Microtubule-associated protein 2 and synaptophysin in the preterm and near-term ovine fetal brain and the effect of intermittent umbilical cord occlusion.

We have determined the change in immunoreactivity (IR) for microtubule-associated protein 2 (MAP-2) and synaptophysin (SYN) as markers for dendritic and presynaptic nerve development, respectively, in the ovine fetal brain with advancing gestation and in response to intermittent umbilical cord occlusion (UCO), which might then contribute to adverse neurodevelopment. Fetal sheep (control and experimental groups preterm at 111-115 and near term at 132-138 days of gestation; term = 145 days) were studied over 4 days with UCOs performed by inflation of an occluder cuff for 90 seconds every 30 minutes for 3 to 5 hours each day. Animals were then euthanized and fetal brains assessed for IR of MAP-2 and SYN. In control animals, the IR of SYN increased in the gray matter with advancing gestation consistent with a developmental increase in presynaptic vesicles and/or nerve terminals as expected; however, the IR of MAP-2 decreased in all brain regions studied, suggesting concurrent refinement in dendritic branching and spine development. Intermittent UCO as studied with marked but limited hypoxemia resulted in a decrease in IR of SYN for the brain regions of the preterm animals when protein turnover is higher and indicates decreased presynaptic vesicle formation; whereas, MAP-2 IR was selectively increased in the hippocampus CA1 and thalamus of the near-term animals, consistent with reactive dendritic change and heightened vulnerability for neuronal injury. As such, intermittent cord compressions in the ovine fetus can impact protein markers for dendritic and presynaptic nerve development depending on their timing, which might then lead to alterations in synapse formation and neuronal circuitry.

The impact of labor at term on measures of neonatal outcome.

OBJECTIVE: The purpose of this study was to determine risk assessments for a spectrum of neonatal outcomes with elective cesarean delivery versus a trial of labor for previous cesarean section and otherwise healthy patients who deliver at term. STUDY DESIGN: The perinatal/neonatal database of St. Joseph's Health Care, London, Ontario, Canada, was used to obtain the umbilical cord pH and base excess values, incidence of adverse neonatal outcomes, and patient demographics for all term (> or =37 weeks of gestation), singleton, liveborn, or intrapartum demise infants with no major anomalies who were delivered between January 1992 and March 2002 (n = 33,709 infants). Patient groupings (all patient, patient with previous cesarean delivery, and low-risk patient) with no labor versus labor were studied by a comparison of mean values/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. RESULTS: Labor was associated with a small drop in umbilical artery pH from approximately 7.27 to 7.25 and base excess from approximately -3.1 to -5.4 mmol/L, but this was generally well tolerated, with no difference in the incidence of 5-minute Apgar scores of <7 for any of the patient population groupings. Neonatal respiratory morbidity was increased generally in the group of elective cesarean delivery patients, which resulted in increased neonatal intensive care unit triage/admission even out to 7 days; some of this risk was likely to persist even with a policy of elective cesarean delivery after 39 weeks of gestation. Although we found no significant difference in the incidence of pathologic acidemia at birth with an umbilical artery pH <7.00, there was a risk for intrapartum/neonatal death that could be attributed to labor events per se that ranged from 1 of 882 for the patients with previous cesarean delivery to 1 of 3406 for the low-risk patients. CONCLUSION: For otherwise healthy patients at term, the risk of adverse neonatal outcomes is low, with the choice between elective cesarean delivery and trial of labor in general balancing the low risk of increased respiratory morbidity and thereby neonatal intensive care unit triage/admission against the extremely low risk of labor-related infant death and severe morbidity. However, this balance for the patients with previous cesarean delivery appears shifted, with less benefit from a trial of labor in terms of reduced respiratory morbidity and neonatal intensive care unit triage/admission and with increased labor-related severe morbidity/death, albeit with all of these still at a low level.

Cerebral leucine uptake and protein synthesis in the near-term ovine fetus: relation to fetal behavioral state.

Behavioral/sleep state activity may impact on synthetic processes within the brain, thus accounting for the developmental change in such activity and suggesting a role in the brain's growth and development. We have therefore determined the cerebral uptake of leucine and [(14)C]leucine during continuous tracer infusion as measures of leucine metabolism in relation to behavioral state activity, as well as the regional flux of leucine into brain tissue in the ovine fetus near term. The cerebral fractional protein synthetic rate and the absolute protein synthetic rate averaged approximately 20%/day and approximately 1 g/day, respectively, as measured for the whole brain, which is considerably higher than anticipated protein accretion and indicates a high rate of protein turnover with protein synthesis closely linked to protein degradation. Measures of protein synthesis were significantly higher in the pituitary gland, which may be attributed to the active synthesis and export of peptide hormones from this region. Cerebral leucine and [(14)C]leucine uptakes averaged approximately 630 and approximately 1,000 nmol. 100 g(-1). min(-1), with the latter higher than leucine unidirectional flux and thus supporting a degree of leucine oxidation by the brain. Cerebral leucine metabolism as studied was affected by behavioral state activity, with uptake measurements for both leucine and [(14)C]leucine significantly increased during the high-voltage electrocortical/non-rapid eye movement state by 1.7-fold and 2.8-fold, respectively, indicating that protein synthesis and degradation must also be increased at this time, and supporting a role for behavioral state activity in the brain's growth and development.