Decrease In Fetal Heart Rate Research Articles

Central nervous system regulation of reflex responses to hypotension during fetal life

The ability of the fetus to survive, grow, and successfully complete the transition from fetal to neonatal life is critically dependent on the appropriate regulation of fetal blood pressure, blood volume, and fluid dynamics. This is a short review of the physiological mechanisms controlling the fetal cardiovascular system, focusing mainly on the neural and endocrine elements in the schema of cardiovascular function and control. The fetal cardiovascular system is arranged anatomically to provide for perfusion of the umbilical-placental circulation, the organ of gas exchange of the fetus, and to largely bypass the lungs. Fetal blood volume and pressure, maintained at levels that are appropriate for this function, are influenced by neural and endocrine control mechanisms, which are similar to, but quantitatively different from, the adult animal. Baroreceptors and chemoreceptors located in the carotid sinuses and aortic arch sense changes in blood pressure and blood gases and comprise the afferent limb of the major reflexes that maintain normal fetal blood pressure and volume. Fetal hypotension stimulates reflex decreases in fetal heart rate, which are apparently mediated by chemoreceptor input. Arginine vasopressin responses to hypotension are most likely mediated by baroreceptor input. Recent evidence suggests that the reflex responses to hypotension in the fetus are modulated by paracrine or endocrine factors. For example, baroreceptor or chemoreceptor reflex pathways are modulated by the endogenous production of prostanoids and by the preparturient changes in fetal plasma estrogen concentration.

Analysis of Umbilical Artery Flow Parameters during Fetal Variable Decelerations Using Computerized Doppler Waveforms

Umbilical artery velocity waves were obtained by Doppler ultrasonography before, during, and after 20 episodes of fetal heart rate (FHR) variable decelerations (VD) during the active stage of labor in 8 women. During 50% of the VD periods, the umbilical artery resistance flow parameters increased significantly (p < 0.01). The increase in resistance preceded the decrease in FHR in six episodes (30%) of VD (AR-VD group; arterial resistance VD) and did not precede the change in FHR in another ten episodes (50%) of VD (VR-VD group; venous resistance VD). In the AR-VD group the FHR accelerations occurred before the decelerations in only 1 case (17%), while in the VR-VD group FHR accelerations preceded the decelerations in 8 out of the 10 episodes (80%). Using these Doppler studies, it may be possible to differentiate between two groups of VD: AR-VD – which are caused by umbilical artery occlusion and thus preceded by a measurable increase in umbilical artery resistance – and VR-VD – which are not preceded by a measurable increase in umbilical artery resistance and may be caused by fetal hypoxia.

Gestational age related changes in cardiac dynamics of the fetal baboon.

To provide insight into the maturation of neural mechanisms governing fetal heart rate and rate variability, seven chronically instrumented fetal baboons were monitored under steady state conditions between 120 and 165 days gestation (term 175 d). Forty records of 24 h duration (5-7 records/fetus) were evaluated. For each fetus, heart rate decreased with gestational age (mean+/-SD, r = -0.530+/-0.324, P <0.05). In contrast, there were increases with age in markers of various components of autonomic control of fetal R-wave to R-wave interval (RRi) variability as reflected in a positive correlation with age for all fetuses of SD RRi (r = 0.656+/-0.347, P < 0.01), root mean squared differences in RRi (r = 0.686+/-0.223, P <0.05), and power at low frequency in the RRi spectrum (r = 0.800+/-0.161 P < 0.01). In each of the seven fetuses, scatter plots of RRi as a function of the prior RRi (Poincare plots) had increased dispersion around the median with gestational age (0.605+/-0.371, P<0.05). Additional measures of variability evaluated changes in RRi from one interval to the next (deltaRRi). The incidence of sustained deltaRRi changes, either decelerations or accelerations, rose with gestation (r = 0.920+/-0.057, P < 0.001) while the incidence of no detected deltaRRi changes (<+/-1 ms) diminished (r = - 0.649+/-0.364, P <0.05). Sequential decreases in fetal heart rate, increases in RRi variability and increases in changes in RRi and deltaRRi with age imply an overall maturation in autonomic cardio-regulatory control processes. Increases with gestation in measures of high frequency components of variability are compatible with enhanced parasympathetic modulation of fetal heart rate.

