-
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE: Recent guidelines classify variable decelerations (VAR) without detail as to degree of depth. We hypothesized that VAR severity is highly correlated with fetal base deficit (BD) accumulation. STUDY DESIGN: Seven near-term fetal sheep underwent series of graded umbilical cord occlusions (UCO) resulting in mild (30 bpm decrease), moderate (60 bpm decrease) or severe (decrease of 90 bpm to baseline <70 bpm) VAR at 2.5 min intervals. RESULTS: Mild, moderate and severe variable decelerations increased fetal BD (0.21±0.03, 0.27±0.03, and 0.54±0.09 mEq/L per min) in direct proportion to severity. During recovery, fetal BD cleared at 0.12 mEq/l per min. CONCLUSION: In this model, ovine fetuses can tolerate repetitive mild and moderate VAR with minimal change in BD and lactate. In contrast, repetitive severe VAR may result in significant BD increases, dependent upon frequency. Modified guideline differentiation of mild/moderate versus severe VAR may aid in the interpretation of fetal heart rate tracings and optimization of clinical management paradigms.
American journal of obstetrics and gynecology 10/2012; · 3.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Fetal hypoxic episodes may occur antepartum with the potential to induce systemic and cerebral inflammatory responses thereby contributing to brain injury. We hypothesized that intermittent umbilical cord occlusions (UCOs) of sufficient severity but without cumulative acidosis will lead to a fetal inflammatory response. Thirty-one chronically instrumented fetal sheep at ∼0.85 of gestation underwent four consecutive days of hourly UCOs from one to three minutes duration for six hours each day. Maternal and fetal blood samples were taken for blood gases/pH and plasma interleukin (IL)-1β and IL-6 levels. Animals were euthanized at the end of experimental study with brain tissue processed for subsequent counting of microglia and mast cells. Intermittent UCOs resulted in transitory fetal hypoxemia with associated acidemia which progressively worsened the longer umbilical blood flow was occluded, but with no cumulative blood gas or pH changes over the four days of study. Fetal arterial IL-1β and IL-6 values showed no significant change regardless of the severity of the UCOs, nor was there any evident impact on the microglia and mast cell counts for any of the brain regions studied. Accordingly, intermittent UCOs of up to three minutes duration with severe, but limited fetal hypoxemia and no cumulative acidemia, do not result in either a systemic or brain inflammatory response in the pre-term ovine fetus. However, fetal IL-1B and IL-6 values were found to be well correlated with corresponding maternal values supporting the placenta as a primary source for these cytokines with related secretion into both circulations. Female fetuses were also found to have higher IL-1β levels than males, indicating that gender may impact on the fetal inflammatory response to various stimuli.
PLoS ONE 01/2012; 7(6):e39043. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study aimed to determine the effect of varying degrees of intermittent umbilical cord occlusion (UCO) on arterial elastin composition. Over 4 days, chronically catheterized late gestation fetal sheep received 5 total UCO per day lasting 1 min/h (mild group: n = 6), 2 min/h (moderate group: n = 4), 3 min/h (severe group; n = 6); or no occlusion (control group: n = 7). Each group was evaluated for elastin content of the carotid and superior mesenteric artery (SMA), the arterial pressure response to UCO, and plasma cortisol concentration. Elastin content of the carotid artery was significantly increased by severe UCO (9.5 µg/mg versus 6.4 µg/mg; P < .05) and insignificantly increased in mild and moderate groups, whereas UCO had no effect on elastin content of the SMA. This dose- and site-dependent response of the vasculature appears attributable to the hemodynamic changes that accompany UCO.
