Homocysteine and Recurrent Miscarriage - Is There a Link?

Elevated Levels of Homocysteine and Pregnancy Complications

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Is there a link between elevated homocysteine levels and miscarriage?. Universal Images Group/Universal Images Group/Getty Images

If you've had recurrent miscarriages, your doctor may have recommended checking the homocysteine level in your blood. What exactly is homocysteine? How is homocysteine linked with miscarriage and other pregnancy problems?

What is Homocysteine?

Homocysteine is a type of amino acid that is naturally found in the body. At normal levels, it is not harmful, but elevated levels have been found to be associated with miscarriage as well as heart disease..

What Does an Elevated Level of Homocysteine Mean?

An elevated level of homocysteine in the blood results in a condition known as hypercoagulability. The word coagulation refers to blood clotting, and hypercoagulability means that blood clots more easily than it should.

When this occurs in blood vessels, such as the coronary arteries, it may contribute to the clots that block the blood vessels resulting in coronary artery disease.

With pregnancy, it's thought that these tiny blood clots could instead block blood vessels in the placenta, leading to miscarriage.

High Homocysteine and Miscarriage Risk

Elevated homocysteine is not yet proven to cause miscarriage, but there are some commonalities with other conditions which are known to lead to miscarriages. One condition, called antiphospholipid syndrome, may result in both miscarriage and heart disease in an analogous way.

Other Pregnancy Complications Linked with Elevated Homocysteine Levels

Elevated homocysteine is a confirmed risk factor for other problems in pregnancy including:

As with miscarriage, the evidence is conflicting on whether high homocysteine levels cause other pregnancy problems such as:

The Controversy Over Checking Fasting Plasma Homocysteine (tHcy) in Pregnancy

If your doctor checks your homocysteine level, it's important to know that normal homocysteine levels flucuate during pregnancy. In other words, a level taken at one point in time may not, necessarily, represent what your levels are most of the time. There are several nutritional and lifestyle factors that result in day to day variation in level. In addition, changed in blood volume related to pregnancy combined with a number of hormonal changes can result in levels during pregnancy which do not necessarily represent what your level were if you were not pregnant.

The Metabolism and Genetics of Homocysteine Levels

If you have high homocysteine levels, your genetics may be a cause.

People who have variations in the MTHFR gene, especially the C677T variation, are more likely to have high homocysteine levels. And some studies have found a correlation between MTHFR gene variants and increased miscarriage risk.

The leading theory behind the association is that high homocysteine levels in people with MTHFR gene variants pose a miscarriage risk.

Some doctors test for MTHFR gene variants as a part of the recurrent miscarriage testing workup. Others feel it is more valuable to test for homocysteine because not everyone with MTHFR gene variants will have high levels of the amino acid.

What Else Causes High Homocysteine?

MTHFR gene variants are not the only cause of high homocysteine.

MTHFR gene variants are not the only cause of high homocysteine. Your body uses the nutrients folic acid, vitamin B6 and vitamin B12 to metabolize, or use up, homocysteine. People who are deficient in those vitamins can have high homocysteine levels.

A variety of underlying health conditions and medications may also be related to high homocysteine levels.

The Other Health Risks Related to Elevated Homocystein Levels

Though the exact role is unknown, elevated homocysteine levels have been observed in atherosclerosis, heart attacks, stroke, dementia, Parkinson's disease, multiple sclerosis, and epilepsy. It's thought that elevated levels of homocysteine in the blood may have direct toxic effects on both the vascular and nervous system.

Treating Elevated Homocysteine In Recurrent Miscarriages

There are no formal recommendations to check homocysteine levels in women with recurrent miscarriage, and there are no universally recommended treatment protocol for handling elevated homocysteine levels in women who are found to have them.

Some doctors, however, do test homocysteine (or MTHFR gene variants) in women with recurrent pregnancy loss and recommend treatment even in the absence of formal recommendations.

The usual recommendation in women with elevated homocysteine levels is to take high doses of folic acid and B vitamins to improve the body's metabolism of homocysteine. Only do so with your doctors recommendations, however, as elevated levels of these vitamins may not only cause side effects, but could interfere with the absorption of other vitamins. For those who have MTHFR gene variants, supplemental folic acid has not been found to reduce the risk of miscarriage.

A few doctors may recommend anti-clotting therapy, such as heparin or low-dose aspirin, in order to prevent blood clots from forming during pregnancy, but this practice is not standard.

Thankfully, there are studies in progress looking at answers to both the questions on what role elevated homocysteine levels have in pregnancy, and the best way to treat these if present.

Sources:

Ansari, R., Mahta, A., Mallack, E., and J. Luo. Hyperhomocysteinemia and Neurological Disorders: A Review. Journal of Clinical Neurology. 2014. 10(4):281-8.

Hekmatdoost, A., Vahid, F., Yari, Z., Sadeghi, M., Eini-Zinab, J., Lakpour, N., and S. Arefi. Methyltetrahydrofolate vs Folic Acid Supplementation in Idiopathic Recurrent Miscarriage with Respect to Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms: A Randomized Controlled Trial. PLoS One. 2015. 10(12):e0143569.

Levin, B., and E. Varga. MTHFR: Addressing Genetic Counseling Dilemmas Using Evidence-Based Literature. Journal of Genetic Counseling. 2016. 25(5):901-11.

Puri, M., Kaur, L., Walia, G., Mukhopadhhyay, R., Sachdeva, M., Triveldi, S., Ghosh, P., and K. Saraswathy. MTHFR C677T Polymorphism, Folate, Vitamin B12 and Homocysteine in Recurrent Pregnancy Losses: A Case Control Study among North Indian Women. Journal of Perinatal Medicine. 2013. 41(5):549-54.

Murphy, M., and J. Fernandez-Ballart. Homocysteine in Pregnancy. Advanced in Clinical Chemistry. 2011. 53:105-37.

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