Adaptive shut-down of EEG activity predicts critical acidemia in the near-term ovine fetus

Martin G Frasch, Lucien Daniel Durosier, Nathan Gold, Mingju Cao, Brad Matushewski, Lynn Keenliside, Yoram Louzoun, Michael G Ross, Bryan S Richardson, Martin G Frasch, Lucien Daniel Durosier, Nathan Gold, Mingju Cao, Brad Matushewski, Lynn Keenliside, Yoram Louzoun, Michael G Ross, Bryan S Richardson

Abstract

In fetal sheep, the electrocorticogram (ECOG) recorded directly from the cortex during repetitive heart rate (FHR) decelerations induced by umbilical cord occlusions (UCO) predictably correlates with worsening hypoxic-acidemia. In human fetal monitoring during labor, the equivalent electroencephalogram (EEG) can be recorded noninvasively from the scalp. We tested the hypothesis that combined fetal EEG - FHR monitoring allows for early detection of worsening hypoxic-acidemia similar to that shown for ECOG-FHR monitoring. Near-term fetal sheep (n = 9) were chronically instrumented with arterial and venous catheters, ECG, ECOG, and EEG electrodes and umbilical cord occluder, followed by 4 days of recovery. Repetitive UCOs of 1 min duration and increasing strength (with regard to the degree of reduction in umbilical blood flow) were induced each 2.5 min until pH dropped to <7.00. Repetitive UCOs led to marked acidosis (arterial pH 7.35 ± 0.01 to 7.00 ± 0.03). At pH of 7.22 ± 0.03 (range 7.32-7.07), and 45 ± 9 min (range 1 h 33 min-20 min) prior to attaining pH < 7.00, both ECOG and EEG amplitudes began to decrease ~fourfold during each FHR deceleration in a synchronized manner. Confirming our hypothesis, these findings support fetal EEG as a useful adjunct to FHR monitoring during human labor for early detection of incipient fetal acidemia.

Keywords: Acidosis; ECOG; EEG; FHR; Fetus; asphyxia; hypoxia; monitoring.

© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Figures

Figure 1
Figure 1
Acid-base status, arterial oxygen saturation, and glucose during the experiment’s baseline and umbilical cord occlusions (UCOs). Blood samples taken between the mild, moderate, and severe UCO series as well as at pH 2Sat; $, glucose; #, Lactate – all vs. baseline.
Figure 2
Figure 2
Example of an individual ECOG / EEG response to repetitive UCO. TOP: 60 min view of the adaptive brain shut-down pattern visible in ECOG and EEG in response to changes in arterial blood pressure (ABP) and fetal heart rate (FHR). BOTTOM: 10 min zoomed-in window of this pattern.
Figure 3
Figure 3
Cross-correlation function (CCF) analysis of the ECOG/EEG response to FHR decelerations. The baseline, mild, and moderate umbilical cord occlusion (UCO) series (denoted “other”) were compared with the ‘Severe’ UCO series when the adaptive brain shut-down was observed in all fetuses. The four leftmost plots represent the cross-correlation function between the smoothed ECOG/EEG amplitude and FHR with a 10 sec moving average with a delay ranging from −100 sec to 100 sec. For example, a time delay of 0 represents the correlation of the ECOG and FHR values at the same time. When a positive delay of 100 sec is used, the ECOG at time t is compared with the FHR at time t + 100. The two leftmost plots are the “other” groups, and the middle plot is the severe group when the adaptive brain shut-down was mostly observed in all fetuses. The upper plots are for the EEG/FHR correlation and the lower plots are for the ECOG/FHR. One can see that the amplitude of correlations is much higher in the severe group than in all other groups (P < 0.01 and P < 0.001, for EEG and ECOG, respectively), and that the amplitude is much larger in the EEG/FHR correlation than in the ECOG/FHR. The difference in the correlation amplitude is presented as a box plot in the two rightmost plots, with the red bar representing the median of the distribution and the box size represent the 25–75th percentiles. + signifies the outliers of the distributions (beyond the 90th percentile values). High amplitude of the correlation between EEG and FHR implies a strong synchronization between the two signals with an average delay of 30 sec.

