American Journal of Epidemiology Advance Access published online on October 25, 2008
American Journal of Epidemiology, doi:10.1093/aje/kwn320
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mosley and Hobbs Respond to "Folic Acid Fortification and Neural Tube Defects"
Correspondence to Dr. Charlotte A. Hobbs, Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, 1120 Marshall Street, Slot 512-40, Little Rock, AR 72202 (e-mail: hobbscharlotte{at}uams.edu).
Received for publication September 2, 2008. Accepted for publication September 15, 2008.
We appreciate the invited commentary from Drs. Mills and Carter (1) regarding our report of the association between neural tube defects and folate following mandatory fortification in the US population (2). We welcome the authors’ comments on potential recall or ascertainment biases and encourage the interpretation of our findings with these in mind. As stated by Mills and Carter, we believe that these findings from the National Birth Defects Prevention Study provide evidence of the effectiveness of folic acid fortification.
One possible conclusion from our findings, stated both in the Discussion of our article and by Mills and Carter, is that folic acid fortification activities may have reached levels sufficient to prevent most folate-preventable neural tube defects. We encourage caution in assuming that these findings provide final evidence that current fortification levels are optimal. It is unlikely that an identical folic acid supplement dose will protect against all folate-preventable outcomes among all population subgroups.
The exact mechanism by which folic acid prevents birth defects during embryogenesis is unclear. Bioavailability varies by folate source, and individual variability on folate demand may exist by lifestyle factors and genetic susceptibilities. Using a subset of the National Birth Defects Prevention Study population, we have previously reported on the higher concentration of maternal homocysteine levels and a metabolic profile consistent with reduced methylation and increased oxidative stress among women with neural tube defect-affected pregnancies relative to control women (3). Investigators from the National Birth Defects Prevention Study and others are continuing to evaluate the neural tube defect–folate relation among subgroups of women who may be at higher risk of folate-sensitive outcomes, such as Hispanics, women with type I or type II diabetes (4), and obese women (5, 6).
Most promising are the anticipated analyses from the National Birth Defects Prevention Study and other studies that will enable investigators to evaluate gene–environment interactions related to this topic. For example, the interactive effects of smoking and folate may be heightened among specific maternal genotypes. Individual genetic susceptibilities may lead to more targeted clinical and public health recommendations regarding the optimal dose of folic acid intake during reproductive years.
Mills and Carter (1) remind us of the ongoing investigations between folic acid and cardiovascular disease and cancer. Additionally, folic acid also has been associated with other birth defects, including orofacial cleft defects (7–11) and congenital heart defects (12–16), and other adverse reproductive outcomes, including prematurity (17) and preeclampsia (18). Optimal folic acid dosage levels to prevent these outcomes are not known. In light of current understanding of folate, we strongly encourage further research, particularly molecular epidemiologic studies, to better inform public health programs and clinical interventions aimed at optimizing reproductive outcomes.
 |
ACKNOWLEDGMENTS |
|---|
Author affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, Arkansas (Bridget S. Mosley, Charlotte A. Hobbs).
Conflict of interest: none declared.
|
References |
|---|
 TOP References |
|---|
- Mills JL, Carter TC. Invited commentary: Preventing neural tube defects and more via food fortification? Am J Epidemiol (2008) 168(00):0000–0000.
- Mosley BS, Cleves MA, Siega-Riz AM, et al. Neural tube defects and maternal folate intake among pregnancies conceived after folic acid fortification in the United States. Am J Epidemiol (2008) 168(00):0000–0000.
- Zhao W, Mosley BS, Cleves MA, et al. Neural tube defects and maternal biomarkers of folate, homocysteine, and glutathione metabolism. Birth Defects Res A Clin Mol Teratol (2006) 76(4):230–236.[CrossRef][Web of Science][Medline]
- Correa A, Gilboa SM, Besser LM, et al. Diabetes mellitus and birth defects. Am J Obstet Gynecol (2008) 199(3):237. e1–237.e9.[Medline]
- Waller KD, Shaw GM, Rasmussen SA, et al. Pre-pregnant obesity as a risk factor for structural birth defects. Arch Pediatr Adolesc Med (2007) 161(8):745–750.
[Abstract/Free Full Text] - Rasmussen SA, Chu SY, Kim SY, et al. Maternal obesity and risk of neural tube defects: a metaanalysis. Am J Obstet Gynecol (2008) 198(6):611–619.[CrossRef][Web of Science][Medline]
- Badovinac RL, Werler MM, Williams PL, et al. Folic acid-containing supplement consumption during pregnancy and risk for oral clefts: a meta-analysis. Birth Defects Res A Clin Mol Teratol (2007) 79(1):8–15.[CrossRef][Web of Science][Medline]
- Itikala PR, Watkins ML, Mulinare J, et al. Maternal multivitamin use and orofacial clefts in offspring. Teratology (2001) 63(2):79–86.[CrossRef][Web of Science][Medline]
- Berry RJ, Li Z, Erickson JD, et al. Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention. N Engl J Med (1999) 341(20):1485–1490.
[Abstract/Free Full Text] - Shaw GM, Lammer EJ, Wasserman CR, et al. Risks of orofacial clefts in children born to women using multivitamins containing folic acid periconceptionally. Lancet (1995) 346(8972):393–396.[CrossRef][Web of Science][Medline]
- Khoury MJ, Cordero JF, Mulinare J, et al. Selected midline defect associations: a population study. Pediatrics (1989) 84(2):266–272.
[Abstract/Free Full Text] - Botto LD, Mulinare J, Erickson JD. Do multivitamin or folic acid supplements reduce the risk for congenital heart defects? Evidence and gaps. Am J Med Genet A (2003) 121A(2):95–101.
- Botto LD, Mulinare J, Erickson JD. Occurrence of congenital heart defects in relation to maternal mulitivitamin use. Am J Epidemiol (2000) 151(9):878–884.
[Abstract/Free Full Text] - Botto LD, Khoury MJ, Mulinare J, et al. Periconceptional multivitamin use and the occurrence of conotruncal heart defects: results from a population-based, case-control study. Pediatrics (1996) 98(5):911–917.
[Abstract/Free Full Text] - Czeizel AE. Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet. (1996) 62(2):179–183.[CrossRef][Web of Science][Medline]
- Shaw GM, O'Malley CD, Wasserman CR, et al. Maternal periconceptional use of multivitamins and reduced risk for conotruncal heart defects and limb deficiencies among offspring. Am J Med Genet. (1995) 59(4):536–545.[CrossRef][Web of Science][Medline]
- Catov JM, Bodnar LM, Ness RB, et al. Association of periconceptional multivitamin use and risk of preterm or small-for-gestational-age births. Am J Epidemiol (2007) 166(3):296–303.
[Abstract/Free Full Text] - Wen SW, Chen XK, Rodger M, et al. Folic acid supplementation in early second trimester and the risk of preeclampsia. Am J Obstet Gynecol (2008) 198(1):45. e1–45.e7.[Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||