Fetal Breathing Movements Research Articles

Prostaglandin E2 inhibits fetal breathing movements during prolonged reductions in uterine blood flow in sheep

Prostaglandin E2 inhibits fetal breathing movements during prolonged reductions in uterine blood flow in sheep

Cardiovascular and respiratory actions of U50,488H in the unanaesthetized ovine foetus

In an effort to evaluate the feasibility of κ-opioid receptor agonists for use in pregnancy, we have investigated the actions of U50,488H ( trans-3,4-dichloro- N-methyl- N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide) on cardiovascular and respiratory control in the unanaesthetized ovine foetus. Intravenous administration of U50,488H (1.0 mg/kg) to the foetus resulted in an immediate increase in foetal blood pressure ( P < 0.0001) and heart rate ( P < 0.0001) which lasted 15 min, followed by a prolonged loss of heart rate variability for up to 3 h. There was also a significant suppression of foetal breathing movements for 2–3 h ( P < 0.008). Pretreatment with naloxone (12 mg/h) completely blocked the hypertensive and tachycardiac response to U50,488H, but was unable to prevent the loss of variation in heart rate or respiratory depression. These data suggest that U50,488H can exert direct cardiovascular and respiratory actions in the ovine foetus via both opioid and non-opioid mechanisms. The naloxone-insensitive suppression of foetal breathing would severely limit the use of U50,488H as an obstetrical analgesic.

Fetal breathing is not inhibited by ethanol exposure during prolonged reduced uterine blood flow

When prolonged hypoxemia is induced in fetal sheep by reducing uterine blood flow, fetal breathing movements (FBM) return to normal incidence after their initial decrease. Ethanol also inhibits FBM. These experiments were designed to determine the role of fetal oxygenation status in affecting ethanol-induced inhibition of FBM. A 1-h maternal infusion of 1 g ethanol/kg maternal body weight was given to animals following 20 h of reduced uterine blood flow (RUBF; n = 9), as well as to normoxemic (n = 9) fetal sheep, and the effect on FBM, electrocortical activity (ECoG), and electroocular activity (EOG) was determined. In normoxemic fetuses, the incidence of FBM decreased from 26.1 +/- 5.5% to 2.8 +/- 1.6% (p < 0.05) with ethanol, subsequently returning to baseline values over 6 h, but there was no effect of ethanol on FBM incidence in RUBF fetuses (32.8 +/- 9.1%). Ethanol increased the incidence of intermediate ECoG from 16.6 +/- 2.9% to 49.0 +/- 9.8% (p < 0.01) in normoxemic fetuses, but there was no change in RUBF fetuses. We conclude that the adaptive mechanism(s) invoked by fetal sheep during prolonged RUBF abolishes its ability to respond behaviourally to ethanol.

Automated fetal breathing movement detection from internal small displacement measurement.

We have previously proposed a method to measure small displacements of internal tissue which is based on an ultrasonic pulsed Doppler technique. The Doppler frequency shift of the ultrasonic waves due to the tissue movement is detected using a modified quadrature detector, and the displacement of the internal tissue is estimated by using an arctangent method. Based on the algorithm, we have constructed a quantitative monitoring system for fetal breathing movement. The fetal breathing movement is a rhythmic movement of the fetal diaphragm and it is recorded as a nearly sinusoidal displacement with a repetition frequency from 0.5 Hz to 2 Hz. In this paper, an automated fetal breathing movement detection algorithm for the displacement data observed by using the small displacement measurement system is proposed. This method uses a modified autocorrelation technique for detecting the displacement due to the fetal breathing movement. The method is applied to five fetuses of late pregnancy and the result is compared with the manual detection.

Changes in thoracic dimensions induced by breathing movements in fetal sheep.

