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Second stage of labor is considered to be associated with an increased risk of intrapartum fetal hypoxic injury. This is due to a combination of several risk factors such as -the increased frequency, strength and duration of uterine contractions due to higher number and affinity of myometrial oxytocin receptors; -the Ferguson's reflex which leads to a reflex release of endogenous oxytocin in response of the distension of the cervix by descending fetal head in late stages of labor; maternal expulsive efforts with the Valsalva manoeuvre that may reduce maternal oxygenation, as well as reduce the venous return and maternal cardiac output due to increased intrathoracic pressure, winch may lead to reduced placental oxygenation; - and increased fetal intracranial pressure due to head compression leading to a potential decrease in fetal cerebral oxygenation. In addition, the umbilical cord often forms one or more loops around the fetal neck, which may get tightened as the head descends leading to an acute and intermittent cessation of fetal oxygenation. Operative interventions during the second stage of labor such as vacuum, forceps or emergency caesarean section may increase the risk of maternal and fetal trauma. Therefore, an accurate interpretation of the fetal heart rate changes by applying the knowledge of fetal pathophysiology is essential: to timely recognise the onset of fetal decompensation preventing intrapartum hypoxic-ischaemic brain injuries; to avoid erroneous monitoring of the maternal heart rate as fetal heart rate; and to abstain from unnecessary operative interventions due to misinterpretation of the significance of the observed fetal heart rate changes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EC, SF, SP and TG are members of the Editorial Board of International Consensus Guidelines on Physiological Interpretation of CTG. Authors have no conflicts of interests relating this invited review., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study was aimed to assess the effect of intermittent fetal heart rate (FHR) monitoring using Moyo Doppler compared with fetoscope in hospitals of Ethiopia, 2023., Background: To facilitate more prompt identification of a hypoxic fetus, Laerdal Global Health has recently introduced the Moyo FHR monitor. Nevertheless, there exists limited knowledge regarding its efficacy derived from multicenter contextual trials conducted in resource-constrained environments, specifically in Ethiopia., Methods: This randomized trial (PACTR202305607000259) enrolled 2518 low-risk laboring women in the study during the study period, using a simple randomization technique from September 28, 2022, to February 28, 2023. A total of 1259 and 1259 were followed by Moyo and Pinard fetoscope, respectively. A P-value of less than .05 was considered significant., Results: The abnormal FHR was detected among 60 women (5.1%) and 30 women (2.4%) (P = .001) in the Moyo and Pinard fetoscope arms, respectively., Conclusion: The Moyo FHR monitor has demonstrated efficacy in detecting abnormal FHRs when compared with the Pinard fetoscope., Implications for Practice and Research: It is recommended that healthcare systems in low-resource settings consider implementing the Moyo device for FHR monitoring., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Determination of lactate in fetal scalp blood (FBS) during labour has been recognised since the 1970s. The internationally accepted cutoff of >4.8 mmol/l indicating fetal acidosis is exclusive for the point-of-care device (POC) LactatePro™, which is no longer in production. The aim of this study was to establish a new cutoff for scalp lactate based on neonatal outcomes with the use of the StatstripLactate ® /StatstripXpress ® Lactate system, the only POC designed for hospital use., Design: Observational study., Setting: January 2016 to March 2020 labouring women with indication for FBS were prospectively included from seven Swedish and one Australian delivery unit., Population: Inclusion criteria: singleton pregnancy, vertex presentation, ≥35 +0  weeks of gestation., Method: Based on the optimal correlation between FBS lactate and cord pH/lactate, only cases with ≤25 minutes from FBS to delivery were included in the final calculations., Main Outcome Measures: Metabolic acidosis in cord blood defined as pH <7.05 plus BD ecf >10 mmol/l and/or lactate >10 mmol/l., Results: A total of 3334 women were enrolled of whom 799 were delivered within 25 minutes. The areas under the receiver operating characteristics curves (AUC) and corresponding optimal cutoff values were as follows; metabolic acidosis AUC 0.87 (95% CI 0.77-0.97), cutoff 5.7 mmol/l; pH <7.0 AUC 0.83 (95% CI 0.68-0.97), cutoff 4.6 mmol/l; pH <7.05 plus BD ecf ≥12 mmol/l AUC 0.97 (95% CI 0.92-1), cutoff 5.8 mmol/l; Apgar score <7 at 5 minutes AUC 0.74 (95% CI 0.63-0.86), cutoff 5.2 mmol/l; and pH <7.10 plus composite neonatal outcome AUC 0.76 (95% CI 0.67-0.85), cutoff 4.8 mmol/l., Conclusion: A scalp lactate level <5.2 mmol/l using the StatstripLactate ® /StatstripXpress ® system will safely rule out fetal metabolic acidosis., Tweetable Abstract: Scalp blood lactate <5.2 mmol/l using the StatstripLactate ® /StatstripXpress system has an excellent ability to rule out fetal acidosis., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Importance: Supplemental oxygen is commonly administered to pregnant women at the time of delivery to prevent fetal hypoxia and acidemia. There is mixed evidence on the utility of this practice., Objective: To compare the association of peripartum maternal oxygen administration with room air on umbilical artery (UA) gas measures and neonatal outcomes., Data Sources: Ovid MEDLINE, Embase, Scopus, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched from February 18 to April 3, 2020. Search terms included labor or obstetric delivery and oxygen therapy and fetal blood or blood gas or acid-base imbalance., Study Selection: Studies were included if they were randomized clinical trials comparing oxygen with room air at the time of scheduled cesarean delivery or labor in patients with singleton, nonanomalous pregnancies. Studies that did not collect paired umbilical cord gas samples or did not report either UA pH or UA Pao2 results were excluded., Data Extraction and Synthesis: Data were extracted by 2 independent reviewers. The analysis was stratified by the presence or absence of labor at the time of randomization. Data were pooled using random-effects models., Main Outcomes and Measures: The primary outcome for this review was UA pH. Secondary outcomes included UA pH less than 7.2, UA Pao2, UA base excess, 1- and 5-minute Apgar scores, and neonatal intensive care unit admission., Results: The meta-analysis included 16 randomized clinical trials (n = 1078 oxygen group and n = 974 room air group). There was significant heterogeneity among the studies (I2 = 49.88%; P = .03). Overall, oxygen administration was associated with no significant difference in UA pH (weighted mean difference, 0.00; 95% CI, -0.01 to 0.01). Oxygen use was associated with an increase in UA Pao2 (weighted mean difference, 2.57 mm Hg; 95% CI, 0.80-4.34 mm Hg) but no significant difference in UA base excess, UA pH less than 7.2, Apgar scores, or neonatal intensive care unit admissions. Umbilical artery pH values remained similar between groups after accounting for the risk of bias, type of oxygen delivery device, and fraction of inspired oxygen. After stratifying by the presence or absence of labor, oxygen administration in women undergoing scheduled cesarean delivery was associated with increased UA Pao2 (weighted mean difference, 2.12 mm Hg; 95% CI, 0.09-4.15 mm Hg) and a reduction in the incidence of UA pH less than 7.2 (relative risk, 0.63; 95% CI, 0.43-0.90), but these changes were not noted among those in labor (Pao2: weighted mean difference, 3.60 mm Hg; 95% CI, -0.30 to 7.49 mm Hg; UA pH<7.2: relative risk, 1.34; 95% CI, 0.58-3.11)., Conclusions and Relevance: This systematic review and meta-analysis suggests that studies to date showed no association between maternal oxygen and a clinically relevant improvement in UA pH or other neonatal outcomes.

