Fetal Arterial Oxygen Saturation Research Articles

Continuous Transabdominal Fetal Pulse Oximetry (TFO) in Pregnant Ewe Models under Induced Fetal Hypoxia

Fetal heart rate monitoring is a poor predictor of fetal hypoxia for its high false-positive rate. Using a novel TFO, this study aims to demonstrate feasibility of continuous, non-invasive assessment of fetal arterial blood oxygen saturation (fSpO2) in hypoxic in-utero lamb models.

974 Non-invasive transabdominal assessment of In-Utero fetal oxygen saturation in a hypoxic lamb model

Fetal heart rate monitoring is a poor predictor of fetal hypoxia due to its high false-positive rate. Utilizing a novel transabdominal fetal pulse oximeter (TFO), this study aimed to demonstrate the feasibility of non-invasive and direct assessment of fetal arterial blood oxygen saturation in-utero (SaO2) in a hypoxic lamb model. Fetal hypoxia was induced in 3 gravid term ewes (137.3±3.2 days gestation) by placing an inflatable balloon catheter in the infrarenal aorta via the common femoral artery (Fig 1). A fetal carotid arterial line was placed for continuous hemodynamic monitoring and arterial blood gases (ABG). The uterus was closed around the right fetal forelimb, and the laparotomy was closed, leaving the limb exposed for conventional pulse oximetry. The fetus’s depth from the ewe’s skin was determined, and the TFO device was placed on the ewe’s abdomen. The aortic balloon catheter was inflated in a stepwise fashion to decrease the ewe’s distal mean arterial pressure (dMAP) in 5mmHg increments. At each step, dMAP was maintained for 10 min, and fetal ABGs were recorded at 2.5, 5, and 10-min marks. The balloon was fully deflated after two consecutive measurements of fetal SaO2 <15%. The fetus was recovered for 45 min, and the stepwise gradient was repeated for a second round. At each dMAP level, the average fetal oxygen saturation measured by the TFO (SpO2) was compared to the average fetal SaO2. TFO measurements of fetal SpO2 were compared to fetal SaO2 (Fig 2A) and were found to be highly correlative (R=0.64 and p<0.0001) (Fig 2B). The ex-utero conventional clinical pulse oximeter readings from the exposed forelimb had a weak correlation with fetal SaO2 (R=0.16 and p<0.0003). Fetal depth, composed of ewe’s abdominal wall and uterine wall thickness, was 15.0±4.3mm (SD). The novel TFO device can measure fetal SaO2 based on the high correlation of SpO2 and SaO2 despite intervening maternal anatomy. TFO can potentially improve the accuracy of fetal hypoxia detection. Future research will focus on intrapartum validation in lamb models and human pregnancies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

1168: Fetal tolerance of maternal resuscitative endovascular balloon occlusion of the aorta in a sheep model

Hemorrhage is the leading cause of maternal mortality. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an emerging therapy to decrease post-partum hemorrhage but creates profound ischemia to the placenta preventing its use before delivery. Employing partial REBOA (pREBOA) prior to delivery may improve maternal outcomes by decreasing placental perfusion and hemorrhage while still providing a small amount of distal perfusion to the placenta. Yet, this is only a viable strategy if the attenuated blood flow is tolerated by the fetus. Our objective was to evaluate how progressive levels of pREBOA effect the fetus. A REBOA catheter was placed in the distal aorta of 3 gravid ewes at term. Carotid arterial access and an oximeter were placed on the fetuses. The balloon was gradually inflated in 10min increments of attenuated distal mean arterial pressure at the placenta (pMAP) by 5-10mmHg. Fetal arterial blood gases, oxygen saturation and hemodynamic parameters of heart rate (HR) and mean arterial pressure (MAP) were obtained at baseline and each pREBOA inflation increment. Maternal baseline pMAP was 60.3 ±15.0mmHg. Fetal SaO2 declines first appeared at a pMAP of 40mmHg (59.0 ±12.1 vs 37.6 ±14.8%, p=0.0009) and correlated with decreases in fetal SaO2 as the aorta was progressively occluded with pREBOA (R=0.80, p< 0.0001, Fig. 1). Fetal MAP declines began at a pMAP of 35mmHg (51.3 ±5.8 vs 56.1 ±10.1mmHg, p=0.04), as did pH (7.20 ±0.08 vs 7.17 ±0.07, p=0.01). Fetal lactate increases were not seen until the pMAP reached 30mmHg (2.0 ±0.5 vs 2.4 ±0.4mmol/L, p=0.02). Fetal HR did not significantly differ from baseline at any pMAP, including the lowest of 25mmHg (159.7 ±19.1 vs 183.0 ±26.9bpm, p=0.56). All fetuses survived the progressively increasing pREBOA. Physiologic changes in the fetus first appear at a pMAP of 40mmHg. The fetus tolerates attenuation of placental MAP with partial REBOA to a high level before delivery, raising the possibility of employing pREBOA to limit maternal hemorrhage earlier in the perinatal period without injuring the fetus.

