Prenatal diagnosis of the hurler syndrome: Report on 40 pregnancies at risk

In 40 pregnancies at risk for the Hurler syndrome 13 affected fetuses were detected by the demonstration of an α-L -iduronidase deficiency and an increased level of ³⁵S-sulphate incorporation. The diagnoses were confirmed by the analysis of fetal tissues and/or cultured fetal skin fibroblasts. Microassays for α-L -iduronidase, using phenyl α-L -iduronide and more recently 4–methyl-umbelliferyl α-L -iduronide, enabled a reliable diagnosis to be made within 15 to 18 days after amniocentesis. ³⁵S-sulphate incorporation has been a valuable adjunct in cases with a low (heterozygote) enzyme activity.     

Detection of fetal HLA-DQα sequences in maternal blood: A gender-independent technique of fetal cell identification

The objective of this study was to detect fetal HLA-DQα gene sequences in maternal blood. HLA-DQα genotypes of 70 pregnant women and their partners were determined for type A1. We specifically sought couples where the father, but not the mother, had genotype A1. In 12 women, maternal blood samples were flow-sorted. Candidate fetal cells were isolated and amplified by using PCR primers specific for a paternal HLA-DQα A1 allele. Fetal HLA-DQα A1 genotype was predicted from sorted cells; amniocytes or cheek swabs were used for confirmation. Six of twelve sorted samples had amplification products indicating the presence of the HLA-DQα A1 allele; 6/12 did not. Prediction of the fetal genotype was 100 per cent correct, as determined by subsequent amplification of amniocytes or cheek swabs. We conclude that paternally inherited uniquely fetal HLA-DQα gene sequences can be identified in maternal blood. This system permits the identification of fetal cells independent of fetal gender, and has the potential for non-invasive prenatal diagnosis of paternally inherited conditions.     

Maternal age-specific risks for trisomies at 9—14 weeks' gestation

This study provides data on the incidence of fetal trisomies 21, 18, and 13 at 9–14 weeks' gestation in women aged 35–45 years and estimates of maternal age-specific risks in women aged 20–45 years. Our data from 5814 singleton pregnancies undergoing first-trimester karyotyping for the sole indication of maternal age ⩾ 35 years were combined with those from two previous reports and the incidence of the trisomies was calculated from a total of 15 793 pregnancies. Comparison of incidences at 9–14 weeks' gestation with published data at 15–20 weeks' gestation and in livebirths demonstrated that at birth the maternal age-specific incidence of trisomy 21 is 33 per cent lower than at 15–20 weeks' gestation and 54 per cent lower than at 9–14 weeks' gestation. Furthermore, the relative frequency of trisomies 18 and 13 decreases from 30 per cent at 9–14 weeks to 22 per cent at 15–20 weeks and 14 per cent at birth.     

Rapid prenatal diagnosis of aneuploidy from uncultured amniotic fluid cells using five-colour fluorescence in situ hybridization

In this paper we describe the use of five-colour fluorescence in situ hybridization for prenatal diagnosis of aneuploidy using uncultured amniotic fluid cells. The analysis is based on ratio mixing of dual-labelled probes and digital imaging for the detection and visualization of five different probes specific for the five target chromosomes, 13, 18, 21, X, and Y. A retrospective blind analysis of 30 coded uncultured amniotic fluid samples correctly detected fetal sex and five trisomy 21 cases. Multicolour fluorescence in situ hybridization used in this way allows rapid and simultaneous detection of the most frequent aneuploidies.     

MSAFP levels and oesophageal atresia

This study was undertaken to evaluate the relationship between maternal serum alpha-fetoprotein (MSAFP) levels and oesophageal atresia (OA). OA occurred in 16 fetuses of mothers who had an MSAFP test in the study interval. The multiple of the median (MOM) value for MSAFP averaged 1·54 ± 0·65 (range 0·5–2·9 MOM), which was significantly higher than the value seen in controls. The median MOM was 1·35. Using a cut-off of 2·5 MOM, the sensitivity of MSAFP for detecting OA was 19 per cent. Although OA should be considered in the differential diagnosis of an elevated MSAFP level, MSAFP cannot be considered an appropriate screening test for OA given the low sensitivity.     

Flow cytometric method to measure urea-resistant alkaline phosphatase from blood neutrophils for use in the prenatal screening of Down's syndrome

The histochemical measurement of urea-resistant alkaline phosphatase from maternal blood neutrophils is known to have a high detection rate for the prenatal detection of Down's syndrome pregnancies. However, because the histochemical method is laborious and subjective to use, it has not gained widespread acceptance in prenatal screening programmes. We present a simple and objective method for the measurement of urea-resistant alkaline phosphatase by flow cytometry. The method should allow the design of larger studies aimed at evaluating the role of neutrophil urea-resistant alkaline phosphatase in the prenatal screening for Down's syndrome.