Reproductive sciences (Thousand Oaks, Calif.) 10/2011; 18(10):990-7. · 2.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study examined perturbed aortic development and subsequent wall stiffening as a link to later cardiovascular disease. Placental insufficiency was induced in pregnant guinea pigs at midgestation by uterine artery ligation. Near term, fetuses were killed and defined as normal birth weight (NBW), low birth weight (LBW), and intrauterine growth restricted (IUGR). Offspring were classified according to birth weight and killed in adulthood. Collagen and elastin content of aortas were analyzed using Sirius red and orcein staining, respectively. Immunofluorescence was used for detection of α-actin and nonmuscle myosin heavy chain (MHC-B), a marker of synthetic-type vascular smooth muscle cells (VSMCs). Ex vivo generation of length-tension curves was performed with aortic rings from adult offspring. Relative elastic fiber content was decreased by 10% in LBW and 14% in IUGR compared with NBW fetuses. In adulthood, relative elastic fiber content was 51% lower in LBW vs. NBW, and the number of elastic laminae adjusted for wall thickness was 25% lower in LBW (P < 0.01). The percent area stained for MHC-B was sixfold higher in LBW vs. NBW fetuses (P < 0.0001) and threefold higher in LBW vs. NBW adult offspring (P < 0.05). The increase in MHC-B in LBW offspring concurred with a 41% increase in total collagen content and a 33 and 56% increase in relative and total α-actin content, respectively (P < 0.05). Thus aortic wall stiffening in adulthood can be traced to altered matrix composition established under suboptimal intrauterine conditions that is amplified postnatally by the activity of synthetic VSMCs.
AJP Regulatory Integrative and Comparative Physiology 09/2011; 301(6):R1731-7. · 3.34 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We have designed an automated method for analyzing electrocortical (ECoG) activity in the near-term ovine fetus to process and quantitatively classify large amounts of data rapidly and objectively. Seven chronically catheterized fetal sheep were studied for 8h each at ~0.9 of gestation with continuous recording of ECoG activity using a computerized data acquisition system. Multiple ECoG amplitude and frequency parameters were scored from which we established animal specific parameter cut-off values as well as population based duration cut-off values to distinguish low-voltage/high frequency (LV/HF) and high-voltage/low frequency (HV/LF) state epochs, and indeterminate voltage/frequency (IV/F) and transition period activities. We have shown that the incidence of the predominant LV/HF and HV/LF activity states at 45% and 36% of the time, respectively, is comparable to that previously reported using semi-quantitative techniques with visual analysis. However, the duration of these state epochs is considerably shorter due to the detection of brief periods of IV/F activity which would be difficult to capture using visual analysis. Importantly, our findings in the healthy ovine fetus near-term using this automated ECoG scoring methodology now provide a framework from which to study maturational events in younger animals, and under adverse pregnancy conditions.
Brain research 05/2011; 1402:30-7. · 2.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We have studied the maturation of electrocortical (ECoG) activity in fetal sheep and the impact of chronic hypoxemia using a growth restriction model with placental embolizations. Twenty chronically catheterized fetal sheep (control, n=9; hypoxemic, n=11) were monitored at 116-119, 121-126 and 128-134 days gestational age (term=145 days), with ECoG activity scored using automated analysis of amplitude and frequency components to distinguish low-voltage/high frequency (LV/HF) and high-voltage/low frequency (HV/LF) state epochs, along with indeterminate voltage/frequency (IV/F) and transition period activities. We have shown that multiple aspects of ECoG state activity in the ovine fetus undergo maturational change as electrophysiologic measures of brain development. With chronic fetal hypoxemia, some maturational changes continue to occur, i.e. ECoG activity amplitude and 95% SEF, indicating the resiliency of these parameters to adverse conditioning. However, some maturational changes were altered, i.e. LV/HF and HV/LF incidence and duration, and likely regulated and adaptive with a decrease in the brain's nonessential energy needs, while some were altered, i.e. IV/F incidence and duration, and state transition times, and likely indicating a degree of aberrant development in associated control circuitries. This may then have consequences for disturbed sleep-wake patterns during later life and for adverse neurologic sequelae known to be increased in humans born with growth restriction.
