Prenatal Screening for Down Syndrome and Open Neural Tube Defects
What is the Integrated Test?
The Integrated Test is a screening for Down syndrome and open neural tube defects. The information below answers some of the common questions women ask about this screening test. We hope you find it helpful. You are welcome to discuss the test with your health care provider before you decide whether you would like to be screened. If you have any further questions, staff at Women & Infants are available to talk with you at 401-453-7650.
What is Down syndrome?
Down syndrome is caused by the presence of an extra chromosome number 21 in the cells of the developing baby. In an unscreened population, about 1 in every 700 babies is born with Down syndrome. Usually it is not inherited and so a baby can be affected even if there is no history of Down syndrome in the family. Although Down syndrome occurs more frequently as mothers get older, about 70% of babies with Down syndrome are born to women who are younger than 35 years old.
Down syndrome is always associated with mental retardation, and is often associated with physical problems such as heart defects and difficulties with sight and hearing. It is not possible to assess the degree of handicap before the baby is born. About 9 out of 10 babies with Down syndrome will survive their first year, and nearly half of these will reach 60 years of age.
What are open neural tube defects?
The two main kinds of open neural tube defects (NTD) are spina bifida and anencephaly. In the unscreened population, about 1 baby in every 1,000 is born with a neural tube defect.
Open spina bifida is an incomplete closure of the spine. It varies in severity depending on where it’s located on the spine and how big the opening is. Surgery to close the opening is usually performed shortly after birth, and additional surgery is often necessary later in infancy or childhood. Open spina bifida usually causes some amount of paralysis from the waist down and interferes with bowel and bladder control. It often leads to a condition called hydrocephalus (water on the brain) and can sometimes cause mental retardation. One of every 10 babies born with open spina bifida will not survive.
Anencephaly is a very severe birth defect in which the brain and the skull fail to develop properly. It results in either stillbirth or death shortly after birth.
In about 1 in every 5 babies with spina bifida, the spinal opening is covered with skin or thick tissue. This is called closed spina bifida and will not be detected by the blood test. This condition is usually less severe than open spina bifida.
What does the Integrated Test involve?
The Integrated Test is performed in two stages. The first stage is ideally performed at 11 or 12 weeks of pregnancy, but any time between 10 and 13 weeks is acceptable. The second stage is ideally performed at 15 or 16 weeks of pregnancy and no later than 22 weeks.
The first stage involves:
A. an ultrasound examination to precisely determine the gestational age of the pregnancy and to measure the nuchal translucency (NT) thickness, a space at the back of the baby’s neck;
B. taking a blood sample to measure the concentration of the marker, pregnancy associated plasma protein-A (PAPP-A);
C. telling you the recommended date for taking a second blood sample for the second stage of the test.
The second stage involves:
A. taking a second blood sample to measure the concentration of the following four markers:
- alpha-fetoprotein (AFP)
- human chorionic gonadotropin (hCG)
- unconjugated estriol (uE3)
- inhibin-A (inhA); and
B. integrating the measurements from the first and second stages into a single screening result. The NT measurement and the levels of the five markers in your blood are used, together with your age, to estimate your risk of having a pregnancy affected by Down syndrome.
In pregnancies with Down syndrome, PAPP-A, AFP and uE3 levels tend to be low, and NT measurement, inhA and hCG levels tend to be raised. The level of AFP in the second blood sample is also used to determine if there is an increased risk of spina bifida or anencephaly.
Why wait until the second stage to have a risk estimate?
By using information from both stages, the test is safer and more effective than a test using information from the first stage alone. It will better distinguish affected from unaffected pregnancies, reducing the chance that a Down syndrome pregnancy is missed, as well as reducing the chance that you will need an invasive diagnostic test, such as an amniocentesis.
What is a “risk”?
A risk is the chance of an event occurring. For example, a risk of Down syndrome of 1 in 100 means that if 100 women have this risk, we expect that 1 of these women will have a baby with Down syndrome and that 99 will not. This is the same as saying that the baby has a 1% chance of having Down syndrome and a 99% chance that it does not.
When will the results be available?
The results of the test are usually ready within 3 working days of the second blood sample being taken. Results are sent to your health care provider.
Your screening result is either screen positive or screen negative. Screen positive results are telephoned and faxed to your health care provider.
