174 Mineola Boulevard Suite #1 Mineola, New York Tel: Fax:

Transcription

1 If my AFP+ Quad Test is screen negative, does that mean that my baby will be normal? A screen negative result means that your risk for a child with a neural tube defect is 1 in 1000 or less. It also means that your risk for a child with Down syndrome is less than that of a 35-year-old woman. It is never possible to be sure that your baby is going to be normal. The AFP+Quad Test will allow us to identify at least 5 out of 6 cases of open spina bifida and almost all cases of anencephaly. It can also lead to the diagnosis of about 8 out of every 10 cases of Down syndrome and Trisomy 18. Remember, a screening test can never completely rule out the possibility of an open neural tube defect, Down syndrome or Trisomy 18. There are also many other birth defects that cannot be identified with this test. What are the advantages of having the AFP+ Quad Test? The test may give you and your healthcare provider important information about your pregnancy and your developing baby. Twins may be discovered or your expected date of delivery may be corrected so your prenatal care and visits can be adjusted accordingly. If your baby is found to have a serious birth defect, you can receive professional counseling about how your child s physical and mental development may be affected. The individual capabilities and potential of children with birth defects are considerations which you may wish to discuss with your genetic counselor or with other healthcare providers. Other options such as adoption and termination of pregnancy may also be discussed. Further information and support are available through groups such as your local Down Syndrome Society and Spina Bifida Association as listed below: 174 Mineola Boulevard Suite #1 Tel: Fax: The information included in this pamphlet is not intended as a substitute for personal medical advice. Specific situations always require a personal consultation with your healthcare provider. Copyright 2008 All rights reserved. LENETIX Medical Screening Laboratory, Inc. The AFP+QUAD Test Information for Patients Second Trimester Risk Assessement for Down Syndrome and Open Neural Tube Defects March of Dimes National Down Syndrome Society National Association for Down Syndrome Smith-Lemli-Opitz Syndrome Spina Bifida Association Trisomy 18 AFP+QUAD INFORMED CONSENT I have read and understand the information in this pamphlet regarding screening for the AFP+QUAD Test. Yes, I want to have the AFP+QUAD Test. No, I do not want to have the AFP+QUAD Test. Patient Name: Patient Signature: Date: IMPORTANT: Retain Copy in Patient File afp+quad040308

2 AFP+QUAD Test Commonly Asked Questions What is the AFP+ Quad Test? It is a maternal serum test done between the 15th and 22th week of pregnancy that allows us to measure certain substances that come from the developing fetus and placenta and are present in the mother s serum. The substances that we measure are called alpha-fetoprotein (AFP), total βhcg, estriol, and inhibin-a. By finding out what the levels of these substances are in your serum, we can learn certain things about your developing baby. What can the AFP+ Quad Test tell me about my pregnancy? It can tell you whether you are at high risk for having a baby with either an open neural tube defect, Down syndrome or Trisomy 18. Ultimately, about one in twelve patients will have a screen positive AFP+ Quad Test result. If your test result is screen positive it does not necessarily mean that your baby has one of these disorders, but it does mean that your doctor will suggest some additional testing. What are neural tube defects (ontd)? Neural tube defects are a group of birth defects which include open spina bifida and anencephaly. One or two babies out of every 1000 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 and 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. Almost one third of babies born with open spina bifida will not survive past age five. Babies with anencephaly have a large part of the skull missing and the brain is not properly formed. They always die before or very soon after they are born. The level of AFP in the mother s serum tends to be elevated when there is a pregnancy affected by an open neural tube defect. About 90% of all pregnancies with open neural tube defects will be identified through AFP+Quad Testing. Closed neural tube defects (when the spinal opening is covered with skin or thick tissue) will not be picked up by AFP testing. LENETIX MEDICAL SCREENING LABORATORY, INC. - What is Down syndrome? Down syndrome is a common birth defect occurring in about one in every 700 babies. It is a disorder in which an extra chromosome (the number 21 chromosome) is present in the cells of the developing fetus from the time of conception. Down syndrome usually occurs unexpectedly and about 98% of the time is not inherited. Although Down syndrome occurs more frequently as mothers get older, about 75% of babies with Down syndrome are born to women who are younger than 35. Down syndrome is always associated with mental retardation, often in the mild to moderate range. Children with Down syndrome have variable but predictable physical characteristics. About 50% have medical problems such as heart defects. Often surgery can correct these defects. The levels of AFP and estriol in the mother s serum tend to be low while the levels of total β-hcg and inhibin-a tend to be elevated in pregnancies affected by Down syndrome. Overall, approximately 80% of all pregnancies with Down syndrome will be identified through the AFP+Quad Test. However, detection rates vary with maternal age, ranging from 70% in women under 35 to more than 90% in women 35 and older. Can other abnormalities be identified? Yes. The risk of two other disorders can be estimated. One is Trisomy 18, a rare and usually fatal disorder caused by the presence of an extra number 18 chromosome in the cells of the developing baby. The risk of Trisomy 18 can be estimated using AFP, ue3 and total βhcg, and is reported only when the risk is high. The second is called Smith-Lemli-Opitz syndrome, a genetic disorder caused by an error in the synthesis of cholesterol. Smith-Lemli-Opitz syndrome is associated with many problems in the developing baby, most important are mental retardation and poor growth. The risk of Smith-Lemli-Opitz syndrome can also be estimated using AFP, ue3 and total βhcg, is reported only when risk is high. Why do you take age into account? Any woman can have a baby with Down syndrome but the chance of this happening increases as a