References

    1. Astrup J. Energy-requiring cell functions in the ischemic brain. Their critical supply and possible inhibition in protective therapy. J. Neurosurg. 1982;56:482–497.
    1. Attwell D. Laughlin SB. An energy budget for signaling in the grey matter of the brain. J. Cereb. Blood Flow Metab. 2001;21:1133–1145.
    1. Block BS, Schlafer DH, Wentworth RA, Kreitzer LA. Nathanielsz PW. Intrauterine asphyxia and the breakdown of physiologic circulatory compensation in fetal sheep. Am. J. Obstet. Gynecol. 1990;162:1325–1331.
    1. Borgstedt AD, Rosen MG, Chik L, Sokol RJ, Bachelder L. Leo P. Fetal electroencephalography. Relationship to neonatal and one-year developmental neurological examinations in high-risk infants. Am. J. Dis. Child. 1975;129:35–38.
    1. Chik L, Sokol RJ, Rosen MG. Borgstedt AD. Computer interpreted fetal electroencephalogram. I. Relative frequency of patterns. Am. J. Obstet. Gynecol. 1976;125:537–540.
    1. Fletcher AJ, Gardner DS, Edwards CM, Fowden AL. Giussani DA. Development of the ovine fetal cardiovascular defense to hypoxemia towards full term. Am. J. Physiol. Heart Circ. Physiol. 2006;291:H3023–H3034.
    1. Frasch MG, Mansano RZ, Gagnon R, Richardson BS. Ross MG. Measures of acidosis with repetitive umbilical cord occlusions leading to fetal asphyxia in the near-term ovine fetus. Am. J. Obstet. Gynecol. 2009;200:200.e201–200.e207.
    1. Frasch MG, Keen A, Matushewski B. Richardson BS. Comparability of electroenkephalogram versus electrocorticogram in the ovine fetus near term. Reprod. Sci. 2010;17:51A.
    1. Frasch MG, Keen AE, Gagnon R, Ross MG. Richardson BS. Monitoring fetal electrocortical activity during labour for predicting worsening acidemia: a prospective study in the ovine fetus near term. PLoS One. 2011;6:e22100.
    1. Frasch MG, Durosier D, Duchatellier C. Richardson BS. Fetal sheep ECOG and EEG changes accompanying variable FHR decelerations alarm early onset of worsening acidemia. Reprod. Sci. 2012;19:1A–70A.
    1. Gardner DS, Fletcher AJ, Bloomfield MR, Fowden AL. Giussani DA. Effects of prevailing hypoxaemia, acidaemia or hypoglycaemia upon the cardiovascular, endocrine and metabolic responses to acute hypoxaemia in the ovine fetus. J. Physiol. 2002a;540:351–366.
    1. Gardner DS, Fowden AL. Giussani DA. Adverse intrauterine conditions diminish the fetal defense against acute hypoxia by increasing nitric oxide activity. Circulation. 2002b;106:2278–2283.
    1. Giussani DA, Spencer JA, Moore PJ, Bennet L. Hanson MA. Afferent and efferent components of the cardiovascular reflex responses to acute hypoxia in term fetal sheep. J. Physiol. 1993;461:431–449.
    1. Gu W, Jones CT. Parer JT. Metabolic and cardiovascular effects on fetal sheep of sustained reduction of uterine blood flow. J. Physiol. 1985;368:109–129.
    1. Hokegard KH, Eriksson BO, Kjellmer I, Magno R. Rosen KG. Myocardial metabolism in relation to electrocardiographic changes and cardiac function during graded hypoxia in the fetal lamb. Acta Physiol. Scand. 1981;113:1–7.
    1. Itskovitz J, LaGamma EF. Rudolph AM. Heart rate and blood pressure responses to umbilical cord compression in fetal lambs with special reference to the mechanism of variable deceleration. Am. J. Obstet. Gynecol. 1983;147:451–457.
    1. Kaneko M, White S, Homan J. Richardson B. Cerebral blood flow and metabolism in relation to electrocortical activity with severe umbilical cord occlusion in the near-term ovine fetus. Am. J. Obstet. Gynecol. 2003;188:961–972.
    1. Keen AE, Frasch MG, Sheehan MA, Matushewski B. Richardson BS. Maturational changes and effects of chronic hypoxemia on electrocortical activity in the ovine fetus. Brain Res. 2011;1402:38–45.
