MTHFR and Preeclampsia

MTHFR and Preeclampsia

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Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Kari Asadorian - BSN, RN

Medical Reviewer:

Kari Asadorian - BSN, RN
Dr. Nare Simonyan - PhD Pharmaceutical Science

Edited By:

Dr. Nare Simonyan - PhD Pharmaceutical Science

What Is Preeclampsia?

Preeclampsia is a pregnancy disorder involving persistently high blood pressure, which can lead to serious complications in the liver, kidneys, lungs, and/or brain. These complications can occur with or without proteinuria (high levels of protein in the urine) and decreased blood platelets, which often accompanies preeclampsia.1


Preeclampsia usually occurs after the 20th week of pregnancy, most often near term. In pregnant women with previously normal blood pressure, it is diagnosed when systolic blood pressure (SBP) is higher than 140 mm Hg and diastolic blood pressure (DBP) is higher than 90 mm Hg.2 Proteinuria in preeclampsia is defined as protein ≥300 mg within a 24-hour period.


It affects 2-5% of all pregnant women and is the main cause of one-sixth of all preterm births. Women affected by preeclampsia have significantly higher risks of hypertension and cardiovascular disease later in life.3


Major healthcare authorities describe preeclampsia as a leading cause of organ damage, stroke, and long‑term cardiovascular disease in pregnant women, as well as preterm birth, growth restriction, and perinatal death in infants.4

Causes Of Preeclampsia

Risk factors for developing preeclampsia include:

  • First-time pregnancies
  • History of preeclampsia in previous pregnancies
  • Chronic hypertension prior to pregnancy
  • Autoimmune diseases including systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), type 1 diabetes (T1DM), rheumatoid arthritis (RA), and thyroid diseases (e.g., Graves' disease, Hashimoto's)5
  • Kidney dysfunction
  • Multiple-fetus pregnancies
  • Previous stillbirths
  • Older age in pregnancy
  • Obesity during pregnancy
  • Family history, especially in women whose mothers had preeclampsia 
  • Trisomy 13/FLT1 genetic mutation (fms-related receptor tyrosine kinase 1), which can antagonize placental growth factor and vascular endothelial growth factor (VEGF), leading to endothelial dysfunction.6
  • Vitamin D deficiency due to its role in regulating genes related to placental function, including implantation, placental invasion, angiogenesis, immune function, and inflammation.7

How To Prevent Preeclampsia

Key prevention measures include regular monitoring of blood pressure and urine protein levels.

Lifestyle changes (diet, exercise, supplements) and pharmacological intervention may help to reduce risk.8


Diet and lifestyle

  • Diet:
    Pregnant women should aim to consume plenty of fruit and vegetables per day, along with high-fiber foods. Fiber can reduce blood cholesterol, blood pressure, and inflammation, and may also aid in weight management.
    Avoid raw fish and fish with a high mercury content (shark, swordfish, king mackerel, tilefish, marlin, orange roughy, bigeye tuna) during pregnancy. Intake of fat, salt, sugar, and red meat/processed meats should be minimal.

  • Supplements:
    - Vitamin D: Studies show a significant association between vitamin D deficiency and preeclampsia risk. Dose should be individually personalized and under the upper tolerable limit.
    Calcium: Women at heightened risk of pre-eclampsia and/or with a low dietary calcium intake are advised to supplement with calcium.
    - Multivitamins/multiminerals: Women planning pregnancy should take a multivitamin/multimineral supplement containing folate, vitamin D (unless taken separately) and selenium (if status is low) if they are planning on becoming pregnant.


Body weight

Healthy body weight (BMI) prior to conception is recommended. Being overweight or obese significantly increases risk of hypertension and inflammation in pregnancy.


Pharmacological measures

Low-dose (60mg) aspirin is the most evidence-based preventive measure. It is usually given before 16 weeks of gestation and has been shown to decrease risk of preeclampsia and other adverse outcomes in women with higher risk.10

Statins may be used to reduce inflammation and improve vascular function in high-risk women.11

The Connection Between MTHFR, Blood Pressure, And Preeclampsia

Research has established a link between elevated homocysteine levels and preeclampsia, with some studies suggesting that MTHFR gene variants may also play a part.


