Lesley Carmichael

Fetal cerebral, circulatory, and metabolic responses during heart rate decelerations with umbilical cord compression

OBJECTIVE The purpose of this study was to determine the cerebral, circulatory, and metabolic responses of the ovine fetus near term to umbilical cord compression with variable-type fetal heart rate decelerations. STUDY DESIGN Nine fetal sheep, at 0.9 of gestation, were studied before, during, and after umbilical cord occlusion for 1-minute and again after repetitive 1-minute cord occlusions every 5 minutes for 1 hour, with resultant fetal heart rate decelerations of approximately 90 beats/min. Brachiocephalic arterial and sagittal venous blood was analyzed for oxygen content, blood gases and pH, glucose, and lactate. Cerebral and upper body blood flow was measured with the microsphere technique. RESULTS Umbilical cord occlusion with moderate to severe variable-type fetal heart rate deceleration resulted in an immediate drop in arterial PO2 by approximately 7 torr, an increase in PCO2 by approximately 9 torr, and a small but significant increase in lactate levels. Cerebral oxidative metabolism was well maintained but required an increase in fractional oxygen extraction because the variable change in cerebral blood flow was insufficient to maintain oxygen delivery. A redistribution of upper body blood flow was evident, with that to the bran and heart variably maintained or increased whereas that to muscle tissue was markedly decreased. Repetitive umbilical cord occlusion over 1 hour resulted in a significant drop in fetal arterial pH, with the acidemia mixed as PCO2 increased approximately 6 torr, whereas lactate levels increased almost fourfold. CONCLUSION Although cerebral oxidative metabolism appears to be well maintained during moderate to severe variable-type fetal heart rate decelerations with umbilical cord occlusion, the need to increase fractional oxygen extraction and the redistribution of blood flow from carcass tissues may contribute to an accumulation of lactic acid both within the brain and systemically when such an insult occurs repeatedly.

Fetal heart rate and activity patterns in growth-retarded fetuses: Changes after vibratory acoustic stimulation

Seventeen pregnant women who subsequently were delivered of infants with birth weights less than the third percentile were studied for examination of fetal heart rate and fetal activity patterns before and after a 5-second external vibratory acoustic stimulation. None of the fetuses was acidotic at birth. A reduced time was noted during which accelerations in heart rate occurred (50% less) and long-term fetal heart rate variability (25% less) in small for gestational age fetuses compared with age-matched, normally grown fetuses. The incidence of gross fetal body movements was significantly lower (40% less) in small for gestational age fetuses than in those who were appropriate for gestational age. Fetal heart rate and fetal activity patterns after stimulation with the electronic artificial larynx in small for gestational age fetuses were similar to those of appropriate for gestational age fetuses.

Carotid arterial blood flow in the ovine fetus as a continuous measure of cerebral blood flow

OBJECTIVE The purpose of this study was to establish a continuous measure of cerebral blood flow in the ovine fetus with a transit time flow probe. METHODS Seven chronically catheterized fetal sheep were studied near term with placement of a 3R Transonic flow probe on the external carotid artery, just proximal to the internal maxillary artery. Blood flow changes were induced by altering maternal inspired oxygen and carbon dioxide concentrations, with cerebral and extracerebral blood flows also determined by the microsphere technique. RESULTS Although absolute carotid and cerebral blood flow values were only modestly related under the present study conditions (r = 0.60, P < .05), both the percent change and the actual change in carotid arterial blood flow showed a strong linear correlation with that for cerebral blood flow (r = 0.84, P < .01, and r = 0.72, P < .02) but less so with that for extracerebral blood flow (r = 0.44 and r = 0.28). CONCLUSION Measurements of carotid blood flow as studied with a transit time flow probe and induced blood gas changes can provide for a continuous assessment of changes in blood flow to the ovine fetal brain.

Effects of sustained hypoxemia on the sheep fetus at midgestation: Endocrine, cardiovascular, and biophysical responses†

OBJECTIVE The purpose of our study was to examine the effects of induced hypoxia on endocrine, cardiovascular, and biophysical measurements of the ovine fetus at 0.6 (83 to 93 days) of gestation and to compare the fetal responses at this earlier gestation with those reported near term. STUDY DESIGN Fourteen fetal sheep were studied (9 in the hypoxia group and 5 in the control group) at 0.6 of gestation during a 24-hour control period, 8 hours of either sustained hypoxemia or room air, and a 40-hour recovery period. RESULTS Induced fetal hypoxemia resulted in a progressive lactic metabolic acidosis; however, all fetuses had recovered within 24 hours. The fetal endocrine response was variable with norepinephrine, the only measured hormone showing a significant hypoxia-related increase (p less than 0.05). Fetal heart rate and mean arterial blood pressure showed little hypoxia-induced change, although fetal heart rate was significantly increased over the first 2 hours (p less than 0.05). The percent time fetal breathing movements, electroocular activity, and nuchal muscle activity likewise showed little hypoxia-induced change. CONCLUSION The cardiovascular and biophysical response of the preterm fetus to induced hypoxemia is thus much less pronounced than that of the older gestational-aged fetus; this difference may impact on survival and the success of antenatal assessment protocols.

