Pregnancy Information Center

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About Screening for Birth Defects


An expert shares what you need to know about early prenatal tests

By Elaine Brown, MD


Historically, prenatal screening was offered primarily to women older than 35. These mothers were offered amniocentesis, which at that time was the only available option. Amniocentesis is a test that checks for some birth defects, including Down’s Syndrome, Trisomy 18 and neural tube defects. It involves inserting a needle into the amniotic sac (a protective, liquid-filled sack that surrounds the baby in the womb) and removing a small amount of the liquid within (amniotic fluid). Although considered safe, the test does pose potential risks. Also, it’s not done until the second trimester and, if you would consider termination of the pregnancy based on the results, waiting until then can be agonizing.

Experts chose 35 as the age to offer screening because that’s when the risk of Down’s syndrome was equal to the risk of a procedure-related complication due to the amniocentesis. In other words, the risk/benefit ratio tipped at this age to favor testing. But because the total number of babies born to women younger than 35 years old is greater than the number born to older women, most babies with congenital anomalies are actually born to women younger than 35. 

This led to the search for less invasive screening tests and tests that can be done earlier in the pregnancy. Now there’s a long list of possible screening tests that can be done in the first, second, or combined first and second trimesters. Your provider will generally identify which tests are available in your area that will meet your individual needs. The main disadvantage of these tests is that they’re screening tests, which means some cases will fail to be detected. There may also be false positives that could lead to further diagnostic tests such as amniocentesis that involve some risk to the fetus.

Presently, the most efficient and widely used screening test is the "quad" screen (it has an 81% chance of detecting these disorders). Made up of a panel of four blood analytes (alpha-fetoprotein, human chorionic gonadotropin or hCG, unconjugated estriol and inhibin-a), it’s accurate, reliable and non-invasive. The chief disadvantage is that, as with the amniocentesis, the "quad" screen must be delayed until the second trimester. Additionally, the results are difficult to interpret in multiple gestations (twins and higher). And a third factor to remember is that the quad screen is just that, a screening test, and an abnormal result will need to be verified with a diagnostic test like amniocentesis.

Recently, interest has been directed toward first-trimester screening. A combination of special ultrasound measurements and analysis of blood analytes is now being implemented as a tool for getting earlier results. The "nuchal translucency" is a normal, fluid-filled space at the back of the fetal neck. With proper use of ultrasound technique, this space and its overlying skin can be accurately measured in most pregnancies between 10 and 14 weeks gestational age. Abnormalities in this measurement correlate well with fetal Down's syndrome, other fetal aneuploidies and fetal major cardiac anomalies.

Additionally, it’s known that pregnancies affected by fetal Down's syndrome are linked with higher levels of free beta-hCG and lower levels of pregnancy-associated plasma protein-a (PAPP-A). For a given pregnancy with a combination both of a normal ultrasound study and normal values of free beta-hCG/ PAPP-A, doctors can feel comfortable recommending deferral of invasive testing. Alternatively, abnormal values alert doctors to recommend diagnostic testing to confirm results. A large study in the US and UK of first trimester screening using the NT and free beta-hCG/ PAPP-A combination revealed an 82 to 87% detection rate, considered adequate for a first-trimester screening. Other available options include the triple screen (detection rate 69%) and the NT ultrasound alone (64 to 70%).

One disadvantage of this first-trimester screening is that the NT and free beta-hCG/ PAPP-A combination doesn’t screen for spina bifida or ventral wall defects, therefore an alpha-fetoprotein screen is recommended in the second trimester. This additional blood test raises the detection rate to 94 to 96%.

While no single option is ideal for every pregnancy, first-trimester screening with nuchal translucency and free beta-hCG/ PAPP-A has definite advantages when early results are desirable. Today, all women, regardless of age, are offered the option of diagnostic or screening tests. Ideally you want a test that has a high detection rate with low risks to the fetus. Studies have shown that different women have different preferences and should be involved in the decision-making. First trimester screening is just one of the many options currently available to you.


Published on March 6, 2014. Updated on December 4, 2015.


Dr. Elaine Brown completed her residency in obstetrics and gynecology at Harvard. She has more than 15 years of experience in private practice.

Reviewed by Elisabeth Aron, MD, MPH, FACOG on October 5, 2015.