Advertisement

Drug effects on endogenous brain activity in preterm babies

  • Kaija Malk
    Affiliations
    Department of Children’s Clinical Neurophysiology, Helsinki University Central Hospital, Helsinki, Finland
    Search for articles by this author
  • Marjo Metsäranta
    Affiliations
    Chidren’s hospital, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
    Search for articles by this author
  • Sampsa Vanhatalo
    Correspondence
    Corresponding author. Address: Department of Clinical Neurophysiology, Helsinki University Central Hospital (HUCH), P.O. Box 280, FIN-00029 HUS, Finland. Tel.: +358 50 5286119; fax: +358 10 2960116.
    Affiliations
    Department of Children’s Clinical Neurophysiology, Helsinki University Central Hospital, Helsinki, Finland

    Department of Neurological Sciences, University of Helsinki, Finland
    Search for articles by this author
Published:February 19, 2013DOI:https://doi.org/10.1016/j.braindev.2013.01.009

      Abstract

      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 26–33 weeks, 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.

      Abbreviations:

      EEG (electroencephalography), aEEG (amplitude integrated electroencephalography), ELBW (extremely low birth weight), SAT (spontaneous activity transient), iSAT (inter-SAT), F-C (fronto-central derivation), NICU (neonatal intensive care unit), TF (time–frequency analysis), RMS (root mean square), F (fentanyl), PH (phenobarbital), TP (theophylline), GABA (γ-aminobutyric acid), CO2 (carbon dioxide)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Allen M.C.
        Neurodevelopmental outcomes of preterm infants.
        Curr Opin Neurol. 2008; 21: 123-128
        • Tommiska V.
        • Heinonen K.
        • Lehtonen L.
        • Renlund M.
        • Saarela T.
        • Tammela O.
        • et al.
        No improvement in outcome of nationwide extremely low birth weight infant populations between 1996–1997 and 1999–2000.
        Pediatrics. 2007; 119: 29-36
        • Inder T.E.
        • Warfield S.K.
        • Wang H.
        • Huppi P.S.
        • Volpe J.J.
        Abnormal cerebral structure is present at term in premature infants.
        Pediatrics. 2005; 115: 286-294
        • Bittigau P.
        • Sifringer M.
        • Genz K.
        • Reith E.
        • Pospischil D.
        • Govindarajalu S.
        • et al.
        Antiepileptic drugs and apoptotic neurodegeneration in the developing brain.
        Proc Natl Acad Sci USA. 2002; 99: 15089-15094
        • Gressens P.
        • Rogido M.
        • Paindaveine B.
        • Sola A.
        The impact of neonatal intensive care practices on the developing brain.
        J Pediatr. 2002; 140: 646-653
        • Bhutta A.T.
        • Anand K.J.
        Abnormal cognition and behavior in preterm neonates linked to smaller brain volumes.
        Trends Neurosci. 2001; 24: 129-130
        • Smith G.C.
        • Gutovich J.
        • Smyser C.
        • Pineda R.
        • Newnham C.
        • Tjoeng T.H.
        • et al.
        Neonatal intensive care unit stress is associated with brain development in preterm infants.
        Ann Neurol. 2011; 70: 541-549
        • Peterson B.S.
        • Vohr B.
        • Staib L.H.
        • Cannistraci C.J.
        • Dolberg A.
        • Schneider K.C.
        • et al.
        Regional brain volume abnormalities and long-term cognitive outcome in preterm infants.
        JAMA. 2000; 284: 1939-1947
        • Ball G.
        • Boardman J.P.
        • Rueckert D.
        • Aljabar P.
        • Arichi T.
        • Merchant N.
        • et al.
        The effect of preterm birth on thalamic and cortical development.
        Cereb Cortex. 2012; 22: 1016-1024
        • Parikh N.A.
        • Lasky R.E.
        • Kennedy K.A.
        • Moya F.R.
        • Hochhauser L.
        • Romo S.
        • et al.
        Postnatal dexamethasone therapy and cerebral tissue volumes in extremely low birth weight infants.
