Placental glucose transport in heat-induced fetal growth retardation.

In six ewes heat stressed from 39 to 125 days gestation and studied in a normothermic environment at 135 days, fetal and placental masses were less than in control sheep (1,645 vs. 3,112 and 149 vs. 356 g, respectively, P less than 0.01). Umbilical glucose uptakes (Rf,UP) were measured keeping maternal arterial plasma glucose at 70 mg/dl at spontaneously occurring fetal plasma glucose values (state A) and at two additional fetal glucose levels, to determine the transplacental glucose difference (delta) vs. Rf,UP relation. At normal delta of 49.2 mg/dl, Rf,UP was less in the experimental group (3.2 vs. 5.6 mg.min-1.kg fetus-1, P less than 0.05). Differences in placental perfusion and glucose consumption could not account for this result, thus indicating a reduced placental glucose transport capacity. In state A, fetal hypoglycemia enlarged significantly (P less than 0.01) the delta to 56.7 mg/dl and increased Rf,UP approximately 50% over the Rf,UP at a normal delta. In heat-induced fetal growth retardation, fetal hypoglycemia increases the flux of maternal glucose across a placenta with reduced glucose transport capacity.

Venous drainage of the human uterus: respiratory gas studies in normal and fetal growth-retarded pregnancies.

OBJECTIVE: To determine respiratory gas relationships between the uterine veins and umbilical vein in normal and pregnancies complicated by intrauterine growth retardation. STUDY DESIGN: Respiratory gases were measured in both uterine veins and the umbilical vein in eight normal and 13 pregnancies with intrauterine growth retardation. RESULTS: No significant differences were found in the placental versus nonplacental uterine veins. There was a significant correlation for umbilical and uterine venous values of PO2 (p less than 0.002) and PCO2 (p less than 0.004) in appropriate-for-gestational-age pregnancies, umbilical venous PO2 was always less than uterine venous PO2, and PCO2 always greater than uterine. The transplacental gradient was significantly higher in intrauterine growth retarded than appropriate-for-gestational-age pregnancies for both POC2 and PCO2. There was a lower uterine oxygen extraction in intrauterine growth retarded pregnancies (p less than 0.05). CONCLUSION: There is no consistent relationship between placental venous drainage in each uterine vein and placental location. The human placenta simulates a relatively inefficient venous equilibrator and the larger transplacental gradients in intrauterine growth retarded pregnancies may reflect differences in both perfusion pattern and placental structure.

Prenatal diagnosis and management of congenital heart disease.

Thirty-two fetuses were diagnosed as having congenital heart disease (CHD). The major indications for level II echocardiography other than suspected cardiac abnormalities were fetal malformations, nonimmune hydrops and cardiac arrhythmia. Only three patients had a previous history of fetal CHD. No false-abnormal diagnosis of severe CHD was made. Aortic arch anomalies represented the major diagnostic problem among the six correct but incomplete diagnoses. Sixty-one percent of the fetuses were growth retarded, thus confirming the severity of their CHD. Chromosomal anomalies and extracardiac malformations were associated in 19% and 44% of the fetuses, respectively. Obstetric management and fetal prognosis in cases of extracardiac malformations were greatly influenced by the diagnosis of CHD. The poorest perinatal outcome was associated with heart failure. The only intrauterine deaths occurred in that group, and only one neonate survived. The outcome was more favorable in neonates without other malformations or heart failure. Four of ten (40%) of those neonates survived, while the overall perinatal survival rate was 24%.

The correlation of biochemical monitoring versus umbilical flow velocity measurements of the human fetus.

The pulsatility index of the fetal umbilical arteries was evaluated in 14 high-risk pregnant patients delivered by cesarean section between 30 and 35 weeks of gestation. Transabdominal cord sampling by ultrasonic guidance was performed on 10 of these patients. Umbilical arterial and venous blood was obtained in all patients from the doubly clamped cord at the time of cesarean section. The blood samples were analyzed for respiratory gases, acid-base balance, and lactate concentrations. A significant relationship was found between the pulsatility index and pH, PCO2, and lactate concentrations measured on umbilical venous blood sampled in utero. The pulsatility index also correlated with the same variables measured on venous and arterial blood sampled at cesarean section. Umbilical venous blood obtained transabdominally had a significantly higher oxygen content than blood obtained at cesarean section. No significant correlation was found between umbilical venous oxygen content obtained at transabdominal cord sampling and the pulsatility index. At a pulsatility index greater than 1.5, lactate concentrations in umbilical venous blood increased sharply. There would appear to be a curvilinear relationship between umbilical blood flow and these indices of fetal oxygenation, such that moderate increases in pulsatility index were not associated with a significant increase in fetal lactate concentrations.

Fetal endoxins and complications of pregnancy.

Maternal endoxin (digoxinlike substance) is proposed as arising in the fetal area of the fetal adrenal cortex. Its function may be to sensitize the uterus for labor, much as does cortisol in the sheep fetus. Because endoxin is a sodium-potassium-adenosine triphosphatase inhibitor, however, it may also induce maternal vasoconstriction. On our service, normal pregnant women have detectable endoxin after 35 weeks with increasing amounts at term. Specimens of cord blood often have "digoxin" in the therapeutic range. We find that about 40% of women in premature labor and 65% of pregnant women with hypertension have elevated levels of serum endoxin. Postdate gravid women sometimes have very low endoxin levels. Pregnant women with complications and elevated digoxin (endoxin) levels could have specific antidigoxin therapy if endoxin proves to be a modulator of their symptoms. Digoxinlike substances are also sometimes elevated in ill nonpregnant persons, such as those with renal, liver, or heart failure, or hypertension.

The relationship of maternal and fetal glucose concentrations in the human from midgestation until term.

The relationship between maternal and fetal glucose concentrations was investigated in pregnant women at different gestational ages. Maternal and fetal blood samples were obtained during 14 fetoscopies (17 to 21 weeks), four umbilical cord samples (32 to 36 weeks), nine elective cesarean sections with appropriate for gestational age (AGA) fetuses (35 to 39 weeks) and nine elective cesarean sections with small for gestational age (SGA) fetuses (34 to 37 weeks). A significant linear relationship between maternal and fetal glucose concentrations was demonstrated at midgestation (P less than .001) and at late gestation (P less than .001). At equal maternal concentrations there were no significant differences in fetal glucose concentration between the cord samples obtained in late gestation and those obtained at cesarean section. At midgestation fetal glucose concentration is independent of and may exceed maternal concentration at maternal glucose levels less than 4.44 mmol/L. Furthermore, the relationship between maternal and fetal concentrations at maternal glucose concentrations greater than 4.44 mmol/L is significantly different at midgestation from that at late gestation (P less than .01); at equal maternal concentrations there were higher glucose concentrations in the mid trimester fetus. In late gestation as the maternal glucose concentration increases there is an increase in the maternal arterial-umbilical arterial glucose concentration difference and the umbilical glucose/oxygen quotient (P less than .003) reflecting increased glucose utilization by the fetus. There were no significant differences between AGA and SGA babies with respect to these relationships.

The yolk sac in early pregnancy failure.

An attempt was made to visualize the yolk sac in 845 patients scheduled for chorionic villi sampling. The distribution of yolk sac diameters and the interpolating growth curve up to 11 weeks of development were analyzed in 239 pregnant women who were delivered of normal infants. The highest visualizing rate of the yolk sac in normal pregnancies was 97 at 7 weeks of gestation. A total of 130 miscarriages occurred before chorionic villi sampling. In these cases, the diameter of the yolk sac versus crown-rump length tended to be larger than found in normal pregnancies. The visualizing rate of the yolk sac in miscarriages after the embryo had been formed was significantly higher in those women who demonstrated fetal heart activity (82.1%) than in those who did not (54.5%). On the other hand, the yolk sac was observed in 44% of miscarriages without a visible embryo. These findings suggest different types of missed abortion. An abnormal karyotype was observed in 23 of 29 chromosomal analyses performed on aborted specimens. An abnormal karyotype was observed in all eight cases with only a yolk sac-like structure within the gestational sac.

Cord sampling for the evaluation of oxygenation and acid-base balance in growth-retarded human fetuses.

In 14 pregnancies complicated by intrauterine growth retardation, the umbilical cord was sampled before delivery under ultrasonic guidance for rapid fetal karyotyping. Fetal blood was analyzed for respiratory gases, acid-base balance, and lactate concentrations. Two patients were excluded from the study because cord samples were diluted with amniotic fluid. In six patients (group 1), the clinical assessment warranted continuation of pregnancy. Cesarean sections were performed in the remaining eight patients (group 2) within 8 hours of cord sampling. The data from the two groups were compared with those obtained from umbilical venous blood at the time of elective repeat cesarean section in term appropriate for gestational age infants (controls). No significant difference in PO2 was found between groups 1 and 2 and controls. In contrast, there were significant differences in oxygen saturation and acid-base balance between groups 1 and 2. Lactate concentration was inversely correlated with pH and was elevated in five of six fetuses requiring a prompt cesarean section: In two of these five fetuses, nonstress fetal heart rate tracings were reactive. The results suggest that fetal blood biochemistry, and particularly lactate concentration, may represent an additional indicator of fetal well-being in pregnancies complicated by intrauterine growth retardation.

Outcomes of twin gestations at the University of Colorado Health Sciences Center, 1973-1983.

A retrospective study was undertaken of 341 twin pregnancies over a ten-year period at the University of Colorado Health Sciences Center. The perinatal morbidity and mortality were higher than for singleton gestations, but no difference was found between the first and second twins. Bed rest was effective in prolonging gestation and decreasing perinatal mortality (P less than .05). Delivery of the second twin in noncephalic presentation was accomplished vaginally in 46.5%, with external version successful in five of six attempts. The interval between the birth of each twin did not affect outcome.

Respiratory gases, acid-base balance and lactate concentrations of the midterm human fetus.

Respiratory gases, acid-base balance, and lactate and hemoglobin concentrations were measured in 14 fetal blood samples between 17 and 21 weeks of gestation. The samples were obtained at the time of fetoscopy performed for prenatal diagnosis. Results have been compared with two reference groups: (a) 4 patients in whom fetal cord blood sampling was performed at 32-36 weeks of gestation, and (b) 10 patients at the time of elective cesarean section, 35-39 weeks. PO2 and oxygen saturations were significantly higher and hemoglobin concentration lower in the mid-gestation fetus. Acid-base balance was not significantly different. There was a significant correlation between maternal and fetal hemoglobin concentrations. The oxygen affinity of fetal blood was not significantly different from that described for term fetuses with a oxygen saturation of less than 90%.

Factors affecting radioactive microsphere measurement of blood flow in pregnant guinea pigs.

Comparative blood flow studies were performed in pregnant guinea pigs using radioactive microspheres to test the effects of different sphere sizes on blood flow measurements and the relationship between flows obtained intraoperatively and those performed after 5 days of recovery from anesthesia and surgery. We observed that 1.5% of the cardiac output was shunted through the microcirculation of the carcass, gut, skin and endomyometrium when 15 mu microspheres were used. Intraoperative measurements of heart rate, cardiac output and placental blood flow are significantly lower than measurements made after 5 days recovery. These reductions were ameliorated with the addition of a continuous infusion of isoproterenol and the deletion of atropine from the anesthetic.

Metabolic and circulatory studies of fetal lamb at midgestation.

Uterine and umbilical blood flows, the placental clearance of 3H2O, uterine and umbilical uptakes of oxygen, glucose, and lactate were measured in conscious, pregnant sheep at 71-81 days gestation. Fetal weight was 210 +/- 20 g and less than half placental weight. In relation to fetal weight, umbilical flow was 468 +/- 57 ml X min-1 X kg-1, more than double normal values for the mature fetus. Clearance of 3H2O was approximately 12% of the late pregnancy value but high in relation to fetal weight (280 +/- 23 ml X min-1 X kg-1). Fetal oxygen uptake was 10.9 +/- 0.6 ml X min-1 X kg-1, approximately 40% greater than in late gestation. Umbilical uptake of glucose was also relatively high, whereas lactate uptake was low. Uteroplacental tissues consumed more than 80% of the oxygen and glucose taken up by the pregnant uterus. However, uteroplacental utilization rates of oxygen and glucose as well as net lactate production were lower (approximately 50, 30, and 25%, respectively) than in late pregnancy, despite a larger placental mass (486 +/- 22 vs. 302 +/- 12 g).

Protease production by microorganisms associated with reproductive tract infection.

Factors influencing pathogenicity of various microbes found in the female lower genital tract remain incompletely understood. Protease production by cervico/vaginal microorganisms may alter or inactivate a variety of proteins important in host defense and structural-functional integrity including collagen-containing chorioamniotic membranes and uterine cervix. Host tissues may be made more susceptible to other organisms' virulence factors by protease-producing members of genital tract local flora. Microorganisms themselves may also be influenced by the presence of other microbial protease. Nonspecific protease, gelatinase, collagenase, and elastase production was examined for in vitro with use of aerobic (30) and anaerobic (25) strains of microorganisms typical of those isolated from the lower genital tract of women with premature rupture of membranes, chorioamnionitis, and puerperal infection. Microorganisms including Bacteroides bivius, Bacteroides melaninogenicus, Bacteroides fragilis, Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Proteus species, and Propionibacterium acnes produce various proteases. Protease production by both acknowledged pathogenic and commensal bacteria may contribute to the occurrence of reproductive tract morbidity including premature rupture of membranes and preterm labor.

Adjunctive erythromycin treatment for idiopathic preterm labor: results of a randomized, double-blinded, placebo-controlled trial.

Pathogenesis and optimal treatment and prevention of preterm labor remain incompletely understood. Entry of cervical/vaginal microorganisms into lower uterine tissues has been implicated in preterm labor and may be amenable to specific therapy. Fifty-eight women with less than 34 completed weeks of gestation and without other obstetric complications, who were receiving intravenous tocolytics because of uterine contractions and who had cervical alteration (less than 5 cm dilated), were enrolled in a prospective randomized, double-blinded evaluation of 7 days of adjunctive therapy with enteric-coated erythromycin base (333 mg three times daily by mouth) versus placebo. Microbiologic examination included cultures for Neisseria gonorrhoeae, Chlamydia trachomatis, and group B streptococcus. Fifty-eight women with singleton pregnancies (29 erythromycin; 29 placebo) completed the protocol. Among women with cervical dilatation greater than or equal to 1 cm at the beginning of treatment, mean time until delivery was 32.5 days with erythromycin and 22.4 days with placebo treatment (p = 0.027). Of the erythromycin-treated women, seven of eight were delivered at greater than or equal to 37 weeks and only three of nine placebo-treated women were delivered at greater than or equal to 37 weeks (p = 0.035). Orally administered enteric-coated erythromycin as adjunctive treatment of pregnant women in labor less than or equal to 34 weeks is well tolerated. Adjunctive erythromycin given to women treated for preterm labor less than or equal to 34 weeks is associated with prolongation of pregnancy and delivery at 37 weeks only in women with cervical dilatation at the beginning of treatment.

Relationship between metabolic rate and body size in fetal life.

To define the O2 consumption rate (VO2) versus body mass relation during fetal growth, we compared fetal sheep VO2 at mid and late gestation. VO2 per kg wet weight was 37% higher at mid gestation. However, VO2 per kg dry weight was 2.5 times higher, and associated with a high viscera/body weight ratio. Fetal VO2 tends to grow proportionally to body mass because marked decreases in the relative growth of visceral organs and in the VO2/dry weight ratio are accompanied by a decrease in body water.

Umbilical cord prolapse.

Umbilical cord prolapse complicated one of 385 pregnancies occurring at the University of Colorado Health Science Center between 1969 and 1982. Whereas malpresentation of the fetus is frequently associated with prolapse of the funis, nearly 50% of all cases occurred in vertex presentations. Obstetric intervention is associated with nearly one in five cases of cord prolapse and represents a readily preventable cause of maternal and perinatal morbidity.

Comparison of fetal and maternal hind limb metabolic quotients in sheep.

This study compared substrate utilization by the fetal hind limb and the maternal hind limb in 26 sheep at 120 to 135 days of gestation. Catheters were placed in the mother and the fetus to sample femoral arterial and venous blood by use of a nonocclusive technique. Arterial and venous concentrations of oxygen content, glucose, lactate, acetate, and ketoacids were measured simultaneously and were used to calculate metabolic quotients. The fetal hind limb was perfused with arterial blood having a lower oxygen content than the maternal hind limb (3.03 +/- 0.17 versus 4.94 +/- 0.24 mmol/L, p less than 0.001) and had a smaller arteriovenous difference of oxygen content (0.97 +/- 0.05 versus 2.68 +/- 0.104 mmol/L, p less than 0.001). Despite a lower fetal arterial glucose concentration (0.81 +/- 0.05 versus 2.58 +/- 0.13 mmol/L, p less than 0.001), the glucose/oxygen quotient (0.82 +/- 0.05 versus 0.20 +/- 0.02, p less than 0.001) and the arteriovenous difference of glucose (0.13 +/- 0.01 versus 0.08 +/- 0.01 mmol/L, p less than 0.001) were higher in the fetal hind limb than in the maternal hind limb. Both limbs were net producers of lactate. The (glucose + lactate)/oxygen quotient was also higher in the fetal hind limb than in the maternal hind limb (0.68 +/- 0.05 versus 0.12 +/- 0.04, p less than 0.001). In the maternal hind limb, acetate and ketoacids uptake could account for 48% +/- 6% of total oxygen consumption whereas in the fetal hind limb it accounted for only 12% +/- 4% (p less than 0.001). The data demonstrate that, in relation to oxygen uptake, fetal hind limbs have approximately a 2.8% higher rate of perfusion and take up approximately four times as much glucose as the hind limbs of the mother in the resting state.

The effect of a leukotriene receptor antagonist, FPL 55712, on estrogen-induced uterine hyperemia in the nonpregnant rabbit.

Estrogen results in delayed uterine hyperemia. We postulate that the leukotrienes may be the mediators of the uterine vascular responses to estrogen. To test this hypothesis, we gave FPL 55712, a selective leukotriene antagonist, to estrogen-primed, nonpregnant rabbits and measured regional blood flows by the radioactive microsphere technique. In 10 chronically catheterized animals, blood flows were measured in the control condition (C), and again 2 hours after systemic administration of estradiol (EST). Thirty minutes before administration of estradiol, five animals received systemic FPL 55712, whereas five animals received vehicle only. The vehicle group showed the expected increase in uterine blood flow from 0.62 +/- 0.1 to 2.72 +/- 0.4 ml X min-1 X gm-1, and decrease in uterine resistance from 144 +/- 31 to 34 +/- 8 peripheral resistance units (PRU) X gm, with a resistance ratio (estradiol/C) of 0.23 +/- 0.01. Unexpectedly, the FPL 55712 group showed a further increase in uterine blood flow from 0.66 +/- 0.1 to 4.60 +/- 0.3 ml X min-1 X gm-1, and a decrease in resistance from 133 +/- 25 to 17 +/- 1 PRU X gm, with a resistance ratio of 0.13 +/- 0.02. The leukotriene antagonist FPL 55712 potentiates estrogen-induced uterine hyperemia by 77% (P less than 0.001). These data suggest that leukotrienes do not mediate, but rather inhibit, the uterine vascular responses to estrogen.