Moderately elevated first trimester fasting plasma total homocysteine is associated with increased probability of miscarriage. The Reus-Tarragona Birth Cohort Study.

The association between elevated early pregnancy fasting plasma total homocysteine (tHcy) and miscarriage risk was investigated prospectively in participants (n = 544) from the Reus-Tarragona Birth Cohort study. Pregnancy was confirmed before 12 gestational weeks (GW) by ultrasound scan and a fasting blood sample collected. Pregnancies with complications other than miscarriages were excluded. Miscarriages were diagnosed by ultrasound scan and gestational age at the time of miscarriage estimated by embryo size, where possible. Cases in which blood samples were collected more than a week after the miscarriage, or the miscarriage was of known cause, were excluded. Fasting plasma folate, vitamin B12, tHcy, cotinine (biomarker of smoking), red blood cell (RBC) folate, MTHFR 677C > T (rs1801133) and SLC19A1 80G>A (rs1051266) genotypes were determined. The exposed group consisted of participants with first trimester tHcy ≥ P90 (7.1 µmol/L) (n = 57) and unexposed of those with tHcy < P90 (n = 487). Adherence to folic acid supplement recommendations, plasma folate, plasma vitamin B12, RBC folate and prevalence of optimal RBC folate status (≥ 906 µmol/L) were lower in the exposed compared to unexposed group. The prevalences of the MTHFR 677 TT genotype and miscarriage were higher in the exposed group. The relative risks (95% CI) of pregnancy ending in miscarriage were 2.5 (1.1, 5.7) and 2.1 (1.0, 4.5) for participants in the high tHcy and suboptimal RBC folate groups (compared to the reference groups) respectively. Adherence to folic acid supplement recommendations was positively associated, while the MTHFR 677 TT versus CC genotype and smoking versus non-smoking were negatively associated, with RBC folate status.

Early pregnancy folate-cobalamin interactions and their effects on cobalamin status and hematologic variables throughout pregnancy.

Background: Periconception folic acid supplementation is widespread, but how it interacts with cobalamin status is rarely considered. Objective: The aim of this study was to investigate whether first-trimester folate-cobalamin interactions affect pregnancy cobalamin status, hematologic variables, and pregnancy outcomes. Design: In the longitudinal Reus-Tarragona Birth Cohort study from <12 gestational weeks throughout pregnancy, fasting plasma and red blood cell (RBC) folate, plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), total homocysteine (tHcy), hemoglobin, mean cell volume (MCV), postglucose-load serum glucose, gestational hypertension, gestational age at birth, and birth weight were recorded in 563 participants. Results: The highest plasma folate concentrations occurred in the first trimester when folic acid supplement use was extensive. Supplementation beyond the first trimester interacted with time of pregnancy on plasma folate, RBC folate, and tHcy throughout pregnancy (P-interaction <0.001). Plasma folate and RBC folate were higher and tHcy was lower in continued supplement users than in nonusers. Elevated plasma folate (≥30 nmol/L) occurred in 78.9% of women who exceeded the recommended 400 µg folic acid/d. First-trimester folate-cobalamin status interactions were associated with MMA (P-interaction <0.001) throughout pregnancy. When plasma cobalamin was suboptimal (≤221 pmol/L; n = 36), participants with elevated plasma folate (n = 11) had higher MMA concentrations than did those with nonelevated plasma folate (n = 23). First-trimester folate-MMA status interactions were associated with MCV throughout pregnancy (P-interaction <0.01) and with cord plasma holoTC (P-interaction <0.05). The mean difference (95% CI) in MCV (fL) between women with elevated and nonelevated plasma folate status was -2.12 (-3.71, -0.52) for top-quartile plasma MMA (≥0.139 µmol/L) and 0.60 (-0.39, 1.60) for plasma MMA <0.139 µmol/L. Cord plasma holoTC was higher in women with elevated compared with nonelevated plasma folate status only for MMA <0.139 µmol/L. Folate-cobalamin interactions were not associated with the other investigated outcomes. Conclusion: First-trimester folate-cobalamin status interactions were associated with plasma MMA and MCV throughout pregnancy. This trial was registered at www.clinicaltrials.gov as NCT01778205.