Screening for down syndrome accuracy

Prenatal Testing for Down Syndrome | Patient Education

Age-Related Risks

Generally, the chance of having a Down syndrome birth is related to the mother's age. Under age 25, the odds of having a child with Down syndrome are about 1 in 1,400. At age 35, the odds are about 1 in 350. At age 40, the odds are about 1 in 100.

Causes of Down Syndrome

There are three causes of Down syndrome:

Trisomy 21

An estimated 95 percent of people with Down syndrome have trisomy 21, meaning they have three number 21 chromosomes instead of two. We normally have 23 pairs of chromosomes, each made up of genes. During the formation of the egg and the sperm, a woman's or a man's pair of chromosomes normally split so that only one chromosome is in each egg or sperm. In trisomy 21, the 21st chromosome pair does not split and a double dose goes to the egg or sperm. An estimated 95 to 97 percent of the extra chromosome is of maternal origin.

Translocation

Translocation occurs in about 3 to 4 percent of people with Down syndrome. In this type, an extra part of the 21st chromosome gets stuck onto another chromosome. In about half of these situations, one parent carries the extra 21st chromosome material in a "balanced" or hidden form.

Mosaicism

In mosaicism, the person with Down syndrome has an extra 21st chromosome in some of the cells but not all of them. The other cells have the usual pair of 21st chromosomes. About 1 to 2 percent of people with Down syndrome have this type.

Prenatal Testing

Screening tests can identify individuals at increased risk of having a baby with Down syndrome. These tests have no risks of miscarriage, but can't determine with certainty whether a fetus is affected. Diagnostic tests, on the other hand, are extremely accurate at identifying certain abnormalities in the fetus, but carry a small – generally less than 1 percent – risk of miscarriage. We offer options for both screening and diagnostic testing.

Screening Tests

California prenatal screening (CA PNS) – All pregnant individuals in California have access to CA PNS, also called sequential integrated screening. This noninvasive screening process is performed in two steps.

In the first step, which is performed between 10 and 14 weeks of pregnancy, a blood sample is taken from the mother and a nuchal translucency ultrasound is performed to measure the amount of fluid at the back of the baby's neck. If the blood test is scheduled prior to the ultrasound, we can provide the results at the end of the ultrasound appointment. The results of the blood test, the nuchal translucency measurement and the mother's age are used to estimate the risk for Down syndrome and trisomy 18.

The second step is a maternal blood test between 15 to 20 weeks of pregnancy. When the results of this blood test are combined with the results from the first trimester blood test and nuchal translucency ultrasound, the detection rate for Down syndrome increases. This test also provides a personal risk assessment for having a fetus with trisomy 18, Smith-Lemli-Opitz syndrome, an open neural tube defect or an abdominal wall defect.

Diagnostic Tests

Amniocentesis, chorionic villus sampling (CVS) and ultrasound are the three primary procedures for diagnostic testing.

Amniocentesis. Amniocentesis is used most commonly to identify chromosomal problems such as Down syndrome. When the fetus is known to be at risk, it can detect other genetic diseases like cystic fibrosis, Tay-Sachs disease and sickle cell disease.

An amniocentesis procedure for genetic testing is typically performed between 15 and 20 weeks of pregnancy. Under ultrasound guidance, a needle is inserted through the abdomen to remove a small amount of amniotic fluid. The cells from the fluid are then cultured and a karyotype analysis – an analysis of the chromosomal make-up of the cells – is performed. It takes about two weeks to receive the results of the test.

Amniocentesis detects most chromosomal disorders, such as Down syndrome, with a high degree of accuracy. Testing for other genetic diseases, such as Tay-Sachs disease, is not routinely performed but can be detected through specialized testing if your fetus is known to be at risk. Testing for neural tube defects, such as spina bifida, also can be performed.

There is a small risk of miscarriage as a result of amniocentesis – about 1 in 100 or less. Miscarriage rates for procedures performed at UCSF Medical Center are less than 1 in 350.

Chorionic Villus Sampling (CVS). Like amniocentesis, chorionic villus sampling is used most commonly to identify chromosomal problems such as Down syndrome. It can detect other genetic diseases like cystic fibrosis, Tay-Sachs disease and sickle cell disease in at-risk fetuses. The main advantage of CVS over amniocentesis is that it is done much earlier in pregnancy, at 10 to 12 weeks rather than 15 to 20 weeks.

CVS involves removing a tiny piece of tissue from the placenta. Under ultrasound guidance, the tissue is obtained either with a needle inserted through the abdomen or a catheter inserted through the cervix. The tissue is then cultured and a karyotype analysis of the chromosomal make-up of the cells is performed. It takes about two weeks to receive the results.

