Cigarette smoking and fetal breathing movements.

Cigarette smoking caused a reduction in the incidence of fetal breathing movements in normal and abnormal pregnancies. The size of the reduction varied, being greatest in small-for-dates pregnancies and pregnancies complicated by fetal distress in labour and least in pre-eclamptic pregnancies. The fall in the amount of fetal breathing movements was significantly related to the rise in maternal plasma nicotine after smoking but was unrelated to the rise in barboxyhaemoglobin. Smoking non-nicotine (herbal) cigarettes produced increases in carboxyhaemoglobin concentrations similar to those observed after smoking tobacco cigarettes, and was not associated with a fall in the incidence of fetal breathing movements. Chewing gum containing nicotine produced rises in plasma nicotine concentration similar to those observed after smoking tobacco cigarettes and was associated with a significant reduction in the incidence of fetal breathing movements. Hence nicotine appeared to be the factor in cigarette smoke responsible for the reduction in the incidence of fetal breathing movements. Nicotine was present in the cord blood of infants whose mothers smoked. The possible mechanism by which nicotine caused a reduction in the incidence of fetal breathing movements and its possible relevance to the detrimental effects of smoking on the fetus are considered.     

Maternal smoking and fetal breathing movements

Pregnant, habitually smoking women were studied during the last trimester when smoking a standard cigarette, smoking a nontobacco cigarette, or chewing a piece of chewing gum containing 2 or 4 mg. of nicotine. The effects of the experimental interventions were followed on the concentration of nicotine and the percentage of car?yhemoglobin (COHb) in maternal blood, on the amount and pattern of the fetal breathing movements, and on the maternal heart rate, breathing rate, and blood glucose level. The maternal blood concentration of nicotine was increased by the standard cigarette, the 4 mg. nicotine chewing gum, and the 2 mg. nicotine chewing gum in descending order. The COHb percentage in maternal blood was increased by the standard cigarette and to a lower degree by the nontobacco cigarette. A significant increase of apnea and periodic breathing movements in the fetus followed the smoking of a standard cigarette; a similar but nonsignificant change occurred in a dose-related way after the 4 mg. and the 2 mg. chewing gum. The maternal heart rate was positively correlated to the level of blood nicotine. Nicotine appears to be partly responsible for the transient reduction of the fetal breathing movements occurring after smoking one standard cigarette. The suppression of the fetal breathing movements in utero poses the question whether iterated maternal smoking might influence the prenatal assessment of fetal maturity using determination of pulmonary surfactants in the amniotic fluid.     

Maternal glucose injections do not alter the suppression of fetal breathing following maternal ethanol ingestion

In order to determine whether intravenous injections of glucose could reserve the effects of maternal ingestion of ethanol (0.25 gm/kg), glucose (25 gm intravenously) or an equal volume of saline solution was administered to eight pregnant women at 37 to 40 weeks' gestation after ingestion of ethanol. Fetal breathing movements were abolished within 30 minutes after ingestion of ethanol and were not increased by maternal intravenous injections of glucose. Maternal heart rate was increased by ethanol. The disposition of ethanol in maternal blood was not altered by injection of glucose, and fetal gross body movements were not influenced by maternal ingestion of ethanol or by injections of glucose after ethanol.     

Oxygen consumption in fetal lambs after maternal administration of sodium pentobarbital

To determine whether anesthesia lowers fetal oxygen consumption, sodium pentobarbital (10 mg/kg) was given intravenously to seven chronically instrumented pregnant ewes (123 to 144 days' gestation). Oxygen consumption fell by 23% in association with a rise in fetal vascular PO2. Fetal breathing movements were abolished for 50.5 minutes, while the number of fetal heart rate accelerations fell by 80% in the first 30 minutes after pentobarbital injection. It is concluded that anesthesia reduces fetal oxygen consumption, probably by abolishing skeletal muscle activity, and perhaps also by reducing cerebral metabolic rate.     

