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PubMedDate not supplied

Abnormal umbilical cord Doppler sonograms may predict impending demise in fetuses with sacrococcygeal teratoma. A report of two cases.

OBJECTIVE: To identify factors predictive of fetal demise in fetuses with sacrococcygeal teratoma (SCT). METHOD: The recent management of monochorionic twins discordant for a large SCT and a singleton with a large SCT was reviewed. RESULTS: Serial fetal echocardiography and ultrasonography with Doppler flow measurements documented rapid growth of the SCT in both cases with a relatively modest increase in combined cardiac output. No placentomegaly or hydrops was observed at any time. In both fetuses with SCT, evolution of abnormal umbilical artery waveforms was observed with the ultimate development of reversed end-diastolic umbilical arterial flow that was followed by sudden fetal demise. CONCLUSION: Death in these 2 fetuses with large SCTs in the absence of placentomegaly/hydrops or hemodynamic changes suggestive of evolving high-output failure suggests a previously unrecognized mechanism of death in fetuses with large rapidly growing SCTs. In these cases, fetal demise may only be heralded by abnormal umbilical artery waveforms that progress to the premorbid observation of reversed diastolic umbilical artery blood flow. Umbilical artery waveform analysis should be closely monitored with other hemodynamic parameters in fetuses with large SCTs. In such fetuses, depending on the gestational age, abnormalities in umbilical artery waveform should be considered indications for early delivery or in utero intervention to prevent fetal demise.

Adult↗
PubMedDate not supplied

Mild cerebral ventriculomegaly in fetuses: characteristics and outcome.

BACKGROUND: A fetal ultrasonographic (US) finding of mild ventriculomegaly (MVM) is not uncommon, but its prognostic significance is not clearly defined. OBJECTIVE: To evaluate the clinical and US characteristics and outcome of fetuses with mild dilatation of the cerebral lateral ventricles. PATIENTS AND METHODS: We reviewed the medical records of 34 consecutive fetuses with US evidence of MVM (atrial width of the lateral ventricles = 10-15 mm) at 18-35 weeks of gestation. RESULTS: Of the 34 fetuses with MVM, 7 underwent karyotype examination and were normal. In 4 of the 34 fetuses the pregnancy was terminated (at autopsy: 1 was normal, 2 had hydrocephalus and for 1 the parents refused autopsy). Eight fetuses that were delivered had congenital malformations; 3 of them died during the early neonatal period. In 6 of the 8 fetuses with malformations, karyotypes were available and 3 had chromosomal aberrations (trisomy 18, 45XO, and triploidy 69XXX). Spontaneous in utero resolution of the MVM occurred in 10/30 (33.3%) of the cases. Of the 26 infants that remained in follow-up, 16 (61.1%) were normal at 1 month and at 2 years of age. CONCLUSIONS: Our data confirm those of previous reports as to the characteristics and outcome of MVM. In the setting of mild fetal ventriculomegaly with a normal karyotype and an absence of malformations, the outcome appears to be favorable.

Adolescent↗
PubMed1990

Hormone ontogeny in the ovine fetus. XXV. Somatotrope desensitization to growth hormone releasing factor (GRF) independent of short-latency, ultrashortloop GH feedback.

Plasma ovine growth hormone (oGH) concentrations are strikingly elevated in the ovine fetus and decline at birth towards the low levels observed in the newborn lamb. We postulated that developmental changes in somatotrope function secondary to GH-releasing factor (GRF) desensitization and GH feedback play a role in the developmental pattern of oGH secretion and tested this hypothesis in vito in chronically catheterized ovine fetuses (123-145 days gestation; term 147 days) and newborn lambs (1-18 days). In the first set of studies, two consecutive intravenous GRF(1-44 amide) boluses (1 microgram/kg) were administered. When the GRF boluses were given 90 min apart, they elicited similar oGH responses, both in fetuses and in newborn lambs. In contrast, when the GRF boluses were given 20 min apart, a significant oGH response was evoked by the first GRF but an oGH response was not detected after the second GRF, either in fetuses or in newborn lambs. When the oGH response GRF(1-44 amide; 1 microgram/kg i.v.) was evaluated 40 min after the start of a human GH infusion (25 micrograms/kg hGH bolus followed by 0.5 microgram/kg/min hGH for 80 min, resulting in mean hGH plasma concentrations of 80 ng/ml), the exogenous hGH did not after the oGH response to GRF, either in fetuses or in newborn lambs. The present in vivo results demonstrate that the fetal and the neonatal somatotrope can be desensitized to GRF and suggest that a short-term latency, ultrashortloop GH feedback mechanism is not operative, either in the ovine fetus or in the newborn lamb.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Ultrastructure of the parathyroid gland of the mouse fetus after calcium chloride or ethylenediaminetetraacetic acid administration.

Ultrastructural changes of the parathyroid glands of 18-day-old mouse fetuses after administration of calcium chloride (calcium) or ethylenediaminetetraacetic acid (EDTA) were examined. Many chief cells in the parathyroid glans of the calcium-treated mouse fetuses contained poorly developed Golgi complexes and cisternae of the granular endoplasmic reticulum and many secretory granules as compared with those of the control fetuses. Many chief cells in the glands of the EDTA-treated mouse fetuses contained well-developed Golgi complexes and cisternae of the granular endoplasmic reticulum and many prosecretory granules as compared with those of the control fetuses. These findings suggest that calcium or EDTA affects the secretory activity of the parathyroid gland of the mouse fetus.

Animals↗
PubMed1994

Placental transport of nutrients to the fetus.

The exchange of nutrients between placenta and fetus involves three major mechanisms: (1) direct placental transfer of nutrients from the maternal to the fetal plasma; (2) placental metabolism and consumption of nutrients; (3) placental metabolism of nutrient substrates to alternate substrate forms. Carbohydrate is transported to the fetus as glucose which is taken up from the maternal plasma by the GLUT 1 transporter and transported to the fetus by facilitative diffusion according to concentration-dependent kinetics. Protein is transported to the fetus as amino acids by specific amino acid transporter proteins. Placental lipid transport to the fetus involves direct transporter mediated transfer of certain fatty acids as well as lipid uptake from lipoproteins, metabolic alteration in the placenta, and release into the fetal plasma. Placental size, architecture, developmental and pathological processes, and interaction with the fetus cooperate with transport and metabolic mechanisms to affect placental-fetal nutrient exchange.

Amino Acids↗
PubMed1996

Treatment of human fetuses and induction of immunological tolerance in humans by in utero transplantation of stem cells into fetal recipients.

Since 1976, we have performed more than 240 fetal tissue transplants (FLTs) to treat 63 patients with severe immunodeficiency disease (IDD), with inborn errors of metabolism (IEM), or with severe aplastic anemia. In both IDD and IEM, FLT into postnatal recipients has demonstrated beneficial effects (67%) of the patients were either cured or improved significantly). In 1988, we developed in utero FLT into human fetuses, taking advantage of the immunological tolerance of young fetuses. The transplants have involved fetuses suffering from various diseases at 12-28 weeks postfertilization with 2 of the 6 cases eventually resulting in abortion. With the 4 other fetuses, a favorable outcome was observed: 3 children are now more than 4 years old, and are alive and well with evidence of engraftment, reconstitution of immunity, and partial correction of beta zero thalassemia. In the fourth case, the fetus is alive and well and birth is expected soon. In utero transplantation of stem cells is a therapy with remarkable advantages: (a) tolerance induction due to the immune immaturity of the host, (b) lack of graft-versus-host disease due to the immaturity of the donor, (c) ideal isolation of the fetus in the maternal uterus, and (d) an optimal environment for donor fetal cell development in the vicinity of host fetal cells and growth factors.