What does a screen positive result for Down syndrome mean?
A screen positive result means that you are in a high risk group for having a baby with Down syndrome. If you are in this group, you will be offered a diagnostic test.
The result is screen positive if the risk of Down syndrome at midpregnancy is 1 in 110 or greater. About 1 or 2 in every 100 women screened will be in this group.
Not all women with screen positive results have a pregnancy with Down syndrome. For example, of about 10 women with screen positive results, only 1 would have an affected pregnancy.
What does a screen positive result for open neural tube defects mean?
A screen positive result means that you are in a group with an increased risk of having a baby with an open neural tube defect. If the result is screen positive, you will be offered an ultrasound examination after 16 weeks of pregnancy, and possibly an amniocentesis.
The result is screen positive when the AFP level is equal to or higher than two times the normal level for your stage of pregnancy.
What does a screen negative result mean?
If the risk of Down syndrome based on the Integrated Test is lower than 1 in 110, and the AFP level is less than two times the normal level for your stage of pregnancy, then the result is called screen negative and a diagnostic test is usually not offered.
Although a screen negative result means that your risk of having a baby with Down syndrome or open neural tube defect is not high, a screen negative result cannot rule out the possibility of a pregnancy with either of these abnormalities.
Does the Integrated Test detect all pregnancies with Down syndrome or an open neural tube defect?
No. About 8 or 9 out of 10 cases of Down syndrome are detected (classified as screen positive). This means that 1 or 2 out of 10 pregnancies with Down syndrome are missed (classified as screen negative). About 4 out of 5 cases of spina bifida are detected, and 1 out of 5 is missed. Nearly all cases of anencephaly are detected.
Why do women with screen negative results occasionally have babies with Down syndrome or an open neural tube defect?
It is uncommon for a woman to have a baby with Down syndrome or an open neural tube defect, and it is even more uncommon for a woman with a screen negative result, but it does sometimes happen.
This is because the screening test cannot completely distinguish affected from unaffected pregnancies. However small the risk is, the test cannot completely rule out the possibility of the baby having Down syndrome or an open neural tube defect.
Can any other abnormalities be identified?
Yes, the risk of two other disorders – trisomy 18 and Smith-Lemli-Opitz syndrome – can be estimated using the Integrated Test.
Trisomy 18 (also known as Edwards syndrome) is a usually fatal abnormality caused by the presence of an extra chromosome number 18 in the cells of the developing baby. In the absence of screening, about 1 in every 7,000 babies is born with trisomy 18. The risk of trisomy 18 can be estimated using PAPP-A, AFP, uE3, and hCG, and is reported only when the risk is 1 in 100 or higher. If your risk is high, you are offered another ultrasound examination and an amniocentesis. This is arranged by your health care provider. The Integrated Test detects 6 out of 10 pregnancies affected with trisomy 18.
Smith-Lemli-Opitz syndrome is a uncommon genetic disorder caused by an error in the synthesis of cholesterol. It is associated with many problems in the developing baby, most important are mental retardation and poor growth. In the absence of screening, about 1 in every 20,000 babies will be born with Smith-Lemli-Opitz syndrome. The risk of Smith-Lemli-Opitz syndrome is estimated using AFP, uE3, and hCG and is reported only when the risk is greater than 1 in 50.
Why do you take my age into account?
Any woman may have a baby with Down syndrome, but the chance of this happening increases as a woman gets older. Therefore, we use age as one of the factors when assessing your risk of having a pregnancy with Down syndrome. It means that an older woman is more likely to have a result in the higher risk group (screen positive) and will therefore be offered a diagnostic test.
For example, for women under the age of 35, fewer than 1% will be screen positive and 82% of all Down syndrome pregnancies will be identified. In women who are 35 or older, about 4% will be screen positive and about 92% of Down syndrome pregnancies will be identified. Overall, about 1% of women will be screen positive and about 85% of Down syndrome pregnancies will be identified.
What happens if I can’t come in for the second blood sample?
If you can’t come in for the second blood test, we will not be able to report a screening result for the Integrated Test. We will contact your health care provider after the recommended date for your second blood sample. If we do not receive your second sample by 22 weeks of pregnancy, a Down syndrome risk will be given based on information from the first stage only.