Effect of maternal cocaine administration on maternal and fetal glucose, lactate, and insulin in sheep

Although cocaine use during pregnancy is an important cause of perinatal morbidity and mortality, there are no reports of its effect on maternal and fetal carbohydrate metabolism. Six pregnant ewes and their fetuses were instrumented under halothane general anesthesia at 113-119 days' gestation. Between 124-135 days' gestation, the ewes received a single infusion of vehicle or cocaine (1.0 or 2.0 mg/kg) into the jugular vein. At least 24 hours was allowed between successive injections. Maternal and fetal blood samples were drawn at 30 and 20 minutes before and at 5, 15, 30, and 60 minutes after the injection. Both maternal and fetal glucose and lactate concentrations increased (P less than .05) after injection of cocaine at 2.0 mg/kg. There were no significant changes in maternal or fetal plasma insulin concentrations after vehicle or cocaine administration. Induction of hyperglycemia and lactacidemia could be mechanisms whereby cocaine exerts its adverse effects during pregnancy.     

Effects of acute hypoxemia on fetal movement in the fetal lamb

Chronically instrumented pregnant models were established using 5 Dorset-Rambouillet pregnant ewes with gestational age between 120 and 138 days. Observation of fetal movements were started on the 3rd postoperative day or later when recovery from the surgery to the physiological condition was confirmed by maternal and fetal biophysical parameters. Fetal movements were observed using real-time ultrasound equipment with linear-array transducer placed on the maternal abdomen. Observation encompassed the control period which lasted one hour followed by an experimental period of fetal hypoxemia created by decreasing maternal FIO2. Observation was also continued during the recovery period when the mother was re-exposed to room air. Maternal and fetal samples were periodically obtained during these periods. Frequency of fetal movements was studied in 10 minute periods under the control and hypoxemic conditions. All fetuses exhibited movements during the control period, ranging 1-42 movements/10 minutes, the mean incidence being 16.9 movements/10 minutes. During fetal hypoxemia (average PaO2 decrease: 8.6 mmHg), fetal movements were significantly reduced to 5.5 movements/10 minutes with complete cessation in some cases. In 4 animals which exhibited complete cessation of both fetal movement (FM) and fetal breathing movement (FBM), FBM disappeared before FM, and reappearance of FM was following by FBM during recovery from hypoxemia.     

Effects of multiple-dose maternal ethanol infusion on fetal cardiovascular and brain activity in lambs

Ethanol (2 gm/kg of maternal body weight administered in four equal doses of 0.5 gm/kg over 5 hours) was infused intravenously into nine chronically prepared pregnant ewes between 124 and 137 days' gestation. The data demonstrated a dose-response relationship between fetal arterial ethanol concentrations and the incidence of fetal breathing movements. Suppression of normal fetal electrocortical activity occurred at a low ethanol concentration and returned to control values at a time of very high arterial ethanol concentrations. This experimental model of a binge drinking episode further supports the hypothesis that ethanol suppresses fetal breathing movements by a direct central mechanism rather than indirectly by alteration of electrocortical activity.     

The effects of maternal hyperoxia on fetal breathing movements in third-trimester pregnancies

Fetal breathing movements and gross fetal body movements were observed before, during, and after maternal hyperoxia induced by inhalation of 50% oxygen in 14 women with normal term pregnancies. Studies were performed with real-time B-scan linear-array ultrasound and were standardized for time of day, maternal nutritional status, postprandial interval, and length of observation. Each study included a 30-minute baseline, followed by 15 minutes of hyperoxia, and 45 minutes of continued monitoring. No significant changes occurred in the mean incidences of fetal breathing movements, gross fetal body movements, the mean breathing rate, or breath interval variability, as analyzed in 5-minute epochs. Maternal PO2, as measured by transcutaneous electrodes, increased to the maximum level after 5 minutes of hyperoxia (155% over control levels). The breathing activity of normal third-trimester fetuses appears to be stimulated maximally in the second and third postprandial hours and cannot be further increased by maternal hyperoxia. This protocol represents a possible clinical strategy for investigating fetuses at risk for intrauterine hypoxia, provided that similar experimental conditions are maintained.     

Placental transfer of the thromboxane synthetase inhibitor ridogrel in the late-pregnant ewe.