    1. Liston R, Crane J, Hughes O, Kuling S, MacKinnon C, Milne K, et al. Fetal health surveillance in labour. J. Obstet. Gynaecol. Can. 2002;24:342–355.
    1. Low JA. The role of blood gas and acid-base assessment in the diagnosis of intrapartum fetal asphyxia. Am. J. Obstet. Gynecol. 1988;159:1235–1240.
    1. Nuyt AM, Segar JL, Holley AT. Robillard JE. Autonomic adjustments to severe hypotension in fetal and neonatal sheep. Pediatr. Res. 2001;49:56–62.
    1. Prout AP, Frasch MG, Veldhuizen RA, Hammond R, Ross MG. Richardson BS. Systemic and cerebral inflammatory response to umbilical cord occlusions with worsening acidosis in the ovine fetus. Am. J. Obstet. Gynecol. 2010;202:82.e1. 9.
    1. Richardson B. Gagnon R. Behavioural state activity and fetal health & development. In: Creasy RK, Resnik R, editors; Maternal-fetal medicine. Philadelphia: WB Saunders Co; 2008. pp. 155–162.
    1. Richardson BS, Rurak D, Patrick JE, Homan J. Carmichael L. Cerebral oxidative metabolism during sustained hypoxaemia in fetal sheep. J. Dev. Physiol. 1989;11:37–43.
    1. Richardson BS, Carmichael L, Homan J, Johnston L. Gagnon R. Fetal cerebral, circulatory, and metabolic responses during heart rate decelerations with umbilical cord compression. Am. J. Obstet. Gynecol. 1996;175:929–936.
    1. Rosen KG, Hrbek A, Karlsson K. Kjellmer I. Fetal cerebral, cardiovascular and metabolic reactions to intermittent occlusion of ovine maternal placental blood flow. Acta Physiol. Scand. 1986;126:209–216.
    1. Ross MG, Jessie M, Amaya K, Matushewski B, Durosier LD, Frasch MG, et al. Correlation of arterial fetal base deficit and lactate changes with severity of variable heart rate decelerations in the near-term ovine fetus. Am. J. Obstet. Gynecol. 2013;208:285. e281–286.
    1. Sokol RJ, Rosen MG. Chik L. Fetal electroencephalographic monitoring related to infant outcome. Am. J. Obstet. Gynecol. 1977;127:329–330.
    1. Thaler I, Boldes R. Timor-Tritsch I. Real-time spectral analysis of the fetal EEG: a new approach to monitoring sleep states and fetal condition during labor. Pediatr. Res. 2000;48:340–345.
    1. Thordstein M, Flisberg A, Lofgren N, Bagenholm R, Lindecrantz K, Wallin BG, et al. Spectral analysis of burst periods in EEG from healthy and post-asphyctic full-term neonates. Clin. Neurophysiol. 2004;115:2461–2466.
    1. de Vries LS. Hellstrom-Westas L. Role of cerebral function monitoring in the newborn. Arch. Dis. Child. Fetal Neonatal Ed. 2005;90:F201–F207.
    1. Wang X, Durosier LD, Ross MG, Richardson BS. Frasch MG. Online detection of fetal acidemia during labour by testing synchronization of EEG and heart rate: a prospective study in fetal sheep. PLoS One. 2014;9:e108119.
    1. Wassink G, Bennet L, Davidson JO, Westgate JA. Gunn AJ. Pre-existing hypoxia is associated with greater EEG suppression and early onset of evolving seizure activity during brief repeated asphyxia in near-term fetal sheep. PLoS One. 2013;8:e73895.
    1. Williams CE, Gunn A. Gluckman PD. Time course of intracellular edema and epileptiform activity fol-lowing prenatal cerebral ischemia in sheep. Stroke. 1991;22:516–521.
    1. Xu A, Matushewski B, Cao M, Hammond R, Frasch MG. Richardson BS. The ovine fetal and placental inflammatory response to umbilical cord occlusions with worsening acidosis. Reprod. Sci. 2015 doi: .
    1. Yumoto Y, Satoh S, Fujita Y, Koga T, Kinukawa N. Nakano H. Noninvasive measurement of isovolumetric contraction time during hypoxemia and acidemia: Fetal lamb validation as an index of cardiac contractility. Early Hum. Dev. 2005;81:635–642.

Source: PubMed

3
Abonner