Գլխավոր էջ Preventive Medicine Increased awareness, knowledge and utilization of preconceptional folic acid in Israel following a...

Increased awareness, knowledge and utilization of preconceptional folic acid in Israel following a national campaign

, , , , ,
Որքա՞ն է ձեզ դուր եկել այս գիրքը:
Ինչպիսի՞ն է բեռնված ֆայլի որակը:
Բեռնեք գիրքը` գնահատելու դրա որակը
Ինչպիսի՞ն է բեռնված ֆայլերի որակը:
Հատոր:
39
Տարի:
2004
Լեզու:
english
DOI:
10.1016/j.ypmed.2004.02.042
Ֆայլ:
PDF, 307 KB
Ներբեռնել (pdf, 307 KB)
Conversion to is in progress
Conversion to is failed

Հիմնական արտահայտություններ

 
che1953
una1189
del805
alla471
gli442
sul403
nel347
lei339
dal256
poi253
dei235
mio231
lui231
suo216
sua211
mia203
uno198
fra187
solo181
fino159
loro151
ora149
ero148
tre137
mano136
alle133
dopo128
cosa128
cui126
0 comments
 

Կարծիք թողնելու համար խնդրում ենք մուտք գործեք կամ գրանցվեք
Կարող եք ակնարկ թողնել գրքի վերաբերյալ և կիսվել ձեր փորձով: Մյուս ընթերցողներին նույնպես հետաքրքիր կլինի իմանալ ձեր կարծիքը իրենց կարդացած գրքերի վերաբերյալ: Անկախ նրանից՝ ձեզ դուր է գալիս գիրքը, թե ոչ, եթե անկեղծորեն և մանրակրկիտ պատմեք դրա մասին, մարդիկ կկարողանան իրենց համար նոր գրքեր գտնել, որոնք կհետաքրքրեն իրենց:
Preventive Medicine 39 (2004) 731 – 737
www.elsevier.com/locate/ypmed

Increased awareness, knowledge and utilization of preconceptional
folic acid in Israel following a national campaign
Yona Amitai, M.D., M.P.H., a,b,* Nirah Fisher, F.N.P., M.S.N., a,b
Miri Haringman, R.N., M.P.H., a,b Hana Meiraz, R.N., M.P.A., b,c
Nira Baram, R.N., M.P.H., b,c and Alex Leventhal, M.D., M.P.H., M.P.A. b
a

Department of Mother, Child and Adolescent Health, Ministry of Health, Jerusalem, Israel
b
The Public Health Service, Ministry of Health, Jerusalem, Israel
c
Public Health Nursing, Ministry of health, Jerusalem, Israel
Available online 15 April 2004

Abstract
Background. To decrease the risk of neural tube defects (NTDs), the Israeli Ministry of Health (MOH) issued guidelines in August 2000
recommending daily folic acid (FA) supplementation for women in their childbearing age, and concurrently launched a national FA
campaign. Campaign effects were assessed by comparing the results of a survey done in 2002 with a baseline survey done in June 2000.
Methods. Both surveys were done within the network of the Public Health Services’ Mother and Child Health Clinics (MCHC). Nursing
staff conducted structured interviews of pregnant women and mothers of newborn infants.
Results. In the 2002 survey (n = 1661), awareness was 85%, correct knowledge was 77.7% and 30.5% utilized FA preconceptionally.
Ratios of awareness, knowledge and utilization were highest among women with post-university education (93%, 84%, 46%), and awareness
and utilization were significantly higher in the 25 – 29 year age bracket (90%, 35%). In the baseline 2000 survey (n = 1719), FA awareness
had been 54.6%, knowledge of the benefits of FA was 17.6% and preconceptional utilization was reported by a mere 5.2%.
Conclusions. A national periconceptional FA campaign in Israel resulted in significant increases in awareness and correct knowledge, and
a sixfold increase in its intake.
D 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved.
; Keywords: Folic acid; Neural tube defects; Prevention; Pregnancy; Periconceptional