Gestational diabetes mellitus (GDM) is a major pregnancy-related disorder with an increasing prevalence worldwide. GDM is associated with altered placental vascular functions and has severe consequences for fetal growth. There is no commonly accepted medication for GDM due to safety considerations. Actions of the currently limited therapeutic options focus exclusively on lowering the blood glucose level without paying attention to the altered placental vascular reactivity and remodelling. We used the fat-sucrose diet/streptozotocin (FSD/STZ) rat model of GDM to explore the efficacy of cinnamaldehyde (Ci; 20 mg/kg/day), a promising antidiabetic agent for GDM, and glyburide/metformin-HCl (Gly/Met; 0.6 + 100 mg/kg/day), as a reference drug for treatment of GDM, on the placenta structure and function at term pregnancy after their oral intake one week before mating onward. Through genome-wide transcriptome, biochemical, metabolome, metal analysis and histopathology we obtained an integrated understanding of their effects. GDM resulted in maternal and fetal hyperglycemia, fetal hyperinsulinemia and placental dysfunction with subsequent fetal anemia, hepatic iron deficiency and high serum erythropoietin level, reflecting fetal hypoxia. Differentially-regulated genes were overrepresented for pathways of angiogenesis, metabolic transporters and oxidative stress. Despite Ci and Gly/Met effectively alleviated the maternal and fetal glycemia, only Ci offered substantial protection from GDM-associated placental vasculopathy and prevented the fetal hypoxia. This was explained by Ci's impact on the molecular regulation of placental angiogenesis, metabolic activity and redox signaling. In conclusion, Ci provides a dual impact for the treatment of GDM at both maternal and fetal levels through its antidiabetic effect and the direct placental vasoprotective action. Lack of Gly/Met effectiveness to restore it's impaired functionality demonstrates the vital role of the placenta in developing efficient medications for GDM., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Intrapartum fetal heart rate (FHR) decelerations may represent interrupted oxygen transfer to the fetus. In many cases, these interruptions are transient and do not result in progressive fetal acidemia with risk for asphyxia and neurological compromise. When significant FHR decelerations are present, reversible causes of reduced fetal oxygen delivery should be considered and corrective measures should be undertaken to optimize oxygenation. In this review, we describe potential intrapartum causes of reduced fetal oxygen delivery and the efficacy of common interventions for an abnormal FHR tracing.

Fetal heart tracings (FHTs) are useful as a window into the oxygenation status of the fetal brain. Patterns in the FHT reflect the oxygen status of the fetal brain. Fetal adaptive response to progressive hypoxemia and acidosis are detectable and produce recognizable patterns in the fetal heart rate. The basic physiology and adaptive responses that regulate the fetal heart rate and physiological fetal adaptations to stress as reflected in the FHTs are described. Mechanisms of oxygen delivery to the fetus including ways in which those mechanisms can be disrupted are reviewed.

Use of intrapartum fetal heart rate (FHR) monitoring has had limited success in preventing hypoxic injury to neonates. One of the most common limitations of FHR interpretation is the failure to consider chronic and acute clinical factors that may increase the risk of evolving acidemia. This manuscript reviews common clinical factors that may affect the FHR and should be considered when determining the need for early intervention based on changes in the FHR.

The fetal heart rate can be used to assess the current metabolic state of the fetus and predict the risk of the evolution of metabolic acidemia through the course of labor. In this chapter, we will present the pathophysiology of the development of fetal acidemia and provide an organized approach to identifying the risk of worsening acidemia using changes noted in the fetal heart rate pattern to allow for interventions that might alter this course.