The role of carbon dioxide in the generation of human fetal breathing movements

To determine the role of carbon dioxide in the generation of fetal respiratory movements, the effect of induced maternal hypocapnia and hypercapnia on fetal breathing movements, gross body movements, and fetal heart rate was studied in 12 healthy pregnant women near term. Patients were studied for a 1-hour control period breathing room air followed by four randomized 15-minute study periods with patients breathing either room air, a prepared gas mixture with 2% or 4% carbon dioxide, or undergoing controlled hyperventilation as determined by monitoring end-tidal PCO2. The percentage of time fetal breathing movements correlated significantly with maternal end-tidal PCO2 (r = 0.62, p less than 0.01), increasing with maternal breathing of 2% and 4% carbon dioxide and decreasing with maternal hyperventilation. Fetal gross body movements, fetal heart rate, and fetal heart rate variability showed no significant changes. It is concluded that as in adults, the carbon dioxide level in fetuses is an important stimulus for the generation of respiratory movements, acting independent of a change in behavioral state. It is hypothesized that tonic carbon dioxide level input is an important determinant of fetal respiratory center drive, but little or no phasic carbon dioxide input exists because of continuous placental excretion, thus resulting in the episodic occurrence of breathing movements with changes in the fetal behavioral state.

The effects of 'sleep promoting agents' on behavioural state in the ovine fetus.

Fetal behavioural states, with similarities to adult sleep states, exist in both the human and ovine fetus near term. The purpose of the present study was to determine the effects of intracerebral administration of pharmacologic agents, known to affect sleep states in the adult, on fetal behavioural states and physiologic correlates using the chronically catheterized ovine fetus near term. Each drug was infused into either the cisterna magna or lateral ventricle for 90 min in one of two doses. Carbachol (1.35 x 10(-5) and 4.25 x 10(-6) M) led to an increase in low-voltage ECOG, eye movement and FBM activities, while scopolamine (4.68 x 10(-4) and 1.56 x 10(-4) M) led to a decrease in low-voltage ECOG and eye movement activity with an increase in high-voltage ECOG activity. L-5-Hydroxytryptophan (5-HTP) (2.04 x 10(-3) and 6.81 x 10(-4) M) infusion led to an increase in FBM, while VIP (3.00 x 10(-7) and 1.00 x 10(-7) M) infusion had no effect on fetal behavioural state parameters. Study results indicate that fetal behavioural states can be altered pharmacologically and in a manner similar to that seen in the adult but with notable differences that may relate to species, developmental or dose-response issues.

Placental compared with umbilical cord blood to assess fetal blood gas and acid-base status.

OBJECTIVE: To estimate the extent to which placental cord blood sampled from the umbilical cord at its insertion into the placenta and after delivery of the placenta, is in agreement with umbilical cord blood sampled from a clamped segment of the umbilical cord after delivery of the infant, for the assessment of fetal blood gas, acid-base status, and hemoglobin levels at birth. METHODS: Forty-eight patients were studied with arterial and venous blood sampling from the umbilical cord and from the placental cord insertion, with subsequent measurement of blood gases, pH, base excess, O2 saturation, and hemoglobin. The relationships of corresponding measurements from the placental and umbilical vein and from the placental and umbilical artery were analyzed using regression analysis, paired analysis of grouped means, and by estimating limits of agreement. RESULTS: The relationships between placental and umbilical cord blood measurements were described using a linear mathematical model, and although respective measurements were all significantly related (P < .01), this was strongest for both venous and arterial base excess and hemoglobin measurements (r values 0.91 to 0.99) and variably weaker for venous and arterial Po2 (and thereby O2 saturation measurements [r values 0.36 to 0.89]) and arterial Pco2 (and thereby pH measurements [r values 0.66 to 0.73]). Whereas base excess and hemoglobin measurements for both the venous and arterial placental and umbilical cord bloods were close in value over the range of values studied, Po2 and thereby O2 saturation values were variably lower in the placental vein compared with the umbilical vein, while Pco2 values were variably lower and thereby pH values conversely higher in the placental artery compared with the umbilical artery. Limits of agreement as a measure of the difference between paired placental and umbilical cord blood measurements were such that only those for base excess and hemoglobin were likely narrow enough to be acceptable for clinical purposes. CONCLUSION: Placental cord blood provides for a close estimate of fetal base excess and hemoglobin status at birth, but with more error for Po2 and thereby O2 saturation and Pco2 and thereby pH due to continued blood gas exchange within and across the placenta after cord clamping. LEVEL OF EVIDENCE: III

