Biomedical subjects
Publications and source records attributed to C H Rodeck.
Since its introduction just over a decade ago, fetoscopy has become an effective procedure for the diagnosis of at least 50 congenital abnormalities. It can also be employed as an aid to therapeutic interventions in utero.
The prenatal diagnosis of severe combined immunodeficiency (SCID) was made in three fetuses by staining fetal blood obtained at fetoscopy with a panel of monoclonal antibodies. There were less than 100 T cells/mm3 of fetal blood in these three cases compared to 2,500/mm3 in 14 immunologically normal fetuses. Cells bearing the cortical thymocyte antigen (NA1/34) were not detected in any of the normal or affected fetal blood samples. Two of the affected fetuses were also homozygous for a deficiency of adenosine deaminase (ADA) with undetectable levels of red cell ADA. All three affected fetuses were aborted and postmortem tissue was obtained in two cases. In both of these cases the thymus was markedly hypoplastic and contained no lymphoid cells. One of these fetuses was homozygous for ADA deficiency and the virtual absence of T cells or thymocytes during the second trimester of pregnancy indicates that placental access to the maternal circulation does not prevent damage to the T lineage stem cells in this disease. Prenatal diagnosis of SCID has previously only been possible in patients with a defined metabolic defect such as ADA deficiency, but these studies indicate that prenatal diagnosis now may be offered for most at risk pregnancies.
The sinusoidal fetal heart rate pattern has been reported to be associated with fetal anemia, hypoxia, administration of alphaprodine while, in other cases, it has been followed by good fetal outcome. In this case study fetoscopy was performed in a patient with thalassemia trait for prenatal diagnosis of thalassemia. Following the insertion of the trocar, bloodstained amniotic fluid was aspirated which resulted to be all fetal in origin. Estimation of feto-maternal hemorrhage was 5.7 ml while the amount of intra-amniotic bleeding could not be assessed. Fetal heart rate, which was recorded throughout fetoscopy, showed a sinusoidal pattern starting two minutes after the fetal hemorrhage which lasted more than ten minutes. Two hours later the fetal heart rate was normal. The pregnancy continued uneventfully and a healthy female baby weighing 3100 g was delivered at 38 weeks' gestation. Review of the literature suggests that a sinusoidal pattern may be caused either by a hemodynamic disturbance or fetal acidosis. In any case it does not always indicate impending fetal death.
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Plasma levels of creatine kinase (CK) were measured in 14 abortuses, nine of which were at risk for Duchenne muscular dystrophy (DMD). The plasma CK level was found to be increased in all abortuses, compared with the value obtained by fetoscopy before the termination. The causes of the increase in CK level were found to be 1) method of termination, 2) physical state of the abortus at delivery, 3) delay between delivery of the abortus and taking the blood sample, and 4) site of blood sampling. It is concluded that even under optimum conditions of termination the plasma creatine kinase level of the abortus is significantly raised above the true level; hence, this measurement is not reliable as a guide to the genetic status of the fetus. Cardiac leakage was the main source of the raised plasma CK level in the abortus and this was corroborated by measurement of myoglobin levels.
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Metachromatic leucodystrophy was excluded in a fetus at risk, by assay of fetal blood collected at fetoscopy. Isolated fetal leucocytes were shown to have activities of arylsulphatase A and cerebroside sulphatase in the heterozygous range. The prediction was confirmed in the newborn.
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Oculocutaneous albinism was diagnosed prenatally by electron microscopic examination of fetal skin samples taken during fetoscopy at 20 weeks of gestation. Melanosome development in hair bulb melanocytes progressed no further than stage II, indicating a lack of melanin synthesis. In 4 age-matched control fetuses, numerous stage IV melanosomes, signifying active melanin synthesis, were identified. The diagnosis was confirmed after the pregnancy was terminated at 22 weeks. Examination of the fetal eye showed absence of pigment in the retinal epithelium and uvea at a stage when ocular melanogenesis would normally be active. This study shows that oculocutaneous albinism can be detected in the second trimester using similar techniques to those employed in the prenatal diagnosis of epidermolysis bullosa and ichthyosis.
Six different methods of chorion biopsy were compared and assessed in 45 patients in the first trimester of pregnancy. A total of 103 biopsies was obtained; it was found that the most reliable, accurate and safe method combined direct transcervical endoscopy with real-time ultrasound scanning, using an aspiration needle.
In a prospective randomized study, 36 patients with spontaneous rupture of the membranes of greater than or equal to 4 h duration were stimulated with 3 mg vaginal prostaglandin E2 pessaries or intravenous oxytocin. Oxytocin stimulation was associated with shorter labours and a lower incidence of abnormal cervimetric progress. Of the patients given prostaglandin pessaries, 40% required a second dose after 4 h for slow progress; 45% of the primigravidae subsequently developed abnormal labour which was corrected by augmentation with oxytocin in all cases. One caesarean section was carried out for disproportion, and the remaining 35 patients were delivered vaginally. Prostaglandin pessaries were not associated with an increased incidence of hyperstimulation or sepsis. In conclusion, although PGE2 pessaries are safe in spontaneous rupture of the membranes, intravenous oxytocin is more efficient in stimulating labour.
Erythropoietin was estimated by radioimmunoassay in serum from 78 cord blood samples, collected in the second and third trimesters in 72 pregnancies. In 43 samples obtained during or after normal pregnancy (from 19 to 42 weeks gestation) erythropoietin levels increased with gestation. Cord blood haemoglobin also increased with gestation, but the rate of increase was less during the last weeks of pregnancy. Erythropoietin levels were similar in the cord blood of infants of the same gestation, whether born vaginally or by caesarean section. The fetus can respond to severe anaemia or hypoxia with increased erythropoietin levels as early as 24 weeks gestation. Elevated erythropoietin levels were found in two out of eight infants born after labour in which there was 'acute' fetal distress, suggesting the presence of unrecognized chronic fetal hypoxia in these pregnancies.
We reviewed the hepatic features in 136 children with alpha 1 antitrypsin deficiency (PiZ). Eighty two were studied prospectively, 74 of whom had chronic liver disease. Sixty seven children with liver disease presented in the first four months of life, four were older infants and children with chronic liver disease, 10 (three with liver disease) were identified in studies of the family of these propositi, and one was identified when she had liver disease associated with infectious mononucleosis. By 17 years of age 20 of these 74 children with chronic liver disease had died, 20 had established cirrhosis, 19 had persisting liver disease, and only 15 had made a complete, clinical and biochemical recovery. The outcome of liver disease was similar in a further 39 previously unreported PiZ infants and children with liver disease who were not prospectively studied. Because liver disease affects only a proportion of infants with PiZ phenotype and because the severity of their liver disease is so variable, we have analysed the outcome of liver disease in 27 observed families and in 20 previously reported families with more than one child with PiZ. In 34 families the outcome of liver disease was similar in the two children. From an analysis of the families with a severely affected child, we conclude that if the first PiZ child of PiZ heterozygote parents has unresolved liver disease, there is a 78% chance that a second PiZ child will have similar liver disease. After careful counselling, fetoscopy, fetal blood sampling, and protease inhibitor phenotyping, possible termination of pregnancy should be carefully considered in these families.
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When endotoxin was compared with phorbol myristate acetate (PMA) for stimulation of phagocytes in the nitroblue tetrazolium (NBT) test, both methods discriminated between affected patients with X-linked chronic granulomatous disease (CGD) and controls, but only the PMA NBT test distinguished female carriers of CGD. Endotoxin provided no stimulation of normal fetal blood whereas PMA was an effective stimulator. Our results indicate the superiority of the PMA NBT test for diagnosis of patients and carriers of CGD and should allow accurate antenatal diagnosis of the disease.
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