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PubMedDate not supplied

The fetus as a patient: an essential ethical concept for maternal-fetal medicine.

The objective of this paper is to provide an ethical analysis of the concept of the fetus as a patient and to identify the clinical implications of this concept for maternal-fetal medicine. The principles of beneficence and respect for autonomy are applied to the viable and previable fetus. We argue that the viable fetus is a fetal patient. The previable fetus is a fetal patient only when the pregnant woman confers such status on it. When the fetus is a patient, directive counseling for fetal benefit is ethically justified. When the fetus is not a patient, counseling should be non-directive.

Beneficence↗
PubMedDate not supplied

Principal substrates of fetal metabolism: fuel and growth requirements of the ovine fetus.

In those fetuses studied, the glucose uptake by the fetus has been a major source of calories, although in all instances it has been insufficient to account for the total fuel requirements of the fetus. The glucose/oxygen quotients in different mammalian fetuses vary from about 0.5 to 0.8. Glucose transport across the placenta has been altered by fetal hyperinsulinaemia and by maternal fasting. Fetal hypoglycaemia is common to both conditions. However, umbilical glucose uptake increases with fetal hyperinsulinaemia and decreases with maternal fasting. During fasting, concomitant with a decrease in fetal glucose supply, there is an increase in amino acid catabolism. A high rate of placental production of both ammonia and lactate has been demonstrated in several mammalian species. Umbilical lactate uptake is sufficient to account for about 25% of the oxygen consumption in the ovine fetus. Ammonia production by the sheep placenta is reflected in increased ammonia concentrations in both the maternal and fetal circulations. In the ovine fetus, transport of umbilical amino acid has exceeded that required for new tissue growth, supporting the observations of a high urea production rate during fetal life. Neutral and basic amino acids represent the bulk of the amino acids transported across the placenta. In contrast there is a net uptake of glutamate from the fetal circulation into the placenta and very little umbilical uptake of aspartic acid. The umbilical uptake of free fatty acids varies markedly among species. In some species, such as the sheep and the cow, no umbilical veno-arterial differences for free fatty acids can be demonstrated.

Amino Acids↗
PubMed1982

Axoglial synaptoid contacts in the neural lobe of the human fetus.

Axoglial synaptoid contacts as well as junctional specializations were examined in the neural lobe of five human fetuses ranging from 7.5 to 19 weeks of ovulation age. Because synapselike contacts (SLC), which have both presynaptic and postsynaptic densities, were observed only in the younger fetus (7.5 weeks), they may be transient structures. Axoglial SLC were also found in older fetuses, but their structural characteristics were different from those found in a 7.5-week fetus in that the cytoplasmic membrane density was found only on the presynaptic side and its extent was decreased. In the youngest fetus observed here (7.5 weeks), puncta adherentia were observed. In the fetuses older than 11 weeks, gap junctions, long adherentia-type junctions with thick filamentous structures, and mixed junctions with both types of contact were found between pituicytes.

Axons↗
PubMed2006

Long-term effects of a midgestational asphyxial episode in the ovine fetus.

We and others have shown previously that fetuses at midgestation can survive 30 min of complete umbilical cord occlusion, although hydrops fetalis (or gross fetal edema) results. To investigate whether this hydrops resolves by late gestation and if there are any long-term consequences of the asphyxial insult on the heart and kidneys, eight fetuses were subjected to 30 min of complete umbilical cord occlusion at 0.6 gestation (90 days; term 150 days) and were compared to a sham group (n = 10). During the occlusion period, fetuses became severely hypoxemic, hypercapnemic, and acidotic, with both blood pressure and heart rate decreasing. Most variables had returned to normal by 2-hr recovery. At 129 +/- 1 days of gestation, approximately 40 days post occlusion, some fetuses were still slightly hydropic as skin fold measurements were increased (P < 0.01), although fetal body weight was not different from the sham group. The two groups had similar heart and kidney weights, ventricular cardiac myocyte nucleation, and glomerular number. By contrast, brain weight was reduced by 37% (P < 0.001) and the cerebral lateral ventricles were grossly dilated. Lungs were 50% smaller than in sham fetuses (P < 0.001). Thus, the hydrops that develops at midgestation as a result of a severe asphyxial episode can, but does not always, fully resolve by late gestation. Also, while fetuses at midgestation can survive this asphyxial episode with no long-term impact in renal or cardiac size, nephron number, or cardiomyocyte nucleation, the brain and lungs are severely affected.

Acidosis↗
PubMed2006

Pharmacokinetic studies of green tea catechins in maternal plasma and fetuses in rats.

