The Danish Fetal Medicine Database: revealing the fruits of collaborative research

Danish fetal medicine specialists have been working in collaboration with geneticists, epidemiologists and other stakeholders to produce a comprehensive national prenatal screening program for trisomy 21. The size of this task should not be underestimated. It has required political will and significant investment in human resources and equipment to enable women to access screening across the entire country. These specialists have worked with software providers to develop a reporting program that is of value to clinicians – ensuring its use and subsequently allowing data to be accessed for ongoing measurement of quality assurance. The fruits of these labors are reported in this month’s Journal (1). Across Denmark, over a 5-year period, more than 90% of pregnant women have been screened by a combination of ultrasound and biochemical assessment at 11–13 weeks’ gestation. The high rate of uptake is a tribute to these specialists’ and society’s ability to ensure equality of access to testing as well as providing evidence of acceptability of the test amongst pregnant women. A total of 268 342 women were screened with annual reported sensitivities and specificities ranging from 82–90% and 95–96.4%, respectively. These data are remarkably similar to those reported in a large number of cohort studies from all areas of the world – and are significant in that they are one of the few datasets that represent a national, population-based sample. We can conclude that the combined first trimester screening test can be effectively applied through a national/regionalbased program to screen for trisomy 21; the caveat being inclusion of a comprehensive quality assurance program. The establishment of a national fetal medicine database that can be linked to other national medical registers has provided Danish specialists with the means to investigate a series of research questions related to fetal development (2). The group have previously reported that this screening program has resulted in a significant (>50%) reduction in the invasive (amniocentesis and chorionic villus sampling) testing rate in Denmark and has also shown that combined first trimester screening is highly effective in predicting risk for trisomies 18 and 13 – with sensitivities of 79 and 87%, respectively (3,4). They have also been able to define the value of combined first trimester screening in detecting atypical chromosomal abnormalities and have produced one of the largest studies describing the impact of chorionicity, defined at the 12-week scan, on outcome of twin pregnancies (5,6). Even as these national, population-based data become available, the next generation screening tool for trisomy 21, based on examination of cell free fetal DNA (cffDNA) has arrived. Available data describing the effectiveness of cffDNA suggest that this test is an order of magnitude more efficient in screening for trisomy 21. However, we should bear in mind (1) that no population-based data for cffDNA testing are available yet and (2) what the cost will be if we do move to genomic screening. The Danish Fetal Medicine Group are already producing cutting edge, population-based data that will be used to define how cffDNA screening is incorporated in clinical practice. The data reported here set the bar for current standards of screening and for economic modeling of alternative strategies (1). Recognition that ‘screening for Down syndrome’ is a euphemism for screening for chromosomal abnormality is reflected in the finding that >30% of atypical abnormalities are detected with the current screening strategy, but would be missed using cffDNA alone (5). The data from cffDNA screening focus attention on reducing screen positive rates, and the group have started to address this using other ultrasound and biochemical models (7,8). The national fetal medicine database has, to date, predominantly been used to report the effectiveness of the Danish screening program. The next challenge will be to use this database to identify associations between early fetal development, obstetric pathologies and morbidities that are recognized in infancy, and then to use these data prospectively to improve perinatal and infant outcomes.