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Anticoagulation with intravenous heparin has been the standard treatment for the management of gestational thromboembolic complications. Catheter-directed thrombolysis is an encouraging approach for the treatment of thromboembolic disease and has not been previously reported during pregnancy. One gravid woman with pulmonary embolism, critically ill, and hemodynamically compromised, and two gravid women with iliofemoral venous thrombosis, who failed to respond to standard treatment with intravenous heparin, were treated with catheter-directed urokinase. All three patients experienced rapid resolution of symptoms and successful pregnancy outcomes. In our three patients, catheter-directed thrombolysis for thromboembolic disease during pregnancy allowed rapid resolution of hemodynamic abnormalities and/or resolution of thrombus. Catheter-directed thrombolysis offered a reasonably safe alternative to prolonged medical management in these young, otherwise healthy, patients. Long-term, it may prevent t...

Electronic fetal monitoring (EFM) was introduced into clinical practice 30 years ago and spread very rapidly in most developed countries. The early optimism that EFM would lead to a marked reduction in fetal neurological injury has not been realized; however, it is now recognized that most such damage is unrelated to perinatal events. Clinical trials have shown that although EFM does reduce the incidence of intrapartum asphyxia, its use is also associated with an increase in cesarean sections. Abnormal fetal heart rate (FHR) patterns are poor predictors of fetal depression at birth when used without additional confirmatory information. An additional problem has been inconsistency in the interpretation of EFM tracings even among experts. This has reduced the clinical effectiveness of EFM and has also contributed to an increase in litigation in cases with adverse neonatal outcomes. Despite these shortcomings EFM continues to be used extensively on most obstetrical services, suggesting that obstetrical physicians and nurses find the technique helpful and will continue to use it until a better alternative comes along. The combination of relevant clinical data with EFM by means of intelligen computer systems may improve both the consistency and predictive value of intrapartum fetal assessment in the future.

OBJECTIVE: Our purpose was to compare the accuracy of maternal perception of preterm uterine activity by self-palpation versus home uterine activity monitoring. STUDY DESIGN: A total of 72,962 uterine activity records of 778 women receiving home uterine activity monitoring services were analyzed. Simultaneously with home uterine activity monitoring, the women indicated by an electronic marker when they felt a "contraction" through self-palpation. The perceptions of the women were compared to the tocodynamometrically measured uterine activity. RESULTS: Using self-palpation, women correctly identified 17.2% of contractions recorded by tocodynamometry. Overall mean percent correct correlation per patient was only 14.1%. Patients missed an average of 85.7% of their contractions. Patients incorrectly perceived contractions that were not present an average of 40.3% of the time. Singleton gestations had significantly better correct correlations than twin gestations. Multiparous women had improved correlations compared with primiparous women. No significant correlation was found between maternal perceptive ability and gestational age. CONCLUSION: Women were unable to perceive accurately the presence or absence of preterm uterine activity through self-palpation compared with simultaneous measurement by home uterine tocodynamometry. (AM J OBSTET GYNECOL 1996;174:672-5.)

OBJECTIVE: Our purpose was to investigate the spatiotemporal properties of the fetal magnetocardiogram. STUDY DESIGN: Fetal magnetocardiogram maps were measured for the first time in 20 subjects from 22 to 39 weeks' gestation. Waveform and topographic maps were used to display the data. RESULTS: The maps showed spatiotemporal properties consistent with simple volume conductor theory: topography was closely related to the presentation of the fetus, Q-wave sources were dipolar and localized, the magnetic heart vector rotated extensively during the QRS complex, and close correspondence was observed between fetal and neonatal maps. Ventricular depolarization and events in the cardiac cycle could be visualized in considerable detail by means of a time series of topographic maps. CONCLUSION: Fetal magnetocardiogram shows excellent spatiotemporal properties and is well suited for in utero studies of fetal heart activity. (AM J OBSTET GYNECOL 1994;170:770-6.)

