Maternal Allopurinol During Fetal Hypoxia Lowers Cord Blood Levels of the Brain Injury Marker S-100B

H.L. Torrance; M.J.N.L. Benders; J.B. Derks; C.M.A. Rademaker; A.F. Bos; P. van den Berg; M.A. Longini; G. Buonocore; M.E. Venegas; H. Baquero; G.H.A. Visser; F. van Bel

doi:10.1542/peds.2008-2228

Maternal Allopurinol During Fetal Hypoxia Lowers Cord Blood Levels of the Brain Injury Marker S-100B

H.L. Torrance, M.J.N.L. Benders, J.B. Derks, C.M.A. Rademaker, A.F. Bos, P. van den Berg, M.A. Longini, G. Buonocore, M.E. Venegas, H. Baquero, G.H.A. Visser, F. van Bel

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

Abstract

BACKGROUND: Fetal hypoxia is an important determinant of neonatal encephalopathy caused by birth asphyxia, in which hypoxia-induced free radical formation plays an important role. HYPOTHESIS: Maternal treatment with allopurinol, will cross the placenta during fetal hypoxia (rimary outcome) and reduce S-100B and free radical formation (secondary outcome).

METHODS: In a randomized, double-blind feasibility study, 53 pregnant women in labor ( 54 fetuses) with a gestational age of >36 weeks and fetal hypoxia, as indicated by abnormal/nonreassuring fetal heart rate tracing or fetal scalp pH of

RESULTS: Allopurinol and oxypurinol concentrations were within the therapeutic range in the mother (allopurinol >2 mg/L and/or oxypurinol > 4 mg/L) but not always in arterial cord blood. We therefore created 3 groups: a placebo (n = 27), therapeutic allopurinol (n = 15), and subtherapeutic allopurinol group (n = 12). Cord lactate concentration did not differ, but S-100B was significantly lower in the therapeutic allopurinol group compared with the placebo and subtherapeutic allopurinol groups (P <.01). Fewer therapeutic allopurinol cord samples had measurable non-protein-bound iron concentrations compared with placebo (P <.01).

CONCLUSIONS: Maternal allopurinol/oxypurinol crosses the placenta during fetal hypoxia. In fetuses/newborns with therapeutic allopurinol/ oxypurinol concentrations in cord blood, lower plasma levels of the brain injury marker protein S-100B were detected. A larger allopurinol trial in compromised fetuses at term seems warranted. The allopurinol dosage must be adjusted to achieve therapeutic fetal allopurinol/oxypurinol concentrations. Pediatrics 2009; 124: 350-357

Original language	English
Pages (from-to)	350-357
Number of pages	8
Journal	Pediatrics
Volume	124
Issue number	1
DOIs	https://doi.org/10.1542/peds.2008-2228
Publication status	Published - Jul 2009

Keywords

neuroprotection
allopurinol
fetal hypoxia
protein S-100B
BIRTH ASPHYXIA
ISCHEMIC ENCEPHALOPATHY
PERINATAL ASPHYXIA
PROTEIN S-100
HYPOTHERMIA
OXYPURINOL
NEWBORNS
PLASMA
SERUM
TRIAL

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Torrance, H. L., Benders, M. J. N. L., Derks, J. B., Rademaker, C. M. A., Bos, A. F., van den Berg, P., Longini, M. A., Buonocore, G., Venegas, M. E., Baquero, H., Visser, G. H. A., & van Bel, F. (2009). Maternal Allopurinol During Fetal Hypoxia Lowers Cord Blood Levels of the Brain Injury Marker S-100B. Pediatrics, 124(1), 350-357. https://doi.org/10.1542/peds.2008-2228

@article{05b5ee8ed8b44924958b2486fe58b7b0,

title = "Maternal Allopurinol During Fetal Hypoxia Lowers Cord Blood Levels of the Brain Injury Marker S-100B",

abstract = "BACKGROUND: Fetal hypoxia is an important determinant of neonatal encephalopathy caused by birth asphyxia, in which hypoxia-induced free radical formation plays an important role. HYPOTHESIS: Maternal treatment with allopurinol, will cross the placenta during fetal hypoxia (rimary outcome) and reduce S-100B and free radical formation (secondary outcome).METHODS: In a randomized, double-blind feasibility study, 53 pregnant women in labor ( 54 fetuses) with a gestational age of >36 weeks and fetal hypoxia, as indicated by abnormal/nonreassuring fetal heart rate tracing or fetal scalp pH ofRESULTS: Allopurinol and oxypurinol concentrations were within the therapeutic range in the mother (allopurinol >2 mg/L and/or oxypurinol > 4 mg/L) but not always in arterial cord blood. We therefore created 3 groups: a placebo (n = 27), therapeutic allopurinol (n = 15), and subtherapeutic allopurinol group (n = 12). Cord lactate concentration did not differ, but S-100B was significantly lower in the therapeutic allopurinol group compared with the placebo and subtherapeutic allopurinol groups (P <.01). Fewer therapeutic allopurinol cord samples had measurable non-protein-bound iron concentrations compared with placebo (P <.01).CONCLUSIONS: Maternal allopurinol/oxypurinol crosses the placenta during fetal hypoxia. In fetuses/newborns with therapeutic allopurinol/ oxypurinol concentrations in cord blood, lower plasma levels of the brain injury marker protein S-100B were detected. A larger allopurinol trial in compromised fetuses at term seems warranted. The allopurinol dosage must be adjusted to achieve therapeutic fetal allopurinol/oxypurinol concentrations. Pediatrics 2009; 124: 350-357",