We carried out a pharmacokinetic study to determine the levels and profiles of catechins in pregnant rats and their fetuses after ingestion of green tea extract (GTE). We measured total catechin levels after enzyme digestions. Dams, at 15.5 days of gestation, were fed with GTE and catechins were measured in the maternal plasma, placenta, and fetus 0, 0.5, 1, 2, 3, 5, 8, 10, 12, 16, and 20 h after maternal GTE intake. The pharmacokinetic changes were analyzed by non compartmental models. We found that maternal plasma concentrations of catechins were about 10 times higher than in placenta and 50-100 times higher than in the fetus. AUC and Cmax levels of (-)-epicatechin (EC) were the highest in plasma while the levels of (-)-epigallocatechin gallate (EGCG) were the highest in the placenta and the fetus. The exposure level of catechin derivatives was higher than the gallate derivatives in maternal plasma after normalization but reversed in the placenta and fetus. The absorption of epi-isomers in plasma was found to be more favorable than their non epi-isomer counterparts. EGCG had the highest level of exposure (AUC) and the highest Cmax in the fetus, implying it may have potential for in utero antioxidant protection.

Animals↗
PubMed2005

Vascular-type disruptive defects in fetuses with homozygous alpha-thalassemia: report of two cases and review of the literature.

BACKGROUND: The thalassemias are an inherited group of heterogeneous anemias in which one or more of the globin chains in the hemoglobin tetramer are absent. Fetuses with homozygous alpha-thalassemia, which is particularly prevalent in people of Southeast Asian extraction, experience deficient alpha-globin chain synthesis and cannot produce hemoglobin F (the primary fetal hemoglobin after 8 weeks' gestation). Instead, they produce an anomalous hemoglobin, hemoglobin Bart's, with an unusually high affinity for oxygen, leading to profound anemia and tissue hypoxia. METHODS AND RESULTS: Here we report on two fetuses with homozygous alpha-thalassemia who displayed structural defects of a vascular disruptive type. Both fetuses demonstrated limb anomalies, including terminal transverse limb deficiencies, and one fetus was found to have a brain malformation consisting of a neuronal migrational defect. The limb anomalies and suspected brain malformation were detected on prenatal ultrasound prior to confirmation of the diagnosis of alpha-thalassemia in one case; in the other case prenatal records were not available. While microcephaly, hydrocephalus, and retarded brain growth have been rarely reported in association with homozygous alpha-thalassemia, this is the first report of a true brain malformation in an affected fetus. Limb anomalies, on the other hand, appear to be more frequent. Recently, aggressive in utero and postnatal therapies for homozygous alpha-thalassemia have been attempted with some success. CONCLUSIONS: Our cases and those from the medical literature suggest that couples need to be counseled about the risks of congenital anomalies of a vascular disruptive type in affected fetuses. Furthermore, data from the literature suggests that in utero therapy may not significantly decrease these risks as such anomalies may be present prior to the institution of therapy. In addition, in hydropic infants with vascular disruptive defects, especially in those of Southeast Asian origin, homozygous alpha-thalassemia should be suspected as a likely etiology.

Adult↗
PubMed2006

Diagnosis, surveillance, and treatment of the anemic fetus using middle cerebral artery peak systolic velocity measurement.

The in utero course of the anemic fetus has improved dramatically, owing to early diagnosis and cordocentesis transfusion. In utero invasive procedures such as amnio- and cordocentesis have become important modalities in the evaluation and treatment of anemic fetuses. However, they carry risks for both the mother and fetus. A valid and sensitive noninvasive means of following the anemic fetus is the evaluation of changes in the middle cerebral artery peak systolic flow velocity (MCA-PSV). This is a sensitive tool for both the evaluation of fetal anemia and response to treatment. Intracerebral vessels respond earliest to the fetal anemic state, and are readily accessible for ultrasound examination. We describe the methodology and evolving clinical applications of MCA-PSV measurement in the fetus, through an overview of the literature describing the development and application of MCA-PSV measurement in fetuses at risk of fetal anemia of various immune and nonimmune etiologies, illustrated by index cases from our center. MCA-PSV measurement is essential in the diagnosis, evaluation, and management of cases of fetal anemia. The use of this modality lessens the need for invasive procedures. The method is readily accessible and should be integrated into the repertoire of all obstetric ultrasound centers.

Anemia↗
PubMed1995

Cardiac flow after fetal blood sampling in normally grown and growth-retarded fetuses.

