Polymicrogyria in a fetus with human parvovirus B19 infection: a case with radiologic-pathologic correlation.

We report the prenatal magnetic resonance imaging (MRI) appearance of polymicrogyria with pathologic correlation in a fetus with congenital parvovirus B19 infection. Prenatal ultrasound revealed non-immune hydrops, but detected no fetal brain abnormalities. A subsequent fetal MRI scan performed at 23 weeks' gestation demonstrated bilateral polymicrogyria, which was confirmed at autopsy. To our knowledge, prenatal diagnosis of polymicrogyria in association with congenital parvovirus B19 infection has not been previously described. This case provides further evidence for brain abnormalities resulting from congenital parvovirus B19 infection, and suggests that fetal neuroimaging with MRI would be of value in suspected cases of congenital parvovirus infection.

Erythrocytosis associated with hemoglobin Rainier: oxygen equilibria and marrow regulation.

Hemoglobin Rainier (beta(145) tyrosine-->histidine) is an abnormal hemoglobin associated with increased oxygen affinity, decreased heme-heme interaction, presence of a Bohr effect, and erythrocytosis, but without obvious clinical sequelae. Regulation of erythropoiesis was studied in affected members of families having either hemoglobin Rainier or Yakima, abnormal hemoglobins associated with erythrocytosis. Apart from the elevated but stable hemoglobin concentration and red cell mass, parameters of red cell production in the subjects were normal. Initially normal values of erythropoietin excretion were increased by phlebotomy indicating a significant hypoxic stress at an otherwise normal hematocrit. This stress led to increased reticulocyte production and an eventual return to the prephlebotomy hematocrit. The erythrocytosis in carriers of hemoglobins Rainer and Yakima appears to be secondary to the increased oxygen affinity and this, with the response to phlebotomy, is consistent with the postulate that the renal sensor tissue regulating erythropoietin production is primarily influenced by the oxygen tensions of venous rather than arterial blood.

Fetal acidemia and electronic fetal heart rate patterns: is there evidence of an association?

OBJECTIVE: Despite the ubiquity of electronic fetal monitoring, the validity of the relationship between various fetal heart rate (FHR) patterns and fetal acidemia has not yet been established in a large unselected series of consecutive pregnancies. The aim of this study was to examine the published literature for evidence of such a relationship. METHODS: Four hypotheses based on assumptions in common clinical use were examined. The literature was searched for relationships between certain aspects of FHR patterns (e.g., degree of FHR variability, depth of decelerations), and fetal acidemia, or fetal vigor (5-minute Apgar score >or=7). We also attempted to relate duration of these patterns to the degree of acidemia. Using standardized FHR nomenclature we defined patterns based on baseline FHR variability, baseline rate, decelerations, and accelerations. RESULTS: The following relationships were observed: (1) Moderate FHR variability was strongly associated (98%) with an umbilical pH >7.15 or newborn vigor (5-minute Apgar score >or=7). (2) Undetectable or minimal FHR variability in the presence of late or variable decelerations was the most consistent predictor of newborn acidemia, though the association was only 23%. (3) There was a positive relationship between the degree of acidemia and the depth of decelerations or bradycardia. (4) Except for sudden profound bradycardia, newborn acidemia with decreasing FHR variability in combination with decelerations develops over a period of time approximating one hour. Most studies identified were observational and uncontrolled (grade III evidence of US Preventive Services Task Force); however, there was general agreement amongst the various studies, strengthening the validity of the observations. CONCLUSIONS: The validity of the relationship between certain FHR patterns and fetal acidemia and/or vigor, is supported by observations from the literature. In addition four assumptions commonly used in clinical management are supported. These conclusions need to be confirmed by a prospective examination of a large number of consecutive, unselected FHR patterns, and their relationship to newborn acidemia. Pending the completion of such studies, these observations can be used to justify certain aspects of current clinical management, and may assist in standardizing the diversity of opinions regarding FHR pattern management.

Prolactin concentrations in the monkey fetus during the last third of gestation.

PRL concentrations were measured in cord plasma obtained at hysterotomy from 26 rhesus monkey fetuses between 111--170 days gestational age (GA). Mean PRL concentrations increased significantly from 23.7 +/- 10.1 (X +/- SE) ng/ml at 121--130 days GA to 126.9 +/- 16.9 ng/ml at 161--170 days GA. A similar significant increase in PRL with age also was observed in samples obtained from 16 fetuses chronically catheterized in utero between 130--155 days GA. Mean PRL levels were 34 +/- 3.2 ng/ml at 131--140 days GA and rose to 82 +/- 9.7 at 150--155 days GA. No difference in PRL concentrations was found between cord blood samples and fetal peripheral blood samples at the ages studied. Maternal PRL levels did not change in samples obtained from chronically catheterized, chair-restrained mothers between 130--155 days GA. A tendency toward an increase in maternal PRL with advancing gestational age was observed in samples collected after hysterotomy. These data indicate that the fetal rhesus monkey demonstrates an increase in plasma PRL similar to that in the human, suggesting a possible physiological role for this hormone in the primate fetus late in gestation.

