High-Risk Pregnancy

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SPEAKER: This video will review of different genetic conditions
that can occur for a fetus during pregnancy
and the testing that can identify many of them.
Please keep in mind that even though we
are focusing on these conditions,
they're unlikely to arise during your pregnancy.
Approximately 97% of all births result
in a baby being born with no birth defects.
Of the remaining 3%, some of those
are due to genetic causes, while others are not genetic.
If you have specific concerns regarding
high risk, positive results, have a family history
of a genetic condition, or have questions or topics
you would like to discuss in more detail,
please speak with your medical provider or ask for a referral
to a genetic counselor.

Our bodies are made of trillions of cells.
Within most of our cells we have chromosomes.
Chromosomes are made of long strings of DNA
which contain all of our genes.
Genes provide the instructions that tell our bodies how
to grow, form, and function.
It is estimated that humans have about 20,000 genes.
People typically have 46 chromosomes
which come in pairs, meaning 23 different chromosomes.
Numbers 1 through 22 are generally
the same in all people.
The last pair are the sex chromosomes.
When there are two X chromosomes,
that person is typically female.
When there is an X and a Y chromosome,
that person is typically male.
You can think of a chromosome like a book.
Most humans have a collection of 46 books.
The DNA is all the pages within those books,
and the genes are the paragraphs on the pages.

A change in someone's genetic information
causes a genetic condition.
The change can be in the total number of chromosomes,
a small amount of DNA being missing or extra,
or in just one single gene.
Thinking back to the book analogy,
there could be a different number
of books, a few pages missing or extra,
some missing or extra words in a paragraph,
or misspelled words within a paragraph.
Any of these could be significant for how
the collection of books is read.
Sometimes, just by chance, an egg or a sperm
may contain a different number of chromosomes.
In our book analogy this would be
like a whole extra or missing book.
A pregnancy from that egg or sperm
will have a chromosome condition.
There are various chromosome conditions
depending on the specific chromosomes involved.
One example of a chromosome condition
is called Down syndrome.
The chances for chromosome conditions
are associated with the age of the egg.
As the age of the egg increases, so
does the risk for chromosome conditions.
At age 25, the chance for a chromosome condition
is approximately 1 in 200, or about 0.5%, while at age 40,
it is about 1 in 50, or about 2%.
That also means that at age 40 there
is a 98% chance that there will not be a chromosome condition.
In fact, at any age the greatest chance
is that there will not be a chromosome condition.
Genetic conditions caused by a small amount
of missing or extra DNA are called microdeletions
and microduplications.
Referring to our book analogy, this
would be like a book having a few missing
or additional pages.
Although the change to the total amount of DNA is small,
this missing or extra DNA contains
many genes, which can cause very significant effects.
The specific symptoms will vary depending
on the genes involved.
In general, these conditions tend to be severe.
The overall possibility for a pregnancy
to have a microdeletion or microduplication
is between 1% and 2%.
And this chance does not change with age.

Most microdeletion and microduplication syndromes
are not inherited from either parent.

Single-gene conditions are caused by changes
to just one gene.
Recalling the book analogy one more time,
this would be like a word in a paragraph
on a page being misspelled, missing, or repeated,
making it difficult or impossible to understand
that paragraph.
For some genes, having just one working copy is sufficient,
and people can carry a change in a gene
without ever knowing or having any symptoms of that condition.
It is estimated that two random individuals who are not
related, have between a 1% and 6% chance of being carriers
for changes in the same gene.
When two individuals carry changes in the same gene,
they have an increased chance to have
a child with that condition.
For other genes, just one non-working copy
will cause a condition.
In this case, the genetic parent has that condition,
and there is a significantly increased
chance their children will have that condition as well.