woman gets older. We use age as one of the factors when working out your risk of pregnancy with Down syndrome. It means that an older woman is more likely to have a result in the higher risk groups (screen positive) and be offered a diagnostic test. 174 Mineola Boulevard Suite #1 Tel: What does it mean if my AFP+ Quad Test result is screen positive? A positive AFP+Quad Test means that you are in a higher risk group for having a baby with an open neural tube defect or a chromosomal abnormality. However, it does not prove by itself that there is anything wrong with the pregnancy. In fact, only a small number of women with screen positive results will have an abnormal baby. If you have a screen positive result, you should consider specific counseling to discuss further testing. What are the tests that will be offered if my AFP+ Quad Test is screen positive? It depends on your particular result. In most cases, after counseling, an ultrasound study (sonogram) will be recommended. Depending on your AFP+Quad Test and the results of the sonogram, an amniocentesis or further diagnostic ultrasound may be recommended. What is ultrasound and what will it show? An ultrasound machine uses sound waves to look at the developing baby. One of the things it can do is check fetal age. Many women will have a screen positive AFP+Quad Test result because the dates of their pregnancies have been misjudged. When this date is adjusted, the test result may become screen negative. Occasionally twins will be discovered and will explain the screen positive result. If the gestational age is correct and you are not carrying twins, either amniocentesis or level II sonography may be suggested. Level II sonography is a detailed examination of the fetus. It cannot be used to diagnose Down syndrome or Trisomy 18, but often can identify spina bifida and other fetal abnormalities. What is amniocentesis and what will it show? Amniocentesis is a procedure in which the doctor obtains a small sample of fluid that surrounds the developing fetus. The sample is then sent to the laboratory for testing. This fluid sample can be used to diagnose both chromosomal problems such as Down syndrome and Trisomy 18, as well as open neural tube defects such as spina bifida. Amniocentesis is an invasive procedure, which means that there is a small risk of miscarriage (less than 1 in 200) associated with it. Results of the test for Down syndrome and Trisomy 18 will take about 7-14 days. Results of the test for spina bifida will take about 2-5 days. What happens if a birth defect is discovered through the AFP+ Quad Test? Your healthcare provider and/or 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. Other options such as adoption and termination of pregnancy will be discussed with you by your healthcare provider.

3 What is Amniocentesis? This diagnostic test, which can be performed after 15 weeks, collects a small amount of amniotic fluid from around the baby. The doctor inserts a very fine needle to extract the fluid which contains cells from the fetus. These cells are then cultured and examined for their genetic content. Test results are usually available in 7 to 14 days. If the chromosome results are negative, it will almost certainly rule out a Down syndrome pregnancy. In addition, AFP evaluation in amniotic fluid can rule out open neural tube defects. Is there a test offered at a later date than the Combined Test? Yes. The Integrated 190 Test is similar to the Combined Test in that it includes Nuchal Translucency testing and PAPP-A blood chemistries in the first trimester, but because the second stage of the test is performed after 15 weeks, CVS is no longer an option as a diagnostic test. However, it is a more accurate and comprehensive test because it includes the Quad Test as a second stage, which examines AFP, total ß-hCG, ue3 and Inhibin A. This second stage is recommended to be drawn at 15 to 16 weeks, but can be performed up to 22 weeks. The possible detection rate for Down syndrome is 90 percent (five percent more accurate than the Combined Test) with only a 2.15% screen positive rate. Patients receive their results within 72 hours after the second trimester blood chemistries are taken, usually around 16 to 17 weeks. Additionally, in contrast to the Combined Test, the Integrated 190 Test helps identify pregnancies at increased risk for open neural tube defects. What happens if a birth defect is discovered through the Combined Test? If your baby is found to have a serious birth defect, you can receive professional counseling from your healthcare provider and/or genetic counselor about how your child s physical and mental development may be affected. The individual capabilities and potential of children with birth defects are considerations which you may wish to consider in your decision-making process. One option would be to continue the pregnancy and make arrangements for appropriate medical services at and after delivery. Other options such as adoption and termination of pregnancy will be discussed with you by your healthcare provider. Further information and support are available through groups and local organizations as listed below: National Down Syndrome Society National Association for Down Syndrome March of Dimes Trisomy 18 Smith-Lemli-Opitz Syndrome COMBINED TEST INFORMED CONSENT 174 Mineola Boulevard Suite #1 Tel: Fax: The information included in this pamphlet is not intended as a substitute for personal medical advice. Specific situations always require a personal consultation with your healthcare provider. Copyright 2008 All rights reserved. LENETIX Medical Screening Laboratory Inc. The COMBINED TEST First Trimester Risk Assessment for Down Syndrome FIRST STAGE Final Results Reported Information for Patients I have read and understand the information in this pamphlet regarding screening for The Combined Test. Yes, I want to have The Combined Test No, I do not want to have The Combined Test COMB-LEN Patient Name: Patient Signature: Date: IMPORTANT: Retain Copy in Patient File

