Amniocentesis with Traditional Chromosome Analysis

To the Point– Amniocentesis is a diagnostic test that can tell you, with very high accuracy, if your baby has a chromosome abnormality such as Down syndrome, by looking directly at the fetal chromosomes. The test is performed by inserting a very thin needle into the sac of fluid surrounding the baby (amniotic sac) utilizing ultrasound guidance and drawing out a small amount of fluid. This amniotic fluid contains fetal cells on which the analysis is performed. Amniocentesis is generally considered safe but not entirely risk-free; there is a risk of miscarriage associated with the procedure (1/200 or less). The procedure is typically done at 15-20 weeks gestation.

FAQs

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THE BASICS

amniocentesis Amniocentesis is a diagnostic test, meaning the results are typically “yes or no” in nature. The procedure itself is usually performed between 15-20 weeks gestation. The test is performed by inserting a very thin needle into the sac of fluid surrounding the baby (amniotic sac) utilizing sonographic guidance and drawing out a small amount of fluid. The fluid contains skin cells from the fetus that have naturally fallen off (just like you lose skin cells every day, so does the fetus) and bladder cells. Each of these cells has a set of chromosomes (see prenatal genetics 101 for more info). So, with amniocentesis, the lab can open up the baby’s cells and look directly at the baby’s chromosomes.

Amniocentesis is performed in the doctor’s office. Most women report that it really does not hurt that badly (we know….it looks and sounds like it would hurt). There is a risk of miscarriage associated with the procedure. For a long time, the risk for miscarriage from amniocentesis was thought to be approximately 1/200, however, new data suggests that it is lower than that. Ultimately, over 99% of the time, everything goes just fine. If you do have an amniocentesis, you need to take it easy for 24-48 hours – ask your doctor for details. You will get results on all of the chromosomes, including the sex chromosomes. So, you will know if it is a boy or a girl .

Amniocentesis does not look for or rule out all birth defects or genetic conditions, but it does rule out age-related chromosome abnormalities such as Down syndrome with over 99% accuracy. Historically, this test was offered only to high-risk pregnancies (eg. maternal age  > 35 at delivery, abnormal screening test, family history of chromosome condition, etc.), however, newer guidelines suggest that amniocentesis be offered to all women, regardless of age. In addition, amniocentesis can also look for evidence of open neural tube defects, such as, spina bifida or anencephaly, if requested by your doctor.

HOW IT WORKS

Amniocentesis is a pretty quick procedure done in your doctor’s office. This may be done by your OB, however, often times OBs will refer their patient to a high-risk pregnancy doctor (perinatologist or Maternal-Fetal Medicine specialist) to perform the procedure. Basically, the doctor will use an ultrasound to guide as they insert a very thin needle into the sac of fluid surrounding the baby. A small amount of fluid is taken out by a syringe, and then the needle is immediately removed. The time that the needle is inside of you is typically less than one minute.

The fluid is sent off to the laboratory where the fetal cells are grown (that’s the part of the process that takes time) and then the chromosomes can be analyzed. The chromosomes are evaluated for any extra (trisomy, such as, Down syndrome) or missing chromosomes (monosomy, such as Turner syndrome). Large deletions (missing sections of a chromosome) or rearrangements of parts of chromosomes can also be detected. Sex chromosomes are obviously seen, so if you don’t want to know if you are having a boy or a girl, make sure you let your doctor know so they don’t spill the beans!

Besides looking at the chromosomes, the lab can also look for evidence of open neural tube defects (spina bifida or anencephaly) by measuring the chemical called alpha-feto protein (AFP) in the amniotic fluid (this is not automatically tested for with amniocentesis, but your doctor may request it). If the baby has an open neural tube defect (ONTD), the AFP will most likely be high. If it is high, the lab can go on to test the fluid for another chemical called acetylcholinesterase, which when present, means there is a very high chance that the baby has an open neural tube defect (ONTD). Open neural tube defects(ONTDs) are a birth defect affecting approximately 1-2/1000 babies born. Risk for open neural tube defects does not increase with age. For more information on open neural tube defects click here.

[make_anchors  name=”Results”] RESULTS

Amniocentesis is a diagnostic test and results are considered to be definitive (yes or no). However, no test is perfect and there are cases when the results are hard to interpret or rare cases of lab error. With traditional chromosome analysis, you will receive information on the chromosomes (looking for evidence of Down syndrome and other Trisomies), gender and possibly the AFP level (looking for open neural tube defects). Amniocentesis with traditional chromosome analysis does not rule out all genetic conditions or all birth defects.

