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. 2023 Mar 16;3(3):CD001691.
doi: 10.1002/14651858.CD001691.pub4.

Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preterm infants

Olga Romantsik  1 , Elisa Smit  2   3 , David E Odd  2   3 , Matteo Bruschettini  1   4
Affiliations

Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preterm infants

Olga Romantsik et al. Cochrane Database Syst Rev. .

Abstract

Background: Intraventricular haemorrhage (IVH) is a major complication of preterm birth. Large haemorrhages are associated with a high risk of disability and hydrocephalus. Instability of blood pressure and cerebral blood in the newborn flow are postulated as causative factors. Another mechanism may involve reperfusion damage from oxygen free radicals. It has been suggested that phenobarbital stabilises blood pressure and may protect against free radicals. This is an update of a review first published in 2001 and updated in 2007 and 2013.

Objectives: To assess the benefits and harms of the postnatal administration of phenobarbital in preterm infants at risk of developing IVH compared to control (i.e. no intervention or placebo).

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL and clinical trial registries in January 2022. A new, more sensitive search strategy was developed, and searches were conducted without date limits. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs in which phenobarbital was given within the first 24 hours of life to preterm infants identified as being at risk of IVH because of gestational age below 34 weeks, birth weight below 1500 g or respiratory failure. Phenobarbital was compared to no intervention or placebo. We excluded infants with serious congenital malformations.

Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were all grades of IVH and severe IVH (i.e. grade III and IV); secondary outcomes were ventricular dilation or hydrocephalus, hypotension, pneumothorax, hypercapnia, acidosis, mechanical ventilation, neurodevelopmental impairment and death. We used GRADE to assess the certainty of the evidence for each outcome.

Main results: We included 10 RCTs (792 infants). The evidence suggests that phenobarbital results in little to no difference in the incidence of IVH of any grade compared with control (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.84 to 1.19; risk difference (RD) 0.00, 95% CI -0.06 to 0.07; I² for RD = 65%; 10 RCTs, 792 participants; low certainty evidence) and in severe IVH (RR 0.88, 95% CI 0.64 to 1.21; 10 RCTs, 792 participants; low certainty evidence). The evidence is very uncertain about the effect of phenobarbital on posthaemorrhagic ventricular dilation or hydrocephalus (RR 0.62, 95% CI 0.31 to 1.26; 4 RCTs, 271 participants; very low certainty evidence), mild neurodevelopmental impairment (RR 0.57, 95% CI 0.15 to 2.17; 1RCT, 101 participants; very low certainty evidence), and severe neurodevelopmental impairment (RR 1.12, 95% CI 0.44 to 2.82; 2 RCTs, 153 participants; very low certainty evidence). Phenobarbital may result in little to no difference in death before discharge (RR 0.88, 95% CI 0.64 to 1.21; 9 RCTs, 740 participants; low certainty evidence) and mortality during study period (RR 0.98, 95% CI 0.72 to 1.33; 10 RCTs, 792 participants; low certainty evidence) compared with control. We identified no ongoing trials.

Authors' conclusions: The evidence suggests that phenobarbital results in little to no difference in the incidence of IVH (any grade or severe) compared with control (i.e. no intervention or placebo). The evidence is very uncertain about the effects of phenobarbital on ventricular dilation or hydrocephalus and on neurodevelopmental impairment. The evidence suggests that phenobarbital results in little to no difference in death before discharge and all deaths during the study period compared with control. Since 1993, no randomised studies have been published on phenobarbital for the prevention of IVH in preterm infants, and no trials are ongoing. The effects of postnatal phenobarbital might be assessed in infants with both neonatal seizures and IVH, in both randomised and observational studies. The assessment of benefits and harms should include long-term outcomes.

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Conflict of interest statement

OR has no interests to declare.

ES has no interests to declare.

DO has no interest to declare.

MB has no interest to declare but is an Associate Editor with the Cochrane Neonatal Group; he was not involved in the editorial process for this review.

Figures

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1
Screen4Me summary diagram.
2
2
Prisma flow diagram.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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4
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Funnel plot of comparison: 1 Phenobarbital versus control, Outcome: 1.1 All intraventricular haemorrhage.
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Funnel plot of comparison: 1 Phenobarbital versus control, Outcome: 1.2 Severe intraventricular haemorrhage.
1.1
1.1. Analysis
Comparison 1: Phenobarbital versus control, Outcome 1: All intraventricular haemorrhage
1.2
1.2. Analysis
Comparison 1: Phenobarbital versus control, Outcome 2: Severe intraventricular haemorrhage
1.3
1.3. Analysis
Comparison 1: Phenobarbital versus control, Outcome 3: Ventricular dilation or hydrocephalus
1.4
1.4. Analysis
Comparison 1: Phenobarbital versus control, Outcome 4: Hypotension
1.5
1.5. Analysis
Comparison 1: Phenobarbital versus control, Outcome 5: Pneumothorax/interstitial emphysema
1.6
1.6. Analysis
Comparison 1: Phenobarbital versus control, Outcome 6: Hypercapnia
1.7
1.7. Analysis
Comparison 1: Phenobarbital versus control, Outcome 7: Acidosis
1.8
1.8. Analysis
Comparison 1: Phenobarbital versus control, Outcome 8: Use of mechanical ventilation
1.9
1.9. Analysis
Comparison 1: Phenobarbital versus control, Outcome 9: Mild neurodevelopmental impairment
1.10
1.10. Analysis
Comparison 1: Phenobarbital versus control, Outcome 10: Severe neurodevelopmental impairment
1.11
1.11. Analysis
Comparison 1: Phenobarbital versus control, Outcome 11: Death before discharge
1.12
1.12. Analysis
Comparison 1: Phenobarbital versus control, Outcome 12: All deaths during study
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Anwar 1986 {published data only}
    1. Anwar M, Kadam S, Hiatt IM, Hegyi T. Phenobarbitone prophylaxis of intraventricular haemorrhage. Archives of Diseases in Childhood 1986;61(2):196-7. [PMID: ] - PMC - PubMed
Bedard 1984 {published data only}
    1. Bedard MP, Shankaran S, Slovis TL, Pantoja A, Dayal B, Poland RL. Effect of prophylactic phenobarbital on intraventricular hemorrhage in high-risk infants. Pediatrics 1984;73(4):435-9. [PMID: ] - PubMed
Donn 1981 {published data only}
    1. Donn SM, Roloff DW, Goldstein GW. Prevention of intraventricular haemorrhage in preterm infants by phenobarbitone. Lancet 1981;2(8240):215-7. [PMID: ] - PubMed
Kuban 1986 {published and unpublished data}
    1. Kuban K, Leviton A, Brown ER, Krishnamoorthy K, Baglivo J, Sullivan KF, et al. Respiratory complications in low-birth-weight infants who received phenobarbital. American Journal of Diseases in Children 1987;141(9):996-9. [PMID: ] - PubMed
    1. Kuban KC, Leviton A, Krishnamoorthy KS, Brown ER, Teele RL, Baglivo JA, et al. Neonatal intracranial hemorrhage and phenobarbital. Pediatrics 1986;77(4):443-50. - PubMed
Mas‐Munoz 1993 {published data only}
    1. Mas-Munoz RL, Udaeta-Mora E, Barrera-Reyes RH, Rivera-Rueda MA, Morales-Suarez M. The effect of phenobarbital on the severity of intraventricular hemorrhage [Efecto del fenobarbital sobre la gravedad de la hemorragia intraventricular]. Boletín Médico del Hospital Infantil de México 1993;50(6):376-82. [PMID: ] - PubMed
Morgan 1982 {published data only}
    1. Morgan ME, Massey RF, Cooke RW. Does phenobarbitone prevent periventricular hemorrhage in very low birth weight babies?: a controlled trial. Pediatrics 1982;70(2):186-9. [PMID: ] - PubMed
Porter 1985 {published data only}
    1. Porter FL, Marshall RE, Moore JA, Miller RH. Effect of phenobarbital on motor activity and intraventricular hemorrhage in preterm infants with respiratory disease weighing less than 1500 grams. American Journal of Perinatology 1985;2(2):63-6. [PMID: ] - PubMed
Ruth 1985 {published data only}
    1. Ruth V. Brain protection by phenobarbitone in very low birthweight (VLBW) prematures - a controlled trial. Klinische Pädiatrie 1985;197(2):170-1. [DOI: 10.1055/s-2008-1033960] [PMID: ] - DOI - 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. [PMID: ] - PubMed
Whitelaw 1983 {published data only}
    1. Whitelaw A, Placzek M, Dubowitz L, Lary S, Levene M. Phenobarbitone for prevention of periventricular haemorrhage in very low birth-weight infants. A randomised double-blind trial. Lancet 1983;2(8360):1168-70. - PubMed

References to studies excluded from this review

Cooke 1982 {published data only}
    1. Cooke RW, Morgan ME. Phenobarbitone to prevent periventricular haemorrhage. Lancet 1982;1(8286):1408. [DOI: 10.1016/s0140-6736(82)92517-x] [PMID: ] - DOI - PubMed
Saliba 1991 {published data only}
    1. Saliba E, Autret E, Khadiry L, Chamboux C, Laugier J. Effects of phenobarbital on cerebral hemodynamics in preterm neonates. Developmental Pharmacology and Therapeutics 1991;17(3-4):133-7. [DOI: 10.1159/000457512] [PMID: ] - DOI - PubMed

Additional references

Aquilina 2012
    1. Aquilina K, Chakkarapani E, Thoresen M. Early deterioration of cerebrospinal fluid dynamics in a neonatal piglet model of intraventricular hemorrhage and posthemorrhagic ventricular dilation. Journal of Neurosurgery: Pediatrics 2012;10(6):529-37. [DOI: 10.3171/2012.8.PEDS11386] [PMID: ] - DOI - PubMed
Ballabh 2014
    1. Ballabh P. Pathogenesis and prevention of intraventricular hemorrhage. Clinics in Perinatology 2014;41(1):47-67. [DOI: 10.1016/j.clp.2013.09.007] [PMID: ] - DOI - PMC - PubMed
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 USA 2002;99(23):15089-94. - PMC - PubMed
Borenstein 2013
    1. Borenstein M, Higgins JP. Meta-analysis and subgroups. Prevention Science 2013;14:134-43. [DOI: 10.1007/s11121-013-0377-7] [PMID: ] - DOI - PubMed
Chen 2008
    1. Chen H, Wei K, Yao Y, Yang Y, Zhou C, Fang X, et al. Multicenter investigative report for the effect of prophylactic phenobarbital on intraventricular hemorrhage in premature infants in China. Journal of Clinical Pediatrics 2008;26(11):986-93.
Cizmeci 2019
    1. Cizmeci MN, Khalili N, Claessens NH, Groenendaal F, Liem KD, Heep A, et al. Assessment of brain injury and brain volumes after posthemorrhagic ventricular dilatation: a nested substudy of the randomized controlled ELVIS trial. Journal of Pediatrics 2019;208:191-7.e2. [DOI: 10.1016/j.jpeds.2018.12.062] [PMID: ] - DOI - PubMed
Cochrane EPOC Group 2017
    1. Cochrane Effective Practice, Organisation of Care (EPOC). Data extraction and management. EPOC resources for review authors, 2017. Available from epoc.cochrane.org/resources/epoc-resources-review-authors.
Crowther 2010
    1. Crowther CA, Crosby DD, Henderson-Smart DJ. Phenobarbital prior to preterm birth for preventing neonatal periventricular haemorrhage. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No: CD000164. [DOI: 10.1002/14651858.CD000164.pub2] - DOI - PMC - PubMed
Deeks 2020
    1. Deeks JJ, Higgins JP, Altman DG. Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch V, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.1 (updated September 2020). Cochrane, 2020. Available from www.training.cochrane.org/handbook.
Egger 1997
    1. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315(7109):629-34. [PMID: ] - PMC - PubMed
Forcelli 2011
    1. Forcelli PA, Kim J, Kondratyev A, Gale K. Pattern of antiepileptic drug-induced cell death in limbic regions of the neonatal rat brain. Epilepsia 2011;52(12):e207-11. [DOI: 10.1111/j.1528-1167.2011.03297.x] [PMID: ] - DOI - PMC - PubMed
Forcelli 2012