Introduction: Studies indicate an association between errors in cardiotocography (CTG) management and hypoxic brain injuries among newborns. Continuing professional education is recommended. We aimed to examine whether the implementation of a national interprofessional CTG education program in Denmark was associated with a decrease in risk of fetal hypoxia measured by umbilical cord pH < 7.00, 5-minute Apgar score <7 or neonatal therapeutic hypothermia. As a secondary aim, we assessed whether the educational intervention was associated with an increase in operative deliveries., Material and Methods: We conducted a historical cohort study from 2009 to 2015 including all intended vaginal deliveries with liveborn singletons in cephalic presentation and gestational age ≥37 weeks. Data were retrieved from the Medical Birth Register and the National Patient Register. The study period was divided in three: pre-implementation (2009-2012), implementation (2013) and post-implementation (2014-2015). Using logistic regression we estimated odds ratios (OR) of fetal hypoxia outcomes using the pre-implementation period as reference. Analyses were adjusted for potential maternal, neonatal and delivery-associated confounders. Missing data were accounted for by multiple imputation., Results: In all, 331 282 deliveries were included. Overall risks of pH < 7.00, Apgar score <7 and therapeutic hypothermia were respectively 0.45%, 0.58% and 0.06%. Adjusted OR in the post-implementation period were 1.12 (95% confidence interval [CI] 1.00-1.26), 0.99 (95% CI 0.90-1.10) and 1.34 (95% CI 0.99-1.82) for the three outcomes, respectively. The pH missingness equaled 12.4%. Odds of emergency cesarean section was unaltered, whereas the odds of assisted vaginal delivery decreased by 14% (0.86, 95% CI 0.84-0.89)., Conclusions: Healthcare professionals are considered the weakest link of CTG technology. We did not find that increasing healthcare professionals' CTG interpretation skills affected the risk of fetal hypoxia. Missing data for pH values were substantial and represent a limitation of the study. We cannot with certainty rule out that missingness masked a true effect of the intervention. Our study indicates that assisted vaginal deliveries can be decreased without an increased risk of fetal hypoxia. Dilution of effect in a complex clinical setting, rare outcomes, insufficient intervention and a possible overestimation of the impact of errors in CTG management might explain the lack of effect., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To investigate the performance of screening for adverse perinatal outcome by the cerebroplacental ratio (CPR) measured within 24 h prior to induction of labor., Methods: This was a prospective observational study of 1902 singleton pregnancies undergoing induction of labor at ≥ 37 weeks' gestation. Doppler ultrasound was used to measure the pulsatility index (PI) in the umbilical artery (UA) and fetal middle cerebral artery (MCA) within 24 h before induction of labor. The measured UA-PI and MCA-PI and their ratio were converted to multiples of the median after adjustment for gestational age. Univariable and multivariable logistic regression analysis was used to determine whether CPR improved the prediction of adverse perinatal outcome provided by maternal characteristics, medical history and obstetric factors. The detection rate (DR) and false-positive rate (FPR) of screening by CPR were estimated for Cesarean section for presumed fetal distress and adverse neonatal outcome, which included umbilical arterial or venous cord blood pH ≤ 7 and ≤ 7.1, respectively, 5-min Apgar score < 7, admission to the neonatal intensive care unit for > 24 h or hypoxic ischemic encephalopathy., Results: A combination of maternal and pregnancy characteristics, including age, weight, racial origin, previous obstetric history, pre-eclampsia, gestational age at delivery and amniotic fluid volume, identified 39% of pregnancies requiring Cesarean section for fetal distress at a FPR of 10%; addition of CPR did not improve the performance of screening. In screening for adverse neonatal outcome by a combination of parity and CPR, the DR was 17% at a FPR of 10%., Conclusion: Low CPR, measured within 24 h prior to induction of labor, is associated with increased risk of Cesarean section for fetal distress and adverse neonatal outcome, but the performance of CPR for such surrogate measures of fetal hypoxic morbidity is poor. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Introduction: Traditional validation of umbilical cord blood samples with positive veno-arterial ΔpH and arterio-venous ΔpCO 2 values confirms the source of samples, whereas negative Δvalues represent mix-up of samples. To investigate whether this is true, the distributions of V-A ΔpO 2 and A-V Δlactate were also explored and related to clinical characteristics. In addition, different cord blood sampling techniques were evaluated., Material and Methods: Register study with cord blood acid-base and clinical data from 27 233 newborns. Clinical characteristics were related to positive, zero and negative Δvalues. Blood samplings from unclamped and double-clamped cords were compared. A two-sided P < 0.05 was considered significant., Results: ΔpH and ΔpCO 2 values distributed into positive, around zero, and negative sub-populations, with significant differences in pH and clinical characteristics between sub-populations. No such sub-populations were distinguished for ΔpO 2 and Δlactate. The 2.5th and 5th ΔpH percentiles were 0.013 and 0.022, respectively, and for ΔpCO 2 0.30 and 0.53 kPa. Applying 5th percentile criteria resulted in 3.5% of "approved" cases showing a ΔpO 2  ≤ 0. Puncture and sampling of the unclamped cord resulted in significantly better sample quality., Conclusions: Unphysiological negative ΔpO 2 values occurred despite correct validation with traditional criteria. Δlactate cannot be used for validation because both positive and negative values are physiological. Positive/around zero/negative ΔpH and ΔpCO 2 sub-populations were associated with significant differences in pH and clinical characteristics, indicating that defective sampling and sample handling are not the sole explanations for negative Δvalues. Prompt puncture and sampling of the unclamped cord resulted in best sample quality., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: Fetal heart rate short term variation (STV) decreases with severe chronic hypoxia in the antenatal period. However, only limited research has been done on STV during labor. We have tested a novel algorithm for a valid baseline estimation and calculated STV. To explore the value of STV during labor, we compared STV with fetal scalp blood (FBS) lactate concentration, an early marker in the hypoxic process., Material and Methods: Software was developed which estimates baseline frequency using a novel algorithm and thereby calculates STV according to Dawes and Redman in up to four 30-minute blocks prior to each FBS. Cardiotocography traces from 1070 women in labor who had had FBS performed on 2134 occasions were analyzed., Results: In acidemic cases (lactate >4.8 mmol/L; Lactate Pro™), median STV 30 minutes prior to FBS was 7.10 milliseconds compared with 6.09 milliseconds in the preacidemic (4.2-4.8 mmol/L) and 5.23 milliseconds in the normal (<4.2 mmol/L) groups (P < .05). There was a positive correlation between lactate and STV (rho = 0.16-0.24; P < .05). Median lactate concentration in cases with STV <3.0 milliseconds (n = 160) was 2.3 mmol/L. When 2 FBS were performed within 60 minutes the change rate of lactate correlated to STV (rho = 0.33; P < .001). Cases with increasing lactate concentration had a median STV of 5.29 milliseconds vs 4.41 milliseconds in those with decreasing lactate (P < .001)., Conclusions: In the early stages of intrapartum hypoxia, STV increases, contrary to findings regarding chronic hypoxia in the antenatal period. The increase in the adrenergic surge is a likely explanation., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: The desire for pregnancy in sickle cell disease (SCD) women has become a true challenge for hematologists, requiring a multidisciplinary approach. Erythrocytapheresis (ECP) is an important therapeutic tool in SCD, but only limited data on starting time and the effects of ECP during pregnancy are available., Study Design and Methods: This is a double-center retrospective cross-sectional study on a total of 46 single pregnancies in SCD women from January 2008 to June 2017. ECP was started at 10.7 ± 5.2 weeks of gestation, and prophylactic enoxaparin (4,000 U daily) was introduced due to the reported high prevalence of thromboembolic events in pregnant SCD women., Results: The alloimmunization ratio was 2.1 per 1,000 and the alloimmunization rate was 5.6%. In early ECP-treated SCD women, no severe vaso-occlusive crisis, sepsis or severe infection, or preeclampsia or eclampsia were observed. We found normal umbilical arterial impedance during pregnancy, suggesting an optimal uteroplacental function in early ECP-treated SCD women. This was also supported by the improvement in newborn birthweights compared to previous studies. In our cohort, three SCD women were started later on ECP (20-25 weeks), and gestation ended with late fetal loss. Placenta pathology documented SCD-related damage and erythroblasts in placental vessels, indicating fetal hypoxia., Conclusions: Collectively, our data generate a rationale to support a larger clinical trial of early ECP program in SCD pregnancy., (© 2018 AABB.)

