Normal Bilirubin Levels In Newborns – Division of Neonatology, Department of Pediatrics, Oakland University William Beaumont School of Medicine, Beaumont Children’s Hospital, Royal Oak, Mich.
Pediatricians and family physicians routinely deal with jaundiced newborns who escape transient exposure to serum bilirubin. Despite published guidelines for the treatment of neonatal jaundice, there are rare infants who develop bilirubin encephalopathy. Canada currently reports the highest incidence in the developed world at 1 in 67,000 to 1 in 44,000 live births.1
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In this review, I present an approach to the treatment of the newborn with jaundice based on published guidelines.2
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5 The aim is to help clinicians recognize and manage neonatal jaundice, intervene when appropriate and, if possible, prevent bilirubin-induced brain damage. Ideally, published guidelines for the management of hyperbilirubinemia, including therapy and exchange transfusion, are based on estimates of when the benefits of these interventions outweigh their risks and costs. These estimates should come from randomized trials or high-quality, systematic observational studies, but such studies are rare. Therefore, guidelines must rely on relatively uncertain estimates of risks and benefits, often with conflicting results. Furthermore, using a single peak bilirubin level to predict long-term behavioral and developmental outcomes is unreliable and often leads to conflicting results. Due to the lack of evidence, the recommendations included in this article, as well as the current guidelines, are mainly based on consensus.
In this article, I will discuss the care of infants at 35 weeks’ gestation or more, and will not focus on hyperbilirubinemia in premature infants. A complete discussion of the approach in premature infants can be found in a recent publication. 6 A summary of the evidence used in this review is provided in Box 1.
The aim of this review is to help clinicians caring for newborns identify and manage those with jaundice. Every month for the past 40 years, I have searched MEDLINE for English-language articles using the terms “newborn jaundice,” “hyperbilirubinemia,” “phototherapy,” “bilirubin encephalopathy,” and “kernicterus.” I reviewed articles on these topics in the Cochrane Database of Systematic Reviews published between 2000 and 2013, as well as recent textbooks. In addition, I reviewed the American Academy of Pediatrics, Canadian Pediatric Society, and Neonatal Jaundice guidelines. British National Institute for Health and Clinical Excellence.
More than 80% of preterm and late preterm infants develop jaundice when examined carefully in the first few days after birth.7
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8 Almost all infants will have a total serum bilirubin level above the normal adult maximum of 17.1 μmol/L (1 mg/dL) because they have increased erythrocyte turnover and produce more than twice the amount of bilirubin produced per day. Adults, 9 and have a transient deficiency in the ability to conjugate and eliminate bilirubin. This imbalance between bilirubin production and conjugation underlies the pathogenesis of neonatal bilirubinemia. 10 The result is a steady rise in total serum bilirubin levels during the first three to five days, and sometimes more (Figure 1), followed by a proportional decline in levels. Bilirubin formation decreases and conjugation increases.
Nomogram to indicate risk among 2,840 neonates based on hour-specific serum bilirubin values at ≥36 weeks gestation and birth weight ≥2000 g or ≥35 weeks gestation and birth weight ≥2500 g. A serum bilirubin level was obtained before discharge, and the value predicted the probability that the bilirubin level would exceed the 95th percentile after the drop zone. Due to sampling bias, this catalog should not be used to represent the natural history of neonatal hyperbilirubinemia. Reproduced with permission from American Academy of Pediatrics Guidelines, 3
At age 96 years, the 50th percentile of total serum bilirubin levels in healthy newborns in Europe and North America is approximately 137–154 μmol/L (8–9 mg/dL), and the 95th percentile is approximately 257–300 μmol/L. L (15- 17.5 mg/dl).11
13 These ranges are usually harmless, but if bilirubin levels are greater than 425–510 μmol/L (25–30 mg/dL), enough bilirubin can cross the blood-brain barrier, causing yellowing and necrosis of the basal ganglia and brainstem nuclei. causes and leads to acute and then chronic bilirubin encephalopathy or kernicterus. Kernicterus is a devastating form of neurological disorder, in its classic form choreoathetoid cerebral palsy, auditory neuropathy and dyssynchrony with auditory neuropathy and dyssynchrony with or without a hearing loss, visual paralysis and enamel dysplasia of primary teeth. century, the exact molecular mechanisms responsible for the cytotoxicity of bilirubin are not fully understood.15
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Population studies in the United States and Europe suggest that kernicterus still occurs in approximately 0.5–1.0 per 100,000 infants born after 35 weeks’ gestation. and colleagues calculated that the incidence of bilirubin encephalopathy in Canada from 2007 to 2008 ranged from 1 in 67,000 live births to 1 in 44,000.