The objective of this study was to evaluate the effect of fetal blood sampling on cardiac flow velocity waveforms. Flow velocity waveforms were measured from the ascending aorta and pulmonary artery immediately before and after fetal blood sampling in 29 normally grown and 12 growth-retarded fetuses. The latter group was characterized by abnormal Doppler indices in the umbilical artery and middle cerebral artery suggestive of uteroplacental insufficiency as the causative factor of the impaired growth. The flow velocity parameters studied were the peak velocity, the time to peak velocity, and the left and right cardiac output and their ratio. In normally grown fetuses, the peak velocity and right and left cardiac output values increased significantly after fetal blood sampling, while no significant changes were observed in the other indices considered. The gestational age at the time of the procedure was positively related to the amplitude of these changes. In growth-retarded fetuses, fetal blood sampling did not induce any significant increase in cardiac output or peak velocities, while in more than 50 per cent of the fetuses these Doppler indices decreased. The amplitude of the decrease was significantly related to the severity of acidosis in the umbilical vein. In conclusion, the cardiac haemodynamic response to fetal blood sampling differs between normally grown and growth-retarded fetuses. This difference may explain the higher rate of complications occurring in the latter group of fetuses after blood sampling.

Blood Flow Velocity↗
PubMed1977

Effect of intraamniotic administration of vitamin A on rat fetuses.

The present study examines the effect of intraamniotic (i/a) administration of vitamin A to rat fetuses. Vitamin A aquasol in concentrations of 50 I.U., 100 I.U., and 300 I.U., was mixed in 5 microliter of saline. On day 13 of gestation, each of the tree experimental subgroups were injected i/a with varying doses of vitamin A. The four control subgroups consisted of: (1) i/a injection of 5 microliter of saline only, (2) amniotic puncture only, (3) laparotomy or (4) i/a injection of sorethytan oleate. The fetuses were recovered on day 18 of gestation, and were weighed and examined for gross malformations. The viable fetuses from the experimental groups showed various malformations such as cleft palate, micrognathia and limb defects. The percentage of resorbed fetuses was significantly high. The control fetuses showed a moderate number of resorptions; however the percentage of malformations was small. The results show that the i/a method can be used effectively to study the direct teratogenic effect of vitamin A on the fetuses.

Abnormalities, Drug-Induced↗
PubMed2006

Metopic suture in fetuses with holoprosencephaly at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVE: To investigate the development of the metopic suture in fetuses with holoprosencephaly at 11 + 0 to 13 + 6 weeks of gestation. METHODS: Three-dimensional (3D) ultrasound was used to measure the height and gap between the frontal bones in 200 normal fetuses and in nine fetuses with holoprosencephaly at 11 + 0 to 13 + 6 (median, 12) weeks of gestation. RESULTS: In the 200 normal fetuses, the height of the frontal bones increased significantly with gestation from a mean of 2.5 mm (5(th) and 95(th) centiles: 1.9 mm and 3.3 mm) at 11 weeks to 6.1 mm (5(th) and 95(th) centiles: 4.6 mm and 8.1 mm) at 13 + 6 weeks. The gap between the two frontal bones did not change significantly with gestation (mean: 1.5 mm; 5(th) centile: 1.0 mm; 95(th) centile: 2.0 mm). In fetuses with holoprosencephaly, the height of the frontal bones was significantly larger (mean difference, 5.6 SDs; range, 3.9-7.7 SDs; P < 0.0001) and the gap was significantly smaller (mean 0.2 mm, range 0-0.8 mm; P < 0.0001) than those in normal fetuses. CONCLUSIONS: Holoprosencephaly is associated with an accelerated development of the frontal bones and premature closure of the metopic suture.

Adult↗
PubMed2002

Developmental stage-specific expression of the alpha and beta subunits of the HIF-1 protein in the mouse and human fetus.

Erythropoietin (Epo) is a glycoprotein hormone that is the primary regulator of erythropoiesis. Transcription of the Epo gene increases in response to hypoxia or anemia. Epo is synthesized in the liver in fetal life and in the kidney later in gestation. In the mammalian fetus the switch in Epo production from the liver to the kidney occurs in the third trimester. Hypoxia-inducible factor (HIF-1) is a heterodimeric transcription factor consisting of an alpha and beta subunit that binds under hypoxic conditions to an enhancer element in the 3' region of the Epo gene. In order to determine if there is a relationship between expression of HIF-1 alpha and beta subunits with the shift in expression of the Epo gene from the liver to the kidney or with the transitional events occurring at birth we analyzed the expression of these mRNAs in mouse and human fetuses at different stages of gestation. Total RNA was extracted from the brain, heart, kidney, liver, and lungs of mice at P15, P17, and P19 of gestation, from newborn mice at Days 1 and 3, from an adult and an anemic adult mouse as well as from human fetuses at 14-22 weeks of gestation. RNA was analyzed by Northern blot and slot-blot hybridization using appropriate cDNA probes. HIF-1alpha and -beta mRNA were expressed in all tissues tested and at all stages of gestation in the mouse and human fetus. Expression of HIF-1alpha and -beta in the mouse fetus was highest in the brain followed by heart, kidney, lung, and liver. Expression in the fetal and newborn mice was higher versus the adult and expression was higher in the anemic versus the normal adult mouse. In the human fetus a higher expression of HIF-1alpha was noted in the brain followed by heart, kidney, lung, and liver. There was a small trend toward a decrease in expression with advancing gestational age. HIF-1beta was expressed to a similar extent in all human tissues examined. Our studies indicate that expression of HIF-1alpha and -beta subunits was not related to the switch in Epo gene expression from the liver to the kidney. Although expression of HIF-1alpha and -beta did not decrease immediately after birth, it is possible that the HIF-1 protein is involved in the various events that occur during transition after birth.