There are many tests available to provide more information
during pregnancy.
There are separate videos in this series which will review
each test in more detail.
While these tests can provide a lot of information,
keep in mind that no test or combination of tests
can guarantee a healthy pregnancy outcome.
But please also keep in mind that most pregnancies have
no medical conditions regardless of how many tests
are being performed.
There are both screening and diagnostic testing options
available during pregnancy.
Screening tests can tell us the probability
that a pregnancy has certain conditions,
but will not provide definitive answers.
Screening tests mostly look for the likelihood
for certain chromosome conditions,
not for microdeletions, microduplications,
or single-gene conditions.
Results are generally categorized as either screen
positive, when there is a high chance the pregnancy has
a condition, or screen negative, when
there is a lower chance that the pregnancy has a condition.
With screening tests, there is a possibility
for the result to be incorrect.
Screening tests are performed through a blood
draw of the pregnant person with no risk of miscarriage.
Ultrasound is another way to learn more about a pregnancy.
Ultrasounds are performed to confirm someone is pregnant,
establish a due date, and check on the anatomy, development,
and growth of the fetus throughout the pregnancy.
Ultrasound can detect certain birth defects
and sometimes show differences which increase suspicion
for a genetic condition.
Other ultrasounds may be recommended
depending on various pregnancy-related factors.
Ultrasound is non-invasive and does not pose a risk
for harming the pregnancy.

Diagnostic tests can tell us definitively
whether a pregnancy has specific conditions.
Diagnostic testing is also significantly more
comprehensive than screening and can
detect chromosome conditions, microdeletion,
and microduplication syndromes, and can also
look for single-gene conditions if indicated.
The results from diagnostic testing
provide a yes or no answer, not a probability.
If the results are positive for a condition,
that is a diagnosis.
If the results are negative, that condition
has been ruled out.
Diagnostic tests are performed by doing a more invasive
procedure where cells from the placenta or amniotic fluid
are collected and used for analysis.
Diagnostic tests involve a procedure-related risk
for miscarriage, which is generally
quoted as between 1 and 455, or about 0.2%, and 1 in 900,
or about 0.1%, depending on the procedure.
This also means that there is about a 99.8% to 99.9% chance
that the procedure would not cause a miscarriage.
One final category of testing that can be performed
is called carrier screening.
This can be performed on the genetic parents
to determine if they carry changes in the same gene.
This testing can be performed before or during pregnancy.
If desired, diagnostic testing can
determine whether the pregnancy has that condition.
Some pregnancies may also have additional considerations
regarding screening and diagnostic testing options.
Some examples of these pregnancies
include multiple gestation pregnancies,
such as twin pregnancies, and pregnancies
achieved via in vitro fertilization, where
specific risks may be elevated.
We hope that this introduction to genetic conditions
and the types of testing has been valuable and informative.
Please watch the additional videos
in this series for more detail about what was reviewed here.

If you feel it would help to discuss these conditions
or tests in more detail beyond the scope of these videos,
please speak with your medical provider
or request a referral for genetic counseling.
Warmest wishes on your pregnancy journey.

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NARRATOR: In this video, we will be discussing what ultrasound is
and what types of ultrasounds you may have during pregnancy.
Ultrasound uses sound waves to form pictures of what
is happening inside the body.
It is common to undergo multiple ultrasounds during pregnancy.
Ultrasound is used to check many aspects of the pregnancy,
including whether there are any birth defects and the size
and development of the fetus.
Please keep in mind that approximately 97% of all births
result in a baby being born with no birth defects.
While ultrasound can detect many birth defects and conditions,
not all conditions can be seen on ultrasound,
and a normal ultrasound cannot guarantee a healthy pregnancy
outcome.
There is no evidence that ultrasound poses a risk when
used in the medical setting.
Let's review common ultrasounds that you may
complete during your pregnancy.
The first ultrasound during pregnancy
is often called a viability scan, or dating ultrasound.
This is usually performed between 6 and 10
weeks of pregnancy.
With this ultrasound, your provider
can usually confirm that you are pregnant,
check that the pregnancy is developing as expected,
and establish your due date.
Most pregnant patients will also be
referred for an ultrasound in the first trimester between 11
and 14 weeks, which provides an early check for birth defects.
This ultrasound may be called an early anatomy,
or first trimester anatomy scan.
At this stage of pregnancy, it is
possible to see the main parts of the fetus
and identify many major birth defects.
However, the pregnancy is still too small
to see all the details of the anatomy.
This scan typically includes a nuchal translucency measurement
of the fluid in the back of the neck, which,
if larger than expected, increases
the concern for certain genetic conditions or birth defects.

