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Transcript of Folic Acid: What’s New? Karla Damus, RN, MSPH, PhD Dept Ob/Gyn and Women’s Health Albert...
Folic Acid:Folic Acid:What’s New?What’s New?
Karla Damus, RN, MSPH, PhDDept Ob/Gyn and Women’s HealthAlbert Einstein College of Medicine
March of Dimes Birth Defects [email protected]
March of Dimes Birth Defects Foundation
Mission:• To improve infant outcomes by preventing infant mortality
and birth defects
The Continuum of Reproductive Health• Improving health of infants requires focusing on the entire
spectrum of reproductive health which extends from prior to conception through the first year of an infant’s life and throughout the woman’s childbearing years
• Preconceptional health is the cornerstone of healthy infants, children, families and communities
Infant MortalityUnited States, 1915-1998
0
20
40
60
80
100
120
1915 1925 1935 1945 1955 1965 1975 1985 1995
Rate per 1,000 live births
Source: National Center for Health Statistics, final mortality data
Prepared by March of Dimes Perinatal Data Center, 2000
Ten Leading Causes of Infant MortalityUnited States, 1998
11.2
11.7
19.1
20.7
24.4
32.9
34.1
71.6
104.0
157.6
0 20 40 60 80 100 120 140 160 180
Pneumonia/Influenza
Hypoxia/Birth Asphyxia
Accidents
Infections
Placenta, Cord Comp.
RDS
Maternal Preg.Comp.
SIDS
Preterm/LBW
Birth Defects
Rate per 100,000 live births
Source: National Center for Health Statistics, 1998 final mortality data
Prepared by March of Dimes Perinatal Data Center, 2000
Leading Cause-Specific Infant Mortality RatesUnited States, 1988 and 1998
208.2
83.6
140.1
36.1
81.4
157.6
104.0
71.6
32.934.1
0
50
100
150
200
250
Birth Defects Preterm /LBW
SIDS MaternalPreg. Comp.
RDS
1988 1998
Rate per 100,000 live births
Source: National Center for Health Statistics, 1988 and 1998 final mortality data
Prepared by March of Dimes Perinatal Data Center, 2000
Leading Cause-Specific Infant Mortality RatesBy Maternal Race, United States, 1998
154.2
71.359.5
26.9 26.3
180.2
277.6
137.9
73.3 71.8
0
50
100
150
200
250
300
Birth Defects Preterm /LBW
SIDS MaternalPreg. Comp.
RDS
White Black
Rate per 100,000 live births
Source: National Center for Health Statistics, 1998 period linked birth/infant death data
Prepared by March of Dimes Perinatal Data Center, 2000
Leading Causes of Infant DeathsUnited States, 1998
Prematurity/LBW14.5% Circulatory 5.1%
Genitourinary 5.9%
Musculoskeletal 7.3%
Nervous Sys. 12.2%
Other 10.7%
Chromosomal 15.2%
Respiratory 15.5%
Heart 28.2%
RDS4.6%
Mat. Comp. ofPreg 4.8%
SIDS10.0%
All Other Causes44.2%
Birth Defects22.0%
Source: National Center for Health Statistics, 1998 period linked birth/infant death data
Prepared by March of Dimes Perinatal Data Center, 2000
Prevalence of NTDs in US
• Neural tube defects (NTDs) are a group ofmalformations of the developing brain andspine, including anencephaly and spina bifida
• about 2500 births/yr in U.S. (1 in 1500 births)
• Birth defects are the leading cause of infant mortality causing 1 out 5 infant deaths
• About 7% of infant deaths due to birth defects are due to NTDs
Neural Tube Defects
Anencephaly: absence of the majority of the brain and surrounding area at birth.
Spina Bifida (“open spine”): defect of the spine that can cause paralysis of varying degrees.
Data not available for these states
Preliminary Neural Tube Defect Ratesby State, 1992-1996
Relative Risk for Spina Bifida By Race/Ethnicity, U.S., 1983-1990
RACE/ETHNICITY ADJUSTED RELATIVE RISK (95% CI)
White 1.00
Black 0.80 (0.72-0.88)
Hispanic 1.41 (1.26-1.58)
Asian/Pacific Islander 0.51 (0.38-0.70)
Native American 1.13 (0.74-1.74)
*Based on 16 state-based birth defects surveillance systemsSource: CDC, Teratology, July/August 1997Prepared by March of Dimes Perinatal Data Center, 1999
NTDs Among Hispanic Infants
• Hispanic infants, particularly US-born Mexicans are at greatest risk for NTDs.
