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Background: Survival in trisomy 13 (T13) and 18 (T18) has increased in recent years, but little is known about the prevalence and management of the non-lethal complications in these populations.

Significance of Problem: A subjectively high rate of direct hyperbilirubinemia (DH) was noted at Children’s Hospital & Medical Center compared to the general population. Defining the prevalence, timing, and risk factors for DH will allow for the development of screening and management guidelines.

Hypothesis, Problem or Question: We hypothesized that infants with T13 and T18 would have high rates of DH, with no significant difference in prevalence between the two populations.

Experimental Design: Retrospective cohort study of infants born between Jan 1, 2012 and March 1, 2020 and admitted to the NICU at Children’s or the Nebraska Medical Center within the first month of life. Data collected included bilirubin, ALT, AST, and GGT levels, liver imaging, and any treatment administered. DH is defined as conjugated bilirubin >1 mg/dL, but the cutoff of >2 mg/dL has a higher association with underlying pathology. Fisher’s exact test and Mann-Whitney U test were used for categorical and continuous variables in DH for both cutoffs.

Results/Data: Thirty-five patients met inclusion criteria: 13 with T13 and 22 with T18. When using the >1 mg/dL cutoff, DH was seen in 7/13 (53.8%) patients with T13 and 9/22 (40.9%) with T18, which was not significantly different between the two diagnoses. Twelve of the 16 infants with DH developed DH in the first two weeks of life and, although it did not reach significance, patients with T13 tended to present with DH earlier than those with T18 (median 5 vs. 12 days of life). DH occurred more often in infants who received TPN (81.3 vs. 36.8%, p=0.016). DH was associated with higher peak AST (p=0.004), ALT (p=0.002), but not GGT (p=0.176) levels. The presence of an abnormal ultrasound was not associated with DH. Six infants were treated with phenobarbital or ursodiol, and 5/6 normalized their conjugated bilirubin levels within one week of starting therapy.

Conclusions: DH was common in infants with T13 and T18, and at a qualitatively higher prevalence than what has previously been reported in the general population, even if excluding those infants who received TPN. Clinicians should consider screening for DH starting within the first week of life in both trisomy 13 and 18, continuing weekly if <1 mg/dL until discharge from hospital.

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Direct Hyperbilirubinemia in Infants with Trisomy 13 and 18

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