OBJECTIVES: To assess the occurrence of placental transfer of the thromboxane synthetase inhibitor ridogrel in the pregnant ewe and to determine its effect on prostanoid levels in the ewe and fetal lamb, on uterine contractility and on maternal and fetal hemodynamics. STUDY DESIGN: Five chronically instrumented pregnant ewes at 122 days of gestation received intravenous infusions of 5 mg/kg/3 h ridogrel and solvent. Maternal and fetal arterial samples were obtained at predetermined intervals to determine concentrations of ridogrel and prostaglandin metabolites TXB2, 6-keto-PGF1alpha, PGF2alpha, and PGE2. Maternal and fetal responses of blood flow and pressures were determined. RESULTS: Fetal ridogrel levels were 25% of maternal concentrations. Ridogrel showed rapid and marked thromboxane synthetase inhibition and augmentation of levels of prostaglandin metabolites. There was no evidence of change in amniotic pressure, uterine blood flow, maternal and fetal blood pressure and heart rate. CONCLUSION: Ridogrel is a potent thromboxane synthetase inhibitor which passes the sheep placenta, does not influence maternal and fetal hemodynamics and uterine contractility, and shows similar antiplatelet activity in the ewe and the fetal lamb.     

The effect of a calcium channel blocker (nifedipine) on uterine blood flow in the pregnant goat

The purpose of this study was to analyze the changes in maternal uterine blood flow, maternal arterial blood pressure, and maternal heart rate with the intravenous administration of nifedipine in pregnant, unanesthetized pygmy goats. Bolus injections of 2.5 to 45 micrograms/kg of maternal weight were used. Uterine blood flow did not fall significantly. A transient fall in maternal arterial blood pressure occurred in the first minute after the injection, but the pressure returned to normal after 5 minutes. Maternal heart rate increased immediately after the bolus of nifedipine and returned toward the control value by 30 minutes.     

Effect of maternal carbon dioxide inhalation on human fetal breathing movements in term and preterm labor

Induced maternal hypercapnia is a potent stimulus to fetal breathing movements in nonlaboring pregnant women. To determine the effect of maternal CO2 administration on fetal breathing movements during spontaneous labor, 14 healthy pregnant volunteers at term and 34 in preterm labor were recruited. If fetal breathing movements were markedly decreased or absent, the subjects were administered a prepared gas mixture of 3% CO2 in air. In term labor and in true preterm labor, fetal breathing movements were markedly decreased and could not be induced by maternal hypercapnia. Among women with suspected preterm labor, initial absence of fetal breathing movements and failure to evoke this response by maternal hypercapnia predicted delivery within 48 hours with a sensitivity of 80% and specificity of 95.5%. Induced maternal hypercapnia fails to stimulate fetal breathing movements in true term and preterm labor and may assist in distinguishing between true and false preterm labor.     

Effect of nicotine upon uterine blood flow in the pregnant rhesus monkey

Acute effects of nicotine upon the uterine blood flow, blood pressure, maternal and fetal acid-base state, and oxygenation were determined in eight pregnant rhesus monkeys near term. Nicotine was infused intravenously to the mother in a dose of 100 microgram/kg per body weight/minute over 20 minutes. The flow rate was measured with the use of the electromagnetic flowmeter. Significant decrease in the uterine arterial blood flow rate, as much as 38% of the control value, was observed during the first 15 minutes of the infusion while aortic pressure increased by 14%. Acidosis and hypoxia resulted in the fetus. Considered together with our previously reported data, the present investigation appears to indicate that the adverse effects of nicotine to the fetus are due to the combined effects of the reduced uterine blood flow and the transmitted nicotine to the fetus.     

Effect of intravenous glucose injection on human maternal and fetal heart rate at term

The effects of maternal intravenous glucose administration (25 gm) on maternal heart rate, fetal heart rate, gross fetal body movements, and fetal heart rate accelerations was measured in 11 healthy pregnant women at 38 to 40 weeks' gestational age. Mean maternal heart rate increased from 78.3 ± 0.8 bpm during the control period to 82.7 ± 0.5 bpm at 30 to 85 minutes following glucose injections (p < 0.01). Mean fetal heart rate rose from 137.8 ± 0.4 bpm to 142.4 ± 0.3 bpm at 50 to 95 minutes following injections (p < 0.001). The incidence of gross fetal body movements and the number, duration, and amplitude of fetal heart rate accelerations did not change following glucose injection. We conclude that maternal glucose administration near term results in a small but significant increase in the mean maternal heart rate and fetal heart rate and no change in the incidence of gross fetal body movements or in fetal heart rate accelerations.     

