Vitamin, mineral and iron supplementation in pregnancy: cross-sectional study
Aim. To assess the use of vitamin, mineral and iron supplements during pregnancy in Zagreb and Novi Sad. Methods. The study was conducted by use of a structured standardized questionnaire consisting of two parts, i. e. data obtained by maternal interview and hospital records. It is designed as a cro...
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Інститут молекулярної біології і генетики НАН України
2010
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| Цитувати: | Vitamin, mineral and iron supplementation in pregnancy: cross-sectional study / M. Leppee, J. Culig, M. Eric, J. Boskovic, N. Colak // Вiopolymers and Cell. — 2010. — Т. 26, № 2. — С. 128-135. — Бібліогр.: 21 назв. — англ. |
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irk-123456789-1538652019-07-06T20:27:14Z Vitamin, mineral and iron supplementation in pregnancy: cross-sectional study Leppee, M. Culig, J. Eric, M. Boskovic, J. Colak, N. Biomedicine Aim. To assess the use of vitamin, mineral and iron supplements during pregnancy in Zagreb and Novi Sad. Methods. The study was conducted by use of a structured standardized questionnaire consisting of two parts, i. e. data obtained by maternal interview and hospital records. It is designed as a cross-sectional study in two countries (Croatia and Serbia). The study included 893 pregnant women from Zagreb and 6099 pregnant women from Novi Sad. Results. In Zagreb, pregnant women reported highest utilization of vitamin-mineral supplements (n = 508; 56.9 %), whereas in Novi Sad these supplements ranked third (n = 408; 20.3 %), following tocolytics and iron supplements. There was no statistically significant difference in the prevalence of congenital malformations between neonates at in utero exposure to vitamins, minerals and iron supplements and those without such exposure in either Zagreb or Novi Sad arm, with the exception of iron and calcium supplementation in the Zagreb arm. Conclusions. In spite of certain study limitations, the results obtained pointed to the unreasonable and potentially harmful use of these supplements in pregnant women from Zagreb. Мета. Oцінити вживання вітаминів, а також харчових добавок, які містять мінерали і залізо, протягом вагітності жінок із Загреба та Нові-Сада. Mетоди. Дослідження проводили із використанням стандартного структурованого опитування, яке складається з двох частин: даних, одержаних під час інтерв’ю, та лікарняних записів. Воно побудовано як кроссекційне дослідження у двох країнах (Хорватії і Сербії). Досліджували 893 вагітні жінки із Загреба та 6099 вагітних жінок з Нові-Сада. Результати. У вагітних жінок із Загреба відмічено найвище вживання вітамінно-мінеральних добавок (n = 508; 56.9 %), у той час як у Нові-Саді воно виявилося в три рази нижчим (n = 408; 20.3 %), включаючи токолітики – препарати, які попереджують передчасні пологи, і добавки заліза. Не виявлено статистичено достовірних розбіжностей у частоті появи вроджених дефектів розвитку у новонароджених, які в пренатальному періоді отримували або не отримували добавки, які містять вітаміни, мінерали і залізо, в обох регіонах, за винятком добавок із залізом та кальцієм у загребській виборці. Выводы. Незважаючи на певні обмеження у дослідженні, результати свідчать про необгрунтоване та потенційно шкідливе застосування таких добавок серед вагітних жінок у Загребі. Цель. Oценить применение витаминов, а также пищевых добавок, содержащих минералы и железо, во время беременности у женщин, проживающих в Загребе и Нови-Саде. Mетоды. Исследование проводили с использованием стандартного структурированного опроса, состоящего из двух частей: данных, полученных в ходе интервью, и записей в больницах. Оно построено как кросс-секционное исследование в двух странах (Хорватии и Сербии). Исследовано 893 беременные женщины из Загреба и 6099 – из Нови-Сада. Результаты. У беременных женщин из Загреба отмечено наиболее высокое употребление витаминно-минеральных добавок (n = 508; 56.9 %), в то время как в Нови-Саде оно оказалось в три раза ниже (n = 408; 20.3 %), включая токолиты – препараты, предотвращающие преждевременные роды, и добавки железа. Не выявлено статистически достоверных различий в частоте появления врожденных дефектов развития у новорожденных, которые в пренатальном периоде получали или не получали добавок, содержащих витамины, минералы и железо, в обоих регионах, за исключением добавок с железом и кальцием в загребской выборке. Выводы. Несмотря на определенные ограничения в исследовании, результаты свидетельствуют о необоснованном и потенциально вредном применении этих добавок среди беременных женщин в Загребе. 2010 Article Vitamin, mineral and iron supplementation in pregnancy: cross-sectional study / M. Leppee, J. Culig, M. Eric, J. Boskovic, N. Colak // Вiopolymers and Cell. — 2010. — Т. 26, № 2. — С. 128-135. — Бібліогр.: 21 назв. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.00014F http://dspace.nbuv.gov.ua/handle/123456789/153865 618.2-083:612.015.6 en Вiopolymers and Cell Інститут молекулярної біології і генетики НАН України |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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Biomedicine Biomedicine |
| spellingShingle |
Biomedicine Biomedicine Leppee, M. Culig, J. Eric, M. Boskovic, J. Colak, N. Vitamin, mineral and iron supplementation in pregnancy: cross-sectional study Вiopolymers and Cell |
| description |
