EUROCAT Northern Netherlands

Update: March 2022

This chapter presents uptake of prenatal screening tests and pregnancy outcomes from 2011-2020 for Down-, Edwards and Patau syndrome and selected structural anomalies. During this period the combined test was still available next to NIPT, but the first trimester ultrasound screening was not yet part of the screening program.

Prenatal screening for congenital anomalies

The prenatal screening program is monitored annually by the regional centers for prenatal screening. The monitoring report (Monitor 2020, ‘Prenatale screening op down-, edwards- en patausyndroom en het Structureel Echoscopisch Onderzoek’) can be found at the website of the RIVM. In 2020 in Northeast Netherlands (exceeding the Eurocat NNL region), first trimester screening for Down-, Edwards- and Patau syndrome was performed in 9,495 pregnancies through NIPT and in 215 pregnancies through the CT. The uptake was 37.8% for NIPT and 0.9% for the CT. NIPT resulted in 0.5% in a positive result (i.e. indication that fetus is affected with Down-, Edwards- or Patau syndrome). An anomaly scan was performed in 23,254 pregnancies, corresponding with an uptake after counseling of 88,1%. A structural anomaly was suspected in 3.9% of pregnancies.

Prenatal diagnosis and pregnancy outcome for Down-, Edwards- and Patau syndrome

In 2011-2020 Eurocat NNL registered 497 cases with Down-, Edwards- or Patau syndrome. Total prevalence in this period was 21.1, 7.7 and 2.7 per 10,000 births respectively. Time trends are reported in chapter 6 of the ‘Jaaroverzicht’

Prenatal diagnosis

Of these 497 cases, 371 (75.7%) were prenatally diagnosed. The proportion of Down-, Edwards- and Patau syndrome cases that were prenatally diagnosed increased during this 10 year period from 75% in 2011 to 86% in 2020 (X2 for trend=9.0, p=0.003; figure 1 and supplementary table). Looking at Down syndrome and Edwards- and Patau syndrome separately, a significant increasing trend was seen for Down syndrome (X2 for trend=5.2, p=0.02), where the proportion of cases with a prenatal diagnosis increased from 66% in 2011 to 87% in 2020. Proportion of prenatally diagnosed cases with Edwards- or Patau syndrome was high and fluctuated between 85% and 100% (figure 1 and supplementary table).

Figure 1 - Proportion prenatally diagnosed cases with Down syndrome and with Edwards- or Patau syndrome, Eurocat Northern Netherlands 2010-2019.

Total cases Down syndrome: 333, total cases Edwards syndrome: 121, total cases Patau syndrome: 43. Line shows the proportion prenatally diagnosed cases with Down-, Edwards- and Patau syndrome together (DEP), bars show proportion prenatally diagnosed for Down syndrome and Edwards/Patau syndrome separately.

First positive prenatal 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 54% of the prenatally diagnosed Down syndrome cases the first positive prenatal test was a positive CT or NIPT, in 42% it was an abnormal finding at US and in 4% it was a positive CVS or amniocentesis. For Edwards- and Patau syndrome on the other hand, abnormal findings at US accounted for 67%, a positive screening test (CT or NIPT) for 30% and a positive invasive test (CVS or amniocentesis) for 3%.

Table 1 – Prenatal diagnosis, first positive prenatal test and outcome of pregnancy after prenatal diagnosis for Down- and Edwards- and Patau syndrome, Eurocat Northern Netherlands 2011-2020

Outcome of pregnancy overall

Overall, 44% (n=145) of the Down syndrome cases were live born, 9% (n=30) resulted in a fetal death and 47% (n=158) resulted in a termination of pregnancy. For Edwards- and Patau syndrome, these proportions were 6% (n=10), 17% (n=28) and 77% (n=126) respectively. The live born cases with Edwards- or Patau syndrome all died after birth.

Outcome of pregnancy after prenatal diagnosis

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 (of which 7 (16%) died after birth). For Edwards- and Patau syndrome the proportions were 80% terminations, 14% fetal deaths and still births and 5% 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 84% of the Down syndrome cases and in 9% the outcome of pregnancy was a live birth. 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 34% 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 96% of the cases. When the ultrasound was the first positive test (an ultrasound finding followed by a prenatal diagnosis), termination of pregnancy occurred in 73% of the cases and in 19% there the pregnancy ended in a fetal death or still birth (figure 2a and figure 2b).

Figure 2 - Pregnancy outcome after a first positive prenatal test, followed by prenatal diagnosis for Down syndrome and Edwards/Patau syndrome, Eurocat Northern Netherlands 2010-2019

Prenatal diagnosis and pregnancy outcome for structural anomalies (NTD, severe heart defects and abdominal wall defects)

In 2011-2020 Eurocat NNL registered 138 cases with non-chromosomal neural tube defects (NTD), 357 cases with non-chromosomal severe heart defects and 84 cases with non-chromosomal abdominal wall defects. Total prevalence in this period was 8.7, 22.6 and 5.3 per 10,000 births respectively. Time trends are reported in chapter 6 of the ‘Jaaroverzicht’.

Prenatal diagnosis

Prenatal diagnosis occurred in 98% (n=134) of the cases with NTD’s and in 95% (n=82) of the cases with an abdominal wall defect. For severe CHD the proportion prenatally diagnosed was 61% (n=214) and fluctuated between 46% in 2012 and 71% in 2020 (See supplementary table)

First positive prenatal test

For the prenatally diagnosed cases we determined 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) and at what time in pregnancy this ultrasound was performed (before 14 weeks, 14-22 weeks or after 22 weeks).
In 32% of the prenatally diagnosed NTD cases an ultrasound in the first trimester, before 14 weeks, was the first positive prenatal test, 66% the NTD was detected at ultrasound between 14 and 22 weeks. For severe CHD the vast majority was detected in the second trimester of pregnancy (88%), whereas for abdominal wall defects about half were detected in the first trimester and half in the second trimester, see table 2.

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 2010-2019

* severe heart defects include ICD10 codes Q200 persistent ductus arteriosus, Q201 double outlet right ventricle, Q203 complete transposition of great vessels, Q204 single ventricle, Q212 atrioventricular septal defect, Q213 tetralogy 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 congenital mitral stenosis, Q233 congenital mitral insufficiency, Q234 hypoplastic left heart syndrome, Q251 coarctatio of aorta,Q252 atresia of aorta, Q262 total anomalous pulmonary venous connection

Outcome of pregnancy after prenatal diagnosis

After a prenatal diagnosis of NTD, termination of pregnancy occurred in 84% of the cases, a fetal death or still birth occurred in 4% and in 12% there was a live birth (of which 25% (4/16) died after birth). For severe CHD termination of pregnancy occurred in 30% and 63% resulted in a live birth. For abdominal wall defects 41 % were termination of pregnancy and about half were 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. This is most likely related to the severity of the anomaly. 

Supplementary tables

Number of cases and proportion prenatally diagnosed for Down-, Edwards- and Patau syndrome per birth year, Eurocat Northern Netherland 2011-2020

Number of cases and proportion prenatally diagnosed for non-chromosomal neural tube defects (NTD), severe congenital heart defects (CHD) and abdominal wall defects per birth year, Eurocat Northern Netherland 2011-2020.