Should you test for MTHFR gene mutation while pregnant or after miscarriage?
October 22, 2024
After pregnancy loss, many women search the web for answers about what might have caused their miscarriage.
Unfortunately, they may come across misinformation, such as concerns about the MTHFR (methylenetetrahydrofolate reductase) gene mutation. MTHFR gene variants are often falsely linked to miscarriage – with articles and forums dedicated to conversations about the gene and myths about potential ill effects on pregnancy.
The MTHFR gene codes for the MTHFR enzyme, which helps convert the 5,10-methylenetetrahydrofolate we consume into 5-methyltetrahydrofolate, the primary form of folate in our blood and the form utilized in the remethylation of homocysteine to methionine, an essential amino acid. This enzymatic function helps repair DNA, build cells, and manage the body’s levels of the chemical homocysteine, which can cause inflammation, excess clotting, and blood vessel damage.
When the MTHFR gene is mutated, folate conversion is slightly less effective, and homocysteine levels can rise. However, changes from an MTHFR gene mutation are typically so minor that no risk is posed to a pregnancy.
No peer-reviewed, validated research has associated MTHFR variants with pregnancy loss. And MTHFR gene mutations are very, very common.
There are two particular variants in MTHFR that are often included in a test of the gene. Over half of all people have a variant in one or both of their two copies of the gene. About 25% of Hispanic people and 10% to 15% of white people in North America have a variant on both copies of their MTHFR gene. Because of this, we do not recommend genetic testing or screening for MTHFR mutations. Even if we find a mutation, it will not provide context for the cause of a miscarriage.
However, we do recommend that women optimize their health through nutrition – such as getting enough folate – and manage chronic health conditions that cause inflammation. Inadequate folate consumption among those with mutations can increase the risk for hyperhomocysteinemia, which can increase the risk for atherosclerosis and arterial blood clots.
There are many acquired causes of hyperhomocysteinemia unrelated to MTHFR mutations including renal disease, diabetes, vitamin deficiencies, and some rare metabolic diseases. Mild to moderate elevations in homocysteine alone have not been shown to increase the risk for venous clots. Laying this groundwork of good nutrition will improve your health in the short term and set you up for the healthiest possible pregnancy in the future.
After pregnancy loss, it is natural to seek answers. Miscarriage is not your fault, and getting misinformation can add to the anxiety and pain of grieving the loss. Let’s clear the air and answer common questions and the myths surrounding MTHFR gene variants and pregnancy.
"Genetic testing can be performed to identify whether a chromosome abnormality was involved. Most abnormalities that are identified occurred by chance and do not mean that a person has a high risk of another miscarriage."
Can the MTHFR gene mutation affect pregnancy?
More than half of people have a variant on at least one of their MTHFR genes, and a significant slice of the population has two genes with variants. Almost none of these people have adverse effects. Still, myths persist about three conditions that are often mistakenly attributed to MTHFR gene mutations.
Miscarriage
There has been no proven link between MTHFR gene variants and miscarriage. An MTHFR mutation changes only that specific gene, not the entire chromosome. Approximately 60% of early miscarriages are due to chromosomal abnormalities that change or duplicate an entire chromosome, such as:
- Trisomy 16: An extra copy of chromosome 16.
- Triploidy: Having three sets of chromosomes instead of two.
- Turner syndrome: One of the two sex chromosomes is missing or incomplete.
Genetic testing can be performed on tissue from a miscarriage to identify whether a chromosome abnormality was involved. Most abnormalities that are identified occurred by chance and do not mean that a person has a high risk of another miscarriage. However, in about 5% of cases of recurrent miscarriage, the cause is due to a balanced chromosome translocation in one of the parents, a genetic condition in which chromosomes are rearranged but no genetic material is lost or gained. This condition can increase the risk of miscarriage for that couple from the average of 15%-25% up to 30%.
Spina bifida
A baby’s neural tube, which forms the spine and surrounding structures during early pregnancy, should fuse completely before birth. If it doesn’t, gaps or openings in the spine can result in spina bifida – one of the most common birth defects.
Spina bifida damages the spinal cord and nerves, complicating movement, sensation, and control of the bladder and bowels.
Spina bifida can also be associated with very low folate levels. However, the MTHFR gene does not decrease folate levels enough to cause spina bifida. Most people, even those with two MTHFR gene mutations, will get enough folate in a balanced diet to help prevent a fetus from developing spinal bifida. Adequate folate levels in advance of conception are well validated to be impactful in reducing the risk of neural tube defects.
The rates for spina bifida are 1 in every 2,875 births in the U.S. – far fewer than the number of people with an MTHFR gene mutation.