The dimensions of the three major axes of the thorax (longitudinal, transverse and antero-posterior) were monitored in utero from the ultrasonic transit-time between pairs of piezo-electric transducers chronically implanted at opposite sides of the thorax in five fetal sheep at 119-122 days of gestation; tracheal and vascular catheters and diaphragmatic EMG electrodes were also implanted. To measure thoracic length, ultrasound transducers were implanted on the diaphragm and over the upper sternum and manubrium sterni. A pair was implanted on opposite sides of the chest to measure thoracic width, and another pair was implanted over the lower thoracic spine and lower sternum (antero-posterior dimension). The width of the thorax either decreased (mean 0.6 +/- 0.2 mm) or increased (mean 0.7 +/- 0.1 mm) during fetal breathing movements (FBM). The depth of the thorax (antero-posterior dimension) usually decreased (mean 0.9 +/- 0.1 mm) during FBM. The distance between the upper sternum and the diaphragm decreased by 1.0 +/- 0.1 mm (left side) and 1.6 +/- 0.3 mm (right side) during inspiratory efforts. The distance between the upper thorax and a fixed point on the lower thoracic spine decreased by a similar amount. Overall, fetal thoracic dimensions changed by 1-3%. The largest changes measured, and the most surprising, were reductions, rather than increases, in the separation between the dome of the diaphragm and the upper thorax; this suggests that, during inspiratory efforts, the upper thorax moves caudally by a greater distance than the diaphragm. FBM induce complex and variable changes in thoracic dimensions; these are likely to induce small alterations in the shape of the lungs that may act as a stimulus to lung growth.

Rebound increase in fetal breathing movements after 24-h prostaglandin E2 infusion in fetal sheep.

We investigated the hypothesis that the precipitous decrease in prostaglandin E2 (PGE2), a potent inhibitor of fetal breathing, from high plasma concentrations during labor causes a rebound stimulation of breathing without newborn concentrations falling below prelabor fetal values. Fetal plasma PGE2 concentration was gradually increased from 384 +/- 82 (SE) pg/ml in 2-h steps [0 (baseline), 1.5, 3, and 6 micrograms/min] to labor levels (1,230 +/- 381 pg/ml at 6 micrograms/min) and then was maintained for 24 h (n = 9). PGE2 at 1.5 micrograms/min significantly decreased breathing incidence [from 42 +/- 4 (baseline) to 14 +/- 4%] and breath amplitude (from 2.1 +/- 0.5 to 1.5 +/- 0.2 arbitrary units) and increased breath-to-breath interval (from 1.16 +/- 0.07 to 1.56 +/- 0.06 s). No further dose-related changes were observed. During the first 2 h after PGE2 infusion was stopped, PGE2 concentration returned to basal (352 +/- 64 pg/ml) but breathing incidence and amplitude were significantly higher (74 +/- 8% and 2.4 +/- 0.3 arbitrary units, respectively) and breath-to-breath interval was significantly lower (0.95 +/- 0.10 s) than were basal levels. Changes arose within approximately 15 min and were maintained for at least 4 h. Breathing did not change significantly in the saline-treated group (n = 7). Results suggest that the rapid decrease in plasma PGE2 concentration at birth promotes the onset of breathing.

Dynamic sensitivity of carotid chemoreceptors to CO2 in the newborn lamb.

In previous studies we examined the development of the response of carotid and aortic chemoreceptors to hypoxia in the lamb and kitten (Blanco et al, 1984; Hanson et al, 1989; Kumar & Hanson, 1989). Recently we have been examining the question of whether the response of the arterial chemoreceptors to CO2 also develops post-natally. The issue is important because, whilst elevation in arterial PCO2 (PaCO2) stimulates fetal chemoreceptors and fetal breathing movements, the effect of rapid changes in PaCO2 on chemoreceptors in the neonate is largely unknown. Because CO2 production is linked to metabolism, it provides an important component of the drive to breathe in the neonate, especially at an age when the response to hypoxia is poor. This might be an important consideration in apnoea and respiratory failure in the neonate. Environmental temperature will, of course, affect metabolism and overheating has been proposed to play a role in the aetiology of certain types of respiratory failure, including sudden infant death syndrome. In previous studies (Watanabe et al, 1993) we found that environmental temperatures affected the gain of respiratory chemoreflex responses to changes in PaO2 and PaCO2. However, without direct information on chemoreceptor responses to CO2, the mechanisms underlying such effects cannot be determined. For this reason we embarked on a study of the maturation of carotid chemoreceptor responses to CO2 in the lamb. Preliminary data on the maturation of steady state and dynamic responses to CO2 has already been published (Calder et al, 1995). In this report we concentrate on the adaptive nature of the chemoreceptor response to CO2.