4 The COMBINED Test Early Risk Assessment Various choices in Risk Assessment for Down syndrome can be found on the graph below. This brochure discusses the Combined Test. Before undergoing risk assessment, please consider which options are best suited for you by discussing it with your healthcare provider. Who is at risk? Without screening, one baby out of every 700 would be born with Down syndrome. Although any woman may give birth to an affected baby, a woman s risk increases as she ages. The chart above compares the detection rates (the percentage of Down syndrome pregnancies that will be found) with the screen positive rates (the chance that a woman s test result will be called positive indicating an increased risk of having a baby with Down syndrome). For example, with the 2nd Trimester Quad Test at a 5% screen positive rate, 78% of the cases of Down syndrome will be detected. With the 1st Trimester Combined Test, at a 5% screen positive rate, 85% of cases of Down syndrome will be detected. The Combined Test can also detect approximately 85% of fetuses affected with Trisomy 18. What are Down syndrome & Trisomy 18? Down syndrome is the most common cause of severe mental handicaps and physical problems such as heart defects, visual and auditory difficulties in newborns. While it is not possible to assess how severely each Down syndrome baby will be affected, it is known that nine out of ten babies will survive their first year and nearly half of those will grow to maturity and reach 60 years of age. Down syndrome occurs when either the whole or a segment of the long arm of chromosome 21 is present in three copies instead of two. Because Down syndrome is usually not inherited, a family with no previous history can still have a Down syndrome baby. Trisomy 18, which is caused by an extra chromosome 18, results in serious mental retardation and physical deformities including major heart defects. Only 1 out of 10 babies affected with Trisomy 18 lives past the first year of life. As with Down syndrome, the risk of having an affected child gradually increases with age of the mother. Why do you take age into account? Any woman can have a baby with Down syndrome but the chance of this happening increases as a woman gets older. Your age is used in calculating 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 groups (screen positive) and be offered a diagnostic test. What is the Combined Test? By utilizing information from an ultrasound of the baby and maternal serum analysis, the Combined Test is performed between 11 weeks 0 days and 13 weeks 6 days of pregnancy. It is suitable for women of all ages. The Combined Test is an assessment of risk identifying women who are at an increased risk of having a baby with Down syndrome, but it cannot determine definitely whether or not the baby is affected. Women with a greater risk can be offered diagnostic tests such as a chorionic villus sampling or an amniocentesis. These diagnostic tests will actually identify which fetuses are affected. Copyright All Rights Reserved By LENETIX MEDICAL SCREENING LABORATORY, INC What are the advantages of having the Combined Test? The Combined Test is performed in the first trimester, thereby providing results at a point in pregnancy when early diagnostic testing such as chorionic villus sampling (CVS), is available as an option. What does the Combined Test measure? After a patient s serum is drawn, your healthcare provider and laboratory look for two substances in the serum that are markers of Down syndrome: Pregnancy Associated Plasma Protein-A (PAPP-A) and total beta-human chorionic gonadotropin (total ß-hCG). In affected pregnancies, the PAPP-A tends to be lower than normal while the total ß -hcg levels are usually elevated. At the same time a specialized ultrasound called Nuchal Translucency (NT) measures the thickness of the fetal neck. The values of these three markers are used together with the mother s age to estimate the risk of having a Down syndrome pregnancy. The results of the Combined Test, which will be sent to your healthcare provider, will usually be ready in two working days. Results will be classified as either screen positive or screen negative. Does the Combined Test detect all pregnancies with Down syndrome? No. Seventeen of twenty or 85% of pregnancies with Down syndrome will be detected (in the screen positive group). Therefore, three out of 20 (15 percent) of pregnancies with Down syndrome will have a screen negative result and so will be missed by the Combined Test. This is because risk assessment tests cannot completely distinguish affected from unaffected pregnancies. What does a screen negative test mean? If the risk of Down syndrome based on age and the level of the three markers is lower than one in 200, then the result is called screen negative and a diagnostic test would not usually be offered. Although a screen negative test result means that the patient is not at high risk for having a baby with Down syndrome, a screen negative result does not completely rule out the possibility of a pregnancy with Down syndrome. All patients undergoing first trimester screening and/or CVS should still consider a 16 week maternal serum AFP test to rule out open neural tube defects. What does a screen positive result mean? A screen positive result means that you are in a higher risk group for having a baby with Down syndrome. If your result is in this group, you will be offered genetic counseling to discuss your options, one of which is a diagnostic test. About one in 20 women who take the Combined Test are screen positive and have a risk greater than one in 200. Most women with screen positive results do not have a pregnancy with Down syndrome. For example, of 50 women with screen positive results, only one would have a pregnancy with Down syndrome. What further diagnostic tests will be offered if the results are screen positive? Patients will be offered Chorionic Villus Sampling (CVS) or an amniocentesis. There is a small risk associated with these procedures. Patients who would consider CVS if they had a screen positive test should have the Combined Test as early as possible, preferably close to 11 weeks, 0 days. About one in 100 to 200 women has a miscarriage as a result of CVS and about one in 270 women has a miscarriage following an amniocentesis. The detection rate for Down syndrome after a CVS or amniocentesis is greater than 99 percent. What is Chorionic Villus Sampling (CVS)? CVS is a diagnostic procedure that extracts a small amount of placental material and tests these cells. The material may be obtained through the cervix of the uterus with a very fine straw or via a needle placed through the abdomen. The placenta is usually an excellent source for genetic material of the fetus. This test is performed transcervically or transabdominally between 10 to 12 weeks of gestation, but only transabdominally after 12 weeks gestation. Results are usually available in five to seven days, and the detection rate is greater than 99 percent for chromosomal abnormalities, such as Down syndrome. Follow-up evaluation for open neural tube defects is necessary.