Pulsoximetric monitoring of fetal arterial oxygen saturation and fetal pulse at stage II of labor to predict acidosis in newborn Holstein Friesian calves

During stage II of parturition, the bovine fetus is at risk of oxygen deficiency caused by insufficient gas exchange between the dam and the fetus. The early detection of this critical condition, followed by assistance at calving, can help to improve the vitality of the newborn calf, or even prevent it from being born dead. By using pulse oximetry, the arterial oxygen saturation, as well as the pulse rate, can be continuously and non-invasively measured. The aim of our study was to identify critical thresholds for the parameters ‘arterial oxygen saturation (FSpO2)’ and ‘pulse rate (PR)’ that indicate a severe postnatal risk for calves to suffer from acidosis. FSpO2 and PR from 40 bovine fetuses were recorded during the last 25 min of calving with a commercially available pulse oximeter (Radius-7, Masimo Corporation, Irvine, USA). The calves were tested immediately after birth for acidosis by analyzing their blood with a portable blood gas analyzer (VetScan iStat1, Abaxis Inc., Union City, USA). Retrospectively, the pulsoximetric data were scanned for predefined patterns. The validity of these patterns to predict acidosis in newborn calves was analyzed by using receiver operating characteristics (ROC) curve analyses. In general, PR was a stronger predictive parameter for acidosis than FSpO2, with the greatest area under the curve (AUC) for the PR criteria ‘Pulse rate > 120 beats per minute (bpm) for at least 2 min’, with an AUC of 0.764, in contrast to an AUC of 0.613 for the best FSpO2 criteria ‘FSpO2 < 40% for at least 50% of the measurement’. Further studies should investigate whether vitality after calving can be improved and fetal death rate can be reduced when obstetric assistance is performed as soon as one of these criteria apply to the bovine fetus. For more practical implementation in the field, improvement of the device’s hardware would be necessary.

