A screening test can determine if an unborn baby has an increased likelihood for Down syndrome. Because the chances of having a baby with Down syndrome increase with the age of the mother, many health care providers recommend that women over age 35 have prenatal testing for the condition. Testing the baby before it is born to see if he or she is likely to have Down syndrome allows parents and families to prepare for the baby’s special needs. The simplest test, which is non-invasive, checks the levels of three markers in a drop of the mother's blood. If the markers show an increased likelihood of Down syndrome, additional diagnostic testing can be performed. Options for additional prenatal screening include:

Amniocentesis: This test is an analysis of a small sample of fetal cells from the amniotic fluid in the womb. The sample is taken through a needle, guided by ultrasonic imaging, inserted through the mother's belly. This test cannot be performed until the 14th to 18th week of pregnancy, and it usually takes additional time to determine whether the cells contain extra material from chromosome 21. The risk of a miscarriage caused by amniocentesis is low.

Chorionic Villus Sampling (CVS): This test is an analysis of a small tissue sample of chorionic villi - tiny, finger-shaped growths found in the placenta. The genetic material in chorionic villus cells is the same as the genetic material of the baby's own cells. The tissue sample is taken with a thin catheter inserted into the mother's vagina and guided by ultrasonic imaging through the cervix and into the placenta. The sample can also be collected through a long, thin needle inserted through the belly. This test is conducted at 9 to 11 weeks of pregnancy, and carries a 1-2% risk of miscarriage.

Percutaneous Umbilical Blood Sampling (PUBS): This test – an analysis of blood from the fetus – is the most accurate screening method. The blood sample is taken through a needle, guided by fluoroscopic imaging, inserted through the mother's belly and into the baby's umbilical cord. Results are usually available within three days. This test cannot be performed until the 18th to 22nd weeks, and it carries the greatest risk of miscarriage.

Once the baby is born, a genetic test called a chromosome analysis is performed on a sample of the baby's blood or skin cells to confirm the presence of an extra chromosome 21.