Distribution of oxygenated blood flow at three different routes of extracorporeal membrane oxygenation in exteriorized fetal lambs.

OBJECTIVE: The purpose of this study was to determine which extracorporeal membrane oxygenation (ECMO) route best approximates the normal physiologic pattern of oxygenated blood distribution in fetal lambs submerged in warm saline solution. STUDY DESIGN: Six fetal lambs ranging from 113 to 129 days of gestation were delivered by cesarean section and oxygenated with ECMO in a warm saline solution bath. We compared the distribution of oxygenated blood flow during intact placental circulation with 3 routes of ECMO, from the right atrium to the carotid artery (V-A), from the right atrium to umbilical vein (V-UV), and from the right atrium with umbilical artery to umbilical vein [(V + UA)-UV], in exteriorized fetal lambs. Distribution of oxygenated blood flow was determined by nonradioactive colored microspheres. RESULTS: The ECMO blood flow rate through the catheters during V-A, V-UV or (V + UA)-UV ECMO ranged at 150 to 300 ml/min. Among the 3 different routes of ECMO, the oxygenated blood distribution in (V + UA)-UV showed the best correlation with placental-fetal blood flow, particularly in the brain and heart. CONCLUSION: This study indicated that (V + UA)-UV ECMO most closely approximates normal intact placental-fetal blood flow distribution in fetal lambs.

Obstetric emergencies precipitated by malignant brain tumors.

OBJECTIVE: Our goal was to present a case series of pregnancy-associated malignant brain tumors. STUDY DESIGN: A review was conducted from 1978-1998 at 5 hospitals. RESULTS: Ten women were diagnosed with a malignant brain tumor during pregnancy (n = 8) or post partum (n = 2). Patients diagnosed antenatally exhibited severe symptoms, manifest between 27 and 32 weeks' gestation. Six were emergently delivered of their infants because of maternal deterioration, and 2 were delivered electively in the early third trimester after documentation of fetal pulmonary maturity. There were 4 maternal deaths and 1 neonatal death; all of the other infants maintained viability. CONCLUSIONS: Malignant brain tumors rarely occur in pregnancy. In contrast to reports that describe an indolent course, each of the 8 antenatal patients experienced a neurologic crisis. If symptoms are amenable to pharmacologic control, we advocate delivery in the early third trimester after documentation of fetal pulmonary maturity. To minimize temporal lobe or cerebellar herniation in neurologically unstable patients, a consideration should be made for cesarean delivery with the patient under general anesthesia, followed by immediate neurosurgical decompression.

Histologic and biochemical study of the brain, heart, kidney, and liver in asphyxia caused by occlusion of the umbilical cord in near-term fetal lambs.

OBJECTIVE: We sought to determine the relationship between the degree of histologic changes in the brain, heart, kidney, and liver in fetal lambs after severe asphyxia and to analyze the role of oxidative stress in the pathogenesis of fetal multiple organ failure. STUDY DESIGN: Eight chronically instrumented near-term fetal lambs were asphyxiated by partial umbilical cord occlusion for approximately 60 minutes until the fetal arterial pH reached <6.9 and the base excess reached <-20 mEq/L. An additional 6 fetuses were used as sham-asphyxiated controls. Fetal heart rates, blood pressure, fetal breathing movements, and arterial blood gases and acid-base states were serially monitored. The brain, heart, kidney, and liver were collected 72 hours after asphyxia, processed, and histologically examined after hematoxylin and eosin staining. Fetal brain histologic features were classified into 5 grades, with 5 being the most severe damage. The other organs were examined histologically by pathologists who were blinded to the treatment. Each organ was assayed for tissue concentrations of thiobarbituric acid-reactive substances, superoxide dismutase, glutathione, lactate, and glucose. RESULTS: Myocardial changes of necrosis, phagocytosis, and contraction bands occurred in only 2 of the most severely (grade 5) brain-damaged fetuses. The same 2 cases showed fatty changes and congestion in the liver. In the kidney all asphyxiated cases showed tubular necrosis, but glomeruli were generally spared. Of the measures of oxidative stress, only liver tissue levels of thiobarbituric acid-reactive substances and superoxide dismutase were significantly higher in the asphyxiated group than in the control group, but there was no correlation with the degree of damage. Lactate level was higher only in the heart in the asphyxiated fetuses. CONCLUSION: Renal tubular damage was seen with all degrees of asphyxia, despite variable brain damage. Histologic changes in the myocardium and liver were seen only with the most severe brain damage. Oxidative stress appears to play a role in the pathogenesis of liver damage.