The effect of mechanical strain on fetal rat lung cell proliferation: comparison of two- and three-dimensional culture systems.

Normal growth of the fetal lung is dependent on fetal breathing movements. We have previously reported that an intermittent strain, which simulates normal fetal breathing movements, stimulates DNA synthesis and cell division of mixed fetal rat lung cells maintained in organotypic culture. To examine which cell type is responding to mechanical strain and to investigate whether the effects of strain on cell proliferation and mechanotransduction are affected by tissue architecture, we isolated fetal lung cells and subjected them to intermittent strain either as two-dimensional monolayer cultures or as three-dimensional organotypic cultures. Strain enhanced DNA synthesis of mixed cells, epithelial cells, and fibroblasts when cultured in a three-dimensional configuration. In contrast, no stimulatory effect on cell proliferation was observed when cells were strained as monolayer cultures. Intracellular signals, induced by strain, and cell morphology also varied depending on the culture conditions. These results suggest that mechanical strain stimulates the proliferation of both epithelial cells and fibroblasts and that the response of fetal lung cells to mechanical strain in vitro depends on cellular architecture.

Effect of prolonged catecholamine infusion on heart rate, blood pressure, breathing, and growth in fetal sheep.

Norepinephrine and epinephrine were infused into fetal sheep for 24 h to compare the effects on fetal heart rate, blood pressure, breathing movements, and tissue growth with those of prolonged reductions in uterine blood flow. Norepinephrine concentrations increased (p < 0.01) from 871 +/- 71 to 6831 +/- 1090 pg/mL (2 h) with norepinephrine infusion, and epinephrine concentrations increased from 310 +/- 95 to 1424 +/- 288 pg/mL (2 h) with epinephrine infusion. Fetal pH decreased (p < 0.01) from 7.37 +/- 0.01 to 7.29 +/- 0.02 at 0.5 h of the norepinephrine infusion and returned to control values by 2 h, whereas fetal lactate concentrations increased (p < 0.05) from 1.6 +/- 0.2 to 4.6 +/- 1.0 mmol/L at 2 h and remained elevated for 12 h. Lactate concentrations also increased with epinephrine infusion. Fetal heart rate increased (p < 0.05) from 176 +/- 5 to 246 +/- 6 and 220 +/- 6 beats/min in the 1st h of norepinephrine and epinephrine infusions, respectively, with a subsequent decline. Fetal blood pressure increased (p < 0.05) from 43 +/- 3 and 40 +/- 2 to 53 +/- 3 and 47 +/- 2 mmHg (1 mmHg = 133.3 Pa) during the 1st h of norepinephrine and epinephrine infusions, respectively, remaining elevated for 24 h. Fetal body weights were not different between the groups of animals, although liver/body weight ratio was less (p < 0.05) in epinephrine-infused fetuses (0.030 +/- 0.001) compared with vehicle-infused animals (0.036 +/- 0.002). There was no change in DNA synthesis rate in any of the fetal organs, despite changes in organ-specific DNA and protein content. Our results indicate that the changes in fetal cardiovascular and behavioural function, as well as tissue growth, that occur with prolonged reductions in uterine blood flow are not mediated solely by elevated circulating catecholamine concentrations.

Fetal breathing movements in late diabetic pregnancy: relationship to fetal heart rate patterns and Braxton Hicks' contractions.