Fetal heart rate variability was derived from fetal magnetocardiogram recordings in ten subjects at gestation ages 32–38 weeks. Maternal interference was negligible and R-wave detection was highly reliable. Oscillations suggestive of respiratory sinus arrhythmia (RSA) were prominent in many of the heart rate tracings. Spectral analysis was used to quantify heart rate variability and to examine the influence of the RSA-like oscillations on heart rate variability. The oscillations were associated with increased power in the frequency range 0.4–1.0 Hz (P ≤ 0.05). Magnetic recording appears to offer significant advantages for investigation of beat-to-beat fetal heart rate throughout the latter stages of pregnancy.

Twenty-five mid-gestation guinea pigs were studied to determine the nature of spontaneous uterine contractures and elucidate the temporal relationship between blood flow and contractile activity. In the first protocol, 15 mid-gestation guinea pigs with indwelling vascular catheters were studied. Blood flows were measured by radioactive microsphere technique during rest, uterine contracture, and, in six animals, 1 minute after contracture activity. During contracture, maternal blood flow to the placenta closest to the electrode fell to 81.3 ± 5.3% of control (n = 15, P ±. 01) and then rose to 130.4 ± 10.2% of control (P ≤. 01) 1 minute after a contracture. The corresponding relationships were also significant for placental vascular resistance and constitute a reactive hyperemic response of the placenta to uterine contracture. No such phenomenon was observed in the more remote placentas on either the ipsilateral or contralateral side.To investigate the nature of contractile activity, electrodes were placed ...

In order to determine the effect of the narcotic analgesic oxymorphone hydrochloride (Numorphan, DuPont) on fetal heart rate (FHR) variability, mathematical indices of short-term and long-term FHR variability were determined continuously from R–R intervals of the electrocardiogram in eight chronically instrumented ovine fetuses for 60 min before and after a maternal intravenous bolus of 0.04 mg/kg oxymorphone. The index of short-term variability decreased from 12.7 ± 2.0 during control to 9.7 ± 1.7 during the period from 10 to 30 min after oxymorphone administration during periods of low-voltage, high-frequency electrocortical activity (LVHF ECoG) (P < 0.05). Mean FHR was decreased from 169 ± 8 beats per minute (bpm) during control to 155 ± 7 bpm 30 to 50 min after oxymorphone (P < 0.05). Fetal electrocortical activity was also determined and the decrease in FHR short-term variability occurred despite an increase in the percent time spent in LVHF electrocortical activity from 53 ± 4% during the control pe...

The principal objective of antenatal testing is to detect fetal hypoxia before the fetus has suffered lasting harm. This article summarizes some of the mechanisms by which fetal oxygen consumption is maintained under normal conditions, and adaptations that occur in response to hypoxemia. Alterations in the fetal heart rate are prominent in the fetal response to hypoxemia and are the basis of some methods of antenatal testing. The principal mechanisms underlying these fetal heart rate changes are described. Adaptations in the distribution of blood flow that permit the fetus to deal with reduced oxygen levels are summarized. Developmental trends in fetal motility and behavior are outlined, and also how these are modified by fetal growth retardation and maternal diabetes. Fetal movements are suppressed during acute hypoxemia, but with gradually developing hypoxemia, normal movement patterns may continue until the fetus becomes acidemic. This may limit the use of these biophysical variables in antenatal testing.

Atrial and ventricular fetal heart rate tracings from a patient with isolated congenital complete heart block treated with dexamethasone showed a remarkable degree of correlation and greater reactivity for the ventricular than the atrial fetal heart rate. Ventriculophasic sinus arrhythmia was present continually in the atrial fetal heart rate tracings.

Magnetoencephalography was used to noninvasively record auditory evoked responses from fetuses in utero at 34 to 37 weeks' gestation. The recordings were similar to auditory evoked responses from neonates at age 7 to 14 days.

Background Ductus arteriosus constriction is a known complication of exposure to indomethacin in utero. Nonimmune hydrops associated with indomethacin use has been reported in only six cases, all twins over 32 weeks' gestation. Case We present a case of fetal hydrops associated with tricuspid regurgitation and ductal constriction developing within 30 hours of instituting indomethacin tocolysis in a 28-week singleton gestation. Discontinuation of indomethacin resulted in partial resolution of these findings 72 hours later. A normal infant was delivered subsequently. Conclusion Ultrasonographic screening for signs of constriction of the ductus arteriosus should be done within 48 hours of instituting indomethacin therapy at any gestational age.