The effects of xylazine on uterine activity, fetal and maternal oxygenation, cardiovascular function, and fetal breathing

Various pharmacologic agents used in the experimental study of physiologic processes may have pronounced effects on the systems under study. We have studied the effects of xylazine (Rompun) on myometrial activity, fetal and maternal pH, blood gases, heart rate, and fetal breathing movements in chronically catheterized fetal sheep. Xylazine is widely used as a premedication for various forms of animal operations, including the instrumentation of the chronically catheterized fetal sheep preparation. Animals were studied on postoperative day 5. Xylazine had pronounced effects on maternal PaO2 and heart rate that lasted for at least 3 hours. Fetal heart rate and PaO2 returned to preinjection levels within 60 minutes. Myometrial activity doubled in the first 60 minutes after administration of xylazine and did not return to preinjection levels for 3 hours. Fetal diaphragmatic electromyographic activity was almost completely absent in the first and second hours, with a return to normal within 4 hours. These changes were absent in the saline solution-injected control animals. The observed changes in uterine activity and fetal breathing may have been direct effects of xylazine itself or the result of increased uterine activity. The different duration of changes in the ewe and fetus suggests a compensatory mechanism at the uteroplacental level or in the fetoplacental unit.     

Maternal hypoxemia and fetal breathing movements.

Fetal breathing movements (FBM) were observed daily using a real-time B-mode ultrasound method in a patient with sickle cell anemia in crisis. Observations were made on 2 occasions in the presence of maternal hypoxemia (PO2 less than or equal to 40 mmHg), and FBM were noted to be absent. Conversely, when maternal PO2 was 60 mmHg or greater, FBM were present 23--80% of the time. The FBM were reduced or absent within 90 minutes of maternal Demerol injection. These observations suggest that the human fetal response to hypoxemia may be similar to that observed under expermental conditions in the animal fetus.     

Fetal hemodynamic response to maternal intravenous nicotine administration.

OBJECTIVES: Our study was designed to test the hypothesis that maternally administered nicotine has significant effects on fetal hemodynamics and umbilical systolic/diastolic ratios. STUDY DESIGN: Nine pregnant ewes received maternal intravenous infusions of 10, 20, and 30 micrograms/kg/min of nicotine. Maternal and fetal blood pressure, heart rate, and uterine and umbilical blood flow were recorded. RESULTS: Maternal intravenous administration of nicotine (10, 20, and 30 micrograms/kg/min of maternal body weight) produced significant (p < 0.05) increases in fetal blood pressure (2%, 11%, and 25%, respectively), decreases in fetal heart rate (0%, 8%, and 12%), and decreases in umbilical blood flow (0%, 0%, and 19%). Umbilical systolic/diastolic ratios increased slightly at the 30 micrograms/kg/min dose of nicotine, but these changes did not reach significance. Maternal blood pressure increased (10%, 25%, and 53%), and uterine vascular resistance increased (5%, 64%, and 344%) significantly (p < 0.05); uterine blood flow increased at the 10 micrograms/kg/min dose (+5%) and decreased by 23% and 42% at the highest two doses of nicotine. CONCLUSION: Maternal nicotine administration in late-term pregnant sheep produced significant increases in fetal arterial blood pressure and umbilical vascular resistance, decreased fetal heart rate, and umbilical blood flow but did not significantly alter systolic/diastolic ratios.     

The effects of long- and short-term maternal caffeine ingestion on human fetal breathing and body movements in term gestations

The possible effects of long- and short-term maternal ingestion of caffeine during normal human pregnancy on the breathing and body movements of third-trimester fetuses were studied in 14 patients, selected by a dietary questionnaire, and divided into two equal groups: high consumers (greater than 500 mg/day) (group 1) and low consumers (less than 250 mg/day) (group 2). All mothers followed a standard study protocol and underwent overnight fasting; studies began with a 30-minute control period, followed by oral administration of 200 mg caffeine, and a 180-minute subsequent observation period with continued maternal fasting. Blood samples for glucose and caffeine were obtained every 30 minutes and continuous recording of fetal breathing and body movements were entered on a microcomputer for off-line analysis. The two groups were similar for all obstetric outcome features. Plasma glucose levels were similar and constant in both groups whereas caffeine levels increased significantly at 60 minutes after administration; mean plasma caffeine levels were significantly higher in group 1 than in group 2 at all intervals. Fetal breathing rates and body movement incidences were similar in both groups before and after caffeine administration. Fetal breathing movement incidence decreased significantly in group 2 but was sustained at baseline levels in group 1 throughout the study. High long-term ingestion of caffeine during pregnancy is associated with higher maternal plasma caffeine levels and fetal breathing activity when compared with low caffeine ingestion. Short-term administration of 200 mg caffeine does not appear to have a significant physiologic impact on these activities.     