5 What does a screen negative result mean? If the risk of Down syndrome, based on the Integrated Test, is lower than 1 in 190 and the AFP level is less than two and one half times the normal level for your stage in pregnancy, then the result is called screen negative and a diagnostic test would not be offered. Although a screen negative means that you are not at high risk of having a baby with Down syndrome or an open neural tube defect, a screen negative result does not completely rule out the possibility of a pregnancy with either of these abnormalities. Why do women with screen negative results occasionally have babies with Down syndrome or an open neural tube defect? It is unusual for women to have a baby with either of these abnormalities, and it is even more unusual 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, we cannot rule out the possibility of the baby having Down syndrome or an open neural tube defect. What is Amniocentesis? Amniocentesis is a procedure in which the doctor obtains a small sample of fluid that surrounds the developing fetus. The sample is then sent to the laboratory for testing. This fluid sample can be used to diagnose both chromosomal problems such as Down syndrome and Trisomy 18, as well as open neural tube defects such as spina bifida. Amniocentesis is an invasive procedure, which means that there is a small risk of miscarriage (less than 1 in 200) associated with it. Results of the test for Down syndrome and Trisomy 18 will take about 7-14 days. Results of the test for spina bifida will take about 2-5 days. What are the advantages of risk assessment? The test may give you and your healthcare provider important information about your pregnancy and your developing baby. If your baby is found to have a serious birth defect, you can receive professional counseling about how your child s physical and mental development may be effected. The individual capabilities and potential of children with birth defects are considerations which you may wish to discuss with your genetic counselor or other healthcare provider. Other options, such as adoption and termination of pregnancy may be discussed with you by your healthcare provider. Further information and support are available through groups such as your local Down Syndrome Society and Spina Bifida Association. Further information and support are available through groups and local organizations as listed below: March of Dimes National Down Syndrome Society National Association for Down Syndrome Trisomy 18 Smith-Lemli-Opitz Syndrome Spina Bifida Association INTEGRATED TEST INFORMED CONSENT I have read and understand the information in this pamphlet regarding screening for the Integrated Test. Yes, I want to have the Integrated Test. No, I do not want to have the Integrated Test. 174 Mineola Boulevard Suite 1 Tel: Fax: The information included in this pamphlet is not intended as a substitute for personal medical advice. Specific situations always require a personal consultation with your healthcare provider. Copyright 2007 All rights reserved. LENETIX Medical Screening Laboratory, Inc. The INTEGRATED Test Information for Patients First and Second Trimester Risk Assessment for Down Syndrome and Open Neural Tube Defects No test can guarantee that your baby will be free of all birth defects, but if the result of the amniocentesis is negative, it will almost certainly rule out Down syndrome or other chromosome abnormalities. Patient Name: Patient Signature: Date: IMPORTANT: Retain Copy in Patient File INT-LEN indd

6 There are many choices for risk assessment for Down Syndrome as indicated on the graph below. This brochure discusses the Integrated test. Before undergoing maternal risk assessment, please consider which options are best suited for you by discussing it with your healthcare provider. What does the Integrated Test involve? The Integrated test is performed in two stages. The first stage is ideally performed at 12 weeks of pregnancy, but any time between 11 and 13 weeks 6 days of pregnancy is acceptable. The second stage is ideally performed at 15 or 16 weeks of pregnancy but no later than 22 weeks. The first stage involves: An Ultrasound scan examination to precisely determine the gestational age of the pregnancy through the crown rump length. Taking a sample of your blood to measure the concentration of pregnancy associated plasma protein-a (PAPP-A). A Nuchal Translucency (NT) measurement between 11 weeks 0 days and 13 weeks 6 days. The second stage involves: Taking a second sample of your blood to measure the concentration of the following four markers: alpha-fetoprotein (AFP) unconjugated estriol (ue3) inhibin-a human chorionic gonadotropin (total ß-hCG) The INTEGRATED Test Risk Assessment By integrating the measurements from the first and second stages, a single risk assessment result is produced. 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 Down syndrome pregnancy. In pregnancies with Down syndrome, PAPP-A, AFP and ue3 levels tend to be low and nuchal translucency measurement, inhibin, and total ß-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 open spina bifida or anencephaly. 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 (1.4 per 1000) 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. Down syndrome is the most common cause of severe mental disability and is often associated with physical problems such as heart defects or difficulty 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 (ONTDs) are spina bifida and anencephaly. Babies with spina bifida have an opening in the spine that can result in damage to the nerves controlling the lower part of the body. This causes weakness and paralysis of the legs, and sometimes bowel and bladder problems. Babies with problems are also more likely to have a collection of fluid on the brain, called hydrocephalus, which can be treated surgically but may lead to mental disability. Babies with anencephaly have a large part of the skull missing and the brain is not properly formed. They always die before or very soon after they are born. 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. Can other abnormalities be identified? Yes. The risk of two other disorders can be estimated. One is Trisomy 18, a rare and usually fatal disorder caused by the presence of an extra number 18 chromosome in the cells of the developing baby. The risk of Trisomy 18 can be estimated using PAPP-A, AFP, ue3 and total ß-hCG, and is reported only when the risk is high. The second is called Smith-Lemli-Opitz syndrome, a genetic disorder caused by an error in the synthesis of cholesterol. Smith-Lemli-Opitz syndrome is associated with many problems in the developing baby, most important are mental retardation and poor growth. The risk of Smith-Lemli-Opitz syndrome can also be estimated using AFP, ue3 and total ßhCG and is reported only when risk is high. 