Christina Churchill, Susan Dudley, PhD and Emily E. Mazurak
Updated August 2014
Down syndrome is the most common cause of developmental disability in the United States. Children with Down syndrome typically have mild to moderate mental retardation, along with several distinctive physical characteristics and medical problems.
Approximately one out of every 800 babies is born with Down syndrome and there are currently more than 400,000 individuals living with Down syndrome in the United States. Due to a genetic mistake that occurs at the earliest stages of development, individuals have an extra copy of chromosome-21 in their cells.
According to the National Down Syndrome Society, the likelihood that a baby will be born with Down syndrome increases with maternal age. While fewer than 1 in 1000 children born to mothers who are under 30 have Down syndrome, the odds increase to 1 in 105 among 40 year old mothers, and to 1 in 20 for women pregnant at age 45. For this reason, many older pregnant women are interested in getting prenatal Down syndrome screening.
There are several prenatal screening and diagnostic tests for Down syndrome. Each test comes with its own advantages and disadvantages because they vary in terms of:
- How early in pregnancy they can be used. These tests occur either late in the first trimester (weeks 11-13) or in the second trimester (weeks 15-18)
- How complex the tests are. They can range from simple maternal blood tests, to a special fetal ultrasound test, to tests of tissue samples collected from inside the mother’s uterus
- How risky they are to the health of the mother and the survival of the baby
- How accurately they can detect every case of Down syndrome (false negative rate)
- How frequently they mistakenly indicate Down syndrome when it is not actually present (false positive rate)
Is Earlier Screening Practical?
In the United States, most Down screening is done during the second trimester of pregnancy. By the time the test results are made available to the parents, the pregnancy is well advanced. Many people would favor first-trimester screening if parents could be assured that the results will be accurate.
A 2005 study by Malone and colleagues from Columbia University suggested that first-trimester screening can, in fact, be very effective when several tests are combined to calculate risk of Down syndrome. For this study, the researchers tested more than 38,000 pregnant women in order to determine the most accurate results with the smallest potential for harm at the earliest point in pregnancy. They compared first-trimester tests, second-trimester tests, and test that spanned both first and second trimesters.
The same researchers found that when the mother’s age is taken into account, 87% of Down cases can be detected by combining a specialized ultrasound test and a simple maternal blood test at 11 weeks of pregnancy. Researchers used a specialized 20-minute sonogram measuring the thickness of the skin on the back of the fetus’s neck along with a maternal blood test measuring pregnancy associated plasma protein-A (PAPP-A) and the free beta subunit of human chorionic gonadotropin (fßhCG).
The researchers also found that in situations where the specialized ultrasound test is inconclusive or not available, doctors can combine the 11-week maternal blood test with a second-trimester maternal blood test taken at 15-18 weeks. By measuring for a-fetoprotein, total hCG, unconjugated estriol (uE3), and Inhibin-A., doctors are able to detect 96% of Down cases.
Experts believe that this will be an important breakthrough for parents whose pregnancies are at risk because of maternal age or other factors. It means that only 13 babies with Down syndrome would be missed out of every 80,000 pregnant women screened in the general population.
Earlier Screening and Later Testing
Earlier, non-invasive screening tests can provide many advantages. Most of the time the results will be negative, and the parents’ anxiety will be put to rest. The sooner parents learn if Down syndrome is probable, the more time they have to weight their options and make difficult decisions. Through their research, Malone and other Columbia University researchers found that is that there is a 5 in 100 chance that the screening test will indicate Down syndrome when it is not actually present (a false positive result). Unfortunately with the earlier testing, 13 babies with Down syndrome would be missed for every 80,000 pregnant women screened.
Additional diagnostic testing can be performed on babies who screen positive for Down syndrome, using amniocentesis or chorionic villus sampling (CVS). To date, amniocentesis and CVS are the most accurate tests available. Since both of those tests have a risk of causing miscarriage, it is very important that the initial screening be as accurate as possible. First-trimester screening will mean that parents can be better informed in making decisions about whether they want to risk having these more invasive but more accurate tests.
For parents who choose to continue their pregnancies after a Down syndrome diagnosis, first-trimester results give them more time to become educated and prepared for raising a child with Down syndrome. Those who decide to terminate their pregnancies could do so at an earlier point, when there are fewer risks to the woman’s health.
For more information on Down syndrome, please visit:
National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health & Human Development: http://www.nichd.nih.gov/health/topics/down/conditioninfo/Pages/default.aspx
National Down Syndrome Society: http://www.ndss.org/
Nemours Foundation: http://kidshealth.org/parent/medical/genetic/down_syndrome.html#
National Down Syndrome Society. Down Syndrome Fact Sheet. Availiable at: http://www.ndss.org/Down-Syndrome/Down-Syndrome-Facts/. Accessed August 4, 2014.
Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock CH, Bukowski R, Berkowitz RL, Gross SJ, Dugoff L, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, Dukes K, Bianchi DW, Rudnicka AR, Hackshaw AK, Lambert-Messerlian G, Wald NJ, D’Alton ME. First-trimester or second-trimester screening, or both, for Down’s syndrome. New England Journal of Medicine. 2005; 353:19.