Magnesium sulfate, maternal hypothermia, and fetal bradycardia with loss of heart rate variability

Background: Fetal bradycardia and decreased heart rate variability can indicate a nonreassuring fetal status. However, there can be iatrogenic, physiologic, or pathologic causes. Case: A patient in premature labor received toxic levels of magnesium sulfate for tocolysis. Elevated maternal serum magnesium levels correlated inversely with maternal temperature and both fetal heart rate and fetal heart rate variability. There was also a relative decrease of the maternal heart rate from baseline. When the magnesium levels returned to normal, these vital signs returned to normal. Conclusion: Magnesium sulfate therapy can result in maternal hypothermia and a decrease in fetal heart rate and heart rate variability. Maternal hypothermia might be the cause of fetal bradycardia. A direct action of magnesium on the fetal heart might be the cause of heart rate variability.

Characteristics of fetal heart rate changes during the expulsive stage of bovine parturition in relation to fetal outcome

Abstract Objective To characterize fetal heart rate (FHR) patterns of nonacidotic (N-AC) and acidotic (AC) calves during the expulsive stage of parturition. Animals 32 calves born to heifers, either unassisted or by moderate traction. Procedure Cardiotocograms (CTG) evaluated qualitatively (visual) and quantitatively by a moving window technique (width 10, shift 5 minutes) for baseline FHR, variability, and periodic alterations (accelerations and decelerations). Results Significant differences were apparent between increase in baseline FHR of N-AC and AC calves; change in FHR (Δ-FHR), taking into account individual FHR, is a more discriminating parameter. The predominant reaction to uterine contraction is a decrease in FHR; variable decelerations were the most common type in both groups, and late decelerations were seen only in AC calves. Additional characteristics of variable decelerations were more frequently seen in AC calves. Conclusions CTG parameters during expulsion can discriminate between AC and N-AC calves, but specific characteristics are not exclusively restricted to AC or N-AC calves. Clinical Relevance CTG recordings during bovine parturition in cattle provide information on the fetal condition and can be used in the future to study the effects of medication and manipulations to the fetus. (Am J Vet Res 1996;57:1373-1381)

IMMEDIATE CHANGES IN UMBILICAL BLOOD FLOW AFTER TRANSCERVICAL CHORIONIC VILLUS SAMPLING PERFORMED BY BIOPSY FORCEPS

Transvaginal ultrasonography with colour Doppler was used to evaluate the immediate changes on the fetal heart rate (FHR) and the fetal umbilical artery pulsatility index (PI) after chorionic villus sampling (CVS). This prospective study included 279 consecutive singleton pregnancies, between 10 and 13 weeks, of women who underwent transcervical CVS in our institution. All Doppler measurements were obtained transvaginally before and immediately after CVS. Structural malformations detected by ultrasound were excluded. Student's t- and Wilcoxon texts were performed for statistical analysis. The results showed no significant decrease in FHR (mean 1.04 beats, t = 1.68, P = 0.94) and a significant elevation of umbilical artery PI (mean 0.12, t = - 6.51, P < 0.001) post-CVS. This difference was only significant in procedures performed at less than 11 weeks' gestation, since there was no significant change for those procedures performed thereafter. These preliminary data suggest that acute fetal haemodynamic changes are induced by CVS and may have clinical effects. Hypotheses on possible vascular mechanisms are discussed. Colour Doppler could widen the possibilities for more accurate in vivo assessment and research on CVS-related placental injury.

