Ovine fetal breathing and swallowing activity in response to plasma glucose changes.

Fetal swallowing activity generally occurs simultaneously with fetal breathing movements (FBM) in sheep. The present study investigated the FBM and swallowing responses to altered fetal plasma glucose. Fetal lambs were chronically prepared with laryngeal, esophageal and diaphragm electromyogram (EMG) wires, an esophageal flow probe and vascular catheters. Beginning at 138 +/- 1 day, FBM and swallowing were monitored during control periods and in response to intravenous glucose infusions (14 mg/kg/min for 120 min) to fetuses of fed and fasted ewes. Glucose infusions to fetuses of fed ewes resulted in significant increases in fetal plasma glucose (21.2 +/- 0.7 to 40.5 +/- 1.9 mg/dl) and time breathing (46.2 +/- 6.3 to 60.0 +/- 9.5 min/2 h). In response to maternal fasting, fetal glucose levels (13.4 +/- 1.0 mg/dl) and time breathing (23.0 +/- 7.2 min/2 h) decreased significantly. Glucose infusion to fetuses of fasted ewes resulted in significant increases in time breathing (50.3 +/- 13.4 min/2 h) and diaphragmatic EMG activity (1,295 +/- 654 to 3,012 +/- 1,182 spikes/2 h). There was no change from basal levels of fetal EMG swallows (83.2 +/- 4.3 swallows/2 h) or esophageal flow (40.8 +/- 7.9 ml/2 h) in response to maternal fasting or fetal glucose infusions.     

Ovine hourly fetal urine production: relation to fetal electrocortical activity

OBJECTIVE: Ultrasound studies of hourly urine production rate in human fetuses have suggested that a fall in urine production occurs in state 2F (fetal quiet sleep) secondary to a state-dependent decrease in renal blood flow. We sought to ascertain the relationship between fetal hourly urine production rate and behavioral state in the near-term ovine fetus, a model in which urine production and fetal brain activity can be directly measured. METHODS: Six ewes with singleton pregnancies were prepared with vascular and amniotic fluid catheters. Fetuses were prepared with hindlimb vascular catheters, a bladder catheter, and biparietal ECoG electrodes. After at least 5 days of recovery (ga 130 +/- 2 days; term = 145-150 days), each animal was monitored for a 6-h period. Urine production was measured by draining the bladder catheter through a drop counter and fetal ECoG was continuously recorded (sampling rate of 50 Hz). ECoG activity was analyzed using power spectral analysis and periods of active and quiet sleep identified using both signal amplitude and corresponding 85% spectral edge frequency. RESULTS: Basal fetal arterial pH (7.36 +/- 0.01), pO2 (22.0 +/- 1.2 mmHg) and pCO2 (47.0 +/- 1.6 mmHg) and plasma (295 +/- 2 mOsm/kg) and urine (179 +/- 3 mOsm/kg) osmolalities were within normal ranges. Active and quiet sleep comprised 50 +/- 2 and 43 +/- 1% time, respectively. There was no difference in hourly urine production rate in active sleep (21.4 +/- 9.7 ml/h) and quiet sleep (18.8 +/- 7.7 ml/h). CONCLUSIONS: 1) Hourly fetal urine production rate is independent of ECoG activity state in the near-term ovine fetus. 2) Assuming only minor species differences, ultrasound measurement of human fetal hourly urine production rate can be performed without concern for fetal neurobehavioral state changes.     

Ovine fetal cardiorespiratory response to nicardipine

Nicardipine, a calcium antagonist associated with decreased uterine blood flow in near-term pregnant rabbits and fetal asphyxia after maternal administration in the rhesus monkey and sheep, was infused directly to the fetus in six chronically prepared pregnant ewes at 128 days' gestation. Changes in fetal mean arterial and diastolic blood pressure levels at 2 and 30 minutes after bolus injection of 50 micrograms were minimal; by 60 minutes these values had returned to preinfusion levels. No significant changes were observed after infusion of 100 micrograms of nicardipine. Fetal heart rate, fetal arterial blood gas values, and maternal cardiovascular variables did not change at either dose. Fetal plasma concentrations of nicardipine were 78 +/- 28 ng/ml and 114 +/- 48 ng/ml at 30 minutes after infusion of 50 micrograms and 100 micrograms, respectively, well within the range previously reported to be associated with fetal asphyxia. These data suggest that the previously reported fetal acidosis from maternal infusion of nicardipine may be primarily due to a decrease in maternal uterine blood flow rather than a direct fetal effect of the drug.     

Ovine fetal lung fluid response to intravenous saline solution infusion: fetal atrial natriuretic factor effect

The fetal lung, a significant source of in utero fluid production, has been postulated to serve a regulatory role in maintenance of fetal body fluid homeostasis. Whereas the fetus responds to intravascular saline solution infusions with increased urine output, the fetal lung fluid response to this stimulus is unclear. Tracheal fluid output was measured in four chronically catheterized ovine fetuses (mean gestation, 129 +/- 1 days) subjected to successive 40-minute intravenous 0.9% saline solution infusions at rates of 0.5 and 1 ml/min/per kilogram of body weight. Tracheal fluid output decreased significantly (1.7 +/- 0.1 to 1.1 +/- 0.1 ml/10 min, p less than 0.01) during the infusion and returned to basal levels during the recovery period. Lung fluid osmolality and electrolyte concentration did not change. Fetal plasma atrial natriuretic factor increased significantly in response to the saline solution infusion (364 +/- 90 to 790 +/- 286 pg/ml, p less than 0.05) and returned to basal levels during the recovery period. There was a significant inverse correlation between plasma atrial natriuretic factor levels and tracheal fluid output. These results suggest that increased fetal plasma atrial natriuretic factor decreases lung fluid production. Lung fluid does not appear to compensate for fetal body water excess. Rather, lung fluid production appears to promote intrauterine pulmonary growth and to facilitate the transition to the extrauterine environment.     

Ovine fetal lung fluid response to atrial natriuretic factor

The fetal lung is an important site of fluid production and is postulated to serve a regulatory role in fetal fluid balance. To assess the role of atrial natriuretic factor on fetal lung liquid production, we studied the effect of intravenous atrial natriuretic factor infusion on tracheal fluid production in fetal sheep with chronic vascular and tracheal catheters. Ovine fetuses (mean gestation = 130 days +/- 1 day) received successive 40-minute intravenous infusions of increasing doses of synthetic fragment 1-28 atrial natriuretic factor (5, 25, and 100 ng/min.kg-1). In response to the 25 ng/min.kg-1 infusion, fetal tracheal fluid production decreased from 1.2 +/- 0.3 ml/10 min to 0.6 +/- 0.2 ml/10 min (p less than 0.05), and remained suppressed during the 100 ng/min.kg-1 infusion (0.5 +/- 0.2 ml/10 min). There was a significant inverse correlation between tracheal fluid production and fetal plasma atrial natriuretic factor levels (r = -0.61, p less than 0.001). Basal tracheal fluid sodium and potassium concentrations (147 +/- 1 mEq/L and 5 +/- 1 mEq/L) and osmolality (291 +/- 3 mOsm) did not change during the atrial natriuretic factor infusion periods. The observation that atrial natriuretic factor acts to decrease fetal lung fluid production suggests that atrial natriuretic factor may be important in the fetal adaptive response to extrauterine life.     

Ovine fetal urine production following maternal intravenous furosemide administration

The response of the ovine fetus to maternal furosemide administration was studied in six chronically catheterized fetal lamb preparations. These studies indicate that in the chronic sheep model maternally administered diuretics do not augment fetal urine production. Additionally, passage of the drug from the maternal intravascular compartment to the fetal intravascular compartment could not be demonstrated. It is suggested that on the basis of these data, the results of the "Lasix challenge test" should be interpreted with caution when they are used to evaluate human fetal renal function.     

Normal standards for fetal neurobehavioral developments--longitudinal quantification by four-dimensional sonography

AIM: To construct normal standards for fetal neurobehavioral development using longitudinal observations through all trimesters by four-dimensional sonography. SUBJECT AND METHODS: A group of 100 healthy normal singleton pregnancies were recruited for longitudinal 4D US examinations to evaluate fetal neurodevelopmental parameters between 7 to 40 weeks' gestation. Variables of maternal and fetal characteristics including gestational age, eight fetal movements patterns in the first trimester and 14 parameters of fetal movement and fetal facial expression patterns recorded thereafter for the construction of fetal neurological charts. RESULTS: Measurement of 7 parameters in the first trimester and 11 parameters in the second and third trimesters correlated with gestational age (P<0.05). Those parameters have been followed longitudinally through all trimesters and showed increasing frequency of fetal movements during the first trimester. A tendency towards decreased frequency of facial expressions and movement patterns with increasing gestational age from second to third trimesters has been noticed. CONCLUSION: With 4D sonography, it is possible to quantitatively assess normal neurobehavioral development. There is urgent need for further multicentric studies until a sufficient degree of normative data is available and the predictive validity of the specific relationship between fetal neurobehavior and child developmental outcome is better established.     

Predicting preterm birth: Cervical length and fetal fibronectin

Spontaneous preterm birth remains the leading cause of neonatal morbidity and mortality worldwide, and accounts for a significant global health burden. Several obstetric strategies to screen for spontaneous preterm delivery, such as cervical length and fetal fibronectin measurement, have emerged. However, the effectiveness of these strategies relies on their ability to accurately predict those pregnancies at increased risk for spontaneous preterm birth (SPTB). Transvaginal cervical shortening is predictive of preterm birth and when coupled with appropriate preterm birth prevention strategies, has been associated with reductions in SPTB in asymptomatic women with a singleton gestation. The use of qualitative fetal fibronectin may be useful in conjunction with cervical length assessment in women with acute preterm labor symptoms, but data supporting its clinical utility remain limited. As both cervical length and qualitative fetal fibronectin have limited capacity to predict preterm birth, further studies are needed to investigate other potential screening modalities.     

Ovine fetal cardiovascular responses to packed red blood cell transfusions

Fifteen transfusions were performed in normal or anemic chronically catheterized sheep fetuses ranging in weight from 0.73 to 3.62 kg and in age from 91 to 135 days' gestation (term = 147 days). During the transfusions, an average of 29.0 +/- 2.5 (SE) ml/kg of packed maternal red blood cells (hematocrit = 78%) were given intravenously over 30 minutes and fetal hematocrit increased from 28.5% +/- 1.2% to 43.8% +/- 1.6%. Circulating blood volume increased by 13.9 +/- 2.3 ml/kg at 1 hour after transfusion and remained at this level at 24 hours. An average of 15.1 +/- 2.4 ml/kg of plasma was lost from the circulation at 1 hour after the transfusion. Fetal vascular pressures increased significantly during the transfusions and the rise in arterial pressure was greater than that in venous pressure (p less than 10(-6]. Heart rate decreased by 23 beats/min at the end of the transfusion and remained 13 beats/min below control after 1 hour (p less than 10(-6]. From the measured blood volume changes, formulas were developed so that the fetal blood volume before the transfusion and the posttransfusion hematocrit could be accurately calculated (r greater than 0.90). Thus this study shows that packed cell transfusions increase fetal blood volume by only 50% of the transfused volume because of a loss of plasma from the circulation and that the pretransfusion blood volume and the posttransfusion hematocrit can be accurately calculated from readily measured variables.     

Indicated preterm birth for fetal anomalies

Between 2% and 3% of pregnancies are complicated by fetal anomalies. For most anomalies, there is no advantage to late preterm or early-term delivery. The risks of maternal or fetal complication are specific for each anomaly. Very few anomalies pose potential maternal risk. Some anomalies carry ongoing risks to the fetus, such as an increased risk of fetal death, hemorrhage, or organ damage. In a limited number of select cases, the advantages of late preterm or early-term birth may include avoiding an ongoing risk of fetal death related to the anomaly, allowing delivery in a controlled setting with availability of subspecialists and allowing direct care for the neonate with organ injury. The optimal gestational age for delivery cannot be determined for all pregnancies complicated by fetal anomalies. For most pregnancies complicated by anomalies, there is no change to obstetrical management regarding timing of delivery. For those that may benefit from late preterm or early-term delivery, variability exists such that each management plan should be individualized.     

Biochemical predictors of preterm labor: fetal fibronectin and salivary estriol

Preterm birth is a major complication of pregnancy and remains a leading cause of neonatal morbidity and mortality worldwide. Improvements in the authors' understanding of the pathophysiology of preterm labor have led to the development of novel diagnostic tools of use to identify women at greatest risk for preterm birth. Currently two FDA-approved biochemical tests are available in the United States: (1) fetal fibronectin and (2) salivary estriol. The presence of a positive fetal fibronectin test in the midtrimester of pregnancy is strongly associated with early spontaneous preterm birth. In contrast, a positive salivary estriol test is associated with late preterm birth, thus limiting its clinical use. Both tests have low test sensitivity and are currently used clinically for their negative predictive values. That is, women who screen negative are at very low risk for preterm birth and, thus, no interventions are indicated to prevent preterm birth. Women with a positive test are at increased risk and would be candidates for intervention. One of the main limitations of fetal fibronectin and salivary estriol, and an array of other proposed markers, is the fact that while these markers may aid in identification of women at increased risk for preterm birth, the authors currently have no clearly effective obstetric interventions for preterm-birth prevention in these high-risk women. Use of tocolytics, antimicrobials, or progesterone therapy currently has limited or unproven benefit in the management of women deemed at increased risk using these markers. Thus, until effective targeted obstetric interventions are available, the use of biochemical markers to identify women at increase risk for preterm birth remains largely research tools.     