Stimulation of testosterone production in vivo and in vitro in the male rhesus monkey fetus in late gestation.

To assess intrauterine fetal testicular function, the carotid or femoral vessels of rhesus monkey fetuses, 129-145 days gestational age, were catheterized following hysterotomy of the mother. The fetus was returned to the uterus, the catheters were exteriorized through the mother's vagina and the pregnancy was allowed to continue. In this chronic preparation, basal levels of testosterone (measured with an RIA with 65% cross-reactivity with 5 alpha-dihydrotestosterone) in male fetal serum were 0.85 +/- 0.29 (SD) ng/ml. Administration of a 10 or 100 IU intra-arterial bolus of hCG into the fetal circulation stimulated in increase in fetal serum testosterone levels of 70 and 630%, respectively. Other fetuses were challenged with bolus infusions of 10 and 50 micrograms of synthetic gonadotropin releasing hormone (GnRH). The lower dose caused an increase in serum testosterone concentrations in only one of four fetuses, while the higher dose resulted in a positive response in all three experiments performed. With this dose, the mean increase in circulating testosterone concentration after 1 h was 105%. In vitro, specific binding of iodinated hCG was demonstrated in testicular homogenates from rhesus fetuses near term and hCG stimulated testosterone biosynthesis in testicular minces. Maximal stimulation was achieved at hCG concentrations between 5 and 50 ng/ml. The data indicate that the testes of fetal rhesus monkeys during late gestation are capable of androgen biosynthesis and can bind and respond to gonadotropin stimulation. Furthermore, the pituitary-gonadal axis in the fetal male monkey is capable of responding to GnRH stimulation at this stage of gestation.

Transabdominal cerclage for fetal wastage due to cervical incompetence.

From 1978-1986, nine transabdominal cervicoisthmic cerclage procedures were performed on eight patients at the University of California, San Francisco. In six of the patients, the decision to perform the procedure was based on failed transvaginal cerclages. In five of these six cases, the cervix had deep traumatic defects. In the remaining two patients, the cervix was extremely short. Before the procedure, the eight patients had 25 pregnancies lasting beyond the first trimester, with 20 fetal losses (fetal salvage rate 20%). After the transabdominal procedure, the eight patients had 13 pregnancies resulting in eight term births, three premature births (at approximately 36 weeks' gestation), and two fetal losses (salvage rate 85%). All infants were delivered by cesarean section. The transabdominal cerclage may increase the fetal salvage rate in selected women when poor obstetric outcome is related to failed transvaginal cerclage and/or an anatomically defective cervix.

Ultrasonography in the evaluation of intrauterine transfusion.

Numerous techniques have been described in the literature to aid the obstetrician in safely and easily performing an intrauterine transfusion. None, however, have addressed themselves to the question of whether the transfused cells actually enter the fetal peritoneal cavity. We have used gray-scale ultrasonography to evaluate this question in 4 patients who had undergone a total of 8 intrauterine transfusions. By scanning the fetal abdomen both before and after the transfusion, we were able to identify the transfused fluid within the fetal abdomen in all cases.

The effect of maternal administration of ephedrine on fetal heart rate and variability.

Ephedrine is the most popular vasopressor used in obstetrics to prevent or treat spinal or epidural hypotension. Fetal heart rate (FHR) changes during epidural anesthesia were studied in 71 patients; it was found that ephedrine administration (57 patients) was associated with significant increases in FHR and beat-to-beat variability. These changes were dose related and were not associated with fetal asphyxia as judged by measurement of fetal scalp blood pH or Apgar scores.

Fructose- 1,6-bisphosphate did not affect hippocampal neuronal damage caused by 10 min of complete umbilical cord occlusion in fetal sheep.

Fructose-1, 6-bisphosphate (FBP) has a neuroprotective effect in neonatal and adult rats. The purpose of this study was to examine the effects of FBP on hippocampal neuronal damage in fetal sheep asphyxiated by 10 min of complete umbilical cord occlusion. Thirteen fetal sheep at 124 days of gestation were surgically instrumented with catheters. Cardiorespiratory parameters were monitored, and biochemical analyses were performed with the blood samples. During the insult seven fetuses were given FBP (500 mg/kg) and six were given iso-osmotic saline, and hippocampal neuronal damage was examined histologically and scored. Cardiorespiratory changes were the same in both groups, and there was no neuroprotective effect of FBP in this study. However the decrease of serum total Ca level implied the Ca- chelating effect of FBP.

Tocolysis with beta-adrenergic receptor agonists.

Beta-adrenergic receptor agonists have been used for tocolysis in the setting of preterm labor for more than three decades. One of these agents, ritodrine hydrochloride, is the only Federal Drug Administration (FDA) approved drug for the treatment of preterm labor. Despite their widespread use, only a few prospective randomized placebo-controlled trials have been performed. These agents have been shown to have more patients deliver beyond 48 hours after the onset of treatment as compared with controls, but have never shown a difference in neonatal outcomes. Because they are one of the few tocolytic agents to have been shown to make a difference when compared with controls, the beta-agonists are commonly used as the control groups in studies examining the efficacy of newer tocolytic agents. In general, agents such as nifedipine, magnesium sulfate, and atosiban have not been shown to be more efficacious than the beta-agonists. However, several studies have shown these agents to have less side effects and lower discontinuation rates than the beta-agonists.

Cardiovascular responses to graded degrees of hypoxaemia in the llama fetus.

The fetal llama exposed to an intense degree of hypoxaemia did not increase cerebral blood flow, but showed a marked peripheral vasoconstriction. The same cardiovascular response is observed in fetal sheep submitted to a extremely severe hypoxaemia, when the initial compensatory vasodilatory mechanisms in brain and heart fail. To investigate whether the fetal llama responses to acute hypoxaemia are adaptive, or whether they are the result of a breakdown of mechanisms of blood flow redistribution that favours the central nervous system, we studied seven fetal llamas (0.6-0.7 of gestation) chronically-catheterized during 1 h of graded and progressive hypoxaemia. Fetal ascending aorta blood gases and fetal cardiac output and its distribution (radiolabelled-microspheres) were measured after 60 min of normoxaemia (B) and at the end of 20 min (H20), 40 min (H40) and 60 min (H60) of hypoxaemia. Data were analysed by ANOVA and Newman-Keuls tests. Each treatment resulted in a lower (P < 0.05) percentage of haemoglobin saturation than hypoxaemia; H40 was lower than H20, and H60 was lower than H20 and H40. No statistical difference was observed among treatments for cardiac output or cerebral blood flow. These results demonstrate that fetal cardiac output and brain blood flow are maintained at all degrees of hypoxaemia, indicating that these cardiovascular responses are an adaptive response in the llama fetus, rather than an index of cardiorespiratory decompensation.

Fetal cerebral metabolism: the influence of asphyxia and other factors.

Cerebral oxidative metabolism has been described in fetal sheep at two stages of development and is known to remain relatively constant over a wide range of oxygen levels in arterial blood. This constancy of oxygen consumption is caused by an increase in cerebral blood flow that matches the reduction in oxygen content and oxygen extraction. Although a number of factors are involved in the hypoxia-associated vasodilation (for example, oxygen, carbon dioxide, adenosine, prostaglandins, arginine vasopressin), its regulation is incompletely understood. During severe asphyxia, however, there is a limit to the vasodilator function, and both cerebral blood flow and oxygen consumption fall. The fetus can tolerate a certain degree of reduced oxygen uptake (possibly to 50% of control level) by various conservation techniques, but severe reductions are associated with neuronal damage. The primary substrate for the fetal brain under normal conditions is glucose, but the fetus can readily use anaerobic glycolysis and produce lactate under conditions of oxygen limitation. Lactate efflux from the brain is relatively slow, so prolonged and severe asphyxia may result in a high tissue level of lactate, which has been implicated in neuronal damage.

The effect of acute maternal hypoxia on fetal oxygenation and the umbilical circulation in the sheep.

The mean oxygen consumption was 8.4 +/- 1.9 ml/min/kg in the near-term fetal sheep. In response to acute maternal hypoxia fetal O2 consumption decreased to lower than 50% of the control values. The decrease was rapidly instituted, proportional to the degree of hypoxia, sustained for up to 47 min and stable over this period. With increasing duration of hypoxia, a progressive metabolic acidosis developed. Recovery of oxygen consumption occurred rapidly after hypoxia ceased, though the acidosis was not resolved until 2 h later. Umbilical blood flow was maintained during maternal hypoxia and umbilical arterial and venous pressures increased. A fetal bradycardia invariably accompanied the hypoxia.

Increased fetal heart rate variability with acute hypoxia in chronically instrumented sheep.

