Detection and false-positive rates of maternal serum markers for Down syndrome screening according to maternal age in women over 35 years of age. A study of the agreement of eight dedicated software packages

Maternal serum markers for trisomy 21 screening (MSS) can be assayed in women ≥35 years in an attempt to reduce the need for invasive procedures and thereby avoid their side effects. Our objective was to compare, in women ≥35, eight different software packages dedicated to second trimester MSS, thus providing reliable data for patient counselling. A simulation study was carried out on 189 sera from women with Down syndrome fetuses and 11 962 sera from mothers of unaffected babies. The first step was to estimate the joint distribution of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (β-hCG). The second step was to calculate trisomy 21 detection and false-positive rates for each software according to maternal age (35–45 years), using the usual 1:250 risk threshold. Agreement between software packages was measured using 2×2 kappa coefficients. Detection rates and false-positive rates increased with maternal age. Depending on the software, 57–71% detection rates were achieved at 35 years with 12–18% false-positive rates. At 45 years, 61–100% detection rates were achieved with 66–95% false-positive rates. Up to 39 years, all softwares were concordant (kappa coefficients >0.75). In the range 35–45 years, false-positive and detection rates increased substantially with maternal age and differences between software packages are observed. Copyright © 2002 John Wiley & Sons, Ltd.     

Minor sonographic signs of trisomy 21 at 15–20 weeks' gestation in fetuses born without malformations: a prospective study

A prospective study was performed on 2119 pregnancies that underwent genetic amniocentesis. Indications for amniocentesis were either maternal age (⩾35) or triple-test results (risk⩾1/380). The study covered a 36-month period and assessed the prevalence of minor ultrasound markers both in fetuses with Down syndrome and normal control fetuses at 15–19 week' gestation. Only fetuses with normal karyotype or trisomy 21 were considered. Six minor sonographic markers were considered: nuchal thickness, pyelectasia, femur observed/expected and humerus observed/expected ratios, bowel echogenicity, and choroid plexus cysts. One or more ultrasound soft markers were present in 23 out of 33 fetuses with Down syndrome (70%) and in 572 out of 2069 normal fetuses (28%). Copyright © 2001 John Wiley & Sons, Ltd.     

Duplication of chromosome 2 in association with ventriculomegaly — a case report

This is a case report of the prenatal diagnosis of a de novo interstitial duplication of chromosome 2 (46,XX,dup(2)(p13p21) de novo) with an associated phenotypic abnormality. This chromosomal duplication is rare, only one has previously been described prenatally. Postnatal reports of similar duplications in this region have described associated dysmorphic features and significant neurodevelopmental delay. In our case, the only ultrasound finding was moderately severe ventriculomegaly. At post-mortem, ventriculomegaly was confirmed and there was associated macrocephaly (head circumference above the 97th centile) with no dysmorphic features seen. Copyright © 2001 John Wiley & Sons, Ltd.     

Maternal uniparental heterodisomy for chromosome 2: detection through ‘atypical’ maternal AFP/hCG levels,with an update on a previous case

We report a case of maternal uniparental disomy 2, detected through routine screening of placental karyotypes following the finding of ‘atypical’ AFP/hCG levels in the second trimester, with intrauterine growth retardation (IUGR) but otherwise normal outcome at term. Although the child remained small, subsequent early physical and mental development has also been normal. Additionally, we report long-term follow-up of an earlier case, again with relatively normal physical and mental development. The significance of atypical AFP/hCG results and the predictive value of prenatal testing for UPD2 in trisomy 2 confined placental mosaicism (CPM) cases are discussed. Copyright © 2001 John Wiley & Sons, Ltd.     

Trisomy 10: ultrasound features and natural history after first trimester diagnosis

We report on the ultrasound features and natural history of trisomy 10. At 12 weeks' gestation in a routine scan examination, the fetus presented with increased nuchal translucency thickness, mild skin oedema, bilateral pleural effusion, marked micrognathia, cardiomegaly, unilateral talipes and reversed A-wave in the ductus venosus blood flow. Karyotyping on chorionic villus sampling (CVS) led to the diagnosis of trisomy 10, which was confirmed by fetal blood sampling at 22 weeks' gestation. As the parents opted to continue with the pregnancy, the natural history and following ultrasound features are described. This is the third case of trisomy 10 in the literature reporting on the physical features. The most frequent ultrasound findings presented in trisomy 10 are increased nuchal translucency, micrognathia, renal agenesis, facial cleft, limbabnormalities, cardiac defects and early severe growth retardation. Copyright © 2001 John Wiley & Sons, Ltd.