[A multicenter randomized controlled study on the efficacy and safety of Yinzhihuang oral solution for the treatment of neonatal indirect hyperbilirubinemia in term newborn infants].

OBJECTIVE

A large-scale prospective multicenter randomized controlled trial was conducted to evaluate the efficacy and safety of Yinzhihuang oral solution for the treatment of neonatal indirect hyperbilirubinemia in term newborn infants. Yinzhihuang oral solution is a herbal extract with the main components of Herba Artemisiae Scopariae, Scutellaria, Lonicera Japonica and Gardenia jasminoides.

METHODS

A total of 16 hospitals participated in this study. From March to September 2010, the term infants whose bilirubin level ≥ 40 th percentile for age in hours were enrolled, except for those who received exchange transfusion or had signs of bilirubin encephalopathy. All the 1177 cases were divided randomly into three groups: phototherapy group (409 cases), phenobarbital combined with phototherapy group (373 cases) and Yinzhihuang oral liquid combined with phototherapy group (395 cases). Phenobarbital and Yinzhihuang oral liquid was started once the infants participated the study, and persisted for 5 days. Phototherapy was added as soon as the bilirubin level reached the lowest threshold (the threshold for infants at higher risk). The demographic data of infants in each group were recorded, the serum bilirubin level before treatment, after treatment for 72 hours and after the treatment completion were checked. The reduction rate of serum bilirubin and the phototherapy rate in different groups were compared. The adverse events were assessed as well.

RESULTS

Of the total of 1177 cases, 707 (60.1%) were male, 1119 cases (95.1%) were of Han ethnicity. The average total bilirubin level before treatment was (282.0 ± 70.9) µmol/L and the highest level was 626 µmol/L. The severe hyperbilirubinemia (total bilirubin level at 342 µmol/L to 427 µmol/L) accounted for 15.8% (186 cases), and the extremely severe hyperbilirubinemia (total bilirubin > 427 µmol/L) accounted for 2.5% (30 cases). After treatment for 72 hours, the reduction of bilirubin was not significantly different among three groups (F = 2.89, P = 0.056). After completion of treatment, the reduction rate of bilirubin in Yinzhihuang group was higher than that of the other two groups (F = 5.55, P = 0.004). The rate of infants who did not receive phototherapy in Yinzhihuang group was higher than that in phenobarbital group (χ(2) = 47.38, P = 0.000). In Yinzhihuang group, more infants had bowel movements more than five times a day. The incidence of rashes was higher than that in phenobarbital group (P = 0.019), but no significant difference was found as compared with that in phototherapy group (P = 0.339).

CONCLUSIONS

About 18% of the term infants who were admitted for jaundice had severe or extremely severe hyperbilirubinemia. Yinzhihuang oral solution combined with phototherapy is effective in bilirubin reduction. Early treatment with Yinzhihuang oral solution may inhibit further increase in bilirubin levels, reduce the phototherapy requirement.