Chapter five

Figure 12 shows that there were 1,559 babies with Down’s syndrome, 423 babies with Edwards’ syndrome and 152 babies with Patau’s syndrome delivered in England in 2019. This represents a prevalence of 25.4 per 10,000 total births or one in every 394 births for Down’s syndrome, 6.9 per 10,000 births or one in every 1,449 births for Edwards syndrome and 2.5 per 10,000 births or one in every 4,000 births for Patau’s syndrome, figures which are consistent with those reported for 2018.

Table 13 shows that the live birth prevalence remains consistent with previous years’ data, with 11.2 per 10,000 live births or one in 893 live births for Down’s syndrome, 0.8 per 10,000 live births or one in 12,500 for Edwards’ syndrome and 0.2 per 10,000 births, or one in 50,000 for Patau’s syndrome respectively.

Trisomy definitions

Trisomy

Babies normally inherit 2 copies of each chromosome, one from their mother and one from their father. A baby with a trisomy has 3 copies of a particular chromosome. The imbalance in the genetic material causes the baby to have developmental difficulties and physical differences or anomalies.

Meiotic non-disjunction

This is the most common way in which a trisomy arises. During the formation of the egg or sperm, a chromosome pair does not separate properly, so the egg or sperm contains a complete extra copy of one chromosome. This occurs randomly but is more common in older mothers.

Translocation trisomy

This is rarer and occurs when 2 different chromosomes are physically joined together, so are inherited as a single unit. One of the parents may carry this translocation in a balanced form, meaning that there is the right amount of genetic material, but it is arranged in the wrong order. However, they can pass on the translocation in an unbalanced form, meaning that the baby has too much (or too little) genetic material. Importantly, translocation trisomy indicates a significant recurrence risk in subsequent pregnancies, so families in this situation are offered genetic counselling.

Mosaic trisomy

Only some cells in the body have an extra copy of the chromosome. The rest of the body cells usually have a normal set of chromosomes. Mosaic trisomies occur due to random errors in cell division after conception. Mosaic trisomies can have milder effects, but this can vary depending on the proportion of cells with the additional chromosome, and where in the body these cells are located.

Partial trisomy

Extra genetic material is present, but only from part of the chromosome, not the entire chromosome. Babies with partial trisomies are not included in the data for chapter 5 as, depending on the size of the partial trisomy, the outcomes and timing of diagnosis may vary. This means that prevalence estimates for Down’s syndrome, Edwards’ syndrome and Patau’s syndrome presented in this chapter vary slightly to those displayed in Table 1.

Figure 12

The number of babies with Down’s syndrome, Edwards’s syndrome and Patau’s syndrome born in England in 2019, and categorised by the timing of diagnosis. The data in this chart can be found in table 10, table 11 and table 12.

Figure 12 and table 10, table 11 and table 12 show that most babies with a trisomy were diagnosed antenatally; 58.6% of Down’s syndrome, 74.2% of Edwards’ syndrome and 67.8% of Patau’s syndrome diagnoses were antenatal. For pregnancies with a trisomy that were diagnosed antenatally, the TOPFA rate was broadly similar across all 3 conditions, at 88% for Down’s syndrome, 86.9% for Edwards’ syndrome and 86.4% for Patau’s syndrome.

Postnatal diagnoses include babies where a woman has chosen to decline antenatal tests, whether this is screening or diagnostic cytogenetic tests, but will also include testing performed following a miscarriage, TOPFA or stillbirth. In a proportion of postnatal diagnoses, the presence of a trisomy may have been clinically suspected due to a structural anomaly seen on ultrasound scan, for example a heart anomaly or a higher chance screening result, but the presence of the trisomy was not confirmed until after the baby was delivered.

Considering both antenatal and postnatal diagnoses for babies born in 2019, 43.9% with Down’s syndrome were live born as were 10.9% of babies with Edwards syndrome and 9.9% of babies with Patau’s syndrome.

Figure 13 shows that for both antenatal and postnatal diagnoses, in the majority a full karyotype was the most definitive test recorded, with rapid aneuploidy testing being the second most frequently recorded test method. However, this does not necessarily represent all completed tests as some babies will have received both antenatal and postnatal testing by multiple methods but only one test is included for these purposes, prioritising antenatal over postnatal testing and karyotyping or microarray over rapid aneuploidy testing.

Figure 13

Timing of diagnosis and laboratory test method for babies born with Down’s syndrome, Edwards’ syndrome and Patau’s syndrome in 2019.

Table 14 shows that antenatal diagnoses were primarily made from chorionic villus sampling (CVS) (54.9%) or amniocentesis (42.9%), with fetal blood sampling less commonly. Postnatal diagnoses include blood or saliva taken after a live birth, with venous blood representing 76.7% of all postnatal samples, and post-mortem tissue specimens tested following a late miscarriage, TOPFA, or a stillbirth also seen frequently in the data.

Down’s syndrome, Edwards’ syndrome and Patau’s syndrome can arise by several different mechanisms, outlined in the trisomy definitions listed above . As expected, figure 14 shows that meiotic non-disjunction (which is strongly associated with maternal age) accounted for the majority of babies diagnosed with Down’s syndrome, Edwards’ syndrome or Patau’s syndrome, with fewer translocation and mosaic cases being observed. Mosaic trisomies are likely to be under-ascertained as low-level mosaicism (especially of trisomy 21) may result only in mild or sub-clinical features and so may be diagnosed much later or remain undiagnosed. Babies where the genetic type of trisomy is unspecified are those where conventional karyotyping failed or was not performed, that is, they were diagnosed only by a rapid aneuploidy test or microarray; these latter tests cannot distinguish between standard and translocation trisomies.

Figure 14

The number of babies diagnosed with Down’s syndrome, Edwards’ syndrome and Patau’s syndrome born in England in 2019 categorised by chromosome and underlying genetic mechanism.

Babies where the genetic type of trisomy is unspecified are those where conventional karyotyping failed or was not performed, that is, they were diagnosed only by a rapid aneuploidy test or microarray; these latter tests cannot distinguish between standard and translocation trisomies.

Figures 15 and 16 show timing of diagnosis and differences in outcome split by geographical region. Where a baby has had both a prenatal and a postnatal diagnostic test, the earlier diagnosis is taken as the point of ascertainment. There is variation in both the timing of diagnosis and outcomes of pregnancy across the regions. There is likely to be several reasons behind this, including differences in the population, differences in maternal age and uptake of screening. There may also be some regional variation in ascertainment and data completeness, which could underestimate the number of miscarriages and TOPFAs.

Figure 15

Timing of diagnosis for babies with Down’s syndrome, Edwards’ syndrome and Patau’s syndrome delivered in 2019, by NCARDRS region. Where a baby has had both a prenatal and a postnatal diagnostic test, the earlier diagnosis is taken as the point of ascertainment.

Figure 16

Outcome of pregnancy for Down’s syndrome, Edwards’ syndrome and Patau’s syndrome delivered in 2019, by NCARDRS region.