Female↗
PubMed1980

Compensatory adrenal hypertrophic response in fetuses of calorie-malnourished rats.

Fetuses of ad libitum fed and calorie-restricted rats were unilaterally adrenalectomized on day 19. By day 20 ad libitum fed fetuses exhibited compensatory adrenal hypertrophy, but calorie-restricted fetuses did not. As this may be due to the elevated corticosteroid levels of the calorie-restricted dams, unilateral adrenalectomy was performed on fetuses of control and restricted rats bilaterally adrenalectomized on day 15. Fetuses of restricted and control rats exhibited compensatory hypertrophy. One effect of calorie restriction may be to increase the amount of maternal corticosteroids acting on the fetus.

Adrenal Cortex↗
PubMed1982

Parathyrin and calcium homeostasis in the fetus.

The response of plasma parathyrin (PT) in cattle fetuses to changes in plasma calcium was investigated in utero. Resting plasma calcium levels for 4 fetuses averaged 3.1 mg/dl higher than for their mothers. Fetal PT levels (0.67 ng/ml) were half those of the mother (1.40 ng/ml). Hypocalcemia induced by EDTA infusion evoked a rise in plasma PT in 2 or 3 fetuses. The relationship between plasma PT and calcium levels in these fetuses was curvilinear, PT rising from about 0.7 ng/ml at 13 mg calcium/dl to a plateau of about 1.6 ng/ml below 10 mg calcium/dl. This contrasted with one of the mothers in which PT rose above 3 ng/ml when plasma calcium fell from 9 to 7 mg/dl. During infusion of EDTA to mother or fetus there were no changes in plasma calcium or PT levels in the respective fetus or mother.

Animals↗
PubMed1986

Circulatory changes in fetuses with imminent asphyxia.

Blood flow was measured in 11 term fetuses who were later delivered by means of emergency caesarean section because of cardiotocographic changes indicating imminent asphyxia. Blood flow was recorded in the fetal descending aorta and in the intraabdominal part of the umbilical vein by combined real-time and 2-MHz pulsed Doppler ultrasound method. In all 11 fetuses, the waveform of the maximum aortic blood velocity was changed in a typical way with elimination of the diastolic flow (zero flow). In 4 of the fetuses, a short-lasting reversal of the diastolic flow occurred. In 5 fetuses, the pulsatility index of the aortic flow was increased, and the aortic volume flow was pathologically low in 3 fetuses. In the umbilical vein, the volume flow was within normal limits in all cases. The umbilical flow, which normally is continuous and nonpulsatile, showed heart-synchronous pulsations in 3 of the fetuses. The typical changes in the aortic diastolic flow occurred 1-3 days before the onset of the cardiotocographic changes. This suggests that the changes in the fetal aortic blood velocity might be a clinically useful early sign of imminent asphyxia.

Amniotic Fluid↗
PubMed1989

Mean red cell volume in normal, anemic, small, trisomic and triploid fetuses.

A reference range for fetal mean red cell volume (MCV) with gestation was established from the study of samples obtained by cordocentesis from 466 pregnancies undergoing prenatal diagnosis for non-erythrocyte abnormalities. The mean MCV decreased from 145 fl at 16 weeks to 113 fl at 36 weeks of gestation. Alterations in MCV were investigated in 154 red cell isoimmunized and 231 small for gestational age (SGA) fetuses. In red cell isoimmunization, significant macrocytosis was observed when the fetal hemoglobin concentration deficit was greater than or equal to 6 g/dl. In the chromosomally normal SGA fetuses (n = 178), the MCV was increased and the magnitude of macrocytosis was significantly associated with gestation and the degrees of fetal 'smallness' and fetal hypoxemia. However, the most severely macrocytotic SGA fetuses were those with triploidy (n = 22). In the SGA fetuses with other chromosomal defects (n = 31), the MCV was higher than the controls but lower than that of the chromosomally normal hypoxemic fetuses. It is suggested that in severe growth retardation there is developmental delay in the normal evolution from hepatic to medullary hemopoiesis and this is most marked in triploid fetuses. In contrast, in red cell isoimmunization the switch to medullary erythropoiesis is normal, but in severe anemia there is secondary recruitment of hepatic erythropoiesis.

