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Lucina Suarez, PhD Kate Hendricks, MD Texas Department of Health

Neural Tube Defects Among Mexican Americans Living on the Texas-Mexico Border: Effects of Folic Acid and Dietary Folate. Lucina Suarez, PhD Kate Hendricks, MD Texas Department of Health. Prepared by Zunera Gilani , 2002. Suggested Readings.

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Lucina Suarez, PhD Kate Hendricks, MD Texas Department of Health

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  1. Neural Tube Defects Among Mexican Americans Living on the Texas-Mexico Border:Effects of Folic Acid and Dietary Folate Lucina Suarez, PhD Kate Hendricks, MD Texas Department of Health Prepared by Zunera Gilani, 2002

  2. Suggested Readings • Suarez L, Hendricks KA, Cooper SP, et al. Neural tube defects among Mexican Americans living on the US-Mexico border : Effects of folic acid and dietary folate. Am J Epidemiol 2000; 152: 1017-23. • Shaw GM, Schaffer D, Velie EM,et al. Periconceptional vitamin use, dietary folate, and the occurrence of neural tube defects. Epidemiology 1995; 6: 219-26. • Harris JA, Shaw GM. Neural tube defects-why are rates high among populations of Mexican descent? Environ Health Perspect 1995; 103 (suppl 6): 163-4. • Hendricks KA, JS Simpson, Larsen RD. Neural tube defects along the Texas-Mexico border, 1993-1995. Am J Epidemiol 1999;149 : 1119-27.

  3. Neural Tube Defects • NTDs are malformations of the developing brain and spinal cord • NTD closure occurs during the fourth week of embryosis • The most common NTDs are anencephaly and spina bifida • Numerous studies have shown a 50% to 100% reduction in NTDs by taking .4 mg of folic acid daily • NTD prevalence is higher among Mexican Americans (9-16 per 10,000) than non-Hispanic whites (6 per 10,000) and African Americans (5 per 10,000)

  4. Background • Cameron County, on the Texas-Mexico border, had the highest prevalence in the US since the 1970s--29 per 10,000 in 1991 Texas Mexico Cameron County Brownsville

  5. US Prevalence per 10,000 Births • Hawaii 1988-94 7.2 • Iowa 1985-90 9.0 • California 1989-91 9.3 • Atlanta 1990-91 9.9 • Arkansas 1985-89 10.3 • South Carolina 1992-94 16.0

  6. Prevalence in Mexican Americans(per 10,000 births) • Cameron County, Texas 1990-92 21.2 • Texas-Mexico border 1993-95 14.9 Mexico-born 15.1 US-born 9.5 • California 1989-91 Mexico-born 16.0 US-born 6.8

  7. Folic Acid Supplements Estimated Risk Reduction from Clinical Trials

  8. Folic Acid Supplements Estimated Risk Reduction from Case-Control Studies

  9. Shaw 1995 : Results on Folic Acid Supplements by Race/Ethnicity OR 95% CI Mexican American 1.0 0.4-2.1 Non-Hispanic White 0.6 0.4-1.1 African American 0.5 0.1-3.2

  10. Shaw 1995: Results on Combined Folate Intake from Vitamins and Diet Folate µgMexican American Non-Hispanic <228 referent referent 228-399 1.0 (0.4-2.4) 0.6 (0.2-1.7) 400-999 0.8 (0.3-1.9) 0.6 (0.2-1.5) ≥1000 0.6 (0.2-2.0) 0.3 (0.1-0.8)

  11. Specific Aims of Texas Border Study To determine the extent that preconception intake of: • supplemental folic acid • dietary folate alone • folic acid and folate from combined sources reduces the risk of NTDs in Mexican American women

  12. Case Definition • Cases were ascertained through active surveillance of the 14 counties along the Texas-Mexico border (Jan 1995-May 2000) • Cases were identified from multiple sources including hospitals, birthing centers, midwives, genetic clinics, abortion clinics

  13. Population-basedCase-Control Study • Cases included all clinically apparent NTDs at all gestational ages prenatally diagnosed, induced or spontaneously aborted still or live born • Controls were randomly selected from normal live births, frequency matched by hospital and year

  14. Measurement Instruments • In-person interviews, English or Spanish, one month postpartum • Extensive mother questionnaire health and reproductive history, demographics, nutritional supplements, drug use, environmental exposures • 98-item food frequency questionnaire • Exposure in the periconceptional period, 3 months before to 3 months after conception

  15. Main Exposure Variables • Folic acid supplements prenatal vitamins, multivitamins or single-ingredient folic acid tablets • Dietary folate based on food frequency questionnaire • Combined supplemental folic acid and dietary folate

  16. maternal age education annual income country of birth cigarette smoking alcohol use diabetes obesity gravidity previous pregnancy loss prenatal care oral contraceptive use Confounding Variables

  17. Study Participation Rates Case womenControl women Identified for study 225 378 Completed interview 184 225 Refused interview 26 101 Moved 15 52

  18. NTD type 83 anencephaly 84 spina bifida 17 encephalocele Gestation 41 <20 weeks 70 >35 weeks Pregnancy outcome 94 live births 27 still births 4 miscarriages 59 elective terminations Distribution of Cases

  19. Demographic and Risk Factor Characteristics

  20. Crude ORs for NTD Risk Factors

  21. Daily Vitamin Use AmongCase and Control Women

  22. Use of Folic Acid-Containing Vitamins

  23. Frequency Distribution ofAverage Daily Dietary Folate Intake

  24. Periconceptional Vitamin Use

  25. Effect of Preconceptional Use ofFolic Acid-Containing Vitamins on NTD Risk OR95% CI Crude 0.7 0.2-2.1 Adjusted 0.8 0.2-2.6 • Odds ratios are compared to non-users alone • Adjusted for education, age, previous pregnancy loss, and obesity

  26. Effect of Dietary Folate on NTD Risk

  27. Effect of Combined Dietary and Supplemental Folate

  28. Main Findings • Mild to no benefit in using folic acid containing vitamins (20% reduction) • 30% risk reduction for combined intakes of ≥1.0 mg per day, adjusted for covariates

  29. Underlying Population Factors • Economically disadvantaged and medically underserved • Distinct gene admixture with Amerindian population • Traditional yet atypical dietary pattern • Environmental contaminants • pesticides or fumonisins • Higher frequencies of specific folate pathway gene polymorphisms

  30. Study Limitations • Low power • Low prevalence of exposure • Homogeneous dietary exposure

  31. Potential Biases Food Frequency Questionnaire • FFQs less valid among low-educated populations • FFQs overestimate absolute levels of folate intake • Referenced a single period from 3 months before to 3 months after conception (pregnancy influenced recall)

  32. Potential Biases • Differential recall period between cases and controls (ie, gestational age) • Differential participation rates (60% vs 82%) • Controls demographically similar to source population

  33. Inconclusive results because of methodological problems • Almost no exposure to folic acid • Homogeneous dietary exposures • Sources of bias would push estimated effects toward the null

  34. Recommendations • Test this hypothesis in a Mexican American population more highly exposed to folic acid • Pursue all recommended prevention strategies • Motivate Mexican American women of childbearing age to take folic acid routinely • Fortify foods consumed by this population

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