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Commentary: One-carbon metabolism has major implications for fetal growth and development beyond neural tube defects.

a 56 -g reduction in birthweight of infants per standard deviation (SD) increase in homocysteine levels during pregnancy. However, a comparison of women in the lowest vs highest quartile for homcysteine suggests the potential for much greater effects (differences of 110–150 g). In addition, somewhat unusually, the estimates of the effect of maternal homocysteine on birthweight using a genetic proxy in the study by Yajnik and colleagues show a much stronger association (a reduction of about 250 g per SD of homocysteine) than the observational biomarker-birthweight association. This implies that the ‘real’ effect of one-carbon metabolism and its related nutrients (in the absence of confounding by other factors) is much greater than the 50 g reported, and is even greater that the difference in birthweight of offspring from smoking and non-smoking mothers (around 150 g to 200 g difference) 2 and suggests a key role of this pathway in fetal growth and development.