• In a total of 6 selected states, Hispanic infants had a significantly higher rate of NTDs than non-Hispanic white infants.
• Not all birth defects surveillance programs collect data on Hispanic ethnicity.
Infant Deaths due to NTDs by Race/Ethnicity, United States, 1996
7.9
9.9
16.317.9
9.5
16.8 16.8
02
468
10121416
1820
Blacknon-
Hispanic
Whitenon-
Hispanic
Hispanic Mexican PuertoRican
Cuban Central /So.
American
Rate per 100,000 live births
Source: National Center for Health Statistics, 1996 period linked birth/infant death filePrepared by March of Dimes Perinatal Data Center, 1999
Healthy People 2010 MCH Objectives Related to Folic Acid and Neural Tube Defects
• Reduce the incidence of spina bifida and other NTDs to no more than 3 per 10,000 live births– 1996 Baseline: 6
• Increase the proportion of women who consume 400 mcg of folic acid daily to at least 80%– 1997 Baseline: 30%
• (Developmental) Increase mean red blood cell folate among women 18-44 years– Potential data source: National Health And Nutrition Examination Survey (NHANES)
What is Folic Acid
• Folate is a water-soluble B vitamin derived from folate polyglutamates
• Found in green leafy vegetables, organ meats, some fresh fruits
• Susceptible to destructive oxidation with 50-95% destroyed in canning and cooking
Definitions
• FOLIC ACID (FA) = pteroylglutamic acid
synthetic, used in fortified foods & supplements
• FOLATES = pteroyl - poly - glutamic acid
appear naturally in foods or are formed in vivo
Folic Acid (FA): Background
• FA deficiency described as"tropical macrocytic anemia"in 1930's
• Pure FA isolated from spinachin 1945 (folium Latin for leaf)
• Antifolates found to cause neuraltube defects (NTD's) in 1950's
Folic Acid (FA) Deficiency
• FA deficiency redefined in 1990's• hematological, embryonic, fetal, pregnancy health
• Now clear that FA deficiency is common
• FA deficiency predisposes to:
• NTD’s
• Other birth defects (cleft lip +/- palate, cardiac, etc)
• Low birth weight and prematurity
• Atherosclerotic vascular disease (stroke, CAD)
• Colorectal and cervical cancer
'81-S. Wales'80-Smithells
'90-Cuba'91-UK-MRC'92-Hungary
'88-Atlanta'89-W. Australia'89-CA/Illinois'89-Boston
'93-New England
0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2
Multivitamin & Folic AcidNeural Tube Defect Studies, 1980-1999
Risk Ratio With 95% Confidence Intervals
'95-California
Randomized trialsNon-randomized trialsObservational studies
2.4
'99-P.R. China
NTDs Relationship to FA Status
• NTD’s linked to antifolates, 1950's
• RBC folate in NTD mothers, 1976
• Essentially all clinical studies of FA, 1981-99: 50-85% in NTD’s
• Biochemical basis of NTD’s not known ( DNA; homocysteine ?)
FA: Role in Metabolism
Coenzyme in 1-carbon transfer reactions:
• biosynthesis of purines & pyrimidines (DNA/RNA)
• biosynthesis of serine & methionine
• degradation of histidine
• degradation of homocysteine
Folic Acid Recommendations
USPHS September, 1992• All women of childbearing potential should
consume 0.4 mg (400 micrograms) of folic acid daily
Food & Nutrition Board of IOM, 1998• Men (14 yr & older) 400 µg any source
• Women (14 yr & older) 400 µg synthetic + food
• Pregnancy 600 µg synthetic + food
• Lactation 500 µg any source
SummaryFolic Acid - Neural Tube Defect Science
• Increasing blood/RBC folate concentration decreases the risk of NTD’s
• Consumption of 400 micrograms of folic acid daily prior to conception - as part of a healthy diet - decreases the risk of NTD’s in all populations up to 70%
• Ethnic and genetic variations in NTD risk remain poorly characterized
Bioavailability of Food Folates
• Folates are lost from foods by:- preparation (heat, oxidation, leaching into
water)- inhibition of essential gut enzymes by inhibitors in food, extremes in pH and rapid transit time
• Under controlled conditions, 30-80% of folate is absorbed
• One careful 92-day metabolic study found no more than 50% bioavailability of various food folates
FA to Prevent NTDs
• Diet
• Fortification of grain products with folic acid
• Multivitamin with 0.4 mg FA from beforeconception through first 28 daysRemember: > 50% pregnancies unplanned
Dietary Folates/FA
orange juice
spinach
turnip greens
asparagus
pinto beans
beef liver
fortified bread (slice)
fortified noodles
fortified brkf. Cereal
Food Avg. µg in serving Bioavailability (%)
109
102
85
101
147
184
35
192
100 or 400
43
63
50
100
100
100
Consumption of Folic Acid & Dietary Folate:Effect on Red Cell Folate, Ireland 1996.
