MTHFR and Pregnancy Complications

Is Testing Right for Me? I Have My Test Results

MTHFR and Pregnancy Complications

What Is MTHFR?

MTHFR stands for "methylenetetrahydrofolate reductase." MTHFR is an enzyme that helps process vitamin B9, which is also called folic acid or folate. Folate helps the body breakdown, use, and make new proteins.

One of folate's most important jobs involves changing an amino acid called homocysteine into another amino acid called methionine. Both of these amino acids are essential for many body functions. However, having too much homocysteine may raise your risk for a number of health conditions.

MTHFR Variants

Our DNA is made up of thousands of genes. These genes contain instructions for making enzymes essential for survival. For example, the MTHFR gene provides instructions for making the MTHFR enzyme. Changes in the gene can cause problems with the enzyme it makes.

Two common changes in the MTHFR gene make an enzyme that doesn't work as well as normal. These changes or "variants" are called C677T and A1298C. The C677T variant causes more problems with the MTHFR enzyme than the A1298C variant.

MTHFR and Possible Health Effects

When MTHFR isn't working as well as usual, it processes less folate. Less folate leads to a buildup of homocysteine. Too much homocysteine has been linked to health problems like abnormal clotting, heart disease, and some pregnancy complications.

No one knows yet if homocysteine causes these health problems or if health problems cause high homocysteine. Researchers are just beginning to look at whether treating high homocysteine with B vitamins, like folate, also lowers the risk for these conditions.

Having two MTHFR variants may cause higher homocysteine. While researchers have also looked for a link between MTHFR and the health problems related to high homocysteine, the results haven't been clear. Some studies find a link and others don't. Usually, if there is any risk from MTHFR, it is relatively small.

 MTHFR variants seem to have more impact in other countries where people don't get as many B vitamins as people in the U.S.

It is rare that you or your doctor would need to know if you have MTHFR variants.

This section focuses on MTHFR and abnormal blood clotting. If you've had a blood clot, like a deep vein thrombosis, you may want to read about factor V Leiden and prothrombin gene mutations.

There is also a section about MTHFR and pregnancy complications.

Next: MTHFR and Pregnancy Complications

Why are you considering MTHFR variant testing?

I have had a blood clot.

I have a known risk factor for clotting, like factor V Leiden or a prothrombin mutation.

I have had pregnancy complications.

I have higher than normal amounts of homocysteine in my blood.

I have a family history of MTHFR variants.

None of these

People who have had a blood clot are more likely to have high homocysteine. This doesn't mean that homocysteine causes the clot. No one knows yet why these are linked or if lowering homocysteine will prevent these problems.

MTHFR variants seem to be less important than homocysteine levels, especially in the North America. Remember that MTHFR variants don't cause high homocysteine in people who get enough B vitamins, especially folate. Many foods in North America are made with extra folate.

If any test is done, many experts recommend just measuring blood homocysteine levels. This test will find high homocysteine, no matter what the cause is. If you decide to have MTHFR testing anyway, this is what your results will probably mean:

  • If you have two MTHFR variants, you are more likely to develop high homocysteine — but only if you don't get enough B vitamins. However, many people have two MTHFR variants and/or high homocysteine and don't have abnormal blood clots. So, homocysteine and MTHFR alone don't explain your clot. Your MTHFR results also don't necessarily mean that you need more B vitamins, but you might if you have high homocysteine. You should talk to your doctor before starting or stopping any vitamin supplements or other drugs.
  • If you have one or no MTHFR variants, you don't have a tendency to develop high homocysteine from MTHFR variants. One variant isn't enough to cause high homocysteine on its own. There are many other possible reasons for high homocysteine. These results don't mean that your homocysteine is normal or that you won't develop high homocysteine in the future.

More than one reason for clotting greatly raises the risk for making an abnormal blood clot. Since you have a clotting risk factor already, your doctors may recommend testing for a group of conditions that could raise your risk even more.

High homocysteine is one risk factor for clotting. MTHFR variants can cause high homocysteine in people who don't get enough B vitamins. MTHFR variants seem to be less important than homocysteine levels, especially in North America where many foods are made with extra folate.

Many experts recommend just measuring blood homocysteine levels. This test will find high homocysteine, no matter what the cause is. If you decide to have MTHFR testing anyway, this is what your results will probably mean:

  • If you have two MTHFR variants, you are more likely to develop high homocysteine — but only if you don't get enough B vitamins. If you have or get high homocysteine, your clotting risk could go up. However, many people with two MTHFR variants and/or high homocysteine never have a blood clot. Your MTHFR results don't necessarily mean that you need more B vitamins, but you might if you have a blood test that finds high homocysteine. You should talk to your doctor before starting or stopping any vitamin supplements or other drugs.
  • If you have one or no MTHFR variants, you don't have a tendency to develop high homocysteine from MTHFR variants. One variant isn't enough to cause high homocysteine on its own. These results don't mean that your homocysteine is normal or that you won't develop high homocysteine in the future.

