Hypothalamic-pituitary control of perinatal prolactin secretion in Macaca mulatta.

Sequential changes in maternal and fetal plasma and amniotic fluid concentrations of prolactin (PRL) and growth hormone (GH) were examined after these intravascular administration of thyrotropin releasing hormone (TRH) or L-dopa alone or combined directly to the near-term Rhesus fetus. The neonatal plasma responses to these same stimuli were also examined. Fetal and neonatal plasma PRL levels increased immediately after TRH injection and remained elevated from baseline levels (102-800%) throughout the 45 min sampling period. Maternal plasma PRL levels also increased markedly. Although amniotic fluid concentrations were more variable, the trend was an increase. After L-dopa injection, fetal and neonatal plasma PRL values declined 26-62% from baseline levels. Maternal plasma PRL concentrations also declined 30-50%, but amniotic fluid PRL concentrations progressively increased. When L-dopa and TRH were administered together, fetal plasma PRL levels declined 14-40% from initial levels, but maternal plasma PRL levels did not change in a consistent manner, and amniotic fluid PRL levels remained stable. There was no change from baseline fetal or neonatal plasma GH concentrations in these experiments. The plasma PRL responses of the primate conceptus to these stimuli are consistent with those found in the adult; the unresponsiveness of plasma GH is not. The direction and magnitude of changes in both maternal plasma and amniotic fluid PRL concentrations provide indirect evidence of placental transfer of TRH and L-dopa in some experiments, and require a biophysical explanation not apparent in others.

The role of antepartum testing in the management of postterm pregnancies with heavy meconium in early labor.

The documented association between heavy meconium in early labor and increased perinatal morbidity and mortality has alerted physicians to the presence of a potential high-risk fetal condition and to the possible need for immediate fetal blood pH determination. The purpose of this study was to determine whether antepartum fetal assessment can predict whether a postterm fetus with heavy meconium in early labor is at low or high risk for an adverse perinatal outcome. Eight hundred thirty-nine postterm patients were followed with antepartum testing, consisting of twice-weekly fetal heart rate (FHR) testing and ultrasonic amniotic fluid volume estimation. Overall, patients with heavy meconium in early labor had a significantly greater frequency of fetal distress. However, when women with heavy meconium in early labor were separated according to their antepartum testing results, those with normal results were found to have no greater risk for fetal distress or perinatal morbidity than women with normal testing and subsequently clear amniotic fluid. These findings suggest that postterm patients with heavy meconium in early labor and normal antepartum testing can be managed in labor in the same manner as low-risk patients without meconium.

Dietary sodium manipulation and vascular responsiveness during pregnancy in the rabbit.

The interrelationship of sodium intake and blood pressure regulation during pregnancy is not clear. The effects of dietary sodium loading and restriction on plasma levels of catecholamines, mean arterial pressure, and vascular response to two pressor agents, Levophed and angiotensin II, were investigated in 49 chronically prepared primigravid rabbits. Sodium loading increased mean arterial pressure (p less than 0.005), but did not alter the response to either pressor agent. Sodium restriction did not alter mean arterial pressure, but did increase plasma norepinephrine (p less than 0.05) and epinephrine (p less than 0.02). Negative correlations between plasma levels of norepinephrine and vascular response to infusions of both pressor agents were observed during sodium restriction, -0.61 (p less than 0.05) for angiotensin II, and -0.74 (p less than 0.05) for norepinephrine. A similar correlation of -0.81 (p less than 0.05) was observed for angiotensin II in control animals. Norepinephrine appears to play a significant role in blood pressure maintenance and vascular response in pregnancy. This role is enhanced during sodium restriction.

A system for inducing hyperthermia in sheep.

A system that produces hyperthermia in pregnant sheep in a consistent and reproducible manner was designed. The experimental approach was through control of ambient temperature and relative humidity in a closed chamber; the sheep was unable to lose its metabolic heat in an environment of 42 degrees C and 75% relative humidity. This system resulted in a steady and progressive temperature rise of 2.5 degrees C in the maternal abdominal aorta in 120 +/- 17 min.

Plasma renin activity in sheep pregnancy after fetal or maternal nephrectomy.

The effect of bilateral fetal or maternal nephrectomy on basal and diuretic-stimulated plasma renin activity (Pra) was examined in 9 chronically catheterized Dorset sheep. After fetal nephrectomy, there was an initial rapid decrease in fetal PRA with t1/2 of 42-84 min, followed by a slower decrement with 1/2 350-720 min. There was no change in maternal PRA during this period. Similarly, after maternal nephrectomy, the decrease in maternal PRA had two exponential components and there was no associated change in fetal PRA. These data, and the maternal and fetal PRA responses to intravenous furosemide, have demonstrated that renin does not cross the sheep placenta and that fetal PRA is independent of the maternal PRA level.

Effect of propranolol infusion on the umbilical and uterine circulations of pregnant sheep.

Propranolol was infused intravenously for 60 minutes to five ewes (4 mug per kilogram per minute) or five fetal sheep (10 mug per kilogram per minute). The umbilical blood flow was significantly decreased by 18 per cent from control at 60 minutes with either maternal or fetal propranolol infusion. Uterine blood flow and maternal and fetal mean arterial pressure did not significantly change. Maternal and fetal heart rates decreased 18 and 9 per cent from control, respectively, during maternal propranolol infusion. With propranolol to the fetus, fetal heart rate decreased 15 per cent and maternal heart rate did not change. During all infusion, maternal and fetal arterial pH, PCO2 and PO2 remained within normal physiologic limits.

Effects of hypercapnia on uterine and umbilical circulations in conscious pregnant sheep.

Changes in the uterine and umbilical circulations during induced hypercapnia were studied in nine unanesthetized near-term pregnant sheep. Blood flows were measured with electromagnetic flow transducers and arterial pressures with vascular catheters implanted under anesthesia 2-16 days prior to experiments. Hypercapnia was induced in the fetus alone by giving acetazolamide iv to the fetus, 100-200 mg/kg. Mean fetal arterial Pco2 increased from 49.5 to 63.4 mmHg but no significant changes in umbilical blood flow occurred. Stepwise increases in both maternal and fetal arterial Pco2 were induced by increasing maternal inspired CO2 concentration to a maximum of 12%. No dignificant changes occurred in uterine or umbilical circulations until hypercapnia was severe (maternal arterial Pco2 greater than 60 mmHg, fetal arterial Pco2 greater than 70 mmHg). With severe hypercapnia uterine vascular resistance increased significantly and uterine blood flow decreased despite an increase in maternal arterial pressure; fetal arterial pressure and umbilical blood flow increased significantly, but umbilical vascular resistance did not. We conclude that hypercapnia in conscious pregnant sheep is associated with significant changes in uterine and umbilical circulations, but only when hypercapnia is severe. Carbon dioxide is unlikely to be a factor in normal physiological regulation of the uteroplacental circulation in this species.

The rabbit: a suitable model for investigation of vascular responsiveness during pregnancy.

The decreased vascular response to angiotensin II that characterizes normal pregnancy is lost in pregnancy induced hypertension and associated with an increase in response to norepinephrine. These alterations in vascular responsiveness have not been thoroughly investigated and are poorly understood. Suitable models manifesting physiologic conditions known to exist in human pregnancy have not been satisfactorily demonstrated. We investigated the chronically catheterized and unmedicated rabbit for similarities of four conditions known to occur during human pregnancy. We compared mean arterial pressure and vascular response to angiotensin II and to norepinephrine in 19 non-pregnant and 16 pregnant animals. Plasma levels of angiotensin II, norepinephrine, epinephrine, and dopamine levels were measured and compared. We found striking similarities for conditions investigated in our rabbit model when compared with data reported in the literature for human pregnancy. We conclude the rabbit is a suitable model for investigating alterations of vascular response during pregnancy.

Fetal pancreatic glucagon responses in glucose-intolerant nonhuman primate pregnancy.

Rhesus monkey pancreatic alpha-cell function in streptozotoc-induced glucose-intolerant pregnancy is similar to that in normal primate pregnancy. Specifically, basal maternal and fetal plasma glucagon levels equate, and the fetal alpha cell does not respond to the glucagonogenic stimulus of either intravenous alanine or insulin-induced hypoglycemia. This contrasts with the accelerated maturation of the fetal beta cell in glucose-intolerant pregnancy, and does not support the concept of functional coupling of the pancreatic islet by a common glucose-based process. Fetal plasma glucagon levels do increase after L-dopa injection to the fetus. These data indicate that alpha cell unresponsiveness is a function of the glucagon-releasing mechanism rather than inadequate hormonal synthesis.

Cortisol facilitates ovine fetal/maternal water transfer.

After the infusion of 500 ml 20% mannitol to 12 pregnant ewes, we studied fetal plasma osmolality responses in chronically catheterized fetal lambs at 129-140 days' gestation. To compare the effects of arginine vasotocin (AVT) alone and AVT plus cortisol on fetal/maternal water transfer, the mannitol infusion was repeated during a 2-h fetal infusion of AVT alone (7 microU/kg/min) and during infusion of AVT with cortisol (50 micrograms/h) (eight and six animals, respectively). The fetal osmolar response to maternal mannitol administration was compared to the response following the baseline mannitol study in the same sheep. In four of the ewes, an identical (sham) study was performed substituting 500 ml normal saline for the mannitol infusion to the ewe. Fetal AVT infusion significantly obtunded the fetal osmolality increment induced by maternal mannitol alone [P less than 0.001, analysis of variance (ANOVA)]. Fetal AVT administered concurrently with cortisol produced an increment in fetal plasma osmolality in response to maternal mannitol that was significantly enhanced compared with that during fetal AVT infusion alone (P less than 0.001, ANOVA). The response to AVT with cortisol was similar to that following mannitol alone. Normal saline (sham protocol) produced no change in maternal or fetal osmolality. These results indicate that fetal AVT inhibits fetal to maternal water transfer following an osmotic stimulus to the ewe, while cortisol (infused with AVT) tends to counteract the inhibitory effect of AVT on fetal/maternal water transfer.

Antepartum predictors of fetal distress in postterm pregnancy.

The purpose of this study was to determine the efficacy of combining nonstress testing with ultrasound assessment of amniotic fluid volume for the antenatal evaluation of the postterm fetus. Postterm patients (884) were managed with amniotic fluid assessments and nonstress tests (including evaluation for variable and late decelerations) twice a week. There were no perinatal deaths or major neonatal morbidity. However, the antenatal testing sensitivity, specificity, negative, or positive predictive values were not improved by combining the two tests. Individually, amniotic fluid assessment was just as accurate a predictor of fetal well-being and was a significantly more sensitive test than the nonstress test. In addition, antenatal predictors of fetal distress and intrapartum signs of fetal distress were almost exclusively those reflective of umbilical cord compromise. These findings stress the importance of antenatal screening for signs of umbilical cord compromise as an early indication of potential fetal compromise. Although the results also suggest that amniotic fluid assessment is superior to the nonstress test, they do not conclusively support the use of amniotic fluid assessment as the sole parameter for postterm antenatal surveillance.

Critical tricuspid insufficiency due to papillary muscle rupture. A result of prenatal hypoxic insult.

Fatal tricuspid insufficiency secondary to papillary muscle rupture due to prenatal hypoxic insult occurred in a full-term newborn. The diagnosis of flail tricuspid valve should be considered when fetal distress is encountered in a newborn with persistent hypoxemia. Prenatal diagnosis of this condition combined with prompt delivery, prostaglandin E1 therapy, and possible surgical repair of the tricuspid valve may improve chances of survival.

Effect of alpha-adrenergic agonist and antagonist infusion on the umbilical and uterine circulations of pregnant sheep.

The effects of the alpha-adrenergic agonists, norepinephrine and methoxamine, and the alpha-antagonist, phenoxybenzamine, on umbilical and uterine blood flows, fetal and maternal heart rates, arterial and venous pressures were examined in near-term chronic sheep preparations. Norepinephrine injection or methoxamine infusion to either fetus or ewe resulted n a respective unilateral fetal or maternal pressur response associated with bradycardial. Uterine blood flow decreased significantly with alpha-agonist administration to either fetus or ewe. Umbilical blood flow did not change with either, but an increase in calculated umbilicalo vascular resistance did occur after fetal administrations of the alpha-agonist. Thus, both the uterine and umbilical vascular beds are responsive to alpha-agonism, but maternal uteroplacental perfusion appears to be more sensitive. alpha-Blockade in either fetus or mother produced no significant changes in umbilical or uterine blood flows or fetal or maternal perfusion pressure suggesting that basal alpha-adrenergic tone is unnecessary for normal maintenance of either fetal or maternal uteroplacental circulation.

Lung lecithin biosynthesis in the nonhuman primate fetus: determination of the primary pathway in vivo.

The two pathways for de novo lecithin (phosphatidylcholine) biosynthesis, choline incorporation (1) and phosphatidylethanolamine methylation (II), were examined simultaneously in lung and other tissues of Rhesus monkey fetuses. Cannulation of interplacental fetal vessels permitted studies on the intrauterine fetus without disruption of fetal-placental-maternal-amniotic fluid anatomic integrity. In contrast to observations with indirect techniques in the same species, direct measurement of the incorporation of isotopic precursors (3H-choline and 14C-ethanolamine) into lecithin indicated that pathway I predominates by 100-fold over PE methylation in pulmonary lecithin synthesis. Fetal liver, brain, and kidney also showed 10--70-gold greater choline incorporation that methylation activity. Measurement of lung phosphatidylcholine production via the two pathways in acidemic fetuses (umbilical venous pH less than 7.20) demonstrated marked inhibition of pathway I, but not II. It is concluded that the choline pathway is the major mechanism of lung lecithin synthesis in fetal primates and that this pathway is pH sensitive in vivo.

Plasma renin activity during ovine pregnancy.

Chronic intravascular catheterization in maternal, fetal, and neonatal sheep was utilized to assess basal plasma renin activity (PRA) and changes in PRA in response to furosemide. Maternal PRA increased from base-line levels during the last trimester of pregnancy and remained elevated for 12 wk postpartum. Fetal basal levels of PRA were variable but usually greater than maternal levels. Intravenous administration of furosemide to pregnant ewes resulted in a prompt and significant increase in maternal PRA with inconsistent changes in fetal PRA. Fetal and neonatal animals with low basal levels showed a significant increase in PRA; maternal PRA did not change. Animals with higher basal levels did not respond to the stimulus, perhaps reflecting a maximum renin secretory rate. These data are consistent with the conclusions that fetal renin originated predominantly from the fetal kidney, that fetal PRA receives no significant contribution from the maternal circulation, and that renin does not cross the ovine placenta.

Perinatal primate parathyroid hormone metabolism.

Near-term fetal and neonatal parathyroid gland function has been studied in the Rhesus monkey. Fetal serum ionized calcium (Ca++) levels are significantly greater than simultaneously obtained maternal levels. Fetal serum parathyroid hormone (PTH) was undetectable both in the basal state and in association with EDTA-induced fetal hypocalcemia. Induced maternal hypocalcemia was associated with increased maternal serum PTH levels and no change in fetal basal serum Ca++ or PTH levels. Only a minimal decrease in simian neonatal serum Ca++ occurred over the first 48 h of life. Normal adult levels of serum PTH were present as early as 6 h of neonatal life. Induced hypocalcemia at 12 h of age resulted in a significant increase in serum PTH levels.

Catecholamine physiology in the ovine fetus. I. Gestational age variation in basal plasma concentrations.

Fifty-five ewes with chronically catheterized singleton gestations were studied to assess changes in basal concentrations of fetal catecholamines with increasing gestational age. All pregnancies were time dated, and measurements of catecholamines were conducted at least 5 days after placement of fetal catheters when fetal metabolic parameters had normalized. Plasma concentrations of catecholamines were measured by radioenzymatic assay. Additionally, fetal heart rate (FHR) and corrected mean blood pressure were analyzed in 32 of the fetuses for correlation with plasma levels of catecholamines. Multiple regression analysis revealed significant inverse correlations of fetal plasma concentrations of catecholamines with gestational age, as follows: norepinephrine (p less than 0.001), epinephrine (p less than 0.05), and dopamine (p less than 0.01). FHR correlated inversely with gestational age (p less than 0.001) and positively with circulating levels of norepinephrine (p less than 0.001).