IDSSG
DOWN SYNDROME SCREENING: A POSITION STATEMENT FROM THE SCIENTIFIC COMMITTEE OF THE INTERNATIONAL DOWN SYNDROME SCREENING GROUP
Chairman: Malcolm Ferguson Smith
*David Aitken, Svetlana Arbuzova, Peter Benn, Jack Canick, Howard Cuckle, Albert Fortuny, *Muir Gray, Yung Hang Lam, Andrew MacRae, *Francoise Muller, Bent Norgaard-Pedersen, Kevin Spencer, Nick Wald, *Martin Whittle
*Agreement not confirmedBACKGROUND
Prenatal diagnosis of Down syndrome and certain other fetal aneuploidies through chromosome analysis of amniocytes or chorionic villus samples (CVS) has become an accepted part of prenatal care. Because amniocentesis and CVS procedures are thought to carry some degree of risk for miscarriage or other (less serious) pregnancy complications, these invasive procedures are generally only acceptable to those at highest risk for an affected pregnancy. Risk can be evaluated on the basis of a combination of maternal age, prior family history, maternal serum biochemical tests and fetal biometric measurements obtained through ultrasonography. Risk evaluation provides an opportunity to re-assure most women that their fetus is unlikely to be affected by a chromosomal disorder and also to reduce the number of unnecessary invasive procedures performed. Those women who are identified as being at high risk can receive genetic counseling, additional testing and appropriate follow-up obstetric care.GOAL OF RISK EVALUATION
Every pregnant woman should have the opportunity to accept or reject amniocentesis or CVS on the basis of the best possible estimate of her personal risk for fetal aneuploidy. Programs involved with risk evaluation aim to provide timely and accurate individual patient-specific estimates of risk for the most common and clinically significant fetal aneuploidies.TECHNOLOGIES AVAILABLE
A range of maternal serum biochemical and ultrasound fetal biometric markers have well-documented efficacy in distinguishing between affected and unaffected pregnancies. Each has validity only within a specified time interval in pregnancy and should not be offered at earlier or later gestational ages. Combination of markers is valid, provided the correlation between them has been taken into consideration in the risk calculation.MEASURING EFFICACY OF PROTOCOLS
The efficacy of risk assessment protocols has traditionally been based on the detection rate (DR, or sensitivity), false-positive rate (FPR), and positive predictive value (PPV), or odds of being affected given a positive result (OAPR). These population-based screening performance indices are of considerable value in comparing different protocols. It should be noted that striving for protocols with high detection rates does not imply that risk assessment programs exist in order to directly reduce the prevalence of aneuploid births. The aim of risk assessment is rather to inform women and help them choose between the options available to them. The relative efficacy of different protocols can be assessed by either fixing the FPR (say 5% or 1%) and comparing the DR, or fixing the DR (say 85% or 75%) and comparing the FPR. For a fixed risk cut-off, both the DR ad FPR will vary between protocols.CHOICE OF PROTOCOL
The use of maternal age as a sole criterion for aneuploidy risk assessment is no longer justifiable. It is recognized that the availability of ultrasound and laboratory resources, early pregnancy referral patterns, economic considerations and other factors are likely to result in geographic differences in the protocols used. No single combination of markers will be appropriate for all situations. Statistical modeling using observational data is a reliable way of estimating the DR, FPR and PPV of different screening protocols. Intervention studies often overestimate the screening performance but may provide important information on the practicality of a specific protocol. Most centres currently use 2 or 3 serum markers at 15-19 weeks, but newer protocols can achieve lower false-positive rates for the same, or a higher, DR. On the basis of both observational studies and intervention projects the Scientific Committee recommends the following [published estimates of FPR to achieve an 85% DR are given in parentheses]: (1) Ultrasound nuchal translucency (NT) at 11-13 weeks combined with concurrent serum markers at 10-13 weeks, for women who want an early result [FPR 2-6%]. (2) Four serum markers at 15-19 weeks, for women who first attend after 13 weeks [FPR 6-10%]. Observational data indicate even better results for the following, although the practicality has still to be confirmed by the publication of implementation projects: (3) Combining (1) and (2) such that the result is reported after (2), as a single risk incorporating all markers [FPR 1-2%]. Reporting a partial result after (1) in some women may potentially lead to a higher FPR.QUALITY ASSURANCE
Laboratories providing maternal serum screening tests must participate in proficiency testing and monitor their performance through epidemiologic monitoring. Fetal ultrasound biometry should only be performed by specifically trained ultrasonographers and there should be an on-going audit of performance. Computer programs used in calculating risk should be checked for design accuracy. Comprehensive registries of aneuploidy should be encouraged, provided confidentiality of individual patient data can be assured. These registries can provide validation of the risks and also have considerable research value.OVERVIEW
Aneuploidy risk assessment is a component of a broader set of prenatal clinical services that includes genetic counseling, chromosome analysis, and obstetrics. Information is provided through non-directive counseling. Each patient makes their own determination whether they wish to receive these services. Respect for ethical values, sensitivities and the decisions made by each patient are of key importance in the delivery of these services.SUMMARY
1. The use of maternal age alone to assess Down syndrome risk should be abandoned.
2. A combination of ultrasound NT measurement and maternal serum markers in the first trimester should be available to women who want an early risk assessment.
3. A four marker serum test should be available to women who first attend for their prenatal care after 13 weeks of pregnancy.
4. There are indications of even better results when first and second trimester markers are incorporated into a single test, although practicality has still to be confirmed.
