bubble_chart Overview

Newborns often experience jaundice, which has complex causes. Severe jaundice can damage the central nervous system, leading to bilirubin encephalopathy.

bubble_chart Etiology

1. Physiological jaundice
   (1) Characteristics
   Appears 2-3 days after birth; peaks at 3-5 days; full-term infants resolve within 7-14 days, while premature infants resolve within 2-3 weeks (some may take up to 4 weeks). Serum bilirubin levels generally do not exceed 205.2 mmol/L (12 mg/100 ml) in full-term infants or 256.5 mmol/L (15 mg/100 ml) in premature infants.
   (2) Causes
   Its occurrence is related to the characteristics of neonatal bilirubin metabolism: (1) Relative overproduction of bilirubin: Neonatal red blood cells have a short lifespan (70-90 days), and the circulating red blood cell count is high, leading to increased red blood cell destruction and thus increased bilirubin production. (2) Deficiency of hepatic receptor proteins: The content of Y protein in hepatocyte cytoplasm is extremely low, resulting in insufficient bilirubin uptake capacity. This usually reaches normal levels 5-10 days after birth. (3) Immature hepatic enzyme systems: Due to the underdevelopment of the enzyme system responsible for forming conjugated bilirubin in hepatocytes—primarily the low content and activity of microsomal glucuronyl transferase—the conversion of unconjugated bilirubin to conjugated bilirubin is limited. These enzymes approach adult levels about one week after birth. (4) Impaired bilirubin excretion: Hepatocytes have a temporary defect in excreting conjugated bilirubin, which can lead to temporary intrahepatic gall fel stasis when bilirubin production is excessive. (5) Increased enterohepatic circulation of bilirubin: The newborn's intestines are initially sterile, with no urobilinogen formation. The β-glucuronidase in the small intestine lumen causes conjugated bilirubin to lose glucuronic acid and revert to unconjugated bilirubin, which is then reabsorbed by the intestines.
   In summary, physiological jaundice results from increased bilirubin production, hepatic immaturity, and enhanced enterohepatic circulation in newborns.
2. Pathological jaundice
   The following conditions suggest pathological jaundice: (1) Early onset, appearing within 24 hours of birth; (2) Severe degree, with serum bilirubin concentrations exceeding the upper limit of physiological jaundice (>12 mg/dl); (3) Rapid progression, increasing by more than 85.5 mmol/L (5 mg/dl) per day; (4) Prolonged duration, or recurrence after resolution, or progressive worsening; (5) Conjugated bilirubin exceeding 34.2 mmol/L (2 mg/dl). For pathological jaundice, the underlying disease cause should be actively investigated. Causes of pathological jaundice include:
   (1) Hemolytic diseases
   1. Hemolytic disease of the newborn is discussed in the section on hemolytic disease of the newborn in this chapter.

2. Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency This disease is an incomplete dominant sex-linked inheritance. Males are more affected than females. It has a high incidence in southern China, especially in Guangdong and Guangxi, as well as among overseas Chinese in Southeast Asia. The onset mostly occurs within 2 weeks after birth, and factors inducing hemolysis include infection, hypoxia, and oxidizing drugs or foods. When diagnosing, family history should be investigated, and the methemoglobin reduction rate should be measured—if reduced, it aids diagnosis. G-6-PD activity assay can confirm the diagnosis.
(II) Neonatal hepatitis syndrome
It is a group of intrahepatic lesions caused by multiple disease causes, forming a combination of diseases. The following four characteristics must be present; absence of any one precludes diagnosis. The essential features are: (1) Occurring in infancy (including the neonatal period); (2) Presence of hepatocellular jaundice, i.e., yellow staining of the infant's skin and sclera, with elevated levels of both direct and indirect bilirubin in the serum, predominantly direct bilirubin; (3) Pathological liver signs, i.e., liver enlargement and/or abnormal texture; (4) Elevated serum alanine aminotransferase levels.
(III) Infectious diseases
In severe bacterial infections such as sepsis or urinary tract infections, bacterial toxins accelerate the destruction of red blood cells and inhibit the activity of glucuronyl transferase.
(IV) Other factors
(1) Prolonged retention of meconium in the intestinal lumen, such as delayed initiation of feeding, hypothyroidism, congenital megacolon, and meconium ileus, all increase the enterohepatic circulation. (2) Use of antibiotics to suppress intestinal flora inhibits the oxidation of conjugated bilirubin in the intestine, leading to hydrolysis into unconjugated forms that are reabsorbed by the intestine. (3) Conditions like cephalohematoma increase bilirubin production. (4) Low body weight, hypothermia, hypoxemia, and hypoproteinemia all affect the activity of hepatic enzymes. (5) Various factors causing perinatal hypoxia and acidosis, such as maternal diseases during pregnancy, abnormalities of the placenta and umbilical cord, difficult delivery, and perinatal asphyxia, all exacerbate physiological jaundice.

