Preconception Testing and Genetic Screening

Preconception testing and genetic screening at a glance

• Preconception testing is the process of screening individuals or couples for potential issues that could affect the ability to achieve a healthy pregnancy before they try to get pregnant.
• These tests can range from routine bloodwork to genetic testing for inheritable diseases or issues that contribute to pregnancy loss.
• Genetic screening before conception is often recommended if one or both partners has a higher risk of passing on certain diseases, like cystic fibrosis or Tay-Sachs disease.

Why consider testing before pregnancy?

Preconception testing and screening can identify factors that could negatively affect your health or your pregnancy. A general history, including family history and laboratory testing, are essential to identify potential issues, which may need to be addressed prior to becoming pregnant.

A routine prenatal screen includes testing for anemia, blood type and infectious diseases. Based on your medical history and ethnic background, additional tests may be recommended.

The routine panel includes: a complete blood count (CBC), blood type and screen, testing for immunity to rubella and varicella (if you have never had chickenpox), and hepatitis B, HIV and syphilis infection testing.

Types of nongenetic preconception testing

While genetic testing is a crucial aspect of preconception testing, it is not the only one. Blood tests can identify both nongenetic conditions we test for before conception and some genetic conditions, like cystic fibrosis. Other inheritable genetic conditions affecting pregnancy and a healthy child require genetic testing.

Complete blood count

The complete blood count (CBC) test checks for anemia, or low iron and/or blood count, which could negatively affect your pregnancy.

Blood type and screen

The blood type and screen checks for specific antibodies in your blood that can affect the health of your pregnancy.

Your red blood cells have two important proteins, the AB protein and the Rh protein. These proteins identify your blood type. Depending on the proteins that coat your red blood cells, your blood type is either A, B, AB, or O (when no protein is present).

The other protein, Rh (Rhesus factor), is either present or absent and designates your cells as A-positive, A-negative, B-positive, B-negative and so forth.

Eighty-five percent of people are Rh-positive and 15 percent are Rh-negative. If a woman is Rh-negative and her partner is Rh-positive, then her baby has a chance of being Rh-positive.

In these cases, the woman can develop antibodies to the baby’s blood. These antibodies can lead to complications of pregnancy in future pregnancies (not the first pregnancy), such as pregnancy loss or growth restriction.

There are ways to significantly reduce the chances of pregnancy complications due to mismatched blood types and antibodies. Therefore it is extremely important to identify which patients will need observation and treatment during pregnancy.

Counsyl preconception testing

Also referred to as the universal genetic test, Counsyl is a non-invasive, saliva-based test that checks for more than 100 genetic diseases, including cystic fibrosis, Tay-Sachs, spinal muscular atrophy, and sickle cell disease.

Insurance typically covers the cost of a Counsyl test. As with other preconception testing, if a couple opts for in vitro fertilization (IVF) it is possible to use pre-implantation genetic diagnosis (PGD) to test embryos for these genetic diseases before they are transferred into the woman’s uterus.

Rubella

Rubella, also known as the German measles, is caused by a virus that is transmitted through coughing or sneezing. All women of reproductive age should be screened for rubella, and if not immune, offered the rubella vaccine prior to conception.

Pregnant women who contract rubella are at risk for having a miscarriage, early death of a newborn, or a child with congenital rubella syndrome (CRS), characterized by deafness, blindness, cataracts, heart defects, mental retardation, bone defects, and damage to the liver and spleen. Serious complications for the mother are rare.

A simple blood test can determine if you are immune to rubella. If you are immune, rubella essentially poses no risk to your pregnancy.

Most people born in the United States have received the MMR, or measles, mumps, rubella vaccine. However, upon testing, not all reproductive age women developed immunity. Therefore, all women of reproductive age should be screened.

Women who are not immune should receive a rubella vaccination four weeks prior to attempting conception. If you were previously vaccinated for rubella but do not have immunity, a series of two shots, one month apart, are recommended.

After the two vaccinations, a woman must wait one month before attempting to become pregnant.

Hepatitis

Hepatitis is a condition caused by various viruses that affect the liver. Hepatitis B and C are the most common viruses to adversely affect pregnancy.

Some women carry this virus without knowing it, and can transmit it to their child. It is important to determine if a woman with hepatitis is healthy enough to proceed with pregnancy. Women who have or are carriers of hepatitis should be thoroughly counseled on pregnancy risks.

There is a vaccine for hepatitis B, which can be received during pregnancy. There is no vaccine for hepatitis C.

HIV

Human immunodeficiency virus, or HIV, is the virus that causes AIDS, a condition in which the immune system fails and life-threatening opportunistic infections may occur.

Many women and men with HIV have no symptoms for years prior to developing AIDS.

If left unidentified and untreated in pregnancy, transmission rates to the baby are approximately 25 percent. With vigilant treatment and management of the mother during pregnancy, transmission rates to the infant may fall to less than two percent.

There is no vaccine for HIV.

Syphilis

Syphilis is a sexually transmissible disease caused by the bacterium Treponema pallidum. Like HIV, syphilis can remain silent for years. It can also mimic many other diseases and cause a wide array of symptoms.

Syphilis can be transmitted to a baby, resulting in stillbirth or infant death. Babies can be born without symptoms and later become developmentally delayed or even die.

Women with syphilis can be treated prior to pregnancy.

Cystic fibrosis genetic screening

Cystic fibrosis (CF) is an inherited lung and digestive disease causing variable symptoms, including lung congestion, pneumonia, diarrhea and poor growth. More than 25,000 Americans have CF, and 850 new cases are diagnosed each year.

Currently there is no cure for CF, though this is an active area of research in the scientific and medical community. The American College of Obstetricians and Gynecologists recommends that your doctor offer screening for CF if you are considering pregnancy.

CF is an inherited disease caused by gene abnormalities. Most people have two normal copies of the CF gene. Couples with normal copies of CF genes are not at increased risk for having a baby with CF. CF carriers have one normal copy and one abnormal copy of the CF gene. An individual with CF has two abnormal copies of the CF gene. 

If both parents are carriers (each has a copy of the abnormal gene), there is a 1 in 4 (25 percent) chance that the baby will have CF.

Many people with CF have severe symptoms and die at a young age despite extensive medical intervention. CF does not affect intelligence or the overall appearance of a child. Some people with CF have so few symptoms that they are unaware that they are even affected.

The average life expectancy for a person affected with CF is approximately 30 years. The average medical cost for an individual with CF is approximately $15,000 to $20,000/ year, or between $300,000 and $500,000 over their lifetime.

CF preconception testing

A blood test can determine if you are a carrier of the most common CF gene mutations. This blood test does not detect all possible mutations. The risk of having a baby with CF is never zero.

If testing shows that both partners are carriers, testing can be performed in pregnancy to determine if your baby is affected with CF.

Alternatively, in vitro fertilization (IVF), and pre-implantation genetic diagnosis can be performed to test embryos for CF, to ensure that a couple does not have an affected child.

Donor oocytes (eggs) or donor sperm from a non-CF carrier may also be used to ensure that the couple does not have an affected child.

Strongly consider testing if you are:

• • A couple with a family history of CF.
  • A couple that would like to know, so that you can prepare for a child with special needs.
  • A couple who would terminate a pregnancy affected by CF.
  • A couple who would pursue IVF to avoid the possibility of a child with CF.

What does a negative CF test mean?

If one individual out of a couple (either the man or the woman) tests negative for the most common CF gene mutations, the overall risk of having a baby with CF is reduced markedly, but not eliminated.

If both couples test negative, the risk is further reduced. To have a child with CF, both parents must be carriers.

For example:

If a Caucasian woman tests negative for the CF gene, the couple’s risk goes from one in 2,500 to one in 12,500 (an 80 percent risk reduction). If both partners test negative, the risk is further reduced to one in 62,500.

If one partner is found to be a carrier, is known to be a carrier, or actually has CF, a negative test in the other partner does not reduce the risk as much.

For example:
If the man is a carrier (has one copy of the CF gene), and the woman is unaffected, the risk to the offspring is one in 250.

The actual risk may be lower, depending on the mutations carried, and consultation with a genetic counselor may be warranted.

Sickle cell anemia testing

Sickle cell anemia is a chronic, hereditary disorder of the blood. It is caused by an abnormal hemoglobin molecule, which makes the oxygen-carrying red blood cells misshaped and prone to collapsing.

The blood cells create blockages in small blood vessels, resulting in painful episodes called “crises” which usually occur as severe, debilitating bone pain. Sickle cell patients are much more prone to infections and are at increased risk for strokes.

Children often have delayed physical and sexual maturation, low self-esteem and depression. They require frequent medical interventions.

What are the chances that my baby will have sickle cell anemia?

Approximately one in 500 African Americans and one in 1,000 Hispanics has sickle cell anemia. Males and females are equally affected. Other ethnic groups at increased risk include Greeks, Italians, Turks, Arabs, Southern Iranians and Asian Indians.

An affected person must have two copies of the sickle cell gene. People with one copy of the gene are generally unaffected. They are called “carriers.” Carriers who have children have a 50 percent chance of passing the abnormal gene to their child.

Approximately one in 12 African Americans is a carrier for sickle cell anemia. For a child to get sickle cell anemia, both parents must carry an abnormal gene.

Preconception testing for sickle cell anemia

Testing for sickle cell is simple, requiring only a blood test. Insurance generally reimburses the cost of sickle cell screening. If one partner’s test is positive, meaning they are a carrier, then the other partner should be tested to determine the risk to a child.

Management options for carriers of sickle cell anemia

Prior to pregnancy, couples may opt to undergo in vitro fertilization (IVF) and perform pre-implantation genetic diagnosis (PGD) to ensure that embryos being placed into the uterus are not affected.