In type-1 diabetic pregnancy, the occurrence of fetal breathing movements (FBM) was studied in relation to the fetal heart rate patterns (HRPs) A and B and to Braxton Hicks' contractions. Simultaneous 2-h recordings of fetal heart rate and body, eye and breathing movements were available for analysis (n = 44). These recordings were made in 20 fetuses of diabetic women at 32-38 weeks of gestation. Uterine activity was monitored at 36 and 38 weeks. For all recordings combined, the median incidences of FBM during HRPs A and B were 23% and 41%, respectively (NS). At low overall breathing activity (< 50% of total observation time), FBM were more numerous during HRP B than during HRP A in 83% of the recordings. However, if the overall breathing activity exceeded 50% of time FBM were preferentially made during HRP A in 93% of the recordings. This relationship was most pronounced at 38 weeks. These results corroborate our previous findings in the healthy near-term fetus. They show even more clearly that the state-dependent occurrence of FBM depends on the fetus' drive to breathe. During the recordings, breathing activity remained unchanged at all gestational ages studied, in contrast to the gradual decline in FBM seen in normal pregnancy. Braxton Hicks's contractions had no effect on FBM, which differs from the specific distribution of FBM during uterine contractions as previously found in uncomplicated pregnancies. We conclude that FBM in late diabetic pregnancy are not influenced by Braxton Hicks' contractions and that they do not show a clear-cut state-dependency. The (neural) mechanism underlying FBM differs from that in normal pregnancy.

Assessment of fetal breathing movements using three different ultrasound modalities.

Twenty-five consecutive women in the third trimester of pregnancy were studied to determine the presence or absence of fetal breathing movements using three different ultrasound imaging techniques. Using real-time B-mode observation of the fetal trunk as the standard, image-directed pulsed wave Doppler insonation of the umbilical vein confirmed the presence of breathing movements with a sensitivity of 100% and the absence of breathing movements with a specificity of 100%. The sensitivity and specificity of color Doppler imaging of the fetal naso- and oropharynx for the presence or absence of fetal breathing movements were 96% and 100%, respectively. In the current study, the detection of fetal breathing movements by three different ultrasound modalities was virtually interchangeable.

Investigating the relationship between fetus EEG, respiratory, and blood pressure signals during maturation using wavelet transform.

In this study, we introduce the fast wavelet transform as a method for characterizing maturational changes in electrocortical activity, respiratory activity, and blood pressure in fetal lambs in early (110-122 days), mid (123-135 days), and late (136-144 days) third trimester (term 145 days). Each recording was 2 hr in duration. Wavelet decomposition was performed for six sets of parameters D2j where 1 < or = j < or = 6. The six series wavelet transforms represent the following signal frequency bands: 1. 16-32 Hz; 2. 8-16 Hz; 3. 4-8 Hz; 4. 2-4 Hz; 5. 1-2 Hz; 6. 0.5-1 Hz. In the early group, power in the electrocephalogram (EEG) was highest in the fourth wavelet band, with relatively low power in the other bands. Increase in gestational age was characterized by increased power in all four wavelet bands. Power in the first wavelet band was significantly increased during low-voltage fast activity (LVFA) in the late group. The respiratory and blood pressure signals showed common frequency components with respect to time and were coincident with the LVFA EEG signal. Respiratory activity was only observed during some of the LVFA periods and was completely absent during high-voltage slow activity (HVSA) EEG. The respiratory signal showed dominant power in the fourth wavelet band, and less power in the third and fifth band. The blood pressure signal was also characterized by dominant power in the fourth wavelet band. This power was significantly increased during periods of respiratory activity. These results suggest a strong relationship between fetal EEG, blood pressure, and breathing movements.

Antisense oligonucleotides for PDGF-B and its receptor inhibit mechanical strain-induced fetal lung cell growth.

