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Preeclampsia linked to hyperhomocysteinaemia

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  • pregnancy, homocysteine, blood pressure

Georgia Marrion ● 1 min read

One potential mechanism proposed for the pathogenesis of preeclampsia is elevated homocysteine levels adversely affecting placental functionality, with various data finding a three- to eightfold increase in risk of disease onset associated with hyperhomocysteinaemia.[1,5,6]

Preeclampsia is a disease that affects 3-8% of pregnancies.[1,2] The International Society for the Study of Hypertension in Pregnancy classifies preeclampsia as the onset of high blood pressure (systolic > 140mmHg and / or diastolic > 90mmHg) with proteinuria (>300mg/day urinary protein) after 20-weeks’ gestation.[3] Other comorbidities that can be present include renal insufficiency, liver disease, neurological or haematological dysfunctions and foetal growth restriction.[3]

This serious disorder is a significant contributor to maternal morbidity and mortality, particularly if it progresses to eclampsia, the incidence of convulsive seizures or HELLP syndrome (haemolysis, elevated liver enzyme, low platelets).[1,4,5]

Despite the frequency and severity of the condition, the aetiology of preeclampsia has yet to be confirmed. However, the increased risk of future cardiovascular disease observed in women with a history of preeclampsia suggests similar physiological processes may occur within these disease states.[2,4]

A 2016 prospective case-controlled study found that high maternal homocysteine was an early and independent predictor of both early onset preeclampsia and preeclampsia with IUGR, however a clear dose-dependent relationship was not clear.[2]

This may have a genetic basis, with a positive association observed between the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and risk of preeclampsia in a 2015 meta-analysis.[1]

Folic acid intake from early pregnancy may be beneficial. Two large prospective cohort studies found that daily folic acid intake in pregnant women, even as low as 0.1mg per day, was associated with a lower rate of preeclampsia onset [4] and a reduced risk of premature birth compared with no folic acid taken.[6]

Further studies are required to determine the role of homocysteine in the aetiology of preeclampsia and the potential impact of folic acid in improving maternal and perinatal outcomes associated with the disease.


  1. 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;32:797-805. [Full Text
  2. Cheng PJ, Huang SY, Su SY, et al. Prognostic value of cardiovascular disease risk factors measured in the first-trimester on the severity of preeclampsia. Medicine 2016;95(5):e2653. [Full Text
  3. Tranquilli AL, Dekker G, Magee L, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP. Pregnancy Hypertens 2014;4:97-104. [Full Text
  4. Wen SW, Guo Y, Rodger M, et al. Folic acid supplementation in pregnancy and the risk of preeclampsia – a cohort study. PloS 2016;11(2):e0149818. [Full Text
  5. Ge J, Wang J, Zhang F, et al. Correlation between MTHFR gene methylation and preeclampsia, and its clinical significance. Genet Mol Res 2015;14(3):8021-8028. [Full Text
  6. Banhidy F, Dakhlaoui A, Dudas I, et al. Birth outcomes of newborns after folic acid supplementation in pregnant women with early and late preeclampsia: a population-based study. Adv Prev Med 2011;2011:doi:10.4061/2011/127369. [Full Text


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Georgia Marrion

Georgia is a naturopath and nutritionist with 15 years’ experience who specialises in women’s health, particularly hormone imbalance and fertility and conception issues as well as and pregnancy and post-partum support. Georgia runs her own naturopathic and nutritional fertility and women’s health clinical practice and is an experienced health and nutrition writer.