Most pregnant patients will be referred
for an ultrasound in the second trimester, around 20 weeks.
This ultrasound has many names, including
anatomy scan, anatomic survey, or detailed or complete
ultrasound.
By this stage of the pregnancy, most
of the main parts of the fetus have formed and are large enough
to see in detail.
So we are able to thoroughly check for birth defects,
like heart anomalies.
Other parts of the pregnancy, including
amniotic fluid, placenta, and uterus, will also be checked.
This is typically when the genitalia
have developed enough to predict the fetal sex as well.
Patients who have an increased risk
for a pregnancy with a heart defect
may be referred for a fetal echocardiogram, or fetal echo,
for short, which is a specialized
ultrasound in the second trimester
that focuses on the heart.
Some patients may also have ultrasound
to check on the pregnancy in the third trimester.
Most commonly, these ultrasounds are
to check the growth of the fetus.
Depending on various factors, there
may be other ultrasounds or types of images recommended
to be taken during a pregnancy.
If you have questions about different types of ultrasounds
and your pregnancy, please speak with your provider.

We hope that this video has been valuable and informative.
Please watch the additional videos
in this series for more detail about various aspects
of genetic conditions and pregnancy.

If you feel it would help to discuss the conditions
or tests in more detail beyond the scope of these videos,
please speak with your medical provider
or request a referral for genetic counseling.
Warmest wishes on your pregnancy journey.
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In this video, we will be discussing
some of the different screening tests
available during pregnancy.
Screening tests are optional and are offered to everyone
regardless of whether the pregnancy is
considered high- or low-risk.
These tests are typically performed through a blood
draw of the pregnant person and do not increase
the risk of miscarriage.
Screening tests provide the likelihood
that a pregnancy has certain conditions.
Unlike diagnostic testing, screening tests only
look for a limited number of conditions,
they are not definitive, and there is a possibility
for the result to be incorrect.
Please keep in mind that no test or combination of tests
can guarantee a healthy pregnancy outcome.
But please also keep in mind that most pregnancies have
no genetic conditions regardless of how many tests are performed.
The two screening tests that will be covered in this video
are cell-free DNA screening (also known as NIPT)
and AFP screening, as well as the possible results
and next steps.
Ultrasound and carrier screening are also
considered types of screening tests.
Please watch the additional videos
in this series for more detail about each of these.
One of the more common screening tests
you will be offered during pregnancy
is called cell-free DNA screening.
Cell-free DNA screening may be referred to by many other names,
including cfDNA, non-invasive prenatal testing (or NIPT),
and non-invasive prenatal screening (or NIPS).
Each testing company will have their own brand
name for this test as well.
Cell-free DNA screening is performed
on a blood sample provided by the pregnant person.
During pregnancy, small fragments
of DNA from the placenta are present in the pregnant person's
bloodstream, and cell-free DNA screening
will predict whether that amount is within the expected range.
Cell-free DNA screening can screen
for the most common chromosome conditions
that babies are born with, which are Down
syndrome, trisomy 18, trisomy 13, and X and Y chromosome
variations.

Some versions of the test may also
include screening for other conditions including
certain microdeletions.
Cell-free DNA screening can also predict the sex of the fetus.
Another common screening test is called
AFP screening, which may also be called msAFP screening.
AFP screening looks for the amount of a protein
called alpha-fetoprotein (or AFP)
present in the blood of a pregnant person, which
tends to be elevated when a pregnancy has certain birth
defects like open neural tube defects or abdominal wall
defects.

The two possible results from these screening tests are
"screen negative" and "screen positive."
Screen negative means that the likelihood
that the fetus has any of the conditions included
in the testing is very low.
Since screening tests are not definitive,
there is a small chance for a false negative result
with any screening.
This means there is still a small chance
that the fetus has one of the conditions included
in the testing even though the results are screen negative.
Some patients with low-risk results
may still elect diagnostic testing
for more definitive answers than screening tests can provide,
or to test for conditions beyond what
can be looked for with the current screening tests.
Screen positive means that means that the likelihood
that the fetus has a condition is increased.
In this case, the results will be
specific about which condition the fetus
is screen positive for.
Since screening tests are not definitive,
there is a chance for a false positive result
with any screening.
This means the fetus may not have any genetic condition
even though the results are screen positive.
We always note that no irreversible actions
such as pregnancy termination should
be taken based upon a screen positive result alone.
When results are screen positive,
patients will be offered the option of follow up
diagnostic testing for more definitive answers
to either diagnose a condition or rule it out.
We hope that this video has been valuable and informative.
Please watch the additional videos
in this series for more detail about various aspects
of genetic conditions and pregnancy.
If you feel it would help to discuss the conditions
or tests in more detail beyond the scope of these videos,
please speak with your medical provider
or request a referral for genetic counseling.
Warmest wishes on your pregnancy journey!

