Biomedical subjects
Publications and source records attributed to F D Frigoletto.
Elective induction of labor, followed by vaginal delivery, was carried out at 25 to 39 weeks' gestation in 14 consecutive patients (15 pregnancies) with an anencephalic fetus. Laminaria tents and prostaglandin drugs were used. The procedures produced no serious untoward effects and required only 3 hospital days.
In order to study the effect of renal disease on urinary estriol clearance rate, we have measured the concentrations of plasma and urinary estriol (E3) in pregnancies of 69 diabetic patients, 25 of whom had nephropathy. No correlation was found between endogenous creatinine clearance (CCr) and estriol clearance (CE3) rates (r = 0.07), and mean CE3 of diabetic patients with diminished CCr (less than 100 ml/min) was not significantly different from that of patients with normal CCr (greater than or equal to 100 ml/min). The ratios between total, unconjugated estriol and urinary estriol concentrations in patients with diminished CCr were not different from those patients with normal CCr. Cases where high plasma estriol and low urinary estriol concentrations coexisted were not found. It is concluded that in this group of diabetic patients, diminished CCr had no discernible effect on urinary CE3 possibly because renal tubular function remained intact. In patients with diabetic nephropathy either urinary or plasma E3 could be used to assess fetoplacental function.
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Twenty-eight fetuses, at 14-22 gestational weeks, were examined by amniography to identify a thoracic, lumbar, or sacral myelomeningocele. The end point was a fluoroscopic spot film with the fetal back in profile, to show the presence or absence of a bulging midline mass. Fetal irradiation was 0.66 rad +/- 0.36 (SD). There were 26 true negatives and one indeterminate examination. The one true positive was in a patient who had just had negative real-time ultrasonography. It is suggested amniography be used (1) when ultrasonography and amniotic fluid alpha fetoprotein determination disagree about the presence of a neural tube defect, and (2) for further confirmation when both these tests are positive.
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Continuous ultrasonic observation of needle placement for aspiration, biopsy, or catheter placement is a novel and specific use of phased array imaging. In the case of IUTx, catheter placement into the fetal peritoneal space is accomplished rapidly, with reduced risk of fetal trauma, and without exposure to ionizing radiation. Experience with 27 transfusions in 11 patients is presented.
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We attempted prenatal diagnosis of hemoglobinopathies in 15 cases--11 for beta-thalassemia and four for sickle-cell disease. Fetoscopy was used in seven cases, and placental aspiration in eight. One premature labor, with fetal loss, followed placental aspiration. Globin synthesis was assessed by incubation of samples with 3H-leucine and chain separation on carboxymethylcellulose columns. Homozygous disease was predicted in two pregnancies, which were interrupted, and the diagnosis confirmed. In one case homozygosity was suspected. A repeat test was advised but not accepted. The fetus had thalassemia trait. One pregnancy was interrupted despite our prediction of thalassemia trait. Eight pregnancies went to term. Seven predictions that the infants would not have homozygous disease were confirmed. One prediction of sickle trait proved to be sickle-cell disease. Although prenatal diagnosis of hemoglobinopathies is feasible, the present frequency of fetal loss and diagnostic error indicates need for improvement.
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To determine whether beta-thalassemia can be detected in the fetus, blood was obtained from abortuses of normal mothers and of mothers with beta-thalassemia trait. The red cells were incubated with radioactive leucine and the globin chains were analyzed by radiochromatography. Two independent methods were utilized to correct the results for contamination by maternal radioactive beta-chain, and the corrected beta/gamma ratios were compared to a previously established range of normal fetal beta/gamma synthetic ratios obtained by similar measurements in pure fetal cells. In the erythroid cells of three fetuses from mothers with beta-thalassemia trait, the beta/gamma synthetic ratio was normal in two. The third had a beta/gamma ratio of 0.04 at 10 1/2 weeks, a 50% reduction, consistent with fetal beta-thalassemia trait. Two other fetuses, derived from parents both of whom had beta-thalassemia trait, were also studied. One had a beta/gamma ratio of 0.029 at 8 weeks, a 65% reduction, also consistent with beta-thalassemia trait. The cells of the other had a ratio of essentially zero at 11 weeks, highly suggestive of homozygous beta-thalassemia. Although further experience will be needed to distinguish the homozygous and heterozygous states reliably, it now appears that the beta-thalassemia gene is expressed in the first trimester. Therefore these data suggest that the antenatal diagnosis of beta-thalassemia is becoming an attainable goal.
Estetrol (15alpha-hydroxyestriol or E4) is considered to be a specific product of fetal liver and has been suggested as a good indicator of fetal well-being. The concentration of unconjugated estetrol (E4) was measured by rapid and specific radioimmunoassay in 1 ml of maternal plasma. E4 levels prior to the 18th week of pregnancy were often undetectable (smaller than 50 pg/ml). The mean plasma E4 level at term of 1.2 ng/ml was 7-fold higher than that observed at 24 weeks of gestation, and no diurnal variations were found. E4 levels in fetal plasma at term were 12-fold higher than those in maternal plasma and no fetal arterial venous differences were found. Umbilical vein but not maternal plasma levels of patients undergoing vaginal delivery were higher than those undergoing cesarean section (P smaller than 0.05) suggesting increased adrenal output of E4 precursors during labor. In patients with severe Rh-isoimmune disease plasma E4 levels were not helpful in assessing fetal well-being. However, in patients with chronic hypertension or pre-eclampsia, subnormal plasma E4 concentrations always preceded intrauterine fetal death. Plasma E4 appears to be a good indicator of fetal well-being in patients with hypertensive disease of pregnancy.
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