Objective: To determine the impact of a multidisciplinary fetal surveillance education program (FSEP) on term neonatal outcomes., Methods: A retrospective cohort study of term neonatal outcomes before (1998-2004) and after (2005-2010) introduction of a FSEP. Clinical data was collected for all term infants admitted to a neonatal intensive care unit (NICU) in Australia between 1998 and 2010. Infants with congenital abnormalities were excluded. Neonatal mortality and severe neonatal morbidity (admission to a NICU, respiratory support, hypoxic encephalopathy) were compared before and after the FSEP was introduced. The rates of operative delivery during this time were assessed., Results: There were 3 512 596 live term births between 1998 and 2010. The intrapartum hypoxic death rate at term decreased from 2.02 to 1.07 per 10 000 total births. More neonates were admitted to NICU after 2005 (10.6 versus 14.6 per 10 000 live births), however fewer babies admitted to the neonatal unit had Apgar scores < 5 at five minutes (55.1-45.5%, RR 0.82, 95% CI 0.7-0.87); and rates of hypoxic ischemic encephalopathy fell from 36% to 30% (RR 0.83, 95% CI 0.76-0.90). There was no increase in rates of emergency in labour caesarean sections (11.7% pre versus 11.1% post, RR 0.95, 95% CI 0.95-0.96)., Conclusions: Introduction of a national FSEP was associated with increased neonatal admissions but a reduction in intrapartum hypoxia, without increasing emergency caesarean section rates.

Hypoxic ischemic insults predispose to perinatal brain injury. Pro-inflammatory cytokines are important in the evolution of this injury. Interleukin-1β (IL-1β) is a key mediator of inflammatory responses and elevated IL-1β levels in brain correlate with adverse neurodevelopmental outcomes after brain injury. Impaired blood-brain barrier (BBB) function represents an important component of hypoxic-ischemic brain injury in the fetus. In addition, ischemia-reperfusion increases cytokine transport across the BBB of the ovine fetus. Reducing pro-inflammatory cytokine entry into brain could represent a novel approach to attenuate ischemia-related brain injury. We hypothesized that infusions of neutralizing IL-1β monoclonal antibody (mAb) reduce IL-1β transport across the BBB after ischemia in the fetus. Fetal sheep were studied 24-h after 30-min of carotid artery occlusion. Fetuses were treated with placebo- or anti-IL-1β mAb intravenously 15-min and 4-h after ischemia. Ovine IL-1β protein expressed from IL-1β pGEX-2T vectors in Escherichia coli (E. coli) BL-21 cells was produced, purified, and radiolabeled with 125 I. BBB permeability was quantified using the blood-to-brain transfer constant (K i ) with 125 I-radiolabeled-IL-1β. Increases in anti-IL-1β mAb were observed in the brain of the mAb-treated group (P<0.001). Blood-to-brain transport of 125 I-IL-1β was lower (P<0.04) across brain regions in the anti-IL-1β mAb-treated than placebo-treated ischemic fetuses. Plasma 125 I-IL-1β counts were higher (P<0.001) in the anti-IL-1β mAb- than placebo-treated ischemic fetuses. Systemic infusions of anti-IL-1β mAb reduce IL-1β transport across the BBB after ischemia in the ovine fetus. Our findings suggest that conditions associated with increases in systemic pro-inflammatory cytokines and neurodevelopmental impairment could benefit from an anti-cytokine therapeutic strategy., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

Fetal macrosomia is defined as birth weight >4000 g and is associated with several maternal and fetal complications such as maternal birth canal trauma, shoulder dystocia, and perinatal asphyxia. Early identification of risk factors could allow preventive measures to be taken to avoid adverse perinatal outcomes. Prenatal diagnosis is based on two-dimensional ultrasound formulae, but accuracy is low, particularly at advanced gestation. Three-dimensional ultrasound could be an alternative to soft tissue monitoring, allowing better prediction of birth weight than two-dimensional ultrasound. In this article, we describe the definition, risk factors, diagnosis, prevention, ultrasound monitoring, prenatal care, and delivery in fetal macrosomia cases., (Copyright © 2016. Published by Elsevier Ltd.)