bubble_chart Treatment Measures

﹝Treatment﹞

(1) Drug Therapy

1. Enzyme inducers stimulate liver cell enzymes to enhance the ability of unconjugated bilirubin to bind with glucuronic acid. Commonly used agents are phenobarbital and nikethamide. Phenobarbital also increases Y protein content, and the combination of the two can enhance efficacy. Phenobarbital is administered at 5mg/kg·d, and nikethamide at 100mg/kg·d, divided into three doses. Since the therapeutic effect appears only after 2–3 days of medication, early administration is recommended.
2. Albumin Albumin 1g/kg is added to 10–20ml of glucose solution for intravenous drip, administered 1–2 times daily. If albumin is unavailable, plasma can be used at 25ml per dose, 1–2 times daily.
3. Adrenocortical Hormones Prednisone 2mg/kg·d or hydrocortisone 10–20mg/kg·d can enhance the activity of liver enzymes and block antigen-antibody reactions.
4. Chinese Medicinals Decoction of Three Yellows or Virgate Wormwood Decoction can be taken orally.
5. Other Symptomatic Treatments Correct acidosis, improve hypoxia, control heart failure, and maintain an appropriate temperature. These measures help improve and maintain the integrity of the blood-brain barrier, which is beneficial for preventing bilirubin encephalopathy.

(2) Phototherapy

1. Principle Under light exposure, unconjugated bilirubin changes from the lipid-soluble Z-form to the water-soluble E-form, which can be excreted via bile and urine. The optimal absorption wavelength for bilirubin is 450–460nm, which is close to the wavelength of blue light, making blue light the most commonly used. Ordinary fluorescent lamps are also effective.
2. Indications (1) Bilirubin levels above 205.2–256.5mmol/L (12–15mg/dl). (2) Early and rapidly progressing jaundice should prompt immediate phototherapy without waiting for the above threshold. (3) Premature and low-birth-weight infants should have relaxed criteria. (4) For those prenatally diagnosed with Rh hemolytic disease, phototherapy should begin as soon as jaundice appears after birth. (5) Phototherapy before and after exchange transfusion can enhance efficacy and reduce the number of transfusions needed.
3. Side Effects and Precautions Common side effects such as diarrhea and rash resolve spontaneously after stopping phototherapy. When serum conjugated bilirubin is significantly elevated, phototherapy may cause the skin to turn bronze ("bronze baby syndrome"), which gradually fades after stopping treatment due to bile stasis. Riboflavin supplementation is required post-phototherapy; in addition to the physiological water requirement, an extra 20–30ml/kg·d should be given. The eyes should be covered with opaque paper or cloth, and the ambient temperature should be regulated. Long-term side effects remain uncertain.
4. Method Intermittent exposure for 6–12 hours, followed by a 2–4 hour break before resuming. Severe cases may require continuous or prolonged exposure with shorter intervals. Both single-sided and double-sided light sources can be used, with double-sided light being more effective. The total power should be 200–400W.

(3) Exchange Transfusion Therapy
Used for severe neonatal hemolytic disease or conditions like sepsis. For hemolytic disease, the goal is to remove specific blood group antibodies, sensitized red blood cells, and bilirubin from the serum. This not only prevents bilirubin encephalopathy but also corrects anemia, though the procedure carries significant risks. Indications are detailed in the section on neonatal hemolytic disease.