Vol.2, No.6, 566-574 (2010) Health
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Birth outcomes and pregnancy complications of women
with uterine leiomyoma—a population-based
case-control study
Ferenc Bánhidy1, Nándor Ács1, Erzsébet H. Puhó2, Andrew E. Czeizel2*
1Second Department of Obstetrics and Gynecology, Semmelweis University, School of Medicine, Budapest, Hungary
2Foundation for the Community Control of Hereditary Diseases, Budapest, Hungary;*Corresponding Author: czeizel@interware.hu
Received 16 December 2009; revised 6 January 2010; accepted 7 January 2010.
Objective Uterine leiomyoma is not a rare path-
ological condition in pregnant women; thus the
aim of the study was to evaluate the recent
progress in the treatment of these pregnant
women on the basis of the association of leio-
myoma in pregnancy (LP) with pregnancy com-
plications and birth outcomes including struc-
tural birth defects, i.e. congenital abnormalities
(CA) in the offspring. Design Cases with CA and
matched controls without CA in the popula-
tion-based Hungarian Case-Control Surveillan-
ce System of Congenital Abnormalities (HCC
SCA) were evaluated. Only women with pro-
spectively and medically recorded LP in prena-
tal maternity logbook and medically recorded
birth outcomes (gestational age, birth weight,
CA) were included to the study. Setting the
HCCSCA, 1980-1996 contained 22,843 cases
with CA and 38,151 matched controls without
CA. Population Hungarian pregnant women and
their informative offspring: live births, stillbirths
and prenatally diagnosed malformed fetuses.
Methods Comparison of birth outcomes of ca-
ses with matched controls and pregnancy com-
plications of pregnant women with or without LP.
Main outcome measures Pregnancy complica-
tions, mean gestational age at delivery and birth
weight, rate of preterm birth, low birthweight,
CA. Results A total of 34 (0.15%) cases had
mothers with LP compared to 71 (0.19%) con-
trols. There was a higher incidence of threat-
ened abortion, placental disorders, mainly ab-
ruption placentae and anaemia in mothers with
LP. There was no significantly higher rate of
preterm birth in the newborns of women with LP
but their mean birth weight was higher and it
associated with a higher rate of large birth-
weight newborns. A higher risk of total CA was
not found in cases born to mothers with LP
(adjusted OR with 95% CI = 0.7, 0.5-1.1), the spe-
cified groups of CAs were also assessed versus
controls, but a higher occurrence of women
with LP was not revealed in any CA group. Con-
clusions Women with LP have a higher risk of
threatened abortion, placental disorders and
anaemia, but a higher rate of adverse birth
outcomes including CAs was not found in their
Keywords: Uterine Leiomyoma in Pregnant Women;
Pregnancy Complications; Preterm Birth;
Large Birth Weight; Congenital Abnormalities;
Population-Based Case-Control Study
Uterine leiomyoma (fibroid) is benign, smooth muscle
tumour and most common non cancerous neoplasm in
women of child-bearing age. Though the onset of uterine
leiomyoma is increasing with advanced maternal age,
this pathological condition occurs in pregnant women as
well and because leiomyoma tends to grow under the
influence of estrogens, 15-30% of leiomyoma may
enlarge during the first trimester of pregnancy [1]. Com-
pressive effect of leiomyoma may distort the intrauterine
cavity and alter the endometrium thus after conception
may interfere implantation, placental development and
the growth of the conceptus mechanically [2]. In addi-
tion there is an increased uterine irritability and contrac-
tility secondary to rapid fibroid growth. Thus the direct
mechanical effect and indirect alteration in oxytocinase
activity may disrupt the normal progression of uterus
and development of the fetus, therefore uterine leio-
F. Bánhidy et al. / HEALTH 2 (2010) 566-574
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myoma is a cause of pregnancy loss, fetal malpresenta-
tion, intrauterine growth retardation and premature la-
bour [3].
However, most studies of pregnancy complications
and birth outcomes in uterine leiomyoma patients were
composed of participants from only one hospital or
clinic [4-7] and the results of population-based studies
have been published only recently [8-9]. The objective
of our study was the evaluation the possible association
between maternal uterine leiomyoma in pregnancy (LP)
and pregnancy complications, in addition adverse birth
outcomes, particularly structural birth defects, i.e. con-
genital abnormalities (CAs) in the population-based data
set of the Hungarian Case-Control Surveillance of Con-
genital Abnormalities (HCCSCA) [10].
The protocol of the HCCSCA included five steps. The
first step was the selection of cases from the data set of
the Hungarian Congenital Abnormality Registry (HCAR),
1980-1996 [11] for the HCCSCA. Notification of CAs is
compulsory for physicians from the birth until the end of
first postnatal year to the HCAR. Most cases with CA
are reported by obstetricians and paediatricians. In Hun-
gary practically all deliveries take place in inpatient ob-
stetric clinics and the birth attendants are obstetricians.
