Chin J Integr Med 2009 Aug;15(4):299-302

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CLINICAL EXPERIENCE
Clinical Observation of Yinzhihuang Oral Liquid () on Prevention of the Premature Infantile Jaundice
CHEN Sheng-ping (), TIAN Li-li (), and LIU Feng-ling ()
ABSTRACT Objective: To observe the clinical efficacy of Yinzhihuang Oral Liquid (YOL, ) to pre-

vent the premature infantile jaundice. Methods: After excluded hemolytic, suffocation, infection, and the very low birth weight, 242 cases of premature infants were randomly assigned to two groups, the treatment group and the control group. Both groups were taken conventional procedures, such as warmth, feeding, and blood glucose monitoring, and the treated group was administered YOL 5 mL each time, twice daily additionally, and the control group without any treatment. The percutaneous bilirubin and blood cells were observed every day. Results: Compared the two groups, the jaundice indices were more significantly different at 24-48 h, 48-72 h, and more than 72 h (P <0.05), but not statistically different at 0-24 h (P >0.05). Hemoglobin, reticulocyte, platelets, and leucocyte were not significantly different between the two groups (P >0.05). Conclusion: YOL as an early intervention has positive significance to decrease the incidence of pathological jaundice in the premature infants, and no significant impact on the blood cells. KEY WORDS premature infants, jaundice, early intervention, Yinzhihuang Oral Liquid, blood cells

Premature infants are prone to get jaundice, bleeding, hard swelling, infection, apnea, and other life-threatening complications due to their growth factors, among which premature infantile jaundice lasted for a long time and more severe, often can cause bilirubin encephalopathy, increasing mortality, and morbidity for premature Infants. Therefore, in the premature infants, the early intervention to reduce nocomplicated bilirubin in body, and prevention of the occurrence of bilirubin encephalopathy have positive significance. This study used Yinzhihuang Oral Liquid (YOL, ) to prevent jaundice in premature infants and the results were reported as follows.

premature infants from the Department of Obstetrics and Gynecology, Xuanwu Hospital, Maternity Hospital, Capital Medical University were enrolled and randomly assigned to two groups. The completely random sample of a large group was adopted, and each premature infant took a three-digit random number, according to Mantissa Single and Double to arrange the treated group and the control group. Between the two groups, the distribution of clinical data showed no significant difference, and the data were showed in the Table 1 (P >0.05).

Treatment
Both groups were taken conventional procedures, such as warmth, feeding, and blood glucose monitoring. In the treatment group, the parents signed the informed consent, and the premature infants were orally administered YOL (Beijing Shuanghe Gaoke Natural Medicine Co., Ltd.), with a small soup spoon in the interval of two breast feedings, 5 mL each time, twice daily for four consecutive days. The control group recieved no treatment.

METHODS
Inclusion Criteria
The included were premature infants except hemolytic premature infants, with severe asphyxia (1 min Apgar score < 7), serious infections, low birth weight, and blood diseases.

Exclusion Criteria
Excluded were premature infants with daily percutaneous bilirubin > 257 mol/L, daily bilirubin increasing equal, or more than 85 mol/L a day, or complicated with infections or other serious diseases of vital organs in the observation period.

Observation Items
The body temperature, weight, stool frequency,
Department of Obstetrics and Gynecology, Xuanwu Hospital, Capital Medical University, Beijing (100053), China Correspondence to: Dr. CHEN Sheng-ping, Tel: 13641116815, E-mail:bingmchen@sina.com DOI: 10.1007/s11655-009-0299-1

Clinical Data
From September 2005 to April 2008, 242

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Chin J Integr Med 2009 Aug;15(4):299-302

Table 1. Distribution of Clinical Data Premature Infants
Weight (g) 2601.2387.1 2620.1401.2 Post-delivery mode (cesarean:vaginal births) 3169 3466 Suffocation (%) 2 3 Complication (%) 32% 34%

Group Control Treated

Gender ratio (Male:Female) 100:93.1 100:92.5

Gestational age (week) 34.12.3 34.52.1

Notes: Square analysis, variance test, Fisher's exact; probability; Complications include pregnancy-induced hypertension, gestational diabetes, hyperthyroidism, and systemic lupus erythematosus, etc.

blood sugar, and blood cells (hemoglobin, reticulocyte, platelet, and leucocyte) were detected and recorded every day. The instrument models MNJ20 was used to measure percutaneous biliary, photoelectric detector (model M1K7222K, Japan) used for blood cells. Preparatory work was adopted in full-term newborn bilirubin values, the skin and vein blood bilirubin values of newborn were measured and compared in 30 samples, including the results confidence interval between the mean standard deviation, so the value of percutaneous bilirubin could be substituted for vein blood bilirubin in clinic. Percutaneous bilirubin measuring equipment was put on the middle of the premature infants' forehead every day after bathing in the morning, three times consecutively, and then the mean value was adopted. Blood sugar and blood cells were also determined at the same time, and the side effects were also observed.

statistical significance, and measurement data was carried out by square analysis, counting data by variance test and Fisher's exact probability. All data were expressed as mean standard deviation.