If you know that you will not be able to submit a second blood sample, please discuss this with your health care provider. You could have screening based on the first blood sample and the ultrasound examination alone, although this is less effective than the Integrated Test.
What happens if the ultrasound examination shows that I am too late for the first stage of the test?
In that case, we will not be able to report a screening result for the Integrated Test. However, you could have screening based on the second stage alone beginning when you are 15 weeks pregnant.
What are the tests that will be offered if my Integrated Test result is screen positive?
It depends on your particular result. If the test is screen positive for Down syndrome or at increased risk for trisomy 18 or Smith-Lemli-Opitz syndrome, an amniocentesis procedure will be offered, sometimes accompanied by a detailed ultrasound examination. If the test is screen positive for open neural tube defects, a targeted ultrasound examination is most commonly offered, although an amniocentesis is often suggested as well.
What is an amniocentesis and what will it show?
An amniocentesis is a procedure in which the doctor obtains a small sample of fluid that surrounds the developing baby by passing a fine needle through the abdominal wall and into the uterus, under the guidance of an ultrasound scan. The sample is then sent for laboratory testing. This fluid sample can be used to diagnose chromosome problems like Down syndrome and trisomy 18, as well as open neural tube defects and Smith-Lemli-Opitz syndrome. An amniocentesis is an invasive procedure, which means that there is a small risk of miscarriage (about 1 in 200) associated with it.
Results of the test for Down syndrome and trisomy 18 usually take one to two weeks. A rapid technique for the diagnosis of Down syndrome and trisomy 18, fluoresence in situ hybridization (or FISH), may be available in your area. FISH results usually take 2 days. Results for the test for open neural tube defects and Smith-Lemli-Opitz syndrome usually take 5 to 7 days.
What is an ultrasound and what will it show?
Ultrasound machines use sound waves to look at the developing baby. This procedure, called sonography, is often used to check fetal age or whether more than one baby is present. Level II or targeted sonography will provide a detailed examination of portions of the baby’s body. It cannot be used to diagnose Down syndrome or trisomy 18, but it can often identify spina bifida and various fetal abnormalities that are associated with Down syndrome, trisomy 18, or Smith-Lemli-Opitz syndrome.
Will these diagnostic tests guarantee that my baby is free of all birth defects?
No test can guarantee that your baby is free of all birth defects, but if the result of the amniocentesis is negative, it will rule out Down syndrome or other chromosome abnormalities.
What happens if my baby does have a birth defect?
A genetic counselor will be available to discuss your baby’s diagnosis in detail and options available to you. One option would be to continue the pregnancy and make arrangements for appropriate medical services at and after delivery. Placing the infant for adoption after birth can also be considered. Another option would be termination of pregnancy.
For more information
If you have additional questions, please speak with your health care provider or call Women & Infants’ Division of Prenatal and Special Testing at 401-453-7650. Additional resources are:
Women & Infants’ Prenatal Diagnosis Center
National Down Syndrome Society
Spina Bifida Association of America
- The Integrated Test is currently the most effective method of screening for Down syndrome.
- The Integrated Test is performed in two stages.
- The first stage takes place between 10 and 13 weeks of pregnancy, when a blood sample is obtained and an ultrasound examination is performed.
- The second stage involves a second blood sample, taken at 15 or 16 weeks of pregnancy (up to 22 weeks is acceptable).
- The Integrated Test is based on information collected on both occasions and uses this to estimate the risk of having a baby with Down syndrome.
- Women with a high risk of having a Down syndrome pregnancy are called screen positive.
- An amniocentesis is offered to those women who are screen positive to determine whether the pregnancy is affected by Down syndrome.
- A screen positive result does not necessarily mean that a pregnancy is affected.
- The Integrated Test includes alpha-fetoprotein (AFP) measurement, used in screening for open neural tube defects.
- Women with screen positive results for open neural tube defects are offered a detailed ultrasound examination and possibly an amniocentesis.
- The Integrated Test can also identify whether you are at high risk of having a baby affected by trisomy 18 or by Smith-Lemli-Opitz syndrome.
- The Integrated Test alone cannot determine whether the pregnancy is definitely affected by Down syndrome or an open neural tube defect.
©2003 Women & Infants Hospital
We thank our colleagues at the Wolfson Institute of Preventive Medicine, London, for permission to edit and reproduce their brochure.