My amniocentesis results are abnormal…things to consider…

Amniocentesis was historically offered to women 35 or older at delivery to look for Down syndrome, as this was one of the first conditions known to increase in incidence as mom’s age increases. As time has passed and technology has improved, the amniocentesis with traditional chromosome analysis is now capable of detecting a variety of chromosome conditions with various levels of severity. If you are reading this and you have received an abnormal result, it may be that you are finding out that your baby has Down syndrome  or it may be something much more severe, such as Trisomy 13 or Trisomy 18 , or something potentially more mild, such as Turner syndrome (45, X) or Klinefelter syndrome (47,XXY). No matter what condition has been diagnosed, we know that this is not necessarily an easy time or what you expected.

If your results indicate a chromosome condition or birth defect, it is often very helpful to take time to talk to your provider, a genetic counselor if you are able, friends and family if you are comfortable, and even get a second opinion if you feel like that may be helpful. Taking time and consulting with others is especially important if your results are confusing, unclear, or if you don’t know much about the condition that has been diagnosed.

Even if you know a bit about the condition, it’s often helpful to get up-to-date information as things have changed dramatically for some conditions. For example, in the case of individuals with Down syndrome, quality of life and life expectancy is quite different than it was 2 generations ago. Also, depending on what website you go to, who you talk to, what you read, you are going to find differing opinions on what life may be like for a child with the condition that has been diagnosed, what it is like to parent a child with the condition, etc. Some people benefit from finding someone who has a child with the same diagnosis and speaking with them directly. Your provider or genetic counselor may be able to help facilitate this.

Ultimately, you have 3 options if you find out through amniocentesis that your baby has a chromosome abnormality, genetic condition or birth defect….

  1. Continue the pregnancy and prepare – READ MORE
  2. Continue and place the baby for adoption – READ MORE
  3. Choose to not continue the pregnancy – READ MORE

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HOW TO DECIDE

To The Point- Deciding about invasive testing like amniocentesis can be tough. If you feel like either way you would continue your pregnancy and raise your child AND you are doing ok mentally with the uncertainty, then the invasive testing may not be for you. If you aren’t sure what you would do if a chromosome abnormality was found AND/OR you are not doing well mentally with the uncertainty, then invasive testing may be the way to go. Read on for more information to help you in this process…..

Deciding whether or not to have a diagnostic test, such as, amniocentesis, is a big decision. For some, it may be a fairly easy call. For others, it may be agonizing. Either way, it warrants thoughtful consideration.

Patients often ask their doctors or genetic counselors, “would you have the amniocentesis?” This is a great question, however, the answer is different for each individual and circumstance. One of the most important aspects of prenatal genetic counseling is that whatever the patient decides is based on their personality, beliefs and values, not the providers. So, instead we offer you some questions to consider.

  • Do you feel like you need yes or no answers to be able to enjoy the rest of the pregnancy (i.e. eat, sleep, etc)?
  • Do you feel like you are ok waiting until the baby arrives to know for sure?
  • If you feel like you need more definitive answers, are you ok with the risk of miscarriage associated with these procedures (amniocentesis- <1/200, CVS, <1/200)?
  • If you knew that the baby had a chromosome condition, would it affect your decision to continue the pregnancy and raise the child?
  • Would you consider other options if there was a chromosome condition present in your baby, such as, placement of the baby for adoption (which is a realistic option) or choosing not to continue the pregnancy?
  • Have you thought about these two scenarios- 1) you don’t have the amniocentesis and you find out at delivery that the baby has a chromosome condition and 2)you do have the amniocentesis and you end up miscarrying the baby. Both situations may be unsettling, but which scenario is more unsettling to you? …these are ethically challenging things to think about and talk about….this is part of why your provider will allow you to make these decisions based on your own personality, beliefs, needs and values.
  • Are there other trusted people in your life that you can turn to for advice and perspective (i.e. religious leader, family member, friend, etc.)?

Another way to look at this is… “What do other people decide to do?”

  1. Don’t get the amniocentesis because…“I wouldn’t do anything even if the test came back indicating that the baby had a chromosome condition.”
  2. Get the amniocentesis because… “I wouldn’t do anything differently if the test came back indicating that the baby had a chromosome condition, but I want to have the information to prepare.”
  3. Get the amniocentesis because…”I am not sure what I would do if the test came back indicating a chromosome condition, but if it indicated a serious disorder I may consider choosing not to continue the pregnancy.”

FAQs

Amniocentesis FAQs

SEE BELOW FOR MORE FAQS REGARDING AMNIOCENTESIS

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FAQs


What are some reasons people choose to have amniocentesis?

