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

Abstract

Several investigators have hypothesized that outpatient preinduction cervical ripening with nitric oxide donors such as isosorbide mononitrate (IMN) would reduce the elapsed time from hospital admission to delivery and improve women's experience of induction of labor. This double-blind randomized placebo-controlled trial investigated whether vaginal self-administration at home by woman at term would improve the process of induction of labor. The study subjects were 350 nulliparous singleton women with cephalic presentation at Ն37 weeks' gestation, requiring cervical ripening before induction of labor. The participants self-administered IMN (n ϭ 177) or placebo (n ϭ 173) vaginally at home without fetal monitoring at 48, 32, and 16 hours before the scheduled time of admission for induction of labor. The primary study outcome measures were the elapsed time interval from hospital admission to delivery and the women's experience of home treatment for cervical ripening. Maternal satisfaction was determined with a questionnaire, using a 10 point scale with 1 ϭ extremely good and 10 ϭ not at all good.There was no statistically significant difference between the 2 study groups in the admission to delivery interval; the mean difference was 1.59 hours, with a 95% confidence interval (CI) of Ϫ5.08 to 1.89, P ϭ 0.37. Compared to placebo, however, IMN was more effective in inducing a mean change in modified Bishop score from recruitment to hospital admission (mean difference: 0.65 [95% CI, 0.14-1.17, P ϭ 0.013]). With regard to maternal satisfaction, the overall experience of home treatment was positive in both groups. Women in the placebo group reported it to be marginally more positive than those in the IMN group (placebo: 3.23 vs. IMN: 3.84; the mean difference was 0.61, with a 95% CI of 0.02-1.21, P ϭ 0.043). No difference between the 2 groups was reported in either pain or anxiety levels or in the willingness to have the treatment in a subsequent pregnancy.These data show that administration of IMN at home is effective in ripening the cervix but does not shorten the admission to delivery interval or improve maternal satisfaction. The investigators conclude from these findings that IMN in this setting has limited clinical value. EDITORIAL COMMENT(The appeal of the nitric oxide donor isosorbide mononitate (IMN) is its potential to induce cervical ripening without precipitating uterine contractions and thereby obviate the need for fetal heart rate monitoring, and allow cervical ripening to be conducted on an outpatient ba-OBSTETRICS Volume 64, Number 11 OBSTETRICAL AND GYNECOLOGICAL SURVEY ABSTRACT This investigation was conducted as part of the Mother-Infant Rapid Intervention at Delivery (MIRIAD) study, a prospective, multicenter trial assessing routine rapid human immunodeficiency virus (HIV) screening of pregnant women in inpatient and outpatient settings. This study compared rapid HIV testing with conventional HIV testing in outpatient obstetric settings among a population of pregnant women who presented late in care wi...

Antenatal Allopurinol Reduces Hippocampal Brain Damage After Acute Birth Asphyxia in Late Gestation Fetal Sheep

“…Only 5 other studies in the literature have reported on antenatally administered allopurinol, but none of them have described any effects on the histology of the brain. 18,19,22,23,43 In the present study, therapeutic ranges of allopurinol and its metabolite oxypurinol have shown to be attainable after antenatal maternal treatment with allopurinol, while no adverse side effects were observed. These findings are in line with previous studies in both animals and humans.…”

“…These findings are in line with previous studies in both animals and humans. 18,22,23,43 Masaoka et al were the first to investigate antenatally administered allopurinol during intermittent umbilical cord occlusion in fetal sheep and described a significantly reduced production of superoxide in the allopurinol-treated animals. 22 This indicates a direct effect of allopurinol in preventing the production of free radicals, in scavenging free radicals once formed, or both.…”

“…[15][16][17][18][19][20][21] Collectively, these properties make allopurinol a strong potential candidate for cerebral neuroprotection arising from I/R damage.…”

Recent Information on the Pathogenesis and Treatment of Hypoxic-Ischemic Brain Lesions in Newborns

“…Голландские исследователи объясняют неоднозначность первых результатов тем, что введение аллопуринола постнатально -слишком поздно для полу-чения клинически значимых антиоксидантных эффектов, поэтому в настоящее время они проводят клиническое исследование, где оцениваются эффекты антенаталь-ного введения препарата [151,152]. Проведенное чуть ранее другими нидерландскими авторами исследование по применению аллопуринола беременными при внутри-утробной гипоксии показало достоверно более низкие концентрации белка S100B -нейромаркера ГИП моз-га -в пуповинной крови новорожденных от матерей, принимавших аллопуринол; клинические исходы пока не оценивались [153]. Еще одно плацебоконтролируемое исследование с участием 60 новорожденных с асфикси-ей было проведено в Турции: аллопуринол назначался новорожденным с рождения в течение 3 дней [154].…”

Hydrogen is neuroprotective and preserves neurovascular reactivity following asphyxia in newborn pigs

“…The authors speculated that drug administration was too late to successfully target the immediate ROS surge after resuscitation. In fact, in a more recent study, the same research group has found that maternal treatment of in utero asphyxiated infants with allopurinol reduced the concentration of the brain injury marker S-100B in infants with therapeutic allopurinol levels [159]. It has been also shown that 95% of cord blood samples had target allopurinol concentrations at the moment of delivery [160].…”