Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: follow-up of two randomised controlled trials

Joepe J. Kaandorp; Frank van Bel; Sylvia Veen; Jan B. Derks; Floris Groenendaal; Monique Rijken; Elise Roze; Monica M.A. Uniken Venema; Carin M.A. Rademaker; Arend F Bos; Manon J.N.L. Benders

doi:10.1136/archdischild-2011-300356

Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: follow-up of two randomised controlled trials

Joepe J. Kaandorp, Frank van Bel, Sylvia Veen, Jan B. Derks, Floris Groenendaal, Monique Rijken, Elise Roze, Monica M.A. Uniken Venema, Carin M.A. Rademaker, Arend F Bos, Manon J.N.L. Benders

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Objective Free-radical-induced reperfusion injury has been recognised as an important cause of brain tissue damage after birth asphyxia. Allopurinol reduces the formation of free radicals, thereby potentially limiting the amount of hypoxia-reperfusion damage. In this study the long-term outcome of neonatal allopurinol treatment after birth asphyxia was examined.

Design Follow-up of 4 to 8 years of two earlier performed randomised controlled trials.

Setting Leiden University Medical Center, University Medical Center Groningen and University Medical Center Utrecht, The Netherlands.

Patients Fifty-four term infants were included when suffering from moderate-to-severe birth asphyxia in two previously performed trials.

Intervention Infants either received 40 mg/kg allopurinol (with an interval of 12 h) starting within 4 h after birth or served as controls.

Main outcome measures Children, who survived, were assessed with the Wechsler Preschool and Primary Scales of Intelligence test or Wechsler Intelligence Scale for Children and underwent a neurological examination. The effect of allopurinol on severe adverse outcome (defined as mortality or severe disability at the age of 4-8 years) was examined in the total group of asphyxiated infants and in a predefined subgroup of moderately asphyxiated infants (based on the amplitude integrated electroencephalogram).

Results The mean age during follow-up (n=23) was 5 years and 5 months (SD 1 year and 2 months). There were no differences in long-term outcome between the allopurinol-treated infants and controls. However, subgroup analysis of the moderately asphyxiated group showed significantly less severe adverse outcome in the allopurinol-treated infants compared with controls (25% vs 65%; RR 0.40, 95% CI 0.17 to 0.94).

Conclusions The reported data may suggest a (neuro) protective effect of neonatal allopurinol treatment in moderately asphyxiated infants.

Original language	English
Pages (from-to)	F162-F166
Number of pages	5
Journal	Archives of Disease in Childhood Fetal and Neonatal Edition
Volume	97
Issue number	3
DOIs	https://doi.org/10.1136/archdischild-2011-300356
Publication status	Published - May 2012

Keywords

HYPOXIC-ISCHEMIC ENCEPHALOPATHY
BIRTH ASPHYXIA
BRAIN-INJURY
PHARMACOLOGICAL NEUROPROTECTION
CEREBRAL-PALSY
BLOOD-LEVELS
HYPOTHERMIA
CHILDREN
MULTICENTER
NEWBORNS

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10.1136/archdischild-2011-300356

http://fn.bmj.com/content/97/3/F162.long

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Kaandorp, J. J., van Bel, F., Veen, S., Derks, J. B., Groenendaal, F., Rijken, M., Roze, E., Uniken Venema, M. M. A., Rademaker, C. M. A., Bos, A. F., & Benders, M. J. N. L. (2012). Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: follow-up of two randomised controlled trials. Archives of Disease in Childhood Fetal and Neonatal Edition, 97(3), F162-F166. https://doi.org/10.1136/archdischild-2011-300356

