Cholestatic jaundice in infants is jaundice caused by elevated conjugated bilirubin, which has potential risk factors and implies abnormal hepatobiliary function. Early detection of cholestatic jaundice and early and correct diagnosis of the cause of jaundice are important for the treatment and prognosis of the disease. A. Etiology Cholestatic jaundice requires prompt diagnosis and treatment It is important to differentiate between children with cholestatic jaundice and those with non-cholestatic jaundice. The most common causes of cholestatic jaundice at 1 month of age are biliary atresia and infantile hepatitis. Other causes include: a1 antitrypsin deficiency, extrahepatic biliary obstruction, such as common bile duct stones and cystic duct cysts; metabolic abnormalities, such as tyrosinemia, galactosemia, hypothyroidism; congenital defects in bile acid metabolism; Alagille syndrome; Citrin defects, infections; and other rare diseases. Among them, jaundice caused by bacterial sepsis, galactosemia, hypopituitarism, or stones is of acute onset and easily alerts parents and physicians for early diagnosis and treatment. It is worth noting that a proportion of children with cholestatic jaundice are often considered to be physiologically jaundiced or breast milk jaundiced because they are well behaved and growing normally. These children can improve their condition and avoid complications if they are seen promptly and receive early treatment. In particular, children with biliary atresia can have their bile flow reestablished and achieve the longest-term survival of the liver if surgery is performed within 45-60 days. II. Initial evaluation of the jaundiced child 1. jaundice, white stools and/or dark urine suggesting possible cholestatic jaundice Infants passing white stools suggest possible cholestasis, especially persistent white stools are highly specific. It is worth noting that a few newborns have been reported in the literature to pass white stools but with less than 3 white stools, and on examination, these newborns do not have liver disease. Due to the dynamic nature of the disease, some children may not have abnormal stool color in the early stages of the disease, such as children with biliary atresia who have incomplete atresia in the early stages and may have normal stool color. Also, the color of the stool varies depending on the cause of the jaundice. Dark urine is also a nonspecific sign of elevated conjugated bilirubin. If a healthy full-term newborn has jaundice with white stools or if jaundice persists beyond 3 weeks of age, he should be further tested for elevated conjugated bilirubin. Total bilirubin and direct bilirubin can cause jaundice in infants, therefore, the analysis of serum bilirubin is important to distinguish the cause of jaundice. 2-week-old infants found to be jaundiced should be tested for total bilirubin (TB) and direct bilirubin (DB) for clinical evaluation. Breastfed children with no other history (absence of dark urine and light colored stools), a normal physical examination, and the ability to be monitored with certainty can be reviewed at 3 weeks of age. If jaundice persists, total bilirubin and direct bilirubin will be measured; TB<5mg/dL with DB>1.0mg/dL; or TB>5mg/dL with DB to TB ratio >20% are considered abnormal. Initial evaluation of infants with elevated conjugated bilirubin Elevated conjugated bilirubin indicates the presence of cholestasis and requires a complete diagnostic evaluation of the etiology. The goal of the evaluation is to determine the etiology of the cholestasis and, at a minimum, to be able to exclude biliary atresia. 1. Children with galactosemia and hypothyroidism should be evaluated or have repeat newborn screening; these disorders need to be managed as soon as possible to avoid sequelae. It should also be noted that children with cholestasis, despite a confirmed diagnosis, still have the potential for other disorders. If the jaundice does not resolve with appropriate treatment according to the initial diagnosis, further evaluation with other methods should be considered. 2. Ultrasonography, which helps to identify anatomical abnormalities such as common bile duct cysts. Ultrasound examination reveals that the gallbladder is small or missing, suggesting extrahepatic biliary obstruction, but the sensitivity of ultrasound examination is only 73%, so extrahepatic biliary obstruction cannot be ruled out by ultrasound results alone. Ultrasound findings of the “triangular sign” (fibrous mass in the porta hepatis) can help diagnose extrahepatic biliary atresia. However, this technique also depends on the skill and experience of the operator. For cholestasis of unknown etiology, ultrasound is recommended to evaluate and assist in the diagnosis. 3. GGT (gamma-glutamyl transpeptidase) xc. GGT has been used to differentiate biliary atresia from infantile liver, especially in older infants with cholestasis. low GGT is helpful to help rule out obstruction; low GGT with elevated AKP suggests intrahepatic cholestasis due to hereditary or metabolic disease. the degree of GGT elevation is not helpful to differentiate the etiology of cholestasis. Further evaluation of children with cholestatic jaundice should distinguish between hepatocellular cholestasis and obstructive cholestasis; whether the cholestasis is physiologic or anatomic; and whether it requires pharmacologic or surgical management. Valuable detection methods include: percutaneous liver aspiration biopsy, nuclear scan, duodenal aspirate analysis, etc. Percutaneous liver puncture biopsy is safe and rapid, and is useful in providing a specific diagnosis. 