Patient's question:
Born to 42 days still yellow, this time of onset and duration: more than a monthDoctor's answer:
Hello, is it physiological or pathological? Please cooperate actively with the doctor for treatment! Neonatal jaundice (eoataljaudice) is caused by the accumulation of bilirubin (most of which is unconjugated bilirubin) in the body. Its causes are complex, including both physiological and pathological factors. Some pathological jaundice can lead to central nervous system damage, resulting in bilirubin encephalopathy. Therefore, it is necessary to strengthen clinical observation of neonatal jaundice, identify the cause as soon as possible, and provide timely treatment.【Characteristics of Bilirubin Metabolism in Newborns】
(1) Excessive bilirubin production
Newborns generate about 8.8 mg/kg of bilirubin daily, while adults only produce 3.8 mg/kg. The reasons are as follows:
- Fetal oxygen partial pressure is low, leading to the production of a larger number of red blood cells. After birth, the oxygen partial pressure increases, resulting in relatively excessive red blood cells and their destruction.
- The half-life of fetal hemoglobin is short, and the lifespan of newborn red blood cells is 20–40 days shorter than that of adults, shortening the cycle of bilirubin formation.
- Other sources of bilirubin production are higher, such as hemoproteins from organs like the liver (e.g., catalase, cytochrome P450) and precursors of bilirubin from ineffective hematopoiesis in the bone marrow (a small number of red blood cells are destroyed during their maturation).
(2) Insufficient ability to transport bilirubin
Newborns immediately after birth often have varying degrees of acidosis, which affects the binding of bilirubin in the blood to albumin. Preterm infants have lower albumin levels than full-term infants, both of which result in insufficient ability to transport bilirubin.
(3) Immature liver function
① The content of Y and Z proteins required for bilirubin uptake in newborn hepatocytes is low and does not reach adult levels until 5–10 days after birth.
② The ability to form conjugated bilirubin is poor, as the content and activity of uridine diphosphate glucuronosyltransferase (UDPGT) in hepatocytes are low (only 0–30% of normal levels). This enzyme cannot effectively conjugate lipid-soluble unconjugated bilirubin (indirect bilirubin) with glucuronic acid to form water-soluble conjugated bilirubin (direct bilirubin). However, this enzyme activity gradually normalizes after one week.
③ The ability to excrete conjugated bilirubin is poor, making it prone to bile stasis.
(4) Characteristics of enterohepatic circulation
Newborn infants have a small number of intestinal bacteria, which cannot reduce bilirubin in the intestines to stercobilinogen or urobilinogen. Additionally, the activity of glucuronidase in the intestinal lumen is high, which can hydrolyze conjugated bilirubin into glucuronic acid and unconjugated bilirubin. The latter is then reabsorbed by the intestine and reaches the liver via the portal vein. Due to these characteristics, newborns' ability to absorb, conjugate, and excrete bilirubin is only 1–2% of that of adults, making them highly susceptible to jaundice. This is especially true when newborns are in states such as hunger, hypoxia, delayed meconium passage, dehydration, acidosis, cranial hematoma, or intracranial hemorrhage, which exacerbate jaundice.
【Classification of Neonatal Jaundice】
(1) Physiological jaundice
Due to the characteristics of bilirubin metabolism in newborns, approximately 50–60% of full-term infants and >80% of preterm infants develop jaundice within 2–3 days after birth, peaking on days 4–5. General condition is good, with jaundice typically resolving within 2 weeks in full-term infants and extending to 3–4 weeks in preterm infants. The previously used upper limit values for serum bilirubin in neonatal physiological jaundice—<205.2 μmol/L (12 mg/dL) for full-term infants and <257 μmol/L (15 mg/dL) for preterm infants—have been questioned, as even smaller preterm infants with bilirubin levels <171 μmol/L (10 mg/dL) may develop bilirubin encephalopathy. International guidelines now specify that serum bilirubin <220.59 μmol/L (12.9 mg/dL) for full-term infants is the threshold for physiological jaundice. Domestic scholars have found through monitoring that the upper limit of physiological jaundice bilirubin levels in normal full-term infants ranges between 205.2–256.5 μmol/L (12–15 mg/dL), with 31.3–48.5% exceeding the original 205.2 μmol/L threshold. Similarly, 42.9% of preterm infants have serum bilirubin levels exceeding 256.2 μmol/L, prompting a nationwide collaborative research to revise China's diagnostic criteria for physiological jaundice.
(2) Pathological jaundice
Pathological jaundice is characterized by the following:
① Jaundice appears within 24 hours of birth.
② Severe jaundice, with serum bilirubin >205.2–256.5 μmol/L or rising by more than 85 μmol/L (5 mg/dL) daily.
③ Prolonged jaundice duration (>2 weeks in full-term infants, >4 weeks in preterm infants).
④ Jaundice that resolves and then reappears.
⑤ Serum conjugated bilirubin >26 μmol/L (1.5 mg/dL).
Active investigation of the cause is necessary for pathological jaundice. The main causes include:
1. Infections
(1) Neonatal hepatitis: Most cases are caused by viral infections in the womb, with cytomegalovirus being the most common. Others include hepatitis B, rubella, herpes simplex, coxsackie, EB virus, listeria, syphilis, and toxoplasma. Infections can be transmitted to the fetus via the placenta or acquired during delivery. Jaundice typically appears 1–3 weeks or later after birth, with pale or grayish-white stools and dark yellow urine. Infants may exhibit anorexia, vomiting, and mild to moderate hepatomegaly.
(2) Neonatal sepsis.
2. Non-infectious
(1) Neonatal hemolytic disease.
(2) Biliary atresia: This condition is now confirmed to be mostly caused by intrauterine viral infections leading to postnatal progressive cholangitis, biliary fibrosis, and atresia. If the wall is weak, it may form a common bile duct cyst. Jaundice typically appears 2 weeks after birth and progressively worsens. Stool color changes from light yellow to white, the liver progressively enlarges with a hard but smooth edge, and liver function changes primarily involve increased conjugated bilirubin. It may gradually progress to cirrhosis after 3 months.
(3) Breast milk jaundice: Approximately 1% of breastfed infants develop breast milk jaundice, characterized by increased unconjugated bilirubin without hemolysis. It often overlaps with physiological jaundice and persists without resolution, with serum bilirubin levels as high as 342 μmol/L (20 mg/dL). Infants are generally well, and jaundice typically decreases after 4–12 weeks. No other causes of jaundice are identified. If jaundice decreases by 3 days after stopping breastfeeding, the diagnosis is confirmed. Current theories suggest that this is due to excessively high β-glucuronidase activity in this type of breast milk, leading to increased reabsorption of bilirubin in the intestines. Some researchers propose that it is caused by a lack of bacteria in the intestines of breastfed infants that can convert bilirubin to urobilinogen and stercobilinogen.
(4) Genetic diseases: G6PD deficiency is common in southern China, with a higher incidence of kernicterus. Other conditions include pyruvate kinase deficiency, spherocytosis, galactosemia, α1-antitrypsin deficiency, and cystic fibrosis.
(5) Drug-induced jaundice: Such as that caused by vitamin K3, K4, and neomycin.