Down syndrome screening
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Screening
Prenatal screening
Pregnant women can be screened for various complications during pregnancy. Many standard prenatal screens can discover Down syndrome. Genetic counseling along with genetic testing, such as amniocentesis, chorionic villus sampling (CVS), or percutaneous umbilical blood sampling (PUBS) are usually offered to families who may have an increased chance of having a child with Down syndrome, or where normal prenatal exams indicate possible problems. Genetic screens are often performed on pregnant women older than 30 or 35.
Amniocentesis and CVS are considered invasive procedures, in that they involve inserting instruments into the uterus, and therefore carry a small risk of causing fetal injury or miscarriage. There are several common non-invasive screens that can indicate a fetus with Down syndrome. These are normally performed in the late first trimester or early second trimester. Due to the nature of screens, each has a significant chance of a false positive, suggesting a fetus with Down syndrome when, in fact, the fetus does not have this genetic abnormality. Screen positives must be verified before a Down syndrome diagnosis is made. Common screening procedures for Down syndrome are given in Table 1.
| Screen | When performed (weeks gestation) | Detection rate | False positive rate | Description |
|---|---|---|---|---|
| Triple screen | 15–20 | 75% | 8.5% | This test measures the maternal serum alpha feto protein (a fetal liver protein), estriol (a pregnancy hormone), and human chorionic gonadotropin (hCG, a pregnancy hormone).[1] |
| Quad screen | 15–20 | 79% | 7.5% | This test measures the maternal serum alpha feto protein (a fetal liver protein), estriol (a pregnancy hormone), human chorionic gonadotropin (hCG, a pregnancy hormone), and high inhibin-Alpha (INHA).[1] |
| AFP/free beta screen | 13–22 | 80% | 2.8% | This test measures the alpha feto protein, produced by the fetus, and free beta hCG, produced by the placenta. |
| Nuchal translucency/free beta/PAPPA screen | 10–13.5 | 91%[2] | 5%[2] | Uses ultrasound to measure Nuchal Translucency in addition to the freeBeta hCG and PAPPA (pregnancy-associated plasma protein A). NIH has confirmed that this first trimester test is more accurate than second trimester screening methods.[3] |
Even with the best non-invasive screens, the detection rate is 90%–95% and the rate of false positive is 2%–5%. False positives can be caused by undetected multiple fetuses (very rare with the ultrasound tests), incorrect date of pregnancy, or normal variation in the proteins.
Confirmation of screen positive is normally accomplished with amniocentesis. This is an invasive procedure and involves taking amniotic fluid from the mother and identifying fetal cells. The lab work can take several weeks but will detect over 99.8% of all numerical chromosomal problems with a very low false positive rate. [4]
Due to the low incidence of Down syndrome, a vast majority of early screen positives are false.[5] Since false positives typically prompt an amniocentesis to confirm the result, and the amniocentesis carries a small risk of inducing miscarriage, there is a slight risk of miscarrying a healthy fetus. (The added miscarriage risk from an amniocentesis is traditionally quoted as 0.5%, but recent studies suggest that it may be considerably smaller (0.06% with a 95% CI of 0 to 0.5%).[6])
A 2002 literature review of elective abortion rates found that 91–93% of pregnancies with a diagnosis of Down syndrome were terminated.[7] Physicians and ethicists are concerned about the ethical ramifications,[8] with some commentators calling it "eugenics by abortion".[9] Many members of the disability rights movement "believe that public support for prenatal diagnosis and abortion based on disability contravenes the movement's basic philosophy and goals."[10]
Postnatal Screening
Persons with Down syndrome need to be closely screened for certain medical conditions. They should have:
- Eye exam every year during infancy
- Hearing tests every 6 - 12 months, depending on age
- Dental exams every 6 months
- X-rays of the upper or cervical spine between ages 3 - 5 years
- Pap smears and pelvic exams beginning during puberty or by age 21
- Thyroid testing every 12 months
References
- ↑ 1.0 1.1 For a current estimate of rates, see Benn, PA, J Ying, T Beazoglou, JFX Egan. "Estimates for the sensitivity and false-positive rates for second trimester serum screening for Down syndrome and trisomy 18 with adjustments for cross-identification and double-positive results". Prenatal Diagnosis. 21 (1): 46–51. PMID 11180240
- ↑ 2.0 2.1 Some practices report adding Nasal Bone measurements and increasing the detection rate to 95% with a 2% False Positive Rate.
- ↑ NIH FASTER study (NEJM 2005 (353):2001). See also J.L. Simplson's editorial (NEJM 2005 (353):19).
- ↑ Fackler, A. "Down syndrome". Retrieved 2006-09-07.
- ↑ Assume the false positive rate is 2% (at the low end), the incidence of Down syndrome is 1/500 (on the high side) with 95% detection, and there is no ascertainment bias. Out of 100,000 screens, 200 will have Down syndrome, and the screen will detect 190 of them. From the 99,800 normal pregnancies, 1996 will be given a positive result. So, among the 2,186 positive test results, 91% will be false positives and 9% will be true positives.
- ↑ Eddleman, Keith A.; et al. (2006). "Pregnancy loss rates after midtrimester amniocentesis". Obstet Gynecol. 108 (5): 1067–1072. Retrieved 2006-12-09. PMID 17077226
- ↑ Caroline Mansfield, Suellen Hopfer, Theresa M. Marteau (1999). "Termination rates after prenatal diagnosis of Down syndrome, spina bifida, anencephaly, and Turner and Klinefelter syndromes: a systematic literature review". Prenatal Diagnosis. 19 (9): 808–812. PMID 10521836 This is similar to 90% results found by David W. Britt, Samantha T. Risinger, Virginia Miller, Mary K. Mans, Eric L. Krivchenia, Mark I. Evans (1999). "Determinants of parental decisions after the prenatal diagnosis of Down syndrome: Bringing in context". American Journal of Medical Genetics. 93 (5): 410–416. PMID 10951466
- ↑ Glover, NM and Glover, SJ (1996). "Ethical and legal issues regarding selective abortion of fetuses with Down syndrome". Ment. Retard. 34 (4): 207–214. PMID 8828339.
- ↑ Will, George (2005-04-14). "Eugenics By Abortion: Is perfection an entitlement?". Washington Post: A37. Retrieved 2006-07-03.
- ↑ Erik Parens and Adrienne Asch (2003). "Disability rights critique of prenatal genetic testing: Reflections and recommendations". Mental Retardation and Developmental Disabilities Research Reviews. 9 (1): 40–47. Retrieved 2006-07-03. PMID 12587137