In the Netherlands, all pregnant women are offered prenatal screening for Down, Edwards and Patau syndrome (trisomy 21, trisomy 18 and trisomy 13) and for structural anomalies. Currently, the prenatal screening program includes screening for common trisomy’s through the Non-Invasive Prenatal Test (NIPT) from 10 weeks gestation and screening for structural anomalies through an anomaly scan around 13 and 20 weeks of gestation.
This chapter presents uptake of prenatal screening tests and pregnancy outcomes from 2010-2023 for Down, Edwards and Patau syndrome and selected structural anomalies. During this period several changes occurred in the prenatal screening program.
We present trends in prenatal screening and diagnosis using time periods related to these changes in the prenatal screening program.
The prenatal screening program is monitored annually by the regional centers for prenatal screening. The monitoring report over 2023 (Professionalsmonitor 2023, Prenatale screening; de NIPT en structureel echoscopisch onderzoek) and report from previous years can be found at the website of the RIVM.
In 2023 in Northeast Netherlands (exceeding the Eurocat NNL region), screening for Down, Edwards and Patau syndrome was performed in 14,192 pregnancies through NIPT corresponding with an uptake of 67.2%. NIPT resulted in 0.56% in a positive result (i.e. indication that fetus is affected with Down, Edwards or Patau syndrome). Since the introduction of the NIPT as second-tier screening test in 2013, the uptake for screening for Down, Edwards and Patau syndrome increased gradually in the Northeastern region, from 21% in 2015 to 47% in 2022 (Figure 1). The 20 weeks anomaly scan was performed in 20, 563 pregnancies (uptake of 87,5%). A structural anomaly was suspected in 3.9% of pregnancies. The 13 weeks anomaly scan was performed in 17,931 pregnancies (uptake of 76.3%). The uptake of the 20 weeks anomaly scan has been constant over the last eight years.
Uptake of the CT/NIPT screening test
In 2010-2023 Eurocat NNL registered 728 cases with Down, Edwards or Patau syndrome. Total prevalence in this period was 22.2, 8.0 and 2.9 per 10,000 births respectively. Time trends for the last 10 years are reported in chapter 6 of the Monitor.
Of the 482 cases with Down syndrome, registered between 2010-2023, 76.5% were prenatally diagnosed. For Edwards (n = 176) and Patau (n = 62) syndrome, 96.6% and 95.2% were prenatally diagnosed respectively. Missing data on time of diagnosis was scarce (n = 8).
Looking at the different time periods related to the changes in the prenatal screening program, an increase in proportion of cases with a prenatal diagnosis was seen for Down syndrome. The average proportion of prenatally detected cases increased from 59% in 2010-2012 (before the introduction of NIPT, only CT) to 65% in 2013-2017 (NIPT available as second-tier test, Trident-1) and 80% in 2018-2022 (NIPT available as first screening test). The proportion of prenatally diagnosed cases with Edwards was 93% in 2010-2012, increasing to 100% in 2018-2023. For Patau syndrome this was 93% in 2010-2012 and increased to 97% in 2018-2022 (Figure 2).
Prenatal detection rate by condition and birth years
For the prenatally diagnosed cases we determined what the first positive prenatal test was: 1) an increased risk at the CT test or a positive result for NIPT, 2) abnormal findings at ultrasound (US), or 3) positive result at chorionic villus sampling (CVS) or amniocentesis (note that first positive prenatal test is defined as first prenatal test whether screening procedure or diagnostic test which indicated a possible congenital anomaly or need for further tests). Of the prenatally diagnosed cases with Down syndrome, the most common first positive prenatal test was CT or NIPT. For Edwards and Patau cases, ultrasound was the most common first positive prenatal test (see Figure 3).
Overall, 41% (n=185) of the Down syndrome cases were live born, 9% (n=42) resulted in a fetal death and 49% (n=221) resulted in a termination of pregnancy. For Edwards and Patau syndrome, these proportions were 7% (n=15), 17% (n=37) and 76% (n=165) respectively. The live born cases with Edwards- or Patau syndrome all died after birth.
After prenatal diagnosis of Down syndrome, termination of pregnancy occurred in 72% of the cases, fetal death or still birth occurred in 9% and in 19% there was a live birth. For Edwards and Patau syndrome the proportions were 79% terminations, 15% fetal deaths and still births and 6% live births (all died after birth).
