[Show abstract][Hide abstract] ABSTRACT: What is the clinical value of anti-Müllerian hormone (AMH) for the prediction of high or low ovarian response in controlled ovarian stimulation for IVF using GnRH antagonist treatment?
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND
Thin endometrium on ultrasound in the course of ovarian hyperstimulation has been thought to be associated with poor success rates after IVF, even in the absence of prior intrauterine surgery or infection. To assess the clinical significance of endometrial thickness (EMT) for IVF outcome, we performed a systematic review and meta-analysis.METHODS
The electronic databases Pubmed, Cochrane and Embase were searched up to October 2013 for articles that studied the association between EMT and IVF outcome. The articles had to be written in the English or Dutch language. Studies were included if two-by-two tables for EMT and pregnancy rates could be constructed. Study quality was scored using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Summary receiver operating characteristic (sROC) curves were estimated to assess the accuracy of EMT in the prediction of pregnancy. In addition, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a Mantel-Haenszel random effect model expressing the association between EMT and pregnancy chances. Meta-regression was performed to determine if female age and number of oocytes at retrieval interacted in the estimated effect of EMT on IVF outcome.RESULTSA total of 1170 studies was retrieved by the search. The overall quality of the 22 studies included in the review and meta-analysis was moderate. The estimated sROC curve indicated a virtually absent discriminatory capacity of EMT in the prediction of pregnancy. A thin endometrium (≤7 mm) was observed in only 2.4% of the reported cases (260/10 724). In these cases a trend towards lower ongoing pregnancy and live birth rates for women with EMT ≤ 7 mm was observed [OR 0.38 (95% CI 0.09-1.5)]. The probability of clinical pregnancy for an EMT ≤ 7 mm was significantly lower compared with cases with EMT > 7 mm [23.3% versus 48.1%, OR 0.42 (95% CI 0.27-0.67)]. Positive and negative predictive values for the outcome of clinical pregnancy 77 and 48%, respectively. The relationship between the number of oocytes and female age on the one hand and pregnancy on the other hand was very weak making correction for these variables unfeasible.CONCLUSIONS
Current data indicate that EMT has a limited capacity to identify women who have a low chance to conceive after IVF. The frequently reported cut-off of 7 mm is related to a lower chance of pregnancy, but occurs infrequently. The use of EMT as a tool to decide on cycle cancellation, freezing of all embryos or refraining from further IVF treatment seems not to be justified based on the current meta-analysis. Further research is needed to investigate the real independent significance of EMT in IVF.
Human Reproduction Update 03/2014; · 9.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
To identify key pathological characteristics of placentas from pregnancies complicated by early intrauterine growth restriction, and to examine their relations with maternal hypertensive disease and umbilical artery Doppler waveform abnormalities.
Single-center retrospective cohort study of singleton pregnancies with abnormal umbilical artery Doppler flow patterns resulting in a live birth <34 weeks of a baby with a weight <10th percentile for gestational age. Umbilical artery end diastolic flow was classified as being either present or absent/reversed (AREDF). Data were stratified into intrauterine growth restriction with or without hypertensive disease and pathological characteristics were compared between these various conditions according to predefined scoring criteria.
Among 164 placentas studied, we found high rates of characteristic histopathological features that were associated with intrauterine growth restriction, including infarction (>5% in 42%), chronic villitis (21%), chronic chorioamnionitis (36%), membrane necrosis (20%), elevated nucleated red blood cells (89%), increased syncytial knotting (93%), increased villous maturation (98%), fetal thrombosis (32%) and distal villous hypoplasia (35%). Chronic inflammation of fetal membranes and syncytial knotting were more common in women with concomitant hypertensive disease as compared to women with normotensive IUGR (p <0.05). Placentas from women with umbilical artery AREDF were more likely to show increased numbers of nucleated red blood cells and distal villous hypoplasia (p <0.05).
Placentas of women with early IUGR show high rates of several histological aberrations. Further, concomitant maternal hypertension is associated with characteristic inflammatory changes and umbilical artery AREDF with signs of chronic hypoxia.
[Show abstract][Hide abstract] ABSTRACT: Free radical-induced reperfusion injury is a recognized cause of brain damage in the newborn after birth asphyxia. The xanthine oxidase inhibitor allopurinol reduces free radical synthesis and crosses the placenta easily. Therefore, allopurinol is a promising therapeutic candidate. This study tested the hypothesis that maternal treatment with allopurinol during fetal asphyxia limits ischemia-reperfusion (I/R) damage to the fetal brain in ovine pregnancy. The I/R challenge was induced by 5 repeated measured compressions of the umbilical cord, each lasting 10 minutes, in chronically instrumented fetal sheep at 0.8 of gestation. Relative to control fetal brains, the I/R challenge induced significant neuronal damage in the fetal hippocampal cornu ammonis zones 3 and 4. Maternal treatment with allopurinol during the I/R challenge restored the fetal neuronal damage toward control scores. Maternal treatment with allopurinol offers potential neuroprotection to the fetal brain in the clinical management of perinatal asphyxia.
