Index of Suspicion in the Nursery

Abstract

A pair of twin sisters in the nursery remain persistently jaundiced at 1 month of age. The dichorionic diamniotic twins were born at 32 weeks’ gestation to a 29-year-old Asian woman. This was her third pregnancy, and she has a 1½-year-old daughter at home. The pregnancy and delivery were uncomplicated, with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively, for the twins. Twin A weighed 1,333 g and twin B weighed 1,469 g. The initial course for these appropriately grown twins was unremarkable, except for some respiratory distress requiring nasal cannula supplemental oxygen, thermoregulation in an isolette, gavage feedings with human milk, and apnea and bradycardia treated successfully with caffeine. They now are in cribs, receiving human milk exclusively, and otherwise well.The mother's blood type is O Rh-positive and the babies’ blood type is B Rh-positive. Results of a direct Coombs test are negative. Serum bilirubin profile, hemoglobin, and phototherapy treatment for one of the twins are outlined in Table 1; the profile is similar for both twins. Physical examination yields unremarkable findings except for jaundice. Both infants are growing along the 25th to 50th percentile for weight and occipitofrontal circumference. No hepatosplenomegaly or pallor is noted. An additional piece of history guides the diagnosis and prevents expensive evaluation.A history of prolonged jaundice in the older sibling while breastfeeding strengthened the suspicions of human milk jaundice. She had remained jaundiced for 3 months and is developmentally normal.Jaundice (serum bilirubin >10 mg%) beyond 2 weeks in a term or a preterm neonate is defined as prolonged jaundice and demands evaluation. The causes and evaluation are different for indirect and direct hyperbilirubinemia.Parenteral nutrition; sepsis, including urosepsis; and anatomic abnormalities of the intra- and extrahepatic biliary tract (biliary atresia) cause direct bilirubinemia. Jaundice caused by parenteral nutrition is diagnosed by history. Urosepsis causing jaundice is diagnosed by blood and urine culture. Abdominal ultrasonography, radioisotope scanning, and liver biopsy are used for diagnosing anatomic abnormalities. Congenital intrauterine infection is suspected in small-for-gestational age babies who have hepatosplenomegaly, microcephaly, chorioretinitis, and intracerebral calcifications in varying combinations.Indirect hyperbilirubinemia can be due to hemolytic and nonhemolytic disorders. Blood group incompatibility, structural abnormalities of the red cell membrane, red cell enzymatic defects, and disorders of hemoglobin synthesis are causes of hemolytic anemia and hemolytic jaundice.Congenital hypothyroidism, galactosemia, bowel obstruction, constipation, and human milk jaundice are examples of nonhemolytic causes of indirect hyperbilirubinemia. Crigler Najjar syndrome is a rare variety of nonhemolytic unconjugated hyperbilirubinemia.The twins in this case had indirect hyperbilirubinemia. Stable hemoglobin values, absence of hepatosplenomegaly, and appropriate reticulocytosis (6% at 1 month of age) made hemolytic anemia and hemolytic jaundice unlikely. A normal peripheral smear, obtained as part of a routine complete blood count, did not reveal abnormal red cell morphology. The state screen results were normal, ruling out galactosemia and hypothyroidism. The family history of human milk jaundice and absence of hemolytic disorders in the family (especially due to their Asian descent) pointed to the diagnosis of human milk jaundice. No confirmatory test can prove the diagnosis, but a trial off human milk on day 32 provided typical results (Table 2).Human milk jaundice, initially described by Arias and associates in 1963, is a poorly understood condition. Postulated mechanisms include: None of the mechanisms has been demonstrated consistently, and conflicting findings between in vivo observations and in vitro experiments have prevented clarification of the pathogenesis.Cessation of breastfeeding resulting in a decline in the serum bilirubin values, with rebound after reintroduction of human milk, was demonstrated in 1963 by Newman and Gross. The rebound generally does not lead to bilirubin concentrations noted before cessation of human milk feeding. No long-term neurodevelopmental effects result from human milk jaundice.Human milk jaundice differs from jaundice associated with breastfeeding or early breastfeeding jaundice. During the period that first-time breastfeeding mothers establish their milk supply, intake in their exclusively breastfed infants may be insufficient. The infants become dehydrated, lose weight, are constipated, develop jaundice, and may develop hypernatremia. Encouraging breastfeeding while supplementing with formula for a limited time resolves the jaundice. Phototherapy and intravenous fluids may be needed, depending on the serum bilirubin value and severity of dehydration. American Academy of Pediatrics guidelines for phototherapy should be reviewed to decide on the indication for phototherapy. Follow-up evaluation of breastfed babies after discharge by their primary pediatricians is recommended to recognize and institute appropriate management of this complication of breastfeeding.Human milk jaundice is a diagnosis of exclusion, but a history of a similar affliction in siblings and lack of hemolytic disorders in the family can be reasonable indicators of the diagnosis and help avoid expensive evaluation.