The 11-14 weeks scan - KH Nicolaides, NJ Sebire, RJM Snijders, AP Souka

Chapter 1

SCREENING FOR CHROMOSOMAL ABNORMALITIES

In prenatal screening for trisomy 21, the term screen positive rate is used interchangeably with the invasive testing rate, because most women with a positive screening test undergo an invasive test, and with false positive rate (FPR) because the vast majority of fetuses in this group are normal.

The first method of screening for trisomy 21, introduced in the early 1970s, was based on the association with advanced maternal age. It was apparent that amniocentesis carried a risk of miscarriage and this in conjunction with the financial cost implications, meant that prenatal diagnosis could not be offered to the entire pregnant population. Consequently, amniocentesis was initially offered only to women with a minimum age of 40 years. Gradually, as the application of amniocentesis became more widespread and it appeared to be ‘safe’, the ‘high-risk’ group was redefined to include women with a minimum age of 35 years; this ‘high-risk’ group constituted 5% of the pregnant population.

In the last 30 years, two dogmatic policies have emerged in terms of screening. The first, mainly observed in countries with private healthcare systems, adhered to the dogma of the 35 years of age or equivalent risk; since the maternal age of pregnant women has increased in most developed countries, the screen-positive group now constitute about 15% of pregnancies. The second policy, instituted in countries with national health systems, has adhered to the dogma of offering invasive testing to the 5% group of women with the highest risk; in the last 20 years, the cut-off age for invasive testing has therefore increased from 35 to 38 years. In screening by maternal age with a cut-off age of 38 years, 5% of the population is classified as ‘high risk’ and this group contains about 30% of trisomy 21 babies.

In the late 1980s, a new method of screening was introduced that takes into account not only maternal age but also the concentration of various fetoplacental products in the maternal circulation. At 16 weeks of gestation the median maternal serum concentrations of a-fetoprotein, estriol, human chorionic gonadotropin (hCG) (total and free-β) and inhibin-A in trisomy 21 pregnancies are sufficiently different from normal to allow the use of combinations of some or all of these substances to select a ‘high-risk’ group. This method of screening is more effective than maternal age alone and, for the same rate of invasive testing (about 5%), it can identify about 50-70% of the fetuses with trisomy 21.

In the 1990s, screening by a combination of maternal age and fetal NT thickness at 10–13+6 weeks of gestation was introduced. This method has now been shown to identify about 75% of affected fetuses for a screen-positive rate of about 5%.

Subsequently, maternal age was combined with fetal NT and maternal serum biochemistry (free β-hCG and pregnancy-associated plasma protein (PAPP-A)) in the first-trimester to identify about 85-90% of affected fetuses. Furthermore, the development of new methods of biochemical testing, within 30 min of taking a blood sample, made it possible to introduce One-Stop Clinics for Assessment of Risk (Figure 3).

In 2001, it was found that in 65-70% of fetuses with trisomy 21 the nasal bone is not visible by ultrasound at 11-13+6 weeks and preliminary results suggest that this finding can increase the detection rate of the first trimester scan and serum biochemistry to more than 95% (Table 1).

Table 1. Comparison of the detection rates (DR), for a false positive rate of 5%, of different methods of screening for trisomy 21. In prenatal screening, the term screen positive rate is used interchangeably with the invasive rate, because most women with a positive screening test undergo an invasive test, and with false positive rate (FPR) because the vast majority of fetuses in this group are normal

hCG human chorionic gonadotropin, PAPP-A: pregnancy-associated plasma protein A

Figure 3 Assessment of risk for chromosomal defects can be achieved by the combination of maternal age, ultrasound examination for measurement of fetal nuchal translucency and assessment for the presence/absence of the nasal bone and biochemical measurement of maternal serum free β-hCG and PAPP-A in an OSCAR at 11–13 weeks of gestation. After counselling, the patient can decide if she wants fetal karyotyping, which can be carried out by chorionic villus sampling in the same visit.