The Role of Folic Acid Fortification in Preventing Fetal Cardiac Defects

Abstract & Commentary

By John C. Hobbins, MD, Professor and Chief of Obstetrics, University of Colorado Health Sciences Center, Denver, is Associate Editor for OB/GYN Clinical Alert.

Dr. Hobbins reports no financial relationship to this field of study.

Synopsis: A Canadian study has shown that mandatory fortification of grain products in 1999 was associated with a significant decrease in congenital heart disease and strongly suggests that adequate intake of folic acid has a beneficial effect on the development of fetal heart, as well as the fetal spine.

Source: Ionescu-Ittu R, et al. Prevalence of severe congenital heart disease after folic acid fortification of grain products: Time trend analysis in Quebec, Canada. BMJ 2009;338:b1673; doi:10.1136/bmj.b1673.

The medical community has been well aware of the importance of adequate intake of folic acid in the prevention of neural tube defects (NTDs). However, less attention has been given to its role in the development of the fetal heart.

In a recent study from Quebec, the authors addressed the possible impact of government-mandated folic acid fortification of flour and pasta products, which was initiated in Canada in 1998.1 Taking into account a natural lag time between mandate and implementation, they used a "before and after" cut-off date of Jan. 1, 1999. Using Quebec provincial databases, the authors assessed the rate of severe congenital heart disease (CHD) in both stillborns and live births occurring 9 years before the cut-off and 7 years after this date. They could not tell which women had prenatal vitamins or supplementation with folic acid, but they postulated that the impact of dietary fortification would be on those who seek prenatal care after the fetal heart has been formed.

For a variety of reasons, the authors were predominantly interested in severe cardiac abnormalities, identified through ICD-9 codes, which included those with or without conotruncal defects such as teratology of Fallot, truncus arteriosus, and transposition complexes.

In the overall study population of 1.3 million births, there were 2083 infants born with severe cardiac defects (1.5/1000 births). Sixty percent were conotruncal in origin. The overall prevalence was about the same in the years prior to 1999. However, after folic acid fortification was implemented, there was a statistically significant drop by 6% (average of 1.6/1000 to 1.47/1000), after which the rate stayed reasonably steady for the next 7 years.

The authors concluded that the folate in pasta and flour did impact the rate of severe CHD, and, therefore, the study results endorsed the concept that adequate dietary intake of folic acid is important in the development of the fetal heart.

Commentary

The neural tube closes between 22 and 29 days post-conception, and a previous Hungarian study has shown that loading patients with folic acid (0.8 mg/day) in the first trimester can diminish the rate of NTDs by 90%.2 However, any decrease in the prevalence of NTDs at birth is also affected strongly by the enhanced early ability now to identify fetuses with the condition through alpha feto-protein (AFP) screening and ultrasound (with virtually 100% sensitivity), and the tendency to terminate pregnancy once the diagnosis is made.

The fetal heart takes longer to develop (between 29 and 49 days post-conception), and has a greater chance to develop abnormally. For example, although the above investigators found an incidence of severe cardiac abnormalities of only 1.67/1000, this figure rises to about 8/1000 when considering all cardiac anomalies. Interestingly, the incidence of babies born with spina bifida has dropped to well below the original 1/1000 figure in the United States, while the rate of CHD at birth has not changed appreciably over the last few years. This could be due to the fact that we are still not as good at picking up cardiac defects in the second trimester with ultrasound (the authors cite a Quebec study showing that only 25% of CHDs were diagnosed in utero3). Also, there is a general impression that contemporary methods of therapy can improve the quality of life appreciably for infants born with CHD, thereby diminishing the desire for women to terminate pregnancy when the diagnosis is made in utero.

So, with diet fortification, do we still need supplemental folic acid before and during pregnancy? The answer is certainly clear regarding NTD since another Canadian study, launched after the inception of folate fortification, showed that only 14% of women had serum folate levels high enough to prevent the development of neural tube defects.4 This could also apply to CHD.

Folate is a co-factor in the metabolism of homocysteine, a culprit in clotting abnormalities, various adverse pregnancy outcomes, and, pertinent to this discussion, abnormal organogenesis. For this reason, extra attention should be given to those with methylenetetrahydrofolate reductase (MTHFR) mutations,5 patients who have either delivered a baby with a cardiac defect or who themselves have a cardiac defect, patients with type 2 diabetes, or obese patients. All of these patients may have a predisposition toward altered folate/homocysteine metabolism.

The standard dose of folic acid is 0.8 mg/day, either delivered in combination with prenatal vitamins or separately for those individuals who are not taking vitamins.

References

  1. Ionescu-Ittu R, et al. Prevalence of severe congenital heart disease after folic acid fortification of grain products: Time trend analysis in Quebec, Canada. BMJ 2009;338:b1673; doi:10.1136/bmj.b1673.
  2. Czeizel AE. Periconceptional folic acid and multivitamin supplementation for prevention of neural tube defects and other congenital abnormalities. Birth Defects Res A Clin Mol Teratol 2009;85:260-268.
  3. Lennon CA, Gray DL. Sensitivity and specificity of ultrasound for the detection of neural tube and ventral wall defects in a high-risk population. Obstet Gynecol 1999;94:562-566.
  4. Shuaibi AM, et al. Folate status of young Canadian women after folic acid fortification of grain products. J Am Diet Assoc 2008;108:2090-2094.
  5. Van Beynum IM, et al. The MTHFR 677C->T polymorphism and the risk of congenital heart defects: A literature review and meta-analysis. QJM 2007;100:743-753.