Effects of xylazine on early bovine pregnancy

The effects of xylazine on early pregnancy in cattle were determined in 39 beef heifers in the first trimester of gestation. Fetal heart rate ( n = 13), maternal heart rate ( n = 8) and uterine contractility ( n = 13) were observed at 3 min before and 3, 10, 60 and 120 min after the administration of xylazine (20 mg i.v.). All heifers were examined for fetal heart beats 1 week after the administration of xylazine. There was a decrease ( P < 0.01) in fetal and maternal heart rate at 3 min after injection. The fetal heart rate returned to pretreatment values within 60 min, whereas maternal heart rate was still depressed at 120 min after treatment. Uterine contractility was markedly increased ( P < 0.001) at 3 min after xylazine administration, but returned to normal within 120 min. Fetal heart beats were observed in 38 of the 39 heifers 1 week after xylazine treatment. A second experiment was designed to assess the effects of increased uterine activity on fetal heart rate after the injection of oxytocin (20 IU i.v., n = 11), the PGF 2α analogue cloprostenol (500 μg i.v., n = 7), and the uterine relaxant clenbuterol (300 μg i.v., n = 11) administered together with xylazine (20 mg i.v.). Oxytocin and cloprostenol caused an increase ( P < 0.05) in uterine contractility, but no changes in fetal heart rate. The injection of xylazine with clenbuterol resulted in a shorter, less pronounced increase in uterine contractility and less depression of fetal heart rate than xylazine alone. It was concluded that the decrease in fetal heart rate observed after the administration of xylazine to the dam is most likely the result of a specific pattern of increased uterine contractility and/or α 2 − receptor-mediated vasoconstriction, resulting in reduced uterine blood flow and subsequent fetal hypoxia and bradycardia. The changes in uterine contractility and fetal heart rate caused by a single injection of 20 mg xylazine in heifers in the first trimester of gestation have no short-term adverse effects on pregnancy.

Acute effects of perinatal hypoxic insult on concentrations of dopamine, serotonin, and metabolites in fetal monkey brain

Seven monkeys (Macaca mulatta) were laparotomized under general anesthesia (halothane, nitrous oxide, oxygen). Fetal hypoxia was induced in four monkeys by occlusion of the umbilical cord with a hydraulic occluder for 5–6 min. Three sham-operated fetuses served as controls. After unclamping, the fetuses were allowed to reperfuse for 20–30 min. To monitor hypoxia, the fetal electrocardiogram was recorded continuously. Hypoxic insult was associated with a decrease in fetal heart rate during the occlusion. After reperfusion, fetuses were immediately sacrificed and neocortex regions dissected on ice, frozen on dry ice and stored at −70°C. Dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, serotonin, and 5-hydroxyindoleacetic acid were assayed by high performance liquid chromatography with electrochemical detection (HPLC/EC) in hippocampus, caudate nucleus and cortical regions. In the hippocampus, there was a significant increase in 5-hydroxyindoleacetic acid concentration. In prefrontal cortex, there was a trend toward an increase in serotonin but no effects on dopamine and homovanillic acid concentrations. Dopamine, serotonin and metabolites were not altered in the caudate nucleus. These data demonstrate that fetal hypoxia followed by reperfusion produced an increase in serotonin concentration measured within the hippocampus and selected cortical areas known to be targets of hypoxic injury.

Fetal reactions to recurrent maternal speech

Pregnant women recited a short child's rhyme, “the target”, aloud each day between the thirty third and thirty seventh weeks of their fetuses' gestation. Then their fetuses were stimulated with tape recordings of the target and a control rhyme. The target elicited a decrease in fetal heartrate whereas the control did not. Thus, fetuses' exposure to specific speech sounds can affect their subsequent reactions to those sounds. More generally, the result suggests that third trimester fetuses become familiar with recurrent, maternal speech sounds.

Response of the premature fetus to stimulation by speech sounds

The response of the premature fetus to speech stimuli was studied in 41 healthy pregnant patients at 26–34 weeks gestation. Speech stimuli consisted of repeated syllables (‘ee’ and ‘ah’) presented externally over the maternal abdomen at either 100, 105, or 110 decibels (dB). Sound stimuli were delivered during periods of both high and low fetal heart rate variability. During periods of low FHR variability, a decrease in fetal heart rate and an increase in the standard deviation of heart rate were found. During periods of high FHR variability, no significant change in either of these measures was observed. This is the first clear demonstration of heart rate responses to speech stimuli in the premature fetus. As is the case in the term fetus, this response is dependent on baseline heart rate variability which is the primary determinant of fetal state. The clinical usefulness of this finding may be limited by the magnitude of the response.