Brain research 05/2011; 1402:38-45. · 2.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study explored arterial remodelling in fetuses growth restricted by hypoxia. Chronically catheterized fetal sheep were made moderately or severely hypoxic by placental embolization for 15 days starting at gestational age 116-118 (term ∼147 days). Cross-sections of the aorta were analysed for collagen and elastin content using histological procedures, while immunofluorescence was applied to measure markers of vascular smooth muscle cell (VSMC) type. In frozen aortae quantitative PCR was used to measure mRNA levels of extracellular matrix (ECM) precursor proteins as well as molecular regulators of developmental and pathological remodelling. Relative to Control (n =6), aortic wall thickness was increased by 23% in the Moderate group (n =5) and 33% (P <0.01) in the Severe group (n =5). Relative to Control, the Severe group exhibited a 5-fold increase in total collagen content (P <0.01) that paralleled increases in mRNA levels of procollagen I (P <0.05) and III and transforming growth factor β (TGF-β1) (P <0.05). The percentage area stained for α-actin was inversely related to fetal arterial oxygen saturation (P <0.05) and total α-actin content was 45% higher in the Moderate group and 65% (P <0.05) higher in the Severe group, compared to Control. A 12% and 39% (P <0.05) reduction in relative elastic fibre content was observed in Moderate and Severe fetuses, respectively. mRNA levels of the elastolytic enzyme, matrix metalloproteinase-2 (MMP-2) were inversely correlated with fetal arterial oxygen saturation (P <0.05) (Fig. 7) and mRNA levels of its activator, membrane-type MMP (MTI-MMP), were elevated in the Severe group (P <0.05). Marked neointima formation was apparent in Severe fetuses (P <0.05) concomitant with an increase in E-selectin mRNA expression (P <0.05). Thus, aberrant aortic formation in utero mediated by molecular regulators of arterial growth occurs in response to chronic hypoxaemia.
The Journal of Physiology 05/2011; 589(Pt 13):3319-32. · 4.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Severe fetal acidemia during labour with arterial pH below 7.00 is associated with increased risk of hypoxic-ischemic brain injury. Electronic fetal heart rate (FHR) monitoring, the mainstay of intrapartum surveillance, has poor specificity for detecting fetal acidemia. We studied brain electrical activity measured with electrocorticogram (ECOG) in the near term ovine fetus subjected to repetitive umbilical cord occlusions (UCO) inducing FHR decelerations, as might be seen in human labour, to delineate the time-course for ECOG changes with worsening acidemia and thereby assess the potential clinical utility of fetal ECOG.
Ten chronically catheterized fetal sheep were studied through a series of mild, moderate and severe UCO until the arterial pH was below 7.00. At a pH of 7.24 ± 0.04, 52 ± 13 min prior to the pH dropping <7.00, spectral edge frequency (SEF) increased to 23 ± 2 Hz from 3 ± 1 Hz during each FHR deceleration (p<0.001) and was correlated to decreases in FHR and in fetal arterial blood pressure during each FHR deceleration (p<0.001).
The UCO-related changes in ECOG occurred in advance of the pH decreasing below 7.00. These ECOG changes may be a protective mechanism suppressing non-essential energy needs when oxygen supply to the fetal brain is decreased acutely. By detecting such "adaptive brain shutdown," the need for delivery in high risk pregnant patients may be more accurately predicted than with FHR monitoring alone. Therefore, monitoring fetal electroencephalogram (EEG, the human equivalent of ECOG) during human labour may be a useful adjunct to FHR monitoring.
PLoS ONE 01/2011; 6(7):e22100. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Studies during early development have shown that the precursor availability of amino acids directly affects protein synthesis both at the whole-body level and for select organ tissues, although this has not been studied for the brain.
We utilized a mixed amino acid infusate and an insulin euglycemic clamp technique in the ovine fetus near term, with increases and decreases in circulating amino acid levels of ∼30 to 40% on average, and determined the impact on cerebral protein synthesis.