Intervention method
Red cell folate mcg/L Pre- / post- intervention
Meanpercentage
change
Supplement400 mcg FA
Fortified food400 mcg FA
Dietary folate400 mcg folate
Dietary advice
Controls
351 - 492
326 - 335
345 - 399
366 - 394
326 - 498
+ 40, p<0.05
+ 52, p<0.05
+ 11, NS
+ 16, NS
+ 5
Cuskelly et al., Lancet; 1996.
China-U.S. Collaborative Folic Acid Project for NTD Prevention, 1993-1996.
Shanghai
Shanxi Province
Zhejiang Province
Jiangsu Province
Hebei ProvinceBeijing
Intervention = 400 mcg Intervention = 400 mcg folic acid supplement dailyfolic acid supplement daily
0.00.0
1.01.0
2.02.0
3.03.0
4.04.0
5.05.0
NorthNorth SouthSouth
41% 41%
NT
D R
ate
/10
00
NT
D R
ate
/10
00 85%85%
No PillsNo Pills PillsPills
Berry RJ, et al., NEJM 1999; 341:1485-90
China Folic Acid Community Intervention ProgramChina Folic Acid Community Intervention Program to Prevent the Occurrence of Neural Tube Defects, 1993 -
1996
Summary of Folic Acid - Neural Tube Defect Science
• Increasing blood/RBC folate concentration decreases the risk of NTD’s
• Consumption of 400 micrograms of folic acid daily prior to conception decreases the risk of NTD’s in all populations up to 85%
• Racial and ethnic variations in NTD risk• Genetic variations in NTD risk remain
uncharacterized
Multivitamin Use/Folic AcidCongenital Heart Defects, 1995-2000
Randomized trial
Observational studies
Outflow tract
Birth Defect Type
Septal defects
All heart defects
Coarctation
Scanlon
Czeizel
Botto
Botto
Czeizel
Botto
Shaw
Czeizel
Werler
Werler
Botto0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.05.0
Risk Ratio and 95% CI
Multivitamin Use/Folic AcidSelected Non-NTD, Non-CHD Birth Defects
Risk Ratio and 95% CI
Oro-facial clefts
Limb
Urinary tract
All defectsexcept NTD
Randomized trialNon-randomized trialObservational studies
Czeizel
ShawYang
Li
ShawHayes
Tolarova Czeizel
Werler
Werler
Werler
0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 5.0
CL +/- CPCP alone
March of DimesNational Folic Acid Campaign: 1999-2002
• March of Dimes Campaign goal is to reduce NTD’s by at least 30% by 2002
• Behavior modification campaign is outcome driven, with three strategies:– professional education– community action– mass media
• National Council on Folic Acid (see March of Dimes website for members www.modimes.org)
• Since 1998, March of Dimes is the lead agency• Partners in campaign
Three Approaches for Changing Behavior
Folic Acid to Prevent NTD’s
• Behavior Strategy; Multivitamin containing 400 micrograms folic acid - as part of a healthy diet - beginning before conception
• Remember: neural tube closes by day 28 pregnancy
• Legislative Strategy; Increase consumption of folic acid by fortification of grain products with folic acid - required of “enriched grain products” since January 1998
• Remember: > 50% pregnancies unplanned
Mass Media:
Increase awareness of folic acid benefits
• TV PSA’s - Traffic Baby, Before you know it, Ready-Not, Stork 1 & 2, Shopping Carts
• Print PSA’s
• Latina Print Materials
• Have conducted continuing evaluation of awareness, knowledge, and behavior
• Let’s look at several TV PSA’s now
March of Dimes Folic Acid Campaign Evaluation
• National telephone surveys conducted by Gallup in
1995, 1997, 1998 and 2000
• Surveys designed to evaluate women’s changing
awareness and reported behaviors related to folic
acid and other pre-pregnancy health issues
• Targeted English speaking women of reproductive
age (18 to 45 years)
March of Dimes Folic Acid Survey
• National telephone surveys conducted by the Gallup Organization in 1995, 1997, 1998 and 2000 commissioned by the March of Dimes and supported by the CDC