Histopathological and hemodynamic studies supporting hypoxia and vascular disruption as explanation to phenytoin teratogenicity.

The limb plates and craniofacial regions in rabbit fetuses were examined shortly after the last dose of phenytoin on day 16 after daily administration by gavage with either 150 mg/kg on days 14-16 or 300 mg/kg on days 15-16. Both treatment regimens resulted in similar changes. Histologically, the digital areas of the limb plates showed extensive edema and dilated blood vessels within 2 h. After 8 h, vascular disruption occurred with hemorrhages. At 24-48 h after dosing, mesenchymal necrosis and, on some occasions, amputation of digits was observed. In the craniofacial region, well-defined superficial hemorrhage was seen in the frontal and nasal region at 8 h. Histologically, subectodermal hemorrhage caused by vascular disruption and microfocal mesenchymal necrosis was observed. At 48 h, some fetuses showed severe diffuse intracranial and superficial hemorrhage, resulting in massive tissue damage, also in the central nervous system (CNS). Maternal heart rate, blood pressure, PO2, and PCO2 were also measured in awake pregnant rabbits 6 h after the last dose on day 16 after daily administration with 150 mg/kg during gestational days 14-16. An attempt was also made to measure fetal heart rate in anesthetized rabbits. The maternal heart rate and blood pressure decreased with about 15% in phenytoin-treated animals, resulting in a decrease in PO2 (approximately 15%) and an increase in PCO2 (approximately 15%). A decrease in fetal heart rate was also registered. The results thus indicate that phenytoin exerts its teratogenic effects by inducing fetal hypoxia, leading to vascular disrupture and necrosis of existing and developing structures.

The acute response of the umbilical artery pulsatility index to changes in blood volume in fetal sheep

This experimental study was designed to test the effects of acute changes in fetal circulating blood volume on the umbilical artery pulsatility index (PI). Six fetal sheep were provided with an electromagnetic flow meter for measurement of umbilical venous blood flow, with catheters for determination of arterial blood pressure and umbilical venous pressure, and with a 5 MHz Doppler transducer around one umbilical artery for flow velocity waveform analysis. A catheter in the inferior vena cava was used to infuse 50 ml of maternal blood (hypervolemia) into the fetal circulation or to withdraw 50 ml of fetal blood (hypovolemia) after volume correction. Hypervolemia resulted in a rise in arterial pressure and umbilical venous pressure, without an effect on PI, umbilical blood flow or placental vascular resistance. Hypovolemia resulted in a decrease in fetal heart rate, arterial pressure, umbilical venous pressure and umbilical blood flow. Calculated placental vascular resistance was not changed, whereas the PI increased by 42%. We conclude that volume loading with 10–15% of fetal circulating volume does not affect the umbilical artery PI, whereas acute reduction of fetal blood volume with the same amount is associated with an increase in the umbilical artery PI, without changes in calculated placental vascular resistance.

Effect of R(-)2,5-dimethoxy-4-methylamphetamine on uterine and umbilical blood flow in conscious pregnant sheep