Fetal sheep received a 6-hour infusion of Primene® 10% (amino acid infusate group) or a co-infusion of insulin and 10% dextrose (insulin/dextrose infusate group) together with a continuous infusion of L-[1-(13)C]-leucine. Measurements were obtained for fetal plasma leucine enrichment at steady-state and brain tissue intracellular free and protein-bound leucine enrichment at necropsy, followed by the determination of cerebral protein fractional synthetic rates (FSR).
Protein FSR for the cerebral cortex averaged ∼58 and ∼39%/day when using the intracellular free and plasma enrichment values for the precursor pool measurements, respectively, providing for maximal and minimal FSR values, and with little difference between the amino acid and insulin/dextrose groups, although significantly higher than respective values for the cerebellum.
Accordingly, there was no evidence of a differential effect of increases versus decreases in circulating amino acids on cerebral protein synthesis as studied, which may be attributed to the saturable nature of the blood-brain barrier transporters for amino acids.
Neonatology 05/2010; 98(4):297-304. · 2.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We have determined venous and arterial cord blood levels for IL-6 and TNFalpha at the time of delivery to assess gestational tissue versus fetal sources in labouring and non-labouring patients at term, and the relationship to labour events.
Fifty-five patients were studied (elective cesarean section n=24, and labouring n=31) with blood sampling from a clamped segment of cord after delivery of the fetus and from the cord at its insertion into the placenta after delivery of the placenta, with subsequent measurement of blood gases, pH, IL-6 and TNFalpha.
Umbilical cord levels for IL-6 were increased by 4 fold in low risk labouring patients, and a further 6 fold when showing histologic chorioamnionitis, but with no evident effect of nuchal cord with 'variable' fetal heart rate decelerations, fetal acidemia, nor of labour duration. IL-6 levels from the cord at its insertion into the placenta were generally higher than those from the respective umbilical levels indicating that placental release of IL-6 into cord blood must be occurring. However, a consistent venoarterial difference for IL-6 and thereby a net flux from the placenta could not be demonstrated. TNFalpha levels for both patient groups were uniformly low for all of the cord measurements with no significant differences noted.
Umbilical cord levels for IL-6 are increased in low risk labouring patients at term in the absence of evident infection which likely involves both gestational tissue and fetal contributions. Cord levels for IL-6 are further increased in low risk labouring patients showing histologic chorioamnionitis which might then contribute to newborn morbidity in these pregnancies.
Early human development 02/2010; 86(2):113-7. · 2.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We hypothesized that repetitive umbilical cord occlusions (UCOs) with worsening acidosis will lead to a fetal inflammatory response.
Chronically instrumented fetal sheep underwent a series of UCOs until fetal arterial pH decreased to <7.00. Maternal and fetal blood samples were taken for blood gases/pH and plasma interleukin (IL)-1B and IL-6 levels. Animals were euthanized at 24 hours of recovery with brain tissue processed for subsequent measurement of microglia and mast cell counts.
Repetitive UCOs resulted in a severe degree of fetal acidemia. Fetal plasma IL-1B values were increased approximately 2-fold when measured at maximal fetal acidosis and again at 1-2 hours of recovery. Fetal microglia cells were increased approximately 2-fold in the white matter and hippocampus, while mast cells were increased approximately 2-fold in the choroid plexus and now evident in the thalamus when analyzed at 24 hours recovery.
Repetitive UCOs leading to severe acidemia in the ovine fetus near term will result in an inflammatory response both systemically and locally within the brain.