keywords = "neuroprotection, allopurinol, fetal hypoxia, protein S-100B, BIRTH ASPHYXIA, ISCHEMIC ENCEPHALOPATHY, PERINATAL ASPHYXIA, PROTEIN S-100, HYPOTHERMIA, OXYPURINOL, NEWBORNS, PLASMA, SERUM, TRIAL",

author = "H.L. Torrance and M.J.N.L. Benders and J.B. Derks and C.M.A. Rademaker and A.F. Bos and {van den Berg}, P. and M.A. Longini and G. Buonocore and M.E. Venegas and H. Baquero and G.H.A. Visser and {van Bel}, F.",

year = "2009",

month = jul,

doi = "10.1542/peds.2008-2228",

language = "English",

volume = "124",

pages = "350--357",

journal = "Pediatrics",

issn = "0031-4005",

publisher = "American Academy of Pediatrics",

number = "1",

}

TY - JOUR

T1 - Maternal Allopurinol During Fetal Hypoxia Lowers Cord Blood Levels of the Brain Injury Marker S-100B

AU - Torrance, H.L.

AU - Benders, M.J.N.L.

AU - Derks, J.B.

AU - Rademaker, C.M.A.

AU - Bos, A.F.

AU - van den Berg, P.

AU - Longini, M.A.

AU - Buonocore, G.

AU - Venegas, M.E.

AU - Baquero, H.

AU - Visser, G.H.A.

AU - van Bel, F.

PY - 2009/7

Y1 - 2009/7

N2 - BACKGROUND: Fetal hypoxia is an important determinant of neonatal encephalopathy caused by birth asphyxia, in which hypoxia-induced free radical formation plays an important role. HYPOTHESIS: Maternal treatment with allopurinol, will cross the placenta during fetal hypoxia (rimary outcome) and reduce S-100B and free radical formation (secondary outcome).METHODS: In a randomized, double-blind feasibility study, 53 pregnant women in labor ( 54 fetuses) with a gestational age of >36 weeks and fetal hypoxia, as indicated by abnormal/nonreassuring fetal heart rate tracing or fetal scalp pH ofRESULTS: Allopurinol and oxypurinol concentrations were within the therapeutic range in the mother (allopurinol >2 mg/L and/or oxypurinol > 4 mg/L) but not always in arterial cord blood. We therefore created 3 groups: a placebo (n = 27), therapeutic allopurinol (n = 15), and subtherapeutic allopurinol group (n = 12). Cord lactate concentration did not differ, but S-100B was significantly lower in the therapeutic allopurinol group compared with the placebo and subtherapeutic allopurinol groups (P <.01). Fewer therapeutic allopurinol cord samples had measurable non-protein-bound iron concentrations compared with placebo (P <.01).CONCLUSIONS: Maternal allopurinol/oxypurinol crosses the placenta during fetal hypoxia. In fetuses/newborns with therapeutic allopurinol/ oxypurinol concentrations in cord blood, lower plasma levels of the brain injury marker protein S-100B were detected. A larger allopurinol trial in compromised fetuses at term seems warranted. The allopurinol dosage must be adjusted to achieve therapeutic fetal allopurinol/oxypurinol concentrations. Pediatrics 2009; 124: 350-357

AB - BACKGROUND: Fetal hypoxia is an important determinant of neonatal encephalopathy caused by birth asphyxia, in which hypoxia-induced free radical formation plays an important role. HYPOTHESIS: Maternal treatment with allopurinol, will cross the placenta during fetal hypoxia (rimary outcome) and reduce S-100B and free radical formation (secondary outcome).METHODS: In a randomized, double-blind feasibility study, 53 pregnant women in labor ( 54 fetuses) with a gestational age of >36 weeks and fetal hypoxia, as indicated by abnormal/nonreassuring fetal heart rate tracing or fetal scalp pH ofRESULTS: Allopurinol and oxypurinol concentrations were within the therapeutic range in the mother (allopurinol >2 mg/L and/or oxypurinol > 4 mg/L) but not always in arterial cord blood. We therefore created 3 groups: a placebo (n = 27), therapeutic allopurinol (n = 15), and subtherapeutic allopurinol group (n = 12). Cord lactate concentration did not differ, but S-100B was significantly lower in the therapeutic allopurinol group compared with the placebo and subtherapeutic allopurinol groups (P <.01). Fewer therapeutic allopurinol cord samples had measurable non-protein-bound iron concentrations compared with placebo (P <.01).CONCLUSIONS: Maternal allopurinol/oxypurinol crosses the placenta during fetal hypoxia. In fetuses/newborns with therapeutic allopurinol/ oxypurinol concentrations in cord blood, lower plasma levels of the brain injury marker protein S-100B were detected. A larger allopurinol trial in compromised fetuses at term seems warranted. The allopurinol dosage must be adjusted to achieve therapeutic fetal allopurinol/oxypurinol concentrations. Pediatrics 2009; 124: 350-357

KW - neuroprotection

KW - allopurinol

KW - fetal hypoxia

KW - protein S-100B

KW - BIRTH ASPHYXIA

KW - ISCHEMIC ENCEPHALOPATHY

KW - PERINATAL ASPHYXIA

KW - PROTEIN S-100

KW - HYPOTHERMIA

KW - OXYPURINOL

KW - NEWBORNS

KW - PLASMA

KW - SERUM

KW - TRIAL

U2 - 10.1542/peds.2008-2228

DO - 10.1542/peds.2008-2228

M3 - Article

C2 - 19564319

SN - 0031-4005

VL - 124

SP - 350

EP - 357

JO - Pediatrics

JF - Pediatrics

IS - 1

ER -

Maternal Allopurinol During Fetal Hypoxia Lowers Cord Blood Levels of the Brain Injury Marker S-100B

Abstract

Keywords

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