Inflammation or blood clots in the mother
Variants in the MTHFR gene can result in a very small elevation in inflammation. High homocysteine levels can also very slightly increase the risk of blood clots by damaging blood vessels and disrupting the balance of clotting factors.
The change from an MTHFR mutation is so minor that it is unlikely to affect the mother’s health or the pregnancy. However, excess inflammation caused by a range of common health conditions can affect maternal and pregnancy health. Some of these include diabetes, autoimmune diseases like rheumatoid arthritis, gastrointestinal diseases like inflammatory bowel disease, and high blood pressure.
As for venous blood clots, factors such as genetic predisposition, prolonged immobility, certain medications, clotting factor abnormalities, or underlying health conditions are more commonly associated with a significant risk of clotting. Anticoagulation medications such as Heparin or Lovenox do not impact any of the pathways related to MTHFR or folate metabolism, so there is no indication for use of these among women with MTHFR mutations.
Most of these conditions can be controlled with support from a health care provider. Managing chronic conditions can improve your long-term health and help you have a healthy pregnancy. Regular sleep, exercise, and a well-rounded diet also can help improve your overall well-being and better manage symptoms from any chronic conditions you have.
Related reading: It’s not your fault: Understanding miscarriage
Get enough folate to manage inflammation
While it’s true that MTHFR gene variants don’t cause high-risk pregnancy or miscarriages, it’s still important to manage your homocysteine levels by getting enough folate.
Overall, women need 400 micrograms (mcg) of folate every day from vitamins B9, B12, and B6. For pregnant women, this number increases to 600 mcg a day. Most people won’t need to change their diet to get enough of this essential vitamin. Folic acid (the artificial form of folate) is a major component of most women’s prenatal vitamins. We recommend taking a vitamin with at least 400 mcg of folic acid for the three months leading up to pursuing conception.
Since around half of pregnancies in the U.S. are unanticipated, daily consumption of a vitamin that has 400 mcg of folic acid can help prevent up to 70% of neural tube defects.
If you’ve previously given birth to a child with a neural tube defect, the recommended dose of folic acid to take before and during pregnancy increases further, to 4 milligrams (4000 mcg). Women who take anti-seizure medications should talk to their doctors about potentially getting additional folate, as some common anti-seizure medications can decrease folate levels in the body.
Most people with MTHFR variants don’t need additional supplements and will get a good amount of folate in any well-balanced diet. Talk with a health care provider if you’ve been experiencing signs of a folate deficiency, including:
- Disturbed vision
- Ulcers in your mouth
- A sore and red tongue
- Exhaustion
- Pins and needles
- Muscle weakness
If you show any of these symptoms, your provider may prescribe folic acid or ask you to increase the folate in your diet. Myths persist that activated folate supplements (not dietary folate) are necessary to decrease homocysteine. This isn’t true – people with MTHFR mutations can still process folate, just at a very slightly reduced rate.
Some ways to get the necessary vitamins to decrease homocysteine levels include:
Folate, also known as Vitamin B9 (600 mcg recommended during pregnancy)
- Leafy greens: ~30-200 mcg per cup cooked
- Legumes: ~180-360 mcg per cup cooked
- Citrus fruits: ~40-50 mcg per medium fruit
- Fortified foods: ~100-400 mcg per serving (varies by product)
- Avocados: ~60 mcg per half avocado
- Brussels sprouts: ~80-100 mcg per cup cooked
Vitamin B12 (2.6 mcg recommended)
- Animal liver and kidneys: ~70-80 mcg per 3.5 ounces
- Fish: ~2.5-5 mcg per 3.5 ounces
- Meat: ~1-3 mcg per 3.5 ounces
- Milk: ~1-1.5 mcg per cup of milk or 1 ounce of cheese
- Eggs: ~0.6 mcg per large egg
Vitamin B12 is only found in animal products. Vegans and vegetarians with limited egg and dairy consumption will need supplements to hit their daily recommended goal.
Vitamin B6 (1.9 mcg recommended during pregnancy)
- Poultry: ~0.6-0.7 milligrams (mg) per 3.5 ounces
- Fish: ~0.9 mg per 3.5 ounces
- Bananas: ~0.4 mg per medium banana
- Potatoes: ~0.6 mg per medium potato
- Nuts: ~1.2 mg per ounce
- Whole grains: ~0.5 mg per cup cooked
The MTHFR gene doesn’t adversely affect pregnancy, though it’s understandable why so many people turn to it to understand pregnancy loss. Instead of any one gene, it’s holistic care of your body and mind that can help you plan for future pregnancies. Keep up with your prenatal appointments and talk with your providers about any concerns.
To talk with an expert about genetic testing during or before pregnancy, call 214-645-8300 or request an appointment online.
