Yasuyuki Kawagoe

Adaptation of cardiovascular responses to repetitive umbilical cord occlusion in the late gestation ovine fetus

1 The impact of repeated umbilical cord occlusion on the normal maturation of fetal heart rate (FHR) and mean arterial pressure (MAP) and the cardiovascular responses to successive umbilical cord occlusion was investigated over a 21 day period in the latter part of gestation. 2 Fifteen chronically instrumented sheep (control group n = 6; occlusion group n = 9) were studied for 21 days (113‐133 days of gestation, term = 145 days) with umbilical cord occlusions (90 s duration) performed every 30 min for 1‐4 h each day. On days 1, 9 and 18, FHR, FHR variation and MAP were monitored continuously and fetal arterial blood gases, pH and metabolites were measured at predetermined intervals. The baroreflex response to 75‐100 μg phenylephrine (i.v.) was tested on days 1 and 18. 3 Basal FHR decreased (ΔFHR: control, 34.6 ± 3.6 beats min−1; occlusion, 36.9 ± 2.7 beats min−1) and MAP increased (ΔMAP: control, 3.1 ± 1.7 mmHg; occlusion, 5.2 ± 2.1 mmHg) to a similar extent in control and occlusion groups between days 1 and 21 of the study. There was a small decline in FHR variation over the 21 day study in occlusion, but not control, group fetuses. 4 The magnitude of the fall in FHR decreased and the rise in MAP increased, despite similar changes in blood gases in response to umbilical cord occlusion, over the course of the 21 day study. Despite a significant decline in the ratio of ΔFHR to ΔMAP on days 9 and 18 compared to day 1, there was no difference between control and occlusion groups in baroreflex sensitivity. However ΔFHR/ΔPO2, an index of chemoreceptor sensitivity, had decreased by day 9 and 18 compared to day 1. 5 The cardiovascular responses to umbilical cord occlusion are altered with repetitive occlusions during the latter part of gestation, with a decrease in ΔFHR/ΔMAP, which does not involve changes in baroreflex sensitivity, but may involve changes in chemoreceptor sensitivity. However, repeated umbilical cord occlusion appears to have no impact on baseline cardiovascular control since there was no change in the normal maturational decrease in FHR and rise in MAP.

Intermittent umbilical cord occlusion in the ovine fetus near term: effects on behavioral state activity.

OBJECTIVE The purpose of this study was to determine the effects on fetal behavioral state activity of intermittent umbilical cord occlusion resulting in repetitive severe short-term hypoxemia. STUDY DESIGN Fifteen near-term fetal sheep (experimental group, n = 8; control group, n = 7) were studied during 4 days while behavioral and cardiovascular parameters were monitored. Each day after a 2-hour control period, cord occlusions were performed in the experimental group animals by complete inflation of an occluder cuff (duration, 90 seconds) every 30 minutes for 3 to 5 hours. Results are presented as group mean +/- SEM. RESULTS During umbilical cord occlusions fetal arterial PO(2) (change of 12 mm Hg), oxygen saturation (change of 40%), and glucose concentration (change of 0.3 mmol/L) fell and PCO(2) (change of 7 mm Hg) rose, but all returned toward control values after release of occlusion. Fetal behavioral state activity was markedly disrupted by 90 seconds of cord occlusion, with animals showing an abrupt flattening of the electrocorticogram. In >90% of instances the first identifiable state after cord release was the high-voltage non-rapid-eye-movement state. There was no apparent change in this response through the 4 days of the study. For experimental group animals the mean percentages of time spent in low-voltage electrocortical state (from 53 +/- 2 to 36 +/- 2), electro-ocular state (from 45 +/- 3 to 28 +/- 3), and fetal breathing activity (22 +/- 4 to 12 +/- 3) were significantly decreased (P <.001) during occlusion hours with respect to nonocclusion hours. CONCLUSION Intermittent umbilical cord occlusion with severe but limited hypoxemia and no cumulative acidosis in the near-term ovine fetus disrupts behavioral state activity, with a flattening of the electrocortical activity during occlusions and an overall decrease in the prominence of the low-voltage rapid-eye-movement state. If such insults are frequent and severe enough, they might have an effect on growth and development of the brain during the perinatal period.

Intermittent umbilical cord occlusion in the ovine fetus: effects on blood glucose, insulin, and glucagon and on pancreatic development.