Introduction
Neural tube defects (NTDs) are severe malformations of
the brain and spine that may occur in the developing fetus
during the first 17 –30 days after conception. They are a
major cause of stillbirth and infant morbidity and mortality.
For those surviving infancy, NTDs are a cause of chronic
medical care costs and human suffering throughout the life
span. Daily consumption of a 400 Ag folic acid (FA)
supplement preconceptionally and throughout the first trimester has been proven effective in reducing the incidence of
NTDs by 50 –79% [1]. Studies have shown an association
between periconceptional multivitamin/FA supplements and
* Corresponding author. Department of Mother Child and Adolescent
Health, Ministry of Health, 20 King David St., Jerusalem 91010, Israel.
Fax: +972-2-6228907.
E-mail address: yona.amitai@moh.health.gov.il (Y. Amitai).

a decrease in the frequency of NTDs and other congenital
anomalies [2– 13]. Lower incidences of congenital anomalies
of the heart [6 –8], the genito-urinary system [8– 10], cleft lip
and palate [10,11], limb reduction defects [7,8,10], imperforate anus [12] and omphalocele [13] have been reported.
Prevalence of neural tube defects in Israel
During the years 2000 – 2001, NTDs in Israel were
diagnosed (prenataly and at birth) in 389 pregnancies (168
cases of anencephaly, 169 spina bifida, 44 encephalocele
and 8 with other types of NTDs) [14]. In the year 2000, the
national birth registry in Israel recorded 2,742 infants with
major congenital malformations. There were 136,434 live
births and the congenital malformation rate was 20.1 per
1,000 live births [15]. Of 892 stillbirths reported, 273
infants were diagnosed with congenital malformations and
the most frequent organ system involved was that of the

0091-7435/$ - see front matter D 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved.
doi:10.1016/j.ypmed.2004.02.042

732

Y. Amitai et al. / Preventive Medicine 39 (2004) 731–737

CNS (n = 100) [15]. Over 600 terminations of pregnancy
based on confirmed congenital fetal malformations were
recorded in Israeli hospitals in the year 2000 [16].
In Israel, the case for action for recommending FA
supplementation to women in the childbearing age is stronger
than in the United States and other industrialized countries for
three reasons. The fertility rate of women in Israel is the
highest of all developed countries. According to UNICEF
data for 2000, the mean fertility rate for the 31 industrialized
countries was 1.7, compared with 2.8 in Israel [17]. The
fertility rate among Moslem Arabs is 4.7 [18]. Therefore, in
Israel, a successful FA campaign would have a wider scope of
influence per woman in regard to the number of pregnancies
affected than in other first world countries. Secondly, the rate
of NTDs in Israel in the years 1999 – 2000 was 1.1 per 1,000
live births in the Jewish population and 2.23 per 1,000 live
births in the Arab population [14]. Live-born, stillborn infants
and electively terminated pregnancies after prenatal diagnosis were included in this analysis. By comparison in the
United States in the years preceding the CDC, FA recommendation the prevalence of anencephaly and spina bifida in
California was 0.90, Iowa 0.90 and Georgia 0.99 per 1,000
live-born and stillborn infants, adjusted to include pregnancy
terminations [19]. The higher prevalence rates in Israel are
due in part to the high rate of consanguinity [14,20]. Other
genetic birth defects are also more common in Israel and there
is an argument to be made for the role of FA in minimizing
these as well [6– 13,15]. Thirdly, due to religious factors,
many Jewish and Arab women in Israel choose to continue
with their pregnancy even when an NTD or other severe
congenital anomaly is diagnosed [14,21]. For these women,
the argument for primary prevention with periconceptional
FA supplements is overwhelmingly compelling. Proper preconceptional FA utilization should result in an improved
pregnancy outcome and a marked decrease in NTDs and
other congenital malformations [1– 13,22,23].
Folic acid guidelines in Israel
To promote FA utilization, the Ministry of Health (MOH)
issued guidelines in August 2000, recommending a daily
400 Ag. FA supplement for all women in their childbearing
years with special emphasis placed on the 3 months preceding conception and throughout the first trimester [24].
The MOH had an existing recommendation for a combined
iron and FA supplement from week 12 of the pregnancy
onward. National guidelines to prevent the recurrence of an
NTD with a daily 4 mg preconceptional FA supplement
have been in effect since 1994.

