Identification of Neonates at Risk for Hazardous Hyperbilirubinemia: Emerging Clinical Insights
Section snippets
Late preterm gestation
Late preterm (340/7–366/7 weeks' gestation) and full-term infants become jaundiced by similar mechanisms, including (1) an increased bilirubin load on the hepatocyte as a result of decreased erythrocyte survival, increased erythrocyte volume, and the enterohepatic circulation of bilirubin; and (2) defective hepatic bilirubin conjugation.17 Late preterm infants evidence a similar degree of red blood cell turnover and heme degradation as their full-term counterparts;18 however, they differ from
Exclusive breast milk feeding
It is likely no coincidence that almost every reported case of kernicterus over the past 2.5 decades has been in breastfed infants.4 As such, exclusive breast milk feeding, particularly if nursing is not going well and weight loss is excessive, is listed as a major hyperbilirubinemia risk factor in the 2004 AAP practice guideline.15 What does the association between exclusive breast milk feeding and kernicterus imply with respect to the etiopathogenesis of marked neonatal jaundice? Numerous
Glucose-6-phosphate dehydrogenase deficiency
G6PD deficiency is an X-linked enzymopathy affecting hemizygous males, homozygous females, and a subset of heterozygous females (by way of nonrandom X chromosome inactivation) and is an important cause of severe neonatal hyperbilirubinemia and kernicterus worldwide.52, 53, 54, 55 Although most prevalent in Africa, the Middle East, East Asia, and the Mediterranean, G6PD deficiency has evolved into a global problem as a result of centuries of immigration and intermarriage.52, 53, 54, 55 It is a
ABO hemolytic disease
Hemolytic disease related to ABO incompatibility is a major risk factor for severe hyperbilirubinemia in the 2004 AAP practice guideline15 and, for all intents and purposes, is limited to infants of blood group A or B born to mothers who are blood group O.72, 73 Although this association exists in approximately 15% of pregnancies, only a small fraction of such infants develop significant hyperbilirubinemia.72, 73 More specifically, of type A or B infants born to mothers who are blood group O,
East Asian ethnicity
Neonates of East Asian ethnicity encompassing the populations of mainland China, Hong Kong, Japan, Macau, Korea, and Taiwan evidence a higher incidence of hyperbilirubinemia than other ethnicities (see Fig. 3)67 and an overall increased risk for a TSB level of 20 mg/dL (342 μmol/L) or greater (odds ratio: 3.1; 95% CI: 1.5–6.3).11 As such, East Asian ancestry is listed as a major risk factor for severe hyperbilirubinemia in the 2004 AAP clinical practice guideline.15 Investigators have
Jaundice observed in the first 24 hours of life
Jaundice appearing in the first 24 hours of life has long been regarded as an abnormal clinical finding and an indication for a bilirubin measurement.15 Approximately 2.8% of newborns evidence jaundice within 18 hours of life and 6.7% within 24 hours (Fig. 4).91 As contrasted with nonjaundiced newborns on the first day of life, newborns who have overt jaundice in the first 24 hours of life are more likely to receive phototherapy (18.9% versus 1.7%; relative risk: 10.1; 95% CI: 4.2–24.4)91 and
Cephalohematoma or significant bruising
Internal hemorrhage, ecchymoses, and other extravascular blood collections enhance the bilirubin load on the liver. Extravascular red cells have a markedly shortened life span, and their heme fraction is quickly catabolized to bilirubin by tissue macrophages that contain heme oxygenase and biliverdin reductase.92 Thus, cephalohematoma, subdural hemorrhage, massive adrenal hemorrhage, and marked bruising can be associated with increased serum bilirubin levels and typically manifest 48 to 72
Previous sibling treated with phototherapy
A history of a previous sibling treated with phototherapy is an identified risk factor for hyperbilirubinemia,11, 95 most notable at higher TSB levels (>15 mg/dL [257 μmol/L]).96 This relationship may reflect recurrent ABO or Rh hemolytic disease97 or exposure to a common environmental factor in addition to a shared genetic background.95 It is known that the recurrence rate of ABO hemolytic disease is high; 88% in infants of the same blood type as their index sibling, with almost two thirds of
Combining clinical risk factor assessment with predischarge bilirubin measurement
Three recent clinical studies suggest that combining clinical risk factor analysis with a birth hospitalization predischarge measurement of TSB or TcB will improve the prediction of subsequent hyperbilirubinemia risk.13, 14, 16 An hour-specific predischarge TSB or TcB level in the high risk zone (>95%) using the percentile-based bilirubin nomogram described by Bhutani and colleagues21 is itself a major risk factor (see Box 1) for severe hyperbilirubinemia.21, 100 Not surprisingly, the clinical
Summary
A myriad of demographic, environmental, and genetic factors have been identified as risks for developing severe hyperbilirubinemia. Late preterm gestational age, exclusive breastfeeding, G6PD deficiency, ABO hemolytic disease, East Asian ethnicity, jaundice observed in the first 24 hours of life, cephalohematoma or significant bruising, and a previous sibling treated with phototherapy are highlighted as major risk factors in the 2004 AAP guideline15 and reviewed herein. It increasingly appears
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ABM Clinical Protocol #22: Guidelines for Management of Jaundice in the Breastfeeding Infant 35 Weeks or More of Gestation—Revised 2017
2022, Breastfeeding: A Guide for the Medical ProfessionIs hyperbilirubinemia a contraindication for neonatal circumcision? A survey of practice patterns of pediatric urologists and a review of the literature
2021, Journal of Pediatric UrologyCitation Excerpt :Population-based data on the prevalence of each etiology contributing to neonatal HB is scant. This is likely due to the multifactorial etiopathogenesis of HB, which includes also genetic contributors and individual factors, which can confer different degrees of risk [12]. Among these several etiologies, the pertinent benign causes of neonatal HB will be discussed.
Disorders in the neonatal period
2021, Biochemical and Molecular Basis of Pediatric DiseaseEffects of massage on newborn infants with jaundice: A meta-analysis
2018, International Journal of Nursing SciencesCitation Excerpt :Neonatal jaundice is a phenomenon of yellow-dyed skin, sclera and other organs in the neonatal period caused by blood bilirubin accumulation, which is a relatively prevalent disease in neonates. More than half of newborns [1,2] and 80% of preterm children [3] develop clinical symptoms of jaundice. The cause of neonatal jaundice is complex.
Glucose-6-Phosphate Dehydrogenase Deficiency and the Need for a Novel Treatment to Prevent Kernicterus
2016, Clinics in PerinatologyCitation Excerpt :The incidence of kernicterus has risen in recent years because of a variety of factors5,40,41: infants are often discharged from the hospital within 24 to 48 hours of birth, despite the fact that TB levels often peak 4 to 5 days after birth; the lack of proper monitoring at home allows the development of kernicterus, which might have otherwise been prevented if the infant were to remain at the hospital.42 Increasing popularity of breast-feeding has also contributed to hyperbilirubinemia and kernicterus.40,43 In developing regions, access to phototherapy and exchange transfusions is often limited.44
Late-preterm birth and neonatal morbidities: Population-level and within-family estimates
2015, Annals of EpidemiologyCitation Excerpt :The rate of late-preterm birth declined somewhat since then, to 8.8% in 2008 [1], although it remains much higher than it was two decades ago. Late-preterm birth has been linked to neonatal respiratory conditions and hyperbilirubinemia [2–4], both of which are not uncommon, often require substantial health care resources [5,6] and have been associated with childhood developmental impairments even when not severe [7–12]. However, preterm birth is strongly associated with socioeconomic status [13], and some of the “effects” of preterm birth, and of late-preterm birth in particular, may thus reflect unobserved confounding factors.
Funding was received from Mario Lemieux Centers for Patient Care and Research of the Mario Lemieux Foundation.