Amniocentesis is now offered to women of all ages and some may choose to have amniocentesis simply because they want as much definitive information regarding age-related chromosome abnormalities as possible. Other reasons you may consider having amniocentesis include the following:

  • You had positive/abnormal results from a prenatal screening test, such as first trimester screening (FTS), sequential screening, quad screening or non-invasive prenatal screening (NIPS). In these situations, if you want yes or no answers, it is recommended to consider having CVS or amniocentesis.
  • You have a family history of a chromosome abnormality (eg. child or previous pregnancy). This puts you at higher risk and based on your previous experience you may feel like you want to know what to expect during your current pregnancy.
  • You are 35 or older at delivery. Historically, women 35 or older (Advanced Maternal Age or AMA) have been routinely offered amniocentesis because of the higher chance of chromosomal conditions, such as Down syndrome as mom ages.
  • You have a family history of a specific genetic condition, or you and/or your partner are known carriers of a genetic condition. If the genetic changes are known in your family, you may be able to have additional testing through amniocentesis to determine if your baby has a specific genetic condition, for example, tay sachs disease, cystic fibrosis, spinal muscular atrophy, Fragile X, etc.


How can the procedure cause a miscarriage?

When the doctor inserts the needle for the amniocentesis, there are a couple of things that can come up and possibly lead to miscarriage.

  • It could introduce an infection to the baby. How? The needle passes through mom on the way to the amniotic sac. If mom has an infection (that she may be unaware of), it can be transferred to the baby and lead to miscarriage. In order to reduce this risk, the procedure is performed under sterile technique.
  • It could cause leakage of the amniotic fluid. How? The needle punctures the sac of fluid surrounding the baby. Typically, this sac seals up shortly after the needle is removed, however, on rare cases this does not happen. Amniotic fluid (clear) would begin leaking out and if this cannot be stopped it may result in miscarriage.


Do they worry about poking the baby with the needle?

Short answer – no. Doctors typically are using ultrasound to guide them to insert the needle into the amniotic sac in a place that is away from baby.



Amniocentesis and CVS are both considered diagnostic, why choose amniocentesis?

Great question. Both amniocentesis and CVS are considered to be the gold-standard diagnostic tests for looking for age-related chromosome abnormalities in the baby.

There are a few advantages of amniocentesis.

  • Amniocentesis is considered less risky than CVS by some. However, in the hands of a specialist who regularly performs CVS, the risks are nearly equivalent.
  • Amniocentesis is looking directly at chromosomes from fetal skin and bladder cells, whereas CVS is looking at the chromosomes from placental cells (chorionic villi is part of the placenta). There can be differences seen in placental cell chromosomes that may or may not reflect what is going on with the baby.
  • In addition to looking for chromosome abnormalities, amniocentesis can also look for evidence of open neural tube defects (ONTDs), for example, spina bifida. CVS does not look for ONTDs. This being said, there are other ways to assess chances of ONTDs besides amniocentesis, including, level II ultrasound in the second trimester and a blood draw on mom in the second trimester called, maternal serum alpha-feto protein (MSAFP). Open neural tube defects occur in approximately 1/500 to 1/1000 babies born and chances of this type of condition do not increase as mom ages.
  • Disadvantages of amniocentesis include the following:
  • Waiting until 2nd trimester. For various reasons, some people would like to know information regarding their baby’s chromosomes earlier in the pregnancy. CVS can be done in the first trimester as early as 10 weeks whereas, amniocentesis is typically done at or beyond 15 weeks gestation.
  • Wait time for results- Final amniocentesis results typically take 10-14 days versus 7-10 days for CVS.


My doctor gave me the option of having microarray versus the traditional chromosome analysis with my amniocentesis. What is the difference?

To the point:

  • Both traditional chromosome analysis and chromosomal microarray can evaluate conditions that are increased in risk as mom’s age increases (e.g. Down syndrome). 
  • Both traditional chromosome analysis and chromosomal microarray can identify other conditions involving missing chromosomes or major chromosome rearrangements
  • Unlike traditional chromosome analysis, chromosomal microarray testing has the capability to detect smaller regions of extra or missing portions of the chromosome, called microduplications or microdeletions which may be associated with mental retardation and birth defects
  • Both traditional chromosome analysis and chromosomal microarray may identify a change where outcome is uncertain, however, this is arguably more likely with chromosomal microarray.
  • Chromosomal microarray testing has approximately a 1-2% chance of identifying what is called a variant of unknown significance (VOUS), meaning, there is not enough data to know whether or not the genetic change will results in abnormalities in the baby; this information may result in substantial anxiety for mom and dad.
  • Chromosomal microarray may detect non-paternity (different father of baby) and consanguinity (parents are closely related to each other, i.e. cousins).
  • Traditional chromosome analysis still considered standard of care, however, recent guidelines from The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine have opened the doors for all women to be offered microarray if they are undergoing diagnostic testing, such as CVS or amniocentesis.