We report high precision assessment of fetal rhythm in utero in a case of isolated congenital complete heart block using fetal magnetocardiography. The recordings reveal a remarkably strong tendency for the atria and ventricles to synchronize, which is manifested by the continual presence of ventriculophasic sinus arrhythmia and frequent episodes of accrochage and isorhythmic AV dissociation.

The first studies of fetal neuromagnetism and fetal cardiomagnetism were published more than ten and twenty years ago, respectively [1,2]. Despite considerable interest generated by these reports, relatively few follow-up studies appeared. In retrospect, this is somewhat surprising given that 1) in several respects, magnetic detection is almost uniquely suited to intrauterine evaluation, and 2) there is a paucity of alternate fetal evaluation techniques that provide functional information. During the last few years, interest in fetal biomagnetism has reemerged, as a number of groups have reported findings at meetings and in the literature. This paper presents fetal MCG and fetal MEG studies performed recently by our group at the University of Wisconsin-Madison.

Fetal cardiac waveform intervals were assessed from fetal magnetocardiogram (FMCG) recordings taken from 59 pregnant women at 17-41 weeks gestation. Beyond 27 weeks' gestation PR and QRS intervals, measured from averaged waveforms, could be obtained from all subjects; however, prior to 21 weeks' gestation the success rate was 50% or less due to low signal-to-noise ratio. QT interval could not be assessed accurately in most subjects. Weak, but statistically significant, correlations with gestational age were found for PR interval (n = 145, R2 = 0.033, P = 0.028) and QRS interval (n = 145, R2 = 0.140, P < 0.0005). Abnormal waveform morphology was documented in several patients with cardiac malformations.

Magnetocardiographic recordings from a fetus at 34 weeks' gestation with a complex heart malformation revealed an unusual fetal arrhythmia, where the rhythm was observed to alternate between extended periods of sinus and junctional rhythms. Fetal heart rate measurement showed that the junctional rhythm was strongly associated with respiratory arrhythmia. We hypothesize that changes in autonomic balance due to the onset and cessation of fetal breathing movements were largely responsible for the rhythm alternations. To our knowledge this is the first report of a fetal junction rhythm and the first observation of fetal respiratory arrhythmia during nonsinus rhythm.

The authors show that oscillations at foetal breathing frequencies observed in foetal heart rate (FHR) tracings obtained from foetal magnetocardiogram (FMCG) recordings are often accompanied by synchronous modulation of FMCG signal amplitude. This implies an association between the FHR oscillations and foetal chest wall movements, corroborating the hypothesis that the oscillations are due to respiratory sinus arrhythmia.

We have measured fetal magneto-cardiograms in three subjects of gestation ages 33–37 weeks. Maternal interference was negligible in all recordings. Accurate measures of heart rate, beat-to-beat variability, and averaged MCG waveforms were derived. The results confirm that magnetic monitoring offers significant advantages for antepartum monitoring and deserves further investigation.

11 fetal lambs with gestational age of 116–35 days were studied while connected to a membrane-oxygenator replacing the ventilatory function of the placenta. Progressive increase in arterial oxygen tension from 20 to 220 mm Hg resulted in progressive decrease in baseline heart rate and baseline arterial blood pressure indicating presence of chemoreceptor activity over this wide range of arterial oxygen tension. The effect of 60 sec complete umbilical cord occlusion was studied at progressively higher arterial oxygen tension and it was concluded that the chemoreceptor activity at fetal normoxic condition is very brisk and is markedly attenuated at hyperoxic levels. Although it was not possible to completely separate baroreceptor and chemoreceptor reflexes involved in cardiovascular response to umbilical cord occlusion, it is postulated that the chemoreceptor and baroreceptor reflexes are complimentary during cardiovascular responses to umbilical cord occlusion.

The appearance of late decelerations and the disappearance of accelerations in the fetal heart rate were observed during the days that preceded intrauterine fetal death in nine chronically instrumented rhesus monkeys. All nine animals had recovered satisfactorily from the initial surgical procedure, as evidenced by normal biophysical and biochemical parameters. After recovery, all the fetuses had shown accelerations and no late decelerations with spontaneous uterine contractions. The mean duration of the preparations was 16.1 days. The duration of the preterminal observation period varied from 3 to 13 days, during which time no experiments were performed. The fetuses died during labor at a mean gestational age of 143 days. Late decelerations were the first sign of fetal deterioration and occurred with a slight but significant decrease in fetal PaO2 without changes in pH, whereas accelerations in fetal heart rate were still present. The loss of accelerations in fetal heart rate was a later phenomenon and was associated with significant reductions in fetal pH and PaO2.

