Prenatal Testing To Risk or Not to Risk?

On the same subject Birth Childbirth Education Birth Intervention Parents

by Elaine Dietsch
		Elaine is a midwife and currently a Lecturer at Charles Sturt University in the School of Nursing, Midwifery and Child Health. She is on the Faculty of the Graduate Diploma in Childbirth Education and has a long history of involvement in Women's Health.

Scene:

Obstetricians consulting room. Recreation of actual "counselling session" that took place one hour after the pregnant woman's blood had been taken for 'triple testing', primarily used to screen for Down's Syndrome (Hammond 1994).

Characters:

1. Obstetrician, named Dr "Nottoobad"
2. Pregnant woman, named Jo
3. Her partner, Phil (who happens to be a general practitioner).

The following questions and answers have been developed as if to assist Jo (or any pregnant woman) in making informed choices regarding prenatal screening ...

What is the risk of Down's Syndrome in babies with mothers of my age?

Age of mother	Risk for baby at birth
20	1/1527
25	1/1352
30	1/895
32	1/659
34	1/446
36	1/280
38	1/167
40	1/97
42	1/55
44	1/30

(Rogers 1997)

What screening tests are available at what stages of gestation to help pick up chromosomal abnormalities in the unborn.

Gestational age (post LMP)	Test
8 - 11 weeks	Chorionic villus sampling (Williamson 1997)
10 - 14 weeks	Nuchal thickness ultrasound test (Berger 1999)
14 - 17 weeks	Maternal blood test - the triple test - alpha fetoprotein, human chorionic gonadotrophin and unconjugated oestriol (Wald, Watt & Hackshaw 1999)
14 - 18 weeks	Maternal blood test - the quadruple test - as for the triple test plus inhibin A (Wald, Huttly & Hennessy 1999)
15 - 16 weeks	Amniocentesis (CEMAT 1998)
18 - 21 weeks	Detailed ultrasound scanning for fetal abnormalities (Howe et al 2000)
20 - 24 weeks	Cordocentesis (Rogers 1997)

What are the decisions and the implications of those decisions if I decide to go ahead with the Triple test?

Is honest, accurate information about persons with Down's syndrome being provided, so that true choice and autonomy are enhanced?

Life expectancy	55 years for the 98+% of person's with Down's syndrome who do not die in infancy from uncorrectable heart defects (Thase 1982)
Average IQ	60 - 70 (able to make decisions) (Pueschel, Canning and Murphy 1978; Rynders & Horrobin 1990) and IQs for people with Down syndrome have steadily risen throughout the 20th century (Pueschel, Canning and Murphy 1978). The majority are in the low, mildly intellectually delayed range (Pueschel, Canning and Murphy 1978). Less than 5% of persons with Down syndrome are severely to profoundly intellectually delayed with early intervention and required education (Connelly, Russell & Morgan 1984).
Reading levels	Kindergarten to 12th grade, with an average of 3rd grade (Rynders, Spiker & Horrobin 1978) -the Sydney Morning Herald is written for a 5th grade reading level.
Employment probability	75 - 90%, with current supported-employment programs (Martin et al 1985).
Independence	The vast majority of adult persons with Down Syndrome are capable of independent or group-home living arrangements (Turnbull & Turnbull 1985).
Impact on families	More likely to be positive than negative (Murphy 1982; Gath 1978).

Who benefits from triple testing?

• The genetics testing industry making the actual testing kits
  
  
• Scientists and researchers who have done the formative studies through promotions, grants and increased incomes
  
  
• Medical professionals including genetic counsellors, obstetricians, general practitioners, nurses, ultrasonographers and allied supporting staff

Is the test cost-effective?

It has been estimated in British Medical Journals that it costs 29,341 pounds to detect one fetus with Down's Syndrome ($190,000 in USA, Evans et al 1994) and 90,000 pounds to provide lifetime care to a person with Down's Syndrome (Sheldon & Simpson 1991). Howe et al (2000) argue that these costings are invalid and the cost for avoiding the birth of one baby with Down's Syndrome is considerably higher. Elkins and Brown (1995) argue that such cost analyses are based on outdated information about institutional costs, family disruption and loss of family productivity when caring for a person with a severe intellectual disability, seldom seen in persons with Down's Syndrome today.

