methods of prenatal diagnosis
The traditional method of screening for Down’s syndrome has been maternal age where amniocentesis or chorionic villous sampling is offered to women aged 35 years or more. This results in the need for an invasive test in 15-20% of pregnant women with a detection of less than half of the fetuses with Down’s syndrome, because the majority of affected fetuses come from the younger age group .A more effective method of screening is based in the combination of: Maternal age. A maternal blood sample for the measurement of the placental products of free β-hCG and PAPP-A . An ultrasound scan at 11-13 weeks: To measure the collection of fluid behind the fetal neck (nuchal translucency). To examine the fetal nose and palate . To measure the fetal heart rate. To assess the flow of blood across the tricuspid valve of the fetal heart and the ductus venosus.
This new method of screening reduces dramatically the number of women requiring an invasive test from about 20% to less than 3% and at the same time increases the detection rate of Down’s syndrome and other major chromosomal abnormalities from less than 50% to more than 95%
1 Maternal age
The risk for trisomy 21: Increases with maternal age .Decreases with gestational age because about 30% of affected fetuses die between the 12th and 40th week of pregnancy. The risk for trisomies 18 and 13 increases
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with maternal age and decreases with gestation.The rate of fetal death between the 12th and 40th week is about 80% .Turner syndrome is unrelated to maternal age. The rate of fetal death between the 12th and 40th week is about 80%. The prevalence is about 1 in 1500 at 12 weeks and 1 in 4000 at 40 weeks .Triploidy is unrelated to maternal age. The prevalence at 12 weeks is about 1 in 2000 but it is highly lethal and is very rarely observed in live births . 2 Serum biochemistry
In trisomy 21 pregnancies maternal serum free β-HCG is about twice as high and PAPP-A is reduced to about half compared to chromosomally normal pregnancies.Performance of screening for trisomy 21 by maternal age and serum free β-hCG and PAPP-A: Detection rate 65%.False positive rate 5%.
3 An ultrasound scan at 11-13 weeks:
3.1 Nuchal translucency
Nuchal translucency (NT) is the sonographic appearance of a collection of fluid under the. skin behind the fetal neck in the first trimester of pregnancy. The term translucency is used, irrespective of whether it is septated or not and whether it is confined to the neck or envelopes the whole fetus .The incidence of chromosomal and other abnormalities is related to the size, rather than the appearance of NT .During the second trimester, the translucency usually resolves and,
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in a few cases, it evolves into either nuchal edema or cystic hygromas with or without generalized hydrops .
The optimal gestational age for measurement of fetal NT is 11+0-13+6 weeks. The minimum fetal crown–rump length (CRL) should be 45mm and the maximum 84mm.The reasons for selecting 11 weeks as the earliest gestation are: Screening necessitates the availability of a diagnostic test and chorionic villous sampling before this gestation is associated with transverse limb reduction defects. Many major fetal abnormalities can be diagnosed at the NT scan, provided the minimum gestation is 11 weeks. The reasons for selecting 13 weeks and 6 days as the upper limit are: To provide women with affected fetuses the option of 1st rather than 2nd trimester termination. The incidence of abnormal accumulation of nuchal fluid in chromosomally abnormal fetuses decreases after 13 weeks. The success rate for taking a measurement decreases after 13 weeks because the fetus becomes vertical making it more difficult to obtain the appropriate image. The magnification of the image should be such that the fetal head and upper thorax occupy the whole screen. A mid sagittal section of the fetus must be obtained .The fetus should be in a neutral position, with the head in line with the spine. When the fetal neck is hyperextended the measurement can be falsely increased and when the neck is flexed, the measurement can be falsely decreased .Care must be taken to distinguish between fetal skin and amnion. The widest part of
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translucency must always be measured. Measurements should be taken with the inner border of the horizontal line of the callipers placed ON the line that defines the nuchal translucency thickness - the crossbar of the calliper should be such that it is hardly visible as it merges with the white line of the border, not in the nuchal fluid .In magnifying the image (pre or post freeze zoom) it is important to turn the gain down. This avoids the mistake of placing the calliper on the fuzzy edge of the line which causes an underestimate of the nuchal measurement .During the scan more than one measurement must be taken and the maximum one that meets all the above criteria should be recorded in the database. The umbilical cord may be round the fetal neck in about 5% of cases and this finding may produce a falsely increased NT. In such cases, the measurements of NT above and below the cord are different and, in the calculation of risk, it is more appropriate to use the average of the two measurements.
The NT thickness in euploid fetuses increases with fetal CRL. In 75-80% of trisomy 21 fetuses the NT thickness is above the 95th centile of the normal range .In trisomy 21 fetuses there is no relationship between NT thickness and maternal age .Maternal age can be combined with fetal NT to provide effective first-trimester screening for chromosomal abnormalities . 3.2 Nasal bone
In the assessment of the fetal nasal bone the gestation should be
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