American journal of obstetrics and gynecology 11/2009; 202(1):82.e1-9. · 3.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Nine fetal sheep were surgically prepared with placement of electrocortical and electro-ocular electrodes for monitoring behavioural state activity to determine the relationship of adjacent low-voltage (LV)/rapid eye movement (REM) and high-voltage (HV)/non-(N)REM epoch durations and the inter-epoch transition time. Animals were subsequently studied over an 8-hour period with behavioural state epoch duration and transition time assessed using paired t-test and regression analysis. For all animals, the duration of LV/REM epochs averaged 14.8+/-0.8 (SEM) minutes which was significantly greater than that for HV/NREM epochs at 10.1+/-0.5 min (P<0.01). The mean duration of LV/REM to HV/NREM transition periods at 93+/-3 s was also significantly longer than that for the HV/NREM to LV/REM transition periods at 78+/-6 s (P<0.05). HV/NREM epoch duration was positively correlated with the prior LV/REM epoch duration with a group mean correlation of 0.59 (P<0.01). HV/NREM epoch duration was likewise positively correlated with the subsequent LV/REM epoch duration with a group mean correlation of 0.46 (P<0.01). We conclude that the transition time into HV/NREM is longer than that into LV/REM for the ovine fetus near term which may involve differences in the rate of maturation of cycling control mechanisms for these two behavioural states and earlier development of REM-on versus REM-off pathways. The positive LV/REM-HV/NREM linkage relationships also support a homeostatic model of behavioural state control whereby LV/REM and HV/NREM timings are both controlled by accumulation of propensity for these states during the other state and favours an interactive process between these states in the brain's growth and development.
Brain research 12/2008; 1250:149-56. · 2.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Increasing frequency of severe variable decelerations is associated with acidemia. However, there is little understanding of its development or normalization rate.
To quantify the time course of acidemia, 10 near-term fetal sheep underwent a series of mild (1 minute every 5 minutes), moderate (1 minute every 3 minutes), and severe (1 minute every 2 minutes) umbilical cord occlusions (UCO), lasting 1 hour each or until fetal arterial pH decreased to less than 7.00.
Each minute of UCO resulted in base deficit (BD) and lactate increases at rates of 0.56 and 0.35 mmol/L per minute, respectively. During a 2 h recovery, BD and lactate normalized at rates of 0.09 and 0.04 mmol/L per minute. BD correlated highly with lactate (r = 0.95; P < .001).
Our findings in the near-term ovine fetus suggest that the knowledge of fetal BD deterioration and recovery rates can aid assessing fetal acidemia during labor.
American journal of obstetrics and gynecology 12/2008; 200(2):200.e1-7. · 3.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We have determined the developmental change in immunoreactivity for brain-derived neurotrophic factor and its high-affinity tyrosine kinase receptor, TrkB, in the ovine fetal brain with advancing gestation and in response to intermittent umbilical cord occlusion, which might then contribute to adverse neurodevelopment. Fetal sheep (control and experimental groups at 0.75 and 0.90 of gestation) were studied over 4 days with umbilical cord occlusions performed in the experimental group animals by complete inflation of an occluder cuff for 90 seconds every 30 minutes for 3 to 5 hours each day. Animals were then euthanized and the fetal brains perfusion fixed and prepared for subsequent histology with the distribution of brain-derived neurotrophic factor and tyrosine kinase receptor immunoreactivity determined by immunohistochemistry. In the control group animals brain-derived neurotrophic factor immunoreactivity decreased in the gray matter, thalamus, and hippocampus but increased in the white matter, while tyrosine kinase receptor immunoreactivity decreased in all regions (most P < .01), with advancing gestation consistent with the developmental change from neurogenesis/gliagenesis to myelination over this time period. Intermittent umbilical cord occlusion as studied with severe but limited hypoxemia resulted in a variable decrease in brain-derived neurotrophic factor and tyrosine kinase receptor immunoreactivity for all brain regions in the preterm animals (most P < .01) when protein turnover is higher, but a selective increase in brain-derived neurotrophic factor immunoreactivity in the hippocampus of the near-term animals consistent with a heightened vulnerability for necrotic/apoptotic injury at this time. As such, brain-derived neurotrophic factor-tyrosine kinase receptor in the ovine fetal brain may be altered with intermittent hypoxic insults over the latter part of pregnancy with potential for longer term neurologic consequences.
Reproductive sciences (Thousand Oaks, Calif.) 10/2008; 15(9):895-905. · 2.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Amino acid infusate (Primene) and insulin euglycemic (insulin + 10% dextrose) clamp techniques were used in the ovine fetus near term and the impact on the incidence of low-voltage and high-voltage electrocortical (ECOG) activities was determined. Fetal sheep were studied over a 2-hour control period and a subsequent 6-hour experimental period.With the Primene infusion, the basic and neutral amino acids were increased by 43% and 25%, respectively, whereas the acidic amino acids showed little change. With the insulin/dextrose infusion, the basic and neutral amino acids decreased by 48% and 30%, respectively, whereas the acidic amino acids were again little changed. A small fall in arterial oxygen saturation and an increase in fetal heart rate for both groups can be attributed to an insulin-mediated increase in fetal metabolic rate. Despite the moderate increases and decreases in circulating amino acid levels, there was no significant change in the mean percent time or duration of fetal ECOG activities for either study group.
Reproductive sciences (Thousand Oaks, Calif.) 06/2008; 15(7):710-9. · 2.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although antenatal glucocorticoids have well-known benefits for infants who are born preterm by the enhancement of pulmonary maturation, adverse effects on brain growth and development have been reported in several animal-based studies. We have used the chronically catheterized ovine fetus to determine the effects of synthetic glucocorticoids that are administered at doses used clinically on cerebral protein synthesis during early brain development using [13C]-leucine tracer method.
Chronically instrumented pregnant sheep at 0.85 gestation received 2 intramuscular injections of betamethasone at 170 microg/kg maternal weight or saline 24 hours apart together with a continuous infusion of L-[1-(13)C]-leucine to the fetus on the second day of experimentation. Measurements were obtained for fetal plasma leucine enrichment at steady-state and brain tissue intracellular free and protein-bound leucine enrichment at necropsy, followed by the determination of cerebral protein fractional synthetic rates (FSRs). A coefficient of variation was determined for plasma and tissue enrichment measurements to assess the inherent methodologic variance with the use of [13C]-leucine tracer technology.
The cerebral protein FSR averaged approximately 112% per day and approximately 35% per day when the intracellular free and plasma enrichment values were used for the precursor pool measurements, respectively, providing for maximal and minimal FSR values. There were no differences between cortical and cerebellar tissues nor between the saline control and the betamethasone animal groups. The coefficient of variation for the plasma-enrichment values averaged approximately 2%; the coefficient of variation for the tissue enrichment values averaged approximately 10%, with an inverse relationship between the [13C]-leucine enrichment values and the coefficient of variation values.
Although cerebral FSR values for the preterm ovine fetus are high and indicate high rates of protein synthesis and degradation, we found no evidence that these are altered by betamethasone as used clinically and thereby do not account for the reported structural alterations in the brain after a single-course of antenatal glucocorticoids.
American journal of obstetrics and gynecology 02/2008; 198(1):103.e1-6. · 3.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although the benefits of antenatal glucocorticoids are well known for infants who are born preterm, there is increasing evidence of adverse effects on brain development, which may relate to altered metabolic activity. We have determined the effect of maternal glucocorticoid administration at doses that are used clinically on cerebral substrate metabolism in the preterm ovine fetus.
Chronically instrumented pregnant sheep at 0.85 gestation received 2 intramuscular injections of betamethasone at 170 microg/kg maternal weight (n = 13) or saline (n = 10) 24 hours apart together with a continuous infusion of L-[1-(13)C] leucine to the fetus. Fetal cerebral substrate arteriovenous differences (O2, glucose, leucine, leucine enrichment) and blood flow (fluorescent microspheres) were measured at baseline, 24 hours after the first betamethasone/saline injection (late beta/saline 1), and 4 hours after the second betamethasone/saline injection (early beta/saline 2) to obtain substrate deliveries and fractional extractions.