The MTHFR enzyme is required for healthy methylation, DNA synthesis, folate metabolism, homocysteine breakdown, and many other processes. MTHFR C677T and A1298C variants may be associated with an increased risk of preeclampsia due to their role in homocysteine metabolism and cardiovascular health.


Previous studies have shown the MTHFR A1298C variant to be a significant risk factor for vascular-related pregnancy complications. Women with MTHFR A1298C polymorphism or elevated homocysteine levels have an increased risk of placental vasculopathies.12


Preeclampsia is characterized by a high sFlt1/PlGF ratio. Soluble fms-like tyrosine kinase-1 (sFlt-1) is an anti-angiogenic protein that restricts the formation of new blood vessels.  Placental growth factor (PIGF) is a pro-angiogenic protein that helps healthy blood vessels grow and develop in the placenta. In a healthy pregnancy, sFlt-1 levels should be low, and PlGF should be high. In preeclampsia, the placenta produces excess sFlt-1 which blocks and reduces PlGF.13 A 2025 study involving 675 pregnant women found that those with MTHFR C677T had significantly higher sFlt-1 levels and sFlt-1/PlGF ratio. Women with preeclampsia were more likely to have a MTHFR C677/A1298 variant than controls.14


There is long‑standing evidence that high homocysteine is associated with hypertension in pregnancy, including endothelial dysfunction and preeclampsia.15 MTHFR variants are linked to elevated homocysteine. A 2025 study found that pregnant women with hypertension were found to have significantly higher homocysteine levels than women with normal blood pressure. Elevated homocysteine levels were also positively correlated with the severity of hypertensive disorders, with the highest concentrations in those with severe preeclampsia and eclampsia.16


MTHFR C677T has also been associated as an independent risk factor for impaired renal function in pregnant women with preeclampsia.17

MTHFR And Preeclampsia

Key takeaways

  • Icon Preeclampsia is a serious hypertensive pregnancy disorder that can lead to organ failure
  • Icon Causes may include history of hypertension, genetics, comorbidities, obesity, and vitamin D deficiency
  • Icon Risks may be reduced with monitoring of blood pressure, diet, lifestyle changes, and nutritional supplementation

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Frequently Asked Questions About MTHFR And Preeclampsia

Does MTHFR cause preeclampsia?

MTHFR is not a direct cause of preeclampsia, but it has been associated with high homocysteine, which is a significant risk factor in preeclampsia.

Which vitamin deficiency causes preeclampsia?

Vitamin D deficiency has been associated with higher risk of preeclampsia, which may be due to its role in regulating genes related to placental function, including implantation, placental invasion, and angiogenesis. It also modulates immune function and inflammation.18

Do obgyns test for the MTHFR gene?

No, there is no routine screening for MTHFR variants in pregnancy as major healthcare organizations have stated there is no link between MTHFR and pregnancy loss.

Can the MTHFR gene cause high blood pressure?

Yes, the MTHFR C677T variant is associated with an increased risk of hypertension and cardiovascular disease. This has been linked to increased homocysteine levels, impaired methylation, and low B vitamin levels, especially folate and B12.19

Can you have a healthy pregnancy with MTHFR?

Yes, women with a MTHFR variant can have a healthy pregnancy. The severity of a MTHFR mutation varies significantly between individuals. Some people may need to monitor their homocysteine levels and supplement with active folate rather than folic acid.