Anemia, Hemolytic, Autoimmune↗
PubMed1990

Evaluation of the preload condition of the fetus by inferior vena caval blood flow pattern.

Using pulsed Doppler ultrasound, blood flow in the inferior vena cava (IVC) was studied in 47 normal fetuses from 24 to 40 weeks of gestation and 35 abnormal fetuses, with the exception of those with arrhythmias. The abnormal fetuses were divided into 4 groups according to diagnosis, i.e., 6 cases of heart disease with hydrops (group 1), 9 cases of heart disease without hydrops (group 2), 11 cases of hydrops without heart disease (group 3), and 9 cases of other fetal diseases (group 4). By measuring the velocity of IVC blood flow, we defined a new index, the change in parallel with reverse flow velocity, and called it the preload index (PLI). In normal fetuses, PLI values ranged from 0 to 0.37 and had no relation with gestational age. The PLI was significantly higher in groups 1-3 than in normal fetuses. In group 1, the PLI was also higher than in group 2. In group 3, the PLI values in 4 cases of chylothorax, 1 of chyloascites and 1 of cytomegalovirus infection were significantly lower than in the remaining 5 cases where the cause of hydrops was undetermined. The PLI was normal in 9 fetuses with other diseases and no hydrops. The PLI was increased in conditions in which excessive preload, tricuspid regurgitation, or some kind of structural heart disease were present.

Blood Flow Velocity↗
PubMedDate not supplied

Circulating hematopoietic stem cell populations in human fetuses: implications for fetal gene therapy and alterations with in utero red cell transfusion.

Circulating progenitor cell populations in normal human fetuses and fetuses with various hematological problems were evaluated. Thirty blood samples from 21 human fetuses (17-36 weeks of gestation) were assayed for erythroid, myeloid, and mixed-cell progenitor cells. The mean number of progenitor cells/10(4) blood mononuclear cells in the normal fetal population was 103 +/- 47. Granulomonocytic and mixed progenitor cells (capable of giving rise to both erythroid and myeloid progeny) were the predominant progenitor types in these samples, with pure erythroid progenitors barely detectable. The frequency of progenitor cells in the samples from fetuses with hematological disorders was within the range of normal in all but 1 fetus infected with parvovirus in whom very few progenitor cells were detected. The frequency of progenitor cells in the blood did not change after intravascular red cell transfusion for alloimmunization despite the large volumes transfused, indicating that transfusion may have triggered a release of progenitor cells into the circulation. Progenitor cells in human fetal blood are present in distributions similar to those commonly detected in cord blood. Their total number in the circulating blood is in the same order used for pediatric and adult bone marrow transplantation. These results can be used to calculate the number of colony-forming cells which could be obtained from a fetus by in utero apheresis and which could be made available for autologous fetal gene therapy.

Antigens, CD34↗
PubMedDate not supplied

Cardiac expression of sarcoplasmic reticulum calcium ATPase in fetuses with trisomy 21 and trisomy 18 presenting with nuchal translucency.