“The potential for complex results and detection of clinically uncertain findings identified by prenatal chromosomal microarray testing can result in substantial patient anxiety. This underscores the critical need for comprehensive patient pretest and posttest genetic counseling from qualified personnel about the benefits, limitations, and results of testing so that patients can make informed decisions.”- American College of Obstetrics & Gynecology/Society for Maternal Fetal Medicine statement

Traditional chromosome analysis, also known as karyotype analysis or cytogenetic analysis, can evaluate the number of chromosomes and the basic structure of each chromosome (e.g. any extra or missing chromosomes or any major rearrangements of the chromosomes). Traditional chromosome analysis can rule out common chromosome conditions like Down syndrome, Trisomy 18, Trisomy 13 and sex chromosome conditions. It can also detect large deletions and duplications of chromosomal material that are visible under the microscope.  Traditional chromosome analysis is still considered the standard of care.  However, recent guidelines from The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine have opened the doors for all women to be offered microarray if they are undergoing diagnostic testing, such as CVS or amniocentesis.

Besides detecting the vast majority of things that traditional chromosome analysis can detect, microarray testing has the capability to zoom in on parts of the chromosomes that are too small to visualize using a microscope, allowing detection of smaller regions of extra or missing portions of the chromosome.  Conditions in which several instructions or genes are missing are called microdeletion syndromes. Conditions in which there are several genes duplicated are called microduplication syndromes. Microdeletion and microduplication syndromes are typically associated with mental retardation and birth defects. There are over 150 genetic conditions that can be detected with microarray testing.  These conditions are not typically increased in risk as mom’s age increases.

In terms of detecting chromosome abnormalities involving an extra chromosome, such as Down syndrome, CMA is just as good as traditional chromosome analysis.  The differences come in when detecting abnormalities involving smaller genetic changes.  Among fetuses with an abnormal ultrasound finding, CMA found clinically relevant chromosomal deletions or duplications approximately 4% of cases that were not detected with traditional chromosome analysis. In cases sampled for advanced maternal age or positive screening results, microarray analysis picked up an abnormality in 1.7% of pregnancies that had a normal traditional chromosome analysis1.

Besides the possibility of detecting conditions like Down syndrome and other genetic conditions, microarray testing may also detect what are called variants of unknown significance (VOUS).  These are changes in the baby’s DNA that may or may not affect the baby’s development but there is not enough data to know for sure.  Recent studies have shown that approximately 1-2% of patients receive a result that is a VOUS1.  Many labs request samples of mom and dad’s blood to look at their DNA to help interpret the meaning of a VOUS; in some cases this can be helpful but not always.  When a VOUS is found in the baby during the pregnancy, it may cause a lot of anxiety in mom and dad as the outcome for baby may be very uncertain.  This is one of the main reasons that genetic counseling and informed consent prior to having prenatal chromosomal microarray is very important.

Prenatal chromosomal microarray results take approximately 7-10 days to receive, compared to 10-14 days for traditional karyotype analysis, and may be called out over the phone or given to you in person by your provider.  Chromosomal microarray may be offered to all women undergoing invasive testing, such as amniocentesis or CVS, but this is an optional test and is always your choice.

There are certain situations where microarray will be offered or recommended based on abnormalities on ultrasound.  However, if you are being offered microarray for no specific indication here are some thoughts to consider…

Microarray is an exciting technology that is relatively new within the arena of prenatal testing.  Before assuming that more is better, you need to take a step back and think about a few things.  First of all, do you want to know all of this information in the first place and would it change your decisions about how you would proceed with the pregnancy, etc.  Secondly, and often understated, there is a real chance, 1/50 or greater1, that you may get results that indicate there is a difference or change found in the baby’s DNA, but we don’t know exactly what it means because technology is ahead of us.  This can cause a lot of anxiety.  Microarray testing during pregnancy cannot necessarily be equated with microarray testing after the baby is born, when you can actually see the baby, know what he/she looks like, etc.  Finding out uncertain information about the prognosis of the baby during the pregnancy can be especially challenging and make decision-making extremely difficult.  Microarray testing may also reveal information about the future health of the parents and also may detect things like non-paternity (if the father is someone other than previously thought) and consanguinity (if parents are closely related to each other).   Microarray testing does not rule out all birth defects or genetic conditions.  Like other prenatal testing options, the choice is always up to you to make.

1.  Hillman et al. Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta-analysis. Ultrasound Obstet Gynecol 2013; 41: 610–620.





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