References

  1. Kaltrina Kutllovci Hasani, Nurxhan Ajeti, Nandu Goswami; "Understanding Preeclampsia: Cardiovascular Pathophysiology, Histopathological Insights and Molecular Biomarkers"; Med Sci (Basel); 2025 Aug

    https://pmc.ncbi.nlm.nih.gov/articles/PMC12452302/

  2. Dhruvikumari D Sharma, Nidhi R Chandresh, Ayesha Javed, Peter Girgis, Madiha Zeeshan, Syeda Simrah Fatima, Taneen T Arab, Sreeja Gopidasan, Vineesha Chowdary Daddala, Kalgi V Vaghasiya, Ameena Soofia, Maneeth Mylavarapu; "The Management of Preeclampsia: A Comprehensive Review of Current Practices and Future Directions"; Cureus; 2024 Jan

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10832549/

  3. Pensée Wu, Randula Haththotuwa, Chun Shing Kwok, Aswin Babu, Rafail A. Kotronias, Claire Rushton, Azfar Zaman, Anthony A. Fryer, Umesh Kadam, Carolyn A. Chew-Graham, Mamas A. Mamas; "Preeclampsia and Future Cardiovascular Health: A Systematic Review and Meta-Analysis"; Circulation: Cardiovascular Quality and Outcomes; 2017 Feb

    https://www.ahajournals.org/doi/full/10.1161/CIRCOUTCOMES.116.003497

  4. Evdokia Dimitriadis, Daniel L. Rolnik, Wei Zhou, Guadalupe Estrada-Gutierrez, Kaori Koga, Rossana P. V. Francisco, Clare Whitehead, Jon Hyett, Fabricio da Silva Costa, Kypros Nicolaides, Ellen Menkhorst; "Pre-eclampsia"; Nature Reviews Disease Primers; 2023 Feb

    https://www.nature.com/articles/s41572-023-00417-6

  5. Megha Singh, Steven Wambua, Siang Ing Lee, Kelvin Okoth, Zhaonan Wang, Fathima Fazla Ahamed Fayaz, Kelly-Ann Eastwood, Catherine Nelson-Piercy, John A Reynolds, Krishnarajah Nirantharakumar, Francesca Crowe; on behalf of MuM-PreDiCT; "Autoimmune diseases and adverse pregnancy outcomes: an umbrella review"; BMC Med.; 2024 Mar

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10913233/

  6. Ralph McGinnis, Valgerdur Steinthorsdottir, Nicholas O Williams, Gudmar Thorleifsson, Scott Shooter, Sigrun Hjartardottir, Suzannah Bumpstead, Lilja Stefansdottir, Lucy Hildyard, Jon K Sigurdsson, John P Kemp, Gabriela B Silva, Liv Cecilie V Thomsen, Tiina Jääskeläinen, Eero Kajantie, Sally Chappell, Noor Kalsheker, Ashley Moffett, Susan Hiby, Wai Kwong Lee, Sandosh Padmanabhan, Nigel A B Simpson, Vivien A Dolby, Eleonora Staines-Urias, Stephanie M Engel, Anita Haugan, Lill Trogstad, Gulnara Svyatova, Nodira Zakhidova, Dilbar Najmutdinova, The FINNPEC Consortium, The GOPEC Consortium, Anna F Dominiczak, Håkon K Gjessing, Juan P Casas, Frank Dudbridge, James J Walker, Fiona Broughton Pipkin, Unnur Thorsteinsdottir, Reynir T Geirsson, Debbie A Lawlor, Ann-Charlotte Iversen, Per Magnus, Hannele Laivuori, Kari Stefansson, Linda Morgan; "Variants in the fetal genome near FLT1 are associated with risk of preeclampsia"; Nature Genetics; 2017 Jun

    http://doi.org/10.1038/ng.3895

  7. Krishnanand PS, Sangeeta B. Singh, Shikhaa Mahajan, Divya Mangla; "Association Between Vitamin D Levels and Hypertensive Disorders of Pregnancy"; Cureus; 2025 Nov

    https://assets.cureus.com/uploads/original_article/pdf/366134/20251220-248783-8l4ofh.pdf

  8. Abigail Perry, Anna Stephanou, Margaret P Rayman; "Dietary factors that affect the risk of pre-eclampsia"; BMJ Nutr Prev Health; 2022 Jun

    https://pmc.ncbi.nlm.nih.gov/articles/PMC9237898/#s4

  9. Chrysoula Giourga, Sousana K Papadopoulou, Gavriela Voulgaridou, Calliope Karastogiannidou, Constantinos Giaginis, Agathi Pritsa; "Vitamin D Deficiency as a Risk Factor of Preeclampsia during Pregnancy"; Diseases; 2023 Nov

