Biomedical subjects
Publications and source records attributed to F Daffos.
Fetal blood sampling under ultrasound guidance has permitted the opening of the fetal vascular compartment for diagnosis and therapy. Under very strict conditions, this procedure allows the clinician to use fetal blood analysis as a complementary routine examination.
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Blood samples were studied, prior to medical terminations of pregnancy, in two second trimester fetuses with HIV-positive mothers. Fetal blood was obtained from the umbilical vein under ultrasound guidance. No evidence of infection was found in either fetus. In particular, lymphocyte subpopulations were at normal levels and cultures yielded no reverse transcriptase activity. Postmortem findings were normal. Reliable means for prenatal diagnosis of HIV infection, with a minimal risk of false-negative results, have yet to be developed. However, further studies using fetal blood sampling should be useful for the management of HIV-positive pregnancies.
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Vitamin K status was evaluated using coagulation studies and/or vitamin K1 assays in a total of 53 normal fetuses and 47 neonates. Second trimester fetal blood samples were obtained for prenatal diagnosis under ultrasound guidance. Endogenous vitamin K1 concentrations (determined by high performance liquid chromatography) were substantially lower than maternal levels. The mean maternal-fetal gradient was 14-fold at mid trimester and 18-fold at birth. Despite low vitamin K levels, descarboxy prothrombin, detected by a staphylocoagulase assay, was elevated in only a single fetus and a single neonate. After maternal oral supplementation with vitamin K1, cord vitamin K1 levels were boosted 30-fold at mid trimester and 60-fold at term, demonstrating placental transfer. However, these levels were substantially lower than corresponding supplemented maternal levels. Despite elevated vitamin K1 concentrations, supplemented fetuses and neonates showed no increase in total or coagulant prothrombin activity. These results suggest that the low prothrombin levels found during intrauterine life are not due to vitamin K deficiency.
When infection with Toxoplasma gondii occurs during pregnancy, there is a risk that the parasite will cause severe congenital toxoplasmosis. We developed a method of diagnosing and treating congenital toxoplasmosis in utero. Diagnosis was based on the identification of maternal acute infection, followed by culture of fetal blood and amniotic fluid, testing of fetal blood for toxoplasma-specific IgM and nonspecific measures of infection, and ultrasound examination of the fetal brain. Treatment included the administration of antibiotics to all mothers with confirmed acute infection during pregnancy, with more intensive antibiotic treatment of those who had infected fetuses and who chose to continue the pregnancy. We report a prospective study of 746 documented cases of maternal toxoplasma infection, in which the infants were followed for at least three months. Infection was diagnosed antenatally in 39 of 42 fetuses. Twenty-four of the 39 pregnancies were terminated, and 15 were continued. All the mothers were treated with spiramycin throughout pregnancy; if fetal infection was demonstrated, pyrimethamine and either sulfadoxine or sulfadiazine were added to the regimen. Of the 15 fetuses with congenital toxoplasmosis who were carried to term, all but 2, who had chorioretinitis, remained clinically well during follow-up. We conclude that prenatal diagnosis of congenital toxoplasmosis is practical and that prenatal therapy in women who wish to continue their pregnancies reduces the severity of the manifestations of the disease.
Fetal magnetic resonance (MR) imaging was performed at 33 weeks of gestation for investigation of a posterior fossa abnormality found at ultrasound screening. Fetal movements were abolished by vecuronium injected under ultrasound guidance into the umbilical vein. MR images showed atrophy of the left cerebellar lobe with cisternal dilatation. These were confirmed postnatally by CT scan.
We have used a Y-chromosome specific DNA probe in a controlled study to determine the presence of Y-chromosome material and to detect numerical abnormalities in uncultured amniotic fluid cells by fluorescent hybridization. Using this non-radioactive method, we correctly predicted fetal sex within 48 h in all but 3 of 54 cases and identified an XYY syndrome. The technique was previously tested with no false-positive or false-negative results on cultured interphase or metaphase nuclei of fetal fibroblasts and adult T-lymphocytes. Fluorescent in situ hybridization was applied to long-term fixed cytogenetic preparations up to 44 months old and was shown to be reliable.
The presence of Toxoplasma gondii in amniotic fluid was demonstrated using tissue culture in four of nine cases of congenital toxoplasmosis, whereas Toxoplasma gondii antigen was undetectable using a sensitive enzyme immunoassay technique. Parasites were identified in monolayers four days after inoculation using an indirect immunofluorescence assay. Since tissue culture may provide evidence of infection within a few days, this method is proposed for early prenatal diagnosis of congenital toxoplasmosis.
