EUROCAT Northern Netherlands

This chapter presents uptake of prenatal screening tests and pregnancy outcomes from 2012-2021 for Down, Edwards’ and Patau syndrome and selected structural anomalies. The first trimester anomaly scan was implemented per September 1st 2021 and the combined test (CT) was abandoned per October 1st 2021.

Prenatal screening for congenital anomalies

The prenatal screening program is monitored annually by the regional centers for prenatal screening. The monitoring report (Monitor 2021, Prenatale screening op down-, edwards- en patausyndroom en het Structureel Echoscopisch Onderzoek) can be found at the website of the RIVM. In 2021 in Northeast Netherlands (exceeding the Eurocat NNL region), screening for Down, Edwards’ and Patau syndrome was performed in 10,738 pregnancies through NIPT and in 61 pregnancies through the CT. The uptake was 42.9% for NIPT and 0.3% 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). The 20 weeks anomaly scan was performed in 21,293 pregnancies, corresponding with an uptake after counseling of 85.7%. A structural anomaly was suspected in 4.4% of pregnancies. The uptake of the 13 weeks anomaly scan (available from September 1, 2021) was 66%.

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

In 2012-2021 Eurocat NNL registered 500 cases with Down, Edwards’ or Patau syndrome. Total prevalence in this period was 21.4, 7.7 and 2.7 per 10,000 births respectively. Time trends are reported in chapter 6 of the ‘Jaaroverzicht’.

Prenatal diagnosis

Of these 500 cases, 384 (77.6%) were prenatally diagnosed. The proportion of Down, Edwards’ and Patau syndrome cases that were prenatally diagnosed increased during this 10 year period from 62% in 2012 to 89% in 2021 (X2 for trend=15.5, p<0.001; figure 1 and supplementary table). Looking at Down, Edwards’ and Patau syndrome separately, a significant increasing trend was seen for Down syndrome (X2 for trend=12.1, p<0.001), where the proportion of cases with a prenatal diagnosis increased from 49% in 2012 to 86% in 2021. Proportion of prenatally diagnosed cases with Edwards’ or Patau syndrome was high and fluctuated between 86% 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 2012-2021.

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 52% of the prenatally diagnosed Down syndrome cases the first positive prenatal test was a positive CT or NIPT, in 45% it was an abnormal finding at US and in 3% it was a positive CVS or amniocentesis. For Edwards’s and Patau syndrome on the other hand, abnormal findings at US accounted for 69%, a positive screening test (CT or NIPT) for 28% and a positive invasive test (CVS or amniocentesis) for 3%.

Outcome of pregnancy overall

Overall, 42% (n=141) of the Down syndrome cases were live born, 8% (n=28) resulted in a fetal death and 50% (n=167) resulted in a termination of pregnancy. For Edwards’ and Patau syndrome, these proportions were 6% (n=10), 16% (n=25) and 81% (n=129) 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 8% and in 20% there was a live birth (of which 7 (16%) died after birth). For Edwards’ and Patau syndrome the proportions were 82% terminations, 12% 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 85% of the Down syndrome cases and in 9% the outcome of pregnancy was a live birth (Figure 2a). 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’ or Patau syndrome, termination of pregnancy occurred in 95% of the cases (Figure 2b). When the ultrasound was the first positive test (an ultrasound finding followed by a prenatal diagnosis), termination of pregnancy occurred in 76% of the cases and in 16% there the pregnancy ended in a fetal death or still birth.

Figure 2. Pregnancy outcome for Down syndrome (a) and Edwards/Patau syndrome (b) after a first positive prenatal test, followed by prenatal diagnosis, Eurocat Northern Netherlands 2012-2021

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

In 2012-2021 Eurocat NNL registered 136 cases with non-chromosomal neural tube defects (NTD), 342 cases with non-chromosomal severe heart defects and 87 cases with non-chromosomal abdominal wall defects. Total prevalence in this period was 8.7, 21.8 and 5.6 per 10,000 births respectively. Time trends are reported in chapter 6 of the ‘Jaaroverzicht’.

Prenatal diagnosis

Prenatal diagnosis occurred in 96% (n=129) of the cases with NTD’s and in 94% (n=81) of the cases with an abdominal wall defect. For severe CHD the proportion prenatally diagnosed was 65% (n=223). (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 33% 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 (91%), whereas for abdominal wall defects about half were detected in the first trimester and half in the second trimester, see table 2.

Outcome of pregnancy after prenatal diagnosis

After a prenatal diagnosis of NTD, termination of pregnancy occurred in 85% of the cases, a fetal death or stillbirth occurred in 3% and in 12% there was a live birth (of which 27% (4/15) died after birth). For severe CHD termination of pregnancy occurred in 30% and 64% 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 (figure 3). This is most likely related to the severity of the anomaly.

Figure 3. Pregnancy outcome for neural tube defects (a) and severe heart defects (b) and abdominal wall defects after a first positive prenatal test, followed by prenatal diagnosis, Eurocat Northern Netherlands 2012-2021

Supplementary tables

Number of cases and proportion prenatally diagnosed for Down, Edwards’ and Patau syndrome per birth year, Eurocat Northern Netherlands 2012-2021.

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 Netherlands 2012-2021.