Pregnant sheep and their fetuses were instrumented between 110 to 120 days of gestation (term, 145 days) for monitoring maternal and fetal arterial blood pressure, heart rate and blood flow in the maternal uterine and fetal intra-abdominal umbilical arteries. The administration of 2,5-dimethoxy-4-methylamphetamine (DOM, a 5-HT 2 agonist) i.v. to the ewe in doses ranging from 1 to 20 μg/kg of ewe body weight produced dose-dependent decreases in the blood flow of the uterine and umbilical arteries. This was accompanied by an increase in the arterial blood pressure of the mother and fetus and a decrease in the fetal heart rate. DOM significantly increased the vascular resistance to blood flow in the uterine and umbilical arteries. The maximal increase in the vascular resistance of the uterine and umbilical arteries was 19.6- and 2.6-fold, respectively. Ketanserin, a 5-HT 2 antagonist (1 mg/kg), administrated 30 min prior to DOM significantly inhibited the reduction in blood flow in the uterine and umbilical arteries to DOM and blocked the increased vascular resistance in these vessels. The inhibitory effects of ketanserin on the responses to DOM in the uterine and umbilical arteries were surmountable. Our results indicate that DOM is a potent constrictor of the uterine and umbilical vasculature which may lead to fetal distress as evidenced by a decrease in fetal heart rate and arterial blood PO 2. 5-HT 2 receptor stimulation by DOM may be involved in these effects since they were blocked by ketanserin.

Behavioral changes in fetal sheep caused by vibroacoustic stimulation: The effects of cochlear ablation

We measured the effects of 2 minutes of vibroacoustic stimulation on the activity of unanesthetized fetal sheep in utero. We were unable to detect any changes in activity after stimulation with a model 5C electrolarynx. With more powerful stimulation using a mechanical oscillator, fetal electrocortical activity desynchronized. Fetal breathing and eye movements changed with electrocortical activity and there was an increase in nuchal muscle activity. Stimulation caused a small decrease in fetal heart rate. Responses to stimulation were not seen in four of the five fetuses with bilateral cochlear ablation. These results indicate that in fetal sheep the auditory apparatus is necessary for the detection of vibroacoustic stimuli. The difference in responsiveness of the sheep and human fetus appears to be because of a difference in central processing after detection of the stimulus.

Sinoaortic denervation attenuates the reflex responses to hypotension in fetal sheep

Hypotension in fetal sheep stimulates reflex decreases in heart rate and increases in the secretion of several hormones, including adrenocorticotropin (ACTH), cortisol, vasopressin, and renin. However, little is known about the afferent limb(s) of the reflex(es) controlling these responses. Fetal sheep between 122 and 134 days gestation were prepared with chronic vascular catheters, intravascular balloon-tipped catheters, and amniotic fluid catheters. Seven fetal sheep were also subjected to sinoaortic denervation, and nine remained intact. After recovery from surgery for 2-5 days, fetuses were subjected to a 10-min period of hypotension produced by vena caval obstruction, produced by inflation of balloons in the superior and inferior venae cavae. Vena caval obstruction produced decreases in fetal heart rate and increases in fetal plasma ACTH, vasopressin, and renin activity, which were related to the degree of hypotension. Prior sinoaortic denervation attenuated all of these responses. It is concluded that afferent fibers in the carotid sinus and/or aortic depressor nerves mediate part of the heart rate, ACTH, vasopressin, and renin responses to vena caval obstruction in late-gestation fetal sheep.

Comparison of high-dose opioid antagonist effects on ovine fetal cardiovascular function.

The opioid antagonists, naloxone (NOX) and naltrexone (NTX), were found to produce dose-dependent increases in fetal mean arterial pressure over a dose range of 5-80 mg/kg. There was a concomitant decrease in fetal heart rate up to 40 mg/kg. Above this dose, NOX and NTX caused an increase in heart rate as well as blood pressure. NTX produced similar effects in maternal ewes, although at lower doses (mg/kg) than those needed for fetal lambs. There were no age-related differences in antagonist effects in two fetal age groups studied (100-116 and 124-144 days of gestation). The partial antagonist, levallorphan (LVL), produced effects which were qualitatively similar to those produced by NOX and NTX in doses up to 20 mg/kg. These effects were not stereospecific, as the enantiomer of LVL, dextrallorphan, produced similar effects at equal doses. Pretreatment with the alpha 1-adrenoreceptor antagonist, prazosin, abolished the opioid antagonist effects on fetal blood pressure. We postulate that high doses of opioid antagonists activate sympathetic systems to increase fetal blood pressure through mechanisms which do not involve interactions with mu, delta or kappa opioid receptors.

