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OBJECTIVE: We sought to determine whether a critical cardiac output and oxygen delivery exist in normal pregnancy. We also sought to determine the role of fetoplacental oxygen demand on maternal oxygen transport variables in response to decreased maternal cardiac output. STUDY DESIGN: We studied 10 adult female sheep, 5 nonpregnant and 5 pregnant. We placed a flow-directed thermodilution catheter in the pulmonary artery and a balloon-tipped catheter in the right atrium of the sheep. We also placed a catheter for pressure monitoring and blood sampling in the descending thoracic aorta in both the mother and fetus. We decreased maternal cardiac output by incremental inflation of the right atrial balloon. We measured maternal cardiac output by intravenous bolus thermodilution technique. We also measured maternal and fetal acid-base status and serum lactate concentrations. We calculated a variety of maternal cardiorespiratory variables, including systemic oxygen delivery, systemic oxygen consumption, and fractional whole body tissue oxygen extraction. RESULTS: The nonpregnant sheep displayed a critical cardiac output below which there was an abrupt decrease in oxygen consumption. In contrast, there was no critical level of cardiac output in the pregnant sheep. Maternal oxygen consumption was linearly dependent on cardiac output. Maximum fractional oxygen extraction was significantly lower in the pregnant sheep than in the nonpregnant sheep. CONCLUSION: States of low cardiac output in the pregnant sheep are associated with a lack of a critical cardiac output; the flow-dependent oxygen consumption observed is the result of either an impairment in tissue oxygen extraction or some degree of metabolic arrest or a combination of both. If this unique cardiac output - oxygen consumption relationship is seen in human pregnancy, it could have significant implications in the care of the critically ill obstetric patient. (Am J Obstet Gynecol 1996;175:222-8.)

Accurate assessment of gestational age and fetal weight in the pregnant ewe is important in both acute and longitudinal perinatal studies. We describe two morphometric methods based on the length of the fetal metatarsal bone. These measurements can be made intraoperatively or at postmortem. Metatarsal bone lengths can be used to better predict gestational age and fetal weight than previously described methods.

To determine whether the high oxygen affinity of fetal blood, compared with that of the adult, is advantageous to the fetus during fetal anemia we studied 16 chronically catheterized fetal lambs. Half of the lambs had hemoglobin-oxygen affinity reduced acutely by isovolemic exchange transfusion with fresh adult whole blood; the other half served as controls. In both groups of fetuses, we measured fetal oxygen delivery, oxygen consumption, and acid-base state at normal fetal hematocrit levels and during reductions in the hematocrit level of 30% (moderate anemia) and 60% (severe anemia) produced by isovolemic exchange transfusions with plasma. At normal fetal hematocrit levels, reductions in hemoglobin-oxygen affinity had no effect on fetal oxygen consumption or acid-base state. During moderate anemia, fetal oxygen delivery decreased in both series of fetuses, but oxygen consumption and base excess fell only in those fetuses whose circulations contained adult hemoglobin. During severe anemia, oxygen consumption and base excess decreased in both groups of fetuses, although these changes were more pronounced in fetuses with adult hemoglobin than in those with fetal hemoglobin. Our data indicate that, even though a high hemoglobin-oxygen affinity may not be essential to a healthy fetus, it is critical for normal metabolism in a fetus subjected to a hypoxic stress such as anemia.

In 11 chronically catheterized fetal lambs (123 +/- 6, mean +/- SD, days of gestation; term = 147 days), we measured fetal oxygen delivery and oxygen consumption before and during reductions in umbilical blood flow (Qumb). Qumb was reduced by inflation of a balloon occluder located just proximal to the origin of the common umbilical artery. Measurements were made while the unanesthetized maternal sheep received either room air or 100% oxygen to breathe. In oxygen-treated fetuses, oxygen concentrations in umbilical venous blood (Cuvo2) and arterial blood (Cao2) were increased over a wide range of Qumb when compared with those of room air-treated fetuses. Because of these responses, fetal oxygen delivery (Do2 = Qumb X Cuvo2) and oxygen consumption [Vo2 = Qumb(Cuvo2-Cao2)] were greater in oxygen-treated fetuses than in room air-treated fetuses during episodes of reduced Qumb. In oxygen-treated fetuses, Vo2 decreased from normal levels only when Qumb was less than or equal to 75 ml/min/kg of fetus, whereas in room air-treated fetuses Vo2 decreased at Qumb less than or equal to 150 ml/min/kg. Our data indicate that oxygen administration to the pregnant sheep increases oxygen delivery to the fetus during times of reduced umbilical perfusion and that this supplemental oxygen supply provides an oxygen reserve with which the fetus can maintain oxidative metabolism. These data may be relevant to those clinical conditions, such as umbilical cord compression in labor, that are associated with reductions in umbilical blood flow.

The effects of dexamethasone on maternal and fetal hemodynamic states and fetal oxygenation were determined in chronically instrumented unanesthetized pregnant ewes and fetal lambs. Intravenous injections of pharmacologic doses of dexamethasone to the mother failed to alter maternal blood pressure, heart rate, blood flow in the uterine artery supplying the pregnant horn, or uterine vascular resistance. Direct administration of dexamethasone to the fetus had no effect on fetal blood pressure, heart rate, acid-base state, or oxygenation. Furthermore, direct fetal administration of dexamethasone did not produce premature parturition.

In 101 diabetic pregnant women (Classes A through D) 146 determinations of the lecithin/sphingomyelin ( L/S ) ratio were carried out. Gestational ages were verified by serial fetal cephalometry. No L/S ratios of more than 2.0 were found before 341/2 weeks' gestation; however, in 42 per cent of patients the L/S ratio was below 2.0 at 36 weeks' gestation or later. Respiratory distress syndrome (RDS) was found in 16 neonates of women with L/S ratios of 2.0 or higher; however, RDS incidence varied depending on the mode of delivery. Abdominal delivery was performed before 37 weeks' gestation in 19 patients with L/S ratios of 2.0 or higher and resulted in neonates with RDS in 41 per cent of cases. Vaginal delivery was accomplished before 37 weeks' gestation in 10 patients with L/S ratios of 2.0 or higher and no subsequent neonatal RDS was observed. After 37 weeks' gestation neonatal RDS is rare, irrespective of mode of delivery. The data presented suggest that similar numerical values of the L/S ratio at different gestational ages have a different predictive value for the occurrence of neonatal RDS.

Changes in the distribution of portal venous blood flow to the left and right lobes of the liver and through the ductus venosus were determined from before birth through 9 days of age in 25 chronically catheterized fetal and newborn lambs. Blood flow distribution was calculated by means of the radionuclide-labeled microsphere technique. With umbilical cord clamping portal venous blood flow distribution to the right lobe of the liver decreased when compared to that in the term fetus; distribution to the left lobe and ductus venosus increased. More than 50% of portal blood flow was shunted through the ductus venosus during the first hour after birth. Ductus venosus shunts of at least 25% of total portal blood flow were noted in half the lambs between the second and sixth days of life. Portal venous distribution to the right lobe was inversely related to the fraction of portal blood flow shunted through the ductus venosus. The ratio of right lobe weight to total liver weight was significantly correlated with the ratio of right lobe flow to total liver flow (r = 0.73; P less than 0.001). The conclusion is that large and persistent ductus venosus shunts are normal during the first postnatal week in lambs.

Perinatal outcome and obstetric practices during 1970 and 1977 were compared. None of the 6,740 fetuses delivered with birth weights of 1,000 gm or greater in 1970 had electronic fetal monitoring (EFM). In 1977, 5,987 of 8,174 fetuses delivered had EFM (72.7%). High-risk factors were significantly more frequent in the pregnant patient population in 1977. The incidence of intrapartum stillbirths and severe birth asphyxia was significantly lower in 1977. These reductions remained significant when corrected for changes in obstetric practices other than EFM as well as for changes in patient population. The neonatal death rate was not significantly changed. The primary cesarean section rate increased from 4.4% to 10.1%, mostly because of a greater number of cesarean sections done for failure to progress in labor and breech presentation. Only 15% of the overall increase in cesarean section rate was because of a greater frequency of the indication of fetal distress. The incidence of severe birth asphyxia was the same among the unmonitored patients in 1970 and 1977. In 1977, however, the monitored patients had a significantly lower incidence of severe birth asphyxia than the unmonitored patients.

Betamethasone was administered to six rhesus-sensitized pregnant women carrying seven fetuses in an attempt to accelerate fetal pulmonary maturation. A reduction in optical density of amniotic fluid at 450 mμ was observed in all cases following steroid therapy; however, only minimal changes were noted in the lecithin-sphingomyelin ratio. The implications of these findings for the management of rhesus-sensitized pregnancies are discussed.

In adult nonpregnant animals and human beings, glucocorticosteroids increase circulating leukocytes (predominantly neutrophils) and decrease lymphocytes, monocytes, and eosinophils. We were interested in studying effects of glucocorticoids on leukocyte counts during pregnancy to determine any differences between responses in the nonpregnant and pregnant states. After general anesthesia was administered, we placed catheters in a carotid artery and a jugular vein in pregnant sheep and in fetal lambs. Six days after surgery, we administered dexamethasone intravenously to the mother (0.2 mg. per kilogram) or to the fetus (0.06 mg. per kilogram) and obtained maternal and fetal jugular venous blood samples immediately before (control) and 3, 6, 12, 24, 48, and 72 hours after steroid injection. administration of dexamethasone to the mother significantly increased total leukocyte and neutrophil counts (leukocytes per cubic millimeter blood) and decreased lymphocyte and eosinophil counts, but it did not change monocyte counts. Leukocyte counts returmed to control values within 48 hours. Administration of dexamsthasone to the fetus rapidly increased total leukocyte and neutrophil counts, decreased monocyte and eosinophil counts, and had no effect on lymphocyte counts. Fetal leukocyte counts returned to control values by 24 hours after dexamethasone injection. Our results suggest that maternal and fetal leukocytes can respond to glucocorticoids as they do in the adult nonpregnant state.

We evaluated the effects of alterations in fetal hematocrit on fetal oxygenation in 10 chronically catheterized fetal lambs. Hematocrit was varied from 10% to 55% by slow isovolemic exchange transfusions with plasma or packed red blood cells obtained freshly from donor fetuses. At each hematocrit studied, we measured umbilical blood flow (Qumb) and the oxygen concentrations in umbilical venous blood (CUVO2) and arterial blood (CAO2) and calculated fetal oxygen delivery (Qumb X CUVO2), oxygen extraction [(CUVO2 - CAO2)/CUVO2], and oxygen consumption [Qumb (CUVO2 - CAO2)]. Fetal oxygen delivery was maximal at a fetal hematocrit of 33% (mean oxygen delivery = 23 ml of oxygen per minute per kilogram of fetus) and decreased as hematocrit was raised or lowered from that value. Despite these reductions in oxygen delivery, fetal oxygen consumption was relatively stable (at about 7 ml of oxygen per minute per kilogram) at hematocrits ranging from about 16% to 48% because of compensatory increases in fetal oxygen extraction. Regardless of whether oxygen delivery decreased because of anemia or polycythemia, fetal oxygen consumption was maintained as long as oxygen delivery was greater than about 14 ml of oxygen per minute per kilogram of fetus. When oxygen delivery was less than 14 ml of oxygen per minute per kilogram, fetal oxygen consumption fell while arterial blood base deficit increased, indicating that oxygen supply was inadequate for fetal oxygen demands. These results indicate that fetal aerobic metabolism can be sustained over a wide range of fetal hematocrits. Furthermore, our data support the concept that the level of fetal oxygen delivery is an important determinant of the adequacy of fetal oxygenation.

We studied the effects of acute isovolemic maternal anemia on several variables of uterine and fetal oxygenation to answer these two questions: (1) Does maternal anemia cause reductions in oxygen delivery to the uterus, placenta, and fetus? (2) If so, what is the impact of such reductions on fetal oxidative metabolism? In 15 chronically catheterized pregnant sheep and fetal lambs, we measured uterine and umbilical blood flows and uterine and fetal oxygen deliveries, oxygen extractions, and oxygen consumptions at various, randomly selected maternal hematocrits ranging from 30% to 8%. We altered maternal hematocrit by performing isovolemic exchange transfusions with plasma or packed red blood cells. Uterine and umbilical blood flows were measured with the radionuclide-labeled microsphere technique, and the variables of oxygenation were calculated with modifications of the Fick principle. Decreases in maternal hematocrit led to linear reductions in oxygen delivery to the uterus, placenta, and fetus. Despite reductions in oxygen delivery of up to 50%, fetal oxygen consumption was maintained, because of compensatory increases in oxygen extraction. When hematocrit (and thus fetal oxygen delivery) was reduced by more than 50%, fetal oxygen consumption and the arterial blood base excess both decreased, indicating that, at these hematocrit levels, the supply of oxygen to fetal tissues was inadequate for the demands for oxygen by these tissues.

The purpose of our experiments was to relate blood flow and oxygen delivery (blood flow x arterial blood oxygen concentration) to fetal organs as functions of fetal hematocrit. In 12 chronically catheterized fetal lambs, we observed two patterns of responses of fetal organs and tissues to isovolemic alterations in fetal hematocrit from 12% to 55%. In group 1 organs (brain, heart, adrenal glands), blood flows increased as hematocrit was either raised or lowered from normal such that oxygen delivery to these organs was stable over the entire range of hematocrits studied. In group 2 organs (gastrointestinal tract organs, spleen, kidneys, placenta, and carcass), blood flows varied little over the range of hematocrits from 12% to 40% or 45% but decreased at hematocrits greater than or equal to 40% to 45%. Because of these flow responses, oxygen delivery to these organs and tissues was maximal at hematocrits ranging from 32% to 38%. Our data indicate that the various organs of the unanesthetized fetal lamb respond in different ways to alterations in hematocrit. It is of particular interest that, in the great majority of the organs of the fetus, oxygen delivery is maximal at hematocrits considered normal for the fetal lamb in utero.

In nine chronically catheterized fetal lambs (120 to 135 days; term 147 days), umbilical venous blood flow and its distribution were measured by the radionuclide-labeled microsphere technique before and during autonomic blockade with atropine (0.20 to 0.25 mg/kg; seven studies) or phentolamine (0.10 to 0.12 mg/kg; six studies). Atropine significantly increased mean fetal heart rate (182 to 207 beats/min), descending aortic blood pressure (49 to 55 mm Hg), and umbilical venous blood flow (210 to 239 ml/min/kg fetus), without changing umbilical venous blood pressure. Phentolamine decreased mean descending aortic pressure (48 to 45 mm Hg), but did not affect heart rate, umbilical venous blood pressure, or umbilical venous blood flow. Neither atropine nor phentolamine altered the distribution of umbilical venous blood flow to the ductus venousus, the liver, or the other fetal organs. These data indicate that the cholinergic nervous system only indirectly affects the basal umbilical venous blood flow in the near-term fetal lamb. This effect is small and is secondary to associated changes in heart rate and arterial blood pressure. Neither the cholinergic nor the α-adrenergic systems influence the basal distribution of umbilical venous blood flow.