P. L. Noble

UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10–14 weeks of gestation

BACKGROUND Prenatal diagnosis of trisomy 21 currently relies on assessment of risk followed by invasive testing in the 5% of pregnancies at the highest estimated risk. Selection of the high-risk group by a combination of maternal age and second-trimester maternal serum biochemistry gives a detection rate of about 60%. We investigated assessment of risk by a combination of maternal age and fetal nuchal-translucency thickness, measured by ultrasonography at 10-14 weeks of gestation. METHODS The risk of trisomy 21 was estimated for 96127 women of median age 31 years (range 14-49) with singleton pregnancies. Ultrasonography was done by 306 appropriately trained sonographers in 22 centres. Risk of trisomy 21 was calculated from the maternal age and gestational-age-related prevalence, multiplied by a likelihood ratio depending on the deviation from normal in nuchal-translucency thickness for crown-rump length. The distribution of risks was investigated and the sensitivity of a cut-off risk of 1 in 300 was calculated. Phenotype was assessed by fetal karyotyping or clinical examination of liveborn infants. FINDINGS The estimated trisomy-21 risk, from maternal age and fetal nuchal-translucency thickness, was 1 in 300 or higher in 7907 (8.3%) of 95476 normal pregnancies, 268 (82-2%) of 326 with trisomy 21, and 253 (77.9%) of 325 with other chromosomal defects. The 5% of the study population with the highest estimated risk included 77% of trisomy-21 cases. INTERPRETATION Selection of the high-risk group for invasive testing by this method allows the detection of about 80% of affected pregnancies. However, even this method of risk assessment requires about 30 invasive tests for identification of one affected fetus.

Fetal karyotyping in twin pregnancies: selection of technique by measurement of fetal nuchal translucency

Objective To examine the usefulness of selecting the appropriate techque for fetal karyotyping in twin pregnancies by using maternal age and fetal nuchal translucency thickness to determine risk for chromosomal defects in each fetus.

FIRST-TRIMESTER URINE FREE BETA hCG, BETA CORE, AND TOTAL OESTRIOL IN PREGNANCIES AFFECTED BY DOWN'S SYNDROME: IMPLICATIONS FOR FIRST-TRIMESTER SCREENING WITH NUCHAL TRANSLUCENCY AND SERUM FREE BETA hCG

We have examined maternal urine concentrations of beta core, free beta human chorionic gonadotrophin (hCG), and total oestriol in 373 control pregnancies and 43 pregnancies affected by aneuploidy (including 22 cases of Downs syndrome) in an attempt to see if any of the analytes have a value in Downs syndrome screening between the tenth and 14th week of pregnancy. We have compared the performance of these analytes against nuchal translucency measurement combined with maternal serum free beta hCG at the same period of pregnancy. Our results show that levels of urine free beta hCG and beta core are increased in Downs syndrome with average multiple of the median levels of 1·81 and 2·91, respectively. Urine total oestriol was reduced (0·83) whilst maternal serum free beta hCG was increased (1·72). In trisomy 18 the levels of all analytes were reduced, although serum free beta hCG was the most discriminating. The spread of results in the control and the Downs group for urine beta core was more than three times than that for serum free beta hCG and with urine free beta hCG it was two times wider. In combination with maternal age, urine total oestriol had a 32 per cent detection rate at a fixed 5 per cent false‐positive rate; urine beta core 34 per cent, urine free beta hCG 36 per cent, maternal serum free beta hCG 44 per cent, and nuchal translucency 82 per cent. In combination with nuchal translucency, urine total oestriol added an extra 1 per cent detection, urine beta core an extra 2 per cent, urine free beta hCG an extra 3 per cent, and serum free beta hCG an extra 5 per cent. It is unlikely that any of the urine markers will be of value in first‐trimester screening. Optimal first‐trimester screening programmes will rely for the foreseeable future on nuchal translucency, serum free beta hCG, and possibly pregnancy‐associated plasma protein A.

Management of twin pregnancies discordant for anencephaly.

Objective To examine options of management and outcome of twin pregnancies discordant for anencephaly.

Maternal serum free β-hCG at 10 to 14 weeks of gestation in trisomic twin pregnancies

Maternal serum free β‐hCG was measured at 10 to 14 weeks of gestation in 136 normal twin pregnancies and in 12 twin pregnancies where one or both fetuses had trisomy 21. The values were compared with a normal range from 4181 singleton pregnancies. In the normal twins the median free β‐hCG (65 ng/mL) was about twice as high as in singletons (34 ng/mL z=−12.1, P < 0.0001). In the trisomy 21 group the median free β‐hCG (95 ng/mL) was significantly higher than in normal twins (z= 2.1, P < 0.05). However, only one of the trisomic pregnancies had a level above the 95th centile. In twin pregnancies maternal serum free β‐hCG at 10 to 14 weeks of gestation is unlikely to be useful in the prediction of fetal trisomy 21.

Maternal serum inhibin-A and free β-hCG concentrations in trisomy 21 pregnancies at 10 to 14 weeks of gestation

Objective To determine the relation between maternal serum inhibin‐A and free β‐hCG concentrations in chromosomally normal pregnancies and to compare the two biochemical markers for their sensitivity in identifying trisomy 21 pregnancies.

Maternal serum S100 protein in normal and Down syndrome pregnancies

Protein S100 is a low molecular weight (10–12 kD) calcium‐binding protein the beta subunit of which is coded for at the 22.2–22.3 region of the long arm of chromosome 21. This region has also been shown to be responsible for the phenotypic expression of Down syndrome. Previous studies demonstrated increased immunoreactivity to protein S100 in brain tissue from adults with Down syndrome. We have previously observed a higher concentration of S100 protein in the fetal blood of trisomy 21 fetuses compared with normal subjects. The aim of this study was therefore to investigate the use of measuring S100 protein concentration in maternal blood for Down syndrome screening.