The advantage of CVS over amniocentesis is that the test is performed much earlier in pregnancy, so results are typically available by the end of the third month. A disadvantage is that spinal cord defects cannot be detected. Expanded alpha fetoprotein (AFP) blood testing or ultrasound can be performed later in the pregnancy to screen for spinal cord defects.

There is a small risk of miscarriage as a result of CVS – 1 in 100 or less. Miscarriage rates for procedures performed at UCSF Medical Center are less than 1 in 350.

Ultrasound. The primary purpose of ultrasound is to determine the status of a pregnancy – the due date, size of the fetus and if the mother is carrying multiples. Ultrasound also can provide some information about possible birth defects in a fetus. All patients at UCSF Medical Center undergo a comprehensive ultrasound examination before any invasive tests are performed. Results of the ultrasound are explained at the time of the visit.

In some patients, an ultrasound raises concern of a possible abnormality in the fetus. We have extensive experience in performing and interpreting ultrasounds in pregnancy.

If You Receive a Positive Result

If you receive positive results on a screening test, we recommend that you discuss this with your doctor and a genetic counselor. Options for further diagnostic testing will be explained. The decision as to whether to have invasive genetic testing is up to you.

If a diagnostic test finds a genetic abnormality, the significance of such results should be discussed with experts familiar with the condition, including a medical geneticist and a genetic counselor, as well as your own doctor.

UCSF Health medical specialists have reviewed this information. It is for educational purposes only and is not intended to replace the advice of your doctor or other health care provider. We encourage you to discuss any questions or concerns you may have with your provider.

Related clinic

Prenatal Diagnostic Center

1825 Fourth St., Third Floor
San Francisco, CA 94158

(415) 476-4080

M-F, 8 a.m. - 5 p.m.

Understanding a Diagnosis of Down Syndrome

Is What I’m Feeling Normal?

Learning that your baby has Down syndrome is not an easy thing for anyone to face, and right now you may be experiencing a roller coaster of emotions. While everyone handles the diagnosis in their own way, certain reactions are common in new or expectant parents of a child with a disability.

For the majority of parents, the period immediately following the diagnosis is filled with uncertainty and doubt. For example, you might worry about how the condition will impact your child’s life and whether or not you are equipped to handle all the responsibilities of raising a child with a disability. If your child has health complications, you may have additional fears and concerns. It is natural to experience denial, anger, depression, and other stages of grief as you adjust to the news that your baby has Down syndrome. Even for parents who knew they were at a higher risk of having a child with Down syndrome or have received a positive diagnosis, acceptance can be difficult or, at first, seem impossible.

Know that whatever you may be feeling is normal. More importantly, know that you are not alone. There are many sources of support available to new parents of children with Down syndrome. In time and with the right support, you can expect the intensity of painful emotions to subside, and new, positive feelings to take their place. One of the best places to turn to for encouragement and reassurance is other parents of children with Down syndrome. Often, other parents can help you look beyond your baby’s diagnosis and delight in the joys of parenthood. They have been through what you are going through, and can be an invaluable source of support.

How Can I Get In Touch with Other Parents of Children with Down Syndrome?

One of the best ways to meet other parents is to get involved in a local Down syndrome parent support group. These groups can provide you with an excellent forum for sharing your feelings and concerns as a new parent, and an opportunity to learn from the experiences of others who have been in your shoes. Learning more about Down syndrome can also help ease some of your uncertainty, and support groups are a great place to start gaining knowledge. In addition to providing emotional support, other parents can recommend useful Down syndrome resources and help you understand the new terminology.

NDSS has a network of more than 375 affiliates. In addition to having support group meetings, most affiliates offer a wide range of programs and services for individuals with Down syndrome and their families, such as sibling workshops, expert-speaker presentations, early intervention programs, social activities and events to raise public awareness. Support group membership can provide benefits to you and your family now and in the future, so we encourage you to contact your local group and explore this option.

If there is no Down syndrome-specific support group in your area, your hospital or pediatrician may be able to provide contact information for other parents who have agreed to serve as a resource. There may also be a general support group for parents of children with disabilities that you can join. Alternately, you may consider starting your own support group to network with others. NDSS can provide you with information on how to get started.

What Are Some Other Things I Can Do to Take Care of Myself?