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 test result, we would expect that 1 of these women would have a baby with Down syndrome and that 99 would not. This is the same as a 1% chance that the baby has Down syndrome and a 99% chance that the baby does not. Why do you take age into account? Any woman can have a baby with Down syndrome but the chance of this happening increases as a woman gets older. We use age as one of the factors when working out your risk of 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 be offered a diagnostic test. 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 distinguish affected from unaffected pregnancies more effectively, reducing the chance that a Down syndrome pregnancy is missed. It also reduces the chance that you will need an invasive diagnostic test, such as amniocentesis. What happens if the ultrasound scan shows that I am too late for the first stage of the test? We cannot report a screening result for the Integrated Test. You could have a screening test based on the second stage alone (the AFP+QUAD test). 174 Mineola Boulevard Suite 1 Tel: What happens if I cannot attend for the second blood test? If you do not attend for the second stage of the Integrated test, a screening result cannot be reported. We will try to contact your healthcare provider on two occasions after the recommended date for your second blood sample. If we do not receive your second blood sample a Down syndrome risk is given based on information from the first stage only. If you know you will not be able to attend for the second blood test, please discuss this with your doctor. You could have the screening based on the first blood test and the ultrasound examination alone (the Combined test) but this is less effective than the Integrated Test. When will the results of the second stage be available? The results of the test are usually ready within three working days of the second blood sample being taken. Results are sent to your doctor, midwife or healthcare professional. The result will be either screen negative or screen positive. Screen positive results are telephoned and faxed to your doctor, healthcare professional, or midwife. If you do not receive your results or have further questions please telephone LENETIX at (516) to speak to a genetic counselor. What does a screen positive result for Down syndrome mean? A screen positive result means that you are in a higher risk group for having a baby with Down syndrome. If your result is in this group, you will be offered a diagnostic amniocentesis. The result is called screen positive if the risk of Down syndrome in your pregnancy is 1 in 190 or greater. About 1 in every 50 women screened will be in this risk group. Most women with screen positive results do not have a pregnancy with Down syndrome. 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 your result is in this group, you will be offered an ultrasound scan examination at 18 to 20 weeks of pregnancy, and possibly an amniocentesis. This is organized by your doctor or hospital. The result is screen positive if the AFP level is equal to or higher than two and one half times the normal (median) level for your stage in pregnancy.

7 What does a screen negative result mean? If the risk of Down syndrome, based on the Integrated 190, is lower than 1 in 190 and the AFP level is less than two and one half times the normal level for your stage in pregnancy, then the result is called screen negative and a diagnostic test would not be offered. Although a screen negative means that you are not at high risk of having a baby with Down syndrome or an open neural tube defect, a screen negative result does not completely rule out the possibility of a pregnancy with either of these abnormalities. Why do women with screen negative results occasionally have babies with Down syndrome or an open neural tube defect? It is unusual for women to have a baby with either of these abnormalities, and it is even more unusual 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, we cannot rule out the possibility of the baby having Down syndrome or an open neural tube defect. What is Amniocentesis? Amniocentesis is a procedure in which the doctor obtains a small sample of fluid that surrounds the developing fetus. The sample is then sent to the laboratory for testing. This fluid sample can be used to diagnose both chromosomal problems such as Down syndrome and Trisomy 18, as well as open neural tube defects such as spina bifida. Amniocentesis is an invasive procedure, which means that there is a small risk of miscarriage (less than 1 in 200) associated with it. Results of the test for Down syndrome and Trisomy 18 will take about 7-14 days. Results of the test for spina bifida will take about 2-5 days. What are the advantages of risk assessment? The test may give you and your healthcare provider important information about your pregnancy and your developing baby. If your baby is found to have a serious birth defect, you can receive professional counseling about how your child s physical and mental development may be effected. The individual capabilities and potential of children with birth defects are considerations which you may wish to discuss with your genetic counselor or other healthcare provider. Other options, such as adoption and termination of pregnancy may be discussed with you by your healthcare provider. Further information and support are available through groups such as your local Down Syndrome Society and Spina Bifida Association. Further information and support are available through groups and local organizations as listed below: March of Dimes National Down Syndrome Society National Association for Down Syndrome Trisomy 18 Smith-Lemli-Opitz Syndrome Spina Bifida Association INTEGRATED 190 INFORMED CONSENT I have read and understand the information in this pamphlet regarding screening for the Integrated 190. Yes, I want to have the Integrated 190 Test. No, I do not want to have the Integrated 190 Test. 174 Mineola Boulevard Suite #1 Tel: Fax: The information included in this pamphlet is not intended as a substitute for personal medical advice. Specific situations always require a personal consultation with your healthcare provider. Copyright 2008 All rights reserved. LENETIX Medical Screening Laboratory, Inc. INTEGRATED 190 Information for Patients First and Second Trimester Risk Assessment for Down Syndrome and Open Neural Tube Defects FIRST STAGE SECOND STAGE Final Results Reported No test can guarantee that your baby will be free of all birth defects, but if the result of the amniocentesis is negative, it will almost certainly rule out Down syndrome or other chromosome abnormalities. Patient Name: Patient Signature: Date: IMPORTANT: Retain Copy in Patient File INT web