At 10-14 weeks of gestation about 80% of fetuses with chromosomal defects have abnormal accumulation of subcutaneous fluid in the nuchal region that is visualized by ultrasonography as nuchal translucency. A possible cause for this translucency is cardiac dysfunction due to the associated defects in the heart and great arteries. The aim of this study was to investigate whether in cardiac tissue from trisomic fetuses, compared to normals, there is an alteration in the steady state levels of expression of the genes encoding sarcoplasmic reticulum calcium ATPase (calcium ATPase), which is known to be downregulated in postnatal heart failure. After termination of pregnancy at 10-18 weeks of gestation, mRNA was extracted from cardiac tissue in 11 trisomy 21 and 4 trisomy 18 fetuses. Densitometric analysis of the Northern and slot blots was used to determine the steady state levels of expression of calcium ATPase and the values from the trisomic fetuses were compared to those of 30 normal controls at 10-18 weeks. Calcium ATPase gene expression did not change significantly with gestation at 10-18 weeks. In trisomic fetuses there was no significant decrease in calcium ATPase expression and expression levels of calcium ATPase were not related to increased nuchal translucency. However, the levels expressed in fetuses are already very low and cardiac dysfunction as a potential etiological factor cannot be excluded.

Abortion, Induced↗
PubMedDate not supplied

Alterations in ventricular filling in small-for-gestational-age fetuses.

OBJECTIVE: This study was designed to evaluate if fetal diastolic cardiac function is compromised in small-for-gestational-age (SGA) fetuses with documented fetal well-being at the biophysical profile. STUDY DESIGN: We have compared indices of diastolic cardiac flow in singleton SGA fetuses with forward diastolic flow in the umbilical artery at Doppler velocimetry and documented fetal well-being (n = 10) with those of appropriate-for-gestational-age (AGA) controls with documented fetal well-being matched for gestational age at ultrasound (n = 20). RESULTS: At the mitral valve, velocity time integral (VTI) (0.059+/-0.011 vs. 0.069+/-0.011 m, p = 0.04), peak velocity of the A wave (0.426+/-0.043 vs. 0.498+/-0.087 m/s, p = 0.005), and acceleration time of the E wave (0.046+/-0.004 vs. 0.053+/-0.007 s, p = 0.008) were significantly different between SGA and AGA fetuses. At the right atrioventricular valve, only VTI was significantly different between SGA and AGA fetuses (0.065+/-0.014 vs. 0.078+/-0.011, p = 0.03). CONCLUSIONS: These findings suggest that SGA fetuses have significantly lower left and right ventricular diastolic filling compared with AGA fetuses without significant changes in diastolic function.

Blood Flow Velocity↗
PubMed1994

Effects of Braxton-Hicks contractions on fetal heart rate variations in normal and growth-retarded fetuses.

The objective of this study was to evaluate whether Braxton-Hicks contractions induce changes in fetal heart rate variation in normal and growth-retarded fetuses. 110 uncomplicated singleton pregnancies were cross-sectionally studied as well as 16 pregnancies complicated by fetal growth retardation secondary to uteroplacental insufficiency. Fetal heart rate variability was analyzed by a commercially available computerized system (2CTG Hewlett Packard, Italy) 10 min before and 10 min after the Braxton-Hicks contraction. All the included fetal heart rate tracings fulfilled the following criteria: (1) presence of a single Braxton-Hicks contraction in the 20 min considered; (2) absence of fetal heart rate decelerations after the contraction, and (3) stable fetal heart rate behavioral pattern in the period analyzed. 82 tracings of normal fetuses were analyzed during an active fetal heart rate pattern (type B) and the remaining 28 during a quiet pattern (type A). In both patterns no significant differences in delta value, long-term irregularity, short-term variability and interval index were found before and after the contraction. All the tracings of growth-retarded fetuses were analyzed during the fetal heart rate pattern A. Short-term variation and interval index significantly decreased during the first 5 min after the contraction while no significant differences were found in the other indices investigated. The decrease in these indices was significantly more marked in those fetuses developing fetal distress within 7 days. In conclusion, Braxton-Hicks contractions induce a significant decrease of short-term variation and interval index only in growth-retarded fetuses. This can be useful in the early identification of fetal compromise in such fetuses.

Cross-Sectional Studies↗
PubMed1989

Outcome of fetuses with abnormal biophysical profile.