(MCHC) staff, FA ‘‘posters’’ for all MCHC, and a patient
handout on FA, available in Hebrew, Arabic and Russian.
Interviews were conducted on national radio programs;
articles were published in local magazines and newspapers; and lectures were given in multidisciplinary settings.
A health education kit that included articles, pamphlets
and a magnetized reminder to take FA was prepared and
distributed. Jewish and Moslem religious leaders were
contacted and included in the campaign. Almost all
marriages in Israel are conducted within a religious framework (>90%) and the clergy was asked to distribute the
FA brochure to all couples registering for marriage. In
addition, the FA brochure was distributed to all mikvaot
(post-menstrual ritual baths). District offices of the MOH
developed their own local strategies such as telex advertisements through cable television and community health
education days.
Baseline assessment in July 2000
Before issuing the MOH guidelines in July 2000, a
baseline survey was conducted in June 2000, of pregnant
woman and mothers of newborn infants followed by the
Public Health Service at the MCHC. The baseline survey
addressed FA awareness, knowledge and preconceptional
intake and was conducted by the MOH via its MCHC
network. In the 2000 survey, FA awareness was 54.6%,
correct FA knowledge was 17.6%, and FA preconceptional
utilization was 5.2% nationally, as reported by the 1,719
respondents.
Demographic details were not requested on the baseline
survey.
Folic acid survey in August 2002
In August 2002, to assess the effects of our FA campaign
and to determine the extent of its influence on FA awareness, knowledge and preconceptional utilization, we conducted a repeat survey. As in the baseline 2000 survey, the
follow-up survey was conducted by the MOH via the
MCHC network. The target population was the same for
both surveys and consisted of pregnant woman and mothers
of newborn infants (under age 2 months) followed by the
Public Health Service at the MCHC. In our current survey,
in addition, we attempted to ascertain if there were any
demographically high-risk groups (religion, age, education
and parity) regarding preconceptional FA awareness, knowledge and utilization to better evaluate our current campaign
and plan future strategy.

Folic acid campaign
Methods
A national FA campaign was launched concurrently
with the issue of the guidelines. The campaign focused
on the dissemination of FA knowledge and consisted of inservice education for all Maternal Child Health Clinics

The target population consisted of all pregnant women
and mothers of infants under age 2 months who presented at
the MCHC for either prenatal or newborn care.

Y. Amitai et al. / Preventive Medicine 39 (2004) 731–737

733

Results

Fig. 1. Folic acid awareness, knowledge and utilization: 2000, 2002.

The survey was conducted both on women in the
prenatal service and women who entered the service for
infant care. We surveyed the pregnant population to
minimize bias recall. However, only approximately 60%
of Israeli women are followed by the public health
services clinics prenatally. Prenatal care is offered at
the MCHC and also through the ‘‘kupot cholim’’ (sick
funds), health maintenance organizations. In regards to
the infant and toddler population, the government-sponsored MCHCs provide care to approximately 84% of all
children from birth to school age. Both groups of
women were therefore included to insure a representative
population.
A total of 2,334 questionnaires were distributed via
district health offices to 521 MCHC throughout the country.
Three to five questionnaires were distributed to each
MCHC, in proportion to the population served. The public
health nursing staff at the individual clinics conducted a
structured interview. During the study period, sampling was
done on the first women who presented at the individual
Child Health Clinics.
Folic acid awareness was defined as ever having heard of
FA. A multiple-choice question was used to evaluate correct
FA knowledge. ‘‘FA prevents many birth defects’’ was the
designated answer. Folic acid intake was defined as having
taken FA on a regular basis for the 2 months preceding the
current pregnancy. Women were also queried as to when
they had begun their prenatal care and whether they had
taken FA in the first 3 months of their current pregnancy on
a regular basis.
Religion was classified as Jewish, Moslem Arab, Christian Arab, Druze and other. Due to the small numbers in the
individual non-Jewish groups, they were combined and
subsequently called Arab. Educational status was defined
by years of education.
Statistical analysis was performed using SPSS 11.

A total of 1,661 (71%) questionnaires were returned from
395 MCHC (76%). The population was comprised of 784
(49%) pregnant women and 827 (51%) mothers of
newborns (N = 1,611). The rates of FA awareness, FA
correct knowledge and FA utilization were 83.8%, 76.2%
and 28%, respectively, for pregnant women and 86.5%,
79% and 33% for the women who were mothers of
newborns. When adjusted for age and education, there
was no significant (P > 0.5) difference between the two
groups and they were therefore combined for further variable analysis.
Globally, FA awareness was reported by an overwhelming majority of the women (85%).
This represented a significant improvement over our
baseline survey finding of 54.6% (P < 0.001). Correct
knowledge of FA periconceptional benefits quadrupled
from 17.6% to 77.7% (P < 0.001) and FA intake
increased sixfold from 5.2% to 30.5% (P < 0.001)
(Fig. 1).
Religion
Of the 1,618 questionnaires received where religion was
delineated, 521 belonged to the Arab population (31%)
(Table 1).
FA awareness, knowledge and utilization rates as defined
by religion are presented in Table 2. The Arab population in
our present survey demonstrated improved FA awareness
(74%), knowledge (67%) and utilization (21%). The Jewish
population in comparison exhibited significantly higher
rates of FA awareness (91%), knowledge (83%) and utilization (35%).
Education
A majority of the women in our current survey (83%)
had at least 12 years of education, 44% had completed some

Table 1
Selected sociodemographic characteristics of survey women
N (%)

Mean age/
standard
deviation

Jewish
1,097 (66)
28.7* (5.3)
Moslem
359 (21.7)
27 (5.2)
Christian
68 (4.1)
27.1 (5.0)
Druze
79 (4.8)
27.4 (4.4)
Other
15 (0.9)
26.4 (5.5)
Total Arab
521 (31.4) 27.1 (5.1)
(Non-Jewish)
Unknown
43 (2.6) 30.3 (5.8)
Total
1661(100) 28.2 (5.3)
* Significant at P < 0.001 vs. Arab.
** Significant at P = 0.008 vs. Arab.

Mean number
of children/
standard
deviation

Mean years
of education/
standard
deviation

2.3**
2.6 (1.5)
2.1 (1.3)
2.5 (1.5)
1.3 (0.6)
2.5 (1.5)

13.7* (2.6)
11.4 (2.9)
12.6 (2.4)
11.4 (2.7)
13.1 (2.6)
11.6 (2.9)

2.1 (0.9)
2.4 (1.7)

11.6 (5.8)
13.0 (2.9)

734

Y. Amitai et al. / Preventive Medicine 39 (2004) 731–737

Table 2
Folic acid awareness, knowledge and utilization as defined by religion
FA awareness
[N (%)]
Jewish
Moslem
Christian
Druze
Other
Total Arab
(Non-Jewish)
Unknown
Total

991
266
46
58
12
382

(91.0)*
(74.3)
(67.6)
(73.4)
(80)
(73.5)

34 (79.1)
1407 (85.2)

FA correct knowledge
[N (%)]
851
218
41
49
9
317

(82.5)**
(67.5)
(67.2)
(64.5)
(64.3)
(66.9)

33 (80.5)
1201 (77.7)

FA utilization
[N (%)]
379
79
10
19
1
109

(34.8)***
(22.1)
(14.9)
(24.4)
(7.1)
(21.2)

15 (35.7)
503 (30.5)

* Significant at P < 0.001 vs. Arab.
** Significant at P < 0.007 vs. Arab.
*** Significant at P < 0.002 vs. Arab.

post-secondary education, and 20% had completed at least
16 years of education. FA awareness, knowledge and
utilization increased dramatically and were positively correlated with years of education (Fig. 2: P < 0.001).
Age
Folic acid awareness, knowledge and utilization rates
varied by age. Women aged 25– 29 had the highest rates
of awareness, knowledge and utilization (90%, 76%,
35%) when compared with women aged 17– 19 (67%,
58%, 18%). Data on awareness, knowledge and utilization of FA by age group are presented in Fig. 3. There
was a significant correlation between age group and, FA
awareness (P < 0.001) and FA utilization (P = 0.035).
Knowledge of FA was not significantly correlated with
age (P = 0.147).
General indicators
When the data was examined by logistic regression, the
most consistent and significant predictors of FA awareness,