What is the likelihood of a miscarriage if I am pregnant with a fetus with Down's Syndrome?

40% of fetuses with Down's Syndrome will be spontaneously miscarried after 12 weeks (Haddow 1998).

What is the incidence of miscarriage of all pregnancies following CVS or amnio?

Amniocentesis - 1% (Enkin 1994).

Chorionic villus sampling - 2 - 3%.  With the excess of fetal deaths occuring before 20 weeks in Europe and after 20 weeks in Canada (Canadian CVS Trial 1991; European CVS Trial 1991)

How reliable is an anomaly ultrasound scan at 18 - 22 weeks?

A detailed ultrasound at 18 - 22 weeks will detect 55% of fetuses with anomalies (Boyd, Chamberlain & Hicks 1998) but increase the false positive rate 12 fold.

What conditions will not be picked up by CVS?

• Absence of limbs
• Spina bifida
• Congenital heart disease
• Hydrocephalus

What are the risks involved with CVS?

Fetal loss:

• Fetal loss - thought to be 2 - 3% in experienced hands

• The excess of fetal deaths occurred before 20 weeks in the European Trial (1991) but after 20 weeks gestation in the Canadian Trial (1989)

• Stillbirth and neonatal death are more common following CVS than Amniocentesis (Grant, 1992)

• Compared with amniocentesis, fewer women are able to achieve a term birth or have a normal birthweight baby. (Enkin, 1994)

• Unknown effects of large doses of ultrasound on fetus

• Possible risk of IUGR (unconfirmed)

• Oromandibular-limb hypogenesis syndrome

• Transverse limb defects

  • apparent causal association between CVS and limb reduction defects is greatest before 9 completed weeks of pregnancy, suggesting that the embryo should be left alone during the phenocritical stage of development (Mastroiaovo et al, 1993 & Firth et al, 1994; Williamson, 1997)

  • Froster and Jackson (1996) argue that there is no correlation between gestational age at CVS and severity of defects. Furthermore the results of their cohort study did not indicate any increased risk of limb defects after CVS.

• infants born to mothers who have early amniocentesis or CVS have a higher number of talipes, haemangiomas and minor digit abnormalities (Greenough et al, 1997)

Infection (Sweet, 1997)

Limitations of the test:

• Does not test for neural tube defects

Bleeding:

• Possibility of some risk of vascular disruption.

• Potential risk of Rh iso-immunisation (Rh immune globulin must be administered if mother is Rh- and father Rh+.

• More bleeding following CVS than amniocentesis (Enkin, 1994)

Miscellaneous:

• Loss of amniotic fluid is a possibility but does not appear to adversely affect the fetus.

• Maternal-paternal stress

• Possible sex selection abuse.

• Between 2.2% and 10% of CVS tests "fail" i.e. there is either an inadequate specimen (1 - 6%); the cells do not grow (0.4 - 2%) or the result is inconclusive (0.8 - 2%).

• failure rates are higher with CVS than with Amniocentesis (Enkin, 1994).

• occasionally the test results are ambiguous or later prove to be incorrect.

• False positives being more common than false negatives and more common with CVS than amniocentesis.

• Cytogenic abnormality is more often diagnosed after CVS than Amniocentesis.

• The greater number of false positive diagnoses was due to more frequent ambiguous findings, including mosaics and confined placental abnormalities.

Chorionic Villus Sampling is not a satisfactory test for early prenatal diagnosis for women at relatively low risk of fetal abnormality. Alternatives must be sought, but should be rigorously evaluated before deciding whether they should be introduced into clinical practice (Grant, 1992).

What is mosaicism?

Mosaicism is when different cells analysed in the laboratory have differing chromosomes, a condition occurring in a small percentage of people. The individual will have both normal and abnormal cells. It occurs as a result of a chromosomal "accident" occurring after fertilisation. The outcome for the baby is difficult to predict, depending on the timing of the accident, the type of tissue affected, what the chromosome types are, the proportion for each type of cell and other variables. The wide variation found in phenotypes in individuals with Down Syndrome can be explained in part by mosaicism. If only a small portion of cells are affected, there may be no effect on the development of the individual. There is a high risk for the children of a mosaic parent to have a chromosomal abnormality (Raff, 1994). The CVS may occasionally show mosaicism even when this is not present in the baby. Mosaicism occurs in approximately 1% of CVS's and usually requires an amniocentesis to confirm the result. A very stressful time for the parents involved!!!!

Why can't amniocentesis be performed earlier than 15-16 weeks LMP?

First trimester (11 - 12 gestational weeks) amniocentesis is an alternative but has more adverse effects, including:

• neonatal respiratory problems (Greenough et al., 1997 and Angus, 1997).
• talipes equinovarus (CEMAT, 1998)
• amniotic fluid leakage (CEMAT, 1998)
• spontaneous fetal loss (CEMAT, 1998)
• cytogenic-culture failure (CEMAT, 1998)

In mid-trimester amniocentesis, 12 - 15 mls of amniotic fluid is aspirated for cytogenetic analysis. When a similar volume of amniotic fluid is removed by early amniocentesis, it represents a significant proportion of the total amniotic fluid volume in the first trimester. The fluid depletion, which may persist for 7 - 10 days, is considered to impair development of fetal lungs and extremities and, possibly, contribute towards procedure-related congenital abnormalities and miscarriages (Tharmaratnam, Sadek, Steele et al 1998). By removing only 7mls, the incidence of adverse side effects can be reduced but not eliminated (Tharmaratnam, Sadek, Steele et al 1998).

What are some of the drawbacks with amniocentesis?

Amniotic fluid cell chromosome studies have three major drawbacks:

1. It takes 2 - 3 weeks from the time the sample is taken until the result is available.
2. It is not usually carried out before 14 - 16 weeks of pregnancy.
3. Culture failure occurs in about 2% of samples (Enkin, 1994)

NOTE: The risk of fetal loss is approximately 0.5 - 1%.

In addition there is a risk of about 0.5% of a baby with very low birthweight and of neonatal respiratory problems. There is a high incidence of feto-maternal bleeding. (Enkin, 1994)

What is nuchal thickness or nuchal translucency?

In the fetus fluid collects behind the neck, a little like ankle oedema in later life. It occurs partly because of the fetus's tendency to lie on it's back and partly because of the laxity of the skin of the neck. It is more pronounced when there is a congenital heart condition, less fetal movement, Down's syndrome or a combination.

The more fluid that is accumulated the greater the risk of an abnormality being present. Nuchal transparency or thickness can be measured at 10 - 14 weeks gestation, after this the lymphatic system is likely to have developed enough t drain off any accumulated fluid.

About 90% of fetuses with 3mm (high) nuchal transparenecy at 12 weeks are not affected at birth, while 10% will have major abnormalities. Only 10% of babies with a measurement of 6mm (very high) will be unaffected.

Almost one in five of all attempts to measure fetal nuchal translucency will be unsuccessful (Haddow 1998)

What is the triple test actually measuring?

Triple test measures:

Alpha-fetoprotein:

• Made by the fetal yolk sac and fetal liver
• Generally present throughout the fetus
• Processed and excreted into the amniotic fluid, swallowed and reprocessed by the fetus
• Small amount crosses the placenta and can be measured in maternal blood
• If a major open defect such as spina bifida or omphalocoele is present AFP levels will be high
• Levels will be low when a fetus is affected by Downs Syndrome
• AFP alone identifies approximately 20% of fetuses with Downs Syndrome, and will miss approximately 80%

Human Chorionic Gonadotrophin:

• Levels will be higher than average when a fetus has Downs Syndrome

Unconjugated oestriols:

• Rates of detection of Downs Syndrome are low and so Inhibin A is considered a more useful measure - Haddow et al

Inhibin A

• May also be measured
• Pregnancy associated protein A concentrations are lower in a fetus affected with Downs Syndrome

Other factors considered:

• The pregnant woman's age, race, weight and diabetic status.

