Methylation metabolites in amniotic fluid depend on gestational age

• Published in: Prenatal diagnosis 2013-09, Vol.33 (9), p.848-855
• Main Authors: Imbard, Apolline, Blom, Henk J., Schlemmer, Dimitri, Barto, Rob, Czerkiewicz, Isabelle, Rigal, Odile, Muller, Françoise, Benoist, Jean-François
• Format: Article
• Language: English
• Subjects: Adult; Amniotic Fluid - metabolism; Betaine - metabolism; Choline - metabolism; Female; Gestational Age; Humans; Methionine - metabolism; Methylation; Methyltransferases - metabolism; Pregnancy; Retrospective Studies; S-Adenosylhomocysteine - metabolism; S-Adenosylmethionine - metabolism; Sarcosine - analogs & derivatives; Sarcosine - metabolism
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.4142

ABSTRACT Objective Methylation metabolism is essential for fetus development. However, normative data for amniotic fluid (AF) concentrations of methylation metabolites at different gestational ages are lacking. We aimed to determine in AF reference values of 14 intermediates involved in methylation. Methods Two hundred sixty‐eight AFs sampled between 14 and 39 weeks of gestation were retrospectively selected in our AF bank. Next, we measured methionine (Met)‐cycle intermediates [S‐adenosyl Met (AdoMet), S‐adenosyl‐l‐homocysteine (AdoHcy), total Hcy, Met, and methyl malonic acid] and methyl donors and methyl acceptors (betaine, dimethylglycine, sarcosine, free and total choline, free and total ethanolamine, creatine, and guanidinoacetate) by liquid chromatography coupled with tandem mass spectrometry. Results Reference ranges according to gestational age were determined for each parameter. Strong correlations between metabolites directly connected in their metabolic pathway and between total Hcy and betaine were observed. Conclusion Methionine, an essential amino acid required for protein synthesis, is the only parameter that dramatically decreases with gestational age. The AdoMet/AdoHcy ratio exponentially increases from 25 weeks of gestation, which could reflect increasing methylation capacities. The negative correlation between betaine and total Hcy together with a constant betaine to dimethylglycine ratio during gestation suggests that betaine may be used as a methyl donor during fetal life. © 2013 John Wiley & Sons, Ltd. What's already known about this topic? Methylation metabolism is essential for the fetus development. What does this study add? This article provides detailed normative data for AF concentrations of methylation intermediates at different gestational ages. These data are of importance to provide a base to explore the involvement of remethylation pathway in the physiopathology of disorders such as neural tube defects, inborn errors of metabolism, and others for which transmethylation impairment has been suggested such as cancer and epigenetic modification.