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Figure 1.

Simplified scheme to show the roles of choline and its metabolites.

BHMT: betaine-homocysteine S-methyltransferase.

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Figure 2.

Schematic to show the role of choline in one-carbon metabolism intersecting with the methionine-homocysteine cycle.

Measured metabolites are shown in orange boxes; enzymes are shown in bolded alphabets. 10-Formyl-THF: 10-formyl-tetrahydrofolate; 5,10-CH = THF: 5,10-methenyltetrahydrofolate; 5,10-CH2-THF: 5,10-methylenetetrahydrofolate; 5-CH3-THF: 5-methyltetrahydrofolate; BADH: betaine aldehyde dehydrogenase; BHMT: betaine-homocysteine S-methyltransferase; CBS: cystathionine beta synthase; CHDH: choline dehydrogenase; Cys: cysteine; cSHMT: cytoplasmic serine hydroxymethyltransferase; DD: dimethylglycine dehydrogenase; DHF: dihydrofolate; DHFR: dihydrofolatereductase; DMG: dimethylglycine; dUMP: 2′-deoxyuridine 5′-monophosphate; FTD: 10-formyl-tetrahydrofolate dehydrogenase; FTS: 10-formyl-tetrahydrofolate synthase; GDC: glycine decarboxylase; Gly: glycine; GNMT: glycine N-methyltransferase; Hcy: homocysteine; MAT, methionine adenosyltransferase; Met: methionine; MS: methionine synthase; mSHMT: mitochondrial serine hydroxymethyltransferase; MTCH: 5,10-methylenetetrahydrofolate cyclohydrolase; MTHFD: 5,10-methylenetetrahydrofolate dehydrogenase; MTHFR: 5,10-methylenetetrahydrofolate reductase; MTs, S-adenosyl methionine-dependent methyltransferases; SAH, S-adenosyl homocysteine; SAHH: S-adenosyl homocysteine hydrolase; SAM: S-adenosyl methionine; Sarc: sarcosine; SDH: sarcosine dehydrogenase; Ser: serine; THF: tetrahydrofolate; TS: thymidylate synthase. Not all enzymes and intermediates are shown in this pathway.

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Table 1.

Plasma methyl nutrients and metabolites, folate and vitamin B12 at 16 weeks of gestation1.

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Figure 3.

Scatter plot to show the correlation between estimated maternal choline intake and plasma free choline.

The results for plasma free choline were skewed and transformed to natural log values for analysis, r = 0.200, p = 0.013.

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Table 2.

Correlation coefficients among plasma methyl nutrient and metabolites, folate and vitamin B121.

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Table 3.

Characteristics of infants assessed at 18 months of age.

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Table 4.

Unadjusted and adjusted regression analyses of the association between infant neurodevelopment at 18 months and maternal plasma methyl donors at 16 weeks of gestation.

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Figure 4.

Scatter plots to show the relationship between infant cognitive scores and maternal plasma choline metabolites.

Plasma metabolite concentrations were normalized by a single natural log transformation (A, B and C). Infant cognitive development was assessed using the Bayley Scales of Infant Development III. The antilog of the natural log is equivalent to the exponential of the natural log value, that is 2.718 to the exponential of the value plotted on the x axis or ex. The results were analysed for 154 mother-infant pairs using Pearson correlation analysis, A. choline r = 0.190, p = 0.019, B. betaine r = 0.288, p = 0.0003, C. dimethylglycine, r = 0.157, p = 0.053.

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