Homocysteine and folate concentrations in early pregnancy and the risk of adverse pregnancy outcomes: the Generation R Study

Abstract

Objective To investigate associations between early pregnancy homocysteine, folate and vitamin B12 concentrations and placental weight, birthweight and adverse pregnancy outcomes.Design Population-based birth cohort study.Setting Rotterdam, the Netherlands.Population Cohort of 5805 pregnant women.Methods To analyse homocysteine, folate and vitamin B12 concentrations, blood was drawn in early pregnancy. These concentrations were divided into quintiles. Information on birth outcomes was retrieved from medical records. Multivariate regression analyses were used.Main outcome measures Placental weight, birthweight, small for gestational age at birth (SGA) (<5th centile), prematurity and preeclampsia.Results High homocysteine concentrations (highest quintile) were associated with lower placental weight (difference 30 g; P < 0.001) and birthweight (difference 110 g; P < 0.001), and increased risk of SGA [odds ratio (OR) 1.7; P = 0.006] compared with lowest quintile (reference). Low folate concentrations (lowest quintile) were associated with lower placental weight (difference 26 g; P = 0.001) and birthweight (difference 125 g; P < 0.001), and increased risks of SGA (OR 1.9; P = 0.002), prematurity (OR 2.2; P = 0.002) and pre-eclampsia (OR 2.1; P = 0.04) compared with highest quintile (reference). The risk of developing SGA and preeclampsia was substantially higher in women who had higher homocysteine and lower folate concentrations. No associations were found with vitamin B12.Conclusions Higher homocysteine and lower folate concentrations in early pregnancy are associated with lower placental weight and birthweight, and higher risk of adverse pregnancy outcomes. These findings suggest that high homocysteine and low folate concentrations in early pregnancy may adversely influence placentation and subsequently affect the success of pregnancy and birth outcomes.

Maternal dietary intake of folate, vitamin B12 and MTHFR 677C>T genotype: their impact on newborn’s anthropometric parameters

“…Takimoto et al (2011) reported a significant increase in birth weight (b = 0.08; 95 % CI 0.01, 0.15) associated with dietary intake of vitamin B 12 during the third trimester of pregnancy, while Sukla et al (2013) observed that women with deficient plasma vitamin B 12 were two times more likely of having a low weight infant than those without this deficiency. Other authors did not find an association between vitamin B 12 and birth weight (Relton et al 2005, Bergen et al 2012.…”

“…Pregnant women carriers of 677C[T polymorphism in MTHFR gene have an enzymatic variant with less activity and, therefore, less 5-methyltetrahydrofolate availability. In these women, a deficient dietary intake of vitamin B 12 can produce an increase of maternal serum Hcy levels, which during pregnancy have been related with alterations in the vascular endothelium at the placental level, leading to adverse reproductive effects such as preeclampsia, miscarriage and restricted fetal growth (Bergen et al 2012). Another potential mechanism is that vitamin B 12 deficiency reduces the methionine metabolism and can affect the patterns of epigenetic modifications such as DNA methylation that alter the gene expression and thus affect the fetal development (Rush et al 2014).…”

Vitamin B-12 and Perinatal Health

“…These findings suggest that, in addition to deficiencies of vitamins B-12 and folate alone, unbalanced vitamin B-12 and folate intake or status may interact and increase risk of adverse pregnancy outcomes (100, 101). Higher tHcy concentrations were associated with significantly increased risk of LBW in a study in Netherlands (89). Similarly, in a study in Japan, maternal tHcy concentrations were associated with significantly lower birth weight: each 0.1-mmol/L increase in maternal tHcy concentrations during the third trimester was associated with a 151-g lower infant birth weight (P < 0.01) (102).…”

Vitamin B12 Deficiency in Pregnancy and Lactation: Is there a Need for Pre and Post-natal Supplementation?

“…A number of studies have reported an association of vitamin B12 deficiency with infertility, IUGR, preeclampsia and early pregnancy loss [58][59][60][61][62][63]. One study in Chinese women found that inadequate preconception vitamin B12 (<258 pmol/L) was associated with a 60% increased risk of preterm delivery [64].…”