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Stacey A. Missmer,^1,2 Lucina Suarez,³ Marilyn Felkner,³ Elaine Wang,⁴ Alfred H. Merrill Jr.,⁴ Kenneth J. Rothman,⁵ and Katherine A. Hendricks⁶

¹Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA; ²Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; ³Texas Department of State Health Services, Austin, Texas, USA; ⁴School of Biology, Georgia Institute of Technology, Atlanta, Georgia, USA; ⁵Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA; ⁶Medical Institute, Austin, Texas, USA

Abstract
Along the Texas-Mexico border, the prevalence of neural tube defects (NTDs) among Mexican-American women doubled during 1990-1991. The human outbreak began during the same crop year as epizootics attributed to exposure to fumonisin, a mycotoxin that often contaminates corn. Because Mexican Americans in Texas consume large quantities of corn, primarily in the form of tortillas, they may be exposed to high levels of fumonisins. We examined whether or not maternal exposure to fumonisins increases the risk of NTDs in offspring using a population-based case-control study. We estimated fumonisin exposure from a postpartum sphinganine:sphingosine (sa:so) ratio, a biomarker for fumonisin exposure measured in maternal serum, and from maternal recall of periconceptional corn tortilla intake. After adjusting for confounders, moderate (301-400) compared with low (≤ 100) consumption of tortillas during the first trimester was associated with increased odds ratios (ORs) of having an NTD-affected pregnancy (OR = 2.4 ; 95% confidence interval, 1.1-5.3) . No increased risks were observed at intakes higher than 400 tortillas (OR = 0.8 for 401-800, OR = 1.0 for > 800) . Based on the postpartum sa:so ratio, increasing levels of fumonisin exposure were associated with increasing ORs for NTD occurrences, except for the highest exposure category (sa:so > 0.35) . Our findings suggest that fumonisin exposure increases the risk of NTD, proportionate to dose, up to a threshold level, at which point fetal death may be more likely to occur. These results also call for population studies that can more directly measure individual fumonisin intakes and assess effects on the developing embryo. Key words: case-control study, corn, fumonisins, Mexican Americans, mycotoxins, neural tube defects. Environ Health Perspect 114:237-241 (2006) . doi:10.1289/ehp.8221 available via http://dx.doi.org/ [Online 29 September 2005]

Address correspondence to L. Suarez, Texas Department of State Health Services, Epidemiology Research Services Branch G-401, 1100 West 49th St., Austin, TX 78756-3199 USA. Telephone: (512) 458-7729 ; Fax: (512) 458-7229. E-mail lucina.suarez@dshs.state.tx.us

We thank L. Marks for assistance on the seasonal fumonisin data ; M. Trucksess, U.S. Food and Drug Administration, for the tortilla analyses ; and D. Miller and J. Villanacci for their helpful insight.

Funding was provided by Centers for Disease Control and Prevention (CDC) Birth Defects Branch cooperative agreement U85/CCU608761-05 and Texas Birth Defects Research Center/CDC cooperative agreement U50/CCU613232. P. Blackshear (National Institute of Environmental Health Sciences) provided funding for laboratory services so that the second batch of serum could be tested.

The authors declare they have no competing financial interests.

Received 18 April 2005 ; accepted 29 September 2005.