In order to develop an approach to the diagnosis and management of the jaundiced newborn, it is necessary to understand the nonpathologic factors that can affect bilirubin levels in the normal newborn infant as well as the natural history of neonatal bilirubinemia. Many factors have been identified in large epidemiologic studies as having some effect on neonatal bilirubin levels,1 but their clinical relevance is often questionable. Those that have been shown in recent studies to have an important influence on total serum bilirubin (TSB) levels are listed in Table 6-1.
Table 6-1. Risk Factors for the Development of Hyperbilirubinemia in Infants of 35 or More Weeks Gestation ||Download (.pdf)
Table 6-1. Risk Factors for the Development of Hyperbilirubinemia in Infants of 35 or More Weeks Gestation
|Elevated predischarge TSB or TcB level11,57,70,75,118,119|
|Jaundice observed in the first 24 h117 or prior to discharge71,116|
|Blood group incompatibility with positive direct antiglobulin test, other known hemolytic disease (e.g., G6PD deficiency, hereditary spherocytosis) (see Chapters 1 and 8)|
|Decreasing gestational age11,69–71|
|Previous sibling with jaundice or who received phototherapy12,13|
|Vacuum extraction delivery, cephalhematoma, or significant bruising11,57–59|
|Exclusive breastfeeding, particularly if nursing is not going well and weight loss is excessive11,22,71,94|
|East Asian race3,11|
|Macrosomic infant of a diabetic mother29,31|
|Maternal age ≥25 years11|
Mean maximum TSB concentrations in East Asian, Native American, and some Hispanic infants (primarily those of Mexican descent) are significantly higher than those in white infants.2–6 In a study of Hispanic infants, 31% had peak TSB levels >15 mg/dL6 compared with 3–10% of infants in other US populations.7,8 The mechanisms responsible for these differences are unknown, although there is some evidence that in the Native American population, increased bilirubin production plays a role.5 Black infants in the United States and Great Britain have lower TSB levels than white infants.3,9–11
Neonatal jaundice runs in families. Khoury et al.12 studied a population of 3301 newborns born to male US army veterans between 1966 and 1986. If one or more previous siblings had a TSB >12 mg/dL, the subsequent sibling was three times more likely than controls (10.3% vs. 3.6%) to develop a TSB >12 mg/dL, and if a prior sibling had a TSB level >15 mg/dL, the risk in the subsequent sibling was increased 12.5-fold (10.5% vs. 0.9%). These relationships applied whether or not the siblings were breastfed or formula fed. The familial nature of hyperbilirubinemia has also been documented in Chinese and Danish infants.13,14
The genetics of neonatal jaundice and the inborn errors ...