Vladimír Gregor

Gradual implementation of first trimester screening in a population with a prior screening strategy: population based cohort study

Objective. To evaluate the implementation of first trimester screening in the Czech Republic during 1996–2007 on the number of infants born with numerical chromosomal anomalies, the gestational age at diagnosis and the number of invasive procedures. Design. A population based cohort study. Setting. National Registry of Congenital Anomalies, 53 Czech Republic Genetic Departments. Population. About 100,000 pregnancies per year. Main outcome measures. Primary outcomes were the rates of fetuses and newborns with diagnosed numerical chromosomal anomalies and the gestational age at diagnosis. Secondary outcomes were the rates of chorion villus sampling (CVS) and amniocenteses and the contribution of age groups on the detection rate of trisomy 21. Results. The number of newborns with Downs syndrome decreased from 5.42/10,000 in 1996 to 3.66/10,000 newborns in the 2007. The total incidence of Downs syndrome increased from 13.42 to 20.66/10,000. The detection rate in women <35 years increased from 35.59 in 1996 to 45.08 in 2007; in women >35 years from 23.73 to 38.52. The number of amniocenteses/detected case of Downs syndrome was 124 in 1996 and 123 in 2007. The corresponding number of CVS decreased dramatically from 83 in 1996 to 10 in 2007. Conclusions. Despite the increase of maternal age and the corresponding increase of Downs syndrome, the number of newborns with Downs syndrome decreased. Implementation of the first trimester combined screening leads to a shift towards earlier diagnosis of all major chromosomal abnormalities.

OP22.09: Does NIPS change the spectrum of detected major chromosomal aberrations (CHA)? Population-based data

Methods: Three gravidae presenting with specific fetal sonographic findings: 1) ventriculomegaly with encephalocele; 2) severe polyhydramnion, and 3) enlarged echogenic kidneys, underwent amniocentesis for CMA, and Genome-Wide Human SNP array was used to analyse DNA from amniocytes. The Genomic Oligoarray and SNP array evaluation tool v3.0 was used to detect recessive loci associated with the reported clinical findings. Candidate regions were further interrogated using the National Genetic Database. Results: Three fetuses from three distinct nuclear families in which the parents shared a similar ethnicity (either Ashkenazi or Bukharan Jews) but no reported consanguinity, were assessed. No copy number changes were observed, however evaluation of regions of homozygosity revealed a relevant candidate gene for the specific phenotype for each fetus. Using the National Genetic Database a specific mutation was examined in both parents (c.1167dupA mutation in the FKTN gene, c.167ins6[TTTCCC] mutation in the BSND gene and c.3761_3762delCCinsG in the PKHD1 gene, respectively). Both parents were found to be carriers and the fetuses homozygotes to the mutation. Conclusions: For the first time, specific sonographic pathology, data from ROH extracted from CMA results, and information regarding common founder mutations in distinct ethnic subgroups were combined to create a comprehensive streamlined approach to provide effective genetic diagnosis and counselling within the time constraints of ongoing pregnancy.

OP04.06: Implementation of first trimester screening in a population with a prior screening strategy—population based cohort study

Objectives: To evaluate the implementation of first trimester screening in the studied population during 1996–2007 on the number of infants born with numerical chromosomal anomalies, the gestational age at diagnosis, and the number of invasive procedures. Methods: Population based cohort study. National Registry of Congenital Anomalies, 53 Genetic Departments. Population – about 100,000 pregnancies per year. Primary outcomes were the rates of fetuses and newborns with diagnosed numerical chromosomal anomalies and gestational age at diagnosis. Secondary outcomes were the rates of chorion villus sampling and amniocentesis and the contribution of age groups on the detection rate of trisomy 21. Results: The number of newborns with Down syndrome (DS) decreased from 5.42/10 000 in 1996 to 3.66/10 000 newborns in the 2007 (P < 0.001). The total incidence of DS increased from 13.42 to 20.66/10 000. The detection rate in women < 35 years increased from 11.85 in 1993 to 45.08 in 2007; in women > 35 years from 22.21 to 38.52 (P < 0.001). The number of amniocenteses/detected case of DS was 124 in 1996 and 123 in 2007. The corresponding number of CVS decreased from 83 in 1996 to 10 in 2007 (P < 0.001). Conclusions: Despite the increase of maternal age and the corresponding increase of DS, the number of newborns with DS decreased. Implementation of the first trimester combined screening lead to a shift towards earlier diagnosis of all major chromosomal abnormalities and a decrease in the number invasive procedures required.