Maternal global methylation status and risk of congenital heart diseases.
OBJECTIVE
To investigate whether the association between the maternal methylation status as reflected by low S-adenosylmethionine and high S-adenosylhomocysteine, is detrimental for cardiogenesis and congenital heart disease (CHD) in the offspring.


METHODS
As part of a case-control study in the western part of the Netherlands, we evaluated 231 mothers of children with CHD and 315 control mothers of nonmalformed children. The total case group was analyzed and stratified into isolated (n=180) and nonisolated CHDs (n=51). The latter subgroup was further subdivided into Nonsyndromic (n=20), Down Syndrome (n=19), and Other Syndromes (n=12). A multivariable general linear model was used to test for differences between the case groups and controls. All analyses were adjusted for current B vitamin supplement use.


RESULTS
Plasma total homocysteine was significantly different between the total case group (median, range 10.3, 4.0-43.8, P=.026) and the nonisolated cases (11.1, 5.5-43.8, P=.006) compared with the controls (10.0, 5.3-42.0). The subgroup of Down Syndrome presented significantly higher total homocysteine and S-adenosylhomocysteine levels and a lower S-adenosylmethionine/S-adenosylhomocysteine ratio than controls.


CONCLUSIONS
Maternal hyperhomocysteinemia, and not hypomethylation, is a risk factor for having a child with CHD. Maternal hypomethylation, however, seems to be associated with offspring having CHD and Down syndrome.
van Driel
Lydi M J W
LM
Departments of Obstetrics and Gynecology, Division of Obstetrics and Prenatal Medicine, Pediatrics, Pediatric Cardiology CAHAL-Centre for Congenital Anomalies of the Heart Amsterdam/Leiden, the Netherlands.
de Jonge
Robert
R
Helbing
Willem A
WA
van Zelst
Bertrand D
BD
Ottenkamp
Jaap
J
Steegers
Eric A P
EA
Steegers-Theunissen
Regine P M
RP
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D004314:Down Syndrome / Q000453:epidemiology / Q000209:etiology; D005260:Female; D006321:Heart / Q000196:embryology; D006330:Heart Defects, Congenital / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications*; D007223:Infant; D016014:Linear Models; D008745:Methylation; D011247:Pregnancy; D011248:Pregnancy Complications; D011256:Pregnancy Outcome / Q000453:epidemiology; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D012435:S-Adenosylhomocysteine / Q000097:blood*; D012436:S-Adenosylmethionine / Q000097:blood*
D015415:Biomarkers; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine