Neural%20Tube%20Defects%20Among%20Mexican%20Americans%20Living%20on%20the%20Texas-Mexico%20Border:%20Effects%20of%20Folic%20Acid%20and%20Dietary%20Folate

1
Neural Tube Defects Among Mexican Americans
Living on the Texas-Mexico BorderEffects 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 1999149 1119-27.

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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

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Folic Acid Supplements

• Estimated Risk Reduction from Clinical Trials

Author Location NTD Type Study Size Risk Reduction
Laurence 1981 Wales Recurrence 111 57
Smithells 1983 England Recurrence 1052 88
Vergel 1990 Cuba Recurrence 214 100
MRC 1991 Europe Recurrence 1195 72
Kirke 1992 Ireland Recurrence 261 100
Czeizel 1992 Hungary Occurrence 4156 100
Milunsky 1989 USA Occurrence cohort 13870 73
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Folic Acid Supplements

• Estimated Risk Reduction from Case-Control
  Studies

Author Location CaseControl Risk Reduction
Winship, 1984 England 764764 86
Mulinare, 1988 Atlanta 1811480 60
Mills, 1989 Illinois-California 565567 11
Martinez-Frias, 1992 Spain 1673616574 30
Bower, 1992 Australia 75150 89
Werler, 1993 Boston-Philadelphia 2321558 60
Shaw, 1995 California 295247 35
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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

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Shaw 1995 Results on Combined Folate Intake from
Vitamins and Diet

• Folate µg Mexican American Non-Hispanic
• lt228 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)

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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

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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

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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

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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

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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
Confounding Variables

• maternal age
• education
• annual income
• country of birth
• cigarette smoking
• alcohol use

• diabetes
• obesity
• gravidity
• previous pregnancy loss
• prenatal care
• oral contraceptive use

17
Study Participation Rates

• Case women Control women
• Identified for study 225 378
• Completed interview 184 225
• Refused interview 26 101
• Moved 15 52

18
Distribution of Cases

• NTD type
• 83 anencephaly
• 84 spina bifida
• 17 encephalocele
• Gestation
• 41 lt20 weeks
• 70 gt35 weeks

• Pregnancy outcome
• 94 live births
• 27 still births
• 4 miscarriages
• 59 elective terminations

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Demographic and Risk Factor Characteristics
20
Crude ORs for NTD Risk Factors
Risk Factor OR 95 CI
Age gt25 years 0.9 0.6-1.3
Mexico-born 1.1 0.8-1.7
Education 7 years 0.6 0.3-1.0
Cigarette smoking 1.8 1.0-3.0
Alcohol use 1.3 0.8-1.9
Diabetes 1.6 0.7-3.3
Obesity 1.8 1.1-2.8
Prior pregnancy loss 1.9 1.1-3.3
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
Vitamin Use Case Women Case Women Control Women Control Women
Vitamin Use No. No.
None (6 month interval) 102 44.7 126 5.3
Preconception Any use 1-3 months before conception 11 6.0 10 4.4
Daily use every month before conception 5 2.7 9 4.0
Postconception (use 1-3 months after) 102 55.4 126 56.0
25
Effect of Preconceptional Use ofFolic
Acid-Containing Vitamins on NTD Risk

• OR 95 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
Daily Folate Intake (mg/day) OR 95 CI Adj OR 95 CI
.925-.431 1.0 referent  1.0 referent 
.432-.613 1.0 0.6-1.7 1.0 0.6-1.8
.614-.786 0.7 0.4-1.1 0.7 0.4-1.2
.787-2.10 0.7 0.4-1.3 0.8 0.4-1.4
27
Effect of Combined Dietary and Supplemental
Folate
Folate Intake (mg/day) OR 95 CI Adj OR 95 CI
lt.400 1.0 referent 1.0 referent
.400-.999 0.8 0.5-1.3 0.9 0.5-1.4
1.000 0.7 0.3-1.3 0.7 0.3-1.4
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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