An intermittent mechanical strain regimen, which simulates fetal breathing movements, has been shown to enhance DNA synthesis and cell division of fetal rat lung cells. The signaling mechanism through which the physical stimulus is transduced is unknown. Herein, we report that mechanical strain (5% elongation, 60 cycles/min) of fetal lung cells, cultured in a three-dimensional environment provided by Gelfoam sponges, increased the mRNA levels of platelet-derived growth factor B (PDGF-B) and beta-receptor (PDGF-beta-R) within 5 min of the onset of strain. Both PDGF-BB and PDGF-beta-R proteins were increased after a 24-h intermittent strain (15 min/h). Phosphorothioate antisense PDGF-B oligonucleotides (ON) at 15 microM abolished the strain-enhanced DNA synthesis and cell growth. Scrambled PDGF-B ON had no such effect. A neutralizing PDGF-BB antibody (10 micrograms/ml) also attenuated strain-induced DNA synthesis. Furthermore, the strain-induced stimulatory effect on DNA synthesis of fetal lung cells was blocked by tyrphostin 9 (1 microM), a PDGF receptor-associated tyrosine kinase inhibitor, but not by its inactive structural analogue tyrphostin 1. Antisense but not sense PDGF-beta-R ON (10 microM) also abrogated the strain-enhanced DNA synthesis. These results suggest that physical forces such as fetal breathing movements regulate fetal lung cell growth by controlling PDGF-B and PDGF-beta-R gene expression.

A randomised controlled trial of simple compared with complex antenatal fetal monitoring after 42 weeks of gestation

To compare the impact on perinatal outcome of two different protocols for antenatal fetal monitoring after 42 weeks gestation. A prospective randomised controlled trial. Liverpool Maternity Hospital. One hundred and forty-five women with singleton, uncomplicated pregnancies after 42 weeks of gestation. Random allocation to fetal monitoring by either: 1. a modified biophysical profile comprising of computerised cardiotocography, amniotic fluid index, and assessment of fetal breathing, tone and gross body movements; or 2. standard cardiotocography and maximum pool depth. Cord pH at delivery, number of abnormal monitoring tests, intrapartum management, mode of delivery and neonatal outcome. There were significantly more abnormal antenatal monitoring results in the modified biophysical profile group (47.2% vs 20.5%; odds ratio = 3.5, 99% CI = 1.3-9.1). There were no differences in cord blood gases, neonatal outcome, or in outcomes related to labour and delivery between the two groups, but a trend towards more obstetric interventions in the modified biophysical profile group was noted. Amniotic fluid volume after 42 weeks was more likely to be labelled as abnormal with amniotic fluid index than with maximum pool depth (44.4% vs 15.1%; odds ratio = 4.5, 99% CI = 1.6-12.8). The results suggest that after 42 weeks fetal monitoring with the modified biophysical profile does not improve pregnancy outcome as measured by umbilical cord pH, but is more likely to yield an abnormal result. The higher incidence of abnormal monitoring results in the modified biophysical profile group was likely to be caused by different methods of amniotic fluid assessment in the modified biophysical profile group (amniotic fluid index) and simple monitoring group (maximum pool depth). The use of amniotic fluid index as a test of fetal wellbeing in prolonged pregnancy may lead to more obstetric interventions with, as yet, unclear impact on the perinatal outcome.

Alpha 1‐ and alpha 2‐adrenoreceptor actions of phentolamine and prazosin on breathing movements in fetal sheep in utero.

1. We studied the effects of systemic administration of the alpha 1- and alpha 2-adrenoreceptor antagonist phentolamine and the selective alpha 1-adrenoreceptor antagonist prazosin on fetal breathing movements (FBM) and electrocortical activity (ECoG) in fetal sheep. In one group of fetuses (group I; n = 7) the effects of phentolamine were measured during normoxia and hypoxia. In the second group of fetuses (group II; n = 8) the effects of either phentolamine, or combined phentolamine and prazosin, or prazosin alone, were measured during normoxia. 2. In group I fetuses, the incidence of FBM increased after phentolamine treatment. An increase in the incidence and mean episode duration of low-voltage ECoG (LV-ECoG) was also measured after phentolamine treatment. These effects of phentolamine persisted during hypoxia. 3. In group II fetuses a pronounced decrease in the incidence of FBM occurred after administration of prazosin following either phentolamine or saline pretreatment. These effects of prazosin on FBM were independent of an effect on ECoG activity. 4. We conclude that catecholamines have a stimulatory role on FBM mediated via an alpha 1-adrenoreceptor mechanism. Phentolamine leads to an increase in FBM by preferentially antagonizing presynaptic alpha 2-adrenoreceptors over postsynaptic alpha 1-adrenoreceptors. This influence of phentolamine on FBM may be secondary to its effect on ECoG. Promotion of LV-ECoG by catecholamines is mediated via an alpha 1-independent mechanism.