50%-99% of patients with biliary atresia are correctly diagnosed by liver puncture biopsy. Liver biopsy has a sensitivity of 99% and a specificity of 92% for the diagnosis of biliary atresia (BA), with a slightly lower specificity for the diagnosis of infantile liver. It is important to note that liver biopsy is affected by the dynamic nature of the disease in the diagnosis of neonatal cholestasis, as the manifestation of the disease varies over time. Liver biopsy performed early in the course of biliary atresia may be difficult to differentiate from infantile liver. Liver biopsy reveals cholestasis and injury of the intrahepatic bile ducts and can provide a specific diagnostic basis. For example, a1 antitrypsin deficiency with positive PAS; Alagille syndrome with bile duct deficiency; sclerosing cholangitis with necrotizing bile duct damage; and other characteristic manifestations of metabolic and storage diseases may also be found. For cholestasis of uncertain etiology, a percutaneous liver aspiration biopsy is performed and the pathological findings are described by a pathologist with expertise in pediatric liver disease. Liver puncture is performed early in the course of the disease (less than 6 weeks of age) and needs to be repeated if the pathologic findings are not sufficiently clear. 2.Nuclide scan Intravenous injection of radioactive material drains into the intestine within the expected time. If there is no visualization in the area of the intestinal scan 24 hours after injection, it suggests biliary obstruction or hepatocellular dysfunction. The sensitivity of the nuclide scan for the diagnosis of biliary atresia is high, and children with complete biliary obstruction do not excrete radioactive material at all. The specificity of a nuclide scan for biliary atresia or other obstructive disease is low, and some children with normal anatomy do not excrete tracers. Despite its high sensitivity, nuclide scanning is time consuming, expensive, and has false-positive and false-negative results, so the Cholestasis Guidelines Committee believes that it is only of value if other methods cannot rule out biliary obstruction. 3. Duodenal fluid aspiration analysis Duodenal fluid is collected by tube placement or provocation test and analyzed for bilirubin concentration, and a positive result is obtained if the bilirubin concentration of the aspirate is lower than the serum bilirubin concentration. A small amount of literature considers the analysis of bilirubin concentration in duodenal aspirates for the diagnosis of biliary obstruction. The sensitivity of the duodenal aspirate analysis method is similar to that of the nuclear scan, and the technique is not very demanding and inexpensive. However, the technique is not widely used because it is time-consuming, invasive, and inconvenient. The guidelines suggest that duodenal aspiration fluid analysis can be considered if other methods fail to detect bile duct obstruction. 4.Magnetic resonance cholangiopancreatography (MRCP) MRCP requires deep sedation or general anesthesia as well as advanced techniques and extensive clinical experience to evaluate cholestasis, and the committee believes that this method is not routinely used. 5. endoscopic retrograde cholangiopancreatography (ERCP) This technique is increasingly used in the analysis of cholestasis in smaller infants. erCP involves endoscopic cannulation of the biliary tract as well as the hepatopancreatic potbelly and injection of contrast contrast medium to visualize the biliary system, and the patient requires general anesthesia. Small pediatric lateral view duodenoscopy has advanced the spread of this technique in small infants. It has a high sensitivity and specificity. The cost of equipment and the expertise required to perform it have both limited the use of ERCP. Prior to performing ERCP, a liver puncture biopsy should be performed. Since ERCP can clarify the cause of cholestasis in newborns and avoid abdominal exploratory surgery, it can be performed in small infants when specialized personnel and equipment are available. V. SUMMARY Identification of jaundice and detection of stool/urine abnormalities in children older than 2 weeks of age can help in early detection of the condition and timely diagnosis. If the condition does not improve after appropriate treatment according to the initial diagnosis, further complete evaluation should be done. Children should be evaluated promptly even if they appear well, as these children may have serious conditions that require urgent treatment, such as extrahepatic biliary obstruction. If diagnosed early and treated surgically, the patient’s liver can achieve longer-term survival. Laboratory tests for cholestasis should include direct bilirubin. TB should be considered abnormal if it is <5 mg/dl and DB >1.0 mg/dl, or TB >5 mg/dl and DB >20%. 2-week-old infants found to be jaundiced should be tested for TB and DB for clinical evaluation, and in breastfed children with no other history (no dark urine or light stools) and a normal physical examination and able to confirm monitoring, they can be If jaundice persists, TB and DB should be tested. Liver puncture biopsy has the highest diagnostic accuracy. However, because of the progressive and dynamic nature of extrahepatic biliary atresia, percutaneous hepatic aspiration biopsy may also be missed. Nuclear scan can rule out extrahepatic biliary obstruction. Ultrasound is used to rule out anatomic abnormalities and may be of more use as imaging studies develop and if the “triangular sign” (fibrous mass in the porta hepatis) can be confirmed ERCP can be used in well-equipped centers with experienced pediatric gastroenterologists. analysis is still relatively rare. Duodenal aspirate analysis or provocation tests should be used in children in remote areas or when other tests are not available. In conclusion, neonatal cholestasis needs to be diagnosed more quickly to achieve better treatment and improve patient prognosis. The guidelines help the clinician in the diagnosis. During the evaluation process, clinicians should not rely solely on a single test to determine the cause of cholestasis; remain alert to the patient, detect jaundice in a timely manner, choose an appropriate and time-saving diagnostic method in the context of the actual situation; and report the condition to a superior physician and make a timely referral for a definitive diagnosis and timely treatment. In addition, scientific research in this field needs to be further deepened and developed.