Maternal serum screening for Down syndrome

This document was published more than 2 years ago. The nature of the evidence may have changed.

A more recent review of the literature is reported in Methods of Early Prenatal Diagnosis, SBU report 182, published 2006.

Findings by SBU Alert

Version: 1

Method and target group

The average incidence of Down syndrome is 1 per 650 births. The risk of having a child with Down syndrome increases with the age of the mother. Nevertheless, most children with Down syndrome are born to women under 35 years of age. Currently, chromosomal analysis via amniocentesis is offered to pregnant women 35 years of age and older. This examination carries a risk for miscarriage of approximately 1 percent. Analysis of biochemical markers in the mothers blood (serum) during gestational weeks 14-15 is an alternative method to identify a risk group. An analysis of the test results, the length of pregnancy as determined by ultrasound, and the mothers age can be used to identify a risk group who can be appropriate for amniocentesis to establish a diagnosis.

Patient benefits and risks

An analysis of serum markers makes it possible to identify a risk group in a more effective way than by using age alone as a risk indicator. This means that substantially fewer amniocentesis examinations are required to detect a fetus with Down syndrome. Hence, miscarriage of a healthy fetus can be avoided. A disadvantage in using these types of serum markers is that they cannot be analyzed prior to gestational weeks 14 or 15 and the followup amniocentesis may thereby be delayed.

Ethical aspects

All fetal diagnostic tests are associated with ethical dilemmas for individuals and society in the short and long term. It is not feasible to recommend a uniform strategy that is based on scientific principles. Rather, the use of available tests must be driven by the wishes of the parents. Hence, it is important to provide parents with evidence-based, comprehensible information on the expected consequences of various tests and advise them that other disorders might also be identified.

Economic aspects

The health economic studies which have been conducted show that the costs of detecting a fetus with Down syndrome are lower when using serum markers compared to using age alone as a risk indicator.

Scientific evidence

There is good* scientific documentation on the diagnostic characteristics of the serum marker test. There is poor* scientific documentation on a range of different consequences in clinical use.

Using serum markers may have potential advantages, but until further evidence becomes available they should be used only in cases that allow scientific followup of the intended, and unintended, effects. A basic requirement is that parents should be provided with accurate, fundamental, and comprehensible information.

*This assessment by SBU Alert uses a 4-point scale to grade the quality and evidence of the scientific documentation. The grades indicate: (1) good, (2) moderate, (3) poor, or (4) no scientific evidence on the subject.

This summary is based on a report prepared at SBU in collaboration with Assoc. Prof. Jan Wahlström, Sahlgrenska University Hospital, Göteborg. It has been reviewed by Assoc. Prof. Connie Jörgensson,Lund University Hospital, Lund and Margareta Sten Linder, Dr, Karolinska Hospital, Stockholm.

The complete report is available in Swedish only.

Alert is a joint effort by the Swedish Council on Technology Assessment in Health Care (SBU), the Medical Products Agency, the National Board of Health and Welfare, and the Federation of Swedish County Councils.

References

  1. Cuckle H. Screening for Down´s syndrome. Statistical modelling is best tool for formulating screening policy. BMJ 2000:321(7263):763.
  2. Epidemologiskt centrum, Socialstyrelsen. Preliminära siffror.
  3. Hook EB, Lindsjö A. Down´s Syndrom in live births by single year maternal age age in a Swedish study: comparison from a New York State study. Am J Hum Genet 1978;30:19-27.
  4. Kolbye A, Möller Pedersen K. Tripletest. En sammenfattende MTV og sundhedsekonomisk vurdering. Odense Universitet, Institut for Helsetjenesteforskning. 2000.
  5. Nöhr-Jensen L, Christiansen C, Hyldgaard L, Woelke M, Strömkjaer H. Tripletest til alle gravide? En Medicinsk Teknologi Vurdering. Aarhus Universitet 2000.
  6. Penrose LS. The relative effect of paternal and maternal age in mongolism. J Genet 1933;27:219-24.
  7. Petrou S, Henderson J, Roberts T, Martin M-A. Recent economic evaluations of antenatal screening: a systematic review and critique. J Med Screen 2000;7:59-73.
  8. Poon LLM, Leung TN, Lau TK, Lo YMD. Prenatal detection of fetal Downs syndrom from maternal plasma. Lancet 2000;356:1819-20.
  9. Salonen R, Kurki L, Lappalainen M. Experiences of mothers participating in maternal serum screening for Down´s syndrome. Eur J Hum Genet 1996;4(2):113- 9.
  10. Saltvedt S, Almström H. Fetal loss rate after second trimester amniocentesis at different gestational age. Acta Obstet Gynecol Scand 1999;78(1):10-14.
  11. SBU-rapport: Rutinmässig ultraljudsundersökning under graviditet. Stockholm 1998.
  12. Schackely P, McGuire A, Boyd PA, Dennis J, Fitchett M et al. An economic appraisal of alternative prenatal screening programmes for Down´s syndrome. J Public Health Med 1993;15:175-84.
  13. Tabor A, Philip J, Madsen M, Bang J, Obel EB, Norgaard-Petersen B. Randomised controlled trial of genetic amniocentesis in 4606 low-risk women. Lancet 1986;i:1287-93.
  14. Wald NJ, Kennard A, Hackshaw A, McGuire A. Antenatal screening for Down´s syndrome. Health Technol Assessment 1998;2.
  15. Wald NJ, Watt HC, Hackshaw AK. Integrated screening for Down´s syndrome based on tests performed during the first and second trimester. NEJM 1999;341(7):461-67.

SBU Assessment presents a comprehensive, systematic assessment of available scientific evidence. The certainty of the evidence for each finding is systematically reviewed and graded. Full assessments include economic, social, and ethical impact analyses.

SBU assessments are performed by a team of leading professional practitioners and academics, patient/user representatives and SBU staff. Prior to approval and publication, assessments are reviewed by independent experts, SBU’s Scientific Advisory Committees and Board of Directors.

Published: 12/1/2000
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