People who have had pregnancy problems like early losses, placental abruption, or preeclampsia are more likely to have high homocysteine. This doesn't mean that homocysteine causes the pregnancy problems. No one knows yet why these are linked or if lowering homocysteine will prevent these problems.

MTHFR variants seem to be less important than homocysteine levels, especially in North America. Remember that MTHFR variants don't cause high homocysteine in people who get enough B vitamins, especially folate. Many foods in North America are made with extra folate. Prenatal vitamins with extra folate are prescribed for pregnant women and women planning to become pregnant.

If any test is done, many experts recommend just measuring blood homocysteine levels. This test will find high homocysteine, no matter what the cause is. If you decide to have MTHFR testing anyway, this is what your results will probably mean:

  • If you have two MTHFR variants, you are more likely to develop high homocysteine — but only if you don't get enough B vitamins. However, many people have two MTHFR variants and/or high homocysteine and don't have pregnancy problems. So, homocysteine and MTHFR alone don't explain your pregnancy problems. Your MTHFR results also don't necessarily mean that you need more B vitamins, but you might if you have high homocysteine. You should talk to your doctor before starting or stopping any vitamin supplements or other drugs.
  • If you have one or no MTHFR variants, you don't have a tendency to develop high homocysteine from MTHFR variants. One variant isn't enough to cause high homocysteine on its own. There are many other possible reasons for high homocysteine. These results don't mean that your homocysteine is normal or that you won't develop high homocysteine in the future.

If you have had a higher-than-normal blood homocysteine level, the most common reason is B vitamin deficiency — especially folate. Low kidney function and several other medical conditions and lifestyle issues can cause high homocysteine. See Who Is At Risk for High Homocysteine for more information.

MTHFR variant testing isn't recommended for everyone with high homocysteine. If you and your doctor decide that you need treatment, that decision is based on your high homocysteine — not the MTHFR results. MTHFR testing may not change your healthcare.

If you decide to have testing, this is what your results will probably mean:

  • If you have two MTHFR variants, the results may help explain why you have high homocysteine. This is especially true if you also don't get enough B vitamins. Your MTHFR results don't mean that you need more B vitamins, but your homocysteine results probably do. You should talk to your doctor before starting or stopping any vitamin supplements or other drugs.
  • If you have one or no MTHFR variants, your results don't explain your high homocysteine. One variant isn't enough to cause high homocysteine on its own.

MTHFR gene variants are inherited. If you have a close family member with a variant, you have a higher chance to have a variant. You need to have inherited two variants — one from each parent — to be at risk for high homocysteine caused by MTHFR. Even people with two MTHFR variants usually have normal homocysteine because they get enough B vitamins.

Most experts don't recommend testing family members of someone with one or more MTHFR variants. MTHFR variants are extremely common and usually don't change your medical care.

If you are concerned, you might consider having blood homocysteine testing. Your homocysteine levels, not your MTHFR results, are most useful to help you and your doctor decide if you need more B vitamins. If you decide to have MTHFR testing anyway, this is what your results will probably mean:

  • If you have two MTHFR variants, you are more likely to develop high homocysteine — but only if you don't get enough B vitamins, especially folate. Many foods in North America are made with extra folate, so MTHFR variants may have less effect here. Your MTHFR results don't necessarily mean that you need more B vitamins, but you might if you have high homocysteine. You should talk to your doctor before starting or stopping any vitamin supplements or other drugs.
  • If you have one or no MTHFR variants, you don't have a tendency to develop high homocysteine from MTHFR variants. One variant isn't enough to cause high homocysteine on its own. There are many other possible reasons for high homocysteine. These results don't mean that your homocysteine is normal or that you won't develop high homocysteine in the future. Good diet and lifestyle choices are always recommended.

High homocysteine and MTHFR variants have been linked to many other health conditions. These aren't covered here. However, the issues are generally the same regardless of the health condition. Homocysteine levels are usually more important than MTHFR variants. Vitamin supplements of folate, B6, and B12 can usually lower homocysteine. However, we usually don't know that lowering homocysteine will actually lower the risk for the health problem.

If you have a reason for MTHFR testing that isn't covered here, talk to your doctor or a genetic counselor about whether testing might be useful for you.