Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2016 May 5;2016(5):CD001240.
doi: 10.1002/14651858.CD001240.pub3.

Prophylactic barbiturate use for the prevention of morbidity and mortality following perinatal asphyxia

Leslie Young  1 , Marie Berg, Roger Soll
Affiliations
Meta-Analysis

Prophylactic barbiturate use for the prevention of morbidity and mortality following perinatal asphyxia

Leslie Young et al. Cochrane Database Syst Rev. .

Abstract

Background: Seizures are common following perinatal asphyxia and may exacerbate secondary neuronal injury. Barbiturate therapy has been used for infants with perinatal asphyxia in order to prevent seizures. However, barbiturate therapy may adversely affect neurodevelopment leading to concern regarding aggressive use in neonates.

Objectives: To determine the effect of administering prophylactic barbiturate therapy on death or neurodevelopmental disability in term and late preterm infants following perinatal asphyxia.

Search methods: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 11), MEDLINE via PubMed (1966 to 30 November 2015), EMBASE (1980 to 30 November 2015), and CINAHL (1982 to 30 November 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials (RCT) and quasi-RCTs.

Selection criteria: We included all RCTs or quasi-RCTs of prophylactic barbiturate therapy in term and late preterm infants without clinical or electroencephalographic evidence of seizures compared to controls following perinatal asphyxia.

Data collection and analysis: Three review authors independently selected, assessed the quality of, and extracted data from the included studies. We assessed methodologic quality and validity of studies without consideration of the results. The review authors independently extracted data and performed meta-analyses using risk ratios (RR) and risk differences (RD) for dichotomous data and mean difference for continuous data with 95% confidence intervals (CI). For significant results, we calculated the number needed to treat for an additional beneficial outcome (NNTB) or for an additional harmful outcome (NNTH).

Main results: In this updated review, we identified nine RCTs of any barbiturate therapy in term and late preterm infants aged less than three days old with perinatal asphyxia without evidence of seizures. Eight of these studies compared prophylactic barbiturate therapy to conventional treatment (enrolling 439 infants) and one study compared barbiturate therapy to treatment with phenytoin (enrolling 17 infants). Prophylactic barbiturate therapy versus conventional treatment: one small trial reported a decreased risk of death or severe neurodevelopmental disability for barbiturate therapy (phenobarbital) versus conventional treatment (RR 0.33, 95% CI 0.14 to 0.78; RD -0.55, 95% CI -0.84 to -0.25; NNTB 2, 95% CI 1 to 4; 1 study, 31 infants) (very low quality evidence).Eight trials comparing prophylactic barbiturate therapy with conventional treatment following perinatal asphyxia demonstrated no significant impact on the risk of death (typical RR 0.88, 95% CI 0.55 to 1.42; typical RD -0.02, 95% CI -0.08 to 0.05; 8 trials, 429 infants) (low quality evidence) and the one small trial noted above reported a significant decrease in the risk of severe neurodevelopmental disability (RR 0.24, 95% CI 0.06 to 0.92; RD -0.43, 95% CI -0.73 to -0.13; NNTB 2, 95% CI 1 to 8; 1 study, 31 infants) (very low quality evidence).A meta-analysis of the six trials reporting on seizures in the neonatal period demonstrated a statistically significant reduction in seizures in the prophylactic barbiturate group versus conventional treatment (typical RR 0.62, 95% CI 0.48 to 0.81; typical RD -0.18, 95% CI -0.27 to -0.09; NNTB 5, 95% CI 4 to 11; 6 studies, 319 infants) (low quality evidence). There were similar results in subgroup analyses based on type of barbiturate and Sarnat score. Prophylactic barbiturate therapy versus other prophylactic anticonvulsant therapy: one study reported on prophylactic barbiturate versus prophylactic phenytoin. There was no significant difference in seizure activity in the neonatal period between the two study groups (RR 0.89, 95% CI 0.07 to 12.00; 1 trial, 17 infants).