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10660864/

  10. Jillian T. Henderson, Kimberly K. Vesco, Caitlyn A. Senger, Rachel G. Thomas, Nadia Redmond; "Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality [Internet]"; Agency for Healthcare Research and Quality; 2021 Sep

    https://pubmed.ncbi.nlm.nih.gov/34644040/

  11. Devin D SMITH, Maged M COSTANTINE; "The role of statins in the prevention of preeclampsia"; American journal of obstetrics and gynecology; 2023 Feb

    https://pmc.ncbi.nlm.nih.gov/articles/PMC8237152/

  12. Sarra Klai, Najiba Fekih-Mrissa, Sonia El Housaini, Naziha Kaabechi, Brahim Nsiri, Radhouen Rachdi, Nasredine Gritli; "Association of MTHFR A1298C polymorphism (but not of MTHFR C677T) with elevated homocysteine levels and placental vasculopathies"; Blood Coagulation & Fibrinolysis; 2011 Jul

    https://journals.lww.com/bloodcoagulation/abstract/2011/07000/association_of_mthfr_a1298c_polymorphism__but_not.4.aspx

  13. Nataliia Sergeevna Karpova, Olga Pavlovna Dmitrenko, Tatyana Sergeevna Budykina; "Literature Review: The sFlt1/PlGF Ratio and Pregestational Maternal Comorbidities: New Risk Factors to Predict Pre-Eclampsia"; Int J Mol Sci.; 2023 Apr

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10095124/

  14. Hedia Zitouni, Vera Chayeb, Nozha Raguema, Marwa Ben Ali Gannoun, Sameh Bendhaher, Ines Zouari, Fulin Liu, Kamel Gaddour, Touhami Mahjoub, Jean Guibourdenche, Wassim Y Almawi; "Association of MTHFR C677T and A1298C variants with preeclampsia risk and angiogenic imbalance in Tunisian women"; Pregnancy Hypertension; 2025 Mar

    https://www.sciencedirect.com/science/article/abs/pii/S2210778925000030?via%3Dihub

  15. Virupaksha Ajjammanavar, Bhamathi Mikkilineni, Sowmya Koteshwara; "A Comparative Study of Serum Homocysteine Levels in Pregnant Women with Hypertensive Disorders and Normotensive Pregnant Women"; Journal of Obstetrics, Gynecology and Cancer Research; 2026 Sep

    https://www.jogcr.com/article_722021.html

  16. Virupaksha Ajjammanavar, Bhamathi Mikkilineni, Sowmya Koteshwara; "A Comparative Study of Serum Homocysteine Levels in Pregnant Women with Hypertensive Disorders and Normotensive Pregnant Women"; Journal of Obstetrics, Gynecology and Cancer Research; 2026 Sep

    https://www.jogcr.com/article_722021.html

  17. Lin Yun, Meiqi Ge, Rui Xu, Fei Zheng, Xueqiang Zhao, Xinran Li; "C677T Gene Polymorphism of MTHFR Is a Risk Factor for Impaired Renal Function in Pregnant Women With Preeclampsia in the Chinese Han Population"; Frontiers in Cardiovascular Medicine; 2022 May

    https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.902346/full

  18. Krishnanand PS, Sangeeta B. Singh, Shikhaa Mahajan, Divya Mangla; "Association Between Vitamin D Levels and Hypertensive Disorders of Pregnancy"; Cureus; 2025 Nov

    https://assets.cureus.com/uploads/original_article/pdf/366134/20251220-248783-8l4ofh.pdf

  19. Martina Rooney, Catherine F Hughes, J J Strain, Michelle Clements, Helene McNulty, Mary Ward; "Impact of the MTHFR C677T polymorphism on blood pressure and related central haemodynamic parameters in healthy adults"; J Hum Nutr Diet.; 2022 Jul

    https://pmc.ncbi.nlm.nih.gov/articles/PMC9541256/

Katie Stone - Naturopath

About the Author

Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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