8 INTEGRATED 190 Risk Assessment There are many choices for risk assessment for Down Syndrome as indicated on the graph below. This brochure discusses the Integrated 190 test. Before undergoing maternal risk assessment, please consider which options are best suited for you by discussing it with your healthcare provider. (This chart is an artist s graphical rendering for counseling purposes only.) What does the Integrated 190 Test involve? The Integrated 190 is performed in two stages. The first stage is ideally performed at 12 weeks of pregnancy, but any time between 11 weeks to 13 weeks and 6 days of pregnancy is acceptable. The second stage is ideally performed at 16 weeks to 18 weeks of pregnancy, but may be preformed as early as 15 weeks 0 days and no later than 22 weeks. The first stage involves: An Ultrasound scan examination to precisely determine the gestational age of the pregnancy through the crown rump length. Taking a sample of your blood to measure the concentration of pregnancy associated plasma protein-a (PAPP-A). A Nuchal Translucency (NT) measurement between 11 weeks 0 days and 13 weeks 6 days. The second stage involves: Taking a second sample of your blood to measure the concentration of the following four markers: alpha-fetoprotein (AFP) unconjugated estriol (ue3) inhibin-a human chorionic gonadotropin (total ß-hCG) By integrating the measurements from the first and second stages, a single risk assessment result is produced. 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 Down syndrome pregnancy. In pregnancies with Down syndrome, PAPP-A, AFP and ue3 levels tend to be low and nuchal translucency measurement, inhibin, and total ß-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 open spina bifida or anencephaly. 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 (1.4 per 1000) 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. Down syndrome is the most common cause of severe mental disability and is often associated with physical problems such as heart defects or difficulty 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 (ONTDs) are spina bifida and anencephaly. Babies with spina bifida have an opening in the spine that can result in damage to the nerves controlling the lower part of the body. This causes weakness and paralysis of the legs, and sometimes bowel and bladder problems. Babies with problems are also more likely to have a collection of fluid on the brain, called hydrocephalus, which can be treated surgically but may lead to mental disability. Babies with anencephaly have a large part of the skull missing and the brain is not properly formed. They always die before or very soon after they are born. 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. Copyright All rights reserved. LENETIX Medical Screening Laboratory, Inc. 174 Mineola Blvd. Suite #1 Mineola, NY Tel: Can other abnormalities be identified? Yes. The risk of two other disorders can be estimated. One is Trisomy 18, a rare and usually fatal disorder caused by the presence of an extra number 18 chromosome in the cells of the developing baby. The risk of Trisomy 18 can be estimated using PAPP-A, AFP, ue3 and total ß-hCG, and is reported only when the risk is high. The second is called Smith-Lemli-Opitz syndrome, a genetic disorder caused by an error in the synthesis of cholesterol. Smith-Lemli-Opitz syndrome is associated with many problems in the developing baby, most important are mental retardation and poor growth. The risk of Smith-Lemli-Opitz syndrome can also be estimated using AFP, ue3 and total ßhCG and is reported only when the risk is high. 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 test result, we would expect that 1 of these women would have a baby with Down syndrome and that 99 would not. This is the same as a 1% chance that the baby has Down syndrome and a 99% chance that the baby does not. Why do you take age into account? Any woman can have a baby with Down syndrome but the chance of this happening increases as a woman gets older. We use age as one of the factors when working out your risk of 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 be offered a diagnostic test. 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 distinguish affected from unaffected pregnancies more effectively, reducing the chance that a Down syndrome pregnancy is missed. It also reduces the chance that you will need an invasive diagnostic test, such as amniocentesis. What happens if the ultrasound scan shows that I am too late for the first stage of the test? We cannot report a screening result for the Integrated 190 Test. You could have a screening test based on the second stage alone (the AFP+QUAD test). 174 Mineola Boulevard Suite #1 Tel: What happens if I cannot attend for the second blood test? If you do not attend for the second stage of the Integrated 190 Test, a screening result cannot be reported. We will try to contact your healthcare provider on two occasions after the recommended date for your second blood sample. If we do not receive your second blood sample a Down syndrome risk is given based on information from the first stage only. If you know you will not be able to attend for the second blood test, please discuss this with your doctor. You could have the screening based on the first blood test and the ultrasound examination alone (the Combined test) but this is less effective than the Integrated 190 Test. When will the results of the second stage be available? The results of the test are usually ready within three working days of the second blood sample being taken. Results are sent to your doctor, midwife or healthcare professional. The result will be either screen negative or screen positive. Screen positive results are telephoned and faxed to your doctor, healthcare professional, or midwife. If you do not receive your results or have further questions please telephone a LENETIX representative at (516) to speak to a genetic counselor. What does a screen positive result for Down syndrome mean? A screen positive result means that you are in a higher risk group for having a baby with Down syndrome. If your result is in this group, you will be offered a diagnostic amniocentesis. The result is called screen positive if the risk of Down syndrome in your pregnancy is 1 in 190 or greater. Most women with screen positive results do not have a pregnancy with Down syndrome. 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 your result is in this group, you will be offered an ultrasound scan examination at 18 to 20 weeks of pregnancy, and possibly an amniocentesis. This is organized by your doctor or hospital. The result is screen positive if the AFP level is equal to or higher than two and one half times the normal (median) level for your stage in pregnancy.