Authors' conclusions: We found only low or very low quality evidence addressing the use of prophylactic barbiturates in infants with perinatal asphyxia. Although the administration of prophylactic barbiturate therapy to infants following perinatal asphyxia did reduce the risk of seizures, there was no reduction seen in mortality and there were few data addressing long-term outcomes. The administration of prophylactic barbiturate therapy for late preterm and term infants in the immediate period following perinatal asphyxia cannot be recommended for routine clinical practice. If used at all, barbiturates should be reserved for the treatment of seizures. The results of the current review support the use of prophylactic barbiturate therapy as a promising area of research. Future studies should be of sufficient size and duration to detect clinically important reductions in mortality and severe neurodevelopmental disability and should be conducted in the context of the current standard of care, including the use of therapeutic hypothermia.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

1
1
Study flow diagram: review update.
2
2
Forest plot of comparison: 1 Barbiturates versus control, outcome: 1.7 Seizures within neonatal period.
1.1
1.1. Analysis
Comparison 1 Barbiturates versus control, Outcome 1 Death or major neurodevelopmental disability.
1.2
1.2. Analysis
Comparison 1 Barbiturates versus control, Outcome 2 Death.
1.3
1.3. Analysis
Comparison 1 Barbiturates versus control, Outcome 3 Major neurodevelopmental disability in survivors examined.
1.4
1.4. Analysis
Comparison 1 Barbiturates versus control, Outcome 4 Cerebral palsy.
1.5
1.5. Analysis
Comparison 1 Barbiturates versus control, Outcome 5 Developmental delay in survivors examined.
1.6
1.6. Analysis
Comparison 1 Barbiturates versus control, Outcome 6 IQ in survivors.
1.7
1.7. Analysis
Comparison 1 Barbiturates versus control, Outcome 7 Seizures within neonatal period.
1.8
1.8. Analysis
Comparison 1 Barbiturates versus control, Outcome 8 Respiratory depression.
1.9
1.9. Analysis
Comparison 1 Barbiturates versus control, Outcome 9 Hypotension requiring inotropic support.
1.10
1.10. Analysis
Comparison 1 Barbiturates versus control, Outcome 10 Abnormal neurologic exam at discharge.
2.1
2.1. Analysis
Comparison 2 Phenobarbital versus phenytoin, Outcome 1 Seizures within the first 7 days of age.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Avasiloaiei 2013 {published and unpublished data}
    1. Avasiloaiei A, Dimitriu C, Moscalu M, Paduraru L, Stamatin M. High‐dose phenobarbital or erythropoietin for the treatment of perinatal asphyxia in term newborns. Pediatrics International 2013;55(5):589‐93. [PUBMED: 23659666] - PubMed
Gathwala 2011 {published data only}
    1. Gathwala G, Marwah A, Gahlaut V, Marwah P. Effect of high‐dose phenobarbital on oxidative stress in perinatal asphyxia: an open label randomized controlled trial. Indian Pediatrics 2011;48(8):613‐7. [PUBMED: 21169640] - PubMed
Goldberg 1986 {published data only}
    1. Goldberg RN, Moscoso P, Bauer CR, Bloom FL, Curless RG, Burke B, et al. Use of barbiturate therapy in severe perinatal asphyxia: a randomized controlled trial. Journal of Pediatrics 1986;109(5):851‐6. [PUBMED: 3534201] - PubMed
Hall 1998 {published data only}
    1. Hall RT, Hall FK, Daily DK. High‐dose phenobarbital therapy in term newborn infants with severe perinatal asphyxia: a randomized, prospective study with three‐year follow‐up. Journal of Pediatrics 1998;132(2):345‐8. [PUBMED: 9506654] - PubMed
Ruth 1991 {published data only}
    1. Ruth V, Korkman M, Liikanen A, Paetau R. High‐dose phenobarbitol treatment to prevent postasphyxial brain damage: a 6‐year follow up [abstract]. Pediatric Research 1991;30:638. [DOI: 10.1203/00006450-199112000-00091] - DOI
Singh 2004 {published data only}
    1. Singh D, Kumar P, Majumdar S, Narang A. Effect of phenobarbital on free radicals in neonates with hypoxic ischemic encephalopathy ‐ a randomized controlled trial. Journal of Perinatal Medicine 2004;32(3):278‐81. [PUBMED: 15188805] - PubMed
    1. Singh D, Kumar P, Narang A. A randomized controlled trial of phenobarbital in neonates with hypoxic ischemic encephalopathy. Journal of Maternal‐Fetal and Neonatal Medicine 2005;18(6):391‐5. [PUBMED: 16390805] - PubMed
Vargas‐Origel 2004 {published data only}
    1. Vargas‐Origel A, Espinosa‐Garcia JOG, Muniz‐Quezada E, Vargas‐Nieto MA, Aguilar‐Garcia G. Prevention of hypoxic‐ischemic encephalopathy with high‐dose, early phenobarbital therapy [Prevencion de la encefalopatia hipoxico‐isquemica mediante Fenobarbital en forma temprana y a dosis alta]. Gaceta Medica de Mexico 2004;140(2):147‐53. [MEDLINE: ] - PubMed
Vela 1987 {published data only}
    1. Vela F, Duran JA, Chunga F, Serrano JS, Valls A. Preventive treatment of convulsions in perinatal asphyxia [Tratamiento profilactico de convulsiones en asfixia perinatal]. Anales Espanoles de Pediatria 1987;27(2):95‐9. [PUBMED: 3662273] - PubMed
Velaphi 2013 {published data only}
    1. Velaphi S, Mokhachane M, Mphahlele R, Beckh‐Arnold E. Effect of prophylactic phenobarbital on seizures, encephalopathy and mortality in neonates with perinatal asphyxia. South African Journal of Child Health 2013;7(1):17‐21.

References to studies excluded from this review

Kuzemko 1972 {published data only}
    1. Kuzemko JA, Hartley S. Treatment of cerebral irritation in the newborn: double‐blind trial with chloral hydrate and diazepam. Developmental Medicine and Child Neurology 1972;14(6):740‐6. [PUBMED: 4566107] - PubMed
Ruth 1988 {published data only}
    1. Ruth V, Virkola K, Paetau R, Raivio KO. Early high‐dose phenobarbital treatment for prevention of hypoxic‐ischemic brain damage in very low birth weight infants. Journal of Pediatrics 1988;112(1):81‐6. [PUBMED: 2447257] - PubMed
Srinivasakumar 2015 {published data only}
    1. Srinivasakumar P, Zempel J, Trivedi S, Wallendorf M, Rao R, Smith B, et al. Treating EEG seizures in hypoxic ischemic encephalopathy: a randomized controlled trial. Pediatrics 2015;136(5):e1302‐9. [PUBMED: 26482675] - PubMed
van Rooij 2010 {published data only}
    1. Rooij LG, Toet MC, Huffelen AC, Groenendaal F, Laan W, Zecic A, et al. Effect of treatment of subclinical neonatal seizures detected with aEEG: randomized, controlled trial. Pediatrics 2010;125(2):e358‐66. [PUBMED: 20100767] - PubMed
Wilkinson 1989 {published data only}
    1. Rochefort MJ, Wilkinson AR. The safety and efficacy of alternative anticonvulsant regimes to control newborns seizures [abstract]. Early Human Development 1989;19:218.
    1. Wilkinson AR, Rochefort MJ. Phenytoin reduces frequency and duration of neonatal seizures in the newborn: a randomised trial of four anticonvulsants [abstract]. Pediatric Research 1989;26:522.

References to ongoing studies

IRCT2014090919101N1 {published data only}
    1. Gholamreza P. The effect of phenobarbital on the outcome of early ischemic encephalopathy. www.irct.ir/searchresult.php?id=19101&number=1 (accessed 27 March 2016).

Additional references

Bittigau 2002
    1. Bittigau P, Sifringer M, Genz K, Reith E, Pospischil D, Govindarajalu S, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proceedings of the National Academy of Sciences of the United States of America 2002;99(23):15089‐94. [PUBMED: 12417760] - PMC - PubMed
Buttke 1994
    1. Buttke TM, Sandstrom PA. Oxidative stress as a mediator of apoptosis. Immunology Today 1994;15(1):7‐10. [PUBMED: 8136014] - PubMed
Cherubini 1991
    1. Cherubini E, Gaiarsa JL, Ben‐Ari Y. GABA: an excitatory transmitter in early postnatal life. Trends in Neurosciences 1991;14(12):515‐9. [PUBMED: 1726341] - PubMed
Clozel 1985
    1. Clozel M, Daval JL, Monin P, Debruc C, Morselli PL, Vert P. Regional cerebral blood flow during bicuculline‐induced seizures in the newborn piglet: effect of phenobarbital. Developmental Pharmacology and Therapeutics 1985;8(3):189‐99. [PUBMED: 4006653] - PubMed
Demopoulos 1977
    1. Demopoulos HG, Flamm ES, Seligman MC, Jorgensen E, Ransohoff J. Antioxidant effects of barbiturates in model membranes undergoing free radical damage. Acta Neurologica Scandinavica 1977;64:152‐3. [PUBMED: 268766] - PubMed
Glass 2009
    1. Glass HC, Glidden D, Jeremy RJ, Barkovich AJ, Ferriero DM, Miller SP. Clinical neonatal seizures are independently associated with outcome in infants at risk for hypoxic‐ischemic brain injury. Journal of Pediatrics 2009;155(3):318‐23. [PUBMED: 19540512] - PMC - PubMed
Gluckman 1992
    1. Gluckman PD, Williams CE. When and why do brain cells die?. Developmental Medicine and Child Neurology 1992;34(11):1010‐4. [PUBMED: 1358734] - PubMed
Gluckman 2005
    1. Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005;365(9460):663‐70. [PUBMED: 15721471] - PubMed
GRADEpro 2008 [Computer program]
    1. Brozek J, Oxman A, Schünemann H. GRADEpro [Version 3.2 for Windows]. McMaster University, 2008.
Gunn 1998
    1. Gunn AJ, Gunn TR, Gunning MI, Williams CE, Gluckman PD. Neuroprotection with prolonged head cooling started before postischemic seizures in fetal sheep. Pediatrics 1998;102(5):1098‐106. [PUBMED: 9794940] - PubMed
Gunn 2008
    1. Gunn AJ, Wyatt JS, Whitelaw A, Barks J, Azzopardi D, Ballard R, et al. Therapeutic hypothermia changes the prognostic value of clinical evaluation of neonatal encephalopathy. Journal of Pediatrics 2008;152(1):55‐8. [PUBMED: 18154900] - PubMed
Guyatt 2011a
    1. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction‐GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2011;64(4):383‐94. [PUBMED: 21195583] - PubMed
Guyatt 2011b
    1. Guyatt GH, Oxman AD, Vist G, Kunz R, Brozek J, Alonso‐Coello P, et al. GRADE guidelines: 4. Rating the quality of evidence ‐ study limitations (risk of bias). Journal of Clinical Epidemiology 2011;64(4):407‐15. [PUBMED: 21247734] - PubMed
Guyatt 2011c
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 7. Rating the quality of evidence ‐ inconsistency. Journal of Clinical Epidemiology 2011;64(12):1294‐302. [PUBMED: 21803546] - PubMed
Guyatt 2011d
    1. Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso‐Coello P, Rind D, et al. GRADE guidelines 6. Rating the quality of evidence ‐ imprecision. Journal of Clinical Epidemiology 2011;64(12):1283‐93. [PUBMED: 21839614] - PubMed
Guyatt 2011e
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 8. Rating the quality of evidence ‐ indirectness. Journal of Clinical Epidemiology 2011;64(12):1303‐10. [PUBMED: 21802903] - PubMed
Higgins 2011
    1. Higgins JPT, Greene S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Holmes 1998
    1. Holmes GL, Ben‐Ari Y. Seizures in the developing brain: perhaps not so benign after all. Neuron 1998;21(6):1231‐4. [PUBMED: 9883716] - PubMed
Hossman 1983
