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Early pregnancy folate-cobalamin interactions and their effects on cobalamin status and hematologic variables throughout pregnancy.
Am J Clin Nutr. 2018 02 01; 107(2):173-182.AJ

Abstract

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.

Authors+Show Affiliations

Units of Preventive Medicine and Public Health, Department of Basic Medical Sciences and Obstetrics and Gynecology, Department of Medicine and Surgery, Faculty of Medicine and Health Sciences, Pere Virgili Institute of Health Research, Rovira i Virgili University, Reus, Spain.Units of Preventive Medicine and Public Health, Department of Basic Medical Sciences and Obstetrics and Gynecology, Department of Medicine and Surgery, Faculty of Medicine and Health Sciences, Pere Virgili Institute of Health Research, Rovira i Virgili University, Reus, Spain.Units of Obstetrics and Gynecology, Department of Medicine and Surgery, Faculty of Medicine and Health Sciences, Pere Virgili Institute of Health Research, Rovira i Virgili University, Reus, Spain. Units of Obstetrics and Gynecology, University Hospitals Sant Joan, Reus and Joan XXIII, Tarragona, Spain. Biomedical Research Networking Center for the Pathophysiology of Obesity, Carlos III Institute of Health, Madrid, Spain.Units of Preventive Medicine and Public Health, Department of Basic Medical Sciences and Obstetrics and Gynecology, Department of Medicine and Surgery, Faculty of Medicine and Health Sciences, Pere Virgili Institute of Health Research, Rovira i Virgili University, Reus, Spain. Biomedical Research Networking Center for the Pathophysiology of Obesity, Carlos III Institute of Health, Madrid, Spain.Section of Pharmacology, Department of Internal Medicine, University of Bergen, Bergen, Norway.Units of Obstetrics and Gynecology, Department of Medicine and Surgery, Faculty of Medicine and Health Sciences, Pere Virgili Institute of Health Research, Rovira i Virgili University, Reus, Spain. Units of Joan XXIII, Tarragona, Spain.Units of Preventive Medicine and Public Health, Department of Basic Medical Sciences and Obstetrics and Gynecology, Department of Medicine and Surgery, Faculty of Medicine and Health Sciences, Pere Virgili Institute of Health Research, Rovira i Virgili University, Reus, Spain.Units of Obstetrics and Gynecology, Department of Medicine and Surgery, Faculty of Medicine and Health Sciences, Pere Virgili Institute of Health Research, Rovira i Virgili University, Reus, Spain. Units of Obstetrics and Gynecology, University Hospitals Sant Joan, Reus and Joan XXIII, Tarragona, Spain.Units of Preventive Medicine and Public Health, Department of Basic Medical Sciences and Obstetrics and Gynecology, Department of Medicine and Surgery, Faculty of Medicine and Health Sciences, Pere Virgili Institute of Health Research, Rovira i Virgili University, Reus, Spain.Units of Preventive Medicine and Public Health, Department of Basic Medical Sciences and Obstetrics and Gynecology, Department of Medicine and Surgery, Faculty of Medicine and Health Sciences, Pere Virgili Institute of Health Research, Rovira i Virgili University, Reus, Spain. Biomedical Research Networking Center for the Pathophysiology of Obesity, Carlos III Institute of Health, Madrid, Spain.

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29529156

Citation

Solé-Navais, Pol, et al. "Early Pregnancy Folate-cobalamin Interactions and Their Effects On Cobalamin Status and Hematologic Variables Throughout Pregnancy." The American Journal of Clinical Nutrition, vol. 107, no. 2, 2018, pp. 173-182.
Solé-Navais P, Salat-Batlle J, Cavallé-Busquets P, et al. Early pregnancy folate-cobalamin interactions and their effects on cobalamin status and hematologic variables throughout pregnancy. Am J Clin Nutr. 2018;107(2):173-182.
Solé-Navais, P., Salat-Batlle, J., Cavallé-Busquets, P., Fernandez-Ballart, J., Ueland, P. M., Ballesteros, M., Ornosa-Martín, G., Inglès-Puig, M., Colomina, J. M., & Murphy, M. M. (2018). Early pregnancy folate-cobalamin interactions and their effects on cobalamin status and hematologic variables throughout pregnancy. The American Journal of Clinical Nutrition, 107(2), 173-182. https://doi.org/10.1093/ajcn/nqx041
Solé-Navais P, et al. Early Pregnancy Folate-cobalamin Interactions and Their Effects On Cobalamin Status and Hematologic Variables Throughout Pregnancy. Am J Clin Nutr. 2018 02 1;107(2):173-182. PubMed PMID: 29529156.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Early pregnancy folate-cobalamin interactions and their effects on cobalamin status and hematologic variables throughout pregnancy. AU - Solé-Navais,Pol, AU - Salat-Batlle,Judith, AU - Cavallé-Busquets,Pere, AU - Fernandez-Ballart,Joan, AU - Ueland,Per M, AU - Ballesteros,Mónica, AU - Ornosa-Martín,Gemma, AU - Inglès-Puig,Montserrat, AU - Colomina,Jose M, AU - Murphy,Michelle M, PY - 2017/05/02/received PY - 2017/11/20/accepted PY - 2018/3/13/entrez PY - 2018/3/13/pubmed PY - 2019/5/17/medline SP - 173 EP - 182 JF - The American journal of clinical nutrition JO - Am J Clin Nutr VL - 107 IS - 2 N2 - 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. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/29529156/Early_pregnancy_folate_cobalamin_interactions_and_their_effects_on_cobalamin_status_and_hematologic_variables_throughout_pregnancy_ DB - PRIME DP - Unbound Medicine ER -