Animals↗
PubMed1981

Hyperglycaemia induced by glucose infusion in the unrestrained pregnant rat during the last three days of gestation: metabolic and hormonal changes in the mother and the fetuses.

Continuous glucose infusion was used to induced mild hyperglycaemia in unrestrained pregnant rats during the last three days of pregnancy. Control pregnant rats were infused with distilled water. Fetuses were studied after normal or prolonged pregnancy. Fetuses from glucose-infused rats, compared with controls, showed higher plasma glucose levels, increased plasma insulin and lower plasma glucagon concentrations. Pregnancy prolonged until day 23.5 resulted in a rise in the glucagon/insulin ratio from 6.5 to 67 in fetuses from control rats and from 1.3 to 13 in fetuses from glucose-infused rats. Concurrently in fetuses from control rats, liver phosphoenolpyruvate carboxykinase activity increased markedly and liver glycogen stores decreased sharply. In fetuses from glucose-infused rats, liver phosphoenolpyruvate carboxykinase activity rose and glycogen content decreased, but to a lesser extent. These results show that both the A and B cells of the rat fetal pancreas are sensitive to chronic glucose stimulation.

Animals↗
PubMed1989

Topography of the pelvic autonomic nerves in human fetuses between 21-29 weeks of gestation.

A topographical study concerning the autonomic nerves in the pelvis of human fetuses was performed by investigating 300-600 microns thick sections through fetal pelves, impregnated with the epoxy resin E 12 and cut with a diamond wire-saw. In addition the inferior hypogastric plexus of a 26-week old male fetus was dissected by lateral approach. In 21-29-week old fetuses the pelvic autonomic nerves are relatively thick. Thus the nerves stand out well against surrounding structures and their topographical relationships can exactly be determined. The inferior hypogastric plexus of 21-29-week old fetuses is situated on a curved line between the rectum and the ventrally adjacent structure. It constitutes a rectangular plate, which cannot be subdivided into individual plexuses for the different pelvic organs. The fetal plexus is heavily ganglionated. Large ganglia, forming the so-called ganglion of "Frankenhaeuser", are found in the female as well as in the male fetus. In the fetal pelvis the connective tissue compartments are still clearly arranged, because adipose tissue is not yet abundant. The greater part of the inferior hypogastric plexus is situated exactly at the border between a dense visceral tissue medially and a loose parietal tissue laterally. The plexus does not share a common connective tissue cover with the pelvic blood vessels. In fetuses the inferior hypogastric plexus lies in close vicinity to serveral organs, but the pelvic floor is the only region where the nerves can hardly be separated from the surrounding structures.

Autonomic Nervous System↗
PubMed1980

Increased somatomedin and cartilage metabolic activity in rabbit fetuses injected with insulin in utero.

The effect of insulin injection in fetal rabbits on plasma somatomedin activity and cartilage metabolism was investigated. One fetus in each of 12 litters was injected with 1 unit of insulin zinc suspension subcutaneously on day 27 of gestation and a control fetus was injected with the same volume of 0.154 mol/l saline. The litter was delivered by caesarean section on day 29 and each fetus identified. Plasma somatomedin activity was determined by fetal rabbit cartilage bioassay. Costal cartilage from individual fetuses was incubated in medium containing [3H]thymidine or [35S]sulphate as indicators of cell replication and matrix synthesis respectively. Individual values for somatomedin activity or cartilage isotope uptake were ranked within a litter. In each case the rank in the litter of the insulin-injected fetus, but not the saline-injected fetus, was significantly higher than the mean rank of the litter. Insulin did not stimulate cartilage metabolism in vitro.

Animals↗
PubMed1978

The endocrine pancreas of the fetus from diabetic pregnant rat.