        Pediatrics. 2007; 119: 265-272
        • Volpe J.J.
        Cerebral white matter injury of the premature infant-more common than you think.
        Pediatrics. 2003; 112: 176-180
        • Counsell S.J.
        • Edwards A.D.
        • Chew A.T.
        • Anjari M.
        • Dyet L.E.
        • Srinivasan L.
        • et al.
        Specific relations between neurodevelopmental abilities and white matter microstructure in children born preterm.
        Brain. 2008; 131: 3201-3208
        • Narberhaus A.
        • Segarra D.
        • Caldu X.
        • Gimenez M.
        • Junque C.
        • Pueyo R.
        • et al.
        Gestational age at preterm birth in relation to corpus callosum and general cognitive outcome in adolescents.
        J Child Neurol. 2007; 22: 761-765
        • Khazipov R.
        • Luhmann H.J.
        Early patterns of electrical activity in the developing cerebral cortex of humans and rodents.
        Trends Neurosci. 2006; 29: 414-418
        • Katz L.C.
        • Crowley J.C.
        Development of cortical circuits: lessons from ocular dominance columns.
        Nat Rev Neurosci. 2002; 3: 34-42
        • Minlebaev M.
        • Colonnese M.
        • Tsintsadze T.
        • Sirota A.
        • Khazipov R.
        Early γ oscillations synchronize developing thalamus and cortex.
        Science. 2011; 334: 226-229
        • Katz L.C.
        • Shatz C.J.
        Synaptic activity and the construction of cortical circuits.
        Science. 1996; 274: 1133-1138
        • Kilb W.
        • Kirischuk S.
        • Luhmann H.J.
        Electrical activity patterns and the functional maturation of the neocortex.
        Eur J Neurosci. 2011; 34: 1677-1686
        • Vanhatalo S.
        • Palva J.M.
        • Andersson S.
        • Rivera C.
        • Voipio J.
        • Kaila K.
        Slow endogenous activity transients and developmental expression of K+-Cl− cotransporter 2 in the immature human cortex.
        Eur J Neurosci. 2005; 22: 2799-2804
        • Vanhatalo S.
        Kaila K development of neonatal EEG activity: from phenomenology to physiology.
        Semin Fetal Neonatal Med. 2006; 11: 471-478
        • Vanhatalo S.
        • Kaila K.
        Spontaneous and evoked activity in the early human brain.
        in: Lagercrantz H. Ment H.P. Evrard P. The Newborn Brain: Neuroscience and Clinical Applications. 2nd ed. Cambridge University Press, Cambridge, UK2010: 229-243 ([chapter 15])
        • Vanhatalo S.
        • Tallgren P.
        • Andersson S.
        • Sainio K.
        • Voipio J.
        • Kaila K.
        DC-EEG discloses prominent, very slow activity patterns during sleep in preterm infants.
        Clin Neurophysiol. 2002; 113: 1822-1825
        • Bell A.H.
        • Greisen G.
        • Pryds O.
        Comparison of the effects of phenobarbitone and morphine administration on EEG activity in preterm babies.
        Acta Paediatr. 1993; 82: 35-39
        • Eaton D.G.
        • Wertheim D.
        • Oozeer R.
        • Royston P.
        • Dubowitz L.
        • Dubowitz V.
        The effect of pethidine on the neonatal EEG.
        Dev Med Child Neurol. 1992; 34: 155-163
        • Nguyen T.T.S.
        • Vecchierini M.F.
        • Debillon T.
        • Pereon Y.
        Effects of sufentanil on electroencephalogram in very and extremely preterm neonates.
        Pediatrics. 2003; 111: 123-128
        • Young G.B.
        • da Silva O.P.
        Effects of morphine on the electroencephalograms of neonates: a prospective, observational study.
        Clin Neurophysiol. 2000; 111: 1955-1960
        • Sipila S.T.
        • Kaila K.
        GABAergic control of CA3-driven network events in the developing hippocampus.
        Results Probl Cell Differ. 2008; 44: 99-121
        • Hooks B.M.
        • Chen C.
        Distinct roles for spontaneous and visual activity in remodeling of the retinogeniculate synapse.
        Neuron. 2006; 52: 281-291