Fetal heart rate (FHR) and oxygen consumption were determined in 45 studies in 20 chronically instrumented, normoxic sheep. FHR variability was measured by a template device to determine amplitude range, and oscillatory frequency was manually counted over 5-min periods. During 26 min of isocapnic hypoxia, fetal O2 consumption decreased 39% and FHR decreased 18%, and FHR variability increased, the changes being maintained over the treatment period. It is suggested that the maintenance of FHR variability during this profound hypoxia denotes adequate cardiorespiratory compensatory mechanisms during the short period; prolongation of the hypoxia would probably result in fetal cerebral or myocardial decompensation, and disappearance of FHR variability. The increased variability may be due to increased alpha-adrenergic activity.

Fetal heart rate variability and cerebral oxygen consumption in fetal sheep during asphyxia.

This study was designed to examine the relationship between fetal heart rate variability and fetal cerebral oxygen uptake. Fetal sheep were chronically prepared with catheters and electrodes to determine cerebral blood flow (microsphere method), cerebral arteriovenous oxygen difference, and the electrocardiogram. An adjustable occluder was placed on the maternal common internal iliac artery to induce fetal asphyxia by reducing uterine blood flow. Fetal heart rate variability tended to decrease in the first 11 min of asphyxia, when cerebral oxygen consumption was approximately 53% of control. Despite stable cerebral oxygen consumption and worsening metabolic acidosis, however, fetal heart rate variability progressively returned towards normal by 36 min. There was no relationship between the depression of FHR variability and the degree of reduction of cerebral oxygen consumption. Nor was there any relationship between an alteration in regional cerebral blood flow or myocardial blood flow and the return of FHR variability with increasing duration of asphyxia. We conclude that there is an association between loss of fetal heart rate variability and reduced cerebral oxygen consumption, but the reduced variability does not persist with time at this degree of reduced cerebral metabolism in fetal sheep. This appears to be at variance with human clinical experience. Among the explanations for this may be insufficiently severe asphyxia, a species difference, removal of an inhibitor to FHR variability, or progressive use of other substrates for metabolism.

Cardiovascular responses to arginine vasopressin blockade during acute hypoxemia in the llama fetus.

The fetal llama has a marked increase in the peripheral vascular resistance and no augmentation of brain blood flow during hypoxemia. In spite of the substantial plasma arginine-vasopressin (AVP) increase during hypoxemia, up to 8 times greater than in fetal sheep, there are no changes of carotid and femoral blood flows during hypoxemia with a V1 receptor blockade, as is seen in the fetal sheep. The aim of this study was to assess the role of AVP function in mediating the combined ventricular output and organ blood flow in the hypoxemic llama fetus. Six fetal llamas at 0.65 of gestation were instrumented under general anesthesia, and cardiorespiratory responses and blood flows determined under normoxemic and hypoxemic conditions. The AVP effect was determined using a V1 antagonist during normoxemic and hypoxemic conditions. Organ blood flows were measured with the radioactive microsphere technique. No significant differences in organ blood flow or in their vascular resistances were seen between the control and treated fetuses during hypoxemia. We conclude that V1 blockade did not have any important role in the cardiovascular response to acute hypoxemia in the llama fetus, in contrast with lowland fetuses. AVP may be playing a role in other regions, possibly in kidney or lung, during hypoxemia.

Iliac venous aneurysm in a pregnant patient with a renal transplant. A case report.

A 10-cm-diameter iliac venous aneurysm presented as an adnexal mass in a pregnant patient with a renal transplant. She also had a femoral-saphenous arteriovenous shunt for facilitation of dialysis prior to the transplant. Diagnosis was made at laparotomy. The aneurysm was thought to have arisen because of elevation of iliac venous pressure due to the fistula, vascular relaxation and pressure of the uterus on the pelvic veins.

Fetal heart rate monitoring: interpretation and collaborative management.

Effective intrapartum fetal heart rate (FHR) monitoring requires ongoing collaboration among health care providers. Nurses, midwives, and physicians must have a shared understanding of 1) how FHR tracings are interpreted, 2) which FHR patterns are associated with actual or impending fetal acidemia, 3) when and within what time frame the physician or the midwife should be notified of variant FHR patterns, 4) how quickly physicians and midwives should respond when notified of variant patterns, and 5) the indications for and optimal timing of interventions such as operative delivery. This article reviews the literature on FHR monitoring and includes a discussion of the advantages and limitations of different monitoring modalities. An overview of those FHR patterns are associated with presumed fetal acidemia is presented, as well as sample multidisciplinary FHR monitoring guidelines and an exercise in intrapartum FHR pattern evaluation that can be used to initiate development of local FHR monitoring patterns.