A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: childhood outcomes at 5 years

Neil Marlow; Timothy Morris; Peter Brocklehurst; Robert Carr; Frances Cowan; Nishma Patel; Stavros Petrou; Margaret Redshaw; Neena Modi; Caroline J Doré

doi:10.1136/archdischild-2014-307410

A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: childhood outcomes at 5 years

Neil Marlow, Timothy Morris, Peter Brocklehurst, Robert Carr, Frances Cowan, Nishma Patel, Stavros Petrou, Margaret Redshaw, Neena Modi, Caroline J Doré

Birmingham Clinical Trials Unit

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

15 Citations (Scopus)

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Abstract

OBJECTIVE: We performed a randomised trial in very preterm, small for gestational age (SGA) babies to determine if prophylaxis with granulocyte macrophage colony stimulating factor (GM-CSF) improves outcomes (the PROGRAMS trial). GM-CSF was associated with improved neonatal neutrophil counts, but no change in other neonatal or 2-year outcomes. As subtle benefits in outcome may not be ascertainable until school age we performed an outcome study at 5 years.

PATIENTS AND METHODS: 280 babies born at 31 weeks of gestation or less and SGA were entered into the trial. Outcomes were assessed at 5 years to determine neurodevelopmental and general health status and educational attainment.

RESULTS: We found no significant differences in cognitive, general health or educational outcomes between 83 of 106 (78%) surviving children in the GM-CSF arm compared with 81 of 110 (74%) in the control arm. Mean mental processing composite (equivalent to IQ) at 5 years were 94 (SD 16) compared with 95 (SD 15), respectively (difference in means -1 (95%CI -6 to 4), and similar proportions were in receipt of special educational needs support (41% vs 35%; risk ratio 1.2 (95% CI 0.8 to 1.9)). Performance on Kaufmann-ABC subscales and components of NEPSY were similar. The suggestion of worse respiratory outcomes in the GM-CSF group at 2 years was replicated at 5 years.

CONCLUSIONS: The administration of GM-CSF to very preterm SGA babies is not associated with improved or more adverse neurodevelopmental, general health or educational outcomes at 5 years.

TRIAL REGISTRATION NUMBER: ISRCTN42553489.

Original language	English
Pages (from-to)	F320-F326
Number of pages	7
Journal	Archives of disease in childhood. Fetal and neonatal edition
Volume	100
Early online date	28 Apr 2015
DOIs	https://doi.org/10.1136/archdischild-2014-307410
Publication status	Published - Jul 2015

Keywords

Child Development
Female
Granulocyte-Macrophage Colony-Stimulating Factor
Hematologic Agents
Humans
Infant, Extremely Premature
Infant, Newborn
Infant, Small for Gestational Age
Leukocyte Count
Male
Neuropsychological Tests
Neutrophils
Outcome Assessment (Health Care)
Sepsis
Time
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

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10.1136/archdischild-2014-307410Licence: Creative Commons: Attribution (CC BY)

Marlow_et_al_A_randomised_trial_Archives_of_Disease_in_Childhood_2015
Marlow N, Morris T, Brocklehurst P, et al A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: childhood outcomes at 5 years Archives of Disease in Childhood - Fetal and Neonatal Edition 2015;100:F320-F326. http://dx.doi.org/10.1136/archdischild-2014-307410
Final published version, 559 KBLicence: Creative Commons: Attribution (CC BY)

https://fn.bmj.com/content/100/4/F320Licence: Creative Commons: Attribution (CC BY)

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Marlow, N., Morris, T., Brocklehurst, P., Carr, R., Cowan, F., Patel, N., Petrou, S., Redshaw, M., Modi, N., & Doré, C. J. (2015). A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: childhood outcomes at 5 years. Archives of disease in childhood. Fetal and neonatal edition, 100, F320-F326. https://doi.org/10.1136/archdischild-2014-307410

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title = "A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: childhood outcomes at 5 years",

abstract = "OBJECTIVE: We performed a randomised trial in very preterm, small for gestational age (SGA) babies to determine if prophylaxis with granulocyte macrophage colony stimulating factor (GM-CSF) improves outcomes (the PROGRAMS trial). GM-CSF was associated with improved neonatal neutrophil counts, but no change in other neonatal or 2-year outcomes. As subtle benefits in outcome may not be ascertainable until school age we performed an outcome study at 5 years.PATIENTS AND METHODS: 280 babies born at 31 weeks of gestation or less and SGA were entered into the trial. Outcomes were assessed at 5 years to determine neurodevelopmental and general health status and educational attainment.RESULTS: We found no significant differences in cognitive, general health or educational outcomes between 83 of 106 (78%) surviving children in the GM-CSF arm compared with 81 of 110 (74%) in the control arm. Mean mental processing composite (equivalent to IQ) at 5 years were 94 (SD 16) compared with 95 (SD 15), respectively (difference in means -1 (95%CI -6 to 4), and similar proportions were in receipt of special educational needs support (41% vs 35%; risk ratio 1.2 (95% CI 0.8 to 1.9)). Performance on Kaufmann-ABC subscales and components of NEPSY were similar. The suggestion of worse respiratory outcomes in the GM-CSF group at 2 years was replicated at 5 years.CONCLUSIONS: The administration of GM-CSF to very preterm SGA babies is not associated with improved or more adverse neurodevelopmental, general health or educational outcomes at 5 years.TRIAL REGISTRATION NUMBER: ISRCTN42553489.",