Preterm prelabor amniorrhexis: Outcome of live births

To investigate the risk of postnatal death in pregnancies with preterm prelabor amniorrhexis in relation to gestational age at both amniorrhexis and delivery. In 172 singleton pregnancies with preterm prelabor amniorrhexis resulting in live births, postnatal survival and cause of death were examined in relation to gestational age at both amniorrhexis and delivery. In 108 of the patients, the amniotic fluid index (AFI) and fetal breathing movements were determined, and in 98, the internal thoracic circumference and cardiothoracic ratio were also measured. The value of these indices in the prediction of pulmonary hypoplasia was examined. There were 30 (17%) deaths, 18 of which were due to pulmonary hypoplasia and 12 to prematurity-related complications. Survival was related to both gestational age at amniorrhexis (50% for amniorrhexis before 20 weeks' gestation and 98% when amniorrhexis occurred after 25 weeks) and gestational age at delivery (57% for those born at 24-28 weeks' gestation and 96% for those born after 32 weeks). Pulmonary hypoplasia was also related to both gestational age at amniorrhexis (causing 92% of deaths in the group with amniorrhexis at less than 20 weeks' gestation but none of those with amniorrhexis after 23 weeks) and gestational age at delivery (causing 50% of deaths in the group delivered at 24-28 weeks' gestation and 87% of deaths in infants delivered after 28 weeks). Fetal breathing movements were present in 33 and 63% of cases with and without pulmonary hypoplasia, respectively. The corresponding values for internal thoracic circumference below the 2.5 percentile were 33 and 9%, respectively. There were no significant differences in the AFI or cardiothoracic ratio between the cases with and without pulmonary hypoplasia. Multivariate analysis demonstrated that the only characteristic that contributed significantly in distinguishing between cases with and without pulmonary hypoplasia was gestational age at amniorrhexis. In pregnancies with preterm prelabor amniorrhexis, postnatal survival is related to both gestational age at amniorrhexis and gestational age at delivery. Prediction of pulmonary hypoplasia is primarily dependent on gestational age at amniorrhexis.

The Biophysical Profile as a Tool for Prediction of Preterm Delivery

Our objective was to determine if any of the following parameters is a predictor of preterm delivery: gestational age, cervical dilatation, or biophysical profile score. Sixty-two women with certain dates, intact membranes, and preterm contractions more frequent than 300 min underwent a 30-min ultrasonographic assessment of fetal breathing movements, fetal tone, fetal movement and amniotic fluid volume, each of which was scored as 0, 1, or 2 before any tocolytics were given. The total score (0–8) was calculated and cervical dilatation was recorded. All women were subsequently placed on tocolytics. Data were analyzed using survival analysis with stepwise regression of the covariates to determine the predictive values of the total score, its individual parameters, gestational age, and cervical dilatation to the outcome variable of hours to delivery. Gestational age, cervical dilatation and time interval to delivery were categorized and entered into a logistic regression model with the total score and its components to determine predictive odds. Total score (p < 0.0001) and cervical dilatation (p < 0.0001) were the most significant variables associated with time interval to delivery, followed by gestational age (p = 0.035). When the individual biophysical parameters were entered into the model, fetal tone (p < 0.0001), cervical dilatation (p < 0.0001) and gestational age (p < 0.014) were the only variables related to time interval to delivery. Predictive odds of delivery in less than 48 h in relation to fetal tone and cervical dilatation were calculated. Total score, fetal tone, and cervical dilatation were strongly associated with time interval to delivery. Our study did not support fetal breathing movements as a predictor of preterm delivery. Copyright © 1994 International Society of Ultrasound in Obstetrics and Gynecology

Umbilical Venous Doppler Waveform without Fetal Breathing: Its Significance

Umbilical venous waveforms by Doppler ultrasound are seen normally during fetal breathing movements. Each waveform extends two to four fetal cardiac cycles. During Doppler study of gross intrauterine growth retardation (IUGR) and twin to twin transfusion cases, single or double peaked umbilical venous waveforms were detected with each fetal cardiac cycle. Umbilical arterial Doppler study detected minimal, absent, or reverse diastolic flow. In these fetuses, the ratio of right and left ventricular diameters at the atrioventricular valve level was increased, and pulse-wave and color Doppler study showed tricuspid regurgitation. This tricuspid regurgitation caused reverse flow in the umbilical vein from the right atrium and inferior vena cava and produced characteristic venous waveforms. These umbilical waveforms were associated with gross IUGR or cardiac failure of the fetuses with perinatal morbidity and mortality.