Fig. 3. Folic acid awareness, knowledge and utilization as defined by age.

knowledge and utilization were education and religion
(Table 3).
There was a significant correlation between FA knowledge and FA utilization. Women who had correct FA
knowledge were two and a half times as likely to have
utilized FA preconceptionally (P < 0.001, OR = 2.65, CI =
1.9 – 3.7), even after controlling for age (P = 0.002),
education (P < 0.001) and parity (P < 0.001).
An additional 156 women who had not taken FA on a
daily basis preconceptionally reported taking FA in their
first trimester and had begun prenatal care by the end of the
sixth week of pregnancy. This group of women, however,
was not factored in when we analyzed preconceptional
utilization.

Table 3
Folic acid awareness, knowledge and utilization predictors: adjusted for
maternal status, parity, religion, age group and educational group
Significance

Adjusted
OR

95% Confidence
interval

Awareness
12 Years educationa
13 – 15 Years educationa
z16 Years educationa
Age 25 – 29b
Jewish religionc

0.008
0.000
0.000
0.004
0.000

1.7
3.7
4.2
2.2
2.5

1.144 – 2.401
2.218 – 6.014
2.343 – 7.514
1.283 – 3.614
1.813 – 3.475

Knowledge
Parityd
12 Years educationa
13 – 15 Years educationa
z16 Years educationa
Jewish religionc

0.000
0.000
0.000
0.000
0.007

0.8
2.5
3.3
3.5
1.5

0.763 – 0.904
1.755 – 3.530
2.164 – 4.953
2.230 – 5.547
1.117 – 1.995

Utilization
Parityd
13 – 15 Years educationa
z16 Years educationa
Jewish religionc

0.000
0.015
0.000
0.002

0.8
1.7
2.3
1.5

0.729 – 0.872
1.108 – 2.550
1.483 – 3.481
1.170 – 2.045

a

Odds ratio: vs. 0 – 11 years education.
Odds ratio: vs. age 17 – 19.
c
Odds ratio: vs. Arab.
d
Odds ratio: for each additional child.
b

Fig. 2. Folic acid awareness, knowledge and utilization according to level
of education.

Y. Amitai et al. / Preventive Medicine 39 (2004) 731–737

Discussion
Our study revealed that the intake of FA in the critical
preconceptional period had significantly increased between
2000 and 2002, in the 2 years following the issuing of the
national guidelines and the onset of the FA campaign.
Women have heard about FA, and an overwhelming majority knew about its potential benefit in preventing births
defect. The highest rates of awareness, knowledge and
utilization were found among women aged 25 – 29. The
highest fertility rate in Israel is among women aged 25 –29
in both the Jewish and Arab populations [18]. Our target
population, women who are having babies, has been the one
who has most benefited from the FA campaign.
The campaign was less successful in women with less
than 12 years of education. Women aged 17 – 19 also
reported poor knowledge and utilization of FA. Education
is a timely process and women aged 17– 19 who are having
babies have by definition not had the time to invest in an
education. In similar studies in the Netherlands and the
United States, there is an apparent obstacle in communicating health-related messages to the young and poorly educated segment of the population, and studies have shown a
relationship between less years of education and the prevalence of NTDs [25 –28]. New focus will have to target the
needs of this particular population. An alternative form of
appropriate communication will have to be developed and
the education of future mothers will have to begin while
they are in junior high and high school.
The proportion of the Arabs in the general population in
Israel is approximately 19%. Their representative participation in the survey, however, was 32%, which is equivalent to
their proportion of births in 2001 [18]. In our survey, the
Arab population had significantly fewer years of education
and was significantly younger than their Jewish survey
counterparts. This highlights the question of how to best
communicate a health message to those who are younger
and with less years of education. The Arab population is in
part non-Hebrew speaking and may not have fully benefited
from some of the national media campaigns, although local
programs were done in the Arabic language at the initiative
of the local health district offices.
There has been a significantly dramatic increase in FA
awareness, knowledge and utilization following the campaign, but the fact remains that most women in Israel having
babies are not taking FA preconceptionally although they
are knowledgeable of its benefits. Some of the women
might have been informed of FA during their prenatal care,
and their knowledge when surveyed, did not reflect their
preconceptional knowledge. That would explain in theory
some of the discrepancy between knowledge and behavior.
Significant gaps between knowledge and behavior, however, appear to be universal.
The experience in the United States may very well serve
as a flagship. The Public Health Service in the United States
recommended in 1992 that all women in their childbearing

735

years consume at least 400 Ag of FA a day [29]. In April
1998, the Food and Nutrition Board of the National Academy of Sciences in the United States revised the recommendation and specified a 400 Ag synthetic FA supplement
due to its increased absorption, in addition to a diet rich in
FA [30].
In 2002, 10 years after the U.S. Public Health Service
first recommended FA, a March Of Dimes survey reported
that 80% of the women surveyed had heard of FA [31].
Daily consumption of a multivitamin containing FA, however, was reported by only 31% of the women in their
childbearing years [31]. An increase in FA awareness has
been observed in the United States following each of several
campaigns; however, actual use of daily FA supplements by
women aged 18 – 45 has only increased from 25% in 1995 to
31% in 2002 [19,26,32,33]. Clearly, health behavior habits
are not easily modified.
Our national FA campaign focused on the dissemination
of information and the imparting of knowledge via the
existing network of MCHC and through the media. Behavior modification is a challenging ongoing long-term process,
and although imparting correct knowledge is a cornerstone
of the program, it is clearly not the entire process.
In Israel, the Maternal Child Health staff at the MCHC
provides primary preventive care to women and children.
As such, the nurse establishes an ongoing relationship with
the woman, as her caretaker during the pregnancy and
family planning clinics, and as a health provider to the
infant and toddler. There are multiple opportunities to
reinforce and follow-up on health education messages and
the local public health nurse is aware of the fine nuances
that can better serve the needs of individual communities.
Any contact with a woman in the childbearing years must
be viewed as an opportunity for FA health promotion, every
birth control consultation is a potential birth, and every
childhood immunization is an opportunity for parental
health education, FA discussion and positive behavior
reinforcement.
Due to the huge gap between FA knowledge and its
actual consumption, flour fortification is an alternate strategy that does not necessitate behavior modification. Mandatory fortification with FA has been implemented in the
United States and Canada since 1998 and had begun with
cereal grain enrichment in 1996 [34]. Following FA fortification, a 23% reduction in the birth prevalence of NTDs
occurred in the United States [35]. It is assumed that this
substantial reduction is attributable to fortification since no
concurrent increase in FA dietary supplements has been
documented, while folate blood level increases have been
recorded [31 – 33,35 – 37]. In a report from Nova Scotia, a
reduction of over 50% in the incidence of NTDs was
observed in a local study, following FA fortification [38].
However, the experience in the United States vs. the
experience in China has shown that although flour supplementation is helpful, it does not equal the impact of a
properly administered synthetic FA supplement [1,35 – 37].

736

Y. Amitai et al. / Preventive Medicine 39 (2004) 731–737

In Israel, the Public Health Service adopted the ‘‘triple
strategy approach’’ for optimal reduction of NTDs, by
combining dietary modification instruction, FA supplementation guidelines and voluntary food fortification [39].
Our survey findings suggest that a lot of work remains to
be done on all fronts to improve preconceptional FA
utilization. In particular, we will have to focus on the Arab
population, on the younger women and on those with fewer
years of education. The national initiative will have to be
tailored to meet the needs of the particular groups we have
delineated as having lower FA utilization, while at the same
time working to promote increased preconceptional FA
utilization across the board.
Currently, our national campaign for increasing preconceptional FA utilization is being revamped and modified in
line with our findings and voluntary FA fortification of grain
has begun.

Acknowledgments
We are thankful to the nurses of the Tipot Halav (MCHC)
throughout the country who were instrumental in interviewing the study women. Particular thanks to the following
nurse supervisors for their role in organizing the distribution
of the survey questionnaire: Yael Arbelli, Bracha Avraham,
Chana Ben-Ari, Yardena Ben-Chamu, Gila Benztik, Zahava
Dror, Naomi Eidelstein, Sara Hadar, Hannah Levensohn,
Rachel Maoz, Ron Maybar, Yehudit Pasternak, Mirriam
Payis, Mira Ron, Leora Shachar, Gila Stern, Liora Vasterman, Ilana Yaacobi. In addition, we would like to thank
Professor Joel Zlotogora for his inspiration, Eve Fliesher
and Yaffa Kurtsweil for their assistance in data analysis and
Dr. Rosa Goffen for her helpful comments.