OBJECTIVE To determine whether repetitive umbilical cord occlusion resulting in fetal hypoxemia but not cumulative acidosis also affects fetal glucose levels and the levels of the regulatory hormones insulin and glucagon, by altering glucose delivery and with repetitive insults by inducing fetal glucose production, thus possibly affecting pancreatic development. METHODS Fifteen chronically catheterized fetal sheep were studied over 21 days. Umbilical cord occlusions (UCOs) (duration 90 seconds) were performed every 30 minutes for 3-4 hours each day. Fetal arterial blood was sampled at predetermined times on days 1, 9, and 18 for blood gases, pH, glucose, lactate, insulin, and glucagon. When animals were sacrificed, fetal pancreatic tissues were collected for insulin immunostaining. RESULTS Blood glucose decreased acutely with each UCO but showed a cumulative increase of approximately 30% over the course of each sampling day. Although plasma insulin levels also increased over the course of sampling on days 9 and 18, plasma glucagon levels remained unchanged throughout the study. The percentage of pancreatic islet cells immunopositive for insulin, which averaged 67%, was also unchanged in experimental compared with control animals. CONCLUSION Umbilical cord occlusion during the latter part of pregnancy, which caused severe but limited hypoxemia, also resulted in acute decreases in blood glucose levels because of reduced exogenous glucose delivery and a cumulative increase in glucose in response to repetitive insults, possibly by inducing fetal glucose production, enhancing glucose delivery, or both. However, repetitive UCO as studied had minimal effect on plasma insulin levels and no effect on glucagon levels or on pancreatic immunostaining for insulin, and thus had no evident effect on pancreatic development.

Antithrombin improves the maternal and neonatal outcomes but not the angiogenic factors in extremely growth-restricted fetuses at <28 weeks of gestation.

Abstract Aims: Severe preterm fetal growth restriction (FGR) remote from term is problematic. We aimed to investigate the effect of maternally-administered antithrombin on maternal and neonatal outcomes. A prospective, one-arm, pilot study was performed in 14 women with severe FGR (≤5th centile) at <28 weeks of gestation, without hypertensive disorders. Maternal plasma concentrations of soluble Feline McDonough Sarcoma (FMS)-like trypsin kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured and categorized into three groups: group 1; low sFlt-1 and high PlGF, group 2; moderate sFlt-1 and low PlGF, and group 3; high sFlt-1 and low PlGF. Antithrombin was administered for 3 days. The incidence of perinatal mortality, infant morbidity, and the period of pregnancy prolongation were compared. Results: In group 1 (n=4), their pregnancies were extended for longer periods and the maternal and infant outcomes were good. The prolongation periods were shorter in groups 2 (n=3) and 3 (n=7), which resulted in poor maternal [severe preeclampsia or hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome] and infant outcomes. Conclusions: The evaluation of the maternal sFlt-1 and PlGF at 21–27 weeks of gestation is useful in the managements of severe FGR. Antithrombin treatment could prolong the pregnancies with low sFlt-1 and high PlGF without negatively affecting maternal or fetal health.

Clinical Application of Pulse Transit Time and Correlation With Intrapartum Fetal Heart Rate Monitoring: A Preliminary Study of 18 Full-Term Infants

The authors show that pulse transit time and blood pressure are reciprocal in fetal goat models. They applied this technique in clinical settings to correlate changes in pulse transit time with fetal heart rate monitoring patterns and acid-base status. In 18 uncomplicated pregnancies, pulse transit time was obtained from electrocardiograms to pulse oximeter waveform and averaged during each baseline period, defined by the interpretation of fetal heart rate monitoring. According to a > 10% change from the control value, chronological changes were categorized into shortened, unchanged, and prolonged. Pulse transit time was available in 82% ± 11% of the recordings. In 15 fetuses, 2 (13%) showed prolonged, 7 (47%) showed shortened, and 6 (40%) showed unchanged conditions. Comparisons of the shortened and unchanged categories revealed that severe variable deceleration was significantly increased, and half or more fetuses showed hypoxemia in the shortened category. Shortening of pulse transit time, theoretically indicating a hypertensive condition, was more frequently associated with severe variable decelerations, suggesting that the pulse transit time may supplement the interpretation of fetal heart rate monitoring.