Premature labour induced by cortisol in the unrestrained pregnant rabbit.

The relationship between electrical activity (EMG) of the uterus, progesterone levels and gap junctions was studied in pregnant rabbits delivering either prematurely (cortisol-induced) or spontaneously at term. Electrodes were implanted in the myometrium and a catheter was inserted into the jugular vein for continuous infusion of saline or cortisol from gestational age 25 days. A tether and swivel system was used to connect the electrodes and catheter to the recording unit thus allowing protection of the wires and catheters while enabling the rabbit to move freely. The EMG was recorded continuously from day 25 of pregnancy until animals either delivered or were sacrificed at predetermined days of gestation. Both rabbit groups showed a similarity in patterns of EMG, progesterone levels and gap junction formation. We conclude that preterm labour induced by cortisol mimics normal term labour.

Fetal renal failure associated with intrauterine growth retardation.

Four preterm infants with severe intrauterine growth retardation had renal failure from birth. The amount of asphyxia associated with the birth process did not fully explain the renal failure. Before delivery all for fetuses had severe oligohydramnios and an empty urinary bladder. These observations strengthen the view that severe intrauterine growth retardation may be accompanied by oligohydramnios caused by fetal renal failure.

The rationale for biochemical monitoring of the fetus.

1. Rates for perinatal mortality and low Apgar scores have not been affected by fetal intensive care (electronic monitoring +/- fetal blood sampling) in any randomized controlled trial to date. 2. Acidosis at birth may be susceptible to improvement by fetal intensive care but has not been tested adequately in more than a few women. 3. Birth asphyxia which is followed by evidence of cerebral dysfunction within the first 48 hours of life can be significantly altered by current technics of fetal intensive care. 4. The evidence suggests that cognitive disorders and cerebral palsy occur as long term sequelae of hypoxic-ischaemic encephalopathy in a small percentage of survivors. However, factors which predate the onset of labour are more likely to be responsible for cerebral palsy than factors associated with labour. 5. Future developments might include the following: (i) To establish that umbilical arterial pH and/or lactate and/or Apgar score is predictive for neonatal outcome such as hypoxic-ischaemic encephalopathy or other markers of asphyxia. (ii) To determine whether umbilical arterial pH and/or lactate is significantly different when continuous biochemical monitoring is used versus traditional intermittent fetal blood sampling, i.e. does continuous monitoring prevent acidosis? In the present state of development of continuous biochemical monitoring technics in labour it seems unlikely that, at the present time, we could answer the larger question of whether such monitoring can prevent the neurological complications of hypoxic-ischaemic encephalopathy and the subsequent developmental problems including cerebral palsy. Finally, we must not forget that labour and delivery represents a relatively small time period in relation to the total duration of pregnancy with a ratio of approximately 1:355. Thus, it is not surprising that many of the problems of neurologic development are difficult to trace back to a particular stage in pregnancy. Careful monitoring of labour and delivery may help to counteract the tendency to blame this period of pregnancy for all subsequent developmental problems of the child.

The effect of mild hypoxemia maintained for twenty-four hours on maternal and fetal glucose, lactate, cortisol, and arginine vasopressin in pregnant sheep at 122 to 139 days' gestation.

The effects of prolonged mild hypoxemia on the fetus have received little attention. We investigated the response to a decrease in fetal arterial Po2 of 5 mm Hg or less sustained for a period of 24 hours in the chronically instrumented fetal lamb. Hypoxemia was induced by an infusion of nitrogen via the maternal trachea for 24 hours in 13 pregnant sheep at 122 to 139 days' gestation. Two control periods of air infusion via the maternal trachea for 24 hours were alternated with hypoxemia. Fetal hypoxemia was not associated with any change in fetal pH. During the first and second exposures to hypoxemia, there was an increase in fetal plasma lactate of 22.8 +/- 22.3 and 15.3 +/- 14.6 mg.dl-1 (mean +/- SD) above preliminary values (p less than 0.05) compared with the control period. Fetal plasma cortisol also increased by 5.7 +/- 6.1 and 9.5 +/- 5.4 ng.ml-1 (mean +/- SD) (p less than 0.05) compared with the control period. These results suggest that the fetal lamb at 122 to 139 days' gestation is highly sensitive to small decrements in Po2 of 5 mm Hg or less.

Maternal, fetal, and newborn tissue PO2 in sheep measured with galvanic oxygen electrodes.

Tissue PO2 was measured with galvanic oxygen electrodes chronically implanted in maternal and fetal tissues of two pregnant ewes. Labor commenced after 3 days in one ewe and after 11 days in the other. Tissue PO2 was measured in both newborn lambs. Fetal tissue PO2 during labor was less than 3 mm Hg but rose to values similar to those found in adult tissues in the newborn period. Function of the electrode and response of the tissue to change in oxygenation was challenged by administration of 100% oxygen to the pregnant ewe or newborn lamb, and by administration of intravenous epinephrine to the ewe. These tests suggested that all electrodes were functioning satisfactorily in vivo and that tissue PO2 was responding as anticipated. Recalibration of electrodes after removal from the tissues confirmed that their response in vitro was similar to that obtained before implantation.

