Maternal Dietary and Supplemental Myo-Inositol Intake during the Periconceptional Period and Risk of Congenital Heart Defects

Abstract

Background: Although animal studies indicate maternal myo-inositol intake reduced the risk of congenital heart defects (CHDs) in offspring, this association in humans is rarely studied. A case-control study was conducted to explore this association using data from the National Birth Defects Prevention Study (NBDPS).

Study Design: Live births, stillbirths, and terminations with nonsyndromic CHDs delivered from October 1997 through December 2011 were included as cases. Live births without major structural birth defects, delivered from October 1997 through December 2011, were included as controls. Maternal intake of myo-inositol, copper, zinc, folic acid/folate, and alcohol were calculated using the 58-item Willett food frequency questionnaire and questions that collected intake of cereals, food supplements, supplements, medications, and alcoholic beverages. Associations between myo-inositol intake and CHDs in offspring were assessed using logistical regression models. Additive interactions and multiplicative interactions were assessed between myo-inositol intake and intake of folic acid/folate, copper, zinc, and alcohol.

Results: A total of 11,402 singletons with any CHD and 11,415 singleton controls were included. High intake of myo-inositol (≥ 500 mg/day) from maternal diet and supplements was associated with decreased odds of any CHD in offspring (OR = 0.87; 95% CI: 0.82–0.92). A strong negative association between maternal folic acid/folate intake and truncus arteriosus (OR = 0.56, 95% CI: 0.33–0.95) among women with high dietary myo-inositol intake was observed. The negative association between total myo-inositol intake and CHDs was observed for the occurrence of common truncus (OR = 0.48, 95% CI: 0.22–1.03) in the high copper intake group, d-transposition of the great arteries (OR = 0.74, 95% CI: 0.60–0.92) in the high zinc intake group, and aortic stenosis (OR = 0.70, 95% CI: 0.51–0.97) among alcohol users. Multiplicative interactions between myo-inositol intake and intake of zinc, alcohol, and folic acid/folate on the occurrence of several CHD subtypes were observed (P < 0.05).

Conclusions: Maternal myo-inositol intake reduced the occurrence of CHDs in offspring. The negative association between folic acid/folate intake and CHDs in offspring was strengthened by maternal myo-inositol intake. Future studies with the measurement of myo-inositol levels in tissue or a more sophisticated assessment of dietary myo-inositol intake should be conducted to verify these findings.