9 Why do women with screen negative results occasionally have babies with Down syndrome or an Open Neural Tube Defect? It is unusual for women to have a baby with either of these abnormalities, and it is even more unusual 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, we cannot rule out the possibility of the baby having Down syndrome or an open neural tube defect. 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 your result is in this group, you will be offered genetic counseling and the option of a diagnostic test such as CVS or amniocentesis. The result is called screen positive if the risk of Down syndrome in your pregnancy is 1 in 200 or greater in the first trimester or 1 in 270 or greater in the second trimester. Most women with screen positive results do not have a pregnancy with Down syndrome. For example, of 20 women with screen positive results for Down syndrome, only one would actually have a pregnancy with Down syndrome. 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 your result is in this group, you will be offered genetic counseling, an ultrasound scan examination at 18 to 20 weeks of pregnancy, and the option of an amniocentesis. This is organized by your doctor or hospital. What is Chorionic Villus Sampling (CVS)? If your result is screen positive in the first trimester then CVS may be an option. CVS is a diagnostic procedure that extracts a small amount of placental material which is usually an excellent source of genetic material from the fetus. This test is performed either transcervically or transabdominally between 10 to 12 weeks of gestation, but only transabdominally after 12 weeks gestation. There is a small risk associated with CVS. Less than one percent of women may have a miscarriage as a result of the procedure. Results are usually available in five to seven days, and the detection rate is greater than 99 percent for chromosomal abnormalities, such as Down syndrome. Follow-up evaluation for open neural tube defects is necessary. Amniocentesis is an invasive procedure, which means that there is a small risk of miscarriage (less than 1 in 200) associated with it. Results of the test for Down syndrome and Trisomy 18 will take about 7-14 days. Results of the test for open spina bifida will take about 2-5 days. No test can guarantee that your baby will be free of all birth defects, but if the result of the amniocentesis is negative, it will almost certainly rule out Down syndrome and/or other chromosome abnormalities. What are the advantages of risk assessment? The test may give you and your healthcare provider important information about your pregnancy and your developing baby. If your baby is found to have a serious birth defect, you can receive professional counseling about how your child s physical and mental development may be effected. The individual capabilities and potential of children with birth defects are considerations which you may wish to discuss with your genetic counselor or other healthcare provider. Other options, such as adoption and termination of pregnancy may be discussed with you by your healthcare provider. Further information and support are available through groups such as your local Down Syndrome Society and Spina Bifida Association. Further information and support are available through groups and local organizations as listed below: March of Dimes National Down Syndrome Society National Association for Down Syndrome Smith-Lemli-Opitz Syndrome Spina Bifida Association Trisomy 18 MODIFIED SEQUENTIAL INFORMED CONSENT I have read and understand the information in this pamphlet regarding screening for the Modified Sequential Test. Yes, I want to have the Modified Sequential Test. 174 Mineola Boulevard Suite 1 Mineola, New York Tel: Fax: The information included in this pamphlet is not intended as a substitute for personal medical advice. Specific situations always require a personal consultation with your healthcare provider. Copyright 2007 All rights reserved. LENETIX Medical Screening Laboratory, Inc. MODIFIED SEQUENTIAL TEST 2007 REVISED CUTOFFS Information for Patients First and Second Trimester Risk Assessment for Down Syndrome and Open Neural Tube Defects What is Amniocentesis? Amniocentesis is usually performed between 15 and 20 weeks, and is a procedure in which the doctor obtains a sample of amniotic fluid that surrounds the developing fetus. The sample is then sent to the laboratory for testing. This fluid sample can be used to diagnose both chromosomal problems such as Down syndrome and Trisomy 18, as well as open neural tube defects such as spina bifida. mod-seq-len No, I do not want to have the Modified Sequential Test. Patient Name: Patient Signature: Date: IMPORTANT: Retain Copy in Patient File

10 What does the Modified Sequential test involve? The Modified Sequential test is performed in two stages. The first stage is ideally performed at 12 weeks of pregnancy, but any time between 11 and 13 weeks of pregnancy is acceptable. The second stage is ideally performed at 16 to 18 weeks of pregnancy, but may be performed as early as 15 weeks and no later than 22 weeks. The first stage involves: An Ultrasound scan examination to precisely determine the gestational age of the pregnancy through the crown rump length (CRL) of the baby. Taking a sample of your blood to measure the concentration of pregnancy associated plasma protein-a (PAPP-A) and total human chorionic gonadotropin (total ß-hCG). A Nuchal Translucency (NT) measurement between 11 weeks 0 days and 13 weeks 6 days. After the first stage evaluation two risk groups are identified. 