Aim. To assess the use of vitamin, mineral and iron supplements during pregnancy in Zagreb and Novi Sad. Methods. The study was conducted by use of a structured standardized questionnaire consisting of two parts, i. e. data obtained by maternal interview and hospital records. It is designed as a cross-sectional study in two countries (Croatia and Serbia). The study included 893 pregnant women from Zagreb and 6099 pregnant women from Novi Sad. Results. In Zagreb, pregnant women reported highest utilization of vitamin-mineral supplements (n = 508; 56.9 %), whereas in Novi Sad these supplements ranked third (n = 408; 20.3 %), following tocolytics and iron supplements. There was no statistically significant difference in the prevalence of congenital malformations between neonates at in utero exposure to vitamins, minerals and iron supplements and those without such exposure in either Zagreb or Novi Sad arm, with the exception of iron and calcium supplementation in the Zagreb arm. Conclusions. In spite of certain study limitations, the results obtained pointed to the unreasonable and potentially harmful use of these supplements in pregnant women from Zagreb. |
| format |
Article |
| author |
Leppee, M. Culig, J. Eric, M. Boskovic, J. Colak, N. |
| author_facet |
Leppee, M. Culig, J. Eric, M. Boskovic, J. Colak, N. |
| author_sort |
Leppee, M. |
| title |
Vitamin, mineral and iron supplementation in pregnancy: cross-sectional study |
| title_short |
Vitamin, mineral and iron supplementation in pregnancy: cross-sectional study |
| title_full |
Vitamin, mineral and iron supplementation in pregnancy: cross-sectional study |
| title_fullStr |
Vitamin, mineral and iron supplementation in pregnancy: cross-sectional study |
| title_full_unstemmed |
Vitamin, mineral and iron supplementation in pregnancy: cross-sectional study |
| title_sort |
vitamin, mineral and iron supplementation in pregnancy: cross-sectional study |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| publishDate |
2010 |
| topic_facet |
Biomedicine |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/153865 |
| citation_txt |
Vitamin, mineral and iron supplementation in pregnancy: cross-sectional study / M. Leppee, J. Culig, M. Eric, J. Boskovic, N. Colak // Вiopolymers and Cell. — 2010. — Т. 26, № 2. — С. 128-135. — Бібліогр.: 21 назв. — англ. |
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Вiopolymers and Cell |
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2025-07-14T05:18:18Z |
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| fulltext |
Vitamin, mineral and iron supplementation in
pregnancy: cross-sectional study
M. Leppee1, J. Culig1, 2, M. Eric3, J. Boskovic4, N. Colak5
1Andrija Stampar Institute of Public Health
16, Mirogojska, Zagreb, Croatia, 10000
2School of Medicine, Josip Juraj Strossmayer University
4, Josipa Huttlera, Osijek, Croatia, 31000
3School of Medicine, University of Novi Sad
3, Hajduk Veljkova, Novi Sad, Serbia, 21000
4Faculty of Pharmacy and Biochemistry
1 A. Kovacica, Zagreb, Croatia, 10000
5Colpharm d. o. o.
16, Trnska cesta, Siroki Brijeg, Bosnia and Herzegovina, 88220
marcel.leppee@stampar.hr
Aim. To assess the use of vitamin, mineral and iron supplements during pregnancy in Zagreb and Novi Sad.
Methods. The study was conducted by use of a structured standardized questionnaire consisting of two
parts, i. e. data obtained by maternal interview and hospital records. It is designed as a cross-sectional
study in two countries (Croatia and Serbia). The study included 893 pregnant women from Zagreb and 6099
pregnant women from Novi Sad. Results. In Zagreb, pregnant women reported highest utilization of vi-
tamin-mineral supplements (n = 508; 56.9 %), whereas in Novi Sad these supplements ranked third
(n = 408; 20.3 %), following tocolytics and iron supplements. There was no statistically significant
difference in the prevalence of congenital malformations between neonates at in utero exposure to vitamins,
minerals and iron supplements and those without such exposure in either Zagreb or Novi Sad arm, with the
exception of iron and calcium supplementation in the Zagreb arm. Conclusions. In spite of certain study
limitations, the results obtained pointed to the unreasonable and potentially harmful use of these
supplements in pregnant women from Zagreb.
Keywords: vitamins, minerals, pregnancy, Zagreb, Novi Sad.
Introduction. Vitamins are substances necessary for
life. Quite frequently, use of supplements containing
multiple vitamins (multivitamins) is routinely advised
to pregnant women. Multivitamins usually contain
vitamins A (retinol), D (calciferol), C (ascorbic acid), E
(tocopherol), vitamin B complex, B1 (thiamine), B2
(riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (py-
ridoxine), vitamin B12 and folic acid. These supple-
ments may also contain iron, calcium, and other mine-
rals. Vitamin utilization in pregnancy varies from
country to country. Although necessary for life, vita-
min K (menadione) is not included in vitamin
supplements because it is found in food in adequate
amounts. Liposoluble vitamins A, D and E may exert
teratogenic effects when administered in high doses.
Water soluble vitamin C and B complex vitamins are
128
ISSN 0233-7657. Biopolymers and Cell. 2010. Vol. 26. N 2
Ó Institute of Molecular Biology and Genetics NAS of Ukraine, 2010
safe in doses recommended by the National Academy
of Sciences (NAS). Vitamin deficiency can also cause
serious problems.
