Birth defects research. Part A, Clinical and molecular teratology

Biomarkers of the one-carbon pathway in association with congenital diaphragmatic hernia.

PMID 22730308


Homocysteine is an intermediate of the one-carbon (1-C) pathway and increased concentrations have been related to neural crest-related congenital anomalies. The neural crest and the 1-C pathway might be involved also in the etiology of Congenital Diaphragmatic Hernia (CDH). In 22 CDH and 28 control newborns and their mothers, general characteristics were obtained by standardized questionnaires. The 1-C pathway intermediates total homocysteine (tHcy), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were determined in cord blood. Correlations between maternal and newborn factors and risk estimates were investigated by univariate and multivariable logistic regression analyses. Birth weight (2962 vs. 3418 gram; p < 0.001) was lower and gestational age (270 vs. 277 days; p = 0.006) was shorter in case children. Control mothers were slightly older (32 vs. 35 year; p = 0.05). Other characteristics were comparable between case and control children and mothers. The concentrations of homocysteine, SAM and SAH, and the SAM/SAH ratio were comparable (tHcy: 8.57 vs. 8.56 μmol/l, p = 0.99; SAM: 152.7 vs. 157.3 nmol/l, p = 0.76; SAH: 43.5 vs. 48.9, p = 0.26; ratio: 3.8 vs. 3.5, p = 0.50). Maternal and newborn characteristics were not correlated to the biomarker concentrations. In conclusion, the biomarkers of methylation determined in cord blood are not associated with CDH risk. Maternal and child characteristics could not predict newborn biomarker concentrations of the 1-C pathway.