References
[1] Berry RJ, Zhu L, Erickson JD, Song L, Moore CA, Hong W, et al.
Prevention of neural-tube defects with folic acid in China. China – US
collaborative project for neural tube defect prevention. NEJM 1999;
341:1485 – 90.
[2] Mulinare J, Cordero JF, Erickson JD, Berry RJ. Periconceptional use
of multivitamins and the occurrence of neural tube defects. JAMA
1988;260:3141 – 5.
[3] Czeizel AE, Dudas I. Prevention of the first occurrence of neural tube
defects by periconceptional vitamin supplements. NEJM 1992;327:
1832 – 5.
[4] Khoury MJ, Shaw GM, Moore CA, Lammer EJ, Mulinare J. Does
periconceptional multivitamin use reduce the risk of neural tube
defects associated with other birth defects. Am J Med Genet 1996;
61:30 – 6.
[5] MRC Vitamin Study Research Group. Prevention of neural tube
defects: results of the medical research council vitamin study. Lancet
1991;338:131 – 7.
[6] Botto LD, Khoury MJ, Mulinare J, Erickson JD. Periconceptional
multivitamin use and the occurrence of conotruncal heart defects:
results from a population based case-control study. Pediatrics 1996;
98:911 – 7.

[7] Shaw GM, O’Malley CD, Wasserman CR, Tolarova MM, Lammer
EJ. Maternal periconceptional use of multivitamins and reduced risk
for conotruncal heart defects and limb deficiencies among offspring.
Am J Med Genet 1995;59:536 – 45.
[8] Czeizel AE, Dobo M, Dudas I, Gasztonyi Z, Lantos I. The Hungarian
Periconceptional Service as a model for community genetics. Community Genet 1998;1:252 – 9.
[9] Li DK, Daling JR, Mueller BA, Hickok DE, Fantel AG, Weiss NS.
Periconceptional multivitamin use in relation to the risk of congenital
urinary tract anomalies. Epidemiology 1995;6:212 – 8.
[10] Werler MM, Hayes C, Louik C, Shapiro S, Mitchell AA. Multivitamin supplementation and risk of birth defects. Am J Epidemiol 1999;
150:675 – 82.
[11] Shaw GM, Lammer EJ, Wasserman CR, O’Malley CD, Tolarova
MM. Risk of orofacial clefts in children born to women using multivitamins containing folic acid periconceptionally. Lancet 1995;345:
393 – 6.
[12] Myers MF, Li S, Correa-Villasenor A, Li Z, Moore CA, Hong SX,
et al. Folic acid supplementation and risk for imperforate anus in
China. Am J Epidemiol 2001;154:1051 – 6.
[13] Botto LD, Mulinare J, Erickson JD. Occurrence of omphalocele in
relation to maternal multivitamin use: a population-based study.
Pediatrics 2002;109:904 – 8.
[14] Zlotogora J, Amitai Y, Nitzan Kalsuski D, Leventhal A. Surveillance of neural tube defects in Israel. Isr Med Assoc J 2002 Dec;
(4):1111 – 4.
[15] Congenital Malformations in Israel 1995 – 2000. Unpublished. Ministry of Health, Maternal child and Adolescent Department, Public
Health Services, Israel; May 2002.
[16] Central Bureau of Statistics. Unpublished internal memo. Jerusalem,
Israel; 2001.
[17] UNICEF. The state of the world’s children 2002. New York: United
Nations Children’s Fund; 2002.
[18] Statistical abstract of Israel, no. 53. Jerusalem, Israel: Central Bureau
of Statistics; 2002.
[19] Cragan JD, Roberts HE, Edmonds LD, Khoury MJ, Kirby RS, Shaw
GM, et al. Surveillance for anencephaly and spina bifida and the
impact of prenatal diagnosis—United States, 1985 – 1994. CDC
MMWR 1994 August 25;44(SS-4):1 – 13.
[20] Jaber L, Halpern GJ, Shohat T. Trends in the frequencies of consanguineous marriages in the Israeli Arab Community. Clin Genet 2000
Aug;58(2):106 – 10.
[21] Jaber L, Dolfin T, Shohat T, Halpern GJ, Reish O, Fejgin M. Prenatal
diagnosis for detecting congenital malformations: acceptance among
Israeli Arab women. Isr Med Assoc J 2000 May;2(5):346 – 50.
[22] Scholl TO, Johnson WG. Folic acid: influence on the outcome of
pregnancy. Am J Clin Nutr 2000 May;71(5):1295S – 303S.
[23] Powers RW, Evans RW, Majors AK, Ojimba JI, Ness RB, Crombleholme WR, et al. Plasma homocysteine concentration is increased in
preeclampsia activation.and is associated with evidence of endothelial
activation. Am J Obstet Gynecol 1998 Dec;179(6 Pt 1):1605 – 11.
[24] Ministry of health, maternal, child and adolescent health department,
public health nursing. guidelines for folic acid administration: pregnant women and women in their childbearing years. Practice Guidelines August; 2000.
[25] De Walle HEK, Cornel MC. Three years after the Dutch folic acid
campaign: growing socioeconomic differences. Prev Med 2002;35(6
Pt 1):65 – 9.
[26] Erickson JD. Folic acid and prevention of spina bifida and anencephaly. 10 years after the U.S. public health service recommendation.
MMWR 2002;51(RR-13):1 – 3.
[27] Farley TF, Hambridge SJ, Daley MF. Association of low maternal
education with neural tube defects in Colorado, 1989 – 1998. Public
Health 2002 Mar;116(2):89 – 94.
[28] Meyer RE, Siega-Riz A. Sociodemographic patterns in spina bifida
birth prevalence trends—North Carolina, 1995 – 1999. MMWR 2002;
51(RR-13):12 – 5.

Y. Amitai et al. / Preventive Medicine 39 (2004) 731–737
[29] CDC. Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR
1992;41(RR-14):1 – 7.
[30] Institute of medicine. Dietary reference intakes: thiamin, riboflavin,
niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin
and choline. Washington (DC): National Academy Press; 1998
(April).
[31] March of Dimes A. Folic acid and the prevention of birth defects: a
national survey of pre-pregnancy awareness and behavior among
women of childbearing age, 1995 – 2002. Conducted by the Gallup
Organization. White Plains (NY): March of Dimes Foundation; 2002
(May) [Publication no. 31-1677-02].
[32] Ahluwalia IB, Daniel KL. Are women with recent live births aware of
the benefits of folic acid? MMWR 2001;50(RR06):3 – 14.
[33] March of Dimes. Folic acid and the prevention of birth defects: A
national survey of pre-pregnancy awareness and behavior among
women of childbearing age, 1995 – 2001. Executive summary.
[34] Food and Drug Administration KL. Food standards: amendment of

[35]

[36]

[37]
[38]

[39]

737

standards of identity for enriched grain products to require addition of
folic acid. Fed Regist 1996;61(44):8781 – 97.
Mathews TJ, Honein MA, Erickson JD. Spina bifida and anencephaly
prevalence—United States, 1991 – 2001. National center for health
statistics. MMWR 2002;51(RR-13):9 – 11.
Williams LJ, Mai CT, Edmonds LD, Shaw GM, Kirby RS, Hobbs
CA, et al. Prevalence of spina bifida and anencephaly during the
transition to mandatory folic acid fortification in the United States.
Teratology 2002 Jul;66(1):33 – 9.
MMWR. Folate status in women of childbearing age—United States
1999. 2000; 49(42):962 – 5.
Persad VL, Van den Hof MC, Dube JM, Zimmer P. Incidence of open
neural tube defects in Nova Scotia after folic acid fortification. CMAJ
2002;167:241 – 5.
Nitzan Kaluski D, Amitai Y, Haviv A, Goldsmith R, Leventhal A.
Dietary folate and the incidence and prevention of neural tube defect:
a proposed triple intervention approach in Israel. Nutr Rev 2002;
60:303 – 7.