Here is a question that was posted by a physician to the ASCLS Cosumer Web Forum.
We have a patient who has delivered a normal baby in 2013. She recently called to let us know that her twin sister was pregnant with twins and lost one of them at 31 weeks due to the MTHFR mutation. My patient wants to be tested before she decides to have any more children. Please advise.
Thank you for your questions. The short answer is that it is not necessary for your patient to be tested, though you may wish to order a thrombosis risk profile for her peace of mind. Here's some detail.
There are several thrombosis risk factors that are associated with pregnancy loss and venous thromboembolic disease, especially the acquired risk factor lupus anticoagulant with its associated anti-phospholipid antibodies. There are also several "thrombophilic" mutations, notably antithrombin, protein C, and protein S deficiency; the factor V Leiden mutation, and the prothrombin 20210 mutation.These are the assays that comprise a typical thrombosis risk factor profile.
However, there are many medical and anatomic reasons for pregnancy loss, particularly in the case of twins. The thrombosis risk factors are only part of the picture, thus their absence only goes partway in assuring a successful pregnancy.
The MTHFR 667 mutation is no longer considered a thrombosis risk factor, though it has been shown to associate with homocysteinemia (elevated blood homocysteine). There are several reasons for this change. First, MTHFR 667 is so common (about 11% of North Americans are homozygous for MTHFR 667), it is now classified as a polymorphism and not a mutation. Second, although homocysteinemia has been associated with thrombosis, mostly arterial clotting like heart attacks and strokes, reducing the level of homocysteine in people with homocysteinemia provides no improvement in their risk of a thrombotic event. This seems odd, but it has been proven repeatedly with clinical trials. Finally, since 1998, US public health policy requires folate supplementation of cereal grains, consequently fewer North Americans now have homocysteinemia, whether they have the MTHFR 667 polymorphism or not. By the way, there is an additional MTHFR polymorphism, 1298, but it has been "demoted" just like MTHFR 667. Reference laboratories still offer the MTHFR 667 and 1298 polymorphism tests, but they no longer include them in their standard thrombosis risk testing profile.
I'm posting this to invite your comments about the MTHFR mutations and thrombosis risk.