Preeclampsia, Folate, and your Genes.

Updated: Jul 14

The world of Nutrigenomic research has been advancing, giving medical providers the opportunity to take individualized medicine to a whole new level. This is especially meaningful during pregnancy, a very delicate period of time when we take every precaution to support the best possible outcomes for mother and baby.


An important nutritional discovery took place in 1965, when we acknowledged the importance of adequate folate (Vitamin B9) for healthy fetal neurological development.

Folate is a nutrient needed for building neurotransmitters, DNA and for “methylation reactions,” a process involved in many physiological functions including DNA synthesis and repair, producing myelin for healthy brain and nerve cells, red blood cell production, and much more!


It’s not hard to see why these activities are crucial to growing a healthy fetus, and why optimal folate levels are important for a healthy pregnancy. For more information about folate, see our folate handout on our website: www.naturespathfamilywellness.com/handouts.


The genes involved in folate metabolism include:

  • DHFR

  • MTHFD1

  • MTHFR

  • MTRR

  • MTR

  • FOLR1

  • FOLR2

  • SLC19A1

  • MTHFS

  • SHMT

MTHFR is the most well-known and researched gene. More than a 1/3rd of the US population carries a genetic variant or Single Nucleotide Polymorphism a.k.a “SNP,” in one of these genes. These SNPs slow the enzymes that break down folate into a form that the body can use. For example, individuals with SNPs in their MTHFR gene can have almost 75% less available active folate (5-MTHF) due to having a slow acting MTHFR enzyme.


SNPs that affect folate processing and methylation have been shown to influence pregnancy and may increase the risk of pregnancy related conditions including preeclampsia, HELLP Syndrome, eclampsia, uteroplacental insufficiency, intrauterine growth restriction, recurrent pregnancy loss, gestational hypertension, placental abruption, neural tube defects, Down syndrome, subfertility, and miscarriage.


The relationship between these genetic SNPs and Preeclampsia is of particular interest because this condition is a major cause of maternal and perinatal mortality. Preeclampsia is a disorder that occurs during the second half of pregnancy and is characterized by constriction of maternal blood vessels, which causes high blood pressure and potential damage to maternal organs, including the placenta.


*A key sign of organ damage is protein loss through the urine (proteinuria), something your doctor or midwife will look for.


Research shows a hereditary component to preeclampsia that comes from both the maternal and paternal genes, both men and women born of a preeclamptic pregnancy are more likely to have a preeclamptic pregnancy of their own. Mothers with the MTHFR C677T genetic variant may have up to 5 times the risk of developing preeclampsia when compared to mothers without the genetic variant.

(FYI: This risk increases dramatically in areas of high air pollution!)


A clue to understanding why defects with folate processing may contribute to preeclampsia is by diving deeper into how we think preeclampsia occurs in the first place…


The basic idea is that early on in pregnancy the placenta doesn’t develop well and poorly attaches to the wall of the uterus. This leads to poor blood flow from mother’s uterus to the placenta, which causes the distressed placenta to release inflammatory chemicals. These chemicals are damaging to the mother’s own blood vessels, and cause her vessels to constrict, which decreases the blood flow to the mother’s body and organs, including the placenta. Decreased blood flow to the placenta perpetuates this cascade that we call preeclampsia.

It is a vicious cycle and it is very dangerous for both mother and baby!


So what does the process of preeclampsia have to do with folate?

  • Folate helps keep blood vessels wide and open through a chemical called nitric oxide, therefore a folate deficiency can affect how well blood vessels dilate and allow for healthy blood flow.

  • Additionally, the amino acid Homocysteine requires folate to be broken down. If folate is deficient, homocysteine will become elevated which leads to the production of toxic "free radicals." These free radicals cause inflammation and a nasty process called "endothelial dysfunction," which causes decreased placental growth.

Together, these processes may explain the connection between how genetic variants that decrease available folate can contribute to the process of preeclampsia.


Some other folate related “SNPs” that are associated with preeclampsia:

  • The genetic variant MTR A2756G in either mother or fetus increases the likelihood of developing preeclampsia and Intrauterine Growth Restriction, however this risk goes down significantly when mothers supplement with adequate folate (yay!).

  • Mothers with 2 copies (homozygous) of the MTHFD1 G1958A SNP may have increased risk of developing intrauterine growth restriction, which is associated with preeclampsia.

  • MTRR SNPs may be associated with Preeclampsia, as placentas from preeclamptic pregnancies can have 50% less expression of the MTRR gene when compared to normal pregnancies.


Nutritional and supplemental folate to support genes and reduce risk of pregnancy complications:

  • Eat plenty of natural folate containing foods such as: Fresh green leafy vegetables, legumes (lentils, chickpeas, pinto beans, black-eye peas, peas, black beans, edamame, tofu), avocados, asparagus, broccoli sprouts, beets, non-fortified brewer’s yeast, liver and kidney, nuts and seeds, and fruits (oranges, papaya, mango, pomegranate, kiwi, strawberry).

  • Supplement with at least 400 mcg of folate in the forms of 5-mthf and calcium folinate (not folic acid!) for at least 4 weeks before trying to conceive and continued supplementation until at least 12 weeks after conception (we recommend supplementing throughout the entire pregnancy!).

  • It may be advantageous to supplement with methylated folate, the most usable form that doesn’t require the body’s enzymes to process.

  • One study showed that women with a history of preeclampsia from a previous pregnancy, who supplemented with methyl-folate had half the rates of recurrent preeclampsia!. (we recommend supplementing throughout the entire pregnancy!).


References:

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3. Wu X, Yang K, Tang X, et al. Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for preeclampsia: a meta-analysis. J Assist Reprod Genet. 2015. doi:10.1007/s10815-014-0408-8

4. Haram K, Mortensen JH, Nagy B. Genetic aspects of preeclampsia and the hellp syndrome. J Pregnancy. 2014. doi:10.1155/2014/910751

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6. Khidri FF, Waryah YM, Ali FK, Shaikh H, Ujjan ID, Waryah AM. MTHFR and F5 genetic variations have association with preeclampsia in Pakistani patients: A case control study. BMC Med Genet. 2019. doi:10.1186/s12881-019-0905-9

7. Zhang Y, He X, Xiong X, et al. The association between maternal methylenetetrahydrofolate reductase C677T and A1298C polymorphism and birth defects and adverse pregnancy outcomes. Prenat Diagn. 2019. doi:10.1002/pd.5396

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