Prostaglandin E2 decreases fetal breathing movements, but not pulmonary blood flow, in fetal sheep.

Fetal breathing movements are vital for normal fetal lung growth. Inhibition of these fetal breathing movements is associated with pulmonary hypoplasia. Pulmonary hypoplasia also occurs subsequent to alterations in other factors, such as a significant decrease in pulmonary blood flow. The prostaglandin system is known to have profound effects on both fetal breathing movements and on the pulmonary vascular system. We studied six late-gestation chronically instrumented fetal sheep by using an electromagnetic flow transducer around the left pulmonary artery to determine whether a decrease in fetal breathing movements, subsequent to a continuous infusion of prostaglandin E2 (PGE2), is associated with a decrease in pulmonary blood flow. A continuous PGE2 infusion of 0.88 +/- 0.11 microgram.kg-1.min-1 over 120 min led to a significant decrease in fetal breathing movements (control 40.5 +/- 3.6%, infusion 3.3 +/- 1.6%; P < 0.001). In contrast, the PGE2 infusion had no effect on mean left pulmonary artery blood flow (control 27.7 +/- 9.3 ml.min-1.kg-1, infusion 23.8 +/- 7.0 ml.min-1.kg-1. The PGE2 infusion demonstrated central effects in the percentage of time the fetus was in high-voltage electrocortical activity (control 41.9 +/- 2.5%, infusion 56.5 +/- 5.4%; P < 0.05) and in the amount of time spent in low-voltage electrocortical activity without fetal breathing movements (control 17.5 +/- 2.7%, infusion 40.2 +/- 4.8%; P < 0.05). A significant decrease in the fetal heart rate during the infusion was seen with no effect on either the systemic or pulmonary blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal lung liquid: a major determinant of the growth and functional development of the fetal lung.

1. During fetal life the lung develops as a liquid-filled organ. This liquid is produced by the fetal lung and leaves via the trachea from where it is either swallowed or enters the amniotic sac. Fetal lung liquid plays a crucial role in the growth and development of the lungs by maintaining them in a distended state. It is now recognized that the retention of liquid within the future airways is required to maintain the lungs at an appropriate level of expansion in order to stimulate their growth. Indeed, it is likely that most, if not all, of the conditions and malformations that lead to inadequate growth of the fetal lung do so by reducing the volume of lung liquid and hence the degree of lung expansion. 2. The volume of fetal lung liquid is principally regulated by the resistance to lung liquid efflux through the fetal upper airway and by the presence of diaphragmatic activity associated with fetal breathing movements (FBM). During non-breathing periods, the relatively high resistance offered by the upper airway to the efflux of lung liquid opposes the loss of liquid from the lung, thereby maintaining fetal lung expansion. During episodes of FBM, when the larynx is actively dilated and the resistance to lung liquid efflux is reduced, lung liquid leaves the lungs at an increased rate. However, selective inhibition of diaphragmatic muscle activity in the foetus leads to a reduction in lung liquid volume, rather than an increase. This finding indicates that during periods of FBM, rhythmical contractions of the diaphragm retard the loss of lung liquid and help to maintain lung expansion when the upper airway resistance is reduced. It is now apparent that the maintenance of lung expansion by FBM is the basis for their role in promoting fetal lung growth. 3. Successful transition from intra-uterine to extra-uterine life is dependent upon the clearance of liquid from the fetal lungs at the time of birth so that the lungs may effectively function as an organ of gas exchange.(ABSTRACT TRUNCATED AT 400 WORDS)