Several countries have published guidelines for the care of newborns with jaundice, including the USA (American Academy of Pediatrics, 2004), 3 Canada (Canadian Pediatric Society, 2007) 4 and the UK (National Institute for Health and Clinical Excellence) 2 . and the American Academy of Pediatrics guideline published in 2009.5. The 2009 update clarified the distinction between “risk factors for hyperbilirubinemia” and “risk factors for neurotoxicity” and established a firm recommendation to measure total serum bilirubin or transcutaneous bilirubin in every child. A structured algorithm was provided for follow-up based on the presence of risk factors for hyperbilirubinemia and the region in which total serum bilirubin or transcutaneous bilirubin fell before discharge (Figure 2). Key elements of the 2004 American Academy of Pediatrics guidelines are presented in Box 2, and risk factors for hyperbilirubinemia and neurotoxicity are presented in Boxes 3 and 4. Cases of kernicterus malpractice The clinical failure of physicians following these guidelines accounts for most, but not all, of the kernicterus patients seen today.
An algorithm that provides management and follow-up recommendations according to predischarge bilirubin measurements, gestational age, and risk factors for subsequent hyperbilirubinemia. G6PD = glucose-6-phosphate dehydrogenase.
Box 2: Key elements of the American Academy of Pediatrics guideline on the management of hyperbilirubinemia in neonates ≥35 weeks’ gestation3
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Bilirubin levels in newborns are unlike other laboratory measurements. The ever-changing balance between bilirubin production and clearance results in hourly fluctuations in total serum bilirubin levels unique to neonates. Figure 1 shows why it is essential to interpret the total serum bilirubin level in hours depending on the child’s age. Levels are meaningless unless compared to the child’s age in hours.3
19 Total serum bilirubin levels also vary depending on the ethnic composition of the population, incidence of breastfeeding, and other important genetic and epidemiologic factors. group have lower levels than white infants. 12 Important to remember, however, is that 12% of black male infants and 4% of black female infants have glucose-6-phosphate dehydrogenase (G6PD) deficiency, 20 putting them at risk. For severe hyperbilirubinemia and kernikteru (which will be discussed later).1
In addition, hospital stays are now shorter. Monitoring for jaundice and measurement of total serum bilirubin levels were convenient when infants remained in the hospital for three or more days after birth. Nowadays, a baby is often discharged from the vagina before the age of 48 and in some cases before 24 hours. Figure 1 shows that bilirubin levels usually peak on the fourth or fifth day after birth. Therefore, the diagnosis and management of the jaundiced child has changed from an inpatient to an outpatient problem, so appropriate outpatient follow-up is critical3
Clinical assessment of jaundice can be difficult, and detection of jaundice by digital pressure skin blanching in a well-lit room or near a window does not correlate well with total serum bilirubin levels.16
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22 In prematurely discharged infants, bilirubin levels are low enough to warrant additional testing, initiation of phototherapy, or close follow-up. Consequently, using the jaundice grade to estimate the serum bilirubin level during the child’s hospital stay is insufficient to make these surveillance and monitoring decisions with confidence. Recognizing these limitations, experts now recommend that all infants be measured for total serum bilirubin or transcutaneous bilirubin before hospital discharge.4
5 In addition, nursing protocols should require measurement of total serum or transparent bilirubin (respectively) in any neonate who develops jaundice in the first 24 hours.3
As jaundice progresses from the face to the trunk and then to the extremities, the skin at a given bilirubin level
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