References:

1. Angus, G. 1997. Lecture given to GMHS Women's Health and Sexual Health Nurses, 11.9.97
   
   
2. Berger, A. (1999). Using fetal nuchal tranlucency to screen for major congenital cardiac defects at 10 - 14 weeks of gestation: population based cohort study: Science commentary: What is fetal nuchal translucency? British Medical Journal, 318, (7176), p. 85.
   
   
3. Boyd, P., Chamberlain, P. & Hicks, N. (1998). 6 year experience of prenatal diagnosis in an unselected population in Oxford, UK. The Lancet, 352, (9140), pp. 1577 - 1581.
   
   
4. Canadian CVS Trial. (1989). Canadian Collaborative CVS-Amniocentesis Clinical Trial Group. Canadian multi-centre randomised clinical trial of CVS and Amniocentesis. The Lancet, 1, pp. 1 - 6.
   
   
5. CEMAT (The Canadian Early and Mid-Trimester Amniocentesis Trial (CEMAT) Group. 1998. 'Randomised trial to assess safety and fetal outcome of early and midtrimester amniocentesis', The Lancet, Vol. 351, 24.1.98, pp. 242 - 247.
   
   
6. Connolly, M., Russel, F. & Morgan, J. (1984). Evaluation of children with Down syndrome who experienced early intervention: third follow-up study. Journal of the American Physical Therapy Association, 64, pp. 1515 - 8, cited in Elkins, T. & Brown, D. (1995). Ethical concerns and future directions in maternal screening for Down Syndrome. Women's Health Institute, 5, (1), pp. 15 - 20.
   
   
7. Elkins, T. & Brown, D. (1995). Ethical concerns and future directions in maternal screening for Down Syndrome. Women's Health Institute, 5, (1), pp. 15 - 20.
   
   
8. Enkin, M., Keirse, M., Renfrew, M. & Neilson, J. (1994). A guide to effective care in pregnancy and childbirth 2nd edition. Oxford University Press.
   
   
9. European CVS Trial. (1991). MRC Working Party on the evaluation of chorionic villus sampling. Medical Research Council European Trial of CVS. The Lancet, 337, pp. 1491 - 99.
   
   
10. Evans, M., Chik, L., O'Brien, J., Chen, B. et al (1994). Mom's and dad's: improved specificity and cost-effectiveness of biochemical screening for aneuploidy. Presented at the 13th Annual Meeting of American Gynaecological and Obstetrical Society, cited in Elkins, T. & Brown, D. (1995). Ethical concerns and future directions in maternal screening for Down Syndrome. Women's Health Institute, 5, (1), pp. 15 - 20.
    
    
11. Firth, H, Boyd, P, Chamberlain, P, Mackenzie, I. Morris-Kay, G & Huson, S. 1994. Analysis of limb reduction in babies exposed to chorionic villus sampling. The Lancet. 30.4.94. Vol 343: 1069 - 71.
    
    
12. Froster, U; & Jackson, L. 1996. Limb defects and chorionic villus sampling: results from an international registry, 1992 - 1994. Lancet. Vol 347, No 9000 24.2.96 pp 489 - 494.
    
    
13. Gath, A. (1978). The school-age siblings of Mongol children. British Journal of Psychology, 123, pp. 161 - 7, cited in Elkins, T. & Brown, D. (1995). Ethical concerns and future directions in maternal screening for Down Syndrome. Women's Health Institute, 5, (1), pp. 15 - 20.
    
    
14. Grant, A. 1992. Chorionic Villus Sampling compared with amniocentesis. In: Pregnancy and Childbirth Module (eds Enkin, Keirse, Renfrew & Neilson). Cochrane Database of systematic Reviews. 06007. Disk Issue 2.
    
    
15. Grayson, A. (1996). The triple test decision. Modern Midwife, August 1996, pp. 16 - 19.
    
    
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18. Haddow, J. (1998). Antenatal screening for Down's Syndrome: where are we and where next? The Lancet, 352, (9125), pp. 336 337.
    
