Optimizing the management of acute, prolonged decelerations and fetal bradycardia based on the understanding of fetal pathophysiology.

Any acute and profound reduction in fetal oxygenation increases the risk of anaerobic metabolism in the fetal myocardium and, hence, the risk of lactic acidosis. On the contrary, in a gradually evolving hypoxic stress, there is sufficient time to mount a catecholamine-mediated increase in the fetal heart rate to increase the cardiac output and redistribute oxygenated blood to maintain an aerobic metabolism in the fetal central organs. When the hypoxic stress is sudden, profound, and sustained, it is not possible to continue to maintain central organ perfusion by peripheral vasoconstriction and centralization. In case of acute deprivation of oxygen, the immediate chemoreflex response via the vagus nerve helps reduce fetal myocardial workload by a sudden drop of the baseline fetal heart rate. If this drop in the fetal heart rate continues for >2 minutes (American College of Obstetricians and Gynecologists' guideline) or 3 minutes (National Institute for Health and Care Excellence or physiological guideline), it is termed a prolonged deceleration, which occurs because of myocardial hypoxia, after the initial chemoreflex. The revised International Federation of Gynecology and Obstetrics guideline (2015) considers the prolonged deceleration to be a "pathologic" feature after 5 minutes. Acute intrapartum accidents (placental abruption, umbilical cord prolapse, and uterine rupture) should be excluded immediately, and if they are present, an urgent birth should be accomplished. If a reversible cause is found (maternal hypotension, uterine hypertonus or hyperstimulation, and sustained umbilical cord compression), immediate conservative measures (also called intrauterine fetal resuscitation) should be undertaken to reverse the underlying cause. In reversible causes of acute hypoxia, if the fetal heart rate variability is normal before the onset of deceleration, and normal within the first 3 minutes of the prolonged deceleration, then there is an increased likelihood of recovery of the fetal heart rate to its antecedent baseline within 9 minutes with the reversal of the underlying cause of acute and profound reduction in fetal oxygenation. The continuation of the prolonged deceleration for >10 minutes is termed "terminal bradycardia," and this increases the risk of hypoxic-ischemic injury to the deep gray matter of the brain (the thalami and the basal ganglia), predisposing to dyskinetic cerebral palsy. Therefore, any acute fetal hypoxia, which manifests as a prolonged deceleration on the fetal heart rate tracing, should be considered an intrapartum emergency requiring an immediate intervention to optimize perinatal outcome. In uterine hypertonus or hyperstimulation, if the prolonged deceleration persists despite stopping the uterotonic agent, then acute tocolysis is recommended to rapidly restore fetal oxygenation. Regular clinical audit of the management of acute hypoxia, including the "the onset of bradycardia to delivery interval," may help identify organizational and system issues, which may contribute to poor perinatal outcomes.

The duration of intrapartum supplemental oxygen administration and umbilical cord oxygen content.

BACKGROUND: Maternal oxygen (O2) administration is a commonly performed intrauterine resuscitation technique though to improve fetal oxygenation. However, hyperoxygenation is known to be harmful in both neonates and adults. Currently, there are no formal recommendations on whether a certain dose or duration of O2 may be most helpful in improving umbilical cord gases or neonatal outcomes. OBJECTIVE: We tested the hypothesis that prolonged supplemental O2 exposure during labor is associated with increased umbilical cord O2 concentrations. STUDY DESIGN: This was a planned secondary analysis of a randomized noninferiority trial comparing O2 with room air in laboring patients. Patients were randomized to receive either 10 L/min O2 or room air at any point during active labor when they developed a category II fetal heart tracing that would otherwise require resuscitation. The primary outcome variable for this analysis was partial pressure of O2 in the umbilical vein. The secondary outcome variable was partial pressure of O2 in the umbilical artery. These outcome variables were compared between patients with short durations of O2 exposure and those with long durations of O2 exposure, defined as <75th percentile and ≥75th percentile of duration, respectively. The outcomes were also compared among the groups that received room air, O2 for short durations, and O2 for long durations. RESULTS: Among the 99 patients with paired and validated cord gases who were included in this analysis, the partial pressure of O2 in the umbilical vein was significantly lower in patients who received O2 supplementation for longer durations than in those who received O2 for shorter durations (median interquartile range 25.5 [21.5-33] vs 32.5 [26.5-37.5] mm Hg; P<.03). There was no difference in the partial pressure of O2 in the umbilical artery or other cord gases between the short and long duration O2 supplementation groups. Other methods of intrauterine resuscitation were similar between the short and long duration O2 supplementation groups. There was no difference in the partial pressure of O2 in the umbilical artery or in the umbilical vein when the room air, short duration O2 supplementation, and long duration O2 supplementation groups were compared. CONCLUSION: Longer durations of O2 exposure are not associated with a higher partial pressure of O2 in the umbilical cord. In fact, patients with longer durations of O2 exposure had lower partial pressure of O2 in the umbilical vein, suggesting impaired placental O2 transfer with prolonged O2 exposure.

Response to category II tracings: Does anything help?

Electronic fetal monitoring (EFM) is the most commonly used tool to screen for intrapartum fetal hypoxia. Category II EFM is present in over 80% of laboring patients and poses a unique challenge to management given the breadth of EFM features that fall within this category. Certain Category II patterns, such as recurrent late or recurrent variable decelerations, are more predictive of neonatal acidemia than others. A key feature among many published algorithms for Category II management is the use of intrauterine fetal resuscitation techniques including maternal oxygen administration, amnioinfusion, intravenous fluid bolus, discontinuation of oxytocin, and tocolytic administration. The goal of intrauterine resuscitation is to prevent or reverse fetal hypoxia. This is most likely to be successful if the etiology of the Category II EFM pattern is identified and targeted resuscitative measures are performed.

Overexpression of miR-124 Protects Against Neurological Dysfunction Induced by Neonatal Hypoxic-Ischemic Brain Injury.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of lifelong disabilities worldwide, without effective therapies and clear regulatory mechanisms. MicroRNAs (miRNAs) act as a significant regulator in neuroregeneration and neuronal apoptosis, thus holding great potential as therapeutic targets in HIE. In this study, we established the hypoxia-ischemia (HI) model in vivo and oxygen-glucose deprivation (OGD) model in vitro. Zea-longa score and magnetic resonance imaging were applied to verify HI-induced neuronal dysfunction and brain infarction. Subsequently, a miRNA microarray analysis was employed to profile miRNA transcriptomes. Down-regulated miR-124 was found 24 h after HIE, which corresponded to the change in PC12, SHSY5Y, and neurons after OGD. To determine the function of miR-124, mimics and lentivirus-mediated overexpression were used to regulate miR-124 in vivo and in vitro, respectively. Our results showed that miR-124 overexpression obviously promoted cell survival and suppressed neuronal apoptosis. Further, the memory and neurological function of rats was also obviously improved at 1 and 2 months after HI, indicated by the neurological severity score, Y-maze test, open field test, and rotating rod test. Our findings showed that overexpression of miR-124 can be a promising new strategy for HIE therapy in future clinical practice.

Ex Utero Extracorporeal Support as a Model for Fetal Hypoxia and Brain Dysmaturity.

BACKGROUND: Congenital heart disease (CHD) is associated with abnormal fetal brain development, a phenomenon that may be related to decreased cerebral oxygen delivery in utero. We used an artificial womb model to test the hypothesis that decreasing fetal oxygen delivery would reproduce physiologic changes identified in fetuses with CHD. METHODS: Experimental (hypoxemic) fetal lambs (mean gestational age, 111 ± 3 days; n = 4) and control animals (112 days; n = 5) were maintained in the artificial womb for a mean of 22 ± 6 days. Oxygen delivery was reduced to 15.6 ± 1.0 mL/kg/min in the hypoxemia animals versus 21.6 ± 2.0 mL/kg/min in the control animals. Blood chemistry analysis and sonographic evaluation were performed daily. An additional control group (n = 7) was maintained in utero and harvested for analysis at gestational age 134 ± 4 days. RESULTS: Physiologic variables were monitored continuously, and no statistical differences between the groups were identified. Fetal oxygen delivery and arterial partial pressure of oxygen were remarkably lower in the experimental group longitudinally. Increased umbilical artery and decreased middle cerebral artery resistance resulted in a lower cerebral to umbilical resistance ratio, similar to the brain sparing effect observed in human fetuses with CHD. Experimental brains were smaller than control brains in relation to the calvarium on magnetic resonance. CONCLUSIONS: Sustained hypoxemia in fetal sheep leads to altered cerebrovascular resistances and loss of brain mass, similar to human fetuses with CHD. This unique model provides opportunities to investigate the pathologic process underlying CHD-associated brain dysmaturity and to evaluate potential fetal neuroprotective therapies.

Perinatal Asphyxia from the Obstetric Standpoint: Diagnosis and Interventions.

Perinatal asphyxia is a general term referring to neonatal encephalopathy related to events during birth. Asphyxia refers to a deprivation of oxygen for a duration sufficient to cause neurologic injury. Most cases of perinatal asphyxia are not necessarily caused by intrapartum events but rather associated with underlying chronic maternal or fetal conditions. Of intrapartum causes, obstetric emergencies are the most common and are not always preventable. Screening high-risk pregnancies with ultrasound, Doppler velocimetry, and antenatal testing can aid in identifying fetuses at risk. Interventions such as intrauterine resuscitation or operative delivery may decrease the risk of severe hypoxia from intrauterine insults and improve long-term neurologic outcomes.

Preventing deaths from complications of labour and delivery.

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.

Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses: a case for the afferent cholinergic anti-inflammatory pathway?

BACKGROUND: Neuroinflammation in utero may contribute to brain injury resulting in life-long neurological disabilities. The pivotal role of the efferent cholinergic anti-inflammatory pathway (CAP) in controlling inflammation, e.g., by inhibiting the HMGB1 release, via the macrophages' α7 nicotinic acetylcholine receptor (α7nAChR) has been described in adults, but its importance in the fetus is unknown. Moreover, it is unknown whether CAP may also exert anti-inflammatory effects on the brain via the anatomically predominant afferent component of the vagus nerve. METHODS: We measured microglial activation in the ovine fetal brain near term 24 h after the umbilical cord occlusions mimicking human labor versus controls (no occlusions) by quantifying HMGB1 nucleus-to-cytosol translocation in the Iba1+ and α7nAChR+ microglia. Based on multiple clinical studies in adults and our own work in fetal autonomic nervous system, we gauged the degree of CAP activity in vivo using heart rate variability measure RMSSD that reflects fluctuations in vagus nerve activity. RESULTS: RMSSD correlated to corresponding plasma IL-1ß levels at R = 0.57 (p = 0.02, n = 17) and to white matter microglia cell counts at R = -0.89 (p = 0.03). The insult increased the HMGB1 translocation in α7nAChR+ microglia in a brain region-dependent manner (p < 0.001). In parallel, RMSSD at 1 h post insult correlated with cytosolic HMGB1 of thalamic microglia (R = -0.94, p = 0.005), and RMSSD at pH nadir correlated with microglial α7nAChR in the white matter (R = 0.83, p = 0.04). Overall, higher RMSSD values correlated with lower HMGB1 translocation and higher α7nAChR intensity per area in a brain region-specific manner. CONCLUSIONS: Afferent fetal CAP may translate increased vagal cholinergic signaling into suppression of cerebral inflammation in response to near-term hypoxic acidemia as might occur during labor. Our findings suggest a new control mechanism of fetal neuroinflammation via the vagus nerve, providing novel possibilities for its non-invasive monitoring in utero and for targeted treatment.

Cord blood mononuclear cells prevent neuronal apoptosis in response to perinatal asphyxia in the newborn lamb.

Perinatal asphyxia is a significant cause of death or long-term neurodevelopmental impairment. Hypothermia, currently the only effective treatment, leads to modest improvements, but new therapeutic strategies are required. Umbilical cord blood (UCB) mononuclear cells have potent anti-inflammatory properties and may reduce neuropathology. This study examined whether autologous UCB mononuclear cells were neuroprotective when administered to newborn lambs at 12 h after birth asphyxia. At caesarean section, birth asphyxia was induced by clamping the umbilical cord until mean arterial blood pressure decreased to 18-20 mmHg. Asphyxia (n = 20) or control (n = 11) lambs were resuscitated and maintained, with magnetic resonance spectroscropy (MRS) performed at 12 and 72 h, and were then killed at 72 h. Cord blood was collected once the cord was clamped, and mononuclear cells were isolated and labelled fluorescently and administered to control (n = 3) or asphyxia (n = 8) lambs. Asphyxia induced a significant increase in cellular apoptosis (caspase-3 immunopositive) within all brain regions examined, including cortex, hippocampus, thalamus, striatum and subcortical white matter (P < 0.01 vs. control). Additionally, asphyxia induced significant and widespread astrogliosis and increased inflammatory cells (activated microglia and macrophages). The administration of UCB mononuclear cells (asphyxia+UCB) significantly decreased neuronal apoptosis, astrogliosis and inflammation (P < 0.05 vs. asphyxia alone). Asphyxia+UCB lambs also demonstrated decreased brain metabolites lactate:choline (P = 0.01) and lactate:N-acetylaspartate (P < 0.01) from 12 to 72 h, detected using MRS. Autologous UCB mononuclear cell treatment restores normal brain metabolism following perinatal asphyxia, and reduces brain inflammation, astrogliosis and neuronal apoptosis, supporting its use as a neuroprotective therapy following asphyxia.

Carbon Monoxide Exposure During Pregnancy.

IMPORTANCE: Carbon monoxide (CO) is the leading cause of poisoning in the United States and is associated with high maternal and fetal mortality rates. Given the nonspecific signs and symptoms of toxicity, cases may go unsuspected or attributed to other etiologies. As CO adversely affects both mother and fetus, it is important for practitioners to recognize and treat poisoning in a timely manner. OBJECTIVE: We seek to assist practitioners with understanding the physiology and recognizing the presentations of both acute and chronic CO poisoning, as well as provide information on diagnosis and treatment options. We also conducted a review of cases described in the literature during the past half century to show varying presentations and treatment methodologies. EVIDENCE ACQUISITION: A qualitative literature search was conducted using PubMed and Google Scholar for articles published between 1970 and 2014 that assessed cases of CO poisoning during pregnancy. Excluded studies were not in English or contained nonhuman subjects. RESULTS: Nineteen published reports of CO poisoning during pregnancy described in varying levels of detail were found in the literature from 1971 to 2010. CONCLUSIONS AND RELEVANCE: Carbon monoxide poisoning requires a high degree of suspicion. Diagnosis is made based on initial history and physical evaluation and assessment of environmental CO levels; presenting carboxyhemoglobin levels may be poor indicators of severity of disease. Oxygen therapy should be initiated promptly in all possible cases with consideration of hyperbaric oxygen therapy in cases of significant maternal exposure. Treatment requires a longer duration for fetal CO elimination than in the nonpregnant patients. Importantly, practitioners should educate pregnant patients on prevention.

[Protection effect of recombiant human erythropoietin preconditioning against intrauterine hypoxic-ischemic brain injury and its influence on expression of caspase-3 protein in brain tissue].

OBJECTIVE: To investigate the effects of recombine human erythropoietin (rhEPO) on neural cells apoptosis and the expression of Caspase-3 protein in brain tissue of fetal rats after intrauterine hypoxic-ischemic brain injury. METHODS: Forty-four Sprague-Dawley rats on 19 days of pregnancy were divided into rhEPO treated group, ischemia-reperfusion group and sham-operated group. Intrauterine hypoxic-ischemic injury of fetal rats was induced by bilateral occlusion of the utero-ovarian artery for 20 min. rhEPO (5000 U/kg) was injected into rats through caudal vein in rhEPO treated group while saline was injected into rats in hypoxic-ischemic group 30 min before hypoxic-ischemic injury. The brain samples in rhEPO treated group and hypoxic-ischemic group were obtained at 30 min, 3 h, 6 h, 24 h and 48 h respectively after artery clamping. There was no hypoxic-ischemic injury in sham-operated group, so the brain samples were obtained at 24 hours after sham operation. Neuroapoptosis in brain tissue was measured by TdT mediated dUTP-biotin nick end labeling (Tunel) staining. The expression of Caspase-3 protein was observed by immunohistochemistry. RESULTS: The number of apoptosis cells in fetal rat hippocampus after intrauterine hypoxic-ischemic increased progressively with reperfusion. Compared with the I/R group, the number of apoptosis cells decreased in rhEPO treated group (P < 0.01). The expression of Caspase-3 increased rapidly after 3 hours from the reperfusion in the I/R group. Compared with the I/R group, there was less expression of Caspase-3 in rhEPO treated group (P < 0.01). CONCLUSION: rhEPO showed the effects to inhibit the apoptosis of fetal neural cells and the expression of Caspase-3 protein due to intrauterine hypoxic-ischemic brain injury.

[Caesarean sections under regional anesthesia: pros and cons of supplementary oxygen]. / Sectio caesarea in Regionalanästhesie : Pro und Kontra der supplementären Sauerstoffgabe.

The routine administration of supplemental oxygen to women undergoing elective caesarean section under regional anesthesia in order to optimize oxygen supply to the fetus is common anesthetic practice in many German hospitals. However, this practice has been controversially discussed in the non-German literature for many years. This review presents and discusses the pros and cons of routinely providing supplemental oxygen to a parturient during caesarean section on the basis of the literature published over the last 30 years. Proponents of routine oxygen administration point to potential and unforeseeable risks of caesarean sections and consider the prophylactic administration of oxygen based on physiological considerations to be advantageous in terms of patient safety. Interestingly, data regarding the effects of an increased maternal FIO2 on improvement of fetal oxygenation are inconsistent, therefore, no unambiguous recommendation concerning which FIO2 to choose can be given. Opponents of routine oxygen supplementation allude above all to an increase in free radical activity in both mother and fetus; however, data in this respect are not consistent either. As supplemental oxygen to patients undergoing elective caesarean section without any risk factors under regional anesthesia is associated with potential risks while no advantage has so far been demonstrated, routine administration of oxygen has to be challenged and is no longer considered to be indicated by many. On the contrary, in cases of emergency with a concomitant risk of hypoxia for mother and fetus, administration of oxygen is indispensable in the light of present data.

[A 25-year study (1983-2008) of children's health outcomes after hyperbaric oxygen therapy for carbon monoxide poisoning in utero]. / Devenir des enfants intoxiqués au monoxyde de carbone en période foetale et traités par oxygéno- thérapie hyperbare--etude d'une cohorte constituée sur 25 ans de 1983 a 2008.

Carbon monoxide (CO) poisoning during pregnancy can be fatal for the fetus, or cause bone malformations or encephalopathy, depending on the stage of pregnancy at which the poisoning occurs. Fewer cases of death and encephalopathy have been reported since the adoption of maternal hyperbaric oxygen (HBO) therapy in this setting, but these children's long-term psychomotor development and growth remains to be documented. A prospective single-center cohort study spanning 25 years (1983 - 2008) included all pregnant women living in the Nord-Pas-de-Calais region of France who received HBO for CO poisoning and who gave birth to a living child. A descriptive analysis of the women and children was performed first. A control group of children was created by matching with anonymous files from local authorities. The results of the children's compulsory health & development assessments were used to compare the two groups. 406 women were included in the study, of whom 6 were expecting twins. The psychomotor development of 412 children was monitored, up to the day 8 assessments in 388 cases, the year 2 assessments in 276 cases, and the year 6 assessments in 232 cases. Sixty children have not yet reached the age of 6 years. No significant differences in psychomotor or height/weight criteria (p > 0.05 for both) were found between the exposed and unexposed children. No malformations were reported. These findings support the use of HBO therapy for all expectant mothers exposed to CO poisoning. No specific follow-up of the children is necessary if their neonatal status is normal.

Impact of therapeutic hypothermia on MRI diffusion changes in neonatal encephalopathy.

OBJECTIVE: The objective of this work was to determine the impact of therapeutic hypothermia (TH) on the magnitude and time course of mean diffusivity (MD) changes following hypoxic-ischemic encephalopathy (HIE) in newborns. METHODS: Cerebral MRI scans of infants undergoing whole body TH for HIE from 2007 to 2010 were retrospectively reviewed. The data were analyzed identically to a control group of newborns with HIE previously published, prior to the development of TH. Anatomic injury was defined on T1- and T2-weighted ("late") MRI obtained after the fifth day of life. Since MD values vary regionally, the ratios of MD values for injured and normal tissue were calculated for areas of injury. Normal values were obtained from corresponding brain regions of 12 infants undergoing TH who had no injury on MRI studies. RESULTS: Twenty-three of 59 infants who underwent TH and MRI displayed cerebral injury on late MRI and were included in the study. MD ratios were decreased in all injured infants within the first 7 days of life. The return of MD to normal (pseudonormalization) occurred after the tenth day as compared to 6-8 days in the control group. Infants with severest injury demonstrated greater reduction in MD, but no difference in time to pseudonormalization. CONCLUSION: TH slows the evolution of diffusion abnormalities on MRI following HIE in term infants.

Intrauterine resuscitation during labor.

Intrauterine resuscitative measures are commonly initiated during labor when the fetal heart rate (FHR) pattern is indeterminate or abnormal. The most effective use of these measures is directed at the presumed underlying cause. However, some FHR patterns are nonspecific, while others are such that intrauterine resuscitation will not remedy the situation. The goals of intrauterine resuscitation during labor are, at its best, to reverse any hypoxia that might lead to further deterioration, and at the very least to avoid prolonged periods of indeterminate or abnormal FHR patterns, which may cause unnecessary concern for caregivers and patients and unnecessary operative intervention.

Time of birth and risk of neonatal death at term: retrospective cohort study.

OBJECTIVE: To determine the effect of time and day of birth on the risk of neonatal death at term. DESIGN: Population based retrospective cohort study. SETTING: Data from the linked Scottish morbidity records, Stillbirth and Infant Death Survey, and birth certificate database of live births in Scotland, 1985-2004. SUBJECTS: Liveborn term singletons with cephalic presentation. Perinatal deaths from congenital anomalies excluded. Final sample comprised 1,039,560 live births. MAIN OUTCOME MEASURE: All neonatal deaths (in the first four weeks of life) unrelated to congenital abnormality, plus a subgroup of deaths ascribed to intrapartum anoxia. RESULTS: The risk of neonatal death was 4.2 per 10,000 during the normal working week (Monday to Friday, 0900-1700) and 5.6 per 10 000 at all other times (out of hours) (unadjusted odds ratio 1.3, 95% confidence interval 1.1 to 1.6). Adjustment for maternal characteristics had no material effect. The higher rate of death out of hours was because of an increased risk of death ascribed to intrapartum anoxia (adjusted odds ratio 1.7, 1.2 to 2.3). Though exclusion of elective caesarean deliveries attenuated the association between death ascribed to anoxia and delivery out of hours, a significant association persisted (adjusted odds ratio 1.5, 1.1 to 2.0). The attributable fraction of neonatal deaths ascribed to intrapartum anoxia associated with delivery out of hours was 26% (95% confidence interval 5% to 42%). CONCLUSIONS: Delivering an infant outside the normal working week was associated with an increased risk of neonatal death at term ascribed to intrapartum anoxia.

Influence of carbon monoxide poisoning on the fetal heart monitor tracing: a report of 3 cases.

BACKGROUND: The diagnosis of carbon monoxide poisoning in the third trimester of pregnancy requires an index of suspicion, and the appearance of the fetal heart monitor tracing may help in this regard. CASES: Three cases of third-trimester acute carbon monoxide poisoning occurred. In each pregnancy, the fetal heart monitor tracing on admission was correlated with the maternal carboxyhemoglobin level, and how the pattern changed following the institution of therapy was analyzed. CONCLUSION: In all 3 cases, the initial fetal heart rate pattern demonstrated decreased variability with an elevated baseline and an absence of accelerations and decelerations. Within 45-90 minutes of treatment onset, the baseline fetal heart rate dropped by 20-40 beats per minute, the variability became moderate, and accelerations occurred. Absent accelerations with minimal variability, if caused by uteroplacental insufficiency, are usually preceded by recurrent decelerations. Absent accelerations with minimal variability in the absence of recurrent decelerations may suggest another cause, of which carbon monoxide intoxication can be added to the differential, especially since this disorder often has nonspecific clinical symptoms.