Betaine may be used as a methyl-donor during fetal life

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: 268 AFs sampled between 14 and 39 weeks of gestation (WG) were retrospectively selected in our AF bank. Next, we measured methionine-cycle intermediates (S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), total homocysteine, methionine, methyl malonic acid) and methyldonors and methylacceptors (betaine, dimethylglycine, sarcosine, free and total choline, free and total ethanolamine, creatine, 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 homocysteine 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 WG, which could reflect increasing methylation capacities. The negative correlation between betaine and total homocysteine together with a constant betaine to dimethylglycine ratio during gestation suggest that betaine may be used as a methyl-donor during fetal life.

Imbard, A., et al., Methylation metabolites in amniotic fluid depend on gestational age. Prenat Diagn, 2013