    
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22. Martin, J., Rusch, F., Tynes, J., Brulle, A & White, D. (1985). Work attendance in competitive employment: comparison between employees who are handicapped and those who are mentally retarded. Mental Retardation, 23, pp. 142 - 8, cited in Elkins, T. & Brown, D. (1995). Ethical concerns and future directions in maternal screening for Down Syndrome. Women's Health Institute, 5, (1), pp. 15 - 20.
    
    
23. Mastroiacovo, P et al. 1993. Prenatal Diagnosis, Vol 13, No 11, Nov 1993, pp 1051 - 1056.
    
    
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25. Pueschel, S., Canning, C. & Murphy, A. (1978). Down syndrome: growing and learning. Cambirdge (MA): Andrew, McMeel Parker, pp. 72 - 4, cited in Elkins, T. & Brown, D. (1995). Ethical concerns and future directions in maternal screening for Down Syndrome. Women's Health Institute, 5, (1), pp. 15 - 20.
    
    
26. Raff, B. 1994. Nursing and Genetics for the 21st century. JOGNN, Volume 23, No 6. July/August, 1994 Pp 477 - 480.
    
    
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28. Rynders, J. & Horrobin, J. (1990). Always trainable? Never educable? Updating educational expectations concerning children with Down Syndrome. American Journal of Mental Retardation, 95, pp. 77 - 83, cited in Elkins, T. & Brown, D. (1995). Ethical concerns and future directions in maternal screening for Down Syndrome. Women's Health Institute, 5, (1), pp. 15 - 20.
    
    
29. Rynders, J., Spiker, S. & Horrobin, J. (1978). Underestimating the educability of Down's Syndrome children, American Journal of Mental Deficiency Research, 82, pp. 4 - 10, cited in Elkins, T. & Brown, D. (1995). Ethical concerns and future directions in maternal screening for Down Syndrome. Women's Health Institute, 5, (1), pp. 15 - 20.
    
    
30. Sheldon, T. & Simpson, J. (1991). Prenatal screening for Down's Syndrome, British Medical Journal, 303, pp. 55 - 56, cited in Howe, D., Gornall, R., Wellesley, D., Boyle, T. & Barber, J. (2000). Six year survey of screening for Down's syndrome by maternal age and mid-trimester ultrasound scans. British Medical Journal, 320, (7235), pp. 606 - 610.
    
    
31. Sweet, B (Ed), 1997. Mayes Midwifery 12th Edition. London: Bailliere Tindall, p 46.
    
    
32. Tharmaratnam, S. Sadek, S. Steele, E. et al. (1998). Early amniocentesis: effects of removing a reduced volume of amniotic fluid on pregnancy outcome. Prenatal Diagnosis, 18, (8), pp. 773 - 778.
    
    
33. Thase, T. (1982). Longevity and mortality in Down's Sydrome. Journal of Mental Defieciency Research, 26, pp. 177 - 180, cited in Elkins, T. & Brown, D. (1995). Ethical concerns and future directions in maternal screening for Down Syndrome. Women's Health Institute, 5, (1), pp. 15 - 20.
    
    
34. Turnbull, A. & Turnbull, H. (1985). Developing independence in adolescents with disabilities. Journal of Adolescent Health Care, 6, pp. 108 19, cited in Elkins, T. & Brown, D. (1995). Ethical concerns and future directions in maternal screening for Down Syndrome. Women's Health Institute, 5, (1), pp. 15 - 20.
    
    
35. Wald, N., Huttly, W. & Hennessy, C. (1999). The Lancet, 354, (9186), p. 1264.
    
    
36. Wald, N., Watt, H. & Hackshaw, A. (1999). Integrated screening for Down's Syndrome based on tests performed during the first and second trimesters. The New England Journal of Medicine, 341, (7), pp. 461 - 467.
    
    
37. Williamson, R. (1997). Detecting fetal abnormalities, Australian Family Physician, 26, (3), pp. 245 - 253
    
    

© Elaine Dietsch 2000.