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Maternal Exposure to Nitrogen Dioxide, Intake of Methyl Nutrients, and Congenital Heart Defects in Offspring


Stingone, Jeanette A.; Luben, Thomas J.; Carmichael, Suzan L.; Aylsworth, Arthur S.; Botto, Lorenzo D.; Correa, Adolfo; Gilboa, Suzanne M.; Langlois, Peter H.; Nembhard, Wendy N.; & Richmond-Bryant, Jennifer, et al. (2017). Maternal Exposure to Nitrogen Dioxide, Intake of Methyl Nutrients, and Congenital Heart Defects in Offspring. American Journal of Epidemiology, 186(6), 719-729. PMCID: PMC5610640


Nutrients that regulate methylation processes may modify susceptibility to the effects of air pollutants. Data from the National Birth Defects Prevention Study, 1997-2006, were used to estimate associations between maternal exposure to nitrogen dioxide (NO2), dietary intake of methyl nutrients and the odds of congenital heart defects in offspring. NO2 concentrations, a marker of traffic-related air pollution, averaged across post-conception weeks 2-8, were assigned to 6160 non-diabetic mothers of cases and controls using inverse distance-squared weighting of air monitors within 50 km of maternal residence. Intake of choline, folate, methionine, and vitamins B6 and B12 were assessed using a food frequency questionnaire. Hierarchical regression models, which accounted for similarities across defects, were constructed and relative excess risks due to interaction were calculated. Relative to women with the lowest NO2 exposure and high methionine intake, women with the highest NO2 exposure and lowest methionine intake had the greatest odds of offspring with a perimembranous ventricular septal defect (Odds Ratio: 3.23, 95% Confidence Interval, 1.74, 6.01; Relative Excess Risk due to Interaction: 2.15, 95% Confidence Interval, 0.39, 3.92). Considerable departure from additivity was not observed for other defects. These results provide modest evidence of interaction between nutrition and NO2 exposure during pregnancy.


Reference Type

Journal Article

Year Published


Journal Title

American Journal of Epidemiology


Stingone, Jeanette A.
Luben, Thomas J.
Carmichael, Suzan L.
Aylsworth, Arthur S.
Botto, Lorenzo D.
Correa, Adolfo
Gilboa, Suzanne M.
Langlois, Peter H.
Nembhard, Wendy N.
Richmond-Bryant, Jennifer
Shaw, Gary M.
Olshan, Andrew F.,
for the National Birth Defects Prevention Study