    1. Forcelli P, Janssen MJ, Vicini S, Gale K. Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development. Annals of Neurology 2012;72(3):363-72. [DOI: 10.1002/ana.23600] - DOI - PMC - PubMed
Goddard 1987
    1. Goddard-Finegold J, Armstrong DL. Reduction in incidence of periventricular intraventricular hemorrhages in hypertensive newborn beagles pretreated with phenobarbital. Pediatrics 1987;79(6):901-6. - PubMed
Gould 1987
    1. Gould SJ, Howard S. An immunohistochemical study of the germinal matrix in the late gestation human fetal brain. Neuropathology and Applied Neurobiology 1987;13(6):421-37. - PubMed
GRADEpro GDT [Computer program]
    1. GRADEpro GDT. Version accessed 24 April 2018. Hamilton (ON): McMaster University (developed by Evidence Prime), 2015. Available from gradepro.org.
Hambleton 1976
    1. Hambleton G, Wigglesworth JS. Origin of intraventricular haemorrhage in the preterm infant. Archives of Disease in Childhood 1976;51(9):651-9. - PMC - PubMed
Higgins 2011
    1. Higgins JP, Green S editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Higgins 2020
    1. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editors. Cochrane Handbook for Systematic Reviews of Interventions version 6.1 (updated September 2020). Cochrane, 2020. Available from www.training.cochrane.org/handbook.
Hope 1982
    1. Hope PL, Stewart AL, Thorburn RJ, Whitehead MD, Reynolds EO, Lowe D. Failure of phenobarbitone to prevent intraventricular haemorrhage in small preterm infants. Lancet 1982;1(8269):444‐5. [DOI: 10.1016/s0140-6736(82)91639-7] [PMID: ] - DOI - PubMed
Hope 1988
    1. Hope PL, Gould SJ, Howard S, Hamilton PA, Costello AM, Reynolds EO. Precision of ultrasound diagnosis of pathologically verified lesions in the brains of very preterm infants. Developmental Medicine and Child Neurology 1988;30(4):457-71. - PubMed
Horbar 1992
    1. Horbar J. Prevention of periventricular-intraventricular hemorrhage. In: Sinclair JC, Bracken MB, editors(s). Effective Care of the Newborn Infant. Oxford (UK): Oxford University Press, 1992:562-89.
Karimy 2017
    1. Karimy JK, Zhang J, Kurland DB, Theriault BC, Duran D, Stokum JA, et al. Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus. Nature Medicine 2017;23(8):997-1003. [DOI: 10.1038/nm.4361] [PMID: ] - DOI - PubMed
Kaushal 2016
    1. Kaushal S, Tamer Z, Opoku F, Forcelli PA. Anticonvulsant drug-induced cell death in the developing white matter of the rodent brain. Epilepsia 2016;57(5):727-34. [DOI: 10.1111/epi.13365] [PMID: ] - DOI - PMC - PubMed
Krishnamoorthy 1990
    1. Krishnamoorthy KS, Kuban KC, Leviton A, Brown ER, Sullivan KF, Allred EN. Periventricular-intraventricular hemorrhage sonographic localization, phenobarbital, and motor abnormalities in low birth weight infants. Pediatrics 1990;85(6):1027-33. [PMID: ] - PubMed
Kumar 2021
    1. Kumar J, Meena J, Yadav J, Saini L. Efficacy and safety of phenobarbitone as first-line treatment for neonatal seizure: a systematic review and meta-analysis. Journal of Tropical Pediatrics 2021;67(1):1-13. [DOI: 10.1093/tropej/fmab008] [PMID: ] - DOI - PubMed
Kwan 2004
