Drug effects on endogenous brain activity in preterm babies

Brain Dev. 2014 Feb;36(2):116-23. doi: 10.1016/j.braindev.2013.01.009. Epub 2013 Feb 17.


Background: Animal experiments have suggested that the quality of the early intermittent brain activity is important for shaping neuronal connectivity during developmental phase that corresponds to early prematurity. This is a pilot study aiming to assess whether spontaneous activity transients (SAT) in the early preterm babies are affected by drugs that are routinely used in neonatal intensive care.

Methods: We collected retrospectively seventeen EEG recordings (15 babies, conceptional age 26-33weeks, no brain lesions) that were divided into groups according to drug administration at the time of EEG: phenobarbital, fentanyl, theophylline, and controls. SATs were extracted from the EEG for further analysis with several advanced time-series analysis paradigms.

Results: The visual appearance of SATs was unaffected by drugs. Phenobarbital reduced the total power of the SAT events. Both fentanyl and phenobarbital reduced the length of SATs, and enhanced the oscillations at higher frequencies. Theophylline reduced the oscillatory activity at middle frequencies during SAT, but enhanced oscillations at higher frequencies during time-period prior to SAT.

Conclusions: Our findings suggest, that (i) all drugs examined affect brain activity in ways that are not seen in the visual EEG interpretation, and that (ii) both acute and long term (i.e. developmental) effects of these drugs on brain may warrant more attention as a part of optimizing preterm neurological care.

Keywords: CO(2); Drug therapy; EEG; ELBW; F; F-C; GABA; NICU; Neonatal EEG; PH; Preterm EEG; RMS; SAT; TF; TP; aEEG; amplitude integrated electroencephalography; carbon dioxide; electroencephalography; extremely low birth weight; fentanyl; fronto-central derivation; iSAT; inter-SAT; neonatal intensive care unit; phenobarbital; root mean square; spontaneous activity transient; theophylline; time–frequency analysis; γ-aminobutyric acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Anesthesia / pharmacology
  • Brain / drug effects*
  • Brain / growth & development
  • Electroencephalography*
  • Fentanyl / pharmacology
  • GABA Modulators / pharmacology*
  • Humans
  • Infant, Newborn
  • Infant, Premature / growth & development
  • Phenobarbital / pharmacology*
  • Retrospective Studies
  • Theophylline / pharmacology


  • Adjuvants, Anesthesia
  • GABA Modulators
  • Theophylline
  • Fentanyl
  • Phenobarbital