206: Melanocortin binding activity in term and preterm human placenta

term and preterm human placenta J. Newton, Minying Cai, Hua Xu, Kathryn Reed University of Arizona, Obstetrics and Gynecology, Tucson, AZ, University of Arizona, Chemistry, Tucson, AZ, University of Arizona, Pediatrics, Tucson, AZ OBJECTIVE: The purposes of this study were to compare melanocortin binding activity and melanocortin receptor subtype expression in human placenta samples collected in four clinical settings: preterm notin-labor, preterm labor, term not-in-labor, and term labor. STUDY DESIGN: Following IRB approval, placenta samples were collected at delivery in each of the four clinical settings listed above. Melanocortin binding activity using 125I-NDP-MSH was determined with 1 mg of total membrane protein from each sample. Competition binding assays between the non-selective 125I-NDP-MSH and -MSH analogs that have highly specific receptor subtype agonist activity were used to identify receptor subtype activity. Lastly, 500 ng of total placental RNA was used as original template for quantitative RT-PCR using validated TaqMan probes for melanocortin receptors 1 and 3 (MC1R and MC3R). Average MSH binding activities were compared between groups using two-tailed Students t-test. Relative expression of MC1R and MC3R were compared using the Pfaffl method. RESULTS: Human placenta samples express MSH-binding activity. This activity is significantly higher in the setting of labor compared to not-in-labor, both at term and preterm. Competition binding assays with highly selective receptor agonists showed that MC3R is the predominant melanocortin receptor in human placenta. In the quantitative RT-PCR studies, both MC1R and MC3R are detected at varying expression levels. While MC1R was expressed at a relatively constant level in this sample set, MC3R expression levels were significantly higher in term labor samples compared to preterm not-in-labor samples. CONCLUSION: Melanocortin receptors, which have important physiologic functions including roles in energy homeostasis and inflammation, are expressed in human placenta. The key melanocortin receptor in placental MSH binding activity appears to be the MC3R subtype based on both the RT-PCR and competitive binding assays. Finally, the level of melanocortin binding activity and MC3R gene expression varies with gestational age and in the setting of term and preterm labor. 207 Role of foramen ovale in the regulation of fetal cardiac output: a fetal sheep study with acute ductus arteriosus occlusion Jason Hashima, David Sahn, Muhammad Ashraf, Vanessa Rogers, Stephen Langley, Lowell Davis, Roger Hohimer, Juha Rasanen Oregon Health and Science University, Obstetrics and Gynecology, Portland, OR, Oregon Health and Science University, Pediatric Cardiology, Portland, OR, Oregon Health and Science University, Pediatric Surgery, Portland, OR, Oregon Health & Science University, Maternal Fetal Medicine, Portland, OR OBJECTIVE: We hypothesized that during acute fetal ductus arteriosus (DA) occlusion (DO) foramen ovale (FO) volume blood flow increases, in order to maintain adequate systemic cardiac output. STUDY DESIGN: Nine ewes with singleton pregnancies underwent surgery at 120-126 gestational days (term 145 days) for the placement of a vascular occluder around fetal DA. Fetal carotid artery and jugular vein were cannulated. After a 5-day recovery, fetal heart rate (FHR), right (RVCO) and left (LVCO) ventricular cardiac outputs were measured by ultrasonography. Pulmonary (Qp) and foramen ovale (Qfo) volume blood flows, and systemic CO (combined cardiac output-Qp) were calculated at baseline, 15 and 60 minutes after DO, and 15 minutes after release of DO. Fetal mean arterial (mABP) and central venous (CVP) pressures, and pO2 and oxygen saturation were monitored. RESULTS: All the data are presented as means (SD). * p 0.05, compared with baseline. CONCLUSION: Acute DO in fetal sheep leads to decreased RVCO and increased LVCO, however systemic CO decreases. The rise in LVCO is caused by increased Qp with no change in the Qfo. Fetal CVP increases and arterial oxygen saturation decreases during DO. These findings suggest that fetal foramen ovale has a limited capacity to increase its volume blood flow, at least in response to acutely increased right ventricular afterload. Poster Session I Clinical Obstetrics, Medical-Surgical-Disease, Neonatology, Physiology-Endocrinology www.AJOG.org

Chronic intrauterine hypoxia interferes with aortic development in the late gestation ovine fetus

This study explored arterial remodelling in fetuses growth restricted by hypoxia. Chronically catheterized fetal sheep were made moderately or severely hypoxic by placental embolization for 15 days starting at gestational age 116-118 (term ∼147 days). Cross-sections of the aorta were analysed for collagen and elastin content using histological procedures, while immunofluorescence was applied to measure markers of vascular smooth muscle cell (VSMC) type. In frozen aortae quantitative PCR was used to measure mRNA levels of extracellular matrix (ECM) precursor proteins as well as molecular regulators of developmental and pathological remodelling. Relative to Control (n =6), aortic wall thickness was increased by 23% in the Moderate group (n =5) and 33% (P <0.01) in the Severe group (n =5). Relative to Control, the Severe group exhibited a 5-fold increase in total collagen content (P <0.01) that paralleled increases in mRNA levels of procollagen I (P <0.05) and III and transforming growth factor β (TGF-β1) (P <0.05). The percentage area stained for α-actin was inversely related to fetal arterial oxygen saturation (P <0.05) and total α-actin content was 45% higher in the Moderate group and 65% (P <0.05) higher in the Severe group, compared to Control. A 12% and 39% (P <0.05) reduction in relative elastic fibre content was observed in Moderate and Severe fetuses, respectively. mRNA levels of the elastolytic enzyme, matrix metalloproteinase-2 (MMP-2) were inversely correlated with fetal arterial oxygen saturation (P <0.05) (Fig. 7) and mRNA levels of its activator, membrane-type MMP (MTI-MMP), were elevated in the Severe group (P <0.05). Marked neointima formation was apparent in Severe fetuses (P <0.05) concomitant with an increase in E-selectin mRNA expression (P <0.05). Thus, aberrant aortic formation in utero mediated by molecular regulators of arterial growth occurs in response to chronic hypoxaemia.

Non-invasive monitoring of fetal oxygen saturation

Background. Monitoring of fetal heart-rate is routinely used to judge fetal well-being, though bradycardia is a late sign of hypoxia. Objective. We developed a non-invasive method to directly measure fetal arterial oxygenation. Material and Method. In order to catch the fetal signal, we applied a light source and a photodetector onto the abdomen of pregnant women of about 35 wks gestation. Results. Using sophisticated signal processing techniques (patent pending) we succeeded in separating fetal und maternal pulse signal to a sufficient degree to determine fetal arterial oxygen saturation. Discussion. Although during that first phase of investigation we restricted our study population to healthy pregnancies, there is no obvious reason why our method should not work under fetal pathology. Conclusion. We present a novel method for the monitoring of fetal well-being, measuring fetal oxygenation which if disturbed is the very first step in the chain of adverse events leading to fetal damage. Due to its non-invasive nature and proven clinical feasibility the presented method has the potential to make it the method of choice for prenatal, or intrapartum fetal monitoring.

Predictive value of pulse oximetry for the development of fetal acidosis

To determine the predictive value of fetal pulse oximetry (FPO) for the development of fetal acidosis in cases of non-reassuring fetal heart rate (FHR). In a prospective observational study, pulse oximetry monitoring was examined in cases of non-reassuring FHR during singleton cephalic delivery at 36-42 weeks' gestation. The study examined whether fetal arterial oxygen saturation (FSpO(2)) values <30% for at least 10 min during the last 60 min before delivery increase the risk of fetal acidosis. The predictive reliability of this algorithm and the correlation to fetal acidosis [umbilical artery pH (UApH) <7.15] were analyzed. We included 101 patients with non-reassuring FHR during delivery. The incidence of fetal acidosis was significantly higher when FSpO(2) values <30% were recorded for at least 10 min (P=0.0). An UApH <7.15 was reliably excluded with a negative predictive value of 98.7% and detected with a sensitivity of 92.9%. A low pulse oximetry oxygen saturation <30% for at least 10 min correlates highly with fetal acidosis in cases of non-reassuring FHR. FPO reliably excludes moderate to advanced acidosis and can reduce the frequency of fetal blood analysis (FBA) in cases of non-reassuring cardiotocography (CTG).

T2 and T2* measurements of fetal brain oxygenation during hypoxia with MRI at 3T: correlation with fetal arterial blood oxygen saturation

The purpose of this prospective study was to determine the oxygen saturation of blood in the fetal brain based on T2 and T2* measurements in a fetal sheep model. Five sheep fetuses were investigated during normoxia and hypoxia by 3T MRI. Multi-echo gradient-echo and turbo-spin-echo sequences were performed on the fetal brain. MR-determined oxygen saturation (MR-sO(2)) of blood in the fetal brain was calculated based on T2 and T2* values. Fetal arterial blood oxygen saturation (blood-sO(2)) was measured during the two experimental phases. The slope of MR-sO(2) as a function of blood-sO(2) was estimated and tested for compatibility using the one-sample t-test. During normoxia, mean values for carotid blood oxygen saturation were 67%, 83 ms for T2*, 202 ms for T2 and 96% for MR-sO(2). During hypoxia, arterial blood oxygen saturation, T2* and calculated MR-sO(2) decreased to 22%, 64 ms, and 68% respectively. The one-sample t-test revealed the slope to be significantly different from 0 (T = 5.023, df = 4, P = 0.007). It is feasible to perform quantitative T2 and T2* measurements in the fetal brain. MR-sO(2) and fetal arterial blood oxygen saturation correlated significantly. However, based on these data a reliable quantification of fetal brain tissue oxygenation is not possible.

ΔR2* in Fetal Sheep Brains during Hypoxia: MR Imaging at 3.0 T versus That at 1.5 T

To investigate the feasibility of fetal blood oxygen level-dependent magnetic resonance (MR) imaging at 1.5 T and to compare DeltaR2* in the brains of fetal sheep during hypoxia at 3.0 T with that at 1.5 T. All experimental protocols were reviewed and approved by the local authorities on animal protection. Between January 2006 and May 2006, fetal brain measurements were performed in eight pregnant ewes with 1.5-T and 3.0-T MR imaging units after fetal paralysis was achieved by administering pancuronium bromide. With both imaging units, a T2*-weighted single-shot gradient-echo echo-planar imaging sequence (echo time, 30 msec at 3.0 T and 50 msec at 1.5 T) was used to measure T2* signal changes (DeltaR2*) in the fetal brain in control conditions and during hypoxia (maternal oxygenation, 50%-70%). A carotid catheter was placed and maintained in the fetuses to enable measurement of the fetal arterial oxygen saturation (SaO(2)). DeltaR2* was correlated with fetal SaO(2), and linear regression analysis was performed. A paired t test was used to evaluate differences, with a significance level of P < .05. At both field strengths, a signal intensity decrease on T2*-weighted images during hypoxia was detected. At 1.5 T, mean fetal SaO(2) was reduced from 65.4% +/- 9.2 (standard deviation) during control conditions to 17.7% +/- 6.2 during hypoxia. DeltaR2* and fetal SaO(2) correlated significantly (r = 0.98, P = .018). At 3.0 T, fetal SaO(2) was reduced from 62.4% +/- 7.5 during control conditions to 18% +/- 7.5 during hypoxia. DeltaR2* and fetal SaO(2) also correlated significantly (r = 0.95, P = .012). A linear fit resulted in a slope value of 0.084 +/- 0.003 for 1.5 T and 0.166 +/- 0.016 for 3.0 T. This means a doubled sensitivity of DeltaR2* for oxygen saturation variations at 3.0 T compared with 1.5 T. MR imaging at 3.0 T is more sensitive than that at 1.5 T in the detection of DeltaR2* in the fetal brain during hypoxia. However, there was a signal decrease in the fetal brain in all 1.5-T experiments during hypoxia. Thus it is possible to measure fetal DeltaR2* at 1.5 T, which may be of more practical relevance for the evaluation of pregnant women.

Validation of arterial oxygen saturation measurements in utero using pulse oximetry.

The noninvasive measurement of fetal arterial oxygen saturation using pulse oximetry could be of potential use in assessing fetal well-being in utero during labor. In this study, the accuracy and technical feasibility of reflectance pulse oximetry in utero was evaluated in acutely instrumented fetal sheep using a specially designed sensor. Following recalibration of the analysis algorithms, fetal arterial saturation could be measured by pulse oximetry in utero. Arterial oxygenation measurements obtained using pulse oximetry correlated well with simultaneous in vitro measurements over the range of 6 to 81%. We conclude that in utero pulse oximetry is technically feasible, appears useful and accurate, and merits further evaluation.

Effects of Exposure to Chronic Placental Insufficiency on the Postnatal Brain and Retina in Sheep

Chronic placental insufficiency (CPI) has the potential to affect fetal brain development and to cause brain injury. Our aim was to determine the effects of exposure to CPI during late gestation on brain and retinal structure and brain neurotrophin expression 8 weeks after birth. Six fetal sheep were exposed to CPI, induced by umbilico-placental embolization, from 120 days of gestation until term (approximately 147 days) such that fetal arterial oxygen saturation (SaO2) was reduced by approximately 50%. Nine untreated animals served as controls. During CPI, fetal arterial PO2, SaO2, pH, and growth were reduced (p < 0.05); these animals remained small at 8 weeks after birth. Structural abnormalities were present in the brains and retinae of all CPI-exposed lambs. There was a reduction in retinal width and in the number of retinal tyrosine hydroxylase-immunoreactive dopaminergic amacrine cells (p < 0.05). In the dorsal hippocampus the combined width of strata oriens and pyramidale was significantly reduced (p < 0.05). In the cerebellum there was a significant reduction (p = 0.05) in cerebellar cross-sectional area, most notably in the inner granule cell layer, and a reduction (p < 0.05) in immunoreactivity for the cytoskeletal protein neurofilament-200 in the white matter. Gliosis was present in either the cerebral white matter or cerebellum in all animals and degeneration was seen around blood vessels in 4/6 umbilico-placental embolization animals. There were reductions in brain-derived neurotrophic factor immunoreactivity in the hippocampus (p < 0.05) and tyrosine kinase B immunoreactivity in the cerebellum (p < 0.05). This study shows that late gestational CPI affects morphology and neurotrophin expression of the postnatal brain. These alterations in the brain can apparently persist from fetal life or become established after birth; some changes that were present in the fetus at term did not persist into postnatal life.

Fetal surgery, anaesthesiological considerations

Refined techniques and skills have enabled sophisticated prenatal diagnosis in utero and resulted in the newly evolving specialty of fetal surgery in a few centres worldwide. Most of the procedures performed today have been preceded by extensive experimental research in animals, whereas fetal anaesthesia is mainly based on clinical experience and a few studies performed in pregnant sheep. Major limitations of fetal surgery include the high frequency of preterm labour and delivery which may offset any fetal benefit of the surgical procedure. The development of more potent tocolytic drugs than the drugs currently available may thus be compared to the meaning of potent immunosuppressive agents in organ transplantation. Fetal mortality and maternal morbidity consequently lead to a more cautious way of treatment, as with the development of endoscopic fetal surgery. The invasive fetal surgery is still considered as being in a research stage in most cases. Therefore most procedures are performed as minimally invasive, avoiding substantial risks by accessing the uterus through minimal openings. Some new devices are under investigation for monitoring the myometrial electrical activity and mechanical contractility and the fetal electroencephalogram, the continuous monitoring of the fetal arterial oxygen saturation, PO2 and PCO2, and for monitoring fetal cerebral oxygenation, blood volume and blood flow by near infrared spectroscopy.

The influence of vacuum extractor on fetal oxygenation and newborn status.

The aim of this study was to determine the effects of vacuum extractor assisted delivery on fetal oxygenation and acid-base balance. Sixty-one women were enrolled in the present study. The subjects were divided into two groups. Group A, consisting of 39 women, had normal vaginal deliveries. Group B, consisting of 22 women, underwent a vacuum extractor assisted vaginal delivery. Fetal arterial oxygen saturation (SpO2) monitoring was used in all women after full cervical dilatation. After delivery, umbilical artery pH, pCO2, pO2 and base deficit (BDecf) levels were determined in all neonates. The mean FSpO2 value in Group A was 51.53+/-5.87% and in Group B 48.03+/-6.39% (p<0.03). The mean cord pH value in fetuses of Group A was 7.26+/-0.05, and in Group B 7.17+/-0.09. There was also a significant difference between the two groups with regards to mean pO2, pCO2 and BDecf values. Vacuum assisted vaginal delivery was associated with lower fetal arterial oxygen saturation levels as well as lower cord blood pH values compared to those seen after unassisted vaginal delivery. Although decreased, however, the above parameters remained within normal ranges.

Changes in 5alpha-pregnane steroids and neurosteroidogenic enzyme expression in fetal sheep with umbilicoplacental embolization.

Pregnane steroids have sedative and neuroprotective effects on the brain, due to interactions with the steroid-binding site of the GABAA receptor. In the adult brain, synthesis of the pregnane steroids is increased in response to stress. Therefore, we have used umbilicoplacental embolization to mimic chronic placental insufficiency during late gestation in sheep, to investigate the expression of the steroidogenic enzymes p450scc, 5alpha-reductase type I (5alphaRI), 5alpha-reductase type II (5alphaRII), and allopregnanolone (AP) content in the fetal brain. Umbilicoplacental embolization was induced from 114 d gestation (term approximately 147 d) by daily injection of inert microspheres into the umbilical artery and continued for 17-23 d. Fetal arterial oxygen saturation was reduced to approximately 60% of the preembolization value in each fetus, with a significant reduction in blood arterial Po2, pH, and plasma glucose concentrations (p < 0.05) and a significant increase in blood arterial Pco2 and plasma lactate concentrations (p < 0.05). At postmortem at 131-137 d gestation, embolized fetuses were growth-restricted (2.10 +/- 0.14 kg, n = 5) compared with age-matched controls (4.43 +/- 0.56 kg, n = 7, p < 0.05). Umbilicoplacental embolized fetuses showed increased P450scc expression in the primary motor cortex; 5alphaRI expression was not changed in any of the regions examined, whereas 5alphaRII expression was markedly increased in all brain regions. Brain AP content did not significantly change, whereas plasma concentrations were increased. These findings suggest that the increased expression of p450scc and 5alphaRII may be a response that maintains AP concentration in the fetal brain after compromised placental function and/or intrauterine stress.