Sonographic observation of fetal behavior as a possible indicator for the state of fetal health was quantified with a modified biophysical profile (BPP). The observation time was extended to 40 min, as the fetal rest-activity cycle implies that inactivity may last that long. Gestational age ranged 27-43 weeks. Cardiotocography (CTG) was performed subsequent to an abnormal BPP (ultrasound score 0-4). Reactivity, indicating favorable fetal outcome, was more common in near-term fetuses, suggesting that BPP should be interpreted in relation to gestational age. Therefore, fetuses with an abnormal BPP (n = 29) were each matched and compared with 2 fetuses of same gestational age but normal BPP (ultrasound score 6-8; n = 58). The perinatal mortality and morbidity were significantly higher in infants with abnormal score than in infants with normal score (p less than 0.01). BPP by third trimester sonography helps to diagnose acutely endangered fetuses, and an abnormal fetal movement pattern should lead to further evaluation, i.e. CTG. While BPP scoring, as compared to CTG, is less favorable as a primary surveillance technique and not superior for identifying the hypoxic fetus, additional information is obtained with BPP by diagnosing the growth-retarded and/or malformed fetus.

Cardiotocography↗
PubMed1985

Significance of cardiac defects in the developing fetus: a study of spontaneous abortuses.

We investigated the impact of heart defects on the developing human fetus by examining 412 hearts from consecutive spontaneous abortuses. In each case, the cardiac morphology was correlated with the autopsy findings and the karyotype (unavailable in 115 hearts not successfully cultured). Of the 412 hearts, 10 (2.4%) contained structural defects (six ventricular septal defects, one atrial septal defect with ventricular septal defect, and one each coarctation, atrioventricular septal defect, and tetralogy of Fallot). Only one of 10 had major extracardiac malformations. Of the 277 fetuses with normal karyotype, three (1.1%) had heart defects. Of the 20 fetuses with abnormal karyotype, four (20%) had heart defects. In the remaining three fetuses with heart defects, the karyotype was not obtained. Thus (1) 57% of spontaneous abortuses with congenital heart defects contained major chromosomal abnormalities, (2) the spectrum of heart defects among spontaneous abortuses was similar to that among liveborns, and (3) since the prevalence of heart defects among fetuses without other major abnormalities was similar to that among liveborns, heart defects alone may not jeopardize the survival of a developing fetus.

Abortion, Spontaneous↗
PubMed1990

Doppler studies of vena cava flows in human fetuses. Insights into normal and abnormal cardiac physiology.

We examined vena cava Doppler flow velocity tracings from 69 fetuses between 22 and 40 weeks' gestation. Twenty-three fetuses had arrhythmias. Fifteen fetuses had absent end-diastolic Doppler velocities in the umbilical artery, a condition associated with intrauterine growth retardation, and 15 normal fetuses with normal umbilical artery Doppler velocity ratios were matched by gestational age. In studies in 16 additional fetuses, inferior vena cava Doppler velocity waveforms were compared with superior vena cava Doppler velocity waveforms. Peak velocities and time-velocity integrals of forward or reverse flow during systole, early diastole, and atrial contraction were measured. In addition, the time-velocity integral during flow coincident with atrial contraction (a wave) was expressed as a percent of the time-velocity integral of total forward flow during both systole and early diastole. Systolic-to-diastolic ratios of inferior vena cava forward time-velocity integrals were not significantly different from systolic-to-diastolic ratios of superior vena cava forward time-velocity integrals (p = 0.86), but the percent of blood moving in a reverse direction during atrial contraction in the inferior vena cava was greater than the percent of blood moving in a reverse direction in the superior vena cava (p less than 0.05). Relative forward flow in early diastole in the group of normal fetuses increased with advancing gestational age (r = 0.60, p less than 0.05). During premature atrial contractions flow in the inferior vena cava was reversed, and the percent of reverse flow during atrial systole increased significantly from 4.5 +/- 0.3% to 28.3 +/- 3.7% (mean +/- SEM, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