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 trisomies 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 2010-2022 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 2022 (Professionalsmonitor 2022, Prenatale screening; de NIPT en structureel echoscopisch onderzoek) and report from previous years can be found at the website of the RIVM.
In 2022 in Northeast Netherlands (exceeding the Eurocat NNL region), screening for Down, Edwards and Patau syndrome was performed in 11,328 pregnancies through NIPT corresponding with an uptake of 47.4%. NIPT resulted in 0.44% 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 20,619 pregnancies (uptake of 86.3%). A structural anomaly was suspected in 4.3% of pregnancies. The 13 weeks anomaly scan was performed in 17,370 pregnancies (uptake of 72.7%). The uptake of the 20 weeks anomaly scan is constant over the last eight years.
Figure 1 Uptake of screening tests (combined test and NIPT) for Down, Edwards and Patau syndrome in Northeast Netherlands, 2015-2022.
In 2010-2022 Eurocat NNL registered 665 cases with Down, Edwards or Patau syndrome. Total prevalence in this period was 21.8, 7.8 and 2.7 per 10,000 births respectively. Time trends for the last 10 years are reported in chapter 6 of the ‘Jaaroverzicht’. Of these 665 cases, 503 (77.0%) were prenatally diagnosed (excluding 12 cases with unknown timing of diagnosis).
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 79% in 2018-2022 (NIPT available as first screening test). The proportion of prenatally diagnosed cases with Edwards or Patau syndrome was 93% in 2010-2012 and increased to 99% in 2018-2022, see figure 2.
Figure 2 Proportion prenatally diagnosed cases with Down syndrome and with Edwards or Patau syndrome, Eurocat Northern Netherlands 2010-2022.
Total cases Down syndrome: 448, total cases Edwards syndrome: 161, total cases Patau syndrome: 56. The bars show proportion prenatally diagnosed for Down syndrome and Edwards/Patau syndrome separately. Time of diagnosis unknown: Down syndrome (n=7), Edwards/Patau syndrome (n=5).Time periods reflect changes in prenatal screening program: 2010-2012 screening through the combined test, 2013-2017 NIPT available as second tier test, 2018-2022 NIPT available as first tier test.
For the prenatally diagnosed cases we determined what was the first positive prenatal test (defined as first prenatal test whether screening procedure or diagnostic test which indicated a possible congenital anomaly or need for further tests): 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. In 52% of the prenatally diagnosed Down syndrome cases the first positive prenatal test was a positive CT or NIPT, in 43% it was an abnormal finding at US and in 5% it was a positive CVS or amniocentesis. For Edwards and Patau syndrome on the other hand, abnormal findings at US accounted for 68%, a positive screening test (CT or NIPT) for 28% and a positive invasive test (CVS or amniocentesis) for 4%.
Table 1 – Prenatal diagnosis, first positive prenatal test and outcome of pregnancy after prenatal diagnosis for Down, Edwards and Patau syndrome, Eurocat Northern Netherlands 2010-2022
| Down syndrome | Edwards/Patau syndrome | |||
|---|---|---|---|---|
| Total cases | 448 | (100%) | 217 | (100%) |
| Prenatally diagnosed* | 303 | (68.7%) | 202 | (95.3%) |
| First positive prenatal test** (prenatally diagnosed is 100%) | ||||
| - Screening test (CT/NIPT) | 158 | (52.3%) | 57 | (28.2)% |
| - Ultrasound | 129 | (42.6%) | 137 | (67.8%) |
| - CVS or amniocentesis | 15 | (5.0%) | 8 | (4.0%) |
| Outcome of pregnancy after prenatal diagnosis (prenatally diagnosed is 100%) | ||||
| - Live birth | 59 | (19.5%) | 12 | (5.9%) |
| - Fetal death or stillbirth | 26 | (8.6%) | 30 | (14.9%) |
| - Termination of pregnancy | 218 | (71.9%) | 160 | (79.2%) |
| * Unknown time of diagnosis Down syndrome (n=7), Edwards/Patau syndrome (n=5) ** Unknown first positive prenatal test Down syndrome (n=1) |
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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.
Figure 3. Pregnancy outcome for (a) Down syndrome (b) and Edwards/Patau syndrome after a first positive prenatal test, followed by prenatal diagnosis, Eurocat Northern Netherlands 2012-2022.
DEP: Down, Edwards and Patau syndrome, CT: combined test, NIPT: noninvasive prenatal test, CVS: chorionic villus sampling, LB: live birth, TOPFA: termination of pregnancy for fetal anomaly.
In 2010-2022 Eurocat NNL registered 192 cases with non-genetic neural tube defects (NTD), 461 cases with non-genetic severe heart defects and 113 cases with non-genetic abdominal wall defects. Total prevalence in this period was 9.3, 22.4 and 5.5 per 10,000 births respectively. Time trends are reported in chapter 6 of the ‘Jaaroverzicht’.
Prenatal diagnosis occurred in 96% (n=184) of the cases with NTDs and in 93% (n=105) of the cases with an abdominal wall defect. For severe CHD the proportion prenatally diagnosed was 63% (n=292).
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).
In 33% of the prenatally diagnosed NTD cases an ultrasound in the first trimester, until 14 weeks, was the first positive prenatal test, 67% the NTD was detected at ultrasound after 14 weeks. For severe CHD the vast majority was detected after the first trimester of pregnancy (92%), whereas for abdominal wall defects about half were detected in the first trimester and half after the first trimester, see table 2. 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.
Table 2 – Prenatal diagnosis, first positive prenatal test and outcome of pregnancy after prenatal diagnosis for neural tube defects, severe heart defects and abdominal wall defects, Eurocat Northern Netherlands 2010-2022
| Neural tube defects | Severe heart defects* | Abdominal wall defects | ||||
|---|---|---|---|---|---|---|
| Total cases | 192 | 461 | 113 | |||
| Prenatally diagnosed** | 184 | (95.8%) | 292 | (63.3%) | 105 | (92.9%) |
| First positive prenatal test*** (prenatally diagnosed is 100%) | ||||||
| - Ultrasound <= 14 weeks | 61 | (33.3%) | 21 | (7.2%) | 54 | (51.4%) |
| - Ultrasound >= 15 weeks | 122 | (66.7%) | 267 | (92.1%) | 51 | (48.6%) |
| Outcome of pregnancy after prenatal diagnosis (prenatally diagnosed is 100%) | ||||||
| - Live birth (including postnatal mortality) | 26 | (14.1%) | 176 | (60.3%) | 49 | (46.7%) |
| - Fetal death or stillbirth | 8 | (4.3%) | 19 | (6.5%) | 9 | (8.6%) |
| - Termination of pregnancy | 150 | (81.5%) | 97 | (33.2%) | 47 | (44.8%) |
| * Severe heart defects include ICD10 codes Q200 persistent truncus arteriosus, Q201 double outlet right ventricle, Q202 double outlet left ventricle, Q203 complete transposition of great vessels (TGA), Q204 single ventricle, Q205 corrected TGA, Q206 isomerism atria, Q212 atrioventricular septal defect, Q213 tetralogy of Fallot, Q214 aortopulmonary window, Q2182 pentalogy of Fallot, Q220 pulmonary valve atresia, Q224 tricuspid atresia, Q225 Ebstein’s anomaly, Q226 hypoplastic right heart syndrome, Q230 congenital stenosis of aortic valve, Q232 mitral atresia or stenosis, Q234 hypoplastic left heart syndrome, Q242 cor triatriatum, Q244 subaortic stenosis, Q245 coronary vessel malformation, Q251 coarctation of aorta, Q252 atresia of aorta,Q253 stenosis of aorta, Q262 total anomalous pulmonary venous connection, Q263 Partial anomalous pulmonary venous connection. ** Unknown time of diagnosis: NTD (n=2), severe heart defects (n=8) and abdominal wall defects (n=1). *** Unknown time of ultrasound: severe heart defects (n=4) |
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After a prenatal diagnosis of NTD, termination of pregnancy occurred in 82% of the cases, a fetal death or stillbirth occurred in 4% and in 14% there was a live birth (of which 27% died after birth). For severe CHD, termination of pregnancy occurred in 33% and 60% resulted in a live birth. For abdominal wall defects, 45% were termination of pregnancy and 47% live births.
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 3). This is most likely related to the severity of the anomaly.
Figure 4. Pregnancy outcome for (a) neural tube defects, (b) severe heart defects and (c) abdominal wall defects after the first positive prenatal ultrasound, followed by prenatal diagnosis, Eurocat Northern Netherlands 2010-2022
NTD: neural tube defects, TOPFA: termination of pregnancy for fetal anomaly, US: ultrasound