Objective: Maternal obesity affects one in every five women giving birth worldwide. This condition is associated with adverse perinatal outcomes, as well as increased morbidity and mortality for mother and offspring., Methods: We carried out a prospective study at the University of Pecs Medical Center, Pecs, Hungary, between 1 January 2013 and 1 January 2014. We enrolled 60 obese (body mass index >30 kg/m(2)) low-risk pregnant women and 108 age-, ethnicity-, and parity-matched nonobese pregnant control subjects. The ST segment of the fetal electrocardiogram was assessed by STAN® monitoring. Neonatal outcomes and cord gas analysis of the umbilical vessels were evaluated after birth., Results: No infant with definitive metabolic acidosis was delivered in either group. We observed 32 and 106 ST events in the obese and control group, respectively, but this difference was not statistically significant. To date, none of the infants delivered as part of this study have demonstrated developmental insufficiency., Conclusions: Obesity might not influence the fetal electrocardiogram during labor as an independent risk factor for adverse pregnancy outcomes. Studies with larger cohort sizes are needed to confirm our findings.

The process of labour and delivery remains an unnecessary and preventable cause of death of women and babies around the world. Although the rates of maternal and perinatal death are declining, there are large disparities between rich and poor countries, and sub-Saharan Africa has not seen the scale of decline as seen elsewhere. In many areas, maternity services remain sparse and under-equipped, with insufficient and poorly trained staff. Priorities for reducing the mortality burden are provision of safe caesarean section, prevention of sepsis and appropriate care of women in labour in line with the current best practices, appropriately and affordably delivered. A concern is that large-scale recourse to caesarean delivery has its own dangers and may present new dominant causes for maternal mortality. An area of current neglect is newborn care. However, innovative training methods and appropriate technologies offer opportunities for affordable and effective newborn resuscitation and follow-up management in low-income settings., (Copyright © 2016. Published by Elsevier Ltd.)

Background: Cardiotocography (CTG) has high sensitivity, but less specificity in detection of fetal hypoxia. There is need for adjunctive methods easy to apply during labor. Low fetal heart rate short term variation (STV) is predictive for hypoxia during the antenatal period. The objectives of our study were to methodologically evaluate monitoring of STV during labor and to compare two different monitors (Sonicaid™ and EDAN™) for antenatal use., Methods: A prospective observational study at the obstetric department, Karolinska University hospital, Stockholm (between September 2011 and April 2015). In 100 women of ≥ 36 weeks gestation, STV values were calculated during active labor. In a subset of 20 women we compared STV values between internal and external signal acquisition. Additionally we compared antenatal monitoring with two different monitors in another 20 women., Results: Median STV in 100 fetuses monitored with scalp electrode during labor (EDAN™) was 7.1 msec (range 1.3-25.9) with no difference between early (3-6 cm) and late (7-10 cm) labor (7.1 vs 6.8 msec; p = 0.80). STV calculated from scalp electrode signals were positively correlated with delta-STV (STV internal -external) (R = 0.70; p < 0.01). No significant differences were found between Sonicaid™ and EDAN™ in antenatal external monitoring of STV (median difference 0.9 msec, Spearman Rank Correlation Sonicaid vs delta-STV; R = 0.35; p = 0.14)., Conclusions: Median intrapartum STV was 7.1 msec. Significant differences were found between internal and external signal acquisition, a finding that suggests further intrapartum studies to be analysed separately depending upon type of signal acquisition. Antenatal external monitoring with Sonicaid™ and EDAN™ indicates that the devices perform equally well in the identification of acidemic fetuses. Further studies are needed to assess the clinical value of intrapartum STV.

Purpose of Review: Hypoxic-ischemic brain injury is a leading cause of mortality and morbidity in neonates. Treating such injury by interrupting the excitotoxic-oxidative cascade is of immense importance. This review will focus on novel techniques of neuroprotection and describe the latest advances in established therapeutic methods., Key Findings: Although the primacy of therapeutic hypothermia in treating hypoxic-ischemic encephalopathy is well established, recent research establishes that the arbitrarily chosen regimen of cooling to 33°C for 72 h may indeed be the most appropriate method. The optimal duration of antenatal magnesium therapy for neuroprotection remains unsettled, though it is reassuring that even 12 h or less of magnesium therapy results in comparable neurological outcomes. Combining adjuvant therapies such as melatonin or erythropoietin with therapeutic hypothermia results in favorable neurological outcomes compared with hypothermia alone. Finally, stem cell-based therapies show considerable potential in preclinical studies., Summary: Significant advances have occurred in the management of neonatal brain injury. With establishment of the optimal temperature and duration of hypothermia, combinatory therapies using adjuncts hold the greatest promise. Promising preclinical approaches such as stem cell-based therapy and use of noble gases need to be confirmed with clinical trials.

Objective: Evaluation of the commonly used laboratory and clinical parameters of the newborn shortly after birth. Check thresholds acidemia, and in relation to the method of termination of pregnancy., Design: Retrospective epidemiological study., Setting: Department of Obstetrics and Gynecology, University Hospital, Olomouc., Methods: Of the 26,869 children born in the years 2000 to 2013 Inclusion criteria (complete clinical and laboratory findings after birth) fulfill 23,471 (87.4%) neonates. Methods for evaluation of newborns included Apgar score calculation and arterial umbilical cord blood pH and lactate analysis., Results: A total of 0.7% (157) of the neonates had severe acidosis pH below 7.00 arterial umbilical cord blood, its prevalence varies annually between 0.1 to 1.1%. Cutoff lactate in relation to pH < 7.00 was 6.3 mmol/l (n = 23 471, the sensitivity of 92.99%, specificity 92.15%, AUC = 0.972). For children of low weight < 2500 g the cutoff value is lower, 5.3 mmol/l (n = 2592, 89.66% sensitivity, specificity 91.10% AUC = 0.912). Suprathreshold lactate values was 8.4% (1977) newborns. Correlation of pH and lactate to Apgar evaluation is very low and in the range from 1 to 10 minutes gradually decreases. Worse Apgar evaluation in children of low birth weight do not correspond to laboratory findings acidosis, which is probably related to prematurity and lower energy reserves. Operating cesarean births in particular accounts for more than half of those with worse clinical findings Apgar and pH <7.00, but only 30% supratreshold lactate values. Also worse clinical evaluation after caesarean section is not in accordance with the laboratory findings. Vaginal surgery, especially forceps have a significant share of severe acidosis than cesarean, regardless of their frequency. Risk factor of forceps to pH less 7.00,OR = 9.28 (5.39 -15.77), P = 0.0000000, while caesarean to pH less 7,00 had OR = 1.52 (1.08 to 2.14), P = 0.01408156., Conclusion: The results obtained confirm that acidosis after birth is quite common, although they may not have response on the clinical condition of the newborn after birth. Evaluation of Apgar is little objective for the detection of hypoxia during birth and is influenced by the immaturity of newborn and method of delivery. Lactate levels may contribute to an objective assessment of hypoxia during birth. Values above 6.3 mmol/l can be considered an important indicator of newborn acidosis and birth hypoxia.