Vitamins are classified into Food and Drug Admi-
nistration (FDA) categories according to dosage.
The role of vitamins in the prevention of some con-
genital malformations remains a matter of dispute. Two
different types of congenital anomalies, i. e. cleft lip
and neural tube defects, were in the focus of research
into the use of vitamins in pregnancy. Extremity shor-
tening has been defined as a third type of anomaly
potentially associated with the use of vitamins in
pregnancy.
Numerous studies performed to date have failed to
offer an unambiguous statement on the need of vi-
tamin-mineral supplementation therapy in pregnancy.
Most authors believe that appropriate diet rich in
vitamins and minerals is necessary for the fetus to un-
dergo regular growth and development. In case of
normal maternal diet and adequate intake of all nut-
rients, there is no need for supplementation [1, 2].
However, modern lifestyle and unfavorable dietary
habits frequently result in inappropriate diet during
pregnancy, thus imposing the need of target education
of pregnant women and women planning pregnancy,
along with the intake of food supplements in pregnancy
[3].
One of the most important studies was the inter-
national multicenter study entitled Collaborative Study
on Drug Use in Pregnancy (DUP), initiated in 1987 by
the Mario Negri Institute (Milan, Italy) and cospon-
sored by the World Health Organization (WHO)
Regional Office for Europe (Copenhagen, Denmark).
Two centers from former Yugoslavia, i. e. Zagreb and
Novi Sad were involved.
The study included 14778 pregnant women from
148 maternity wards in 22 countries on 4 continents.
There were 609 women from Zagreb and 296 women
from Novi Sad. Study results showed great country to
country differences determined by the broad spectrum
of medical care, public health issues and customs found
in the various countries included in the study. Only
14 % of women received no medication, whereas 86 %
of women were taking a mean of 2.9 drugs during preg-
nancy [4–7]. Iron and vitamin supplements accounted
for 50 % of drugs administered in pregnancy.
However, it is beyond doubt that the use of some
drugs in pregnancy exceeds the research based medical
recommendations. This primarily applies to the routine
use of iron supplements in pregnancy in industrialized
countries, where the prevalence of anemia does not
exceed 15 %.
Teratogenic factors show selectivity according to
gestational periods. It is well established that first-
trimester (3rd to 8th week of gestation) drug exposure is
critical for the fetus. The period of cell proliferation is
the initial stage of development, from conception to
early postimplantation (the initial two weeks of ges-
tation in humans). During this period, teratogens exert
the «all or nothing» effect, i. e. the embryonal effect is
either very profound and tissue lesions severe, leading
to embryonal death, or only few cells are involved, so
that the embryo can easily replace them and develop
normally. The next stage, organogenesis (3rd to 8th week
of gestation in humans), is a period of highest teratogen
sensitivity because of the fast cell differentiation when
the lesions cannot be corrected. Embryonic phase ex-
tends from the period of cell proliferation to the comp-
letion of organogenesis. Fetal phase as the third stage
of development is relatively insensitive to teratogens,
however, functional impairments, growth retardation
and even fetal death may occur in this period. This sta-
ge is characterized by growth and functional matu-
ration of the already formed organs and systems.
The aim of the study was to assess the prevalence of
vitamin and mineral use and the rate of congenital
malformations in neonates at in utero exposure to these
substances.
Materials and Methods. One arm of the study
(one-month study) was performed at four maternity
hospitals in Zagreb, Croatia: University Department of
Gynecology and Obstetrics, Zagreb University Hos-
pital Center; University Department of Gynecology
and Obstetrics, Sestre milosrdnice University Hospital;
University Department of Gynecology and Obstetrics,
Merkur University Hospital; and University Depart-
ment of Gynecology and Obstetrics, Sveti Duh General
Hospital (part 1).
The other arm of the study (one-year study) was
performed at the Genetic Counseling Unit, Institute for
Children and Adolescents, University Department of
Gynecology and Obstetrics, and Department of Patho-
129
VITAMIN, MINERAL AND IRON SUPPLEMENTATION IN PREGNANCY
logy and Histology, Clinical Center in Novi Sad, Ser-
bia, and included pregnant women presenting to the
Genetic Counseling Unit for risk pregnancy and
pregnant women hospitalized at University Depart-
ment of Gynecology and Obstetrics for delivery or
abortion (part 2).
The study included 893 pregnant women from Zag-
reb and 6099 pregnant women from Novi Sad. Infor-
med consent on their participation in the study was
obtained from all study subjects. The study was appro-
ved by independent Ethics Committee of the School of
Medicine.
Data were collected from the following sources:
1) questionnaire for pregnant women, filled
in by a physician, containing two types of data: hospital
records and information obtained by interview;
2) thorough physical examination of the neo-
nate, performed by a neonatologist according to stan-
dard protocol;
3) thorough pathologic examination of the fe-
tus, performed by a pathologist according to standard
protocols.
Vital data on the newborns, maternal data on
previous deliveries and on medication taken between
hospital admission and delivery were collected from
hospital records.
The other part of the questionnaire contained data
obtained by interview on the mother’s age, level of
education, use of contraception, ultrasound (US)
studies during pregnancy, X-rays during pregnancy,
and use of drugs, alcohol, nicotine and opioid sub-
stances during pregnancy. Following delivery or abor-
tion, the newborns and fetuses were thoroughly exa-
mined and monitored for the occurrence of minor or
major malformations. The use of vitamins, minerals
and iron supplements, and the existence of congenital
malformations in newborns and fetuses at in vitro ex-
posure to these drugs were monitored according to ges-
tational trimesters.
The study was conducted according to the Clinical
Epidemiological Trial Protocol and in line with the
By-Law on Clinical Trials and Good Clinical Practice,
implying due respect of all provisions of Helsinki.
Declaration and recommendations of the World
Medical Association of Physicians Performing Biome-
dical Trials in Humans.
Epidemiological methods were employed in the
study because clinical therapeutic trials in pregnant
women are highly restricted by current ethical prin-
ciples. The trial was designed as a cross-sectional study
to determine exposure of pregnant women to a parti-
cular drug, their disease status, and their newborns’
conditions. Using this method, the prevalence of mal-
formations and pathologic states was determined in the
neonates born to mothers at a particular drug exposure
versus neonates born to mothers free from such a drug
exposure.
All drugs including vitamins, minerals and iron
supplements taken by study women during pregnancy
were classified according to safety level into five FDA
categories.
Our study has the approvals of all relevant ethics
committees from all maternity hospitals. All women
have given written informed consent.
Statistical analysis. Student’s t-test and Chi-square
test with a significance level of p £ 0.05 were used
when appropriate for the evaluation of the results. All
analysis were performed with SigmaStat 3.0 for Win
dows (SPSS Science software products, Chicago, IL,
U. S.).
Results and Discussion. The prevalence of con-
genital malformations in the general population was
2.91 % (n = 26) in Zagreb and 5.35 % (n = 326) in Novi
130
LEPPEE M. ET AL.
Drug
Pregnant women
n %
Zagreb arm
Vitamins and minerals 508 56.9
Diazepam 303 33.9
Iron and folic acid 297 33.3
Oxytetracyclin + nystatin 227 25.4
Novi Sad arm
Tocolytics 536 26.6
Iron 429 21.3
Vitamins and minerals 297 20.3
Antimicrobials 227 19.5
Table 1
Drugs most commonly used in pregnancy
131
VITAMIN, MINERAL AND IRON SUPPLEMENTATION IN PREGNANCY
Sad. The four leading drugs in Zagreb and Novi Sad
are shown in Table 1. The prevalence of congenital
malformations in fetuses and neonates at in utero drug
exposure was 3.03 % (n = 26) in Zagreb and 5.61 %
(n = 113) in Novi Sad.
The vitamins, minerals, iron supplements and fo-
lic acid used during pregnancy and malformations
detected in these fetuses or newborns in Zagreb are
presented in Tables 2 and 3. The number of women
taking these supplements increased with gestational
age. The prevalence of congenital malformations in
fetuses and neonates at prenatal exposure to the action
of vitamins and minerals was 2.76 % (n = 14) and was
quite comparable to the rate found in the general
population (n = 26; 2.91 %). In fetuses and neonates at
prenatal exposure to iron supplements and folic acid,
the prevalence of congenital malformations was
4.04 % (n = 12), exceeding the rate found in the ge-
neral population; however, the difference did not
reach statistical significance.
The use of calcium during pregnancy increased
from 3.4 % (n = 30) in first trimester through 5.3 %
(n = 47) in second trimester to 5.7 % (n = 51) in third
trimester. It should be noted that study women re-
ported negligible or no use of calcium before preg-
nancy. Malformations were found in four fetuses and
neonates with prenatal exposure to calcium.
The vitamins, minerals and iron supplements used in
pregnancy and malformations detected in these fetuses
or newborns in Novi Sad are presented in Table 4.
The prevalence of congenital malformations in fe-
tuses and neonates at in utero exposure to vitamins and
minerals was 4.17 % (n = 17), which was below the rate
found in the general population (n = 326; 5.35 %),
however, the difference was not statistically significant.
In fetuses and neonates at prenatal exposure to iron
supplements, the prevalence of congenital malforma-
tions was 3.03 % (n = 13), which was also below the rate
found in the general population and the difference was
statistically significant (c2 = 4.36, p < 0.05). In fetuses
and neonates at prenatal exposure to folic acid, the
prevalence of congenital malformations was 15.39 %
(n = 2), considerably exceeding the rate found in the ge-
neral population; however, the difference was not statis-
tically significant.
In the Novi Sad arm, positive correlation was
recorded between gestational age and the rate of vitamin,
mineral and iron supplementation. Besides the use of
vitamins and minerals in pregnancy, exposure to other
adverse factors was recorded in 25 pregnant women in
Novi Sad (Table 5).
There was no statistically significant difference in
the rate of congenital malformations according to the use
of study substances between Zagreb and Novi Sad.
Table 2
Maternal use of vitamins, minerals, iron supplements and folic acid, and congenital malformations – Zagreb arm
Drug FDA class No. of women
Trimester
No. of
malformations
I II III
Vitamins and minerals A 508 289 400 465 14
Iron supplements and folic acid A 297 175 172 191 12
FDA = Food and Drug Administration.
Table 3
Congenital malformations according to organ systems involved
Drug
Organ system involved
Total
CV GU HN MS Resp Abd Skin Unknown
Vitamins and minerals 5 3 – 2 – 1 1 2 14
Iron supplements and folic acid 2 4 1 2 2 – – 1 12
CV = cardiovascular; GU = genitourinary; HN = head and neck; MS = musculoskeletal; Resp = respiratory; Abd = abdominal.
The effect of the potential teratogens on the course
and outcome of pregnancy does not only depend on the
gestational age at exposure but also on the amount and
dosage of teratogen exposure. This can best be exem-
plified by vitamin A, as both vitamin A deficiency and
hypervitaminosis have a teratogenic potential. The pre-
sent study suffered from some methodological
limitations, i. e. use of a questionnaire answered by the
study women, where the possible errors in recollection
as well as the impact of educational level and per-
sonality on the answers could not be ruled out. The-
refore, data were in part collected from hospital re-
cords. Considering the length of the study, seasonal
effects on the study results could not be ruled out either.
In large international studies, data have been increa-
singly derived from network databases on prescription
drugs, thus minimizing the possible errors [8, 9]. In the
present study, the Zagreb arm showed the vitamin-
mineral supplements to be most frequently prescribed
to pregnant women, whereas in Novi Sad these sup-
plements ranked third. According to this parameter, the
two study populations did not differ from other settings
included in similar studies, where vitamins and mi-
nerals also predominated in drug utilization during
pregnancy [10, 11]. According to a cross-sectional stu-
dy from Addis Ababa, Ethiopia, iron and vitamins
accounted for the majority of drugs prescribed in
Africa [12].
On the other side of the world, in western Nepal,
the most commonly prescribed drugs were dietary sup-
plements like iron, folate, calcium, and vitamins
(72.8 %) [13].
Teratogenicity of vitamin A hyper- and hypo-
vitaminosis has been reported from previous studies.
High doses of vitamin A lead to the occurrence of cleft
palate, spina bifida, anencephaly, lung agenesis or
hypoplasia, and malformations of genitourinary and
gastrointestinal system, whereas vitamin A deficiency
results in congenital xerophthalmia, anophthalmia,
retinal detachment, microcephaly, and cleft lip [14].
High dietary intake of preformed vitamin A appears to
be teratogenic. Rothman et al. estimated that one of 57
132
LEPPEE M. ET AL.
Table 4
Maternal use of vitamins, minerals, iron supplements and folic acid, and congenital malformations – Novi Sad arm
Drug FDA class
No. of
women
Trimester
No. of
malformations
Malformations
I II III
Vitamins and
minerals
A 408 47 267 398 17
Right ear otopostasis, right kidney hydronephrosis,
pes valgus (n = 3), frenulum linguae breve (n = 10),
hydrocephalus, diastasis m. recti abdominis
Ferrosulfate A 429 11 142 418 13
Cleft palate, atrial septal defect, pes valgus (n = 4),
frenulum linguae breve (n = 6), micrognathia
Folic acid A 13 2 10 13 2 Pes valgus, frenulum linguae breve
FDA = Food and Drug Administration.
Table 5
Novi Sad arm women exposed to additional noxae
Drug Trimester Additional noxae Fetal findings
Vitamins and minerals II and III < 10 cigarettes daily in 12 women
Right kidney hydronephrosis and frenulum
linguae breve in one case each
III Dental X-ray in first trimester Normal finding
III Pelvis X-ray in first trimester Normal finding
II and III Maternal age > 35 in 12 women
Hydrocephalus and frenulum linguae breve
in one case each
infants born to women having used more than 10,000
IU of preformed vitamin A per day in the form of
supplements had a malformation attributable to the
supplement [15].
Vitamin B12 deficiency leads to fetal development
of megaloblastic anemia, while there are no data on the
adverse effects of vitamin B12 high doses. Vitamin C
deficiency results in impaired neural tube develop-
ment, while hypervitaminosis C has been associated
with isolated cases of anencephaly. Maternal vitamin D
insufficiency is common during pregnancy and is
associated with reduced bone-mineral accrual in the
offspring during childhood. Excessive doses of vi-
tamin D may lead to mental retardation, retarded phy-
sical development, strabismus, craniosynostosis, sup-
ravalvular aortic stenosis, inguinal hernia, cryptorchi-
dism in male fetuses, and premature development of
secondary sexual characteristics in female fetuses [16].
Low maternal vitamin E intake during pregnancy is
associated with asthma in 5-year-old children [17].
When administered in low daily doses, vitamins are
classified as fetal risk category A. However, if taken in
high doses, vitamins can exert adverse effects on fetal
development and lead to congenital malformations. In
this context, vitamin A is classified as fetal risk cate-
gory X, vitamin D as category D, and other vitamins as
category C [18].
There are no literature data on the possible terato-
genic effect of minerals. Important problem during pre-
gnancy is the deficit of micronutrient and therefore
supplementation can alleviate deficiencies, but supple-
ments must be taken for an adequate period of time
[19].
Analysis of our study results and the high utili-
zation of vitamins in pregnancy showed that there was
no statistically significant difference between the pre-
valence of congenital malformations in fetuses and
neonates at prenatal exposure to vitamins or vitamin-
mineral supplements and the prevalence of congenital
malformations in the general population. Accordingly,
maternal use of these substances was not associated
with the occurrence of congenital malformations.
Considering the structure of malformations, pre-
natal exposure to vitamins or complex vitamin supple-
ments was mainly associated with minor congenital
malformations, whereas major malformations were on-
ly recorded in two cases (hydrocephalus and hydrone-
phrosis). However, fetal exposure to other harmful no-
xae was involved in both cases and these adverse
effects were more likely the cause of malformation and
functional impairment than the maternal intake of vita-
mins or vitamin complexes.