Fetal heart rate, arterial pressure, and blood volume responses to cortisol infusion.

The purpose of this study was to determine whether physiological amounts of cortisol affect the fetal cardiovascular system. Cortisol (4 micrograms/min) or the vehicle was infused intravenously for 5 h into six chronically catheterized sheep fetuses at 127-143 days gestation (term = 145-150 days). In the cortisol-infused animals, plasma cortisol concentration increased from 2.0 +/- 0.6 (SE) to 8.3 +/- 0.9 ng/ml. There was a concomitant decrease in fetal heart rate of 38 beats/min (P less than 1 X 10(-6)) and an increase in arterial pressure. Estimated blood volume decreased by 6% in the cortisol-infused fetuses compared with the vehicle-infused animals (P less than 1 X 10(-4]. In addition, plasma norepinephrine and epinephrine concentrations decreased to 70% of control at the end of the 5-h cortisol infusion, whereas plasma renin concentration decreased to 34% of control. The simultaneous increase in fetal arterial pressure and decrease in estimated blood volume suggest that fetal vascular resistance increased, whereas vascular compliance and/or nonstressed vascular volume decreased. However, this does not appear to be mediated by increases in circulating vasoconstrictor hormone concentrations or increased sympathetic tone. Thus the present study shows that physiological amounts of cortisol have significant effects on the fetal cardiovascular system but the mechanisms are unknown.

Cyclic variation in fetal heart rate and sympathetic activity

The effects of α- and β-adrenergic blockade on electrocortical activity-related cyclic variability in fetal heart rate and mean arterial pressure were investigated in eight fetal lambs between 119 and 138 days of gestation. In the absence of adrenergic blockade, fetal heart rate during high-voltage slow activity was significantly higher than that during low-voltage fast activity. Propranolol (2.0 mg/hr) produced a decrease in fetal heart rate, but the decrease was only statistically significant during high-voltage slow activity. Phentolamine (5.0 mg/hr) induced a significant increase in fetal heart rate with a small but statistically significant decrease in mean arterial pressure. The cyclic variability in fetal heart rate between low-voltage fast activity and high-voltage slow activity was abolished by propranolol and enhanced by phentolamine. These results indicate that the cyclic variability in the fetal heart rate associated with electrocortical activity can be accounted for by cyclic fluctuation in sympathetic activity.

Metoprolol in the Treatment Oe Mild to Moderate Hypertension in Pregnancy - Effects on Fetal Heart Activity

In a double blind placebo controlled trial of the cardio-selective beta-1-receptor blocker metoprolol for the treatment of hypertension in pregnancy, the effects on the fetal heart rate (FHR) and its cardiotocographic (CTG) pattern were studied. 52 women were allocated to groups which received either 50-100 mg metoprolol twice daily or placebo. CTG tracings were performed weekly. The tracings were analyzed with respect to basal FHR, amplitude of oscillations, FHR accelerations and FHR decelerations. The mothers also noted fetal movements during the 30 minutes the tracings were running. There was a significant decrease in FHR by five to ten beats per minute in the metoprolol-treated group but not in the placebogroup. The number of accelerations and fetal movements was less at the CTG before labour compared to the CTG before treatment in the metoprolol-group but not in the placebo-group.

Acute Fatty Liver of Pregnancy

A 17-year-old-female at 39 weeks gestation, presented with pelvic pain, proteinuria and a decrease in fetal heart rate. Timely caesarean section was performed. The postoperative course was complicated by acute renal failure, acute pancreatitis, acute liver failure, anemia, thrombocytopenia, systemic inflammatory response syndrome (SIRS), prolonged coagulopathy, hyperbilirubinemia, ecclampsia, and psychosis. The clinical features and laboratory abnormalities, in conjunction with the timing of gestational age, led to the diagnosis of acute fatty liver of pregnancy. Prompt diagnosis and supportive care in an intensive care unit provided for a positive outcome.