A sonographic and karyotypic study of second-trimester fetal choroid plexus cysts.

A prospective study was undertaken of 513 women between 15.6-24.1 weeks' gestation who had a level II ultrasound examination followed immediately by a genetic amniocentesis. The presence or absence of fetal choroid plexus cysts was noted and the results correlated with the fetal karyotype. Thirteen cases of choroid plexus cysts were observed sonographically, a prevalence of 2.5%. The size of the cysts ranged from 3-10 mm, with a median of 6 mm. There were no other sonographically detectable congenital abnormalities in these 13 cases, and the fetal karyotype was normal in all. An association between fetal choroid plexus cysts and autosomal trisomies was not found in this series.

The prognostic value of antinuclear antibodies in women with recurrent pregnancy losses: a prospective controlled study.

Because autoimmune diseases are suspected of causing some cases of recurrent pregnancy loss, we sought clinical and serologic evidence of such diseases in a group of 277 women with recurrent pregnancy loss. Using HEp-2 cells as targets for an indirect immunofluorescence test for antinuclear antibodies, we compared the frequency of a positive antinuclear antibody test in the women with recurrent pregnancy loss to that in 299 pregnant controls and 119 nonpregnant controls. The frequency of positive antinuclear antibody tests at a titer of 1:40 or higher was 16.3% in cases, 16.6% in pregnant controls, and 16.8% in nonpregnant controls. Increasing the critical titer to 1:80, however, led to a statistically significant difference between cases (6.9%) and controls (0 and 0.8%, pregnant and nonpregnant, respectively; P less than .0001). Additional serologic tests failed to identify any subclinical autoimmune diseases, although two antinuclear antibody-negative patients later developed systemic lupus erythematosus. Pregnancy outcome in women with antinuclear antibody titers of 1:80 or higher included 52% live births, compared with 65.6% live births in women with three or more pregnancy losses and an entirely normal comprehensive evaluation, a nonsignificant difference. The combination of clinical evaluation and antinuclear antibody tests did not identify new cases of autoimmune disease in this population.

Predicting in vitro tissue culture growth for cytogenetic evaluation of stillborn fetuses.

A prospective study was undertaken of 131 perinatal deaths to determine whether gestational age, body weight, maceration degree and autopsy interval influenced successful in vitro tissue culture for cytogenetic evaluation. Perinatal populations were categorized as neonatal death (NND), fresh stillbirth (FSB), or graded as macerated stillbirth (MAC-0, MAC-1, MAC-2, MAC-3). Metaphase production by at least 15 cells separated 'growth' from 'no growth' categories after sampling liver, kidney and spleen. Body weight and degree of maceration were predictive of successful 'growth', while gestational age and autopsy interval were not. Body weight was significant in separating 'growth' from 'no growth' in NND (P = 0.05), FSB, MAC-0 and MAC-1 (P = 0.01). Growth probabilities were 0.78 (NND), 0.57 (FSB), 0.49 (MAC-0), 0.38 (MAC-1) and zero for MAC-2 and MAC-3. We conclude that (a) tissues from MAC-2 and MAC-3 fetuses do not grow and thus need not be sampled at autopsy, (b) maceration degree and body weight can be used to predict the growth probability in the other categories, (c) tissue samples can be taken during daylight hours, since autopsy interval does not influence successful growth provided the fetus is refrigerated at 4 degrees C, (d) all of the above conclusions have cost-efficiency implications for cytogenetic laboratories.

Mosaicism or pseudomosaicism: the problem of hypermodal cells in amniotic fluid cell culture.

A series of 2029 consecutive amniotic fluid specimens studied for prenatal genetic diagnosis were reviewed and reassessed so as to evaluate the frequency and clinical significance of hypermodal cells in amniotic fluid cell cultures. Hypermodal cells were defined as those with more than 46 chromosomes, and were characterized by an additional structurally normal or structurally abnormal chromosome. Of 2029 specimens, 47 (2.31 per cent) contained a total of 167 hypermodal cells. True fetal mosaicism was detected in three cases (0.14 per cent). All had hypermodal cells in more than one culture flask or colony which contained the same aberrant chromosome complement. In all but one case the babies were normal when only one cell was hypermodal, or when several cells were hypermodal but present in only one colony or one culture vessel. One case had an extra No. 20 chromosome in one cell. Although the child had multiple anomalies, they were not characteristic of trisomy 20, and subsequent chromosomal study on the baby postnatally revealed a 46,XX karyotype. The in situ coverslip technique is recommended as the preferred method for prenatal diagnosis, and it is useful as an aid in differentiating true mosaicism from pseudomosaicism.

Evaluation of inorganic pyrophosphate in amniotic fluid as a mode of prenatal diagnosis of osteogenesis imperfecta.

Using a modified procedure by Solomons and Styner (1969), an evaluation of inorganic pyrophosphate (PPi) was performed on the amniotic fluid of two fetuses at risk for osteogenesis imperfecta (OI) at 14 1/2 weeks gestation. The parents of both cases had a previous child with OI, Type II. The normal control group at 14-16 weeks gestation had PPi values ranging from 22.0-59.2 micrograms/100 ml, with a mean of 38.6 +/- 9.51 micrograms/100 ml. In each at-risk fetus, the amniotic fluid PPi value was within normal range. The first baby was born phenotypically normal at term. Intrauterine radiographic and fetal sonograms were done on the second fetus at approximately 19 weeks gestation. Both showed evidence of OI, Type II. The pregnancy was terminated at 21 weeks. Radiologic studies of the aborted fetus were consistent with OI, Type II. Our results indicate that the evaluation of PPi levels in amniotic fluid is not the method of choice for prenatal diagnosis of OI.

Etiology of recurrent pregnancy losses and outcome of subsequent pregnancies.

Prospective evaluation of 155 couples with two or more consecutive pregnancy losses disclosed uterine morphologic abnormalities in 27%, chromosomal abnormalities in 21 individuals (7.7%, or 15.4% of the couples), and at least one abnormal diagnostic test suggestive of a cause for recurrent pregnancy losses in 106 (68%). A positive test for antinuclear antibody was found in 7.5% of the women, whereas the expected rate in a population of this age is less than 2%. Cervical cultures for Ureaplasma urealyticum (T-strain mycoplasma) were positive in 48% of the women, and 28% of these women had a genetic or uterine abnormality to explain their pregnancy losses. Thyroid function profiles and cervical cultures for Mycoplasma hominis provided no significant information in the evaluation in these couples. With the exception of women with a positive antinuclear antibody, the overall prognosis for later pregnancies was quite good whether the diagnostic evaluation of the couple was normal (77% subsequent live births) or abnormal (71% subsequent live births). The significance of the positive antinuclear antibody in these women is unclear, but further studies and long-term evaluation are necessary to determine the relationship between recurrent pregnancy losses and later development of collagen-vascular diseases.

Origin of lactate dehydrogenase in amniotic fluid.

The origin of protein including enzymes in amniotic fluid is of clinical and research interest. 8 patients were evaluated, with their informed consent, prior to therapeutic abortion. Amniotic fluid, placentas and blood were obtained and lactate dehydrogenase (LDH) isozyme patterns of cell-free amniotic fluid was compared to the LDH patterns of uncultured amniotic fluid cells, maternal serum and RBC, placentas and placental membranes. The LDH isozyme pattern of amnion closely corresponded to that of cell-free amniotic fluid and represents the major source of this enzyme in amniotic fluid.