The American College of Obstetrics and Gynecology recommends that women of all ages be screened for Down syndrome and open neural tube defects. Published in the January issue of Obstetrics & Gynecology, these recommendations follow several years of research, including research conducted at Women & Infants Hospital through the FASTER Trial (First and Second Trimester Evaluation of Risk).
Women are offered several options. First trimester screening provides a Down syndrome risk at the earliest possible time - 10 to 13 weeks pregnancy. Integrated screening provides Down syndrome screening at the lowest false positive rate and includes screening for open neural tube defects, with results available at 15 weeks or later. Second trimester only screening is available for patients not seen in the first trimester of pregnancy.
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 percent 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.
What is the First Trimester Test?
The First Trimester Test is performed between 10 and 13 completed weeks of pregnancy to screen for Down syndrome - this test is not used to screen for open neural tube defects. It combines information from an ultrasound examination of your baby with maternal blood analysis. It is suitable for women of all ages. It is a screening test and cannot determine definitely whether or not a baby has Down syndrome. The test identifies those women who have an increased risk of Down syndrome pregnancy so that they can be offered a diagnostic test (such as chorionic villus sampling). The diagnostic test identifies women who actually have an affected pregnancy.
What does the First Trimester Test involve?
A sample of your blood is taken between 10 and 13 weeks of pregnancy. At the same time, an ultrasound scan is performed. Substances in your blood which are markers of Down syndrome and a specific ultrasound marker will be measured. The blood markers are pregnancy associated plasma protein A (PAPP-A) and human chorionic gonadotropin (free beta-hCG). The ultrasound marker is nuchal translucency (NT) thickness. In pregnancies with Down syndrome, PAPP-A tends to be low, and NT and hCG tend to be raised. The values of these markers are used together with your age to estimate the risk of having a pregnancy affected with Down syndrome.
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: 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; taking a blood sample to measure the concentration of the marker, pregnancy associated plasma protein-A (PAPP-A); and telling you the recommended date for taking a second blood sample for the second stage of the test.
The second stage involves: 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 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 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 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 First Trimester Test and the Integrated Test are usually ready within 3 working days of the 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 in the first trimester is 1 in 230 or greater. About 1 in every 20 women screened will be in this group. Most women with screen positive results do not have a pregnancy with Down syndrome. For example, of about 50 women with screen positive results for Down syndrome, 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 First Trimester Test is lower than 1 in 230, then the result is called screen negative, and a diagnostic test is usually not offered. 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 is not high, a screen negative result cannot rule out the possibility of a pregnancy with Down syndrome.
Does the First Trimester Test or the Integrated Test detect all pregnancies with Down syndrome?
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). With the Integrated Test, 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 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 open neural tube defect.
Why do you take my age into account?
Any woman may have a baby with Down syndrome, but the chance 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 about 4% will be screen positive, while in women who are 35 or older about 15% will be screen positive. Overall, about 5% of women will be screen positive, and about 85% of Down syndrome pregnancies will be identified with the First Trimester Test. Overall, about 1% of women will be screen positive with the Integrated Test.
Can any other abnormalities be identified?
Yes, the risk of another chromosome abnormality, trisomy 18, can be estimated in First Trimester Screening and with 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 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 first trimester screening detects about 6 out of 10 pregnancies affected with trisomy 18. Smith-Lemli-Opitz syndrome, which can be detected using the Integrated Test, 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 or less 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.
What are the tests that will be offered if my First Trimester Test result is screen positive?
If the test is screen positive, you will be offered a diagnostic test, usually chorionic villus sampling (CVS) or possibly an amniocentesis. The diagnostic test will determine whether or not the pregnancy is actually affected. CVS is offered early in pregnancy (usually between 10 and 13 weeks). It involves taking a sample of placental tissue (using local anaesthetic) either by inserting a needle through your abdominal wall or by passing a fine instrument through the cervix. CVS is performed under the guidance of an ultrasound scan and does not involve a stay in the hospital. The CVS sample contains cells which can be used to tell whether or not the baby has Down syndrome. A result is usually ready within 1 to 2 weeks. There is a small risk associated with the CVS procedure. About 1% of women who have CVS will have a miscarriage as a result of the procedure.
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), is available at Women & Infants. 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.
What happens if my baby does have Down syndrome or an open neural tube 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.
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.
Women & Infants' Maternal Fetal Medicine 401-274-1122, ext. 2354
Women & Infants' Prenatal Diagnosis Center 401-453-7510
National Down Syndrome Society 800-221-4602
Spina Bifida Association of America 800-621-3141
We thank our colleagues at the Wolfson Institute of Preventive Medicine, London, for permission to edit and reproduce this information.
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