1. High risk: Patients at a risk of 1 in 200 or greater are offered genetic counseling and the option of an invasive diagnostic test such as CVS or amniocentesis. (See What does a screen positive result for Down Syndrome Mean? ) 2. The remaining patients will benefit from proceeding to the second stage. The second stage involves: Taking a second blood sample to measure the concentration of four different markers: The MODIFIED SEQUENTIAL Test Risk Assessment alpha-fetoprotein (AFP) unconjugated estriol (ue3) inhibin-a total human chorionic gonadotropin (total ß-hCG) The NT measurement and the levels of the five markers in your specimen are used, together with your age, to estimate your risk of having a Down syndrome pregnancy. In pregnancies with Down syndrome, PAPP-A, AFP and ue3 levels tend to be decreased and nuchal translucency measurement, inhibin, and total ß-hCG levels tend to be increased compared to unaffected pregnancies. The level of AFP in the second blood sample is also used to determine if there is an increased risk of open spina bifida, anencephaly or an abnormal opening of the baby s abdominal wall. 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 test result, we would expect that 1 of these women would have a baby with Down syndrome and that 99 would not. This is the same as a 1% chance that the baby has Down syndrome and a 99% chance that the baby does not. 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 (1.4 per 1000) 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. Down syndrome is the most common cause of severe mental disability and is often associated with physical problems such as heart defects or difficulty 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 (ONTD)? The two main kinds of open neural tube defects (ONTDs) are open spina bifida and anencephaly. Babies with open spina bifida have an opening in the spine that can result in damage to the nerves controlling the lower part of the body. This causes weakness and paralysis of the legs, and sometimes bowel and bladder problems. Babies with these problems are also more likely to have a collection of fluid on the brain, called hydrocephalus, which can be treated surgically but may lead to mental disability. Babies with anencephaly have a large part of the skull missing and the brain is not properly formed. They always die before or very soon after they are born. 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. Can other abnormalities be identified? Yes. The risk of two other disorders can be estimated. One is Trisomy 18, a rare and usually fatal disorder caused by the presence of an extra number 18 chromosome in the cells of the developing baby. The risk of Trisomy 18 can be estimated using PAPP-A, AFP, ue3 and total ß-hCG, and is reported only when the risk is high. The second is called Smith-Lemli-Opitz syndrome (SLOS), a genetic disorder caused by an error in the synthesis of cholesterol. Smith-Lemli-Opitz syndrome is associated with many problems in the developing baby, most important are mental retardation and poor growth. The risk of Smith-Lemli-Opitz syndrome (SLOS) can also be estimated using AFP, ue3 and total ßhCG and is reported only when the risk is high. Why is your age taken into account? Any woman can have a baby with Down syndrome but the chance of this happening increases as a woman gets older. We use age as one of the factors when working out your risk of 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 be offered a diagnostic test. Why will some patients have to wait until the second stage to have a risk estimate? Patients with high risk results have been identified in the first stage. Risk assessment ends for them. The remainder of patients proceed to the second stage. At this point, adding additional markers helps distinguish affected from unaffected pregnancies more effectively and reduces the chances that a Down syndrome pregnancy is missed. It also reduces the chance that an invasive diagnostic test, such as amniocentesis will be indicated. What happens if I am too late for the first stage of the Modified Sequential test? We cannot report a screening result for the Modified Sequential test. You could have a screening test based on the second stage alone (the AFP+QUAD test). What happens if I cannot attend for the second stage of the Modified Sequential test? If you do not attend for the second stage of the Modified Sequential test, a screening result cannot be reported. We will try to contact your healthcare provider on two occasions after the recommended date for your second blood sample. If we do not receive your second blood sample a Down syndrome risk is given based on information from the first stage only. If you know you will not be able to attend for the second blood test, please discuss this with your healthcare provider. You could have the screening based on the first blood test and the ultrasound examination alone (the Combined test) but this is less effective than the Modified Sequential test. When will the results of the second stage be available? The results of the test are usually ready within three working days of the second blood sample being taken. Results are sent to your doctor, midwife or healthcare provider. The result will be either screen negative or screen positive. Screen positive results are telephoned and faxed to your doctor, healthcare professional, or midwife. If you do not receive your results or have further questions please telephone LENETIX at (516) to speak with a genetic counselor. What does a screen negative result mean? If the risk of Down syndrome, based on the Modified Sequential test, is lower than 1 in 270 and the AFP level is less than two and one half times the normal level for your stage in pregnancy, then the result is called screen negative and a diagnostic test would not be offered. Although a screen negative means that you are not at high risk of having a baby with Down syndrome or an open neural tube defect, a screen negative result does not completely rule out the possibility of a pregnancy with either of these abnormalities. Copyright All rights reserved. LENETIX Medical Screening Laboratory, Inc. 174 Mineola Blvd. Suite #1 Mineola, NY Tel: