > 8% of BBW after 48 hours and weight loss > 11% of BBW after 72 hours as the cut-off values for prediction of subsequent hyperbilirubinemia, respectively.
We also retrospectively collected exclusively breast-feeding healthy term and near-term newborns born in our nursery between May 1 2002 to June 30 2005. Finally, 771 newborns were enrolled and 182 (23.6%) cases developed significant hyperbilirubinemia during 4th to 10th day 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 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.
Subjects
高膽紅素血症
雙磷尿核苷-尿苷酸轉移1A1基因
母乳性黃疸
新生兒黃疸
活性氧
生理性體重下降
母嬰親善政策
Type
thesis
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