[Show abstract][Hide abstract] ABSTRACT: Abstract Measurement of amniotic fluid (AF) lactate concentration in complicated pregnancies may provide information on the extent of fetal acidemia. However, normalisation for AF volume may be necessary by calculating the lactate:creatinine (L:C) ratio. We measured these AF parameters and compared them to arterial cord blood lactate in 28 term and 10 preterm pregnancies. Cord blood lactate was not correlated to AF lactate, but was correlated to the L:C ratio in the complete study population (R=0.54,p=0.001) and the subgroups. Correlation was strongest in a preterm IUGR subgroup (n=7,R=0.83,p=0.02). The L:C ratio is more accurate in estimating fetal lacticaemia than AF lactate.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 01/2013; · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime.
Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT.
The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines.
BMC Women's Health 09/2012; 12:29. · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI) treatment a large drop is present between embryo transfer and occurrence of pregnancy. The implantation rate per embryo transferred is only 30%. Studies have shown that minor intrauterine abnormalities can be found in 11-45% of infertile women with a normal transvaginal sonography or hysterosalpingography. Two randomised controlled trials have indicated that detection and treatment of these abnormalities by office hysteroscopy after two failed IVF cycles leads to a 9-13% increase in pregnancy rate. Therefore, screening of all infertile women for intracavitary pathology prior to the start of IVF/ICSI is increasingly advocated. In absence of a scientific basis for such a policy, this study will assess the effects and costs of screening for and treatment of unsuspected intrauterine abnormalities by routine office hysteroscopy, with or without saline infusion sonography (SIS), prior to a first IVF/ICSI cycle.
Multicenter randomised controlled trial in asymptomatic subfertile women, indicated for a first IVF/ICSI treatment cycle, with normal findings at transvaginal sonography. Women with recurrent miscarriages, prior hysteroscopy treatment and intermenstrual blood loss will not be included. Participants will be randomised for a routine fertility work-up with additional (SIS and) hysteroscopy with on-the-spot-treatment of predefined intrauterine abnormalities versus the regular fertility work-up without additional diagnostic tests. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months of IVF/ICSI treatment after randomisation. Secondary study outcome parameters are the cumulative implantation rate; cumulative miscarriage rate; patient preference and patient tolerance of a SIS and hysteroscopy procedure. All data will be analysed according to the intention-to-treat principle, using univariate and multivariate logistic regression and cox regression. Cost-effectiveness analysis will be performed to evaluate the costs of the additional tests as routine procedure. In total 700 patients will be included in this study.
The results of this study will help to clarify the significance of hysteroscopy prior to IVF treatment.
BMC Women's Health 08/2012; 12:22. · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In complicated labor, neonatal outcome may depend not only on the extent of fetal asphyxia and acidosis but also on the effects on the fetal cardiovascular system of reactive oxygen species (ROS) generated during the ischemia-reperfusion (I/R) associated with repeated compressions of the umbilical cord. This study tested the hypothesis that maternal treatment with clinical doses of the antioxidant allopurinol in the setting of fetal asphyxia would reduce oxidative stress in the fetal cardiovascular system. The hypothesis was tested in chronically instrumented fetal sheep in late gestation by investigating the effects of maternal treatment with therapeutic doses of allopurinol or vehicle on the fetal cardiovascular system during and after episodes of I/R. The latter were produced by repeated, measured compressions of the umbilical cord. The data show that maternal treatment with allopurinol helped maintain umbilical blood flow and it reduced fetal cardiac oxidative stress after I/R of the type associated with clinically relevant acidemia and repetitive fetal heart rate decelerations. The data support the hypothesis tested and suggest that maternal treatment with allopurinol may offer plausible clinical intervention in the management of perinatal asphyxia in complicated labor.
Pediatric Research 11/2010; 68(5):374-80. · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the relative importance of antenatal and perinatal variables on short- and long-term outcome of preterm growth restricted fetuses with umbilical artery (UA) Doppler abnormalities.