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title = "Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: follow-up of two randomised controlled trials",

abstract = "Objective Free-radical-induced reperfusion injury has been recognised as an important cause of brain tissue damage after birth asphyxia. Allopurinol reduces the formation of free radicals, thereby potentially limiting the amount of hypoxia-reperfusion damage. In this study the long-term outcome of neonatal allopurinol treatment after birth asphyxia was examined.Design Follow-up of 4 to 8 years of two earlier performed randomised controlled trials.Setting Leiden University Medical Center, University Medical Center Groningen and University Medical Center Utrecht, The Netherlands.Patients Fifty-four term infants were included when suffering from moderate-to-severe birth asphyxia in two previously performed trials.Intervention Infants either received 40 mg/kg allopurinol (with an interval of 12 h) starting within 4 h after birth or served as controls.Main outcome measures Children, who survived, were assessed with the Wechsler Preschool and Primary Scales of Intelligence test or Wechsler Intelligence Scale for Children and underwent a neurological examination. The effect of allopurinol on severe adverse outcome (defined as mortality or severe disability at the age of 4-8 years) was examined in the total group of asphyxiated infants and in a predefined subgroup of moderately asphyxiated infants (based on the amplitude integrated electroencephalogram).Results The mean age during follow-up (n=23) was 5 years and 5 months (SD 1 year and 2 months). There were no differences in long-term outcome between the allopurinol-treated infants and controls. However, subgroup analysis of the moderately asphyxiated group showed significantly less severe adverse outcome in the allopurinol-treated infants compared with controls (25% vs 65%; RR 0.40, 95% CI 0.17 to 0.94).Conclusions The reported data may suggest a (neuro) protective effect of neonatal allopurinol treatment in moderately asphyxiated infants.",

keywords = "HYPOXIC-ISCHEMIC ENCEPHALOPATHY, BIRTH ASPHYXIA, BRAIN-INJURY, PHARMACOLOGICAL NEUROPROTECTION, CEREBRAL-PALSY, BLOOD-LEVELS, HYPOTHERMIA, CHILDREN, MULTICENTER, NEWBORNS",

author = "Kaandorp, {Joepe J.} and {van Bel}, Frank and Sylvia Veen and Derks, {Jan B.} and Floris Groenendaal and Monique Rijken and Elise Roze and {Uniken Venema}, {Monica M.A.} and Rademaker, {Carin M.A.} and Bos, {Arend F} and Benders, {Manon J.N.L.}",

year = "2012",

month = may,

doi = "10.1136/archdischild-2011-300356",

language = "English",

volume = "97",

pages = "F162--F166",

journal = "Archives of Disease in Childhood Fetal and Neonatal Edition",

issn = "1359-2998",

publisher = "BMJ Publishing Group",

number = "3",

}

Kaandorp, JJ, van Bel, F, Veen, S, Derks, JB, Groenendaal, F, Rijken, M, Roze, E, Uniken Venema, MMA, Rademaker, CMA, Bos, AF & Benders, MJNL 2012, 'Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: follow-up of two randomised controlled trials', Archives of Disease in Childhood Fetal and Neonatal Edition, vol. 97, no. 3, pp. F162-F166. https://doi.org/10.1136/archdischild-2011-300356

Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: follow-up of two randomised controlled trials. / Kaandorp, Joepe J.; van Bel, Frank; Veen, Sylvia et al.
In: Archives of Disease in Childhood Fetal and Neonatal Edition, Vol. 97, No. 3, 05.2012, p. F162-F166.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia

T2 - follow-up of two randomised controlled trials

AU - Kaandorp, Joepe J.

AU - van Bel, Frank

AU - Veen, Sylvia

AU - Derks, Jan B.

AU - Groenendaal, Floris

AU - Rijken, Monique

AU - Roze, Elise

AU - Uniken Venema, Monica M.A.

AU - Rademaker, Carin M.A.

AU - Bos, Arend F

AU - Benders, Manon J.N.L.