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NARRATOR: In this video, we will be discussing
the different diagnostic testing options
available during pregnancy.
Unlike screening tests, diagnostic testing
is a way to get definitive yes-or-no answers
about a wide range of conditions.
Diagnostic tests are more invasive
than a blood test and involve a procedure-related risk
for miscarriage of about 0.1% to 0.2%,
meaning that the overall chance that diagnostic testing would
not cause a miscarriage is 99.8% or higher.
While these tests can provide a lot of information,
keep in mind that no test or combination of tests
can guarantee a healthy pregnancy outcome.
But please also keep in mind that most pregnancies have
no genetic conditions, regardless of how many
tests are performed.
Diagnostic testing is optional and offered to everyone,
regardless of whether they are considered high or low risk.
Some pursue this testing simply because it is the most
comprehensive and accurate.
Others consider diagnostic testing
because of an increased risk due to an egg age, test results,
or ultrasound findings.
Still, others may have reasons beyond what we have listed here.
Diagnostic testing can detect chromosome conditions like Down
syndrome, microdeletion and microduplication syndromes like
22q11.2 deletion syndrome, and can look for single-gene
conditions like cystic fibrosis, if indicated.
The results from diagnostic testing
either provide a diagnosis or rule out a condition,
rather than giving a probability.
If the diagnostic testing reveals a diagnosis,
your medical provider will discuss
options for that pregnancy, including
continuing the pregnancy, consideration
of any possible treatments, adoption, and pregnancy
termination.
There is no correct decision for what to do after diagnosis.
It is a personal choice for you and your family.
Two main diagnostic tests are available during pregnancy.
One is called chorionic villus sampling, also called CVS.
And the other is called amniocentesis, or amnio,
for short.
Typically, patients only do CVS or amniocentesis, not both.
CVS involves taking a small sample
of the placenta, which is made of cells from the pregnancy.
Using ultrasound as a guide, a specially trained doctor
will obtain a sample of the placenta.
Depending on where the placenta is located in the uterus,
the doctor will either use a catheter passing
through the cervix or insert a needle through the abdomen.

This placenta sample is then sent to a lab for testing.
The risk for miscarriage from the CVS procedure
is approximately 1 in 455, or about 0.2%.
With CVS, there is also a 1% to 2%
risk for an ambiguous result, usually caused by the placenta
not having the same chromosomes as the fetus,
a phenomenon called confined placental mosaicism.
In these cases, amniocentesis is recommended
to clarify the results.
CVS is typically performed between 10 and 14
weeks of pregnancy.
Amniocentesis involves taking a small sample
of amniotic fluid, which contains cells that have
come directly from the fetus.
Using ultrasound as a guide, a specially trained doctor
will insert a needle through the abdomen.
The needle does not actually touch the fetus.
It is only inserted as far as is needed to get the fluid.
This fluid is then sent to the lab for testing.
The risk for miscarriage from the amniocentesis procedure
is approximately 1 in 900, or about 0.1%.
Amniocentesis is typically performed between 16 and 22
weeks of pregnancy.
One possible outcome of diagnostic testing
is for the results to come back negative.
Negative results mean that no mutations, variants, or changes
were found in the chromosome or genes analyzed.
Or in other words, all of the conditions included in the test
have now been ruled out.
It is also possible to receive positive results, which
means that a mutation, variant, or change was
found in the chromosomes or genes for the pregnancy.
When positive, the results will be
specific about the condition that was found.
A positive result on a diagnostic test
is a diagnosis for that condition.
A third type of result can occasionally come up as well.
This result is called a variant of uncertain significance,
or a VUS.
It is an uncertain result because there
was a mutation, variant, or change found,
but there is not enough data to determine
if this should be placed in the positive or negative category.
We hope that this video has been valuable and informative.
Please watch the additional videos
in this series for more detail about various aspects
of genetic conditions and pregnancy.
If you feel it would help to discuss the conditions
or tests in more detail beyond the scope of these videos,
please speak with your medical provider,
or request a referral for genetic counseling.

Warmest wishes on your pregnancy journey.
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SPEAKER: This video will discuss carrier screening, which
is genetic testing performed on individuals to determine
if they are carriers for certain conditions.
Most people are carriers for multiple conditions,
and being a carrier usually will not cause any health concerns
for that person.
A pregnancy might be at increased risk
based upon the carrier screening results
in certain circumstances, which some people may find
valuable to know ahead of time.
This testing is separate from other tests
one may do in pregnancy, such as those
that look for Down syndrome or other chromosome conditions.
Please keep in mind that approximately 97% of all births
result in a baby being born with no birth defects.
While carrier screening can detect many conditions,
not all conditions can be screened for, and normal results
cannot guarantee a healthy pregnancy outcome.
Before we discuss what it means to be a carrier,
let's review some basics about how genetics and our genes
are passed on.
One note, we will be using the term genetic parent
in this video, which refers to the person who
contributed the egg or sperm to that pregnancy.
People typically have 46 chromosomes,
which come in pairs, meaning 23 different chromosomes.
Numbers 1 through 22 are generally
the same in all people.
The last pair are the sex chromosomes.
When there are two X chromosomes,
that person is typically female.
When there is an X and a Y chromosome,
that person is typically male.
Chromosomes are made of long strings of DNA
which contain all of our genes.
Humans have about 20,000 genes which provide the instructions
that tells our body how to grow, form, and function.
In most cases, an individual has two copies
of each gene, one on each chromosome.
Usually, both copies of that gene are functional,
but sometimes a person may be born with a change
to a gene which makes that copy of the gene not work.
This can be inherited in different ways.
Three types of inheritance that we will review
are autosomal recessive inheritance,
autosomal dominant inheritance, and X-linked inheritance.
In autosomal recessive inheritance,
a person with one nonworking copy of a gene
is called a carrier.
When both genetic parents are carriers for the same condition,
each pregnancy from those parents would have a 1 in 4,
or 25%, chance to inherit no working copies of the gene
and therefore be affected with that condition.
That also means that there is a 3 and 4, or 75%, chance
to not have an affected pregnancy each time.
Autosomal recessive conditions can
occur when neither family has any known
history of the condition.
It is estimated that two random individuals who are not related
have between a 1% and 6% chance of being carriers
for changes in the same gene.
In autosomal dominant inheritance,
a person with one nonworking copy of a gene
has that condition.
Each pregnancy from that individual would have 1 in 2,
or 50%, chance of inheriting the condition.
These conditions often run in families.
But new gene changes can also happen just by chance,
particularly when the sperm is from an older person.
In X-linked inheritance, the genes we are referring to
are located on the X chromosome.
Someone with two X chromosomes who
has one nonworking copy of the gene
is called a carrier, while someone with one X and one Y
chromosome who has one nonworking copy of the gene
has the condition.
Carriers of X-linked conditions have a 1 in 4, or 25%, chance
to have an affected pregnancy.
That also means that there is a 3 in 4, or 75%, chance
to not have an affected pregnancy each time.
X-linked conditions can occur when
neither family has any known history of the condition.
The types of conditions included in carrier screening
can result in severe childhood onset disease.
Some of these conditions are treatable,
while others will cause untreatable severe illness
or even a shortened lifespan.
It is possible to do carrier screening
to target just one or a few specific conditions,
and there is also an option to test for hundreds of conditions
all at the same time through testing called expanded carrier
screening.
Expanded carrier screening includes
many autosomal recessive conditions,
some X-linked conditions, and sometimes autosomal
dominant conditions as well.
Carrier screening is performed on a blood or saliva
sample from one or both of the genetic parents.
Carrier screening can be done before or during pregnancy.
The possible results from carrier screening
are negative, positive, and positive at risk for symptoms.
A negative result means you were not
found to be a carrier for the conditions that were looked at.
It is not possible with carrier screening
to absolutely rule out being a carrier.
However, with a negative result, the chance
that you are a carrier for that condition
has been significantly reduced.
A positive result means that you were
identified to be a carrier for a condition.
When results are positive, the report
will be specific about the condition or conditions.
If you were found to be a carrier,
your medical provider will discuss
the result and the next steps with you in more detail.
The final possible result is called positive at risk
for symptoms.
Carrier screening may occasionally
identify that the person being tested
is both a carrier for a specific condition
and could potentially develop symptoms themselves.
If you receive this result, your medical provider
will discuss the results and next step with you
in more detail.
When doing carrier screening for multiple conditions,
someone may receive positive results
for some conditions and then negative results
for the remaining conditions.
If you receive positive or positive
at risk for symptoms results, we encourage
you to share this information with your family members
due to their increased chance to have the same result.
When carrier screening has identified an increased
reproductive risk, the available options
will depend on whether or not someone is already pregnant.
During pregnancy, diagnostic testing
can be performed to determine whether the pregnancy is
affected with the condition.
If the diagnostic testing reveals a diagnosis,
your medical provider will discuss the options
for that pregnancy, including continuing
the pregnancy, consideration of any possible treatments,
adoption, and pregnancy termination.
There is no correct decision for what to do after diagnosis.
It is a personal choice for you and your family.
Before pregnancy, patients can consider whether or not
to do IVF with PGT-M to help select an embryo to transfer
into the uterus.
IVF is where an egg is fertilized by sperm in a lab
and an embryo is formed.
PGT-M is where an embryo is tested for a specific condition
or conditions.

