Prenatal diagnosis and genetic screening : community and service implications / a report of the Royal College of Physicians.

  • Royal College of Physicians of London.
Date:
1989
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Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Prenatal diagnosis and genetic screening : community and service implications / a report of the Royal College of Physicians. Source: Wellcome Collection.

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    Screening for chromosomal disorders Screening for inherited diseases 2.21 A basic level 1 scan, in association with maternal serum AFP screening, is usually routine at about 16 weeks’ gestation; but the best time for detailed anomaly scanning is at around 19 weeks when the fetus is larger and the organ systems are more differentiated. At this stage, a level 3 expert can detect over 90% of major congenital malformations in risk groups, with very few false positives [9]. However, 90% of congenital malformations occur in pregnancies not recognisably at risk, and the only way to detect more of these is by offering routine, skilled level 2 anomaly scanning to every pregnant woman. It has been shown that at some expert centres where systematic level 2 anomaly scanning is performed by trained and supervised midwives, radiographers or technicians with suitable equipment and adequate time, 80% of major structural anomalies can be detected [9]. 2.22 A major malformation detected before 24 weeks of pregnancy is associated in up to 30% of cases with an underlying chromosomal anomaly [10]. Knowledge of the fetal karyotype can be crucial to the parents’ decision whether or not to continue the pregnancy. Therefore, when there is any uncertainty about management, malformed fetuses detected in time for induced abortion should be referred to a level 3 centre for rapid karyotyping on fetal blood or a placental biopsy [11]. 2.23 Ultrasound is often routinely used at around 32 weeks to confirm normal fetal growth and progress of the pregnancy. At present, congenital malformations are most likely to be detected at this stage, when selective abortion is no longer an option. 2.24 The diagnostic method used for detecting fetuses with chromosomal disorders is amniocentesis, or CVS for collecting fetal cells, followed by karyotyping (chromo somal analysis). This method of testing would have to be offered to all pregnant women if all affected fetuses were to be detected. However, because there are obstetric risks and karyotyping is a highly-skilled and labour-intensive procedure, prenatal testing for fetal chromosome anomalies is usually offered only to women at more than 0.5-1% risk of bearing an infant with Down’s syndrome*. Until recently, this applied only to older mothers (over 35-37 years of age), or to women who had already born an affected child, and to couples where one partner carries a chromo somal anomaly. However, karyotyping limited only to these groups can reduce affected births by one third at most, because most Down’s syndrome infants are now born to younger mothers (see paras 1.17 and 1.18). Better primary screening methods for detecting mothers at risk are needed, and promising new developments are described in Chapter 3. 2.25 The feasibility of carrier detection is an important limiting factor in screening for inherited disease. The ideal is to detect carriers before they embark on a pregnancy (prospective carrier diagnosis). This is possible at present only for relatives of patients with a limited number of dominant or X-linked disorders, and for the recessively-inherited haemoglobin disorders and Tay-Sachs disease (See Chapter 4). However, the possibilities for carrier detection using DNA methods (see 2.41) are steadily increasing. 2.26 Carrier detection and prenatal diagnosis for dominant disorders involve some unique problems. For example, in Huntington’s chorea, knowledge of risk leads many family members to remain childless (see ref 46), even though half of them are not carriers. Testing for carrier status would allow non-carriers to reproduce normally, while with prenatal diagnosis, known carriers could reproduce w'ithout * This risk level numerically matches the risk of the obstetric procedure causing a spontaneous abortion, but the risks are not comparable. Either may outweigh the other depending on a couple’s obstetric history and social situation. The real limiting factors in the offer of prenatal diagnosis for chromosomal anomalies are associated with the expense (and tedium) of karyotyping.