The ongoing and well-documented debate about the value of electronic fetal monitoring has focused primarily on the fact that most variant fetal heart rate (FHR) patterns are poor predictors of fetal acid-base status. Most recently, much of this attention has been focused on the implications for clinical management of FHR patterns that the National Institute of Child Health and Human Development has classified as indeterminate: neither normal nor abnormal. Given that a majority of fetuses will have an FHR pattern considered indeterminate at some point in labor, this is an important and worthwhile discussion. It is also important, however, for providers to be able to recognize those patterns that signal the presence of developing acidemia and those that signal the potential presence of an acute obstetric complication that can quickly lead to acidemia and fetal asphyxia, such as a placental abruption or uterine rupture. Early identification of these FHR patterns, and immediate intervention to improve oxygenation or expedite birth, may help improve neonatal outcomes. The first part of this article presents descriptions of theses FHR patterns. The route and timing of birth during these emergencies is then discussed. The last part of the article presents an overview of strategies for optimizing the efficiency of providers, particularly teams of providers, in responding to FHR emergencies. The use of simulation-based training is reviewed, with specific focus on its potential application in the context of preparing for these emergencies., (© 2014 by the American College of Nurse-Midwives.)

Recognition of carbon monoxide is difficult due to its plain physical-chemical properties. Carbon and gas operating heating systems may cause severe poisoning. Carbon-monoxide intoxication may generate severe hypoxic damage and it may cause death. The authors present the case of severe carbon monoxide poisoning affecting one young child and five adults, including a pregnant woman. Because the availability of hyperbaric oxygen therapy is limited in Hungary, urgent cesarean section was performed to avoid intrauterine hypoxic damage. The authors note that there are no standardized non-invasive methods for measuring fetal carbon-monoxide level and that the level of carbon monoxide accumulation is higher and the clearance is longer in the fetus than in the mother. The pathophysiology of carbon monoxide intoxication and therapeutic options in pregnancy are discussed.

While the use of creatine in human pregnancy is yet to be fully evaluated, its long-term use in healthy adults appears to be safe, and its well documented neuroprotective properties have recently been extended by demonstrations that creatine improves cognitive function in normal and elderly people, and motor skills in sleep-deprived subjects. Creatine has many actions likely to benefit the fetus and newborn, because pregnancy is a state of heightened metabolic activity, and the placenta is a key source of free radicals of oxygen and nitrogen. The multiple benefits of supplementary creatine arise from the fact that the creatine-phosphocreatine [PCr] system has physiologically important roles that include maintenance of intracellular ATP and acid-base balance, post-ischaemic recovery of protein synthesis, cerebral vasodilation, antioxidant actions, and stabilisation of lipid membranes. In the brain, creatine not only reduces lipid peroxidation and improves cerebral perfusion, its interaction with the benzodiazepine site of the GABAA receptor is likely to counteract the effects of glutamate excitotoxicity - actions that may protect the preterm and term fetal brain from the effects of birth hypoxia. In this review we discuss the development of creatine synthesis during fetal life, the transfer of creatine from mother to fetus, and propose that creatine supplementation during pregnancy may have benefits for the fetus and neonate whenever oxidative stress or feto-placental hypoxia arise, as in cases of fetal growth restriction, premature birth, or when parturition is delayed or complicated by oxygen deprivation of the newborn.

Objective: Perinatal hypoxia-induced free radical formation is an important cause of hypoxic-ischaemic encephalopathy and subsequent neurodevelopmental disabilities. Allopurinol reduces the formation of free radicals, which potentially limits hypoxia-induced brain damage. We investigated placental transfer and safety of allopurinol after maternal allopurinol treatment during labour to evaluate its potential role as a neuroprotective agent in suspected fetal hypoxia., Design: We used data from a randomised, double-blind multicentre trial comparing maternal allopurinol versus placebo in case of imminent fetal hypoxia (NCT00189007)., Patients: We studied 58 women in labour at term, with suspected fetal hypoxia prompting immediate delivery, in the intervention arm of the study., Setting: Delivery rooms of 11 Dutch hospitals., Intervention: 500 mg allopurinol, intravenously to the mother, immediately prior to delivery., Main Outcome Measures: Drug disposition (maternal plasma concentrations, cord blood concentrations) and drug safety (maternal and fetal adverse events)., Results: Within 5 min after the end of maternal allopurinol infusion, target plasma concentrations of allopurinol of ≥2 mg/L were present in cord blood. Of all analysed cord blood samples, 95% (52/55) had a target allopurinol plasma concentration at the moment of delivery. No adverse events were observed in the neonates. Two mothers had a red and/or painful arm during infusion., Conclusions: A dose of 500 mg intravenous allopurinol rapidly crosses the placenta and provides target concentrations in 95% of the fetuses at the moment of delivery, which makes it potentially useful as a neuroprotective agent in perinatology with very little side effects., Trial Registration: The study is registered in the Dutch Trial Register (NTR1383) and the Clinical Trials protocol registration system (NCT00189007).