We hope that this video has been valuable and informative.
Please watch the additional videos
in this series for more detail about various aspects
of genetic conditions and pregnancy.

If you feel it would help to discuss the condition
or test in more detail beyond the scope of these videos,
please speak with your medical provider
or request a referral for genetic counseling.
Warmest wishes on your pregnancy journey.
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In this video, we'll give an overview of genetic counseling
and why someone might wish to pursue it.
For the scope of this video, we will
be discussing prenatal and preconception
genetic counseling, where the focus is
on reproductive information and pregnancy.
However, there are numerous other types
of genetic counseling appointments that
may be appropriate for you or someone you know,
including oncology, pediatrics, neurology, and cardiology.
Genetic counselors are medical providers
who have extensive training regarding genetic testing
and genetic conditions.
They also understand the complicated emotions
that may come up when discussing genetic testing
and possible genetic conditions.
Genetic counseling is not psychological therapy
and does not take the place of meeting with the therapist.
While genetic counselors will be discussing genetics and biology,
you do not need to have any specialized background
to follow along with these concepts.
Genetic counselors discuss complicated concepts
in ways that are easy for anyone to understand.
In the appointment, your genetic counselor
will give an overview of certain genetic conditions,
discuss the reproductive chances for genetic conditions,
review the pros and cons of different testing options,
work with you to find the testing path that makes the most
sense for your situation, order and interpret
genetic test results, and collect a medical family history
and assess your reproductive chances for these conditions.
There are many reasons why someone
may wish to have a reproductive genetic counseling appointment.
It might be for no other reason than to have
a more in-depth conversation about the different available
genetic testing options.
Other reasons include a desire to pursue
one or multiple genetic tests, wanting
to discuss how medical conditions and family
members may impact someone's reproductive risks,
or because test results or an ultrasound
revealed an increased risk for a genetic condition.
Reproductive genetic counseling can
occur before someone is pregnant or during pregnancy.
Your genetic counselor will tailor your appointment
for what is appropriate for you, as some tests can only
be done during pregnancy, while others can be done at any time.
Most patients will only have one genetic counseling appointment
per pregnancy.
But some patients may see a genetic counselor
a second or third time if new test results become
available which warrant further discussion or follow up.
Genetic counseling appointments are typically
scheduled for one hour.
To prepare for your genetic counseling appointment,
you and your partner may wish to gather information
about medical conditions in family members or your egg
or sperm donor's family.
If someone has been diagnosed with a genetic condition,
obtain as much specific information
as you can about the condition, including
which relative or relatives have the medical condition,
the specific name of the medical condition, at what age
they were diagnosed, and if any genetic testing has been
performed in any relatives.
If genetic testing was performed,
obtain copies of the genetic testing results,
if possible, to ensure your genetic counselor
can give you accurate information about that condition
and the risks for you or your pregnancy.
We hope that this video has been valuable and informative.
Please watch the additional videos
in this series for more detail about various aspects
of genetic conditions and pregnancy.
If you feel it would help to discuss the conditions
or test in more detail beyond the scope of these videos,
please speak with your medical provider
or request a referral for genetic counseling.
Warmest wishes on your pregnancy journey.