When the CT or NIPT provided a positive test result followed by a prenatal diagnosis, pregnancy termination occurred in 85% of the Down syndrome cases and in 9% the outcome of pregnancy was a live birth (Figure 2). When the ultrasound was the first positive test (an ultrasound finding followed by a prenatal diagnosis), termination of pregnancy occurred in 54% of the Down syndrome cases and in 33% there was a live birth. Pregnancy outcome was therefore related to the type of screening test.
After a positive CT or NIPT, followed by prenatal diagnosis of Edwards or Patau syndrome, termination of pregnancy occurred in 95% of the cases (Figure 2). When the ultrasound was the first positive test (an ultrasound finding followed by a prenatal diagnosis), termination of pregnancy occurred in 71% of the cases and in 20% the pregnancy ended in a fetal death or still birth.
When the CT or NIPT provided a positive test result followed by a prenatal diagnosis, pregnancy termination occurred in 85% of the Down syndrome cases and in 10% the outcome of pregnancy was a live birth (Figure 5). When the ultrasound was the first positive test (an ultrasound finding followed by a prenatal diagnosis), termination of pregnancy occurred in 56% of the Down syndrome cases and in 32% there was a live birth. Pregnancy outcome was therefore related to the type of screening test.
After a positive CT or NIPT followed by prenatal diagnosis of Edwards syndrome, termination of pregnancy occurred in 94% of the cases (Figure 2). When the ultrasound was the first positive test (an ultrasound finding followed by a prenatal diagnosis), termination of pregnancy occurred in 79% of the cases and in 17% the pregnancy ended in a fetal death or stillbirth.
After a positive CT or NIPT followed by prenatal diagnosis of Patau syndrome, termination of pregnancy occurred in 100% of the cases (Figure 2). When the ultrasound was the first positive test (an ultrasound finding followed by a prenatal diagnosis), termination of pregnancy occurred in 58% of the cases and in 26% the pregnancy ended in a fetal death or stillbirth.
In 2010-2023 Eurocat NNL registered 206 cases with non-genetic neural tube defects (NTD), 485 cases with non-genetic severe heart defects and 121 cases with non-genetic abdominal wall defects. Total prevalence in this period was 9.4, 22.0 and 5.5 per 10,000 births respectively. Time trends are reported in chapter 6 of the Monitor.
Prenatal diagnosis occurred in 97% (n=154) of the cases with NTDs and in 92% (n=77) of the cases with an abdominal wall defect. For severe CHD the proportion prenatally diagnosed was 60% (n=134).
For the prenatally diagnosed cases we determined the first positive prenatal ultrasound (defined as the first prenatal ultrasound whether performed as dating scan, screening test, or as a diagnostic test which indicated a possible congenital anomaly or need for further tests) and at what time in pregnancy this ultrasound was performed (until 14 weeks or after 14 weeks).
For abdominal wall defects, half of the cases were diagnosed during the ultrasound <14 weeks, and half of the cases were diagnosed during the ultrasound >= 14 weeks. For neural tube defects, the majority was diagnosed during the late ultrasound >= 14 weeks. In cases with severe heart defects, almost all were diagnosed during the late ultrasound >= 14 weeks. We cannot report on the time period in which the first trimester anomaly scan was introduced (starting from September 2021), because the period was too short to report meaningful results.
Overall, 40% (n = 112) of the cases with abdominal wall defects were live born, 14% (n = 39) resulted in a fetal death and 47% (n = 136) resulted in a termination of pregnancy. For neural tube defects, these proportions were 16% (n = 64), 4% (n = 15) and 81% (n = 327) respectively. For severe heart defects syndrome, these proportions were 67% (n = 732), 5% (n = 54) and 5% (n = 54) respectively.
After a prenatal diagnosis of abdominal wall defects, the majority of cases were live births (58%). Termination of pregnancy occurred in 34% of the cases after this prenatal diagnosis. After a prenatal diagnosis of severe heart defects, again the majority of cases were live births (60%), and termination of pregnancy occurred in 34% of the cases. After a prenatal diagnosis of neural tube defects, termination of pregnancy occurred in most of the cases (Figure 7).
For all three anomalies, termination of pregnancy occurred more frequently when the detection of the anomaly was early in pregnancy, than when the anomaly was detected in the second trimester of pregnancy or later (Figure 8). This is most likely related to the severity of the anomaly.
