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Objective: The hypothesis of our study was that both the systemic and uteroplacental circulations would adapt to chronic maternal anemia to ensure that oxygen supply to maternal tissues would be adequate. Study Design: We measured cardiac output and uteroplacental blood flow and calculated systemic and uteroplacental oxygen delivery, extraction, and consumption in pregnant sheep that were anemic for 6 days (hematocrit 14%) and in normal sheep (hematocrit 28%). Results: When compared with normal pregnant sheep, anemic pregnant sheep had increases in cardiac output and uteroplacental blood flow, neither of which was sufficient to prevent systemic or uteroplacental oxygen delivery from decreasing. In spite of decreases in oxygen delivery, systemic and uteroplacental oxygen consumptions were maintained at normal levels because of increases in oxygen extraction. Conclusion: Maternal systemic and uteroplacental circulations are capable of adapting well to chronic maternal anemia.

We previously observed young lambs to be more tolerant of hypoxia; compared with older lambs, they accumulate lactate at a slower rate during comparable reduction in cardiac output, and have a greater percent decrease in cardiac output before onset of systemic lactate accumulation. To determine the mechanism of lactic acidosis and the cause for this "tolerance," we reduced cardiac output progressively in seven chronically catheterized conscious lambs (16.4 + 5.1 d) and measured hepatic and gastrointestinal (GI) blood flow (radioactive microspheres) and delivery, uptake, and extraction of lactate and O2. Hepatic O2 consumption declined proportionately below a critical hepatic O2 delivery (approximately 2 mL O2/min/kg), corresponding to the systemic O2 delivery associated with the onset of systemic lactate accumulation. As hepatic O2 delivery decreased below the critical value, there was initially net hepatic lactate uptake and then a change to net production when the O2 delivery decreased below approximately 1 mL O2/min kg. The GI tract had net lactate production at rest, but surprisingly switched to lactate uptake as cardiac output decreased. The mechanism of lactic acidosis was failure of hepatic lactate uptake to increase despite increased hepatic lactate delivery, as reported in adults subjects. However, in contrast, there was "true" hepatic dysfunction and lactate production only at the lowest levels of cardiac output, after onset of systemic lactate accumulation. Moreover, we speculate that tolerance of young lambs to hypoxia is at least due to two factors: 1) hepatic lactate uptake is maintained beyond the "critical" O2 delivery and fall in hepatic O2 consumption, and 2) there is a switch to lactate uptake by the GI tract serving to buffer the lactate.

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.

We chronically catheterized 15 newborn lambs (9.5 +/- 2.8 days) and measured the distribution of cardiac output by the radionuclide-microsphere technique at hematocrits ranging from 10 volumes % to 55 volumes %. Seven animals were made progressively anemic and eight polycythemic by means of exchange transfusions. Cardiac output and heart rate increased with decreasing hematocrit while whole body oxygen consumption showed a small decrease during severe anemia. Both cerebral and cardiac blood flow markedly increased during anemia which assured a relatively stable oxygen delivery to both organs. The changes seen for blood flow to the carcass (skin, bones, and muscle) were predictable from the effects of blood viscosity: small decreases in flow at the highest hematocrits and small increases in flow at the lowest hematocrits. Consequently, oxygen delivery was as low as 1 ml of oxygen/min/100 g at a hematocrit of 10 volumes %. Renal blood flow remained unchanged while oxygen delivery fell when hematocrit was decreased. Hepatic oxygenation was measured using a modification of the Fick principle. Hepatic blood flow showed only a small decrease as hematocrit increased and changed minimally during anemia resulting in a falling delivery of oxygen with anemia. A stable hepatic oxygen consumption was assured by a marked increase in oxygen extraction during anemia. Two differing organ responses to changes in hematocrit can be seen in the newborn: the brain and heart vary blood flow to assure an adequate delivery of oxygen while a number of other organs show less blood flow regulation and, most likely, vary oxygen removal from blood.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Preterm labor is responsible for a majority of cases of perinatal morbidity and deaths. Prevention of preterm labor is not usually possible; thus pharmacologic treatment is the only recourse available. Numerous agents have been used to treat preterm labor, but none has proved to be superior. This report reviews the current information available about the pharmacology of labor-inhibiting drugs and discusses the clinical approach to the management of preterm labor.

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.

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.

SUMMARY We evaluated the circulation of the liver and ductus venosus, using the radionuclide-labeled mkrosphere technique, in 24 chronically prepared fetal lambs. We placed catheters in fetal descending aorta and inferior vena cava, and hi a carotid artery and an umbilical vein; in 11 fetuses, we aho Inserted a catheter hi a mesenteric vein that drained into the portal vein. After allowing 2-4 days for recovery from the stresses of anesthesia and operation, we measured blood flow to the fetal liver and hs various lobes and through the ductus venosus. Total Mood flow to the liver was 435 ± 122 ml/min per 100 g liver (mean ± SD), of which hepatic arterial flow represented 9%, portal venous flow 18%, and umbilical venous flow 73%. Hepatic arterial and umbilical venous flows were approximately equally divided between left and right lobes, although portal blood flow was directed almost exclusively to the right lobe. The right lobe received 40% more total blood flow than the left, even though the left lobe weighed more than the right. Approximately 53% of umbilical venous blood flow but less than 9% of portal venous blood flow entered the ductus venosus; umbilical venous flow therefore accounted for more than 98% of ductus venosus blood flow. Ductus venosus flow showed a strong linear correlation with umbilical blood flow. However, there was no relationship between ductus venosus flow and gestational age. The results suggest that the liver receives a large Mood flow primarily because of a large umbilical venous contribution. It is not dear whether the fetal liver requires this large flow and peculiar lobar distribution for normal function and growth. It is unlikely, however, that the ductus venosus functions actively to maintain a stable blood flow to the fetal liver. THE LIVER of the fetus receives its blood supply from the hepatic artery, portal vein, and umbilical vein. Total blood flow to the fetal liver must be high, because a large umbilical venous blood flow passes through the liver. Nevertheless, the actual flow that reaches the liver from all three vascular sources has not been measured previously. The relative contributions of hepatic arterial and portal and umbilical venous blood flows to the various lobes of the liver also have not been studied quantitatively. Anatomically, the left lobe of the liver is supplied by branches of the umbilical vein, while the right lobe is supplied by portal venous branches 11 (Fig. 1). Except for occasional small branches, no umbilical blood vessels extend into the right lobe, and no portal blood vessels reach the left lobe. Branches of the hepatic artery supply both lobes, but arterial flow to the whole liver is small.

We studied the vascular reactivity of the systemic and uterine circulations of six pregnant sheep. We placed catheters in a maternal carotid artery and a jugular vein, and then implanted an electromagnetic flow transducer around the uterine artery of the pregnant horn. After allowing 3 days for recovery from anesthesia and operation, we measured mean arterial blood pressure, heart rate, uterine blood flow, and calculated uterine vascular resistance, then separately infused angiotensin and norepinephrine in each ewe at the rate that produced a 20 torr pressor response. Dexamethasone, 0.2 mg. per kilogram of body weight, was then injected intravenously daily for 2 to 4 days. On the day following the final injection of dexamethasone, we separately infused angiotensin and norepinephrine at a rate that, before steroid treatment, produced a 20 torr pressor response. Administration of dexamethasone for 2 to 4 days did not change mean arterial blood pressure, heart rate, uterine blood flow, or uterine vascular resistance. Prior to steroid treatment, angiotensin increased blood pressure, decreased heart rate, but had no consistent effect on uterine blood flow or uterine vascular resistance; norepinephrine increased blood pressure without chenging heart rate, decreased uterine blood flow, and increased uterine vascular resistance. The changes produced by angiotensin and norepinephrine were the same after dexamethasone treatment. These studies indicate that dexamethasone does not influence systemic and uterine vascular reactivity during normal sheep pregnancy.

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.

Ninety-two women in preterm labor were randomly assigned to receive either terbutaline or ethanol. In women with intact membranes, terbutaline was significantly more effective than ethanol in preventing progressive cervical dilation during the first 36 hours of treatment while betamethasone was given to the mother. Additionally, pregnancy was maintained significantly longer in women with intact membranes who were treated with terbutaline (15 ± 4 days) rather than with ethanol (10 ± 3 days). However, only 18% of women in each treatment group maintained their pregnancy beyond 36 weeks’ gestation. In women with ruptured membranes and cervical dilation less than 4 cm, terbutaline was significantly better than ethanol in maintaining pregnancy for a minimum of 36 hours. Serious maternal side effects were not observed with terbutaline or ethanol, although a majority of women also received betamethasone. Neither drug caused serious adverse neonatal effects.

We determined hepatic arterial (QHA) and portal venous (Qpv) blood flows and calculated, utilizing the Fick principle, net hepatic glucose production (PGLUC), O2 delivery (DO2), O2 consumption (VO2), and O2 extraction (VO2/DO2), in 7 chronically catheterized lambs (9-15 d). Studies were done with the lambs fasted and at 1, 2, 3, 4, and 6 hr postprandially. We measured O2 contents (Lex-O2-Con), blood flows (radioactive microspheres), and glucose (glucose oxidase). The table indicates mean results. (* = significantly different from fasting) Our results show that the VO2 of the neonatal liver decreases postprandially. This decreased VO2 is associated with a decreased O2 extraction rather than a decrease in DO2 or hepatic blood flow. Since glucose production is increasing at a time when hepatic oxygen consumption is decreasing, these data indicate that hepatic metabolism shifts postprandially to less oxygen-dependent processes.