    1. Kwan P, Brodie MJ. Phenobarbital for the treatment of epilepsy in the 21st century: a critical review. Epilepsia 2004;45(9):1141–9. [DOI: 10.1111/j.0013-9580.2004.12704.x] [PMID: ] - DOI - PubMed
Levene 1982
    1. Levene MI, Fawer CL, Lamont RF. Risk factors in the developmental of intraventricular haemorrhage in the preterm neonate. Archives of Disease in Childhood 1982;57(6):410-7. - PMC - PubMed
Liang 2009
    1. Liang GL, He YZ, Luo L. Phenobarbitone to prevent intraventricular hemorrhage in preterm infants - an observational study (38 cases). Journal of Medical Theory and Practice 2009;22(4):449-50. [DOI: ]
Liu 2010
    1. Liu Z, Zhao Y, Chen W, Wang H. Efficacy and safety of phenobarbital in preventing intraventricular hemorrhage in premature newborns. Journal of Bengbu Medical College 2010;35(10):1030-2. [DOI: ]
Luyt 2020
    1. Luyt K, Jary SL, Lea CL, Young GY, Odd DE, Miller HE, et al. Drainage, irrigation and fibrinolytic therapy (DRIFT) for posthaemorrhagic ventricular dilatation: 10-year follow-up of a randomised controlled trial. Archives of Disease in Childhood. Fetal and Neonatal Edition 2020;105(5):466–73. [DOI: 10.1136/archdischild-2019-318231] [PMID: ] - DOI - PMC - PubMed
Maitre 2013
    1. Maitre NL, Smolinsky C, Slaughter JC, Stark AR. Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures. Journal of Perinatology 2013;33(11):841-6. [DOI: 10.1038/jp.2013.116] [PMID: ] - DOI - PMC - PubMed
Marshall 2018
    1. Marshall IJ, Noel-Storr AH, Kuiper J, Thomas J, Wallace BC. Machine learning for identifying randomized controlled trials: an evaluation and practitioner’s guide. Research Synthesis Methods 2018;9(4):602-14. [DOI: 10.1002/jrsm.1287] [PMID: ] - DOI - PMC - PubMed
McGowan 2016a
    1. McGowan J, Sampson M, Salzwedel D, Cogo E, Foerster V, Lefebvre C. PRESS Peer Review of Electronic Search Strategies: 2015 Guideline Explanation and Elaboration (PRESS E&E). Ottawa (ON): CADTH, 2016. [URL: https://www.cadth.ca/sites/default/files/pdf/CP0015_PRESS_Update_Report_...] - PubMed
McGowan 2016b
    1. McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS Peer Review of Electronic Search Strategies: 2015 Guideline Statement. Journal of Clinical Epidemiology 2016;75:40-6. [PMID: ] - PubMed
Ment 1985
    1. Ment LR, Stewart WB, Duncan CC. Beagle puppy model of intraventricular hemorrhage. Effect of superoxide dismutase on cerebral blood flow and prostaglandins. Journal of Neurosurgery 1985;62(4):563-9. - PubMed
Moher 2009
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Journal of Clinical Epidemiology 2009;62(10):1006-12. [PMID: ] - PubMed
Mullaart 1994
    1. Mullaart RA, Hopman JC, Rotteveel JJ, Daniels O, Stoelinga GB, De Haan AF. Cerebral blood flow fluctuation in neonatal respiratory distress and periventricular haemorrhage. Early Human Development 1994;37(3):179-85. [DOI: 10.1016/0378-3782(94)90077-9] [PMID: ] - DOI - PubMed
Nakamura 1990
    1. Nakamura Y, Okudera T, Fukuda S, Hashimoto T. Germinal matrix hemorrhage of venous origin in preterm neonates. Human Pathology 1990;21(10):1059-62. - PubMed
Noel‐Storr 2020
