Vol. 15 Issue 9
Icteric Skin, Sclera and Mucous Membranes
A 12-day-old black boy was admitted to our pediatric unit. He had been born at 39 weeks' estimated gestational age by spontaneous vaginal delivery, and his birth weight was 5 pounds, 6 ounces.
The boy's prenatal course had been complicated because his mother had tested positive for group B streptococci. During her pregnancy, the boy's mother was treated adequately with multiple doses of ampicillin (Omnipen) prior to delivery.
The baby's postnatal course was significant for hyperbilirubinemia within the first 24 hours of life. Phototherapy was required. The baby was also screened for sepsis, but the results were negative. Testing for glucose-6-phosphate dehydrogenase (G6PD) produced normal results as well. The baby had B+ blood and was Coombs positive; his mother's blood type is O+.
The infant was discharged at age 7 days. The newborn nursery staff kept in touch with the mother to continue monitoring total serum bilirubin (TSB) levels. The baby's TSB levels continued to increase, prompting inpatient admission. On the day of admission, the boy's TSB was 20.3 mg/dL.
The boy's mother reported that the infant was otherwise doing well – breastfeeding approximately 10 times per day, stooling five to seven times per day and voiding seven to eight times per day. He had no fever. The mother's only concern was the increasing yellow color that was evident in his eyes and on his extremities.
On admission to the pediatric unit, the infant's vital signs were as follows: temperature 99 degrees Fahrenheit, heart rate 148 beats per minute, respiratory rate 40, blood pressure 76/45 mm Hg, and weight 6 pounds, 4 ounces. The infant abnormalities on physical examination were icteric sclera, mucous membranes, face, trunk and extremities.
Hyperbilirubinemia is an excessive level of accumulated bilirubin in the blood characterized by yellowish discoloration of skin, sclera and nails.1 The most common cause is physiologic jaundice, a mild unconjugated bilirubinemia that affects many newborns.1,2
A baby's peak TSB level generally occurs at 72 to 96 hours of life. It is typically 5 mg/dL to 6 mg/dL and does not exceed 17 mg/dL to 18 mg/dL.2 Physiologic jaundice results from the overproduction of bilirubin accompanied by delayed conjugation.3 Breastfeeding is associated with an increased incidence of hyperbilirubinemia.1
Higher levels of TSB are generally the result of a pathologic condition such as hemolysis (immune-mediated as seen in an ABO-Rh incompatability or nonimmune-mediated due to hemoglobinopathies), erythrocyte membrane defects such as spherocytosis or elliptocytosis, or enzyme deficiencies such as G6PD.2-4 Other considerations are sepsis, deficiencies in conjugating enzymes (e.g., Crigler-Najjar and Gilbert syndromes), biliary atresia, birth trauma resulting in bruising or cephalohematoma.3,4
Guidelines from the American Academy of Pediatrics (AAP) recommend that all babies be screened for hyperbilirubinemia before discharge from the hospital.5 For this infant, the TSB was determined at admission for baseline, and the value was 21.2 mg/dL.
Due to the infant's history of ABO isoimmunization, we ordered a CBC with peripheral smear and reticulocyte count. A Coombs' test for antiglobulin had been positive, but G6PD levels were normal for age. This blood test can produce a false negative when testing occurs during a hemolytic process. When clinical signs suggest ABO-Rh incompatibility, the G6PD test should be repeated when the baby is not hemolyzing.
The results of the CBC with peripheral smear and reticuloctye count can be compared with previous levels obtained in the nursery to assess the degree of hemolysis. The results of the CBC are shown in the table. Schistocytes were present on peripheral smear, and the reticuloycte count was 2.
An elevated TSB and an increased reticulocyte count indicates hemolysis.4 In this patient, peripheral smear schistocytes and fragmented red blood cells also indicated hemolysis. Therefore, the infant's history and diagnostic studies led to the diagnosis of hyperbilirubinemia secondary to ABO isoimmunization.
Hemolytic disease of newborn occurs when antigens on fetal and maternal erythrocytes differ.6 A maternal-fetal ABO incompatibility occurs in about 20% to 25% of pregnancies, but hemolytic disease of newborn occurs in approximately 1 in 10 cases of ABO incompatibility.6
A mother with O blood type has circulating antibodies to both A and B antigens.6 The IgG antibodies cross the placental barrier and bind to the respective antigen on the baby's red blood cells.6 The complement and reticulo-endothelial systems act on the red blood cells to cause hemolysis and an increase in circulating bilirubin.
Bilirubin is a product of the enzymatic breakdown of heme.2 Metabolism of bilirubin occurs in the liver, where it is conjugated to a more water-soluble product and excreted in the urine and feces.2 When the liver is unable to handle the increased bilirubin load, levels increase quickly, and hyperbilirubinemia occurs.
For this infant, the AAP recommended initial treatment was high-intensity phototherapy. The baby receives high levels of irradiance (between 430 nm and 490 nm) to the greatest surface area possible.5 The goal is an average of at least 30 µW/cm2.5
Phototherapy transmits an infusion of discrete photons of energy, which are absorbed by bilirubin molecules.7 The bilirubin undergoes photochemical reactions and forms excretable isomers and breakdown products that bypass the liver's conjugating system and can be excreted in the feces and urine without further metabolism.7
We repeated TSB testing 6 hours after the initial TSB and the initiation of phototherapy. The level was 22.9. Hemolysis is suspected if the TSB does not fall or continues to increase despite intensive phototherapy.5
Because this baby's TSB kept rising despite intensive phototherapy, administration of intravenous immunoglobulin (IVIG) was necessary. The recommended dose is 0.5 g/kg to 1 g/kg over 2 hours.5 The infant received 2.5 grams IVIG.
We instructed the nursing staff to surround the bassinet with aluminum foil and remove the boy's diaper. When bilirubin levels are extremely high, it is imperative to expose as much of the infant's surface area as possible. Generally, it is not necessary to remove diapers. But when the infant is reaching values that are close to exchange transfusion levels, the diaper should be removed until a significant decrease in the bilirubin level is noted.5
In this case, we assessed TSB levels according to AAP guidelines and reassessed 4 hours after the start of infusion of IVIG. The baby's TSB level decreased to 15.4 mg/dL. Eight hours later, it was 13.4 mg/dL. Fifteen hours later, the TSB was 12.5 mg/dL. At this point, we stopped phototherapy.
To assess for rebound hyperbilirubinemia, we observed the infant overnight and measured TSB 15 hours after discontinuation of phototherapy. At that point, the TSB was 14.3 mg/dL. Due to the small rate of increase and the reliability of the family, we released the baby to be followed in the nursery until TSB levels reached a plateau.
The exact mechanism of IVIG in hemolytic disease of newborn is unknown.8 IVIG is a solution of globulins containing antibodies normally present in adult human blood. It is thought to act as an immunomodulator, decreasing the rate of hemolysis.8 When hemolytic disease of the newborn is treated with IVIG and phototherapy, hemolysis is reduced decreasing the need for exchange transfusions.5 If the infant had not responded adequately to IVIG, the dose could have been repeated in 12 hours.5 If the infant had been unresponsive to therapy, an exchange transfusion would have been necessary.
An important side note is that infants and children who receive IVIG should not receive live vaccinations such as MMR and varicella for 11 months after administration (depending on the dose) because they may interfere with the desired antibody response.9
The identification and appropriate treatment of hyperbilirubinemia are clinically significant because bilirubin toxicity can result in bilirubin encephalopathy or kernicterus.
1. Wilson D. Health problems of newborns. In: Wong DL, et al, eds. Wong's Essentials of Pediatric Nursing. 6th ed. St. Louis, Mo: Mosby Inc; 2001:245-330.
2. Wong RJ, Stevenson DK. Pathogenesis and etiology of unconjugated hyperbilirubinemia in the newborn. UpToDate. March 17, 2005.
3. Graham MV, Zeilman C. Hyperbilirubinemia in the healthy term infant. In: Uphold CR, Graham MV, eds. Clinical Guidelines in Family Practice. 4th ed. Gainsville, Fla.: Barmarrae Books Inc; 2003:576-580.
4. Parks DK, Yetman RJ. Perinatal conditions. In: Burns CE, et al, eds. Pediatric Primary Care: A Handbook for Nurse Practitioners. 3rd ed. St. Louis, Mo.: W.B. Saunders; 2004:1083-1127.
5. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114(1):297-316.
6. Kline NE. Alterations of hematologic function in children. In: McCance KL, Huether SE, eds. Pathophysiology: The Biologic Basis for Disease in Adults & Children. 4th ed. St. Louis, Mo.: Mosby; 2002:900-929.
7. Maisels MJ. A primer on phototherapy for the jaundiced newborn. Contemp Pediatr. 2005;22(6):38-45.
8. Gottstein R, Cooke RWI. Systematic review of intravenous immunoglobulin in haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed. 2003;88(1):F6-F10.
9. Children's Memorial Hospital. Treatment for Kawasaki disease. Available at: https://www.childrensmemorial.org/depts/infectious/kawasakitreatment.asp. Accessed June 7, 2007.
Jillian Roberts is a family nurse practitioner who lives in Jacksonville, Fla. She recently graduated from a primary care nurse practitioner program and worked as a pediatric RN prior to and during NP school. Mark Toney is the medical director of pediatric inpatient hospital services at Shands Jacksonville Hospital and an assistant professor of pediatrics at University of Florida College of Medicine.