A cost-benefit analysis of a population screening programme for neural tube defects

Population screening for neural tube defects is possible by measuring maternal serum alpha-fetoprotein levels with appropriate follow-up as required. British Columbia has approximately 39 000 births annually and the incidence of neural tube defects is 1–55 per 1000 births (0–94 per 1000 livebirths). Results from a cost-benefit analysis suggest that the outlined screening programme would be cost-beneficial for British Columbia. Other important factors essential to consider before instituting a population screening programme are discussed.     

Normal pregnancy after preimplantation DNA diagnosis of a dystrophin gene deletion

To perform preimplantation DNA diagnosis for Duchenne muscular dystrophy (DMD) in a female carrier of a dystrophin gene deletion of exons 3–18, we developed a polymerase chain reaction (PCR)-based assay of exon 17 sequences. Exon 17 was efficiently amplified in all 50 single blastomeres of normal control embryos and in five blastomeres of one male embryo of the DMD carrier obtained after a first preimplantation diagnosis (PID) for gender determination. In ten blastomeres of another two male embryos of the DMD carrier, no PCR signals were observed, probably as a result of the deletion. After intracytoplasmic sperm injection, embryos were analysed for exon 17 and three of the four embryos showing normal PCR signals were replaced, resulting in a singleton pregnancy. Prenatal diagnosis showed a female karyotype and DNA analysis indicated that the fetus was not a DMD carrier.     

46,XX/46,XY chromosome complement in amniotic fluid cell culture followed by the birth of a normal female child

Experience indicates that the most likely explanation for a mixture of 46,XX/46,XY cells in an amniotic fluid sample is that of maternal cell contamination and that a normal male child is to be expected at birth. We report the birth of a normal female child following prenatal diagnosis of such a mixture. Extensive postnatal studies failed to reveal an XY cell line. The possible sources of the XY cell line are discussed, as are the various techniques that were applied in an effort to discover it's origin. Cross-contamination of samples could be ruled out and there was no evidence of an unsuspected twin pregnancy. It is clear from this case that not all 46,XX/46,XY results obtained in amniotic fluid can be assumed to represent maternal cell contamination and some effort should be made to eliminate other potential sources for such a mixture.     

First trimester amniocentesis between the seventh and 13th weeks: Evaluation of the earliest possible genetic diagnosis

Amniocentesis performed at the 12th week and later gives reliable results. The procedure can be performed using regimens developed for mid-trimester amniotic fluid (AF) cells. Extension to the 10th–11th week is, in principle, feasible. However, the high cytogenetic failure rate is a difficulty and despite a high clone count, the culture time is prolonged. The problem of the relatively high loss of AF could be overcome by cell filtration techniques and replacement of the fluid. Because of the short turnover rate of the AF, this may be unnecessary or replacement with an isotonic solution may be sufficient. (Pseudo)mosaicism appears to occur more frequently in early than in late amniocentesis. As yet, data are too sparse to allow a comparison with chorionic villus sampling. There are no reliable follow-up data from which to estimate the abortion rate and the number of embryonic malformations.     

Fetal nuchal fluid-physiological or pathological?—In pregnancies less than 17 menstrual weeks

For pregnancies less than 17 menstrual weeks, increasing amounts of nuchal fluid increase the risks of chromosome abnormalities with localized nuchal fluid, diffuse nuchal fluid, cystic hygroma, and fetal hydrops having chromosomal risks of 12, 23, 50, and 78 per cent, respectively. The ultrasound appearance of localized or diffuse nuchal fluid is not a specific discriminator, but a fluid depth of greater than or equal to 5 mm may be an indicator of increased risk of fetal chromosomal abnormalities. If the fluid depth is less than 5 mm, there is a stronger negative predictive value and negative likelihood risk of a fetal chromosome abnormality. Gestational age did not improve the fluid depth predictive value. Differentiation of physiological from pathological requires chromosome analysis, serial ultrasound evaluation, and good clinical examination as a newborn and possibly as a young child. Long-term follow-up of those cases identified with resolving nuchal fluid abnormalities is not available and is required for a complete understanding of physiological and pathological aetiologies. Genetic counselling for fetal nuchal fluid would be recommended.     

La maturation sexuelle chez les mâles d'Octopus vulgaris (Cephalopoda: Octopoda), en relation avec le réflexe photo-sexuel

The role of light in induction of sexual maturation in male Octopus vulgaris has been studied on experimentals reared in the laboratory. Experiments were carried out during January, February and March, the time of the year when females do not breed or are just beginning to breed. Males (20 to 500 g) were artificially illuminated for 8 or 16 h/day or kept in complete darkness. Their gonads were compared with those of wild specimens killed a few hours after capture. In the Mediterranean Sea, under natural conditions, O. vulgaris males of less than 150 g never display sexual maturity; under our experimental conditions, young males from 70 g onwards, illuminated 16 h daily, show gonad development. Males of over 150 g, illuminated 16 h daily, have a larger number of spermatophores than wild specimens of individuals illuminated 8 h daily. O. vulgaris reared in complete darkness are sexually more mature than wild individuals. An hypothesis on induction of sexual maturation in the Cephalopoda is proposed.     

The risks of early cordocentesis (12–21 weeks): Analysis of 500 procedures

Five hundred cordocenteses were performed between 12 and 21 weeks. The indications were thalassaemia (386), rapid karyotyping (97), feto-maternal allo-immunization (10), rubella (6), and toxoplasmosis (1). One hundred and ten pregnancies underwent termination on the basis of the result, while 20 of the 370 pregnancies intended to continue were lost to follow-up. Amongst these were 16 fetal losses (4·3 per cent) and 22 premature deliveries (5·9 per cent); no other complications were reported. Four adverse prognostic factors were identified: (a) cord bleeding; (b) fetal bradycardia; (c) prolonged procedure time; and (d) anterior insertion of the placenta. There was no‘obvious’ difference in fetal loss rate with advancing gestation until 19–21 weeks, when the risk of fetal loss decreased to 2·5 per cent.     

Fetal liver alanine: Glyoxylate aminotransferase and the prenatal diagnosis of primary hyperoxaluria type 1

Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the hepatic peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT, EC 2.6.1.44) (Danpure and Jennings, FEBS Lett., 201 , 20–24, 1986). The activity of AGT has been measured in fetal livers of gestational age 14–21 weeks. Activity increases up to 17 weeks and then levels off between 17 and 21 weeks. At this time, the mean AGT activity is about 30 per cent of the mean normal postnatal level. As in adult liver, the AGT enzyme activity and the AGT immunoreactive protein are peroxisomal. Prenatal diagnosis has been performed by measuring AGT enzyme activity and immunoreactive AGT protein on liver biopsies from two fetuses at risk for primary hyperoxaluria type 1. One was unaffected and one was affected.