The technique of fetal blood sampling for prenatal diagnosis has been shown to be both feasible and safe. The availability of fetal blood for direct evaluation has changed our attitude about the problems of both hereditary and acquired immune fetal bleeding disorders. We can continue with the classic approach and use fetal blood sampling for those conditions in which termination may be recommended, but we can also investigate less severe disorders in which the diagnosis allows us to plan the management of the pregnancy and minimize intrapartum and neonatal complications. We report our experience in prenatal diagnosis and management of 103 cases of hereditary and 18 cases of acquired immune bleeding disorders. We have developed specific management plans depending on the disorder under investigation, the severity of the condition in the fetus, and parental wishes. We have performed in utero transfusions of platelets and factor concentrate where appropriate. Efficacy of maternal therapy for fetal conditions can be directly assessed during gestation. Mode of delivery is determined by obstetric conditions and fetal status, directly assessed after appropriate therapy. Closer surveillance of the fetus by fetal blood sampling gives precise information on which to base clinical decisions to provide optimal maternal and fetal outcome.
Fetal blood sampling under ultrasound control is rapidly expanding the study of human fetal biology. Pure fetal blood is required for prenatal diagnosis, establishment of reference ranges for biologic measurements, and assessment of fetal welfare. We present here the methods that we have developed to detect contamination in more than 1500 samples. These include hematologic indexes, blood smear, erythrocyte antigens, beta-human chorionic gonadotropin, and coagulation factor assays. The tests are relatively simple, inexpensive, and widely available. No single test is reliable in all situations, and it is necessary to perform all the tests on each sample of fetal blood. In the clinical setting where irrevocable action may be taken as a consequence of our results, we require absolute assurance of the purity of the sample.
Intrauterine growth retardation is a major contributor to perinatal mortality and morbidity. The most important obstetric problem is to determine which fetuses are well in utero and which are at risk of irreversible damage or severe and prolonged neonatal morbidity. The optimal timing of delivery is at present made by subjective assessment of clinical variables. We present hematologic and biochemical values obtained by fetal blood sampling of 24 idiopathic fetuses with intrauterine growth retardation to give objective information on which to base clinical management. The results show that there is stimulation of erythropoiesis as well as evidence of red blood cell destruction and liver damage. In many cases there is acute decompensation with acid base abnormalities in a setting of chronic hematologic and biochemical changes.
In umbilical vein blood samples collected in 137 fetuses between 19 and 31 weeks of gestation, cortisol (F), cortisone (E), 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (S) were radioimmunoassayed after column chromatography on Sephadex LH-20 of plasma extracts. While F levels plateaued throughout the period considered those of E displayed an increasing pattern which appeared to be comparable with that of unbound F in pregnant women. The declining pattern of S and more particularly of 17-OHP would suggest an increasing utilization and metabolization of these F precursors by the maturing fetus. E was not correlated with either 17-OHP or S but showed a significant correlation with F. S and 17-OHP were correlated with each other and with F. The significance of these correlations was discussed according to the different origin of these steroids and to their metabolic relationships. The application of this method for the prenatal diagnosis of inborn errors of steroid biogenesis is suggested.
Rubella virus-specific IgM and IgA antibodies were quantitated by antibody capture immunoassay in adults after primary infection and after experimentally induced reinfection. Antibodies to rubella virus were also detected in fetuses whose mothers had rubella before week 18 of pregnancy. IgM and IgA concentrations in fetal blood were determined by radial immunodiffusion and enzyme immunoassay, respectively. In primary postnatal infection, IgM antibodies were consistently found until week 8 after onset of the disease, and after week 14 these antibodies were usually no longer detected. The time of disappearance of rubella virus-specific IgA varied with each individual. After vaccination of previously immune volunteers, no change was noted in level of IgA antibody, and no IgM antibody was detected. In infected fetuses, total IgM and IgA concentrations rose significantly, and rubella virus-specific IgM and IgA antibodies were detected as early as week 22 of pregnancy.
We performed 41 intravascular ultrasound-guided fetal transfusions in a total of 20 pregnancies with erythroblastosis fetalis or alloimmune thrombocytopenia. On the basis of this experience, we developed a computer-assisted procedure for determining the volume to be transfused, which provides an adequate final concentration. Fetal weight was estimated using ultrasound measurements. Fetoplacental blood volume was estimated from the regression line: fetoplacental volume (ml) = 1.046 + fetal weight (g) X 0.14. The volume to be transfused was calculated using the simple dilution formula: Vtransfused = Vfetoplacental.(Cfinal - Cinitial)/Ctransfused where C is the hematocrit or platelet count. The entire procedure is computerized, simple and rapid, and avoids resorting to repeated intermediate sampling. The dilution formula used appears to be more reliable than a formula taking into account the volume added, even in erythroblastosis fetalis where relatively large volumes are injected. This suggests rapid plasma loss during the procedure.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.