Impact of prenatal screening on the epidemiology of Down syndrome in the Netherlands: a neonatal perspective

Down syndrome (DS) is the most common chromosome anomaly among live born infants and is associated with intellectual disability and typical clinical features. Furthermore, DS is associated with other morbidities, like cardiac and gastrointestinal defects and thyroid disorders. DS is caused by the presence of a complete extra chromosome 21 (trisomy 21), partial trisomy, translocation or mosaicism of chromosome 21. In recent decades, the life expectancy of children with DS has improved greatly in particular due to early surgical treatment of congenital heart diseases and anomalies of the gastrointestinal tract. Over the past years, various prenatal aneuploidy screening methods have been developed. These screening methods are aimed at enabling pregnant women to obtain information about the health of their unborn child in order to prepare for the birth of a child with a disorder or to terminate the pregnancy in the case of an abnormal test-result. The non-invasive prenatal test (NIPT) is the latest development and is used to examine the pregnant woman’s blood for aneuploidies, including DS, in the foetus. The blood of a pregnant woman contains a small amount of hereditary material (DNA) from the placenta. This DNA is almost always the same as the DNA of the child. The NIPT is more accurate than previous prenatal tests, like the first-trimester combined test (FCT), to detect DS. In case of an abnormal result of the NIPT, invasive diagnostic tests with amniocentesis or chorionic villus sampling are necessary to confirm the result. Both invasive tests have a very small miscarriage risk. Before 2007, there was no formal prenatal aneuploidy screening programme in the Netherlands, although pilot studies were performed and some tests were locally available. A national programme started in 2007 consisting of all pregnant women receiving information about FCT in the first trimester and offering a structural anomaly scan in the second trimester. A risk higher than 1:200 with FCT or abnormal ultrasound findings later in pregnancy was an indication for invasive follow-up testing. Costs were initially fully reimbursed through healthcare insurance for women ≥ 36 years, but from 2015 all women had to pay an additional fee (€165 in 2015, €177 in 2019). In 2014, NIPT was introduced in the Netherlands as a second-tier test (TRIDENT-1 study), offered only to women with an increased risk for trisomy 13 (Patau syndrome), 18 (Edwards syndrome) and 21 (Down syndrome), based on either the results of the FCT or their medical history. On a trial basis, NIPT became available to all pregnant women as an initial (first‐tier) test in April 2017 (TRIDENT-2 study). For NIPT, a fee comparable with that for the FCT is charged (€175 in 2019). While new developments changed the landscape in foetal aneuploidy screening worldwide, the impact on pregnancy, birth and the first days after birth of a child with DS is unknown. Therefore the general aim of this thesis is to analyse and evaluate the impact of prenatal aneuploidy screening on the epidemiology of DS in the Netherlands, from the neonatal perspective. The first part of this thesis (Chapters 2, 3 and 4) focuses on the impact of prenatal aneuploidy screening on livebirth prevalence of DS. Part 2 of this thesis (Chapters 5, 6 and 7) describes the impact of prenatal aneuploidy screening on neonatal characteristics in DS.