Serum Creatinine Patterns in Neonates Treated with Therapeutic Hypothermia for Neonatal Encephalopathy

Elif Keles, Pia Wintermark, Floris Groenendaal, Noor Borloo, Anne Smits, Annouschka Laenen, Djalila Mekahli, Pieter Annaert, Suzan Şahin, Mehmet Yekta Öncel, Valerie Chock, Didem Armangil, Esin Koc, Malcolm R Battin, Adam Frymoyer, Karel Allegaert

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Introduction: There is large variability in kidney function and injury in neonates with neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH). Acute kidney injury (AKI) definitions that apply categorical approaches may lose valuable information about kidney function in individual patients. Centile serum creatinine (SCr) over postnatal age (PNA) may provide more valuable information in TH neonates. Methods: Data from seven TH neonates and one non-TH-treated, non-NE control cohorts were pooled in a retrospective study. SCr centiles over PNA, and AKI incidence (definition: SCr ↑≥0.3 mg/dL within 48 h, or ↑ ≥1.5 fold vs. the lowest prior SCr within 7 days) and mortality were calculated. Repeated measurement linear models were applied to SCr trends, modeling SCr on PNA, birth weight or gestational age (GA), using heterogeneous autoregressive residual covariance structure and maximum likelihood methods. Findings were compared to patterns in the control cohort. Results: Among 1,136 TH neonates, representing 4,724 SCr observations, SCr (10th-25th-50th-75th-90th-95th) PNA centiles (day 1-10) were generated. In TH neonates, the AKI incidence was 132/1,136 (11.6%), mortality 193/1,136 (17%). AKI neonates had a higher mortality (37.2-14.3%, p < 0.001). Median SCr patterns over PNA were significantly higher in nonsurvivors (p < 0.01) or AKI neonates (p < 0.001). In TH-treated neonates, PNA and GA or birth weight explained SCr variability. Patterns over PNA were significantly higher in TH neonates to controls (801 neonates, 2,779 SCr). Conclusions: SCr patterns in TH-treated NE neonates are specific. Knowing PNA-related patterns enable clinicians to better assess kidney function and tailor pharmacotherapy, fluids, or kidney supportive therapies.

Original languageEnglish
Pages (from-to)686-694
Number of pages9
Issue number6
Early online date7 Jul 2022
Publication statusPublished - Dec 2022


  • Acute kidney injury
  • Birth Weight
  • Brain Diseases
  • Creatinine
  • Humans
  • Hypothermia, Induced/adverse effects
  • Infant, Newborn
  • Newborn
  • Perinatal asphyxia
  • Precision medicine
  • Reference values
  • Retrospective Studies
  • Therapeutic hypothermia


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