Diabetes was induced in female rats by streptozotocin administration prior to mating. Pregnant rats were divided into "severe diabetics" (blood glucose concentration above 300 mg/100 ml) and "mild diabetics" (blood glucose ranging from 100 to 200 mg/100 ml). When compared to control fetuses, fetuses from severely diabetic mothers showed a slight decrease of body weight on days 20.5 and 21.5. Fetal pancreatic insulin stores and plasma insulin concentrations were decreased at 19.5, 20.5 and 21.5 days. The insulin response to glucose was impaired both in vivo and in vitro. In contrast, fetuses from mildly diabetic females showed no change in body weight. Pancreatic and plasma insulin concentrations were increased at 19.5, 20.5 and 21.5 days. The response of the beta cells of term fetuses of mild diabetics to glucose stimulation was enhanced in vitro. These results are consistent with the hyperglycaemia-hyperinsulinaemia theory with regard to the fetuses from mildly diabetic rats and with an impairment of insulin biosynthesis and release in fetuses from severely diabetic females.

Animals↗
PubMed1993

Role of the notochord in the development of cephalic structures in normal and anencephalic human fetuses.

Normal and anencephalic human conceptuses were analysed histologically to investigate the role of differentiation of the intracranial notochord and its relation to the formation of the basichondrocranium. We have examined 16 normal embryos and fetuses and 4 anencephalic fetuses. Each developmental stage of formation of the normal basichondrocranium presented specific morphological changes during the course of notochord depletion. In contrast with normal specimens, anencephalic fetuses presented malformations of the basichondrocranium which were always related to an abnormal position of the notochord. Macroscopical differences between craniorachischisis and cranioschisis in fetuses with anencephaly correlated with the existence of two histologically different degrees of malformation. In fetuses with craniorachischisis we found severe disturbances in the shape, position and ossification of the basichondrocranium and in the course of the intracranial notochord. In fetuses with cranioschisis the described disturbances of the basichondrocranium and intracranial notochord were mild. In addition, marked differences in affection of the central nervous system and the hypophysis were observed. These findings suggest different periods of dysmorphogenesis. Our results underline the importance of the chordal mesoderm in the differentiation for the formation of cephalic structures in Man.

Abnormalities, Multiple↗
PubMed1982

[Contents and distribution of Fe, Cu, Zn, Ni, and Mn in fetuses, amniotic fluid, placenta, and uterus of rats].

Fetuses, amniotic fluid, placenta, and uterus were taken from five gravid rats shortly prior to delivery, and the contents of Fe, Cu, Zn, Ni, and Mn were analyzed. Fe, Cu, Zn, and Mn exhibited a similar concentration in dry matter (DM) in all tested reproductive organs, whereby Fe-contents were five to ten times higher than Zn-contents and those five to ten times higher than Cu-contents, which amounted to 10-20 ppm. The Mn-contents range about a factor of ten below. Ni-concentration in DM of fetuses, placenta and uterus is below 1 ppm, whereas in contrast to this, Ni-concentration of 14 ppm in DM of amniotic fluid is 34 times higher than in fetuses and placenta. Uterus contained twice as much Ni as fetuses. Concerning the total content of the individual trace elements, Ni reacts also different as compared to Fe, Cu, Zn, and Mn. Its amniotic content exceeds the fetal content by 40%. Total excretion of Fe, Cu, Zn, Mn, and also DM is distributed differently as compared to Ni. Fetuses contain 60%-70% of these trace elements, placenta 15%-25%, uterus 6%-16%, and amniotic fluid only 1%-2%. Ni, however, is excreted mostly via amniotic fluid by about 35% of total excretion and only by about 25% via fetuses. These findings, concerning Ni, are discussed in detail.

Amniotic Fluid↗
PubMed2000

An investigation of the conus medullaris and filum terminale variations in human fetuses.

The morphologic structure of the conus medullaris and filum terminale was investigated by dissection in 123 human fetuses, obtained from Selçuk University, Faculty of Medicine and Maternity hospital of Konya between 1992-1995. In 78 fetuses, the conus medullaris and filum terminale had a normal morphologic aspect, whereas there was a slight depression or groove formation in the closure region of the caudal neuropore in 45 fetuses. In 15 fetuses, important malformations of the cranium and vertebral column were observed. The morphologic aspects of the conus medullaris in 30 fetuses were abnormal in shape and position, among them 24 fetuses had an abnormal filum terminale (grooved, depressed, thickened or duplicated) whereas it was normal in 6. Deficiency of closure of the caudal neuropore was considered to have a negative effect on the fetal development of the filum terminale.

Cadaver↗