Temporal changes in fetal cardiovascular, behavioural, metabolic and endocrine responses to maternally administered dexamethasone in the late gestation fetal sheep.

OBJECTIVE: To determine the primary (0-12 h) and secondary (12-24 h) effects of dexamethasone on fetal heart rate, short term heart rate variation, blood pressure, breathing movements and electrocortical activity, blood gas exchange, metabolism and adrenocortical function in the late gestation sheep fetus. DESIGN: Comparison of the effects of a single maternally administered intramuscular injection of dexamethasone (12 mg) with those of saline vehicle from 1 h before injection to 24 h post-injection. Fetal cardiovascular and behavioural parameters were recorded continuously. Fetal and maternal blood samples were taken at regular intervals for blood gas, glucose and lactate, cortisol and adrenocorticotrophin measurements. SAMPLE: Sixteen chronically instrumented singleton fetal sheep at 127-133 days of gestation (term is about 147 days). RESULTS: During the primary phase short term heart rate variation fell (P < 0.001), and this was associated with a transient fall in the incidence of fetal breathing movements, a fall in fetal heart rate and a rise in fetal blood pressure. By 12 h there was a significant increase in short term heart rate variation (P < 0.001) and a rise in fetal heart rate, but blood pressure and fetal breathing movements had returned to normal. Dexamethasone significantly reduced fetal PaO2 throughout most of the experimental period, particularly 1 h post-injection (P < 0.005). Fetal and maternal plasma cortisol and adrenocorticotrophin concentrations fell significantly from 1 h post-injection. CONCLUSIONS: The effects of dexamethasone on fetal heart rate variation are more complex than previously described with both a fall and an increase observed depending on the time at which heart rate variation was measured after injection. Dexamethasone also caused a significant fall in fetal PaO2, and although this was not to hypoxic levels in normoxic fetuses it does raise questions about the potential impact of dexamethasone on chronically hypoxic fetuses.     

The effect of intermittent maternal fasting on human fetal breathing movements.

In order to determine the effect of maternal fasting on human fetal breathing movements (FBM), 63 healthy pregnant women with singleton uncomplicated pregnancies of 30 weeks' gestation or more, and who were fasting during Ramadan, were recruited. Maternal blood glucose level and fetal movements were recorded during and after fasting. Statistical comparison of samples before and after a meal was made using Wilcoxon's signed-ranks test. Maternal glucose level during fasting (5.1 +/- 0.5 mmol/l) was significantly (P = 0.01) lower than after breakfast (5.3 +/- 1.0 mmol/l). There was a significant association between maternal glucose levels and numbers of days faster (P = 0.01). The time needed to detect breathing movements was significantly longer (P = 0.005) during fasting than postprandial. The continuous variety of fetal breathing movement was significantly (P = 0.02) less during fasting compared to postprandial. It is concluded that intermittent maternal fasting is associated with a significant alteration in the frequency and pattern of human FBM.     

Cocaine in pregnancy: the effect of maternal administration of cocaine on the maternal and fetal pituitary-adrenal axes.

The effects of cocaine on the maternal and fetal pituitary-adrenal axis in vivo during pregnancy have not been reported. Six pregnant ewes and their fetuses underwent instrumentation at 113 to 119 days' gestation. Ewes were assigned to receive an intravenous bolus injection of vehicle or cocaine (0.5, 1.0, or 2.0 mg.kg-1) at 124 to 136 days' gestation. Maternal arterial blood gases, fetal pH and fetal PCO2 were unchanged after injection of cocaine or vehicle. After administration of 2.0 mg.kg-1 cocaine, arterial fetal PO2 fell 3.2 +/- 1.72 mm Hg (p less than 0.05) at +5 minutes, returning to baseline by +15 minutes. Maternal and fetal adrenocorticotropin levels rose within 5 minutes after the highest cocaine dose (p less than 0.05). There was a significant (p less than 0.05) increase in maternal cortisol at all doses of cocaine and in fetal cortisol at +15 minutes after the 2.0 mg.kg-1.