    1. Hossman KA. Neuronal survival and revival during and after cerebral ischaemia. American Journal of Emergency Medicine 1983;1(2):191‐7. [PUBMED: 6680620] - PubMed
Jacobs 2013
    1. Jacobs SE, Berg M, Hunt R, Tarnow‐Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database of Systematic Reviews 2013, Issue 1. [DOI: 10.1002/14651858.CD003311.pub3; PUBMED: 23440789] - DOI - PMC - PubMed
Kwon 2011
    1. Kwon JM, Guillet R, Shankaran S, Laptook AR, McDonald SA, Ehrenkranz RA, et al. Clinical seizures in neonatal hypoxic‐ischemic encephalopathy have no independent impact on neurodevelopmental outcome: secondary analyses of data from the neonatal research network hypothermia trial. Journal of Child Neurology 2011;26(3):322‐8. - PMC - PubMed
Lorek 1994
    1. Lorek A, Takei Y, Cady EB, Wyatt JS, Penrice J, Edwards AD, et al. Delayed (+ACI‐secondary+ACI‐) cerebral energy failure after acute hypoxia‐ischemia in the newborn piglet: continuous 48‐hour studies by phosphorus magnetic resonance spectroscopy. Pediatric Research 1994;36(6):699‐706. [PUBMED: 7898977] - PubMed
McBride 2000
    1. McBride MC, Laroia N, Guillet R. Electrographic seizures in neonates correlate with poor neurodevelopmental outcome. Neurology 2000;55(4):506‐13. [PUBMED: 10953181] - PubMed
McCord 1985
    1. McCord JM. Oxygen‐derived free radicals in postischemic tissue injury. New England Journal of Medicine 1985;312(3):159‐63. [PUBMED: 2981404] - PubMed
McDonald 1990
    1. McDonald JW, Johnston MV. Physiological and pathophysiological roles of excitatory amino acids during central nervous system development. Brain Research. Brain Research Reviews 1990;15(1):41‐70. [PUBMED: 2163714] - PubMed
Nilsson 1971
    1. Nilsson L. The influence of barbiturate anaesthesia upon the energy state and upon acid‐base parameters of the brain in arterial hypotension and in asphyxia. Acta Neurologica Scandinavica 1971;47(2):233‐53. [PUBMED: 5566570] - PubMed
Penrice 1996
    1. Penrice J, Cady EB, Lorek A, Wylezinska M, Amess PN, Aldridge RF, et al. Proton magnetic resonance spectroscopy of the brain in normal preterm and term infants, and early changes after perinatal hypoxia‐ischemia. Pediatric Research 1996;40(1):6‐14. [PUBMED: 8798238] - PubMed
Perlman 1996
    1. Perlman JM, Risser R. Can asphyxiated infants at risk for neonatal seizures be rapidly identified by current high‐risk markers?. Pediatrics 1996;97(4):456‐62. [PUBMED: 8632928] - PubMed
Perlman 2006
    1. Perlman JM. Summary proceedings from the neurology group on hypoxic‐ischemic encephalopathy. Pediatrics 2006; Vol. 117, issue 3 Pt 2:S28‐33. [PUBMED: 16777819] - PubMed
Pfister 2012
    1. Pfister RH, Bingham P, Edwards EM, Horbar JD, Kenny MJ, Inder T, et al. The Vermont Oxford Neonatal Encephalopathy Registry: rational, methods, and initial results. BMC Pediatrics 2012;12:84. [PUBMED: 22726296] - PMC - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Rivera 1999
    1. Rivera C, Voipio J, Payne JA, Ruusuvuori E. The K+/Cl‐ co‐transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 1999;397(6716):251‐5. [PUBMED: 9930699] - PubMed
Roth 1992
    1. Roth SC, Edwards AD, Cady EB, Delpy DT, Wyatt JS, Azzopardi D, et al. Relation between cerebral oxidative metabolism following birth asphyxia, and neurodevelopmental outcome and brain growth at one year. Developmental Medicine and Child Neurology 1992;34(4):285‐95. [PUBMED: 1572514] - PubMed
Roth 1997
    1. Roth SC, Baudin J, Cady E, Johal K, Townsend JP, Wyatt JS, et al. Relation of deranged neonatal cerebral oxidative metabolism with neurodevelopmental outcome and head circumference at 4 years. Developmental Medicine and Child Neurology 1997;39(11):718‐25. [PUBMED: 9393884] - PubMed
Sant'Anna 2012