Right now, you are very focused on taking good care of your baby. But remember that it’s also important to take good care of yourself at this time. Doing so will keep you feeling healthy, strong and well-equipped to deal with your responsibilities as a new parent. It can also help you develop and maintain a positive frame of mind, which is necessary for meeting new challenges successfully. Here are some tips many new parents have found helpful for reducing anxiety and stress:

BE PATIENT WITH YOURSELF

The road to acceptance is a process, so give yourself time to deal with your emotional responses. Some days you might feel like you’re taking steps backward, but recognize that this doesn’t mean you aren’t making progress. If you feel it would be helpful, do not hesitate to contact a therapist. A therapist can help you find ways to cope and develop confidence in your ability to handle challenges.

BUILD A SUPPORT SYSTEM

It may be tempting to keep to yourself at this time, but doing so can result in feelings of isolation. Reach out to trusted friends or family members. This allows your loved ones to understand what you’re going through and gives them a chance to offer comfort and support. You can always let them know how much help you need or desire, and if you want time alone, don’t hesitate to say so.

Schedule some alone time regularly, and use this time to “recharge.” Read a book, take a warm bath, go for a walk, or just watch your favorite T.V. show. Do something you enjoy and find relaxing, and let yourself enjoy it. Alone time may sound like a luxury, but it is necessary for good health and can do wonders for your productivity and mood.

TAKE CARE OF YOUR PHYSICAL HEALTH

Research shows that a healthy eating and exercise plan can reduce fatigue, irritability, and risk for certain diseases and health complications. Develop a plan that works for you and make an effort to stick to it, especially during times of high stress. Be sure to get regular medical check-ups, too.

PRACTICE “LIVING IN THE MOMENT”

While it is important to plan ahead, worrying about the future can easily lead to anxiety. Although it may be hard, try to focus only on what you can do realistically in the present. If you find yourself getting anxious about a particular situation, try this strategy:

Identify the problem
Research your options
Make a decision
Set a date in the future to evaluate how your decision is working

In the meantime, just go with the decision you made and trust that it will work out.

DON’T LOSE SIGHT OF “THE IMPORTANT THINGS IN LIFE”

Nurture your relationships with your partner, children, friends, and family. Communicate with each other, laugh, do fun things together, celebrate traditions, and be sure to spend quality time with your new baby that doesn’t focus on his or her disability. The fact that your baby has Down syndrome is life-changing. But it doesn’t change the things that are truly important in life!

Screening tests for Down syndrome in the first 24 weeks of pregnancy

Relevance
Down's syndrome (also known as Down's disease or Trisomy 21) is an incurable genetic disorder that causes significant physical and mental health problems and disability. However, Down syndrome affects people in completely different ways. Some have significant symptoms, while others have minor health problems and are able to lead relatively normal lives. There is no way to predict how badly a child might be affected. nine0006

Expectant parents during pregnancy are given the opportunity to have a screening test for Down syndrome in their baby to help them make a decision. If a mother is carrying a child with Down syndrome, then a decision should be made whether to terminate the pregnancy or keep it. The information gives parents the opportunity to plan life with a child with Down syndrome.

The most accurate screening tests for Down syndrome include amniotic fluid (amniocentesis) or placental tissue (chorionic villus biopsy (CVS)) to identify abnormal chromosomes associated with Down syndrome. Both of these tests involve inserting a needle into the mother's abdomen, which is known to increase the risk of miscarriage. Thus, screening tests are not suitable for all pregnant women. Therefore, more often take blood and urine tests of the mother, and also conduct an ultrasound examination of the child. These screening tests are not perfect because they can miss cases of Down syndrome and are also at high risk of being positive when the child does not have Down syndrome. Thus, if a high risk is identified using these screening tests, further amniocentesis or CVS is required to confirm the diagnosis of Down syndrome. nine0006

What we did
We analyzed combinations of serum screening tests in the first (up to 14 weeks) and second (up to 24 weeks) trimesters of pregnancy with or without ultrasound screening in the first trimester. Our goal was to identify the most accurate tests for predicting the risk of Down syndrome during pregnancy. One ultrasound index (neckfold thickness) and seven different serological indexes (PAPP-A, total hCG, free beta-hCG, unbound estriol, alpha-fetoprotein, inhibin A, ADAM 12) were studied, which can be used separately, in ratios or in combination with each other, obtained before 24 weeks of gestation, thereby obtaining 32 screening tests for the detection of Down's syndrome. We found 22 studies involving 228615 pregnant women (including 1067 fetuses with Down syndrome). nine0004

What we found
During Down Syndrome screening, which included tests during the first and second trimesters that combined to determine overall risk, we found that a test that included neckfold measurement and PAPP- A in the first trimester, as well as the determination of total hCG, unbound estriol, alpha-fetoprotein and inhibin A in the second trimester, turned out to be the most sensitive, as it allowed to determine 9out of 10 pregnancies associated with Down syndrome. Five percent of pregnant women who were determined to be at high risk on this combination of tests would not have a child with Down syndrome. There have been relatively few studies evaluating these tests, so we cannot draw firm conclusions or recommendations about which test is best.