Oxidative stress, brain white matter damage and intrauterine asphyxia in fetal lambs.

In order to examine the role of oxidative stress in asphyxia-induced perinatal brain damage, near-term fetal lambs were subjected to umbilical cord occlusion for approximately 60min until fetal arterial pH diminished to less than 6.9 and base excess to less than -20 meq/l. The levels of superoxide, hydrogen peroxide, glutathione (GSH) and thiobarbiturate-reactive substances (TBARS) within brain grey and white matter were determined at 72h to correlate with morphological changes. Although the topography and extent of brain damage varied somewhat from case to case, ranging from focal infarction in grey or white matter to subtle and patchy alterations of white matter, the telencephalic white matter appeared to bear the brunt of damage as compared to other regions. The parietal white matter, in particular was often the seat of early pathological changes that could be seen in isolation. These white matter changes were accompanied by significant increases in hydrogen peroxide and TBARS levels as compared to those in grey matter. In another set of experiments, 8 different brain regions were assayed for TBARS, GSH and superoxide dismutase (SOD). A highly significant rise in the levels of TBARS was again noted in the parietal and frontal white matter. SOD levels were higher in the frontal and parietal white matter, basal ganglia and cerebellum. Cerebral cortical and hippocampal neurons were relatively unaffected until accompanied by more severe damage to grey and white matter at other sites. These results suggest that the developing telencephalic white matter appears to be most vulnerable to the effects of intrauterine fetal asphyxia and that oxidative stress may be a major contributing factor in the pathogenesis of perinatal hypoxic-ischemic encephalopathy.

Two sinusoidal heart rate patterns in fetal lambs undergoing extracorporeal membrane oxygenation.

OBJECTIVES: The study analyzed the phase relationship between fetal heart rate and arterial blood pressure fluctuation during sinusoidal heart rate patterns in fetal lambs. STUDY DESIGN: Thirty-two fetal lambs were placed on extracorporeal membrane oxygenation after cesarean delivery at ages ranging between 113 and 133 days' gestation. Sinusoidal heart rate patterns persisting for >10 minutes were analyzed. The relationships between the sinusoidal heart rate cycles and the arterial blood pressure cycles were quantitatively expressed in degrees by timing the zenith and the nadir of each and assigning a phase-angle index (with 0 [360] and 180 degrees being synchronized and reciprocal, respectively). Simultaneous blood samples were taken from the 4 different sites of the fetal circulation for blood gas and acid-base analysis when the sinusoidal heart rate pattern appeared. Regional cerebral blood flow was determined by means of the colored microsphere technique in 8 fetuses with sinusoidal patterns and 7 control fetuses. RESULTS: Sinusoidal heart rate patterns were observed in 13 (40.6%) of the 32 fetal lambs. Two types of fetal heart rate and arterial blood pressure relationship could be recognized during sinusoidal pattern, the reciprocal type (n = 7) and the synchronized type (n = 9). A reciprocal type of sinusoidal pattern preceded a synchronized type pattern in 3 lambs that showed sinusoidal patterns at different stages of the experiment. The reciprocal type was associated with a higher baseline heart rate and amplitude of the sinusoidal heart rate pattern than was the synchronized type. The synchronized type was associated with a lower pH and base excess than was the reciprocal type. The cerebral blood flow in the medulla oblongata was significantly lower during the synchronized type pattern than during the reciprocal type pattern. CONCLUSION: There are 2 types of sinusoidal heart rate pattern. A synchronized type sinusoidal heart rate pattern may indicate more advanced fetal compromise than is associated with a reciprocal type pattern.

Fetal heart rate patterns in postasphyxiated fetal lambs with brain damage.

OBJECTIVE: We previously showed that in asphyxiated fetal lambs the duration of hypotension correlated well with the severity of histologic damage to the brain, whereas the duration of bradycardia did not. This study compares fetal heart rate patterns with the degree of histologic damage to the brain. STUDY DESIGN: Twelve chronically instrumented near-term fetal lambs were subjected to asphyxia by umbilical cord occlusion until fetal arterial pH was <6. 9 and base excess was <-20 mEq/L. An additional 4 fetuses served as sham-asphyxia controls. Fetal heart rate (from electrocardiogram), arterial blood pressure, fetal breathing movements, and electrocorticogram were continuously monitored before, during, and for 72 hours after asphyxia. Fetal brain histologic features were categorized as mild (group 1, n = 5), moderate (group 2, n = 4), and severe (group 3, n = 3). Long-term fetal heart rate variability expressed as amplitude range was assessed visually every 5 minutes from 30 minutes before asphyxia until 2 hours of recovery and at 6, 12, 24, 48, and 72 hours of recovery. RESULTS: Long-term fetal heart rate variability amplitude decreased from 32 +/- 17 beats/min (mean +/- SEM) preocclusion to 4 +/- 13 beats/min at the end of occlusion (P <.001) without significant differences among the 3 groups. During 10 to 45 minutes of recovery, the long-term variability of group 1 was significantly greater than that of groups 2 and 3. At 24 to 72 hours of recovery, the long-term variability of groups 1 and 2 was significantly higher than that of group 3, which was almost 0. The "checkmark" and sinusoidal fetal heart rate patterns were observed during the recovery period in groups 2 and 3. CONCLUSIONS: Decreased long-term fetal heart rate variability and the "checkmark" and sinusoidal fetal heart rate patterns were indicators of the severity of asphyxial histologic damage in the fetal brain.

Brain lipid peroxidation and antioxidant levels in fetal lambs 72 hours after asphyxia by partial umbilical cord occlusion.

OBJECTIVES: The purpose of this study was to explain the role of oxidative stress in the pathogenesis of brain damage caused by intrauterine fetal asphyxia. STUDY DESIGN: Six chronically instrumented near-term fetal lambs were subjected to asphyxia by partial umbilical cord occlusion for approximately 60 minutes until fetal arterial pH diminished to less than 6.9 and base excess to less than -20 mEq. Another six fetuses surgically prepared but not occluded were used as control. Fetuses were killed after 72 hours and eight different brain regions (frontal and parietal gray matter, frontal and parietal white matter, basal ganglia, thalamus, hippocampus, and cerebellum) were dissected and assayed for thiobarbituric acid reactive substances, glutathione, and superoxide dismutase. RESULTS: Thiobarbituric acid reactive substance levels in asphyxiated animals were elevated in frontal and parietal white matter, basal ganglia, and thalamus compared with those in controls. The concentrations of superoxide dismutase in the asphyxiated group were also higher in frontal and parietal white matter, basal ganglia, and cerebellum compared with those in the control group. Between the two groups, however, glutathione concentrations did not differ significantly. CONCLUSION: These results suggest that oxidative stress may be a major contributing factor to the development of brain damage in intrauterine fetal asphyxia.

Physiologic and histologic changes in near-term fetal lambs exposed to asphyxia by partial umbilical cord occlusion.

OBJECTIVES: Our purpose was to characterize the histologic changes in the asphyxiated fetal lamb brain and to correlate the severity of these changes with fetal physiologic parameters during and after asphyxia. STUDY DESIGN: Seventeen near-term fetuses were used for analysis: control group without manipulation (n = 4, 132 +/- 1.1 days of gestation at autopsy, mean +/- SEM), sham-asphyxia control group (n = 3, 132 +/- 1.3 days), and asphyxiated group, which successfully survived 72 hours after asphyxia (n = 10, 130 +/- 1.0 days). Asphyxia was produced by umbilical cord occlusion lasting for approximately 60 minutes until fetal arterial pH diminished to < 6.9 and base excess to < -20 mEq/L. Fetal heart rate, blood pressure, and electrocorticographic activity were continuously monitored. The fetuses were killed 72 hours after asphyxia, and the brains were fixed in formalin and processed for histologic and immunocytochemical studies. RESULTS: Neuropathologic changes varied from case to case, ranging from almost total infarction of cortical and subcortical structures to extremely subtle and patchy white matter alterations characterized by slight vacuolization of the white matter or slight to moderate increases in cellularity confined to the junction of cerebral cortex and white matter. Even fetuses that showed full recovery of all physiologic parameters, including electrocorticographic activity, demonstrated subtle but distinct white matter lesions. The gray matter, including the hippocampal neurons, was generally spared in these cases. Electrocorticographic parameters, duration of hypotension during asphyxia, and delayed recovery of blood lactate concentrations correlated well with the histologic grading of brain damage. CONCLUSIONS: Asphyxia by partial umbilical cord occlusion in near-term fetal lambs produces variable neuropathologic changes. The mildest change is a white matter lesion characterized by vacuolization and loss of myelin or by increased cellularity in the damaged regions.

Cardiac oxygenation by extracorporeal membrane oxygenation in exteriorized fetal lambs.

OBJECTIVE: The purpose of this study was to determine the degree of cardiac oxygenation produced by different routes of extracorporeal membrane oxygenation in fetal lambs submerged in warm saline solution. STUDY DESIGN: Seven fetal lambs ranging in age from 113 to 133 days of gestation were delivered by cesarean section and oxygenated with extracorporeal membrane oxygenation. To maintain the patency of the ductus arteriosus, prostaglandin E1 was continuously infused intravenously to the fetus. Initially the extracorporeal membrane oxygenation route was from the right atrium to the carotid artery. Then the extracorporeal membrane oxygenation route was changed to flow from the right atrium to the umbilical vein. The fetus was kept in a warm saline solution bath, and the fetal circulation was maintained. Extracorporeal membrane oxygenation flow ranged between 100 and 200 ml/min throughout the experiment. Simultaneous blood samples were taken during both types of extracorporeal membrane oxygenation from the following points in the fetal circulation: premembrane (least oxygenated blood leaving the fetus from the right atrium), postmembrane (oxygenated blood returning to the fetus), the carotid artery, and the left ventricle. The respiratory gases and pH of each sample were measured. Six fetuses received nonradioactive colored microspheres injected into the oxygenated blood returning to the fetus flow before returning to the fetuses during both types of extracorporeal membrane oxygenation. After the animals were killed, microspheres were counted in the myocardium separately taken from the right and left atria and the right and left ventricles to determine cardiac blood flow. RESULTS: During right atrium to carotid artery extracorporeal membrane oxygenation, left ventricle PO2 remained low as postmembrane PO2 increased; these values were not significantly correlated (r = 0.234, p = 0.61). During right atrium to umbilical vein extracorporeal membrane oxygenation, left ventricle and postmembrane PO2 exhibited a significant positive correlation (r = 0.855, p = 0.014). When the extracorporeal membrane oxygenation route was switched from the right atrium to carotid artery to the right atrium to umbilical vein, there was a significant increase in left ventricle PO2 and a decrease in left ventricle PCO2, whereas the respiratory gases and pH remained unchanged at other sites in the circulation. Microsphere counts were consistently higher during right atrium to umbilical vein extracorporeal membrane oxygenation than during right atrium to carotid artery extracorporeal membrane oxygenation in all four samples from different parts of myocardium (p < 0.001 by paired t test). CONCLUSION: More effective cardiac oxygenation is provided by right atrium to umbilical vein extracorporeal membrane oxygenation than by right atrium to carotid artery extracorporeal membrane oxygenation.

Oxygenation in fetal lambs supported by extrauterine right atrium to artery extracorporeal membrane oxygenation.

OBJECTIVE: Our purpose was to determine the adequacy of oxygenation, particularly cranial and cardiac oxygenation, in exteriorized fetal lambs on right atrium to artery extracorporeal membrane oxygenation. STUDY DESIGN: Thirteen fetal lambs were placed on right atrium to artery extracorporeal membrane oxygenation between the gestational ages of 113 and 133 days. Various PO2 and oxygen saturation (SO2) values were obtained by varying the oxygen concentrations at the oxygenator membrane. Blood gases, pH, and SO2 were observed on samples taken before and after membrane oxygenation from the left ventricle and through the cranial carotid arterial catheter. These were compared with control values obtained before the cessation of umbilical circulation. Fetal coronary oxygenation was represented by left ventricle PO2 and SO2 and cranial oxygen by carotid artery PO2 and SO2. RESULTS: We classified oxygen saturation as low, medium, and high on the basis of the level of postmembrane SO2. Carotid artery cranial oxygenation in the low SO2 group was equivalent to control values, but that in the medium and high SO2 groups was significantly higher than in the control group. Left ventricle oxygenation was consistently lower than cranial oxygenation in any SO2 group. In the low group left ventricle oxygenation was significantly lower than the control values. CONCLUSIONS: Right atrium to artery extracorporeal membrane oxygenation appears sufficient to oxygenate the fetal cranial circulation but may be inadequate for the efficient distribution of oxygenated blood into the left ventricle and thus the coronary circulation.

Obstetrics and gynecology.

Treating HIV-infected pregnant patients and the newborn with zidovudine reduced the percentage of HIV-infected infants. Uterine myomas are being treated effectively with gonadotropin-releasing hormone analogues. Nonoperative therapy is being used in the patient with an ectopic pregnancy.

Term early-onset neonatal seizures: obstetric characteristics, etiologic classifications, and perinatal care.

OBJECTIVE: To describe obstetric characteristics and etiologic classifications and assess perinatal care in term neonates with early-onset seizures. METHODS: We performed a retrospective review of neonatal and obstetric records of neonates delivered at term with a diagnosis of early-onset seizures between January 1981 and December 1992 at Long Beach Memorial Medical Center. Data regarding obstetric characteristics and etiologic classifications of the seizures were abstracted from the medical records. Lack of antepartum testing in high-risk patients, delayed intervention with nonreassuring antepartum or intrapartum fetal heart rate patterns, birth trauma, and failure to use prophylactic antibiotics or treat infection were the criteria used for identifying seizures that were potentially preventable. RESULTS: Forty term neonates had early-onset seizures out of 60,712 live births (0.07%). These seizures were attributed to hypoxic events in 15 neonates (37.5%), cerebral malformations in seven (17.5%), cerebral infarcts in seven (17.5%), intracranial hemorrhage in five (12.5%), infection in three, and an unknown etiology in three. Twenty-three neonates had 5-minute Apgar scores of 7 or greater (cerebral malformations excluded). Seven of these neonates (30%) had cerebral infarcts. A review of all records identified nine cases (22.5%) of the early-onset seizures as potentially preventable. CONCLUSION: The majority of the term early-onset neonatal seizures identified did not appear to be preventable. Many of the neonates with 5-minute Apgar scores of 7 or greater had cerebral infarcts.

Abruptio placentae: perinatal outcome in normotensive and hypertensive patients.

OBJECTIVE: The objective of this study was to compare perinatal outcomes of hypertensive and normotensive women experiencing abruptio placentae. Our hypothesis is that hypertensive women have a less favorable perinatal outcome than do normotensive women. STUDY DESIGN: Women with the diagnosis of abruptio placentae delivered between July 1, 1988, and May 31, 1992, composed the study group (n = 226) in this case-control study. The incidence of abruptio placentae was 0.7% during this time. Those women with either multifetal gestations (n = 4) or delivery before 20 weeks' gestation (n = 2) were excluded from data analysis. The remaining 220 patients were divided according to their hypertensive (n = 29) or normotensive (n = 191) status. Maternal and neonatal medical records were reviewed and abstracted for demographic variables, antepartum complications, delivery route, abruptio placentae grade, neonatal gender, birth weight, Apgar score, cord pH, and perinatal mortality. These perinatal outcome variables were compared between the hypertensive and normotensive patient groups. RESULTS: Black women with abruptio placentae were significantly more likely to be hypertensive (p = 0.0078). Hypertensive women with abruptio placentae had the antepartum complication diabetes mellitus significantly more often than did normotensive women (p = 0.032). However, they were similar to normotensive women with regard to the frequency of positive urine drug screen and trauma. Hypertensive women were no more likely to be delivered before 32 or 37 weeks' gestation, have neonates weighing < 1500 or 2500 gm, or to be delivered by cesarean section. Abruptio placentae grades 2 and 3 occurred more often in hypertensive women (p = 0.053), as did significantly lower umbilical cord artery (p = 0.005) and venous (p = 0.003) pH values. Neonates from hypertensive women were no more likely to have low 5-minute Apgar scores or to die than those from normotensive women. CONCLUSION: Although hypertensive women experiencing abruptio placentae are more likely to have higher-grade abruptio placentae and lower umbilical cord pH values, the overall perinatal outcome was not significantly different from that of normotensive women experiencing abruptio placentae.

Variable fetal heart rate decelerations and electrocortical activities.

OBJECTIVE: The purpose of this study was to examine the influence of fetal behavioral states on baroreflex-mediated, variable fetal heart rate decelerations caused by umbilical cord occlusion. STUDY DESIGN: Five chronically instrumented fetal lambs were subjected to intermittent partial umbilical cord occlusion for 1 minute every 3 minutes, lasting 2 hours. Fetal behavioral states determined by electrocorticogram and heart rates by electrocardiogram were monitored continuously during these experiments. RESULTS: The fetuses exhibited an alteration between low- and high-voltage electrocorticogram states. Both the depth and width of the variable fetal heart rate decelerations were greater during high-voltage than during low-voltage electrocorticogram. CONCLUSION: Amplitude and duration of variable fetal heart rate decelerations are affected by fetal behavioral states.

Neonatal seizures after cesarean delivery: higher risk with labor.

A study was done on the occurrence of neonatal seizures in 14,367 infants delivered by cesarean section in a perinatal region in 4 years. Although seizures occurred in 1% of all of these infants, small infants weighing less than 2500 gm at birth had the highest frequency (greater than 4%). Term infants delivered before labor (repeat cesarean section) had the lowest seizure rate (less than 0.2%), and this was a significantly lower (four times) frequency than that seen in term infants delivered by primary cesarean section. These data suggest that brain function as indexed by neonatal seizures can be adversely affected during labor.