        • Wikstrom S.
        • Ley D.
        • Hansen-Pupp I.
        • Rosen I.
        • Hellstrom-Westas L.
        Early amplitude-integrated EEG correlates with cord TNF-alpha and brain injury in very preterm infants.
        Acta Paediatr. 2008; 97: 915-919
        • Kidokoro H.
        • Okumura A.
        • Hayakawa F.
        • Kato T.
        • Maruyama K.
        • Kubota T.
        • et al.
        Chronologic changes in neonatal EEG findings in periventricular leukomalacia.
        Pediatrics. 2009; 124: e468-e475
        • Minlebaev M.
        • Ben-Ari Y.
        • Khazipov R.
        Network mechanisms of spindle-burst oscillations in the neonatal rat barrel cortex in vivo.
        J Neurophysiol. 2007; 97: 692-700
        • Safiulina V.F.
        • Kasyanov A.M.
        • Giniatullin R.
        • Cherubini E.
        Adenosine down-regulates giant depolarizing potentials in the developing rat hippocampus by exerting a negative control on glutamatergic inputs.
        J Neurophysiol. 2005; 94: 2797-2804
        • Palmu K.
        • Wikström S.
        • Hippeläinen E.
        • Boylan G.
        • Hellström-Westas L.
        • Vanhatalo S.
        Detection of ‘EEG bursts’ in the early preterm EEG: visual vs. automated detection.
        Clin Neurophysiol. 2010; 121: 1015-1022
        • Tolonen M.
        • Palva J.M.
        • Andersson S.
        • Vanhatalo S.
        Development of the spontaneous activity transients and ongoing cortical activity in human preterm babies.
        Neuroscience. 2007; 145: 997-1006
        • Thompson B.L.
        • Levitt P.
        • Stanwood G.D.
        Prenatal exposure to drugs: effects on brain development and implications for policy and education.
        Nat Rev Neurosci. 2009; 10: 303-312
        • Stanwood G.D.
        • Levitt P.
        Drug exposure early in life: functional repercussions of changing neuropharmacology during sensitive periods of brain development.
        Curr Opin Pharmacol. 2004; 4: 65-71
        • Colonnese M.T.
        • Kaminska A.
        • Minlebaev M.
        • Milh M.
        • Bloem B.
        • Lescure S.
        • et al.
        A conserved switch in sensory processing prepares developing neocortex for vision.
        Neuron. 2010; 67: 480-498
        • Brockmann M.D.
        • Pöschel B.
        • Cichon N.
        • Hanganu-Opatz I.L.
        Coupled oscillations mediate directed interactions between prefrontal cortex and hippocampus of the neonatal rat.
        Neuron. 2011; 71: 332-347
        • Hellstrom-Westas L.
        • Rosen I.
        • Svenningsen N.W.
        Cerebral function monitoring during the first week of life in extremely small low birthweight (ESLBW) infants.
        Neuropediatrics. 1991; 22: 27-32
        • Lombroso C.T.
        Neonatal polygraphy in full-term and premature infants: a review of normal and abnormal findings.
        J Clin Neurophysiol. 1985; 2: 105-155
        • Lamblin M.D.
        • Andre M.
        • Challamel M.J.
        • Curzi-Dascalova L.
        • d’Allest A.M.
        • De Giovanni E.
        • et al.
        Electroencephalography of the premature and term newborn. Maturational aspects and glossary.
        Neurophysiol Clin. 1999; 29: 123-219
        • Dupont E.
        • Hanganu I.L.
        • Kilb W.
        • Hirsch S.
        • Luhmann H.J.
        Rapid developmental switch in the mechanisms driving early cortical columnar networks.
        Nature. 2006; 439: 79-83
        • Supcun S.
        • Kutz P.
        • Pielemeier W.
        • Roll C.
        Caffeine increases cerebral cortical activity in preterm infants.
        J Pediatr. 2010; 156: 490-491
        • Victor S.
        • Appleton R.E.
        • Beirne M.
        • Marson A.G.
        • Weindling A.M.
        Effect of carbon dioxide on background cerebral electrical activity and fractional oxygen extraction in very low birth weight infants just after birth.
        Pediatr Res. 2005; 58: 579-585