Prenatal cytogenetic diagnosis after transabdominal chorionic villus sampling in the first trimester

First trimester prenatal cytogenetic diagnosis was attempted in 350 pregnancies after trans-abdominal chorionic villus sampling. The cytogenetic investigation was performed using both a short-term method (24 h incubation) and cell culture. Adequate samples were obtained in 99·1 per cent and in all these cases the fetal karyotype was established. A chromosome abnormality was found in 2·0 per cent of cases. A discrepancy between the karyotype obtained after 24 h incubation and the karyotype in cell culture was observed in 2·3 per cent. Maternal cell contamination in the cultures was confirmed in 13 of 181 cases where the 24 h incubation revealed a male karyotype. Studies of culture morphology showed that colonies of convoluted cells may serve as a marker for contamination with maternal cells in culture. For the present, we recommend using a short-term method as well as cell culture for cytogenetic investigation until the problems with karyotype discrepancy and maternal cell contamination have been further clarified.     

S-100 protein and neuron-specific enolase in amniotic fluid as markers of abdominal wall and neural tube defects in the fetus

The aim of this study was to determine whether there is increased leakage of neuron-specific enolase (NSE) and S-100 protein into amniotic fluid in pregnancies with neural tube defects, since both these proteins are produced by neural tissue, and to compare the value of these substances for detecting such defects with that of the more conventional techniques of alpha-fetoprotein (AFP) and acetylcholinesterase (AChE) gel electrophoresis. Amniotic samples from 25 mid-pregnancies (15–17 weeks' gestation) with neural tube defects (14 with open spina bifida and 11 with anencephaly) and from seven mid-pregnancies with abdominal wall defects were compared with a control material consisting of 80 amniotic fluid samples from 80 consecutive mid-pregnancy amniocenteses, with normal karyotypes and AFP concentrations. All of the above cases of abnormalities were primarily detected through increased AFP levels in the amniotic fluid. Amniotic fluid samples from 13 pregnancies with fetuses with autosomal chromosomal abnormalities and seven amniotic fluid samples contaminated with blood were also included in the investigation. It is concluded from the results that the conventional AFP assay combined with AChE gel electrophoresis is the best method for screening amniotic fluid for neural tube defects and defects of the abdominal wall. Neither NSE nor S-100 assay alone proved to be superior for the detection of these cases in mid-trimester amniotic fluid. The S-100 assay, however, could give additional information in cases where AChE gel electrophoresis is not decisive; for example, in samples contaminated with blood.     

First trimester chorionic villus sampling versus mid-trimester genetic amniocentesis-preliminary results of a controlled prospective trial

This controlled prospective study assesses the relative risks of first trimester chorionic villus sampling (CVS) versus mid-trimester gentic amniocentesis (GA). CVS subjects and amnio-centesis controls were comparable with regard to several confounding variables which might influence the risk of pregnancy loss including maternal age, smoking, alcohol consumption, gestational age at study entry, and history of vaginal bleeding or poor prior reproductive outcome. The most common indication for prenatal diagnosis was advanced maternal age (n = 511). In this subgroup, spontaneous abortion (<24 weeks) occurred in 2·9 per cent of CVS subjects versus 4−3 per cent of amniocentesis controls. The sum of spontaneous and therapeutic abortions (<24 weeks) was identical (5·3 per cent) in both groups. Therefore, intervention in the CVS group (i.e., therapeutic abortion for cytogenetic abnormalities) did not influence the observed risk of pregnancy loss. Overall perinatal mortality rates were also similar in both groups. No significant differences were identified for a number of pregnancy outcome parameters including 5 min Apgar score, birth weight, body length, head circumference, gestational age at delivery, preterm delivery, fetal growth retardation, congenital malformations, and neonatal complications. Preliminary results of this controlled prospective study suggest that chorionic villus sampling carries a low and acceptable risk.     

First trimester prenatal diagnosis of haemophilia A: Two years' experience

We evaluated the feasibility, reliability, and acceptability of prenatal diagnosis of haemophilia A by DNA analysis of chorionic villi. Twenty-two women at risk to transmit the abnormal gene were referred for prenatal diagnosis, two of them twice. Two of the 22 women appeared to be non-carriers by DNA analysis. In one of these women, the results were known only after chorionic villus sampling had been carried out. Thirteen of the twenty carriers were heterozygous for an intragenic (Bell or Xbal) marker; six women were only heterozygous for the extragenic DXS52 (Stl4) locus. One of the women was homozygous for all the presently known DNA markers within or closely linked with the factor VIII locus. Twelve of the 22 fetuses at risk were male, ten were female. Seven of the 12 male fetuses were shown to be affected and were subsequently aborted. Four male fetuses appeared to be not affected. In one case, the diagnosis was made by use of an extragenic marker. The woman rejected fetal blood sampling to confirm the diagnosis. After birth, a normal factor VIII level was found in three of the four cases. The fourth pregnancy is still continuing. In one of the 12 male fetuses, no diagnosis at the gene level was possible. DNA analysis is expected to provide maximum certainty as to the phenotype of the fetus for approximately 60 per cent of the women; for another 37 per cent a rate of misdiagnosis of 4–5 per cent applies. In only 3 per cent of the cases will no diagnosis at the gene level be possible as yet. The new possibility of a prenatal diagnosis in the first trimester of pregnancy enabled some of these women to have a family of their own and was appreciated in particular by the women who underwent fetoscopy in an earlier pregnancy.     

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.     

Individual consistency in exploratory behaviour and mating tactics in male guppies

While behavioural plasticity is considered an adaptation to fluctuating social and environmental conditions, many animals also display a high level of individual consistency in their behaviour over time or across contexts (generally termed ‘personality’). However, studies of animal personalities that include sexual behaviour, or functionally distinct but correlated traits, are relatively scarce. In this study, we tested for individual behavioural consistency in courtship and exploratory behaviour in male guppies (Poecilia reticulata) in two light environments (high vs. low light intensity). Based on previous work on guppies, we predicted that males would modify their behaviour from sneak mating tactics to courtship displays under low light conditions, but also that the rank orders of courtship effort would remain unchanged (i.e. highly sexually active individuals would display relatively high levels of courtship under both light regimes). We also tested for correlations between courtship and exploratory behaviour, predicting that males that had high display rates would also be more likely to approach a novel object. Although males showed significant consistency in their exploratory and mating behaviour over time (1 week), we found no evidence that these traits constituted a behavioural syndrome. Furthermore, in contrast to previous work, we found no overall effect of the light environment on any of the behaviours measured, although males responded to the treatment on an individual-level basis, as reflected by a significant individual-by-environment interaction. The future challenge is to investigate how individual consistency across different environmental contexts relates to male reproductive success.