This was a cohort study of 180 neonates with birth weight < 10(th) percentile, gestational age at delivery < 34 weeks and abnormal Doppler ultrasound examination of the UA. Various antenatal and perinatal variables were studied in relation to short- and long-term outcome.
Neonatal and overall mortality (up to 2 years of age) were predicted by low gestational age at delivery. Neonatal mortality was additionally predicted by absent or reversed UA end-diastolic flow, while the presence of severe neonatal complications and placental villitis were additional predictors of both infant (between 28 days and 1 year of postnatal life) and overall mortality. Placental villitis was found to be the only predictor of necrotizing enterocolitis. Low gestational age at delivery, male sex, abnormal cardiotocography, absent or reversed UA end-diastolic flow and the HELLP syndrome predicted respiratory distress syndrome. Abnormal neurodevelopmental outcome at 2 years was predicted by low birth weight (< 2.3(rd) percentile), fetal acidosis (UA pH < 7.00), and placental villitis.
Less advanced gestation at delivery remains an important predictor of short-term outcome in growth-restricted fetuses. In addition, the presence of placental villitis may aid neonatologists in the early identification of infants at increased risk of necrotizing enterocolitis, death and abnormal neurodevelopment at 2 years of age. Abnormal neurodevelopment was related to low weight and acidosis at birth, indicating that the severity of malnutrition and fetal acidosis affect long-term outcome.
Ultrasound in Obstetrics and Gynecology 03/2010; 36(2):171-7. · 3.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy.
The proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia.Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20).Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated.We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test2-sided). Analysis will be by intention to treat and it allows for one interim analysis.
In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia.
Clinical Trials, protocol registration system: NCT00189007.
BMC Pregnancy and Childbirth 02/2010; 10:8. · 2.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are no randomized studies on the effect of antenatal corticosteroids in preterm intrauterine growth restricted (IUGR) fetuses. Fetal lung maturation has been postulated to be enhanced in these fetuses, which may result in little benefit of steroid treatment. Furthermore, corticosteroid treatment may be detrimental, as has been shown in IUGR animal models. The objective of this study was to review the available literature on antenatal steroid treatment of the IUGR fetus. All available reports on antenatal steroid treatment of IUGR and small for gestational age (SGA) fetuses published prior to October 2007 were included in this review. IUGR fetuses are a subgroup of SGA fetuses that are small due to placental insufficiency, which is reflected in abnormal Doppler examination of the umbilical artery. The main outcome measures were respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and neonatal mortality. No difference in neonatal mortality was seen in any of the reviewed studies and RDS, IVH, and NEC incidence did not differ between treated and untreated IUGR fetuses. In SGA fetuses, results on RDS incidence and intracranial outcome were inconclusive. Antenatal steroid treatment does not seem to have an effect on neonatal mortality or morbidity in IUGR fetuses. In SGA fetuses, it remains unclear if antenatal steroid treatment is beneficial due to heterogeneous populations and treatment regimes. A randomized controlled trial should be performed to confirm prior results and answer further questions regarding antenatal steroid treatment of these fetuses.
[Show abstract][Hide abstract] ABSTRACT: Fetal hypoxia is an important determinant of neonatal encephalopathy caused by birth asphyxia, in which hypoxia-induced free radical formation plays an important role.
Maternal treatment with allopurinol, will cross the placenta during fetal hypoxia (primary outcome) and reduce S-100B and free radical formation (secondary outcome).
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 <7.20, received 500 mg of allopurinol or placebo intravenously. Severity of fetal hypoxia, brain damage and free radical formation were assessed by arterial cord blood lactate, S-100B and non-protein-bound-iron concentrations, respectively. At birth, maternal and cord blood concentrations of allopurinol and its active metabolite oxypurinol were determined.
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).
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.
[Show abstract][Hide abstract] 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 <7.20, received 500 mg of allopurinol or placebo intravenously. Severity of fetal hypoxia, brain damage and free radical formation were assessed by arterial cord blood lactate, S-100B and non-protein-bound-iron concentrations, respectively. At birth, maternal and cord blood concentrations of allopurinol and its active metabolite oxypurinol were determined. 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
[Show abstract][Hide abstract] ABSTRACT: Clinical studies suggest that respiratory outcome of infants born preterm may be influenced by placental insufficiency and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. If so, one could expect to see differences in lung maturation indices (lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC)) in the amniotic fluid. The present study investigates lung maturation indices of preterm small for gestational age (SGA) fetuses with or without abnormal Doppler ultrasound examination and with or without maternal hypertension/HELLP syndrome.
Retrospective cohort study of 76 neonates born in our center between 1997 and 2003 with gestational age (GA) <34 weeks, birth weight <p10 for GA and available results from amniocentesis. All analyses were corrected for potential confounders.