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author = "Neil Marlow and Timothy Morris and Peter Brocklehurst and Robert Carr and Frances Cowan and Nishma Patel and Stavros Petrou and Margaret Redshaw and Neena Modi and Dor{\'e}, {Caroline J}",

note = "Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.",

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month = jul,

doi = "10.1136/archdischild-2014-307410",

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Marlow, N, Morris, T, Brocklehurst, P, Carr, R, Cowan, F, Patel, N, Petrou, S, Redshaw, M, Modi, N & Doré, CJ 2015, 'A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: childhood outcomes at 5 years', Archives of disease in childhood. Fetal and neonatal edition, vol. 100, pp. F320-F326. https://doi.org/10.1136/archdischild-2014-307410

TY - JOUR

T1 - A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis

T2 - childhood outcomes at 5 years

AU - Marlow, Neil

AU - Morris, Timothy

AU - Brocklehurst, Peter

AU - Carr, Robert

AU - Cowan, Frances

AU - Patel, Nishma

AU - Petrou, Stavros

AU - Redshaw, Margaret

AU - Modi, Neena

AU - Doré, Caroline J

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PY - 2015/7

Y1 - 2015/7

N2 - OBJECTIVE: We performed a randomised trial in very preterm, small for gestational age (SGA) babies to determine if prophylaxis with granulocyte macrophage colony stimulating factor (GM-CSF) improves outcomes (the PROGRAMS trial). GM-CSF was associated with improved neonatal neutrophil counts, but no change in other neonatal or 2-year outcomes. As subtle benefits in outcome may not be ascertainable until school age we performed an outcome study at 5 years.PATIENTS AND METHODS: 280 babies born at 31 weeks of gestation or less and SGA were entered into the trial. Outcomes were assessed at 5 years to determine neurodevelopmental and general health status and educational attainment.RESULTS: We found no significant differences in cognitive, general health or educational outcomes between 83 of 106 (78%) surviving children in the GM-CSF arm compared with 81 of 110 (74%) in the control arm. Mean mental processing composite (equivalent to IQ) at 5 years were 94 (SD 16) compared with 95 (SD 15), respectively (difference in means -1 (95%CI -6 to 4), and similar proportions were in receipt of special educational needs support (41% vs 35%; risk ratio 1.2 (95% CI 0.8 to 1.9)). Performance on Kaufmann-ABC subscales and components of NEPSY were similar. The suggestion of worse respiratory outcomes in the GM-CSF group at 2 years was replicated at 5 years.CONCLUSIONS: The administration of GM-CSF to very preterm SGA babies is not associated with improved or more adverse neurodevelopmental, general health or educational outcomes at 5 years.TRIAL REGISTRATION NUMBER: ISRCTN42553489.

AB - OBJECTIVE: We performed a randomised trial in very preterm, small for gestational age (SGA) babies to determine if prophylaxis with granulocyte macrophage colony stimulating factor (GM-CSF) improves outcomes (the PROGRAMS trial). GM-CSF was associated with improved neonatal neutrophil counts, but no change in other neonatal or 2-year outcomes. As subtle benefits in outcome may not be ascertainable until school age we performed an outcome study at 5 years.PATIENTS AND METHODS: 280 babies born at 31 weeks of gestation or less and SGA were entered into the trial. Outcomes were assessed at 5 years to determine neurodevelopmental and general health status and educational attainment.RESULTS: We found no significant differences in cognitive, general health or educational outcomes between 83 of 106 (78%) surviving children in the GM-CSF arm compared with 81 of 110 (74%) in the control arm. Mean mental processing composite (equivalent to IQ) at 5 years were 94 (SD 16) compared with 95 (SD 15), respectively (difference in means -1 (95%CI -6 to 4), and similar proportions were in receipt of special educational needs support (41% vs 35%; risk ratio 1.2 (95% CI 0.8 to 1.9)). Performance on Kaufmann-ABC subscales and components of NEPSY were similar. The suggestion of worse respiratory outcomes in the GM-CSF group at 2 years was replicated at 5 years.CONCLUSIONS: The administration of GM-CSF to very preterm SGA babies is not associated with improved or more adverse neurodevelopmental, general health or educational outcomes at 5 years.TRIAL REGISTRATION NUMBER: ISRCTN42553489.

KW - Child Development

KW - Female

KW - Granulocyte-Macrophage Colony-Stimulating Factor

KW - Hematologic Agents

KW - Humans

KW - Infant, Extremely Premature

KW - Infant, Newborn

KW - Infant, Small for Gestational Age

KW - Leukocyte Count

KW - Male

KW - Neuropsychological Tests

KW - Neutrophils

KW - Outcome Assessment (Health Care)

KW - Sepsis

KW - Time

KW - Journal Article

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1136/archdischild-2014-307410

DO - 10.1136/archdischild-2014-307410

M3 - Article

C2 - 25922190

SN - 1359-2998

VL - 100

SP - F320-F326

JO - Archives of disease in childhood. Fetal and neonatal edition

JF - Archives of disease in childhood. Fetal and neonatal edition

ER -

A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: childhood outcomes at 5 years

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Keywords

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