Cerebral (31)P magnetic resonance spectroscopy and systemic acid-base balance during hypoxia in fetal sheep.

The purpose of this study was to investigate cerebral energy metabolism and acid-base homeostasis during impaired oxygen supply in fetal sheep. Systemic acid-base balance was correlated with the sequence in changes of cerebral phosphorus metabolite ratios and intracellular pH. Phosphorus magnetic resonance spectra were obtained from the brain of six fetal sheep simultaneously with repeated measurements of fetal arterial oxygen saturation and acid-base balance. Fetal hypoxia was induced by gradually reducing the oxygen supply to the anesthetized pregnant ewe to establish an intended arterial pH of 7.00 or lower. The ratio of phosphocreatine to inorganic phosphate decreased from 1.08 +/- 0.10 (SD) during the control period to 0.77 +/- 0.29 at an arterial pH between 7.20 and 7.25. The inorganic phosphate level became significantly increased at an arterial pH between 7.10 and 7.15 compared with control values. With ongoing arterial acidosis, cerebral intracellular pH decreased linearly with the arterial pH. At an arterial pH of 7.00, cerebral intracellular pH was decreased from 7.18 +/- 0.03 to 6.71 +/- 0.28, and phosphocreatine and nucleoside triphosphates levels were decreased significantly. In fetal sheep brain, cerebral oxidative phosphorylation (ratio of phosphocreatine to inorganic phosphate) is already affected at a mild arterial acidosis. At an arterial pH of 7.00 or lower, nucleoside triphosphates disappeared, which almost inevitably was followed by death in fetal sheep.

Feasibility of simultaneous application of fetal electrocardiography and fetal pulse oximetry.

Fetal pulse oximetry measures arterial oxygen saturation during delivery. The fetal electrocardiogram STAN S21 analyzes the repolarisation segment of ECG (ST) waveform, which is altered by the intramyocardial potassium release resulting from metabolic acidemia. This study aimed to evaluate the feasibility of a simultaneous application of pulse oximetry and fetal electrocardiography and to estimate any agreement between both methods indicating fetal compromise. In an observational trial 35 fetuses were simultaneously monitored by pulse oximetry (OBS-500) and electrocardiography. The evaluation focused on signal output and on the coincidence of desaturation in fetal pulse oximetry and on ST events. Desaturation was defined as a drop of at least 20% of oxygen saturation from base line level occurring within 1 min (steep desaturation) or duration of time (s) with oxygen saturation below the threshold of 30%. Statistical analysis was performed with the Mann-Whitney U-test for continuous variables. Signal output of the simultaneous application of both sensors was not significantly reduced in the electrocardiogram and in pulse oximetry (8% vs. 12% reduction). In 15 of the 35 fetuses, ST events indicating fetal hypoxia occurred. In these cases, pulse oximetry showed significantly more episodes of desaturation in comparison with fetuses without ST events. Median saturation during the ST events was significantly lower than in the recordings without ST events (60% vs. 74%, p < 0.05). In the umbilical artery these neonates showed significantly lower pH (7.19 vs. 7.33, p < 0.001), significantly higher lactate (5.1 vs. 3.4 mmol/l, p < 0.05) and significantly lower base deficit (-9.4mmol/l vs. -4.0 mmol/l, p < 0.001) levels. The combination of fetal pulse oximetry and fetal electrocardiography appears feasible and indicates signs of intermittent hypoxia. These findings may encourage the development of technology that combines these different methods of monitoring.