PY - 2012/5

Y1 - 2012/5

N2 - Objective Free-radical-induced reperfusion injury has been recognised as an important cause of brain tissue damage after birth asphyxia. Allopurinol reduces the formation of free radicals, thereby potentially limiting the amount of hypoxia-reperfusion damage. In this study the long-term outcome of neonatal allopurinol treatment after birth asphyxia was examined.Design Follow-up of 4 to 8 years of two earlier performed randomised controlled trials.Setting Leiden University Medical Center, University Medical Center Groningen and University Medical Center Utrecht, The Netherlands.Patients Fifty-four term infants were included when suffering from moderate-to-severe birth asphyxia in two previously performed trials.Intervention Infants either received 40 mg/kg allopurinol (with an interval of 12 h) starting within 4 h after birth or served as controls.Main outcome measures Children, who survived, were assessed with the Wechsler Preschool and Primary Scales of Intelligence test or Wechsler Intelligence Scale for Children and underwent a neurological examination. The effect of allopurinol on severe adverse outcome (defined as mortality or severe disability at the age of 4-8 years) was examined in the total group of asphyxiated infants and in a predefined subgroup of moderately asphyxiated infants (based on the amplitude integrated electroencephalogram).Results The mean age during follow-up (n=23) was 5 years and 5 months (SD 1 year and 2 months). There were no differences in long-term outcome between the allopurinol-treated infants and controls. However, subgroup analysis of the moderately asphyxiated group showed significantly less severe adverse outcome in the allopurinol-treated infants compared with controls (25% vs 65%; RR 0.40, 95% CI 0.17 to 0.94).Conclusions The reported data may suggest a (neuro) protective effect of neonatal allopurinol treatment in moderately asphyxiated infants.

AB - Objective Free-radical-induced reperfusion injury has been recognised as an important cause of brain tissue damage after birth asphyxia. Allopurinol reduces the formation of free radicals, thereby potentially limiting the amount of hypoxia-reperfusion damage. In this study the long-term outcome of neonatal allopurinol treatment after birth asphyxia was examined.Design Follow-up of 4 to 8 years of two earlier performed randomised controlled trials.Setting Leiden University Medical Center, University Medical Center Groningen and University Medical Center Utrecht, The Netherlands.Patients Fifty-four term infants were included when suffering from moderate-to-severe birth asphyxia in two previously performed trials.Intervention Infants either received 40 mg/kg allopurinol (with an interval of 12 h) starting within 4 h after birth or served as controls.Main outcome measures Children, who survived, were assessed with the Wechsler Preschool and Primary Scales of Intelligence test or Wechsler Intelligence Scale for Children and underwent a neurological examination. The effect of allopurinol on severe adverse outcome (defined as mortality or severe disability at the age of 4-8 years) was examined in the total group of asphyxiated infants and in a predefined subgroup of moderately asphyxiated infants (based on the amplitude integrated electroencephalogram).Results The mean age during follow-up (n=23) was 5 years and 5 months (SD 1 year and 2 months). There were no differences in long-term outcome between the allopurinol-treated infants and controls. However, subgroup analysis of the moderately asphyxiated group showed significantly less severe adverse outcome in the allopurinol-treated infants compared with controls (25% vs 65%; RR 0.40, 95% CI 0.17 to 0.94).Conclusions The reported data may suggest a (neuro) protective effect of neonatal allopurinol treatment in moderately asphyxiated infants.

KW - HYPOXIC-ISCHEMIC ENCEPHALOPATHY

KW - BIRTH ASPHYXIA

KW - BRAIN-INJURY

KW - PHARMACOLOGICAL NEUROPROTECTION

KW - CEREBRAL-PALSY

KW - BLOOD-LEVELS

KW - HYPOTHERMIA

KW - CHILDREN

KW - MULTICENTER

KW - NEWBORNS

U2 - 10.1136/archdischild-2011-300356

DO - 10.1136/archdischild-2011-300356

M3 - Article

C2 - 22102633

SN - 1359-2998

VL - 97

SP - F162-F166

JO - Archives of Disease in Childhood Fetal and Neonatal Edition

JF - Archives of Disease in Childhood Fetal and Neonatal Edition

IS - 3

ER -

Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: follow-up of two randomised controlled trials

Abstract

Keywords

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