Placental transport of low molecular weight heparin in the pregnant sheep.

Standard heparin, an effective treatment for antepartum thromboembolic disease, is thought to be safe for the fetus since it does not cross the placenta. Recently, a number of low molecular weight heparins have been prepared which have been shown to produce less bleeding than standard heparin for an equivalent antithrombotic effect in experimental animals. These observations suggest that the low molecular weight heparins may also provide superior antithrombotic therapy in antepartum thromboembolic disease. However, it is not known whether the low molecular weight heparins cross the placenta. To determine this, we examined the pharmacokinetics of 125I-labelled standard heparin and a low molecular weight heparin, and their anticoagulant effects in mother and fetus, using a pregnant sheep model. Catheters were inserted into maternal and fetal femoral arteries at 108-119 d gestation (term: 147 d). 1-3 days later the mothers were given a bolus i.v. injection of 5000 anti-Xa units of 125I-labelled standard heparin or low molecular weight heparin, CY 222. Nine serial blood samples were collected over 4 h from both mother and fetus for measurements of radioactivity, anti-Xa activity (chromogenic) and activated partial thromboplastin times. When therapeutic levels of standard and CY 222 heparins were achieved in the mother, there was no detectable radioactivity or anticoagulant effect in the fetus. We conclude that standard heparin and the low molecular weight CY 222 do not cross the placenta in the pregnant sheep.

Myometrial electrophysiologic activity and gap junctions in the pregnant rabbit.

Electromyographic activity of the myometrium, intrauterine pressure, and myometrial gap junctions were examined in rabbits at various stages of pregnancy and during parturition. Electromyographic activity occurred throughout pregnancy and was characterized by electromyographic bursts lasting up to 5 minutes at a frequency of one to four per hour. The gap junction area of plasma membrane showed a significant increase at delivery at a time when electromyographic activity changed to rhythmic bursts of short duration at a frequency of about one per minute. This study shows that the rabbit uterus is active throughout pregnancy; furthermore, the development of large numbers of gap junctions between myometrial cells occurs at a time when uterine activity changes to the expulsive activity required for labor.

Fetal blood and tissue PO2 during maternal oxygen breathing.

The effect of 100% oxygen breathing on fetal blood and tissue PO2 was examined in chronically catheterised fetal sheep of 12 pregnant ewes. Blood PO2 was monitored with intravascular polarographic electrodes and tissue PO2 with galvanic electrodes implanted in various tissues. In non-acidotic healthy fetuses, oxygen breathing increased fetal PO2 by 30% within 3 min in arterial blood and within 5 min in tissues. Thereafter blood PO2 increased by a maximum of 40% at 9 min and tissue PO2 rose by a maximum of 52% at 12 min. Blood PO2 returned promptly to control values after 15 min of oxygen breathing but washout of oxygen from tissues was slower and tissue PO2 remained significantly higher in the post-oxygen versus the pre-oxygen period. Continuation of oxygen breathing for 30 min did not lead to any further increase in tissue PO2. Oxygen breathing did not prevent a decrease in fetal PO2 associated with spontaneous myoelectrical activity of the uterus. It is concluded that maternal oxygen breathing leads to a significant increase in both blood and tissue PO2 in the healthy fetus. The majority of the increase occurs within the first 3-4 min and no further increase in either blood or tissue PO2 is observed after 12 min.

Maternal and fetal tissue PO2 in the pregnant ewe measured with galvanic PO2 electrodes.

Galvanic PO2 electrodes housed in an acrylic disc 1 cm. in diameter have been implanted in maternal and fetal tissues in the pregnant ewe at 109 to 140 days gestation. Of the 102 electrodes implanted, 52% maintained reasonably acceptable calibration values when recovered from the tissues after implantation periods ranging from one to 73 days. Basal tissue PO2 values were generally less than 10 mmHg in the fetus. Physiologic fluctuations (decreases) in fetal tissue PO2 observed at regular intervals during the last one-third of gestation, coincided with a decrease in maternal uterine PO2 and an increase in amniotic fluid pressure and were attributed to uterine contractions.

The effect of epinephrine on blood and tissue PO2 in the rabbit.

Tissue PO2 in the rabbit was measured with galvanic oxygen electrodes chronically implanted in peritoneal and subcutaneous tissues; blood PO2 was measured in arterial and venous blood samples obtained from chronically implanted catheters. The effect of intravenous epinephrine 4 microgram/kg on tissue and blood PO2 was examined in the unanesthetized animal. Basal tissue PO2 values were 43.6 +/- 1.71 mm Hg (mean +/- SEM) for peritoneum and 15.9 +/- 2.51 mm Hg for subcutaneous tissue. These values increased to 112.8 +/- 8.67 mm Hg (peritoneum) and 76.0 +/- 2.24 mm Hg (subcutaneous) after 15 minutes of O2 breathing. Epinephrine led to significant reductions in tissue PO2 during both air and O2 breathing without affecting blood PO2. It is concluded that epinephrine administration alters the relationship between blood and tissue PO2 leading to relative tissue hypoxia despite normal or high blood PO2. These observations are important to an understanding of shock and emphasize the need for further investigation of tissue PO2 as a measure of shock states.

Perinatal changes in plasma carnitine levels in 4 species of mammal.

Plasma levels of carnitine, acetylcarnitine, and beta-hydroxybutyrate rise perinatally in rats, guinea-pigs and sheep but not in rabbits. In the fetus, carnitine levels are high in rabbits and guinea-pigs but not in rats and sheep.

Abnormal fetal heart rate associated with congenital abnormalities.

The fetal heart rate (FHR) records obtained from 3140 patients were reviewed. Thirty-seven patients gave birth to an infant with a major congenital abnormality. Fifty-one per cent of this group demonstrated an abnormal FHR in the antepartum or intrapartum period. The Caesarean Section rate was 48 per cent and perinatal mortality was 50 per cent. In patients with an abnormal antepartum FHR record, an underlying congenital abnormality of the fetus should be considered.

Real-time ultrasound observation of fetal activity in labour.

Fetal activity was observed by realtime ultrasound for one hour in 25 patients in labour. Fetal respiratory movement, although reduced compared to the antenatal period, was observed in 13 patients. In three patients, hiccough-like movements were noted. Fetal body and/or extremity movements were observed in all patients (mean 41/hour) and frequently occurred in episodes. These bursts of movements were significantly correlated with contractions and fetal heart rate (FHR) accelerations. There was a significant association between absent or reduced number of fetal respiratory movements and/or hiccoughs (10 or less/hour) and an abnormal FHR. Absence of any type of fetal activity was also significantly associated with an abnormal FHR. The correlation between fetal activity and conventional methods of fetal assessment is discussed.

A scoring system for nonstressed antepartum fetal heart rate monitoring.

A scoring system developed to assess nonstressed antepartum fetal heart rate records has been evaluated. The system scores from 0 to 2 for each of five factors, i.e., baseline rate, amplitude and frequency of fluctuation, decelerations, and accelerations. A total of 1,367 nonstress tests in 284 patients were retrospectively reviewed. Three groups of patients were delineated with respect to the fetal heart rate scores. When the group with the highest score of 8 to 10 and a perinatal mortality rate (PNM) rate of 4.7/1,000 was compared with the groups having intermediate (5 to 7) and low (less than or equal to 4) scores, there was a highly significant increase in PNM to 69.8/1,000 (p less than 0.01) and 433/1,000 (p less than 0.001), respectively. A significant increase in low Apgar scores at 1 and 5 minutes, in fetal acidosis (low umbilical arterial pH), and in duration of intensive care nursery stay was also seen as the fetal heart rate score progressively deteriorated from the 8 to 10 group to the less than or equal to 4 group. We conclude that this scoring system clearly delineates normal from prepathologic and pathologic changes in fetal heart rate and can be used as warning of impending fetal death.

Follow-up of intrauterine transfused surviving children.

The long-term effects of intrauterine transfusion (IUT) are still being assessed since the procedure was first reported in 1963. Therefore, we undertook a follow-up study on the survivors of 57 infants who received IUT's between 1966 and 1975. Forty-two infants were born alive, but 15 died in the neonatal period. Overall survival was 27/57 (48%). An extensive follow-up examination was carried out at age 22 months to 10 years in 21/27 survivors. Height was below the third percentile in one child and head circumference above the mean and 2 SD in another. Of 21 children, 19 had normal vision, one was slightly myopic, and one had hyperopia. One child had unilateral high-frequency hearing loss. All had normal EEG's and none have mental retardation but 2/21 have "major" and 6/21 have "minor" neurologic signs. No evidence of passive antibody transfer was found, but minor disturbances of immunoglobulin levels were present.

Carnitine content of blood and amniotic fluid.

Free carnitine levels were determined in amniotic fluids between the 10th and 40th week of gestation. They were found to decrease significantly with gestational age. Blood levels of carnitine were lower in pregnant than in nonpregnant women. Levels were found to be higher in cord blood than in maternal blood and usually were higher in the umbilical artery than vein. Intra-arterial injection of L-carnitine into a pregnant ewe did not cause a rise in the fetal blood level of carnitine, which, in contrast to human fetal blood, contained less than half the level of carnitine in maternal blood.