A Novel Review of Homocysteine and Pregnancy Complications

Abstract

Homocysteine (Hct) is a substance produced in the metabolism of methionine. It is an essential type of amino acid gained from the daily diet. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is related to elevated total homocysteine (tHct) expressions, in particular, among women with low folate intake. Hyperhomocysteinemia (HHct) is caused by numerous factors, such as genetic defects, lack of folic acid, vitamin B6 and B12 deficiency, hypothyroidism, drugs, aging, and renal dysfunction. Increased Hct in peripheral blood may lead to vascular illnesses, coronary artery dysfunction, atherosclerotic changes, and embolic diseases. Compared to nonpregnant women, the Hct level is lower in normal pregnancies. Recent studies have reported that HHct was associated with numerous pregnancy complications, including recurrent pregnancy loss (RPL), preeclampsia (PE), preterm delivery, placental abruption, fetal growth restriction (FGR), and gestational diabetes mellitus (GDM). Besides, it was discovered that neonatal birth weight and maternal Hct levels were negatively correlated. However, a number of these findings lack consistency. In this review, we summarized the metabolic process of Hct in the human body, the levels of Hct in different stages of normal pregnancy reported in previous studies, and the relationship between Hct and pregnancy complications. The work done is helpful for obstetricians to improve the likelihood of a positive outcome during pregnancy complications. Reducing the Hct level with a high dosage of folic acid supplements during the next pregnancy could be helpful for females who have suffered pregnancy complications due to HHct.

Factors Involved in Endothelial Dysfunction Related to Angiogenic Disbalance and Oxidative Stress, in Women at High Risk of Term Pre-Eclampsia

“…The association of hyperhomocysteinemia and PE was initially suggested by Decker et al [ 25 , 26 ]. A large number of studies have demonstrated a positive correlation between Hcy and PE and have shown a significant increase in serum Hcy levels in women who develop PE at various stages of pregnancy [ 27 , 28 , 29 ]. In addition, pregnant women complicated by severe PE have shown significantly higher serum Hcy levels than those in the non-severe form.…”

“…ADMA has been shown to increase systemic vascular resistance in humans by acting as an endogenous inhibitor of NOS. An elevation of ADMA levels has been widely described in patients with various cardiovascular and metabolic conditions, such as hypercholesterolemia, atherosclerosis, hypertension, chronic heart or kidney failure, diabetes mellitus, and stroke [ 27 ].…”

Genetic Variants in Folate and Cobalamin Metabolism-Related Genes in Pregnant Women of a Homogeneous Spanish Population: The Need for Revisiting the Current Vitamin Supplementation Strategies

“…Elevated homocysteine levels, derived from the incorrect functioning of the MTHFR enzyme, have also been related to an increased risk of spontaneous abortions [46]. In our series, women with the MTHFR risk allele had a lower frequency of spontaneous pregnancy, i.e., a greater need for assisted fertilization, which may reflect a difficulty in gestation derived from the incorrect functioning of the one-carbon metabolism pathway.…”

Dietary factors that affect the risk of pre-eclampsia

“…Some 85% of studies showed that women with pre-eclampsia had a higher serum homocysteine concentration than those without pre-eclampsia 138. A high concentration of homocysteine could be associated with a lower level of folate or vitamin B 12 139. Folate requirements are increased in pregnancy due to the rapid division of cells in the fetus and increased urinary losses 140.…”