Fetal pH, blood gases, and metabolites were little changed in either group over the course of the study, except for glucose values in the betamethasone animals, which increased 1.4- and 1.9-fold, measured late beta 1 and early beta 2, respectively (both P < .01). Cerebral blood flow, although little changed in the control group or at late beta 1, was decreased at early beta 2 by approximately 30% (P < .05). As such, early beta 2 animals showed a decrease in cerebral O2 delivery of approximately 20% (P = .06) and conversely an increase in cerebral glucose delivery of 1.4- and 1.3-fold at late beta 1 (P < .05) and early beta 2 (P = .08), respectively. Fractional extraction values for these substrates were not changed significantly, which resulted in corresponding decreases in estimated O2 uptake and increases in estimated glucose uptake, such that the glucose/oxygen quotient (as an index of glucose oxidative metabolism) measured 1.6 at early beta 2, which was considerably greater than baseline values at 1.1 (P < .05). Fractional extraction values for leucine and leucine enrichment averaged 2%-3%; although somewhat higher in the betamethasone animals, none of the between or within group differences were significant.
Fetal cerebral metabolism in the preterm ovine fetus is altered by antenatal glucocorticoid administration, which is comparable with that used in human pregnancy, and includes an acute decrease in cerebral blood flow and a probable increase in anaerobic glucose metabolism. Although likely of short duration in conjunction with peak glucocorticoid levels, these metabolic effects may place the developing brain at added risk for superimposed hypoxic injury.
American journal of obstetrics and gynecology 01/2008; 198(1):105.e1-9. · 3.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to further delineate the impact of preterm chorioamnionitis on a spectrum of neonatal outcomes using a large tertiary hospital population.
The perinatal/neonatal and placental pathology databases of St. Joseph's Health Care, London, Ontario, Canada, were used to obtain the umbilical cord gas and pH values, incidence of adverse neonatal outcomes, patient demographics, and placental pathology reports for all preterm (25 to 34 weeks of gestation), singleton, liveborn infants with no major anomalies who were delivered with spontaneous onset of labor or for suspected chorioamnionitis between November 1, 1995, and October 31, 2003. Patient groupings on the basis of placental inflammation and clinical chorioamnionitis were studied by a comparison of mean values and incidences for those neonatal outcomes that were available from the database with the use of linear and logistic regression analysis and controlling for potentially confounding variables.
There were 660 infants who met the inclusion criteria and had placental pathology available of whom 368 (56%) had no placental inflammation, 114 (17%) had placental chorioamnionitis, and 178 (27%) had placental funisitis. Umbilical cord partial pressure oxygen and base excess values were generally higher in the placental inflammation/clinical chorioamnionitis groups, in keeping with enhanced oxygen delivery and an overall decrease in the metabolic contribution to acidosis attributed to altered lactate metabolism in these infants. After adjusting for confounders (primarily differences in gestational age), the incidence of respiratory distress syndrome was significantly decreased in the placental inflammation/clinical chorioamnionitis groups, in keeping with cytokine-induced synthesis of surfactant proteins in these infants. Although the incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, and periventricular leukomalacia was generally unchanged among the groups studied, that for intraventricular hemorrhage and periventricular leukomalacia was lowest in the placental inflammation/no clinical chorioamnionitis patients and highest in the placental inflammation/clinical chorioamnionitis patients, suggesting a differential effect of clinical chorioamnionitis for these outcomes.