Chronically catheterized maternal fetal monkey preparations were used to study pituitary suppression by thyroid hormones in the fetus. Baseline maternal T3, T4, and PRL were all significantly higher than fetal levels of these hormones. TRH was given iv (10 μg/kg) to the mother 3, 6, 12, 20, or 44 h after giving varying doses of T3 to the fetus. Amniotic fluid and fetal tracheal aspirate did not contain detectable TSH. Nonpregnant females and pregnant mothers showed complete suppression of the TSH response to TRH after receiving 20 μg T3 iv 24 h before TRH. Two micrograms of T3 iv to the fetus 3 h before TRH failed to suppress the TSH response (fetal δTSH, 26 μU/ml; δT4, 3.6 μg/dl). Six micrograms of T3 iv (three doses of 2 μg) to the fetus over 36 h achieved a basal T3 level of 2500 ng/dl and lowered fetal δTSH to 9.1 μU/ml. Six micrograms of T3 infused iv to the fetus over 24 h achieved fetal T3 blood levels of 5000 ng/dl, which suppressed δTSH to 2.7 μU/ml. 3,5,-Dimethyl-3'-isopropyl-L-thyronine (DIMIT;...

The exact cause and mechanism of the onset of labor are unknown but the theories are many. There is considerable evidence that prostaglandins are potent stimulants of uterine activity and may play a role in the onset of labor. Prostaglandin release may be the natural mediator of uterine contractions during labor. A group of anti-inflammatory compounds (aspirin-like compounds) that inhibit prostaglandin synthesis include indomethacin and fenoprofen. Inhibition of prostaglandin production is a reasonable approach to inhibiting premature labor. An excised muscle strip technique was used as a screening procedure for pharmacologic depression of human uterine activity in vitro, testing isoxsuprine, mesuprine, Alupent, ritodrine, indomethacin, and fenoprofen. The prostaglandin antagonists indomethacin and fenoprofen exhibited marked depressant activity. These drugs were further tested in an in vivo rhesus monkey preparation measuring uterine activity, maternal blood pressure, uterine blood flow, fetal heart rate, fetal blood pressure, and blood gases. Fenoprofen is effective in reducing uterine contractility without serious maternal or fetal side effects and shows promise as a clinically effective agent for pharmacologic control of premature labor.

Morning and evening simultaneous fetal and maternal plasma samples were analyzed for thyroid-stimulating hormone. An a.m. -to- p.m. variation in fetal concentrations was identified, whereas the majority of the maternal values (28 of 32) were below the sensitivity of the assay. The importance of this cyclic fetal activity is discussed.

The effect of thyrotropin-releasing hormone (TRH) on the pituitary-thyroid axis and on prolactin secretion was studied in pregnant Rhesus monkeys during the latter period of gestation and in non-pregnant female controls. The baseline plasma concentrations of TSH, T3, T4, and prolactin (PRL) of pregnant monkeys did not differ from those of non-pregnant monkeys. After administration of TRH, plasma prolactin rose to higher levels in pregnant monkeys than in non-pregnant monkeys whereas there was a similar response of plasma TSH, T4 and T3 in both groups. The baseline plasma TSH was elevated and plasma T3 was decreased in the fetus compared with the mother. Administration of TRH iv to the maternal monkey caused a larger response in the fetal plasma TSH than in that of the mother and was followed by larger increments in plasma T4 and T3 concentrations in the fetuses than in the mothers. The larger increments of plasma TSH and thyroid hormones in the fetus compared with the mother also occurred when TRH was given iv to the fetus. There was a significant rise of plasma prolactin in both mother and fetus after administration of TRH to mother or fetus; the increase of plasma PRL was much higher in the mother than in the fetus. The data show that TRH can cross the primate placenta in either the maternal to fetal or fetal to maternal direction. The fetal thyroid of the Rhesus monkey during the latter period of gestation can release both T4 and T3 in response to TSH.

Impairment of umbilical cord blood flow has been associated with periodic fetal heart rate changes termed "variable decelerations." These patterns may be observed after amniotomy. A chronic fetal rhesus monkey preparation has been used to investigate this clinical observation. Loss of amniotic fluid produced variable deceleration patterns, while restoration of amniotic fluid volume eliminated such changes. These experimental data demonstrate that amniotic fluid may be critical in protection of the cord and maintenance of normal umbilical cord blood flow.

Continuous fetal heart rate (FHR) monitoring and routine fetal scalp blood sampling was utilized in the evaluations of 366 fetuses during labor. One hundred and six patients had meconium in the amniotic fluid at some time during labor. A total of 26,110 uterine contractions were monitored during these 366 labors. The incidence of FHR patterns as a percentage of uterine contractions was calculated for the meconium and nonmeconium groups. Although there was a 3½ increase in the incidence of low five-minute Apgar scores (less than 7) in the meconium group, signs of fetal distress were, with rare exception, not significantly different from those in the nonmeconium group. The presence of meconium in the amniotic fluid without signs of fetal asphyxia (late decelerations and acidosis) is not a sign of fetal distress and need not be an indication for active intervention. The combination of fetal asphyxia and meconium staining of the amniotic fluid, however, does enhance the potential for meconium aspiration and a poor neonatal outcome. Universal fetal heart rate monitoring and appropriate fetal acid-base evaluation is recommended for following patients with meconium in the amniotic fluid during labor.

The incidence and character of fetal breathing movements (FBMs) were determined by analysis of continuous tracheal pressure recordings in a 48 hour period preceeding fetal death in utero in 7 chronic pregnant monkey preparations (Macaca mulatta). All fetuses were judged normal by blood gas tensions, pH, and fetal heart rate within 48 hours of death. In the normal fetus breathing movements were periodic and a circadian distribution in the incidence of FBMs was observed. Four distinct patterns of FBMs were observed in the normal fetuses. In five fetuses death occurred in the intrapartum period; all five fetuses were breathing at the onset of labor. A progressive fall in the incidence of FBMs was observed in labor coincident with the development of fetal acidemia. In the remaining two fetuses death occurred before labor. Apnea and gasping were observed in all fetuses before death. The duration of apnea and gasping appeared dependent upon the nature of the lethal insult.

The short- and long-term effects of surgical procedures and chair restraint on total plasma cortisol were assessed in the chronic rhesus monkey preparation. Three nonpregnant and six pregnant animals were sampled daily, morning and evening. Fetal plasma specimens were obtained simultaneously from the pregnant animals. In the nonpregnant rhesus monkey, a circadian rhythm is present the day following venous catheterization and chair restraint, with individual values similar to those in trained, unanesthetized animals. In the pregnant animals, a postoperative rise in cortisol is followed by a gradual decline to a plateau and a return of circadian rhythm. No consistent daily fluctuations are seen in fetal cortisol, and although correlated with maternal cortisol, the exact relationship is uncertain. The data indicate that operation, as expected, is stressful but acclimation to the chair occurs.

The fetal heart rate (FHR) response to acute nonacidemic hypoxemia and to acute respiratory acidosis was studied in unanesthetized pregnant monkeys by means of chronically implanted catheters and electrodes. Average FHR and short- and long-term FHR variability were analyzed separately. The FHR response to either hypoxemia or hypercapnia consisted of slowing and increased variability. The slowing was more consistent with hypercapnia than with hypoxemia. Long-term FHR variability increased with both test stresses. The increase in short-term FHR variability was much greater in response to hypoxemia than to hypercapnia. Both the FHR slowing and the increases in variability in response to the test stresses were reduced by prior administration of atropine to the fetus.

The systolic time intervals of the fetal cardiac cycle were studied by means of simultaneous recordings of electrocardiogram (ECG) and ultrasound Doppler cardiogram (DCG) in chronic preparations of fetal rhesus monkeys. Recordings were made under physiologic conditions as well as during various experimental stresses. The pre-ejection period (PEP) showed no significant relationship with heart rate in the unstressed fetuses, but the acceleration of heart rate induced by epinephrine was accompanied by shortening of PEP. The PEP increased with advancing fetal age. The PEP was inversely correlated with left ventricular end-diastolic pressure and arterial pulse pressure, but showed a positive correlation with both systolic and diastolic arterial blood pressure. The PEP also exhibited strong negative correlation with arterial blood pH. The prolongation was essentially the same whether acidosis was of respiratory or metabolic origin. The PEP increased slightly but significantly during nonacidemic hypoxemia; however, there was no correlation between Pao 2 and PEP. Epinephrine shortened the PEP significantly, whereas the effect of atropine was inconsistent. Alteration of the plasma glucose level by injection of insulin or glucose did not affect PEP. These findings demonstrate that the PEP may be a useful indicator of fetal cardiac performance, reflecting both myocardial contractility and the hemodynamic state of the cardiovascular system.

Simultaneous recordings of the fetal electrocardiogram and ultrasound Doppler-cardiogram were used for the determination of the pre-ejection period (PEP) of the fetal cardiac cycles. All 50 fetuses selected for the present study experienced uneventful perinatal lives despite maternal antepartum complications which required hospitalization. A significant positive correlation between the PEP and gestational age of the fetuses was again demonstrated. The PEP of the fetus measured within one week prior to delivery was also found to be significantly correlated with the newborn body weights at birth. Statistical analysis demonstrates that fetal body weight was more closely related to the physiologic lengthening of the PEP.

The VET of the fetal cardiac cycle, measured as the interval between the semilunar valve opening and closing signals of the ultrasound Doppler cardiogram, was studied in chronically catheterized fetal rhesus monkeys. VET varied inversely with FHR between approximately 150 and 250 bpm. Below 150 bpm, however, there was no further prolongation of VET. VET was not related to gestational age. VET, corrected for heart rate, was shortened in the presence of combined hypoxemia and acidosis, but not when either hypoxemia or acidemia was present alone. Corrected VET was shortened by epinephrine, but was not consistently altered by atropine. VET was not affected by changes in the concentration of glucose in fetal blood.

Animal models have played an important role in fetal physiological and behavioural research, and will continue to do so. They can provide important insights into processes and mechanisms, which can then be compared with findings from the more limited observations possible on the human fetus and neonate. Since each species has its own properties, however, one must be cautious in generalizing from findings obtained in these animal models to human fetal physiology and behaviour.

The effect of surgical and experimental manipulations on intrauterine growth of the fetus was investigated in 61 rhesus monkey fetuses in which chronic preparations were attempted. The surgical procedure consisted of hysterotomy and insertion of vascular catheters and included unilateral ligation of the fetal carotid artery. The mother was kept in a restraining chair after the operation for the duration of the preparation (0 to 39 days). Thirty-four fetuses who died within 48 hours after operation served as the control group for the growth parameters. The remaining fetuses that survived 7 days or more after the operation were included in the experimental group. Body weight, crown-rump length, crown-heel length, and foot length of the fetus and placental weight were measured at the termination of the preparation. There were significant linear correlations between all parameters and gestational age. Comparison between the control and experimental groups revealed that none of the parameters from the experimental group differed significantly from those of the control group. No relationships were found between the duration of the preparation and any of the parameters. Total brain weights from 19 fetuses exhibited a significant increase with gestational age and these values were within the normal range reported previously. There were no significant differences in weight between right and left cerebral hemispheres. No evidence of unequal blood flow to the cerebral hemispheres was found with the radioactive microsphere technique. The data suggest that the surgery performed on both the mother and the fetus and prolonged maternal restraint did not alter intrauterine fetal development.

The pre-ejection period (PEP) of the cardiac cycle was studied in 65 antepartum fetuses by means of a noninvasive technique which used simultaneous recordings of abdominal fetal electrocardiogram (FECG) and ultrasound fetal Doppler cardiogram (FDCG). Although most of the fetuses were products of high-risk pregnancies, 45 fetuses had uneventful perinatal courses. The PEP's from these fetuses demonstrated a significant positive relationship with gestational age (p is less than 0.01). Uterine contractions induced for antepartum stress testing of the fetus were founnd to prolong the PEP by approximately 9.1 per cent in five cases (four fetuses). The average PEP of antepartum fetuses between 38 and 40 weeks was shorter than that of intrapartum fetuses by approximately 9.5 per cent. Comparison between clinical outcome and the PEP's of the fetuses who were born within a week after the last determination of PEP revealed a strong correlation between prolonged PEP duration and abnormalities in the perinatal course.

The effect of various catecholamines on fetal breathing movements (FBM) was studied in 10 established chronic fetal rhesus monkey preparations. Norepinephrine, epinephrine, isoproterenol (all 1:10 5 [w/v] in concentration), or saline was infused intravenously to the fetus, each on five separate occasions. The infusion of the catecholamines was started at 0.02 ml/min and increased in a stepwise fashion until the fetus exhibited cardiovascular responses. The infusion rate was then maintained for 30 minutes to observe FBM. The incidence of FBM was determined for each 5-minute period and also expressed as a percentage of preinfusion values. Statistical analysis revealed that the incidence of FBM was significantly increased by isoproterenol and decreased by norepinephrine. Epinephrine did not consistently alter the incidence of the FBM.

We questioned whether the prevailing fetal PaO2 conditions the distribution and organization of states and responses in the fetus and newborn. To investigate this we mechanically ventilated the fetal lungs in chronically instrumented fetal sheep. Electrodes (for ECoG, ECG, EDG and EMG of diaphragm - DP, posterior neck and biceps brachii muscles), catheters (carotid artery, jugular vein, trachea and amniotic cavity), and the endotracheal tube and ventilator tubes were placed at 122-127 days GA. Experiments were begun 3 to 5 days later. Thus far 12 ventilation experiments have been carried out in 5 fetal sheep 3 to 13 days after operation. At the onset of mechanical ventilation both the FHR and fetal blood pressure (BP) decreased abruptly. Ventilatory arrhythmia appeared and its amplitude varied inversely with frequency. During ventilation with either O2 or N2 the proportion of high voltage (HV) ECoG increased. Fetal movements decreased during mild hypoxaemia, continuous tonic neck EMG was not observed. End-inspiratory bursts of DP EMG activity were observed more often during LV at normal and elevated PaO2's and did not beccne continuous in either state and it varied with PaCO2. Switching abruptly to N2 after up to 4 h of hyperoxia did not result in stimulation of phasic DP EMG. At end of experiments PaO2 and PaCO2 returned rapidly to normal fetal levels and normal fetal state-cycling was resumed. Occlusion of the umbilical cord with a constant flew of O2 through the tubes resulted in the initiation of sustained, continuous breathing in only one of 4 such trials. Conclusions: 1. Mechanical ventilation appears to increase HV state. 2. Elevation of PaO2 does not result in ‘arousal’, continuous breathing, or tonic activity in the antigravity muscles. 3. Fetal response to hypoxemia is not modified and 4. umbilical circulation remained open.

We used mechanical ventilation of the fetal lung in utero to alter fetal bleed gases and thus separate the influences of PO2 and PCO2 on the onset of extrauterine breathing. Acute experiments: 7 pregnant sheep were operated under spinal anesthesia at 140-145 days' GA. An endotracheal tube, connecting tubes to the ventilator and a carotid artery catheter were placed in the fetus under local anesthesia, and the uterus was closed. Mechanical ventilation was started using O2, N2 and CO2 to achieve the desired bleed gas pattern. After 2 h the uterus was reopened, the fetus delivered, the umbilical cord clamped and the fetus placed either in a 40°C saline bath or on a cold table. Mechanical ventilation was stopped 2 min after delivery and the time to onset of breathing was observed. Chronic: Fetal electrodes, vascular catheters, endotracheal and ventilator tubes and an inflatable occluder on the umbilical cord were placed in 2 pregnant sheep at 127 days' GA. The fetuses were ventilated in utero 5 or irore days later with O2 or N2 ± CO2. The ventilator was stopped, the cord occluded, and the time to onset of breathing (diaphragm EMG) recorded: Results are given in the table. Conclusions: 1. Cold and hypercapnia are important stimuli for the onset of neonatal respiration. 2. Hypoxia depresses breathing at this time. 3. Cord clamping without change in bleed gases does not result in breathing.