RESULTS
Comparison of the Results of Percutaneous Bilirubin between the Two Groups
In the observation period, at 0-24 h, in each group, one infant reached the pathological jaundice value separately, at 48-72 h one, and at more than 72 h two patients also reached a pathological jaundice value in the control group. All of them withdrew from the trial. Jaundice index at 24-48 h, 48-72 h, and more than 72 h showed to be significantly different between the two groups (P <0.05), but not statistically significant at 0-24 h (P >0.05, Table 2).

Comparison of Blood Cells between the Two Groups

All changes of hemoglobin, reticulocyte, platelet, and leucocyte between the two groups was not

Statistical Analysis
SPSS11.0 software was performed to conduct
Table 2.
Group Treated (n =120) Control (n =122) P value

Comparison of Percutaneous Bilirubin Values between Two Groups ( s )

Percutaneous bilirubin (mol/L) 0-24 h 24-48 h 127.82.3 (n =119) 149.155.8 (n =121) <0.05 48-72 h 201.650.4 (n =119) 230.462.5 (n =120) <0.05 >72 h 235.854.0 (n =119) 257.457.6 (n =118) <0.05

77.321.2 (n =119) 78.123.6 (n =121) >0.05

Note: the number in the parentheses is the case number Table 3.

Group Treated Time 0-24 h 24-48 h 48-72 h >72 h Control 0-24 h 24-48 h 48-72 h >72 h

Comparison of Blood Cells of Premature Infants between the Two Groups ( s)

Case 119 119 119 119 121 121 120 118 Hemoglobin (1012g /L) 223.2021.54 221.5019.30 218.6018.34 215.1016.87 222.8018.25 220.1018.89 217.5018.07 216.2017.11 Reticulocyte (%) 4.832.04 4.771.84 3.271.53 2.610.96 4.822.09 4.721.77 3.241.63 2.631.03 Platelet (109g/L) 234.5059.75 206.7099.07 210.1089.90 203.3097.65 236.5074.86 199.9098.56 208.4090.12 196.7094.76 Leucocyte (109g/L) 23.8021.12 21.2020.03 20.0020.47 18.5017.42 23.7022.04 21.1020.20 20.1020.00 18.7017.01

Chin J Integr Med 2009 Aug;15(4):299-302 significantly different (P >0.05, Table 3).

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Adverse Reactions
Adverse reactions included nausea, vomiting, abdominal distention, constipation, diarrhea, and increasing of stool frequency. Five cases in the treated group had diarrhea, and two cases lost weight of 10%. All these were improved after infusion treatment. No side effects were observed in the control group.

bilirubin, mild to moderate high bilirubin can also have permanent nerve damage to a newborn baby, resulting in abnormal development of the spirit, only by serum total bilirubin level cannot predict the exact outcome, all newborns with high bilirubin should be given positive treatment to minimize the occurrence of sequelae(3). In the causes of premature infants with hyperbilirubinemia, jaundice can be physical and pathological, internal and external (4). The internal factors include erythropoietin, short life, quick damage, and liver cells intake functioning. The external causes include (1) Infection factors, in relation with humoral and cellular immune function immaturity of premature infants. (2) Hypoxia and acidosis, due to premature infants immaturity of the respiratory center, and the lack of carbonic anhydrase in red blood cells, resulting in the amount reduction of carbon dioxide decomposition of carbonate, so it cannot be effectively formed stimulation on the respiratory center, easily cause apnea and cyanose(5), leading to hypoxia and aggravating jaundice. Premature infants are vulnerable to the impact of acidosis, because of the poor regulatory function of premature infants in the acid-base balance; within a few days after birth, about two-thirds premature infants showed metabolic acidosis, and one-third showed respiratory acidosis or respiratory alkalosis (5). Aacidosis may affect the combination of unconjugate bilirubin to albumin and aggravate jaundice. (3) The delay of feeding the excretion of meconium all can increase the circulation of the gut-liver and the absorption of bilirubin, so timely milking and promoting the excretion of meconium, can effectively reduce the gut-liver circulation and reduce bilirubin absorption. (4) Due to preterm infant's immaturity of the heat center, there is less subcutaneous fat and large body surface area, and heat dissipation increases, which is liable to cause hypothermia. Premature infants have a low function of translating the glycogen into the blood sugar, so it easily results in lowering of blood sugar so as to increase premature infant jaundice. YOL, a Chinese medicine, mainly composed of siphonostiga herb, cape jasmine fruit, scutellaria baicalin, and honeysuckle flower. It has the effects of anti-pathogenic microorganism antibacterial and sterilization, inhibiting the body allergic reaction to reduce destruction of red blood cells, reducing red

