| disease | Physiological Jaundice in Newborns |
| alias | Neonatal Hyperbilirubinemia, Physiologic Jaundice |
Physiologic jaundice is not (physiologic jaundice) a condition in newborns where serum bilirubin levels gradually increase from 17-51μmol/L (1-3mg/dl) at birth to 86μmol/L (5mg/dl) or higher 24 hours after birth, clinically presenting as jaundice without other symptoms, and subsiding within 1-2 weeks. In physiologic jaundice, the serum bilirubin in full-term infants does not exceed 204μmol/L (12mg/dl), and in premature infants, it does not exceed 255μmol/L (15mg/dl). However, some premature infants may develop bilirubin encephalopathy even if their serum bilirubin levels are below 204μmol/L (12mg/dl). Therefore, vigilance should be maintained for physiologic jaundice to prevent misdiagnosis of pathologic jaundice or fistula disease.
bubble_chart Pathogen
At 12 weeks of gestational age, a cycle of day and night, bilirubin is already present in the amniotic fluid. This is unconjugated bilirubin secreted into the amniotic fluid by the fetal trachea and bronchial tree. The unconjugated bilirubin produced by the destruction of fetal red blood cells is mostly cleared through the placenta into the maternal circulation, which is why newborns do not have jaundice at birth.
After birth, the newborn must handle the metabolic product of hemoglobin—unconjugated bilirubin—on its own. However, glucuronyl transferase takes 3 to 5 days to mature in full-term infants and 5 to 7 days in premature infants. Combined with the various characteristics of neonatal bilirubin metabolism mentioned earlier, this leads to physiological jaundice in newborns.
bubble_chart Clinical Manifestations
1. Physiological jaundice in mild cases presents as a light yellow color limited to the face and neck, or may spread to the trunk, and the sclera may also be stained yellow. It subsides after 2-3 days, and the skin color returns to normal by the 5th-6th day. In severe cases, jaundice similarly spreads from head to foot and can affect the whole body. Vomitus and cerebrospinal fluid can also be stained yellow, lasting for more than 1 week, especially in some premature infants, which can persist for up to 4 weeks. Their stool remains yellow, and there is no bilirubin in the urine.
2. The color of jaundice in mild cases is light, while in severe cases, the color is darker, but the skin is ruddy, with yellow showing through red.3. Jaundice is mostly seen on the trunk, sclera, and proximal limbs, generally not extending beyond the elbows and knees.
4. Newborns are generally in good condition, without anemia, hepatosplenomegaly, normal liver function, and do not develop kernicterus.
5. Physiological jaundice is more common in premature infants than in full-term infants, may appear slightly delayed by 1-2 days, is more severe, and subsides later, possibly extending to 2-4 weeks.
bubble_chart Auxiliary Examination
Full-term infant:
umbilical bleeding
within 24H of birth
24H--48H
3--7 days
Premature infant:
umbilical bleeding
within 24H of birth
24H--48H
3--7 days
| umbilical bleeding | ～24h | ～28h | 3～7d | |
| Full-term infant | ＜42.8(2.5) | ＜102.6(6) | ＜128.3(7.5) | ＜205.2(12) |
| Premature infant | ＜42.8(2.5) | ＜136.8(8) | ＜205.2(12) | ＜265.5(15) |
(I) Medical History
1. Time of jaundice onset: If jaundice appears within 24 hours, neonatal hemolytic disease should be considered first, followed by congenital infections such as CMV. Jaundice appearing between 2-3 days is most commonly physiological, but ABO hemolytic disease should also be ruled out. Jaundice appearing between 4-7 days is often seen in sepsis or breast milk jaundice. Jaundice appearing after 7 days could be due to sepsis, neonatal pneumonia, biliary atresia, or breast milk jaundice.
2. Rapid progression of jaundice: Neonatal hemolytic disease progresses the fastest, followed by sepsis. Neonatal hepatitis and biliary atresia progress more slowly and persistently.
4. Family history: If there is a family history of favism, G6PD deficiency should be considered. If parents have hepatitis, hepatitis should be ruled out.
5. Pregnancy history, delivery history (premature rupture of membranes, prolonged labor suggesting intrapartum infection), and maternal medication history before labor.
(II) If there is significant pigment in the stool, neonatal hemolytic disease and sepsis should be considered.
1. If there are signs of infection or toxicity, blood and urine cultures should be performed.
2. If there are signs of hemolysis (increased reticulocytes, nucleated red blood cells >2-10/100 white blood cells), maternal and infant ABO and Rh blood types should be checked. A positive Coombs test indicates Rh incompatibility; a positive antibody release test in ABO hemolytic disease. If these tests are negative or the disease starts 3-4 days after birth, G6PD deficiency should be ruled out.
(III) If there is almost no bile pigment in the stool, dark urine, and positive urine bilirubin, neonatal liver fire and biliary atresia should be considered. The former often causes prolonged, almost complete intrahepatic obstruction, making differentiation difficult. The following tests can be helpful.
1. Serial serum bilirubin measurements: Gradual increase suggests biliary atresia, while fluctuations or irregular decreases suggest hepatitis.
2. Serum transaminase levels: Early significant elevation suggests hepatitis.
3. Other laboratory tests: Significant increase in serum 5'-nucleotidase suggests biliary atresia; serum alpha-fetoprotein >40mg/L suggests hepatitis; duodenal drainage containing bile or bile acids can rule out biliary atresia; positive lipoprotein-X (LP-X) suggests biliary atresia.
5. Radionuclide liver and biliary scan: After intravenous injection 99mTc-labeled iminodiacetic acid (IDA) derivatives, slow liver imaging and radioactive concentration in the intestines suggest hepatitis, while rapid liver imaging without intestinal imaging suggests biliary atresia.
6. B-ultrasound: Can detect choledochal cysts; absence of gallbladder suggests biliary atresia.
7. Liver biopsy: Normal liver structure with extensive bile duct proliferation suggests biliary atresia; disordered liver lobule structure, hepatocyte necrosis, and multinucleated giant cells suggest hepatitis.
8. Laparotomy: Should be performed within 2 months. If no gallbladder is found, further exploration is needed; if gallbladder is present, perform cholecystography. If abnormal, perform hepatic portojejunostomy (the earlier the better, no later than 3 months).
bubble_chart Treatment Measures
It can heal on its own, and feeding more sugar water can speed up the disappearance of jaundice, so treatment is not necessary. However, when jaundice is more severe, phototherapy should be administered and further examinations should be conducted to prevent Zabing rational jaundice.
