Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 283 - 294 |
| Number of pages | 12 |
| Journal | Journal of Pineal Research |
| Volume | 56 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2014 |
Cite this
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Antenatal antioxidant treatment with melatonin to decrease newborn neurodevelopmental deficits and brain injury caused by fetal growth restriction. / Miller, Suzanne Lee; Yawno, Tamara; Alers, Nicole Odile; Zakhem, Margie Esmeralda; Supramaniam, Veena Gayathri; van Zyl, Niel; Sabaretnam, Tharani; Loose, Jan Michelle; Drummond, Grant Raymond; Walker, David William; Jenkin, Graham; Wallace, Euan Morrison.
In: Journal of Pineal Research, Vol. 56, No. 3, 2014, p. 283 - 294.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Antenatal antioxidant treatment with melatonin to decrease newborn neurodevelopmental deficits and brain injury caused by fetal growth restriction
AU - Miller, Suzanne Lee
AU - Yawno, Tamara
AU - Alers, Nicole Odile
AU - Zakhem, Margie Esmeralda
AU - Supramaniam, Veena Gayathri
AU - van Zyl, Niel
AU - Sabaretnam, Tharani
AU - Loose, Jan Michelle
AU - Drummond, Grant Raymond
AU - Walker, David William
AU - Jenkin, Graham
AU - Wallace, Euan Morrison
PY - 2014
Y1 - 2014
N2 - Fetal intrauterine growth restriction (IUGR) is a serious pregnancy complication associated with increased rates of perinatal morbidity and mortality, and ultimately with long-term neurodevelopmental impairments. No intervention currently exists that can improve the structure and function of the IUGR brain before birth. Here, we investigated whether maternal antenatal melatonin administration reduced brain injury in ovine IUGR. IUGR was induced in pregnant sheep at 0.7 gestation and a subset of ewes received melatonin via intravenous infusion until term. IUGR, IUGR + melatonin (IUGR + MLT) and control lambs were born naturally, neonatal behavioral assessment was used to examine neurological function and at 24 hr after birth the brain was collected for the examination of neuropathology. Compared to control lambs, IUGR lambs took significantly longer to achieve normal neonatal lamb behaviors, such as standing and suckling. IUGR brains showed widespread cellular and axonal lipid peroxidation, and white matter hypomyelination and axonal damage. Maternal melatonin administration ameliorated oxidative stress, normalized myelination and rescued axonopathy within IUGR lamb brains, and IUGR + MLT lambs demonstrated significant functional improvements including a reduced time taken to attach to and suckle at the udder after birth. Based on these observations, we began a pilot clinical trial of oral melatonin administration to women with an IUGR fetus. Maternal melatonin was not associated with adverse maternal or fetal effects and it significantly reduced oxidative stress, as evidenced by reduced malondialdehyde levels, in the IUGR + MLT placenta compared to IUGR alone. Melatonin should be considered for antenatal neuroprotective therapy in human IUGR.
AB - Fetal intrauterine growth restriction (IUGR) is a serious pregnancy complication associated with increased rates of perinatal morbidity and mortality, and ultimately with long-term neurodevelopmental impairments. No intervention currently exists that can improve the structure and function of the IUGR brain before birth. Here, we investigated whether maternal antenatal melatonin administration reduced brain injury in ovine IUGR. IUGR was induced in pregnant sheep at 0.7 gestation and a subset of ewes received melatonin via intravenous infusion until term. IUGR, IUGR + melatonin (IUGR + MLT) and control lambs were born naturally, neonatal behavioral assessment was used to examine neurological function and at 24 hr after birth the brain was collected for the examination of neuropathology. Compared to control lambs, IUGR lambs took significantly longer to achieve normal neonatal lamb behaviors, such as standing and suckling. IUGR brains showed widespread cellular and axonal lipid peroxidation, and white matter hypomyelination and axonal damage. Maternal melatonin administration ameliorated oxidative stress, normalized myelination and rescued axonopathy within IUGR lamb brains, and IUGR + MLT lambs demonstrated significant functional improvements including a reduced time taken to attach to and suckle at the udder after birth. Based on these observations, we began a pilot clinical trial of oral melatonin administration to women with an IUGR fetus. Maternal melatonin was not associated with adverse maternal or fetal effects and it significantly reduced oxidative stress, as evidenced by reduced malondialdehyde levels, in the IUGR + MLT placenta compared to IUGR alone. Melatonin should be considered for antenatal neuroprotective therapy in human IUGR.
UR - http://onlinelibrary.wiley.com/doi/10.1111/jpi.12121/pdf
U2 - 10.1111/jpi.12121
DO - 10.1111/jpi.12121
M3 - Article
VL - 56
SP - 283
EP - 294
JO - Journal of Pineal Research
JF - Journal of Pineal Research
SN - 0742-3098
IS - 3
ER -