Analysis of calcium intake by mothers to children
with congenital malformations yielded a statistically
significant difference at the level of p < 0.05 in the rate
of congenital malformations between the infants at
prenatal calcium exposure and those free from it,
suggesting an association of maternal calcium intake
and congenital malformations. However, there was no
statistically significant difference at the level of
p < 0.01. The search through relevant literature failed
to yield similar results, suggesting suspicion towards
uncontrolled use of various vitamin-mineral supple-
ments in pregnancy.
Analysis of maternal use of iron supplements (in
Zagreb arm) produced a statistically significant dif-
ference in the rate of congenital malformations bet-
ween the neonates at in utero iron exposure and those
free from this exposure, pointing to an association
between maternal iron intake and congenital malfor-
mations. This finding differed from previous studies
that found no association between congenital mal-
formations and use of iron supplements in pregnancy
[20].
However, our results support the authors that
disapprove uncritical iron prescribing [21], since some
10 % of non-pregnant women of reproductive age
suffer from anemia. In the Novi Sad arm, there was no
statistically significant difference between the infants
at prenatal iron exposure and those without it.
In the present study, the possible effect of particular
vitamins on fetal health could not be determined be-
cause the great majority of study women used combi-
ned multivitamin-mineral supplements. Therefore, the
possible effect of a particular vitamin on fetal malfor-
mations could not be identified.
Conclusions. Additional studies are needed to
investigate the maternal and fetal effects of mineral
supplementation. The use and promotion of vitamin-
mineral supplementation should be discouraged and
abandoned, at least in pregnancy. Instead, the use of
monocomponent supplementation of any vitamin or
133
VITAMIN, MINERAL AND IRON SUPPLEMENTATION IN PREGNANCY
134
LEPPEE M. ET AL.
mineral with demonstrated deficiency should be
supported. For this purpose, it is advised to analyze the
effect of each individual vitamin and mineral, in our
setting iron and calcium.
In spite of the limitations mentioned above, our
study pointed to the possible too much utilization of
vitamins and minerals during pregnancy in Zagreb
women and offered an opportunity to improve the
quality of therapy in this vulnerable period of life. The
study highlighted the issue of reasonable utilization
and the need of developing guidelines for the use of
vitamins, minerals, iron and folic acid supplemen-
tation, considering that these substances are available
as over-the-counter drugs. And the last but not the
least, the first trimester deserves due attention and
management as the most vulnerable period of fetal
development.
Acknowledgements. We would thank all monitors
participating to collect data for this study, and all phy-
sicians collaborating of hospital structures involved
into the study: University Departments of Gynecology
and Obstetrics in four Zagreb hospitals: Zagreb Uni-
versity Hospital Center, Sestre milosrdnice Uni-
versity Hospital, Merkur University Hospital and Sveti
Duh General Hospital and in these institutions in Novi
Sad: Genetic Counseling Unit, Institute for Children
and Adolescents, University Department of Gyneco-
logy and Obstetrics, and Department of Pathology and
Histology, Clinical Center in Novi Sad.
M. ˳ïå, Äæ.Êóë³ã, Ì. Åð³ê, Äæ. Áîñ êî âè÷, Í. Êî ëàê
³òà ìè íè, ì³íå ðà ëè ³ äî áàâ êè çàë³çà ïðè âàã³òíîñò³:
ïå ðå õðåñ íå âèâ ÷åí íÿ
Ðå çþ ìå
Ìåòà. Oö³íèòè âæè âàí íÿ â³òà ìèí³â, à òà êîæ õàð ÷î âèõ äî áà -
âîê, ÿê³ ì³ñòÿòü ì³íå ðà ëè ³ çàë³çî, ïðî òÿ ãîì âàã³òíîñò³ æ³íîê
³ç Çàã ðå áà òà Íîâ³-Ñàäà. Må òî äè. Äîñë³äæåí íÿ ïðî âî äè ëè ³ç
âè êî ðèñ òàí íÿì ñòàí äàð òíî ãî ñòðóê òó ðî âà íî ãî îïè òó âàí íÿ,
ÿêå ñêëà äàºòüñÿ ç äâîõ ÷àñ òèí: äà íèõ, îäåð æà íèõ ï³ä ÷àñ ³í-
òåð â’þ, òà ë³êàð íÿ íèõ çà ïèñ³â. Âîíî ïî áó äî âà íî ÿê êðîñ-
ñåêö³éíå äîñë³äæåí íÿ ó äâîõ êðà¿ íàõ (Õîð âàò³¿ ³ Ñåð᳿).
Äîñë³äæó âà ëè 893 âàã³òí³ æ³íêè ³ç Çàã ðå áà òà 6099 âàã³òíèõ
æ³íîê ç Íîâ³-Ñàäà. Ðå çóëü òà òè. Ó âàã³òíèõ æ³íîê ³ç Çàã ðå áà
â³äì³÷åíî íà é âè ùå âæè âàí íÿ â³òàì³ííî-ì³íå ðàëü íèõ äî áà âîê
(n = 508; 56.9 %), ó òîé ÷àñ ÿê ó Íîâ³-Ñàä³ âîíî âè ÿ âè ëî ñÿ â òðè
ðàçè íè æ÷èì (n = 408; 20.3 %), âêëþ ÷à þ ÷è òî êîë³òèêè – ïðå ïà -
ðà òè, ÿê³ ïî ïå ðåä æó þòü ïå ðå ä÷àñí³ ïî ëî ãè, ³ äî áàâ êè çàë³çà.
Íå âè ÿâ ëå íî ñòà òèñ òè ÷å íî äîñ òîâ³ðíèõ ðîçá³æíîñ òåé ó ÷àñ -
òîò³ ïî ÿ âè âðîä æå íèõ äå ôåêò³â ðîç âèò êó ó íî âîíà ðîä æå íèõ,
ÿê³ â ïðå íà òàëü íî ìó ïåð³îä³ îò ðè ìó âà ëè àáî íå îò ðè ìó âà ëè äî -
áàâ êè, ÿê³ ì³ñòÿòü â³òàì³íè, ì³íå ðà ëè ³ çàë³çî, â îáîõ ðåã³îíàõ,
çà âè íÿò êîì äî áà âîê ³ç çàë³çîì òà êàëüö³ºì ó çà ãðåáñüê³é âè -
áîðö³. Âû âî äû. Íåç âà æà þ ÷è íà ïåâí³ îá ìå æåí íÿ ó äîñë³ä-
æåíí³, ðå çóëü òà òè ñâ³ä÷àòü ïðî íå îá ãðóí òî âà íå òà ïî òåí-
ö³éíî øê³äëè âå çà ñòî ñó âàí íÿ òà êèõ äî áà âîê ñå ðåä âàã³òíèõ
æ³íîê ó Çàã ðåá³.
Êëþ ÷îâ³ ñëî âà: â³òàì³íè, ì³íå ðà ëè, âàã³òí³ñòü, Çàã ðåá,
Íîâ³-Ñàä.
M. Ëèïå, Äæ.Êó ëèã, Ì. Ýðèê, Äæ. Áîñ êî âè÷, Í. Êîëàê
Âè òà ìè íû, ìè íå ðà ëû è äî áàâ êè æå ëå çà ïðè áå ðå ìåí íîñ òè:
ïå ðå êðåñ òíîå èç ó÷å íèå
Ðå çþ ìå
Öåëü. Oöå íèòü ïðè ìå íå íèå âè òà ìè íîâ, à òàê æå ïè ùå âûõ äî -
áà âîê, ñî äåð æà ùèõ ìè íå ðà ëû è æå ëå çî, âî âðå ìÿ áå ðå ìåí íîñ -
òè ó æåí ùèí, ïðî æè âà þ ùèõ â Çàã ðå áå è Íîâè-Ñàäå. Må òî äû.
Èññëå äî âà íèå ïðî âî äè ëè ñ èñ ïîëü çî âà íè åì ñòàí äàð òíî ãî
ñòðóêòó ðè ðî âàí íî ãî îïðî ñà, ñî ñòî ÿ ùå ãî èç äâóõ ÷àñ òåé: äàí -
íûõ, ïî ëó ÷åí íûõ â õîäå èí òåð âüþ, è çà ïè ñåé â áîëü íè öàõ. Îíî
ïî ñòðî å íî êàê êðîññ-ñåê öè îí íîå èñ ñëå äî âà íèå â äâóõ ñòðà íàõ
(Õîð âà òèè è Ñåð áèè). Èññëå äî âà íî 893 áå ðå ìåí íûå æåí ùè íû
èç Çàã ðå áà è 6099 – èç Íîâè-Ñàäà. Ðå çóëü òà òû. Ó áå ðå ìåí íûõ
æåí ùèí èç Çàã ðå áà îò ìå ÷å íî íà è áî ëåå âû ñî êîå óïîò ðåá ëå íèå
âè òà ìèí íî-ìè íå ðàëü íûõ äî áà âîê (n = 508; 56.9 %), â òî âðå ìÿ
êàê â Íîâè-Ñàäå îíî îêà çà ëîñü â òðè ðàçà íèæå (n = 408;
20.3 %), âêëþ ÷àÿ òî êî ëè òû – ïðå ïà ðà òû, ïðåä îò âðà ùà þ ùèå
ïðå æäåâ ðå ìåí íûå ðîäû, è äî áàâ êè æå ëå çà. Íå âû ÿâ ëå íî ñòà -
òèñ òè ÷åñ êè äîñ òî âåð íûõ ðàç ëè ÷èé â ÷àñ òî òå ïî ÿâ ëå íèÿ
âðîæ äåí íûõ äå ôåê òîâ ðàç âè òèÿ ó íî âî ðîæ äåí íûõ, êî òî ðûå â
ïðå íà òàëü íîì ïå ðè î äå ïî ëó ÷à ëè èëè íå ïî ëó ÷à ëè äî áà âîê, ñî -
äåð æà ùèõ âè òà ìè íû, ìè íå ðà ëû è æå ëå çî, â îá îèõ ðå ãè î íàõ, çà
èñ êëþ ÷å íè åì äî áà âîê ñ æå ëå çîì è êàëü öè åì â çà ãðåá ñêîé âû -
áîð êå. Âû âî äû. Íåñ ìîò ðÿ íà îïðå äå ëåí íûå îãðà íè ÷å íèÿ â èñ -
ñëå äî âà íèè, ðå çóëü òà òû ñâè äå ò åëüñòâó þò î íå î áîñ íî âàí íîì
è ïî òåí öè àëü íî âðåä íîì ïðè ìå íå íèè ýòèõ äî áà âîê ñðå äè áå ðå -
ìåí íûõ æåí ùèí â Çàã ðå áå.
Êëþ ÷å âûå ñëî âà: âè òà ìè íû, ìè íå ðà ëû, áå ðå ìåí íîñòü, Çàã -
ðåá, Íîâè-Ñàä.
REFERENCES
1. Jackson A. A., Robinson S. M. Dietary guidelines for pregnan-
cy: a review of current evidence // Publ. Health Nutr.–2001.–
4, N 2B.–P. 625–630.
2. Kind K. L., Moore V. M., Davies M. J. Diet around conception
and during pregnancy – effects on fetal and neonatal outco-
mes // Repr. Biomed. Online.–2006.–12, N 5.–P. 532–541.
3. Glenville M. Nutritional supplements in pregnancy: commer-
cial push or evidence based? // Curr. Opin. Obstet. Gynecol.–
2006.–18, N 6.–P. 642–647.
4. Collaborative Group on Drug Use in Pregnancy (CGDUP).
Medication during pregnancy: an intercontinental coopera-
tive study // Int. J. Gynecol. Obstet.–1992.–39, N 3.–P. 185–
196.
5. Bonati M., Bortolus R., Marchetti F., Romero M., Tognoni G.
Drug use in pregnancy: an overview of epidemiological
(drug utilization) studies // Eur. J. Clin. Pharmacol.–1990.–
38, N 4.–P. 325–328.
6. Lacroix I., Damase-Michel C., Lapeyre-Mestre M., Montas-
truc J. L. Prescription of drugs during pregnancy in France //
Lancet.–2000.–356, N 9243.–P. 1735–1736.
7. Beyens M. N., Guy C., Ratrema M., Ollagnier M. Prescription
of drugs to pregnant women in France: the HIMAGE study //
Therapie.–2003.–58, N 6.–P. 505–511.
8. Shah M. D., Shah S. R. Nutrient deficiencies in the premature
infant // Pediatr. Clin. North Am.–2009.–56, N 5.–P. 1069–
1083.
9. Leppee M. Drugs in pregnancy. PhD thesis. School of Medi-
cine, Josip Juraj Strossmayer University.–Osijek, 2008.
10. Egen-Lappe V., Hasford J. Drug prescription in pregnancy:
analysis of a large statutory sickness fund population // Eur. J.
Clin. Pharmacol.–2004.–60, N 9.–P. 659–666.
11. Piper J. M., Baum C., Kennedy D. L. Prescription drug use
before and during pregnancy in a Medicaid population // Am.
J. Obstet. Gynecol.–1987.–157, N 1.–P. 148–156.
12. Kebede B., Gedif T., Getachew A. Assessment of drug use
among pregnant women in Addis Ababa, Ethiopia // Phar-
macoepidemiol. Drug Saf.–2009.–18, N 6.–P. 462–468.
13. Das B., Sarkar C., Datta A., Bohra S. A study of drug use
during pregnancy in a teaching hospital in western Nepal //
Pharmacoepidemiol. Drug Saf.–2003.–12, N 3.–P. 221–225.
14. Mills J. L., Simpson J. L., Cunningham G. C., Conley M. R.,
Rhoads G. G. Vitamin A and birth defects // Am. J. Obstet.
Gynecol.–1997.–177, N 1.–P. 31–36.
15. Rothman K. J., Moore L. L., Singer M. R., Nguyen U. S., Man-
nino S., Milunsky A. Teratogenicity of high vitamin A intake
// N. Engl. J. Med.–1995.–333, N 21.–P. 1369–1373.
16. Javaid M. K., Crozier S. R., Harvey N. C., Gale C. R., Denni-
son E. M., Boucher B. J., Arden N. K., Godfrey K. M., Cooper
C. Maternal vitamin D status during pregnancy and childhood
bone mass at age 9 years: a longitudinal study // Lancet.–
2006.–367, N 9504.–P. 36–43.
17. Devereux G., Turner S. W., Craig L. C., McNeill G., Martin-
dale S., Harbour P. J., Helms P. J., Seaton A. Low maternal
vitamin E intake during pregnancy is associated with asthma
in 5-year-old children // Am. J. Respir. Crit. Care Med.–
2006.–174, N 5.–P. 499–507.
18. Briggs G. G., Freeman R. K., Yaffe S. J. Drugs in pregnancy
and lactation: 5th ed.–Baltimore: Williams and Wilkins,
1998.–1219 p.
19. Huskisson E., Maggini S., Ruf M. The role of vitamins and mi-
nerals in energy metabolism and well-being // J. Int. Med.
Res.–2007.–35, N 3.–P. 277–289.
20. Seligman P. A. Measurment of iron absorption from prenatal
multivitamin-mineral supplements // Obstet. Gynecol.–
1983.–61, N 3.–P. 356.
21. De Jong-van den Berg L. T., Van den Berg P. B., Haaijer-
Ruskamp F. M., Dukes M. N., Wesseling H. Investigating
drug use in pregnancy. Methodological problems and pers-
pectives // Pharm. Weekbl. (Sci.).–1991.–13, N 1.–P. 32–38.
UDC 618.2-083:612.015.6
Received 12.01.10
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