    1. Sant'Anna G, Laptook AR, Shankaran S, Bara R, McDonald SA, Higgins RD, et al. Phenobarbital and temperature profile during hypothermia for hypoxic‐ischemic encephalopathy. Journal of Child Neurology 2012;27(4):451‐7. [PUBMED: 21960671] - PMC - PubMed
Sarnat 1976
    1. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. Archives of Neurology 1976;33:696‐705. - PubMed
Schünemann 2013
    1. Schünemann H, Brożek J, Guyatt G, Oxman A (editors). GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. Available from http://gdt.guidelinedevelopment.org/central_prod/_design/client/handbook....
Shankaran 2005
    1. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. Whole‐body hypothermia for neonates with hypoxic‐ischemic encephalopathy. New England Journal of Medicine 2005;353(15):1574‐84. [PUBMED: 16221780] - PubMed
Shankaran 2012
    1. Shankaran S, Laptook AR, Tyson JE, Ehrenkranz RA, Bann CM, Das A, et al. Evolution of encephalopathy during whole body hypothermia for neonatal hypoxic‐ischemic encephalopathy. Journal of Pediatrics 2012;160(4):567‐72. [PUBMED: 22050871] - PMC - PubMed
Shellhaas 2007
    1. Shellhaas RA, Soaita AI, Clancy RR. Sensitivity of amplitude‐integrated electroencephalography for neonatal seizure detection. Pediatrics 2007;120(4):770‐7. [PUBMED: 17908764] - PubMed
Siesjo 1992
    1. Siesjo BK. Pathophysiology and treatment of focal cerebral ischaemia. Part II: Mechanisms of damage and treatment. Journal of Neurosurgery 1992;77(3):337‐54. [PUBMED: 1506880] - PubMed
Williams 1991
    1. Williams CE, Gunn A, Gluckman PD. Time course of intracellular edema and epileptiform activity following prenatal cerebral ischemia in sheep. Stroke 1991;22(4):516‐21. [PUBMED: 2024281] - PubMed
Wirrell 2001
    1. Wirrell EC, Armstrong EA, Osman LD, Yager JY. Prolonged seizures exacerbate perinatal hypoxic‐ischemic brain damage. Pediatric Research 2001;50(4):445‐54. [PUBMED: 11568286] - PubMed
Wusthoff 2009
    1. Wusthoff CJ, Shellhaas RA, Clancy RR. Limitations of single‐channel EEG on the forehead for neonatal seizure detection. Journal of Perinatology 2009;29(3):237‐42. [PUBMED: 19052554] - PubMed
Wyatt 2007
    1. Wyatt JS, Gluckman PD, Liu PY, Azzopardi D, Ballard RA, Edwards AD, et al. Determinants of outcomes after head cooling for neonatal encephalopathy. Pediatrics 2007;119(5):912‐21. [PUBMED: 17473091] - PubMed
Yager 2002
    1. Yager JY, Armstrong EA, Miyashita H, Wirrell EC. Prolonged neonatal seizures exacerbate hypoxic‐ischemic brain damage: correlation with cerebral energy metabolism and excitatory amino acid release. Developmental Neuroscience 2002;24(5):367‐81. [PUBMED: 12640175] - PubMed
Yamada 2004
    1. Yamada J, Okabe A, Toyoda H, Kilb W, Luhmann HJ, Fukuda A. Cl‐ uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1. Journal of Physiology 2004;557(Pt 3):829‐41. [PUBMED: 15090604] - PMC - PubMed
Younkin 1986
    1. Younkin DP, Delivoria‐Papadopoulos M, Maris J, Donlon E, Clancy R, Chance B. Cerebral metabolic effects of neonatal seizures measured with in vivo 31P NMR spectroscopy. Annals of Neurology 1986;20(4):513‐9. [PUBMED: 3789667] - PubMed

References to other published versions of this review

Evans 1998
    1. Evans DJ, Levene MI. Anticonvulsants for preventing mortality and morbidity in full term newborns with perinatal asphyxia. Cochrane Database of Systematic Reviews 1998, Issue 3. [DOI: 10.1002/14651858.CD001240; PUBMED: 10796257] - DOI - PubMed
Evans 2001
    1. Evans DJ, Levene MI. Anticonvulsants for preventing mortality and morbidity in full term newborns with perinatal asphyxia. Cochrane Database of Systematic Reviews 2001, Issue 2. [DOI: 10.1002/14651858.CD001240.pub2; PUBMED: 11686984] - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources