Eberhard Mueller-Heubach

Placental transfer and distribution of nicotine in the pregnant rhesus monkey

Abstract Placental transfer and distribution of nicotine in fetal tissues were determined in 10 pregnant monkeys in the third trimester. Nicotine was exchanged rapidly across the placenta between mother and fetus when it was administered into the maternal circulation in a dose of 1 mg. per kilogram of body weight. The concentration of nicotine in the fetal circulation surpassed the maternal level rapidly, reaching maximum in 16 minutes and remaining at a higher concentration for over two hours following the injection. Disappearance of nicotine from the fetal circulation was slower than that from the maternal circulation. The concentration of nicotine in adrenal glands, heart, kidneys, stomach wall, and spleen of fetuses was high; that in placenta and skeletal muscles was low. The amount of nicotine contained in a fetus, however, was only a small fraction of the total dose administered to the mother.

Kell sensitization in pregnancy

Maternal anti-Kell antibody was found in 127 of 127,076 pregnancies during a 16-year period (0.1%). Thirteen Kell-sensitized pregnancies ended with a Kell-positive newborn infant, five of these had a poor perinatal outcome (hydrops, intrauterine or neonatal death, hemoglobin less than 7.9 gm, congestive heart failure). Mothers with Kell-positive infants and poor outcome had anti-Kell titers greater than or equal to 1:128 at delivery. With a maternal anti-Kell titer less than 1:32 at delivery, only one baby was Kell positive and mildly affected by hemolytic disease. Spectrophotometric analysis of amniotic fluid (delta optical density at 450 nm) in three of four pregnancies with poor perinatal outcomes revealed values of delta optical density at 450 nm in the high midzone of Liley within 1 week of delivery. Therefore, Kell-sensitized patients have to be managed differently from patients with rhesus sensitization. A management scheme to optimize perinatal outcome in Kell-sensitized pregnancy is described on the basis of this largest reported series of Kell-sensitized pregnancies.

Pharmacologic inhibition of preterm labor

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.

Fetal renal pulsed Doppler waveform in prolonged pregnancies

OBJECTIVE Our purpose was to determine Doppler waveforms of the fetal human renal artery in prolonged pregnancy in the presence or absence of oligohydramnios. STUDY DESIGN Fifty patients at or after 40 weeks were studied. Ultrasonography was performed to determine the amniotic fluid index by the four-quadrants technique. Two groups of patients were obtained on the basis of the amniotic fluid index. Group 1 had an amniotic fluid index > 5 (normal) (n = 33); group 2 had amniotic fluid index < or = 5 (oligohydramnios) (n = 17). Umbilical artery and fetal renal pulsed Doppler waveforms were determined and analyzed. The fetal renal artery systolic-to-diastolic ratio of the two groups was compared. RESULTS Fetuses with a low amniotic fluid index had a significantly higher ratio. A significant negative correlation coefficient between amniotic fluid index and fetal renal systolic/diastolic ratio was found (r = -0.435 and p < 0.01). CONCLUSIONS In prolonged pregnancies there is a significant relationship between the amniotic fluid index and the fetal renal systolic/diastolic ratio. In pregnancies associated with oligohydramnios the systolic/diastolic ratio is significantly higher than in those with normal amniotic fluid volume. These data suggest that intrarenal flow in prolonged pregnancies complicated with oligohydramnios is significantly different.

Portal venous blood flow distribution to liver and ductus venosus in newborn lambs

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.

Effects of electronic fetal heart rate monitoring on perinatal outcome and obstetric practices

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.

Umbilical venous blood flow and its distribution before and during autonomic blockade in fetal lambs

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 significnatly 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 venosus, 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 alpha-adrenergic systems influence the basal distribution of umbilical venous blood flow.

Effect of betamethasone on analysis of amniotic fluid in the rhesus-sensitized pregnancy

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 mmu 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.

Validation of noninvasive fetal renal artery flow measurement by pulsed Doppler in the lamb

OBJECTIVE Our objective was to evaluate the accuracy of quantitative measurement of blood flow of the left renal artery in the fetal lamb by means of range-gated, two-dimensional pulsed Doppler ultrasonography. STUDY DESIGN Doppler measurements were compared with invasive measurements obtained with a perivascular flow probe (Transonic) placed on the fetal renal artery. Renal blood flow was manipulated acutely either by volume expansion or depletion or by means of pharmacologic agents. With each manipulation values of the left fetal renal artery blood flow were obtained with both methods. The size of the fetal renal artery was determined by postmortem examination. RESULTS A total of 36 paired flow measurements were obtained on five fetuses. One fetus had only Transonic determination of renal blood flow. Pulsed Doppler ultrasonography blood flow and transit-time ultrasonography blood flow estimations were correlated (F = 82.4, R2 = 0.73, p < 0.001). CONCLUSION This study suggests that two-dimensional pulsed Doppler can reliably estimate renal blood flow in the fetal lamb.

Effects of dexamethasone on leukocyte counts in pregnant sheep and fetal lambs

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 returned 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 not 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.