Hemodynamic changes during complete umbilical cord occlusion in fetal sheep related to hippocampal neuronal damage

Objectives: The purpose of our study was to examine the physiologic changes caused by 10 minutes of umbilical cord occlusion in fetal sheep and to determine the correlation between fetal acidemia or cerebral ischemia and hippocampal neuronal damage. Study design: Thirteen fetal sheep were instrumented and catheterized. Carotid artery blood flow (CaF), fetal mean arterial blood pressure (FMABP), pH, PCO2, base excess, oxygen saturation (SatO2), and PO2 were monitored throughout the occlusion study. Brain sections were examined for the hippocampal neuronal damage. Results: Our data showed severe ischemia (CaF: 10 ± 7 mL/min; FMABP: 29 ± 8 mm Hg) and acidemia (pH: 7.0 ± 0.05; base excess: −9.9 ± 2.4 mEq/L) at the end of occlusion. The neuronal damage score had significant correlations with ischemia and also with reperfusion, but not with the acidemic or hypoxic parameters. Conclusion: We demonstrated that the degree of hippocampal damage was correlated with the degree of ischemia and reperfusion. (Am J Obstet Gynecol 2003;188:413-8.)

Extracellular glutamate levels and neuropathology in cerebral white matter following repeated umbilical cord occlusion in the near term fetal sheep

Umbilical cord occlusion causes fetal hypoxemia which can result in brain injury including damage to cerebral white matter. Excessive glutamate release may be involved in the damage process. This study examined the relation between extracellular glutamate levels in the cerebral white matter of the ovine fetus during and after intermittent umbilical cord occlusion and the degree of resultant fetal brain injury. Fetal sheep underwent surgery for chronic catheterisation and implantation of an intra-cerebral microdialysis probe at 130 days of gestation (term ∼147 days). Four days after surgery (day 1), seven fetuses were subjected to 5×2 min umbilical cord occlusions, and on the following day (day 2) they were subjected to either 4 or 5×4 min umbilical cord occlusions; seven fetuses served as controls. Microdialysis samples were collected before, during and after the umbilical cord occlusions to determine extracellular glutamate levels in the cerebral white matter. Fetal blood gas status was measured and the fetal electrocorticogram was recorded continuously. During the periods of umbilical cord occlusions on both days 1 and 2, fetal arterial oxygen saturation, arterial partial pressure of oxygen and arterial pH decreased ( P<0.05) while arterial partial pressure of carbon dioxide increased ( P<0.05). All fetuses showed episodes of isoelectric electrocortical activity during umbilical cord occlusions on both days 1 and 2. In fetuses with patent microdialysis probes there were marked increases of glutamate efflux in the cerebral white matter following umbilical cord occlusion. Fetal brains were removed at autopsy on day 5 and subjected to histological assessment. Brain damage was observed in all fetuses exposed to cord occlusion, particularly in the periventricular white matter, with the most extensive damage occurring in the fetuses with the greatest increases in glutamate levels. We conclude that, in the unanesthetised fetus in utero, glutamatergic processes are associated with umbilical cord occlusion-induced brain damage in the cerebral white matter.

Changes in fetal blood flow in hypoxemia during labor

Objective: The aim of this study was evaluation of intrapartum Doppler velocimetry changes in fetuses with signs of fetal hypoxemia in fetal pulse oximetry (arterial hemoglobin saturation &lt;30%).Study design: Examinations were performed on 44 women in labor with singleton pregnancies. The subject of analysis was Doppler blood flow velocimetry in umbilical cord, fetal brain and lung. In all cases the following examinations were performed: blood flow velocimetry in middle cerebral artery (MCA), umbilical artery (UA), and pulmonary vein (PV). Among fetuses with normal Doppler velocimetry at the time of admission, we selected those with cephalic presentation and non‐reassuring fetal heart rate pattern during labor. The fetuses were included to the group of fetal pulse oximetry monitoring. All cases with signs of fetal distress in ctg and intrapartum fetal arterial oxygen saturation &lt;30% for at least 5 min were included to the study group. Fetuses with abnormal ctg and fetal oxygen saturation &gt;30% constituted the control group.Results: Doppler indices (PI, RI) in MCA were significantly lower in the presence of reduced oxygen saturation. Pulsatility and resistance index in UA in the study group were higher, comparing to the control group. But, there was no statistically significant difference between both groups in analyzing parameters. There were no statistically significant changes in parameters describing blood flow in pulmonary veins in both studied groups.Comments: The combined intrapartum fetal monitoring, including pulse oximetry and Doppler blood flow velocimetry, proved that the reduction of fetal arterial oxygen saturation (&lt;30%) is associated with changes in hemodynamics of fetal cerebral circulation. It has been not observed any changes in blood flow in umbilical artery and pulmonary vein in the presence of decreased fetal saturation.