• Surveys were designed to ascertain women’s awareness and reported behaviors related to folic acid and other pre-pregnancy health issues
• Targeted English speaking women of reproductive age (18 to 45 years)
• 1995 Survey: N=2010
• 1997 Survey: N=2001
• 1998 Survey: N=2115
• 2000 Survey: N=2000
– oversampled women who were pregnant in past 2 years
• Based on these sample sizes 95% confident that the margin of error attributable to sampling and other random effects could be +/- 3 percentage points
• The margin of error is greater for any subset analyses
• Error bias can also be introduced into opinion polls due to question wording and practical difficulties in obtaining responses from telephone interviews
Folic Acid AwarenessHave You Heard of Folic Acid?
52
66 6875
80
0
25
50
75
100
1995 1997 1998 2000 2001 Goal
Percentage of women ages 18-45
Folic Acid-Specific KnowledgeMarch of Dimes Folic Acid Survey
4
1013 14
2
6 710
20
30
0
5
10
15
20
25
30
1995 1997 1998 2000 2001 Goal
Prevents birth defects Should be taken before pregnancy
Percentage of women ages 18-45
Daily Use of Vitamin Containing Folic Acid March of Dimes Folic Acid Survey
2832 32
34
25
30 29
40
32
0
10
20
30
40
1995 1997 1998 2000 2001 Goal*
All Women Women Not Pregnant
Percentage of women ages 18-45
* Goal for non-pregnant women
Characteristics of Non-Pregnant Women Taking Daily Supplement with Folic Acid
March of Dimes Folic Acid Survey, 2000
39
35
32
23
37
30
14
36
31
26
0 10 20 30 40 50
$50,000 +
$40-49,999
$25-39,999
<$25,000
Any College
HS Grad
<HS
35-45
25-34
18-24
Percentage of non-pregnant women ages 18-45
Source of Information on Folic AcidMarch of Dimes Folic Acid Survey
30
10
22 23 24
1315
19 20
31
35 36
0
5
10
15
20
25
30
35
40
1995 1997 1998 2000
Magazine/Newspaper Radio/Television Health care providers
Percentage of women aware of folic acid
Health Professional Research Results: Women want to hear from health care providers
Doctors respond to questions, but often don’t have time to do proactive counseling
Nurses and nutritionists are
willing and able to counsel
women about folic acid
Important to have information
specific to health disciplines
Health Care Provider Education:
Women want to hear about folic acid from their health care provider
• Health Care Provider Resource Kit
• Association of Schools of Public Health Grant
• Grand Rounds
• New Display Board
12.124.0 28.726.8
0
20
40
60
Rarely Sometimes Most times Always
50.0
OB/GYN Baseline SurveyPatient Folic Acid Recommendations
Percent
2001Goal
Selected Responses from March of Dimes Provider Survey on Folic Acid
1998 Ob/Gyn 1999 ACNM 1999 AWHONN 1999 NANN
n=463 n=136 n=319 n=276Folic acid helps to: prevent birth defects 97.4 99.3 98.4 100.0 prevent low birthweight 30.7 40.7 51.1 64.4 prevent cardiovascular disease 40.0 48.9 45.8 46.4 prevent stroke 30.2 43.7 50.2 52.1 prevent fibroids (false) 44.1 23.7 12.9 5.7 prevent colorectal cancer 24.4 43.7 39.8 40.9 decrease homocysteine 37.2 43.7 37.0 37.5
USPHS daily rec 400 mcg 69.9 87.5 51.7 34.3Always recommend folic acid 28.7 45.9 42.6 65.2Always provide preconcep care 15.0 25.0 11.3 6.0Know grains fortified at 140 mcg 14.9 5.3 4.1 2.4Not likely to get fa from diet alone 55.9 63.0 69 67.6Begin fa at least 1 mo prior to preg 89.0 97.0 90.6 86.350% of preg in US unintended 38.0 39.8 26.0 24.3Provider takes MV daily 25.7 35.3 43.0 43.5
Percent of Correct Responses
MOD Folic Acid Surveys Summary
• While awareness of the benefits of folic acid is increasing slightly, only 3 in 4 women were aware of folic acid in 2000– Only 1 in 7 women knew that folic acid can