Other important information to consider
Ultrasounds by themselves have no adverse effects on women, and blood tests can cause discomfort, bruising, and, in rare cases, infection. However, some women who have a high-risk Down syndrome baby on screening and who have had an amniocentesis or CVS are at risk of miscarriage of a non-Down syndrome baby. Parents will need to weigh this risk when deciding whether to perform amniocentesis or CVS after a "high risk" screening test is identified. nine0006

Translation notes:

Translation: Abuzyarova Daria Leonidovna. Editing: Prosyukova Ksenia Olegovna, Yudina Ekaterina Viktorovna. Project coordination for translation into Russian: Cochrane Russia - Cochrane Russia (branch of the Northern Cochrane Center on the basis of Kazan Federal University). For questions related to this translation, please contact us at: [email protected]; [email protected]

Reliability of 1st trimester screening - an article from the Lek-Diagnostic clinic network

1st trimester screening: what is it?

Screening of the 1st trimester is a comprehensive examination aimed at assessing the rate of intrauterine development of the baby by comparing the indicators of a specific gestational age. At this stage, the probability of congenital pathological abnormalities, including Down syndrome, is determined. Screening of the 1st trimester includes two procedures: a biochemical blood test and an ultrasound examination.

Biochemical blood test

Using biochemistry, you can determine the level of hormones that affect the development of genetic abnormalities:

1. B-hCG - is produced from the beginning of pregnancy, from the 9th week the indicator begins to decline. The norm is 50 thousand-55 thousand. mIU/ml.

2. PAPP-A is an A-plasma protein. A natural indicator is 0.79-6.00 mU / l. during the 1st trimester screening period.

The procedure is carried out in the period from 11 to 13 weeks. A woman donates venous blood in the morning on an empty stomach. Among the contraindications: signs of multiple pregnancy, weight problems, diabetes. Biochemistry is mandatory for women after 35 years of age, with genetic anomalies in the family, with miscarriages or infectious diseases in the past. nine0006

Ultrasound

Ultrasound is a safe and informative diagnostic method. It allows you to localize the location of the fetus, its physique, compliance with the size of the norm, and also to identify how correctly the limbs of the unborn child are located.

According to the results of the first ultrasound, the doctor:

Determines the date of conception, and also corrects the gestational age;

Establishes or refutes the fact of the presence of congenital pathologies; nine0006

Estimates the likelihood of pathological pregnancy.

Ultrasound is performed in two ways: transvaginally (the sensor is inserted into the vagina) or abdominally (the sensor is driven along the abdomen). It is optimal to perform the procedure at the 12th week of pregnancy.

Why are parents afraid of Down syndrome?

Down syndrome is a common genetic syndrome. Normally, a set of chromosomes in humans contains 23 pairs. With a genetic anomaly, a mutation of chromosome 21 leads to trisomy - the presence of an extra 21 chromosome. The pathology was first diagnosed in 1866 by John Down. At the moment, the probability of developing the syndrome is 1 in 700 children. nine0006

Why can't Down syndrome be seen on ultrasound?

It is impossible to make an accurate diagnosis of Down syndrome using ultrasound. Based on the results of the procedure, the specialist evaluates the condition of the fetus according to the following parameters:

1. Thickened neck fold. Normally, it is 1.6-1.7 mm. A thickness of 3 mm indicates the likelihood of chromosomal abnormalities.

2. KTR (fetal length). The normal figure varies from 43 to 65 mm (for a period of 12-13 weeks). nine0006

At the next stage, calculations are carried out, the risk of genetic abnormalities is examined. A probability higher than 1:360 is high - however, this is not a diagnosis, but an assumption.

What to do if you are at high risk for Down syndrome?

According to statistics, 70% of women carrying a child with Down syndrome are at risk. In this case, the woman is invited to undergo an additional examination at the medical genetic center. The specialist prescribes a series of tests and amniocentesis is practiced as an invasive diagnosis. nine0006

Features of invasive diagnostics

Amniocentesis is the analysis of amniotic fluid. The procedure is performed by puncturing the abdomen in the area of the embryonic membrane. Its result is a sample of amniotic fluid, which contains fetal cells.

Amniocentesis is performed by one of two methods: