QTc intervals are prolonged in late preterm and term neonates during therapeutic hypothermia but normalize afterwards

Karel Allegaert*, Thomas Salaets, Robert M. Ward, Pieter Annaert, Anne Smits

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)
11 Downloads (Pure)


Background: There are anecdotal reports on reversible QTc prolongation during therapeutic hypothermia (TH) for moderate to severe neonatal encephalopathy after asphyxia. As the QTc interval is a relevant biomarker for pharmacovigilance during medication development, a structured search and review on published neonatal QTc values to generate reference values is warranted to facilate medication development in this specific population. Methods: A structured search and literature assessment (PubMed, Embase, and Google Scholar) with ‘Newborn/Infant, QT and hypothermia’ was conducted (October 2021). Retrieved individual values were converted to QTc (Bazett) over postnatal age (day 1–7). Results: We retrieved 94 QTc intervals (during TH (n = 50, until day 3) or subsequent normothermia (n = 44, day 4–7)) in 33 neonates from 6 publications. The median (range) of QTc intervals during TH was 508 (430–678), and 410 (317–540) ms afterwards (difference 98 ms, or +28 ms/ C decrease). Four additional cohorts (without individual QTc intervals) confirmed the pattern and magnitude of the effect of body temperature on the QTc interval. Conclusions: We highlighted a relevant non-maturational covariate ( C dependent TH) and generated reference values for the QTc interval in this specific neonatal subpopulation. This knowledge on QTc during TH should be considered and integrated in neonatal medication development.

Original languageEnglish
Article number1153
Issue number12
Publication statusPublished - 8 Dec 2021

Bibliographical note

Funding Information:
Funding: This research was funded by FWO Vlaanderen (iPREDICT, FWO Senior research project, fundamental research, GOD0520N).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


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