Environmental factors during fetal life program the health outcomes regarding many diseases in future life. This idea has been supported by worldwide epidemiological studies, but the underlying mechanisms are still poorly understood. Three questions should be answered. (i) Does a common underlying cause of ordinary pathological fetal development exist? (ii) If such a cause exists, which mechanism might develop disease in later life? (iii) Is it possible to prevent this underlying cause and therefore the associated obstetric complications to primarily prevent future life diseases? The objective of this review is to attempt to answer these three questions by using PubMed (extending to October 2012) and other sources. Three data-based answers corresponding to these questions were found: (i) hypoxia, (ii) excessive stimulation of neurogenesis, and (iii) preconditioning/adaptation to hypoxia. The method for such preconditioning/adaptation is intermittent hypoxic training (IHT), in which air with low oxygen concentration is breathed through a mask to protect against subsequent strong adverse influences. Data are cited for IHT applications for the prevention/treatment of diseases in different fields, particularly in obstetrics. Data suggested that all common fetal origins of adult diseases are likely predetermined by changes in the fetal brain; therefore, early detection of these changes must be very important. The use of IHT may be a real means to primarily prevent obstetric complications and therefore, prevent future life diseases.

Background: Fetal hypoxia is common and in vitro evidence supports its role in the programming of adult cardiovascular dysfunction through the generation of oxidative stress. Whether fetal chronic hypoxia programmes alterations in cardiovascular control in vivo, and if these alterations can be prevented by antioxidant treatment, is unknown. This study investigated the effects of prenatal fetal hypoxia, with and without maternal supplementation with vitamin C, on basal and stimulated cardiovascular function in vivo in the adult offspring at 4 months of age in the rat., Methods and Results: From days 6 to 20 of pregnancy, Wistar rats were subjected to Normoxia, Hypoxia (13% O2), Hypoxia+Vitamin C (5mg/ml in drinking water) or Normoxia+Vitamin C. At 4 months, male offspring were instrumented under urethane anaesthesia. Basal mean arterial blood pressure, heart rate and heart rate variability (HRV) were assessed, and stimulated baroreflex curves were generated with phenylephrine and sodium nitroprusside. Chronic fetal hypoxia increased the LF/HF HRV ratio and baroreflex gain, effects prevented by vitamin C administration during pregnancy., Conclusions: Chronic intrauterine hypoxia programmes cardiovascular dysfunction in vivo in adult rat offspring; effects ameliorated by maternal treatment with vitamin C. The data support a role for fetal chronic hypoxia programming cardiovascular dysfunction in the adult rat offspring in vivo through the generation of oxidative stress in utero.

As recently as the year 2000, 100% oxygen was recommended to begin resuscitation of depressed newborns in the delivery room. However, the most recent recommendations of the International Liaison Committee on Resuscitation counsel the prudent use of oxygen during resuscitation. In term and preterm infants, oxygen therapy should be guided by pulse oximetry that follows the interquartile range of preductal saturations of healthy term babies after vaginal birth at sea level. This article reviews the literature in this context, which supports the radical but judicious curtailment of the use of oxygen in resuscitation at birth., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The interruption of placental blood flow induces circulatory responses to maintain cerebral, cardiac, and adrenal blood flow with reduced renal, hepatic, intestinal, and skin blood flow. If placental compromise is prolonged and/or severe, total circulatory failure is likely with cerebral hypoperfusion and resultant hypoxic ischemic cerebral injury with collateral renal, cardiac, and hepatic injury. Management strategies should be targeted at restoring cerebral perfusion and oxygen delivery and minimizing the extent of secondary injury. Specifically, the focus should include the judicious use of supplemental oxygen, avoidance of hypoglycemia and elevated temperature in the delivery room, and the early administration of therapeutic hypothermia to high-risk infants., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Surgery during pregnancy is complicated by the need to balance the requirements of two patients. Under usual circumstances, surgery is only conducted during pregnancy when it is absolutely necessary for the wellbeing of the mother, fetus, or both. Even so, the outcome is generally favourable for both the mother and the fetus. All general anaesthetic drugs cross the placenta and there is no optimal general anaesthetic technique. Neither is there convincing evidence that any particular anaesthetic drug is toxic in humans. There is weak evidence that nitrous oxide should be avoided in early pregnancy due to a potential association with pregnancy loss with high exposure. There is evidence in animal models that many general anaesthetic techniques cause inappropriate neuronal apoptosis and behavioural deficits in later life. It is not known whether these considerations affect the human fetus but studies are underway. Given the general considerations of avoiding fetal exposure to unnecessary medication and potential protection of the maternal airway, regional anaesthesia is usually preferred in pregnancy when it is practical for the medical and surgical condition. When surgery is indicated during pregnancy maintenance of maternal oxygenation, perfusion and homeostasis with the least extensive anaesthetic that is practical will assure the best outcome for the fetus.

Hypoxia-ischemia is a major cause of perinatal brain injury in the newborn. Neotrofin, a neurotrophin agonist, has been shown to provide neuroprotection in several in vivo and in vitro studies. The aim of this study is to investigate the neuroprotective and ameliorating effects of neotrofin treatment after hypoxic-ischemic-injury-induced neuronal cell death, apoptosis in a neonatal hypoxic-ischemic brain injury rat model. Twenty-one seven-day-old Wistar rat pups were used in this study. The groups were: (1) a neotrofin-treated hypoxic-ischemic-group, (2) a saline-treated hypoxic-ischemic-group, and (3) a sham-operated group. Rat pups were subjected to left carotid artery occlusion followed by 2.5h of hypoxic exposure. After the hypoxic exposure, group one received an intra-peritoneal injection of neotrofin at a dose of 60mg/kg. Forty-eight hours after hypoxia, the animals were killed for histopathological evaluation to detect apoptosis and density of neurons. We found that neotrofin attenuates hypoxia-ischemia induced with neuronal density of the hippocampus, the prefrontal and the parietal cortex, and decreased apoptotic cell index in the same regions. Given our results, neotrofin may be useful in reducing brain injury; it possesses clinical relevance for the treatment of hypoxic-ischemic encephalopathy in the newborn., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The creatine-phosphocreatine shuttle is essential for the maintenance of cellular ATP, particularly under hypoxic conditions when respiration may become anaerobic. Using a model of intrapartum hypoxia in the precocial spiny mouse (Acomys cahirinus), the present study assessed the potential for maternal creatine supplementation during pregnancy to protect the developing brain from the effects of birth hypoxia. On day 38 of gestation (term is 39 days), the pregnant uterus was isolated and placed in a saline bath for 7.5 min, inducing global hypoxia. The pups were then removed, resuscitated, and cross-fostered to a nursing dam. Control offspring were delivered by caesarean section and recovered immediately after release from the uterus. At 24 h after birth hypoxia, the brains of offspring from dams fed a normal diet showed significant increases in lipid peroxidation as measured by the amount of malondialdehyde. In the cortical subplate, thalamus and piriform cortex there were significant increases in cellular expression of the pro-apoptotic protein BAX, cytoplasmic cytochrome c and caspase-3. When pregnant dams were fed the creatine supplemented diet, the increase in malondialdehyde, BAX, cytochrome c and caspase 3 were almost completely prevented, such that they were not different from control (caesarean-delivered) neonates. This study provides evidence that the neuroprotective capacity of creatine in the hypoxic perinatal brain involves abrogation of lipid peroxidation and apoptosis, possibly through the maintenance of mitochondrial function. Further investigation into these mechanisms of protection, and the long-term development and behavioural outcomes of such neonates is warranted., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Anatomic and physiologic changes of pregnancy predispose the mother to increased morbidity and mortality whereas increasing risks of a less than optimal outcome for the fetus. The frequency and significance of acute and chronic respiratory conditions in pregnant women have increased in recent years. Clinicians must have an understanding of cardiopulmonary physiology to promptly recognize and treat pregnant women with respiratory conditions ranging from asthma to adult respiratory distress syndrome. Hospitals must establish systems to assure timely assessment, multidisciplinary care, and possibly a plan for transfer to a higher level of care to provide highest quality care to the perinatal patient presenting with a severe respiratory condition to promote optimal outcomes for the woman and the fetus.