Alternatively, donor sperm or donor eggs (oocytes) from a non-carrier could also be considered.

During pregnancy, invasive testing such as amniocentesis or chorionic villi sampling can determine if the baby is affected. Choices regarding termination of an affected child would be made based on the personal beliefs of the parents.

If a child is born with sickle cell anemia, management of symptoms and vigilant medical care is the current mainstay of treatment. Affected individuals can be cured with bone marrow transplants, but these treatments are not widely available.

Genetic testing for diseases and conditions

Many genetic disorders occur when an individual carries two defective genes, one inherited from each parent. If an individual has only one faulty copy of a particular gene, he or she may not show any signs of the disease but remain a “carrier” for it. In such cases, the child receives two defective genes, one from each parent, and develops the disease.

There are over 7,000 known genetic disorders. Many of these are serious and life threatening. Some of the more common ones include: Cystic Fibrosis, Sickle Cell Anemia, Thalassemia Major, Duchenne Muscular Dystrophy, Huntington Disease, Spinal Muscular Atrophy, and others (see below).

People with a higher risk for having a child with a genetic illness below may want to consider genetic screening. This includes individuals with:

• close relatives with genetic illnesses.
• parents who already have a child with a genetic illness
• women who have had two or more miscarriages

Tay-Sachs/Canavan/Gaucher/Dysautonomia genetic screening

Tay-Sachs, Canavan and Gaucher are incurable, hereditary diseases primarily affecting the central nervous system. They result from enzyme deficiencies that cause abnormal metabolism of fatty substances in the brain.

These substances accumulate and destroy brain cells. In most cases of Tay-Sachs and Canavan, the children die before the age of 5. The severity of Gaucher is more variable.

Like cystic fibrosis, both parents need to carry the genes causing these diseases. In general, the only way for a child to be affected is if he or she inherits an abnormal copy from the mother and the father.

Simple blood tests can determine if you are a carrier of the Tay-Sachs, Canavan or Gaucher mutations. All three of these diseases are most common in people with Eastern European Jewish ancestry (Ashkenazi Jews). However, other ethnicities are at increased risk, especially for Tay-Sachs.

Approximately one in 30 Ashkenazi Jews is a carrier for the Tay-Sachs gene, meaning they carry one gene for the disorder. An affected individual has both genes affected. People with Tay-Sachs have two copies of the abnormal gene.

Couples with normal copies of Tay-Sachs genes are not at increased risk for having a baby with Tay-Sachs.

Carriers have one normal copy and one abnormal copy of the Tay-Sachs gene. If both parents are carriers (each has a copy of the abnormal gene), there is a 1 in 4 (25%) chance that the baby will have Tay-Sachs.

If both partners are carriers, additional preconception testing can be performed in pregnancy to determine if your baby is affected with Tay-Sachs.

Alternatively, in vitro fertilization (IVF) can be performed to test embryos for Tay-Sachs, or donor gametes from non-carrier individuals may be used to ensure that a couple does not have an affected child.

Fragile X premutation testing

Fragile X is the most common cause of inherited mental impairment, resulting in a spectrum of dysfunction ranging from learning disabilities to autism and severe mental retardation. Fragile X occurs in approximately one in 3,600 males and one in 5,000 females.

The disorder is caused by the inactivation of a gene, called the FMR1 gene, which is on the X chromosome. Because females have two copies of the X chromosome, a woman might carry the full mutation on one chromosome without knowing it.

However, she is at increased for premature menopause and for having a baby with the disorder.

Males have one X chromosome and one Y chromosome and therefore do not get a back-up copy of the FMR1 gene. This is why they are more severely affected when they inherit one abnormal copy of the FMR1 gene.

Frequently, until a child is born severely mentally retarded, no one ever knew the family was at risk. In fact, the mutation can develop in a family over time.

All X chromosomes contain a section of what are called tri-nucleotide repeats. A normal X chromosome has fewer than 60 tri-nucleotide repeats in Fragile X region. However, these tri-nucleotide sections can expand from generation to generation.

Once the tri-nucleotide repeat section becomes long enough (between 60-200 repeats), it becomes unstable and is very likely to expand in the next generation, resulting in the full mutation. One in 250 women carries the Fragile X premutation.

Individuals with the following should consider preconception testing for Fragile X premutation:

• Family history of autism, learning disabilities or otherwise unexplained mental retardation.
• Premature ovarian failure – these women are at increased risk for having the premutation, and testing should be considered for their siblings.

The prevalence of Fragile X mutations among women with diminished ovarian reserve is being actively studied, but at this time is unknown. Some experts recommend preconception testing for Fragile X mutations among any woman with diminished ovarian reserve under the age of 40.

However, we agree with the committee statement of the American Society for Reproductive Medicine, which recommends that genetic testing among this population not be widely performed until ongoing studies determine the prevalence of Fragile X premutations among these women.