Direct hyperbilirubinemia and cholestasis in trisomy 13 and 18

Am J Med Genet A. 2022 Feb;188(2):548-555. doi: 10.1002/ajmg.a.62552. Epub 2021 Nov 1.


Trisomy 13 and 18 are common chromosomal abnormalities that affect multiple organ systems. There is a paucity of published data, however, on the hepatic complications seen in these patient populations. One of the most common pathologic hepatobiliary issues seen in the newborn period is direct hyperbilirubinemia (DH). Thus, this study sought to estimate the incidence and evaluate possible etiologies of DH in neonates with trisomy 13 or 18. This retrospective cohort study included all infants admitted to our two neonatal intensive care units between 2012 and 2020 with the diagnosis of trisomy 13 or 18. DH is most commonly diagnosed as a direct bilirubin >1 mg/dl but a cutoff of >2 mg/dl is more specific for cholestasis, so both cutoffs were evaluated. Continuous data were compared using Fisher's exact test and categorical variables by the Mann-Whitney U test. Thirty-five patients met inclusion: 13 with trisomy 13 and 22 with trisomy 18. DH of >2 mg/dl was seen in seven (53.8%) patients with trisomy 13 and five (22.7%) with trisomy 18. Using a cutoff of >1 mg/dl, the rate of trisomy 13 was unchanged, but the rate in trisomy 18 increased to 9/22 (40.9%). There was a trend toward more DH in trisomy 13 patients (p = 0.079) versus trisomy 18 and higher rates in infants who received total parenteral nutrition (TPN) (50.0 vs. 13.3%, p = 0.026). The presence of cardiac or ultrasound-defined hepatobiliary abnormalities was not correlated with DH. Due to the high rates of DH in hospitalized neonates with trisomy 13 and 18, we recommend screening newborns with trisomy 13 or 18 for DH starting in the first week of life and continuing at least weekly until 4 weeks of life or until completion of TPN, whichever comes later. Future studies should further evaluate possible etiologies of DH in this population.

Keywords: Edward syndrome; Patau syndrome; conjugated hyperbilirubinemia; screening; total parenteral nutrition.

MeSH terms

  • Cholestasis* / complications
  • Cholestasis* / diagnosis
  • Cholestasis* / epidemiology
  • Humans
  • Hyperbilirubinemia* / complications
  • Hyperbilirubinemia* / epidemiology
  • Infant
  • Infant, Newborn
  • Parenteral Nutrition, Total / adverse effects
  • Retrospective Studies
  • Trisomy 13 Syndrome / complications
  • Trisomy 13 Syndrome / diagnosis
  • Trisomy 13 Syndrome / epidemiology