636 - Acetaminophen Impact on Hepatic and Renal Biomarkers: Secondary Outcomes from a Randomized Controlled Trial

Publication Number: 2621.636

Tiina Ukkonen, Oulu University Hospital, Oulu, Pohjois-Pohjanmaa, Finland; Antti Härmä, Children's Hospital, Rovaniemi, Lappi, Finland; Mikko Hallman, University of Oulu, Oulu, Pohjois-Pohjanmaa, Finland; Outi Aikio, Oulu Univeristy Hospital, Oulu, Pohjois-Pohjanmaa, Finland

Background: Acetaminophen is used for pain management and ductal closure in very low gestational age (gestation < 32wk, VLGA) infants. Although its use in adult and pediatric patients has raised safety concerns, no serious adverse events or increases in hepatic and renal laboratory values have been detected in VLGA infants. However, prior studies remain scarce with low patient numbers (Haslund-Krog 2024; Padavia 2024). We previously conducted a randomized controlled trial on the efficacy and safety of acetaminophen for pain management in intubated VLGA infants during early intensive care (PAS2025, Poster #574).

Objective: To study the short-term effects of intravenous (IV) acetaminophen on hepatic and renal function of VLGA infants.

Design/Methods: In the Premature infants' Paracetamol Study (PreParaS, NCT01938261), intubated VLGA infants were randomly assigned to IV acetaminophen (loading dose 20 mg/kg, maintenance 7.5 mg/kg every 6 hours) or placebo (0.45% NaCl) within 24 hours of birth, for 4 days. Study laboratory samples were collected 48 hours after the first study drug dose, and the leftovers from routine samples were saved. The secondary outcomes of the trial included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), highest measured bilirubin levels, number of phototherapy periods, serum cystatin C (CysC), periods of polyuria and oliguria, and serum sodium levels.

Results: Of the 129 randomized VLGA infants, 62 had acetaminophen and 67 placebo, in the Neonatal Intensive Care Unit of Oulu University Hospital, Oulu, Finland. Baseline data were similar between the two groups (Table 1). After randomization, one infant was excluded due to a chromosomal anomaly and one died early, both from the placebo group. No significant differences in any of the laboratory tests or clinical biomarkers were observed between the two groups (Figure; Table 2). One infant in the placebo group had notably high AST and GGT levels. No infant showed clinical hepatic dysfunction or symptoms of acute kidney injury during neonatal intensive care.

Conclusion(s): In a randomized, controlled trial, the acetaminophen dosing used, compared to placebo, did not cause clinical symptoms, and liver enzymes and renal biomarkers remained low, suggesting safe use in VLGA infants. Larger studies are needed to detect rare adverse events, and follow-up is required to assess long-term effects.

Table 1.
Baseline clinical characteristics.

Table 2.
Hepatic and renal outcomes.

Figure.
Serum ALT, AST, GGT and CysC, see numbers in the table.