Antepartum fetal asphyxia in the preterm pregnancy

OBJECTIVE: The objective of this report was to provide insight into the frequency and characteristics of antepartum fetal asphyxia in pregnancies that are delivered preterm. STUDY DESIGN: The characteristics of 30 pregnancies that were delivered preterm with biochemically confirmed antepartum fetal asphyxia (umbilical artery base deficit of >12 mmol/L) that were derived from >1 decade of experience in a single tertiary care obstetric unit were examined. Antepartum clinical characteristics, fetal assessment tests, and neonatal complications were documented. Fetal asphyxia was classified as mild, moderate, or severe on the basis of an umbilical artery base deficit (>12 mmol/L) and newborn encephalopathy and other organ system complications. RESULTS: Antepartum fetal asphyxia accounted for at least 34% of the fetal asphyxia in the pregnancies that were delivered preterm. Predictive criteria that led to intervention and diagnosis included clinical risk factors and, particularly, abnormal fetal assessment tests. The 50% incidence of moderate or severe asphyxia in the antepartum preterm pregnancies compares with 15% in term pregnancies. Moderate or severe asphyxia occurred with equal frequency with early and delayed intervention. CONCLUSION: Fetal asphyxia in pregnancies that were delivered preterm is present frequently before the onset of labor. Abnormal fetal assessment tests are valuable predictors of antepartum fetal asphyxia. The increased frequency of moderate and severe fetal asphyxia in the pregnancy that is delivered preterm implies a greater likelihood of long-term morbidity or death.     

Ovine maternal and fetal renal vasopressin receptor response to maternal dehydration.

OBJECTIVE: Arginine vasopressin secretion increases in response to increased plasma osmolality or hypovolemia. Dehydration-induced increases in plasma arginine vasopressin levels have been shown to down-regulate arginine vasopressin V2 receptors in adult rat kidneys. Our study determined ovine maternal and fetal renal arginine vasopressin receptor characteristics and receptor response to maternal dehydration. STUDY DESIGN: Eight pregnant ewes (113 +/- 1 days) were dehydrated for 72 hours; eight animals served as controls. Renal medullary tissue was isolated from maternal and fetal kidneys, and arginine vasopressin receptor characteristics determined with saturation and competition assays using tritiated arginine vasopressin, arginine vasopressin, and arginine vasopressin analogs. RESULTS: Euhydrated maternal and fetal renal medullary arginine vasopressin receptor dissociation constant (3.0 +/- 0.3 and 1.9 +/- 0.3 nmol/L) and maximal binding capacity (149 +/- 15 and 111 +/- 33 fmol/mg protein) values were similar. Pharmacologic profiles with selective agonists indicated a predominance of V2 receptors. Dehydration significantly increased maternal and fetal plasma osmolalities (304 +/- 2 to 320 +/- 2; 296 +/- 1 to 319 +/- 3 mOsm/kg water, respectively) and arginine vasopressin levels (3.8 +/- 1.4 to 29.3 +/- 4.6; 4.4 +/- 1.0 to 16.9 +/- 5.0 pg/ml, respectively) but had no effect on arginine vasopressin receptor binding. CONCLUSION: Specific, saturable, single-site tritiated arginine vasopressin binding is present in ovine maternal and fetal renal medullary membranes. Ovine maternal and fetal renal arginine vasopressin receptors do not down-regulate in response to dehydration-induced elevations in plasma arginine vasopressin levels.     

Movement, imaging and neurobehavioral assessment as predictors of cerebral palsy in preterm infants.

OBJECTIVE: To study the relative efficacy of three early predictors of cerebral palsy. METHOD: One Hundred and thirty infants with birth weight <1500 g were recruited. Video recordings of spontaneous general movements were made at 36 and 52 weeks postconceptional age. Magnetic resonance imaging and the neurobehavioral assessment of the preterm infant were done at 36 weeks postconceptional age. Follow-up neurological examination and Bayley assessments were made at 18 months corrected age to make early identification of cerebral palsy. RESULTS: Magnetic resonance imaging gave the best specificity and accuracy of 91 and 84% respectively. General movements at 52 weeks showed an improved specificity and accuracy over performance at 36 weeks postconceptional age. The negative predictive value for all methods tested was between 90 and 97%. Combining the results of magnetic resonance imaging and the neurobehavioral assessment improved the sensitivity of prediction to 80%, suggesting that a holistic approach to early detection of cerebral lesions is preferable to a single test. CONCLUSIONS: The majority of infants who appeared to behave within normal limits and exhibit normal brain structure in the newborn period were classified as neurologically intact at follow-up.     

Antepartum fetal surveillance in the preterm fetus.

Over the past two decades, obstetric and neonatal health care has shifted its attention to the preterm pregnancy. Due to the immaturity of the fetal autonomic nervous system, the usual diagnostic criteria for intervention in the preterm fetus are not available. Alternative methods such as the biophysical profile and Doppler offer the clinician a reasonable alternative in identifying potential fetal compromise.