The significance of prenatal diagnosis of choroid plexus cysts

A case is described of the prenatal diagnosis of choroid plexus cysts at 17 weeks' gestation which persisted beyond 36 weeks but could not be detected after delivery. At birth the child was found to have trisomy 18.     

Prenatal diagnosis of Chediak-Higashi syndrome

We report the first prenatal diagnosis of an affected fetus with Chediak-Higashi syndrome (CHS). Diagnosis was accomplished via fetal blood sampling at 17 menstrual weeks and was confirmed after birth. Retrospective measurement of the largest acid phosphatase-positive lysosomes in cultured amniotic fluid cells and chorionic villus cells showed that in CHS these lysosomes are significantly larger than those in normal cells. This method may be used for prenatal diagnosis of CHS by amniocentesis and chorionic villus sampling (CVS).     

Neonatal lung function following mid-trimester amniocentesis

Three hundred and fifty-four women who underwent midtrimester genetic amniocentesis were matched for age, parity, indication, and smoking history, with an equivalent number of women who had declined the procedure, for the purpose of comparing the neonatal respiratory status of their offspring. There was no evidence that the infants exposed to genetic amniocentesis were compromised.     

Erythroid-specific antibodies enhance detection of fetal nucleated erythrocytes in maternal blood

Fetal nucleated erythrocytes (NRBC) in maternal blood are a non-invasive source of fetal DNA for prenatal genetic screening. We compared the effectiveness of three monoclonal antibodies for the separation of fetal cells from maternal blood by flow sorting. Mononuclear blood cells from 49 healthy pregnant women were incubated with antibody to CD 71, CD 36, and/or glycophorin A (GPA), employed singly or in combination with each other. These monoclonal antibodies recognize surface antigens on haematopoietic precursor cells. Successful isolation of fetal cells was defined as detection of Y chromosomal sequences in maternal blood from women carrying male fetuses, with absence of Y sequences when female fetuses were carried. Thus, gender prediction accuracy was used as a measure of fetal cell separation. Using anti-CD 71 to isolate fetal cells, gender prediction was 57 per cent correct; with anti-CD 36, it was 88 per cent correct. Anti-GPA, an erythrocyte-specific antigen, used alone or in combination with anti-CD 71 or 36, improved gender prediction to 100 per cent. We conclude that antibody to GPA improves the retrieval of fetal NRBC from maternal blood, permitting genetic analysis by the polymerase chain reaction.     

Prenatal diagnosis of isolated bilateral microphthalmia with confirmation by evaluation of products of conception obtained by dilation and evacuation

We describe the prenatal diagnosis of isolated bilateral fetal microphthalmia in a woman at increased risk of having a fetus with microphthalmia. Ultrasound examinations at 161 and 19-5 weeks' gestation demonstrated bilateral fetal microphthalmia with no other associated structural defects. The patient elected to terminate her pregnancy at 19.5 weeks. Pathological evaluation of the products of conception obtained by dilation and evacuation confirmed the prenatal diagnosis of isolated bilateral fetal microphthalmia.     

Prenatal diagnosis,fetal pathology,and cytogenetic analysis of mosaic trisomy 14

While true mosaicism occurs in only 0–25 per cent of genetic amniocenteses, nearly 2–5 per cent of amniotic fluid cell cultures contain a second cell line. In the common practice of prenatal diagnosis, an aberrant cell line confined to a single colony is usually disregarded. We present a case of mosaic trisomy 14 which was not detected on initial chromosome analysis. At birth, multiple malformations were apparent. Newborn cytogenetic studies revealed mosaicism [46,XX/46,XX,-14,+i(14q)] with an isochromosome 14 in 37 per cent of lymphocytes. Additional cells from the initial amniotic fluid culture were analysed post-delivery and the isochromosome 14 identified in only one of 12 total colonies. This case illustrates two important lessons in prenatal diagnosis. First, amniotic fluid cell cultures may not accurately reflect the relative distribution of the normal and abnormal cell lines within a mosaic fetus. Second, while it is generally reasonable to disregard mosaicism confined to a single colony, this policy will, on rare occasion, result in diagnostic error. This should be taken into consideration, particularly when dealing with autosomal trisomies potentially compatible with livebirth.     

Normal development in two six-year-old boys born after prenatal diagnosis of trisomy 20 mosaicism

Prenatal diagnosis of trisomy 20 mosaicism was made in two pregnancies by chromosome analysis of cultured amniotic fluid cells. In both cases, the pregnancy continued to term and a healthy male infant was delivered. Regular assessments up to the age of 6-5 years revealed normal physical and intellectual development in both children.     

Chorionic villus culture for prenatal diagnosis of chromosome defects: Reduction of the long-term cultivation time

We report in detail two series of chorionic villus cultivation for prenatal chromosomal diagnosis. Chorionic villi were sampled from both first- and second-trimester pregnancies. One hundred cultures were treated with trypsin–EDTA for 2 h and collagenase overnight, (method A) and 100 were treated with trypsin–EDTA for 1 h and collagenase for 2 h (method B). Using short-term enzymatic digestion, the cultivation time was reduced from 14 days to 6 days. Sufficient amounts of metaphases of good quality were present in 93 per cent of primary cultures harvested in situ, whereas enough metaphases of sufficiently good quality were in most cases present only after subcultivation of the cultures using method A. The decrease in cultivation time obtained is probably due to a higher yield of viable cells in monocellular suspension, an increased attachment efficiency, and a more rapid attachment of single cells (within 24 h).     

Amniotic fluid alpha-fetoprotein levels and prenatal diagnosis of autosomal trisomies

Pregnancies with fetal trisomy 21 have been associated with low amniotic fluid alpha-fetoprotein levels (AFAFP). This observation led to the suggestion that low AFAFP levels be used as a criterion for completion of a chromosomal analysis in patients who are not otherwise at increased risk for a fetal chromosome abnormality and in whom karyotyping might not have been completed for economic reasons. In order to assess the usefulness of such criteria, we reviewed the AFAFP levels of 90 cases of fetal trisomy 21, 23 cases of trisomy 18, and 10 cases of trisomy 13. These were compared with 2400 control samples with normal chromosome constitution. AFAFP levels were generally lower in pregnancies with trisomy 21, showing a median value of 0·72 MoM. However, 40 per cent of the trisomy 21 samples had AFAFP values greater than 0·8 MoM and 20 per cent were over 1·0 MoM. These data imply that over 50 per cent of Down syndrome cases might have been missed using a cut-off level of 0·70 MoM for completion of chromosome analysis. Using a higher cut-off level will leave only a small percentage of samples unkaryotyped. The distribution of AFP levels in trisomy 13 and 18 is no different from controls; we therefore believe that fetal karyotyping should be completed in every amniotic fluid sample obtained.