Overall, infants born preterm with intrauterine infection were better oxygenated and showed less metabolic acidosis at birth and had incidences of respiratory distress syndrome and intraventricular hemorrhage, which were variably lower. Although there are likely threshold levels of inflammatory cytokines that do give rise to adverse outcome, a minimal level of cytokines may also be beneficial for the transition at birth from intrauterine to extrauterine existence when preterm pending the circumstances (ie, exposure to antenatal steroids) and emphasizing the complex relationship among preterm birth, infection, and adverse neonatal outcome.
American journal of obstetrics and gynecology 12/2006; 195(5):1357-65. · 3.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In this study we sought to determine the effect of brief repeated umbilical cord occlusions (rUCO) on surfactant protein (SP) mRNA levels in the fetal sheep lung at two different gestational ages.
Fourteen fetuses at 112 to 115 days' gestation (control n = 7, rUCO n = 7) and 15 fetuses at 130 to 133 days' gestation (control n = 7, rUCO n = 8) were studied over 4 successive days with rUCO of 90 seconds duration performed every 30 minutes for 3 to 5 hours each day in the rUCO animals. Blood samples were collected for corticotrophin (ACTH) and cortisol measurements. Animals were killed within 1 hour of the final cord occlusion. SP-A, -B, -C, and -D mRNA levels were determined in lung tissue using a ribonuclease protection assay.
Cord occlusions resulted in temporary increases in circulating ACTH on day 1 with both gestational ages, but the elevations were blunted by day 4. Plasma cortisol levels increased transiently with the larger effect being observed on day 4, in particular with the near-term group. With advancing gestational age there was a significant (P < .05) increase in the level of SP-A (control 112-115 days: 0.01 +/- 0.01 vs control 130-133 days: 0.07 +/- 0.02 fmol/mg RNA), SP -B (control 112-115 days: 0.02 +/- 0.01 vs control 130-133 days: 0.07 +/- 0.01 fmol/mg RNA) and SP-C (control 112-115 days: 0.13 +/- 0.09 vs control 130-133 days: 0.51 +/- 0.10 fmol/mg RNA), but not SP-D mRNA levels (control 112-115 days: 0.002 +/- 0.002 vs control 130-133 days: 0.01 +/- 0.002 fmol/mg RNA). At 112 to 115 days, there was no significant change in any of the SP mRNA levels following rUCO compared to controls. However, the same regime of rUCO at 130 to 133 days resulted in an 85% reduction in SP-A and SP-B mRNA content and a 66% reduction in SP-C mRNA levels compared to controls.
The surprising decrease in SP-A and SP-B mRNA levels, which contrasts with other studies, suggests intermittent asphyxial episodes impact differently on surfactant apoprotein mRNA expression than does prolonged hypoxia.
Journal of the Society for Gynecologic Investigation 10/2005; 12(7):510-7. · 2.26 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The sleep-wake cycle has been studied extensively in both adult and fetal mammalian species with emphasis in different areas. Fetal studies have focused on characterization of behavioral states and responses to challenges such as hypoxia, and there have been relatively fewer studies that have investigated the control of fetal behavioral state. The objective of this study was to determine whether cerebral blood flow during cholinergically induced fetal behavioral states was similar to that during spontaneous fetal behavioral states in chronically catheterized near-term sheep fetuses. Injection of carbachol (1.25 microg) into the cisterna magna increased the duration of the subsequent low-voltage electrocortical epoch. Scopolamine infusion (0.3 mg) increased the duration of the subsequent high-voltage electrocortical activity epoch. Cerebral blood flow and oxygen delivery were higher during both spontaneous and carbachol-induced low-voltage/rapid eye movement behavioral state than during spontaneous and scopolamine-induced high-voltage/non-rapid eye movement behavioral state. Thus, pharmacologic manipulation of fetal behavioral state induced a state that resembled spontaneous fetal behavioral state both electrophysiologically and metabolically. This study shows that inducing extended periods of a desired fetal behavioral state is possible and that this method may be used to study their function.
Pediatric Research 06/2005; 57(5 Pt 1):667-73. · 2.70 Impact Factor