The L/S ratio was significantly higher in the abnormal Doppler group as compared to the normal Doppler group (p=0.02). The L/S ratio was significantly lower in hypertensive pregnancies as compared to normotensive pregnancies (p=0.02). Subdivision of the maternal hypertension group showed a significantly lower L/S ratio in the HELLP syndrome group as compared to the normotension group (p=0.04).
The L/S ratio of SGA fetuses is significantly higher in cases with presumed placental insufficiency and significantly lower when pregnancies are complicated by HELLP syndrome. These observations are in line with the hypothesis that placental insufficiency accelerates lung maturation and with recent reports of poorer respiratory outcome in infants from mothers with HELLP syndrome.
Early Human Development 07/2008; 84(7):465-9. · 2.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Respiratory distress syndrome (RDS) incidence is increased in infants of preeclamptic mothers with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. RDS and HELLP syndrome have been associated with oxidative stress and inflammatory processes.
We hypothesize that end-tidal carbon monoxide corrected for inhaled CO (ETCOc), malondialdehyde (MDA) (markers of oxidative stress) and proinflammatory cytokine (IL-6, IL-8) production are higher in infants of preeclamptic mothers with HELLP syndrome than in those of preeclamptic mothers without HELLP syndrome.
Prospective study of 36 infants of preeclamptic mothers (GA <32 weeks) admitted to the Neonatal Intensive Care Unit. ETCOc was measured at 0-12, 48-72 and 168 h postnatally using the CO-Stattrade mark End-Tidal Breath Analyzer. Simultaneously, blood was sampled for MDA, IL-8 and IL-6.
At 0-12 h, ETCOc, MDA and IL-8 values (median[range]) were significantly higher in HELLP infants than in infants from preeclamptic mothers without HELLP (ETCOc 2.2 [1.5-3.9] vs. 1.8 [0.5-2.9] ppm; MDA 2.3 [1.3-4.1] vs. 1.5 [0.4-3.1] mumol/l; IL-8 145 [24-606] vs. 62 [26-397] pg/ml; all p <0.05). MDA remained significantly higher during the first 168 h of life (2.3 [0.8-5.8] vs. 1.1 [0.8-3.7] mumol/l, p = 0.02).
Oxidative stress and proinflammatory cytokine levels are increased in infants of preeclamptic mothers with HELLP syndrome. These processes may cause inactivation of surfactant explaining the increased RDS incidence in these infants.
[Show abstract][Hide abstract] ABSTRACT: To study respiratory outcome in preterm small for gestational age (SGA) fetuses with or without signs of intrauterine growth restriction due to placental insufficiency, and with or without maternal hypertension.
This was a retrospective study of 187 neonates with birth weight <10(th) percentile and gestational age <34 weeks. Results from umbilical artery Doppler velocimetry were used to identify the abnormal Doppler subgroup.
No significant difference in respiratory outcome between SGA fetuses with normal (SGA-N) or abnormal (SGA-A) umbilical artery Doppler examination was found. Within the SGA-A group, the respiratory distress syndrome (RDS) incidence (OR 5.6, 95% CI 1.7-18.3), RDS grade (OR 6.7, 95% CI 1.2-38.5), and need for surfactant (OR 5.3, 95% CI 1.1-24.4) were higher in infants of women with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome as compared to those of normotensive mothers.
Lung maturation is not accelerated with placental insufficiency. SGA-A fetuses of mothers with HELLP syndrome have a significantly poorer respiratory outcome than those with healthy mothers. Possibly, fetuses of mothers with HELLP syndrome are subjected to 'oxidative stress' causing lung damage rather than lung maturation.
Journal of Maternal-Fetal and Neonatal Medicine 08/2007; 20(8):613-21. · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate whether postnatal allopurinol would reduce free radical induced reperfusion/reoxygenation injury of the brain in severely asphyxiated neonates.
In an interim analysis of a randomised, double blind, placebo controlled study, 32 severely asphyxiated infants were given allopurinol or a vehicle within four hours of birth.
The analysis showed an unaltered (high) mortality and morbidity in the infants treated with allopurinol.
Allopurinol treatment started postnatally was too late to reduce the early reperfusion induced free radical surge. Allopurinol administration to the fetus with (imminent) hypoxia via the mother during labour may be more effective in reducing free radical induced post-asphyxial brain damage.
Archives of Disease in Childhood - Fetal and Neonatal Edition 06/2006; 91(3):F163-5. · 3.45 Impact Factor