Biomedical subjects
Publications and source records attributed to F Daffos.
In utero fetal blood sampling was performed in 55 cases for prenatal diagnosis of hemophilia A and B. Fifteen fetuses were found to be affected. However, with this new procedure, it was possible to demonstrate that fetuses were not hemophiliacs in 40 cases. Therefore, pregnancy was not interrupted; these infants were born and definitely proven to be normal. There were no diagnostic errors.
Serum somatomedin C, thymidine uptake stimulating activity, and transferrin were measured in fetal blood collected by ultrasound-guided puncture of umbilical vessels in utero during prenatal assessment for mother-to-fetus transmissible infections. Serum somatomedin C and transferrin were measured by immunoassay. Thymidine activity was measured by assay of [3H]thymidine incorporation into lectin-activated human lymphocytes. Studies were conducted in 48 healthy fetuses at gestational ages 21-28 wk. From 21-24 to 25-28 wk, serum somatomedin C significantly increased from 0.05 +/- 0.06 to 0.24 +/- 0.03 U/ml, while thymidine activity significantly decreased from 1.41 +/- 0.15 to 0.95 +/- 0.06 U/ml. Transferrin levels did not change. These data suggest that the humoral control of fetal growth at midpregnancy involves mechanisms other than direct regulation by somatomedin.
Utilizing an easy and safe procedure for fetal blood sampling in utero we have studied 409 fetuses for prenatal diagnosis of rubella, toxoplasmosis, hemophilia, and hemoglobinopathies. Retrospectively we selected 163 fetuses confirmed as normal at birth and tested between 18 and 30 wk of gestation to establish normal hematological parameters and to follow the evolution of erythropoiesis, differential counts, hemoglobin synthesis, and hemostasis. Total white blood cell and platelet counts did not change during this period. The lymphocytes represented the main population and we observed a decrease of normoblasts during gestation. The results show a progressive increase of red blood cells and hemoglobin. This evolution is demonstrated by the ratio hemoglobin A to acetylated hemoglobin F. No significant modification of hemostasis was observed over a 12-wk intrauterine gestation. These results provide useful reference values for future investigations.
Seventy-two fetal blood samples obtained by umbilical vein puncture under ultrasound guidance for prenatal diagnosis and monitoring purposes were tested for the expression of 38 blood group antigens. The gestational age at sampling ranged from 18 to 34 wk with 76% of fetuses between 20 and 25 wk. Compared to adult red blood cells, the following antigens showed either abnormally decreased frequency, or significantly reduced expression: A, B, A1, H, Lua, Lub, Lea, Leb, P1, P, and I. Selected anti-I and anti-i cold agglutinins, active at room temperature, were used at appropriate dilution, in a rapid slide or spin test to check for possible mixture of the sample with maternal blood and were shown to detect contaminations up to 5%. The test has proved particularly helpful for immediate and in process assessment of foetal origin of the sampled blood.
The autosomal recessive transmission of Glanzmann's thrombasthenia (GT) and Bernard-Soulier syndrome (BSS), together with requests of families who already had children with these diseases, prompted us to investigate the feasibility of their antenatal diagnosis. The preliminary step leading to the early detection of GT or BSS was to characterize, in the normal human fetus, the platelet antigens and glycoproteins (GPs) and to define their normal amounts on the membrane surface. Blood samples from 32 fetuses between 18 to 26 weeks of gestation were collected by direct puncture of the umbilical vein using an ultrasound-guided needle. Polyclonal antibodies from human origin directed against PLA1, Leka antigens, and the GPIIb IIIa complex (IgGL), or murine monoclonal antibodies specific for GPIb (AN51, 6D1), GPIIIa (AP-3), or GPIIb IIIa (AP-2) were studied using platelet suspension immunofluorescence tests. The binding of each antibody was quantified using a cytofluorograph (Ortho 50H). PLA1 and Leka antigens were expressed in normal amounts on fetal platelets as early as 16 weeks of intrauterine life. The GPIIb IIIa complex quantified by polyclonal or monoclonal antibodies was in the same range in fetuses (IgGL = 427 +/- 23 AUF, AP-2 = 459.5 +/- 8.5; AP-3 = 536 +/- 14) and in adults (IgGL = 420 +/- 30; AP-2 = 498 +/- 11; AP-3 = 515 +/- 13). The platelet binding of antibodies that recognized GPIb was higher in fetuses (AN51 = 491.5 +/- 14; 6D1 = 479 +/- 15) than in adults (AN51 = 426.5 +/- 9; 6D1 = 449 +/- 8.7). These results suggest that immunological techniques can be applied as early as 18 weeks of gestation for the antenatal diagnosis of GT and BSS.
The identification of anti-ZWa (-PLA1) alloimmunisation is not very frequent. It can be observed in most perinatal alloimmune thrombocytopenias (PAT) and rare post transfusional purpuras (PTP). On the other hand, the clinical consequences of these immunisations are often dramatic, particularly for the foetuses for which there has been no prevention so far. The retrospective study of 132 cases, 123 PAT and 9 PTP, shows the possible irreversible complications for 18% of the newborns with PAT, but especially for 10% of the foetuses which will show PAT at birth. HLA markers are very useful to detect the people who are likely to develop an anti-PLA1 immunization for they are PLA1 negative and HLA DR3. Then, it becomes possible to prevent the complications of these immunisations. It is what we tried to do through the diagnosis and the treatment of PAT in 3 foetuses.
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Because of various prenatal diagnoses, 606 fetal blood samplings were carried out in 562 pregnancies from the gestational week 17 to 38 with use of a 20-gauge needle guided by ultrasound. The procedure was performed on outpatients under local anesthesia and without medication before or after the procedure. Pure fetal blood was obtained at the first attempt in 588 cases. A second attempt was necessary in 18 cases. Maternal blood contamination was never present. Amniotic fluid dilution was noted in 15 cases. At the beginning of our experience only three cords could not be punctured. The duration of the procedure was less than 10 minutes in 90% of cases. Fifty-eight pregnancies were terminated after consideration of the results of the diagnosis, and 504 pregnancies were continued. The complications found in these pregnancies were premature delivery (5%), growth retardation (8%), in utero death (1.1%), and spontaneous abortion (0.8%). In the future this new procedure could replace fetoscopy and initiate an important field of new investigations.
Free amino acids were determined on fetal plasma samples in 28 pregnancies between 20 and 33 wk gestation. No correlation can be observed between these concentrations and the age of gestation.
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The vitamin K dependent coagulation factor activities were measured in 63 normal human fetuses from 19 to 28 weeks of pregnancy. These activities were included between 9 to 28 percent of normal adult levels. Prothrombin antigen, factor IX antigen and protein C were also measured. There is a good correlation between prothrombin procoagulant activity and antigenicity, suggesting that low level of these vitamin K dependent proteins in fetuses is probably a consequence of liver immaturity.
Prenatal diagnosis of congenital toxoplasmosis was attempted by means of fetal blood sampling at 20-24 weeks' gestation. It was possible to detect in fetal blood samples non-specific laboratory signs of fetal infection, specific antibodies of fetal origin (IgM), and parasitaemia by inoculation of the sample into mice. Amniotic-fluid samples were also inoculated into mice and parasites were often present when the fetus was infected. Ultrasound examination of the fetus was done repeatedly, mainly to detect any enlargement of the cerebral ventricles. Together the results of these examinations allowed a reliable diagnosis, which was confirmed by the presence of necrotic foci of toxoplasmic encephalitis in the fetus in every case. Only 1 case of congenital toxoplasmosis occurred among 209 cases with negative prenatal diagnoses.
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Cortisol (F), Cortisone (E) and dehydroepiandrosterone sulfate (DHAS) were determined in maternal peripheral plasma and umbilical cord plasma between 21 and 30 weeks of amenorrhea. In fetal plasma, DHAS levels were the highest and those of F the lowest. E always exceeded F. The pattern of all these steroids was characterized by a plateau throughout the period considered. In maternal plasma, F levels were more elevated than those of E but lower than DHAS concentrations. All the steroids plateaued as in the fetus. The study of the correlation between the steroids in either the same milieu or in maternal and umbilical cord plasma demonstrated that fetal E was correlated with maternal F and with fetal F while fetal DHAS was inversely correlated with maternal E.
In congenital rubella an acid-labile alpha-interferon was present in sera collected from fetuses between weeks 21 and 29 of gestation and from children with active congenital rubella. This interferon was different from the interferon detected in normal amniotic fluid and was not found in sera from uninfected fetuses or from children with postnatally acquired rubella. The fetal interferon is of interest as a complementary marker to confirm the virus contamination of the fetuses during maternal rubella. The role of the prolonged synthesis of this interferon in congenital rubella disease and its immune defects are discussed.
The serum level of radioimmunoassayable somatomedin-C and the bioassayable growth-promoting activity evaluated by the stimulating effect of serum upon thymidine incorporation into activated lymphocytes have been measured in the blood of term human foetuses. Comparison between those with a low birth weight and those with normal birth weight has shown that small-for-gestational-age subjects have lower somatomedin-C (0.31 +/- 0.03 vs 0.52 +/- 0.03) and thymidine activity (1.03 +/- 0.11 vs 1.50 +/- 0.07) (P less than 0.001). A positive correlation between somatomedin and thymidine activity was found. There was no difference in serum transferrin levels between both groups. It is suggested that somatomedin, and probably other growth-promoting factors measured by the thymidine bioassay, play a role in regulation of the foetal growth.
The fetal karyotype was established during the second or third trimester of 18 at risk pregnancies after fetal blood sampling by direct puncture of the umbilical vein guided by real time ultrasound. Two karyotypes were abnormal. This rapid technique for karyotyping allows the obstetrician to decide early how the pregnancy should be conducted.
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