Maternal smoking during pregnancy greatly enhances perinatal morbidity/mortality and is the major risk factor for Sudden Infant Death Syndrome (SIDS). Studies in developing rodents indicate that nicotine is a neuroteratogen that targets monoamine pathways involved in the responses to hypoxia that are in turn, hypothesized to contribute to these adverse events. We administered nicotine to pregnant Rhesus monkeys from gestational day 30 through 160 by continuous infusion, achieving maternal plasma levels comparable to those in smokers; we examined neurochemical parameters immediately after Cesarean delivery at the end of the exposure period. Nicotine evoked elevations in brainstem serotonin levels and serotonin turnover, indicating hyperactivity of these pathways. The same treatment evoked a deficit in cardiac norepinephrine levels. Both effects were offset by coadministration of the antioxidant, Vitamin C. Brainstem serotonin hyperinnervation is a hallmark of SIDS, and the hyperactivity seen here can also account for the downregulation of serotonin receptors noted in this disorder. Deficient cardiac sympathetic innervation is also consistent with increased vulnerability to hypoxia during delivery or in the agonal event in SIDS. Our results thus indicate that nicotine exposure in a primate model produces brainstem and autonomic abnormalities of the key monoamine systems that govern the response to hypoxia, indicate an important role of oxidative stress in the adverse effects, and point to potential amelioration strategies that could offset these particular effects of nicotine., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In 1995 and 1996, the National Institute of Child Health and Human Development (NICHD) convened a panel of experts in electronic fetal monitoring with the goal of reaching consensus on a set of standardized, unambiguous definitions for fetal heart rate tracings. In 2008, the Eunice Kennedy Shriver NICHD, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine sponsored a second research planning workshop to review and clarify the 1997 definitions, to propose a standard classification system for fetal heart rate tracings, to introduce, in consensus form, key concepts of intrapartum fetal heart rate interpretation and to make recommendations for future research. This article summarizes the proposals and recommendations of the 2008 NICHD Research Planning Workshop.

Introduction: The fetal acoustic stimulation test (FAST) is a simple cost effective screening test for antenatal fetal monitoring. The aim of the study was to evaluate the FAST as a screening test for early intrapartum fetal well being., Methods: An initial non stress test (NST) followed by a FAST using corometric model 146 was carried out in 486 participants in early labour with uncomplicated singleton pregnancies and > 32 weeks gestation. A repeat NST was recorded in the participants who had an initial non reactive NST. The results of the NST and FAST were compared with fetal outcome. Maternal perception of fetal movements after FAST, results of NST before and after FAST, and the babies' 5 minute APGAR scores were measured., Results: Of the 486 participants 413 (85%) noticed fetal movements after FAST. Initial NST was non reactive in 203 (42%) but 149 (31%) became reactive after FAST. Compared to the NST, FAST had a better sensitivity (97% vs 62%, p < 0.001), specificity (100% vs 87%, p = 0.017), positive predictive value (100% vs 98%, p = 0.024), negative predictive value (79% vs 17%, p < 0.001) and accuracy (99%vs 64%, p < 0.001) in predicting 5 minute APGAR < 7 in the baby., Conclusions: FAST is a reliable screening test for assessing fetal well being in early labour. It complements the NST and is better than the NST alone.

In Japan, there has recently been a severe shortage of physicians in regional core hospitals, limiting the acceptance of emergency patients. Searching for available medical institutions over an extended area beyond the regular regional medical area should increase the possibility of finding medical institutions capable of accepting patients. Physician staffed helicopter ambulance system, so called the Doctor-Helicopter service is highly effective in saving patients life, since emergency doctors start to treat patients at the scene. It may be also useful to transport the critically ill patients for a long distance. A 29 year old female diagnosed twin fetus with twin-twin transfusion syndrome needs urgent delivery at about 29 weeks of gestation. The patients had to be transported to the perinatal care center which is 160 km from the hospital to where the patient was admitted because of a lack of NICU. During transportation, the maternal vital signs were stable without cervical dilatation. After arrived at the perinatal center, the patient underwent Caesarian section. Both babies had respiratory distress syndrome and admitted to NICU. With increasing cases in which medical institutions cannot accept peripartum emergency patients, it needs to search for medical institutions over an extended area and transport patients by Doctor-Helicopter.

Background: 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., Methods/design: 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., Discussion: In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia., Trial Registration Number: Clinical Trials, protocol registration system: NCT00189007.

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 (primary 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.