Midtrimester Fetuses Research Articles

Prenatal diagnosis of genetic skin disease by fetoscopy and electron microscopy: report on 5 years' experience

Since our first report 5 years ago (Rodeck, Eady & Gosden, 1980) the combination of fetoscopy and electron microscopy to obtain and examine fetal skin biopsy specimens has become an established method for assessing mid-trimester fetuses at risk for different genodermatoses characterized by specific ultrastructural abnormalities. Our present report concerns 39 fetuses (Table). Table TABLE. Skin biopsy examination of 39 fetuses Risk No. examined No. affected *Epidermolysis bullosa. †Includes one twin pregnancy Junctional EB*† 21 6 Dystrophic EB 6 1 Bullous ichthyosis 2 1 Lamellar ichthyosis 2 0 Harlequin ichthyosis 2 0 Oculocutaneous albinism 4 2 Ectodermal dysplasia 1 0 Neu-Laxova syndrome 1 0 Skin biopsies are taken at 18–21 weeks gestation under direct vision with real-time ultrasound guidance. Usually a minimum of three samples is examined. Biopsies are taken from the limbs and trunk (for epidermolysis bullosa or ichthyosis) or from the scalp or eyebrows (for albinism). Biopsy scars are inconspicuous or very small and have never been a problem. There has been no fetal loss as a direct result of the procedure. We feel that this technique of prenatal diagnosis is now sufficiently well-tried to be offered as a service in the management of certain genetic skin diseases.

Midtrimester fetal heart rate variability and maternal hemodynamics in association with smoking

Maternal heart rate (MHR), blood pressure (BP), the differential index (DI) describing the short-term component of fetal heart rate (FHR) variability, and the interval index (II) describing the long-term component were measured in eight subjects in the midtrimester before, during, and after the mothers smoked a standard cigarette. The analyses of FHR variability were performed by an “on-line” method with an abdominal fetal electrocardiogram used as a triggering signal and with a sample time of 1 minute. An increase of MHR, FHR, and BP with a concomitant decrease of II was observed. Unlike our findings regarding the third trimester, no significant change of DI was observed. A correlation analysis revealed fetomaternal hemodynamic relationships different from those in the third trimester: There was a negative correlation between DI and FHR (p < 0.01) and between DI and MHR (p < 0.01). There was a positive correlation between FHR and MHR (p < 0.001). Unlike our findings regarding the third trimester, no correlation was found between DI and BP or between II and MHR. We suggest that the midtrimester fetus shows the narcotic effect (decrease of II) of one cigarette, as does the term fetus, but fails to show the hypoxic effect (decrease of DI), which has been observed in the term fetus.

A prenatal study of fetal platelet count and size with application to fetus at risk for Wiskott-Aldrich syndrome

Platelet counts and platelet size were determined in midtrimester fetuses to obtain reference values to be used in prenatal diagnosis of inheritable platelet disorders. In 17- to 21-week fetuses, platelet counts ranged between 135 and 283 x 10(9)/L, and thus did not differ from those of newborn infants and adults. Mean platelet volume fell between 6.0 and 7.0 fl, which is in the range for adults. The data were used to exclude Wiskott-Aldrich syndrome in an 18-week fetus at 50% risk of being affected.

The human fetal heart in the second trimester of gestation: A gross morphometric study of normal fetuses

One hundred fifty-three midtrimester fetuses obtained from normal pregnancies teminated for nonmedical reasons were studied to establish normal standard measurements. Mean, standard deviation, range, and percentiles of body weight, foot length, crown-rump length, biparietal diameter, cardiac weight, thickness of ventricles, and ventricular septum were derived by computer analysis. Statistical analysis showed no sex difference. Equations for predicting body weight, cardiac weight, and septal thickness were derived with the use of fetal age and biparietal diameter as variables. The mean ratio of septal to left ventricular wall thickness was 1.14 ± 0.34; a ratio of 1.3 or greater was found in 25% and a ratio of 1.5 or greater in 10% of this cohort. The results are at variance with the reported high incidence of septal hypertrophy seen in normal developing fetal hearts. We suggest that septal hypertrophy, ratio of 1.5 or greater, may reflect disturbances in fetal or placental circulation and warrants careful monitoring of the pregnancy.

