Treatment of neonatal hyperbilirubinemia

OBJECTIVE: To review the recent medical literature on the treatment of neonatal jaundice, focusing on practical aspects that are relevant to pediatricians and neonatologists. SOURCES: An extensive review of the related literature was performed, also including the authors clinical experience in this field of investigation. SUMMARY OF THE FINDINGS: Jaundice is very common among infants during the first days of life. Several factors such as maternal and neonatal history have to be considered before implementing treatment. Significant advances have been made in the past few years concerning the treatment of jaundiced newborn infants. This review focuses on three forms of treatment of neonatal hyperbilirubinemia: phototherapy, exchange transfusion and the use of drugs to reduce serum bilirubin concentration. CONCLUSIONS: Nowadays, the in-depth knowledge about the mechanism of action of phototherapy, the development of intensified phototherapy units and the use of drugs to reduce bilirubin formation, have contributed to significantly decrease the need for exchange transfusion.     

Epidemiology of neonatal hyperbilirubinemia

Interview and record review data from 12,023 singleton deliveries were analyzed to determine the relationships between neonatal hyperbilirubinemia (10 mg/dL or greater) and maternal characteristics. Confounding variables were controlled by multiple logistic regression analysis. There was a statistically significant positive relationship between hyperbilirubinemia and low birth weight, Oriental race, premature rupture of membranes, breast-feeding, neonatal infection, use of the "pill" at time of conception, instrumental delivery, and history of first trimester bleeding. Maternal smoking and black race were negatively related to hyperbilirubinemia and statistically significant. In this study, other previously suspected etiologic factors such as epidural anesthesia, parity, use of oxytocin in labor, and white race were not associated with hyperbilirubinemia.     

Phototherapy for neonatal hyperbilirubinemia

Approximately 60 years ago in England, phototherapy for neonatal hyperbilirubinemia was used in clinical practice. It was introduced in Japan approximately 50 years ago. At that time, the mechanism underlying the serum bilirubin concentration decrease by phototherapy was still unknown. The mechanism was identified by chemists, biochemists, and pediatricians. Clarification started with the report that unconjugated bilirubin was excreted into bile after photoirradiation in Gunn rats. After confirmation of the molecular structure of bilirubin on X‐ray analysis, the mechanism for bile excretion of unconjugated bilirubin was verified based on geometric configurational photoisomers in the Gunn rat. Finally, the reaction and excretion of structural bilirubin photoisomers was proved to be the main mechanism for the decrease in serum bilirubin during phototherapy for neonatal hyperbilirubinemia, which differs from the mechanism in the Gunn rat. The most effective and safest light source and the optimal method to evaluate phototherapy, however, remain unknown. Moreover, as for bronze baby syndrome, which is a well‐known adverse reaction to phototherapy, the etiology is unclear. Hence, we review phototherapy for hyperbilirubinemia including a fundamental understanding of the bilirubin photochemical reactions, and discuss the subclinical carcinogenic risk of phototherapy and the increased mortality rate of extremely low‐birthweight infants due to aggressive phototherapy, which is becoming an increasing problem.     

新生儿高间接胆红素血症病因及临床分析

目的 分析新生儿高间接胆红素血症的病因和临床特点。方法 对1998年1月至2000年1月共收治的126例新生儿高胆红素血症的临床资料进行分析总结。结果 院内外出生者高胆红素血症最常见的原因是围产因素和感染,重度高胆红素主要见于感染和Rh溶血病,126例经过治疗,其中死亡1例、治愈110例、15例黄疸减轻。结论 要降低新生儿高胆红素血症的发病率、致残率和死亡率,做好围产期保健及宣传工作十分重要,蓝光治疗效果好。     

Early prediction of neonatal hyperbilirubinemia

The study aim was to predict, using serum bilirubin, level measured 18 to 24 hours (SB, 18–24) after birth, the occurrence of peak serum bilirubin level >15 mg/dL (hyperbilirubinemia) or the requirement of phototherapy, any time from the second to fifth postnatal day. The study was conducted on a prospective cohort of 274 neonates born in north India. The main outcome measures were (a) hyperbilirubinemia and (b) phototherapy. Serum bilirubin level was estimated at 18–24 hours of age and then daily from second to fifth postnatal day. Exclusion criteria were Rh incompatibility, asphyxia and life threatening congenital malformations; and neonates of women with gestational diabetes or history intake of drugs affecting the fetal liver. Hyperbilirubinemia was found in 12.8%; and 19.3% neonates received phototherapy. Dichotomous SB 18–24, using a cut-off of >3.99 mg/dL, as the “prediction test” had the following sensitivity and specificity for predicting (a) hyperbilirubinemia: 67% and 67%, respectively, and (b) the treatment with phototherapy: 64% and 68%, respectively. We concluded that by using SB 18–24 as the “prediction test”, approximately two-thirds of neonates were test negative and had about one in ten chances of re-admission for treatment of hyperbilirubinemia, if discharged. After further validation, our results will be of benefit to neonates delivered in developing countries.     

Oxidative stress in neonatal hyperbilirubinemia

We investigated the role of bilirubin as an antioxidant in neonatal hyperbilirubinemia (NNH) by measuring malondialdehyde (MDA) levels, a marker of oxidative stress and key antioxidant enzymes viz., superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in otherwise healthy 70 term newborns with NNH and 20 control newborns without jaundice. Jaundiced newborns had significantly lower MDA but higher SOD, catalase and GPx levels. Furthermore, plasma bilirubin showed significant negative correlation with MDA but positive correlation with antioxidant enzyme activities. It is concluded that NNH is associated with lower oxidative stress.     

Immunological profile in neonatal hyperbilirubinemia

Thirty cases of neonatal hyperbilirubinemia of varying etiology, severity and duration; and twenty six normal healthy newborns were subjected to various tests of cellular and humoral immunity. The results revealed a significant depression of all the parameters of cellular immunity in neonatal hyperbilirubinemia of greater than or equal to 10 mg/dl as compared to the control values. The depression of immunological profile in these newborns was seen to be more pronounced with increasing duration and severity of jaundice. A limited assessment of the humoral immunity by the B cell count and serum immunoglobulin IgG levels, however, showed no significant difference from the control.