Regional brain blood flow in the ovine fetus during transition to the low-voltage electrocortical state

Sequential changes in cerebral blood flow and regional distribution were studied in nine chronically catheterized fetal sheep during the transition to the low-voltage ECOG (REM) state to determine the time course for blood flow change within the brain and whether executive centres for REM state generation might thus be identified. Blood flows were measured during the first, second and third minutes after the transition to the low-voltage ECOG state and during the third minute of the subsequent high-voltage ECOG (NREM) state using the radioactive labelled microsphere technique. Blood flow to the brain was increased during the low-voltage REM state when compared to that of the high-voltage NREM state, with the increase evident when measured during the first minute after the state transition and with no sequential change thereafter. Regional blood flow increases during the low-voltage state were greatest to those areas variously associated with the generation of REM state activity, but were again remarkably stable through the first 3 minutes after the state transition. This rapid increase in blood flow within the brain and the regional hierarchy for such, supports the participation of multiple anatomical areas which are highly integrated and act in concert to give rise to what is known as the REM state.

Cerebral metabolism during sustained hypoxemia in preterm fetal sheep

OBJECTIVE The purpose of this study was to determine the effect of sustained hypoxia with resulting metabolic acidosis on cerebral metabolism in the preterm ovine fetus. STUDY DESIGN Twelve fetal sheep were studied at 0.75 of gestation during a normoxic control period, after 1 and 8 hours of sustained hypoxemia, and again after a 1-hour recovery period. Cerebral arteriovenous differences were analyzed for oxygen content, blood gases and pH, glucose, and lactate. Cerebral blood flow was measured with the microsphere technique. RESULTS Induced hypoxemia resulted in a variable degree of fetal acidemia that was entirely metabolic. Although cerebral oxidative metabolism was well maintained throughout the study, cerebral glucose consumption was variably increased when measured after 1 hour of sustained hypoxemia, with a subsequent decrease after 1 hour of recovery. Although lactate was neither consumed nor produced during the control period, by 8 hours of hypoxic study a significant efflux of lactate from the brain was evident, which continued into the recovery period. CONCLUSION Sustained hypoxemia results in an increase in the anaerobic metabolism of glucose by the preterm fetal brain independent of any change in cerebral oxidative metabolism, which may give rise to an accumulation of lactic acid and contribute to neurologic impairment.

Activation of the fetal hypothalamic-pituitary-adrenal axis with prolonged and graded hypoxemia

The purpose of this study was to determine whether activation of the hypothalamic-pituitary-adrenal (HPA) axis and uteroplacental prostaglandin (PG) response occur before metabolic deterioration with a progressive decrease in fetal oxygenation. Twenty-one chronically catheterized fetal sheep were studied between 126 and 135 days’ gestation during a 24-hour normoxic control period and subsequently during 4 experimental days of either prolonged and graded hypoxemia, induced by progressively lowering the maternal inspired oxygen concentration (induced hypoxia, n = 12), or continued study on room air (control, n = 6; spontaneous hypoxia, n = 3). Fetal arterial blood was sampled daily for blood gases and pH, immunoreactive ACTH, Cortisol, and PGE2. Placental cotyledons were obtained at the end of the experiment for measurement of prosta-glandin-H synthase (PGHS) enzymatic activity. For all hypoxia group measurements, progressive reduction in fetal oxygenation resulted in little change in either plasma ACTH or Cortisol until arterial O2 saturation was close to 30% with metabolic acidosis onsetting. This was in keeping with activation of the HPA axis at this time, because ACTH and Cortisol values showed a strong linear correlation (r = 0.77, P < .01). Fetal plasma PGE2 concentrations and cotyledonary PGHS enzymatic activity, although somewhat higher in the hypoxia group animals, were not changed significantly. In response to prolonged and graded hypoxemia in the ovine fetus, activation of the HPA axis occurs only when the degree of hypoxemia is pronounced and close to that associated with metabolic deterioration, which may limit the time for any uteroplacental response and the ability to initiate labor.