Hypertrophic cardiomyopathy in a midtrimester fetus born to a diabetic mother

Hypertrophic cardiomyopathy in a midtrimester fetus born to a diabetic mother

Identification of congenital cardiac malformations by echocardiography in midtrimester fetus.

Fetal echocardiograms were performed in 21 pregnancies before midtrimester termination. All fetal heart specimens were collected and studied morphologically. Eighteen had been diagnosed as normal echocardiographically and this was confirmed anatomically. Deficiency of the atrial septum was suspected in one, and primum and secundum atrial septal defects were found anatomically. Coarctation of the aorta was suspected in another and this was confirmed anatomically. A ventricular septal defect was suspected in one which proved to be normal on dissection.

Hemoglobin synthesis in cultures of hepatic erythroid cells from the human fetus

A recent theory of the control of human fetal hemoglobin synthesis, based on studies in cultured adult marrow, proposes that the phenotypic expression of fetal hemoglobin is largely dependent on the level of differentiation of the parental stem cells; that is, the earlier the progenitor, the greater the ability of its progeny to express fetal hemoglobin [Papayannopoulou, Th., Brice, M. & Stamatoyannopoulos, G. (1977) Proc. Natl. Acad. Sci. USA 74, 2923-2927]. To test this relationship with fetal tissue, we have studied hemoglobin synthesis in cultured human fetal liver, comparing gamma chain synthesis in the descendants of the early progenitors ("bursts") with that in the descendants of the later progenitors ("colonies"). Cells from the livers of midtrimester fetuses were cultured in methylcellulose with erythropoietin. The beta/(beta + gamma) globin synthetic ratio on days 5 to 7, when colonies predominated, was 0.09-0.11, a value characteristic of fetal reticulocytes, and on days 11 and 12, when bursts predominated, was 0.15-0.17. Thus, in fetal liver, the descendants of the earlier progenitor, the burst-forming unit, may be making more beta chains rather than more gamma chains, compared to descendants of the later progenitor, the colonyforming unit. Our data on fetal liver, taken together with the data on adult marrow by others, suggest that the erythroid colonies express the gene characteristic of the age of the organism to a greater degree than bursts, which express beta and gamma genes less specifically. Thus, the capacity for highly selective gene expression characteristic of differentiated cells appears to be less well developed in the burst-forming unit than in the colony-forming unit.

Significance of meconium in midtrimester diagnostic amniocentesis

The importance of meconium passage as a sign of the third-trimester fetus in distress is well known. The significance of similar observations in the midtrimester fetus is much less certain. The increasing use of amniocentesis during the middle trimester for the diagnosis of genetic disease makes ascertainment of such data important. Ten instances of meconium-stained amniotic fluid in the last 514 amniocenteses performed at our institution for antenatal genetic diagnosis are reported. Seven pregnancies have ended at term with normal deliveries. Three pregnancies have terminated with fetal death. Meconium staining may be a sign of impending fetal death when passed during the second trimester. When accompanied by alpha-fetoprotein elevation two of three pregnancies terminated with fetal death.

505 SEPARATION OF FETAL AND ADULT ERYTHROCYTES BY SELECTIVE HEMOLYSIS: AN AID TO PERNTAL DIAGNOSIS OF HEMOGLOBINOPATHIES

Prenatal diagnosis of hemoglobinopathies is difficult if placental blood samples are contaminated by maternal cells, because β/γ ratios exceed the normal fetal range of 0.07 to 0.15. We have shown that fetal reticulocytes have less carbonic anhydrase than adult cells, and resist NH4Cl-, NH4HCO3-mediated (ørskov) hemolysis. To test this approach in actual cases, pure fetal blood was obtained by fetoscopy from two midtrimester fetuses at risk for homozygous β-thalassemia (thal). 2.5% fetal blood was mixed with blood from the β-thal trait mothers. Samples were incubated with 3H-leucine; an aliquot was treated in the ørskov reaction. Red cell size distributions were analysed with a Coulter channelyzer. Globin chains were separated on carboxymethylcellulose columns. In the mixed samples, only small maternal cells were seen with the channelyzer. Following ørskov hemolysis, only large fetal cells were detected. In case 1, β/γ in the mixed sample was 0.42. β/γ fell to zero following ørskov hemolysis, and was zero in pure fetal blood. This fetus had thal major. In case 2, β/γ was 1.97 before and 0.04 after ørskov hemolysis; it was 0.04 in pure fetal blood. This fetus has β-thal trait. ørskov hemolysis provides pure fetal blood from samples with only 2.5% fetal cells and enables the appropriate diagnoses to be made even when low yield samples are obtained.

581 ENRICHMENT OF HUMAN F-CELLS IN FETAL-MATERNAL BLOOD MIXTURES

Recovery of fetus-origin red cells from maternal venous blood could facilitate diagnosis of fetal hemoglobinopathies by the single cell immunodiffusion method, using specific antibodies to Hb variants. Among 40 Black American women in mid-trimester pregnancy who presented for termination of pregnancy, and who had a Hb A phenotype by electrophoresis, the blood of 9 contained an occasional Hb S-cell. In only these 9 cases were S-cells found in the amniotic fluid. This finding prompted development of an F-cell enrichment procedure, assuming a majority of cells which migrate into maternal circulation from the midtrimester fetus contain Hb F. F-cells in term cord blood and from adults with Hb A, AS, or S were more resistant than A-cells or S-cells to hypotonic stress equivalent to 0.45 gm% NaCl. Cells were also subjected to sequential treatment by low Na and differential centrifugation in a molten agar gradient (45C). This yielded a cell fraction in which F-cells in blood of adults were changed from 6% to 48% and in cord blood from 48% to 90%, whereas centrifugation alone on the latter achieved 74% F-cells. Preliminary observations on enrichment of maternal blood in midtrimester pregnancy are equally promising.

Catecholamines during therapeutic abortion induced with intra-amniotic prostaglandin F2α

Serial plasma, amniotic fluid, and urine samples were analyzed for epinephrine (E) and norepinephrine (NE) in eight subjects during midtrimester abortion induced by intra-amniotic prostaglandin F2α (PGF2α). After PGF2α administration, plasma E increased and there was no change in plasma NE levels. Amniotic fluid levels of E and NE decreased initially. During the course of abortion the mean level of E in the amniotic fluid increased after fetal distress and decreased after fetal death, indicating that the midtrimester fetus may respond to stress by the urinary excretion of E. The maternal urinary excretion rates of both E and NE increased following PGF2α. The observation that mean plasma levels and urinary excretion rate changes correlated better with the course of abortion and uterine contractility rather than with the time of PGF2α administration was consistent with the hypothesis that the catecholamine response may be due to the stress of labor rather than to the PGF2α per se.

Catechol estrogen formation by the human fetal brain and pituitary.

Homogenates of central neuroendocrine tissues from 2 male and 1 female midtrimester fetuses were incubated with (23H) estradiol-17beta. Metabolism at the C-2 position was monitored by measuring the tritium incorporated into water in the incubate. Liberation of tritium from the substrate by hypothalamus, limbic tissues, parietal cortex and pituitary occurred to the extent of 5.1-12.7%, 1.6-8.5%, 4.7-10.8%, and 0.9-4.1% of starting radioactivity, respectively. The nature of the product was confirmed by the isolation of 14C labelled 2-hydroxyestrone derivative from separate incubations with 14C-estrone as the substrate. With or without correction for weight of tissue incubated, catechol estrogen formation under these conditions occurs at levels similar to those seen in rat brain homogenates except that in contrast to the rat, the human cortex is also highly active.