prevent birth defects
– 9 out of 10 women did not know that folic
acid should be taken prior to to pregnancy
• Only 1 in 3 women reported consuming a multivitamin containing folic daily
• When asked where they learned about folic acid:
– More than half of women reported the media as their source of information
– Only 1 in 5 women identified their health care provider
• Increases in the proportion of women who consume 400 micrograms of folic acid daily will require continued efforts in:
– Health professional education
– Community action
– Mass media
Targeting High-Risk Populations: Hispanic Women’s Initiative
• Partnering of 4 chapters with the National Alliance of Hispanic Health Community Based Organizations (CBO’s) in:
*Chicago
*Los Angeles
*San Diego
*Phoenix
• Implement a Media and a Word-of-mouth campaign
Focus Group Findings: Hispanic Women
• Sense of fatalism
• Highlighting Latinas’ greater risk creates an
overwhelming emotional response
• “Vitamins” are perceived negatively
• Most women accept that one day they will
get pregnant
• 18-24 year olds are attracted to health and
beauty message
Hispanic Women: Challenges
• Hispanic women less likely to have heard the message, in Spanish or English
• Less likely to know about importance of folic acid before pregnancy
• Hispanic women less likely to take vitamin supplement (even though they report their diet is “worse” in US)
• Some have later entry to prenatal care
• Fear of weight gain from vitamins
Hispanic Women: Opportunities
• Welcome contemplator message of “before”, link message to family’s health
• Very willing to make behavior change for health of future babies
• Acknowledge diet is worse in US and need to make changes
• Younger Hispanic women link general health to beauty
• Open to hear weight gain has no basis in fact
Community Action:
Keep community aware of and focused on health benefits of folic acid
• State Councils
• Campus/Youth Action Kits
• Community Action Kits
National Council on Folic AcidMember Organizations
• Professional Associations
• Government Agencies
• Health and Human Services Non-Profits
• Industry Associations
Reaching the GoalWhat Will It Take?
•Multi-year commitment
•Multi-faceted and comprehensive
approaches
•Incorporating the message in everything
we do in our communities and our
professions
The March of Dimes, the Centers for Disease Control & all members of the National Council on Folic Acid recommends that --
All women of childbearing potential consume 400 micrograms of folic acid every day as part of a healthy diet
Secular trends of spina bifida at birth per 10,000 births, North America, 1890-1990.
10
20
30
Year
1890 1900 1910 19201930 19401950 1960 1970 1980 1990
5
15
25
Rat
e pe
r 10
,000
birt
hs
BostonProvidence
Rochester
NY
Atlanta
U.S.
?
Prevalence of Anencephaly and Spina Bifida, Livebirths, Atlanta, 1968 - 1997
0
5
10
15
20
25
Rat
e pe
r 10
,000
Year68 72 76 80 84 88 92 9670 74 8278 86 90 94 98 00
Multivitamin Change - 1973
PrenatalDiagnosis - 1984
?
Prevalence of Anencephaly and Spina Bifida, Births and Terminated Pregnancies,
Atlanta, 1968 - 1997
0
5
10
15
20
25
Rat
e pe
r 10
,000
Year
Adjusted ASB Rate
BirthsTerminated Pregnancies
68 72 76 80 84 88 92 9670 74 8278 86 90 94 98 00
Prevalence of Anencephaly and Spina Bifida, Births and Terminated Pregnancies,
Atlanta, 1968 - 1997
0
5
10
15
20
25
Rat
e pe
r 10
,000
Year
Adjusted ASB Rate
Terminated Pregnancies
68 72 76 80 84 88 92 9670 74 8278 86 90 94 98 00
Births
Fortification 1998
??