DISCUSSION
Premature infants are prone to get jaundice, bleeding, hard swelling, infection, and other complications due to their weak constitutions, in which premature infant jaundice appears earlier, lasts longer, and often more severe. Because of immature blood-brain barrier in premature infants, bilirubin blood easily accesses the brain and causes bilirubin encephalopathy, which increases premature mortality and disability. Since the hyperbilirubinemia of the nervous system can lead to short-term and long-term permanent damage to premature infants and cause bilirubin encephalopathy, so more attention has been paid to premature infants with hyperbilirubinemia clinically in recent years. The study showed that in the first week, 40%-65% of the normal newborns have jaundice, but 80% of the premature infants have various degrees of jaundice. On the cause of hyperbilirubinemia, in addition to clear neonatal perinatal diseases, perinatal obstetric factors is also an important factor in inducing hyperbilirubilirubinemia. The exact cause for morbidity cannot be found in hyperbilirubinemia cases(1). The research showed that small gestational age, premature, amniotic fluid pollution, fetal distress, premature rupture of fetal membranes, gestational disease, cesarean section, the use of oxytocic hormone, old primiparity, multiple births, and the use of sedatives may potentially cause high serum bilirubin levels to increase. The high level of serum bilirubin is one of important reasons for elevating bilirubin encephalopathy, but it is not the only reason. Other reasons may be premature birth, asphyxia, infections, and hypoproteinemia, premature infants themselves is a risk factor for neonatal jaundice and more liable to suffer from bilirubin encephalopathy than fullterm infants (2). It has been reported that neonates have a high rate of the nervous system sequelae of hyperbilirubinemia; in addition to severe high

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Chin J Integr Med 2009 Aug;15(4):299-302 preventive medication for delaying the increase of premature infant jaundice indices has a positive effect. The blood cell tests including hemoglobin, reticulocyte, platelet, and leucocyte were not significantly different between the two groups after four days of treatment, which showed that YOL was safe to blood cells and had few side effects. This suggested that it might be used clinically.

blood cells hemolysis, and lowering serum bilirubin levels. YOL may reduce the damage to the liver, promote bile secretion and excretion, participate as compositions of enzyme, and regulate the activity of enzymes. It can be directly involved in the body nucleic acid, sugar, fat and protein metabolism and promote liver regeneration and protect the integrity of liver cells, thus avoiding the injury of fat peroxides, promoting enterokinesia and being conducive to the excretion of bile and reducing bilirubin gut-liver cycle(6). For their special physiological characteristics of premature infants, under the condition of warming, feeding, and monitoring of blood sugar, maintaining the stability of body temperature and blood sugar, and ruling out the external interference factors, premature infants were fed with YOL for four consecutive days. The results showed that jaundice indices were significantly different between the two groups at 24-48 h, 48-72 h, and >72 h but not at 0-24 h. Therefore, the authors considered that the prevention of the premature infants could start from the second day. In this study, some premature infants in the control group withdrawn from the trial at 48-72 h and more than 72 h, because of bilirubin values reaching infants pathological jaundice (7). The level of serum bilirubin reaching 257 mol/L or a daily increment of more than 85 mol/L occurred in the control group, which did not occur in the treated group; the results showed that

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1. Li QP, Feng ZC. The latest guideline for neonatal jaundice produced by American Academic of Pediatrics. J Appl Clin Pediatr (Chin) 2006;21:958-959. 2. 3. Cashore WJ. Bilirubin and jaundice in the micropremie. Clin Perinatal 2000;27:171-179. Dong SL, Hua Q, Yu AH, Yang YY, Zhang YY. A long-term follow-up of newborn infants with hyperbilirubinemia. Chin J Pract Pediatr (Chin) 1999;14(2):23-24. 4. 5. 6. Yang XQ, Yi ZW, eds. Pediatrics. 6th ed. Beijing: People's Medical Publishing House; 2004:134. Jin HZ, Huang DM, Guan XJ. Practical neonatology. 3rd ed. Beijing: People's Medical Publishing House; 2004:194-196. Heng XH, Tang ZZ. Observation on efficacy of Yinzhihuang Oral Liquid in the prevention and treatment of 388 cases of neonate jaundice. Maternal Child Healthcare Chin (Chin) 2007;32;4617. 7. Wang Y, He NH. Analysis of high risk factors in 210 neonates with hyperbilirubinemia. Chongqing Med (Chin) 2006;35:1932-1934. (Received August 15, 2008) Edited by ZHANG Wen