    1. Noel-Storr AH, Dooley G, Wisniewski S, Glanville J, Thomas J, Cox S, et al. Cochrane Centralised Search Service showed high sensitivity identifying randomised controlled trials: a retrospective analysis. Journal of Clinical Epidemiology 2020;127:142-50. [DOI: 10.1016/j.jclinepi.2020.08.008] [PMID: ] - DOI - PubMed
Noel‐Storr 2021
    1. Noel-Storr AH, Dooley G, Elliott J, Steele E, Shemilt I, Mavergames C, et al. An evaluation of Cochrane Crowd found that crowdsourcing produced accurate results in identifying randomised trials. Journal of Clinical Epidemiology 2021;133:130-9. [DOI: 10.1016/j.jclinepi.2021.01.006] [PMID: ] - DOI - PubMed
Papile 1978
    1. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. Journal of Pediatrics 1978;92(4):529-34. [DOI: 10.1016/s0022-3476(78)80282-0] - DOI - PubMed
Parodi 2015
    1. Parodi A, Morana G, Severino MS, Malova M, Natalizia AR, Sannia A, et al. Low-grade intraventricular hemorrhage: is ultrasound good enough? Journal of Maternal-Fetal & Neonatal Medicine 2015;28(Suppl 1):2261-4. [DOI: 10.3109/14767058.2013.796162] [PMID: ] - DOI - PubMed
Pasternak 1983
    1. Pasternak JF, Groothuis DR, Fischer JM, Fischer DP. Regional cerebral blood flow in the beagle puppy model of neonatal intraventricular hemorrhage: studies during systemic hypertension. Neurology 1983;33(5):559–66. [DOI: 10.1212/wnl.33.5.599] [PMID: ] - DOI - PubMed
Perlman 1983
    1. Perlman JM, McMenamin JB, Volpe JJ. Fluctuating cerebral blood-flow velocity in respiratory-distress syndrome. Relation to the development of intraventricular hemorrhage. New England Journal of Medicine 1983;309(4):204-9. - PubMed
Review Manager 2020 [Computer program]
    1. Review Manager 5 (RevMan 5). Version 5.4. Copenhagen: The Cochrane Collaboration, 2020.
Romantsik 2019
    1. Romantsik O, Bruschettini M, Ley D. Intraventricular hemorrhage and white matter injury in preclinical and clinical studies. NeoReviews 2019;20(11):e636-52. [PMID: ] - PubMed
Schünemann 2013
    1. Schünemann H, Brożek J, Guyatt G, Oxman A, editor(s). Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach (updated October 2013). GRADE Working Group, 2013. Available from gdt.guidelinedevelopment.org/app/handbook/handbook.html.
Shankaran 1982
    1. Shankaran S, Slovis TL, Bedard MP, Poland RL. Sonographic classification of intracranial hemorrhage: a prognostic indicator of mortality, morbidity and short-term neurologic outcome . Journal of Pediatrics 1982;100:469-75. [DOI: 10.1016/s0022-3476(82)80462-9] [PMID: ] - DOI - PubMed
Shankaran 2020
    1. Shankaran S, Bajaj M, Natarajan G, Saha S, Pappas A, Davis AS, et al. Outcomes following post-hemorrhagic ventricular dilatation among infants of extremely low gestational age. Journal of Pediatrics 2020;226:36-44.e3. [DOI: 10.1016/j.jpeds.2020.07.080] [PMID: ] - DOI - PMC - PubMed
Sharpe 2020
    1. Sharpe C, Reiner GE, Davis SL, Nespeca M, Gold JJ, Rasmussen M, et al. Levetiracetam versus phenobarbital for neonatal seizures: a randomized controlled trial. Pediatrics 2020;145(6):e20193182. [PMID: 10.1542/peds.2019-3182] [PMID: ] - DOI - PMC - PubMed
Sluncheva 2006
    1. Sluncheva B, Vakrilova L, Emilova Z, Kalaĭdzhieva M, Garnizov T. Prevention of brain hemorrhage in infants with low and extremely low birth weight and infants treated with surfactants. Late observation. Akusherstvo i Ginekologiia (Sofiia) 2006;45(3):34-8. - PubMed
Steen 1979
    1. Steen PA, Mitchenfelder JD. Barbiturate protection in tolerant and nontolerant hypoxic mice: comparison with hypothermic protection. Anesthesiology 1979;50(5):404-8. - PubMed
Stoll 2015
    1. Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA 2015;314(10):1039-51. [DOI: 10.1001/jama.2015.10244] [PMID: ] - DOI - PMC - PubMed
Thomas 2020
    1. Thomas J, McDonald S, Noel-Storr AH, Shemilt I, Elliott J, Mavergames C, et al. Machine learning reduces workload with minimal risk of missing studies: development and evaluation of an RCT classifier for Cochrane Reviews. Journal of Clinical Epidemiology 2021;133:140-51. [DOI: 10.1016/j.jclinepi.2020.11.003] [PMID: ] - DOI - PMC - PubMed
Vohr 1989
    1. Vohr BR, Garcia-Coll C, Mayfield S, Brann B, Shaul P, Oh W. Neurologic and developmental status related to the evolution of visual-motor abnormalities from birth to 2 years of age in preterm infants with intraventricular hemorrhage. Journal of Pediatrics 1989;115(2):296-302. - PubMed
Volpe 1995
    1. Volpe JJ. Neurology of the Newborn. 3rd edition. Philadelphia: Saunders, 1995.
Volpe 2008
    1. Vople JJ. Neurology of the Newborn. 5th edition. Philadelphia (PA): Saunders, 2008.
Wimberley 1982
    1. Wimberley PD, Lou HC, Pedersen H, Hejl M, Lassen NA, Friis-Hansen B. Hypertensive peaks in the pathogenesis of intraventricular hemorrhage in the newborn. Abolition by phenobarbitone sedation. Acta Paediatrica Scandinavica 1982;71(4):537-42. - PubMed
Younge 2017
    1. Younge N, Goldstein RF, Bann CM, Hintz SR, Patel RM, Smith BP, et al. Survival and neurodevelopmental outcomes among periviable infants. New England Journal of Medicine 2017;376(7):617–28. [DOI: 10.1056/NEJMoa1605566] [PMID: ] - DOI - PMC - PubMed
Zhang 2009
    1. Zhang ZJ, Yuan J, Meng YQ, Guo JX. An observational study of phenobarbitone in preventing intraventricular hemorrhage in preterm infants. Inner Mongolian Medical Journal 2009;41(5):617-8. [DOI: ]

References to other published versions of this review

Smit 2013
    1. Smit E, Odd D, Whitelaw A. Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preterm infants. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No: CD001691. [DOI: 10.1002/14651858.CD001691.pub3] - DOI - PMC - PubMed
Whitelaw 2001
    1. Whitelaw A. Postnatal phenobarbitone for the prevention of intraventricular hemorrhage in preterm infants. Cochrane Database of Systematic Reviews 2001, Issue 1. Art. No: CD001691. [DOI: 10.1002/14651858.CD001691] - DOI - PubMed
Whitelaw 2007
    1. Whitelaw A, Odd D. Postnatal phenobarbital for the prevention of intraventricular hemorrhage in preterm infants. Cochrane Database of Systematic Reviews 2007, Issue 10. Art. No: CD001691. [DOI: 10.1002/14651858.CD001691.pub2] - DOI - PubMed

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