Paediatricians are working in the neonatal units of inpa-
tient obstetric clinics, or in various inpatient and outpa-
tient paediatric clinics. Autopsy was mandatory for all
infant deaths and common in stillborn fetuses during the
study period. Pathologists sent a copy of the autopsy
report to the HCAR if defects were identified in still-
births and infant deaths. Since 1984 fetal defects diag-
nosed in prenatal diagnostic centres with or without ter-
mination of pregnancy have also been included into the
HCAR. Isolated minor anomalies (e.g., umbilical hernia,
small haemangioma, hydrocele) were recorded but not
evaluated in the HCAR. The total (birth + fetal) preva-
lence of cases with CA diagnosed from the second tri-
mester of pregnancy through the age of one year was 35
per 1000 informative offspring (liveborn infants, still-
born fetuses and electively terminated malformed fetuses)
in the HCAR, 1980-1996, and about 90% of major CAs
were recorded in the HCAR during the 17 years of the
study period [12].
There were three exclusion criteria at the selection of
cases with CAs from the HCAR for the data set of the
HCCSCA. 1) Cases reported after three months of birth
or pregnancy termination were excluded. The longer
time between birth or pregnancy termination and data
collection decreases the accuracy of information about
pregnancy history. This group of excluding cases in-
volved 33% of cases and most had mild CAs. 2) Three
mild CAs (such as congenital dislocation of hip based on
Ortolani click, congenital inguinal hernia, and large
haemangioma), and 3) CA-syndromes caused by major
mutant genes or chromosomal aberrations with precon-
ceptional (i.e. non teratogenic) origin were also ex-
The second step was to ascertain appropriate controls
from the National Birth Registry of the Central Statisti-
cal Office for the HCCSCA. Controls were defined as
newborn infants without CA. In most years two controls
were matched to every case according to sex, birth week,
and district of parents’ residence.
The third step was to obtain the necessary maternal,
particularly exposure data from three sources:
3.1. Prospective Medically Recorded Data
Mothers were asked in an explanatory letter to send us
the prenatal maternity logbook and other medical re-
cords particularly discharge summaries concerning their
diseases during the study pregnancy and their child's CA.
Prenatal care was mandatory for pregnant women in
Hungary (if somebody did not visit prenatal care clinic,
she did not receive a maternity grant and leave), thus
nearly 100% of pregnant women visited prenatal care
clinics, on average 7 times in their pregnancies. The first
visit was between the 6th and 12th gestational week. The
task of obstetricians was to record all pregnancy com-
plications, maternal diseases and related drug prescrip-
tions in the prenatal maternity logbook.
3.2. Retrospective Self-Reported Maternal
A structured questionnaire along with a list of medicinal
products (drugs and pregnancy supplements) and dis-
eases, plus a printed informed consent form were also
mailed to the mothers immediately after the selection of
cases and controls. The questionnaire requested informa-
tion on pregnancy complications and maternal diseases,
on medicinal products taken during pregnancy according
to gestational months, and on family history of CAs. To
standardize the answers, mothers were asked to read the
enclosed lists of medicinal products and diseases as a
memory aid before they filled in the questionnaire. We
also asked mothers to give a signature for informed con-
sent form which permitted us to record the name and
address of cases both in the HCCSCA and in the HCAR.
The mean ± S.D. time elapsed between the birth or
pregnancy termination and the return of the “information
F. Bánhidy et al. / HEALTH 2 (2010) 566-574
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package” (questionnaire, logbook, discharge summary,
and informed consent form) in our prepaid envelope was
3.5 ± 1.2 and 5.2 ± 2.9 months in the case and control
groups, respectively
3.3. Supplementary Data Collection
Regional nurses were asked to visit all non-respondent
case mothers at home and to help mothers to fill-in the
same questionnaire used in the HCCSCA, to evaluate the
available medical records, to obtain data regarding life-
style (smoking, drinking, illicit drug use) through per-
sonal interview of mothers and her close relatives living
together and to ask mothers to sign informed consent.
Regional nurses visited only 200 non-respondent control
and 600 other control mothers as part of two validation
studies [13,14] using the same methods as in non-re-
spondent case mothers because the committee on ethics
considered this follow-up to be disturbing to the parents
of all healthy children.
Overall, the necessary information was available on
96.3% of cases (84.4% from reply to the mailing, 11.9%
from the nurse visit) and 83.0% of the controls (81.3%
from reply, 1.7% from visit). Informed consent form was
signed by 98% of mothers, names and addresses were
deleted in the rest 2%.
The procedure of data collection in the HCCSCA was
changed in 1997 such that regional nurses visited and
questioned all cases and controls, however, these data
have not been validated until now, thus only the data set
of 17 years between 1980 and 1996 is evaluated here.
The fourth step at the evaluation of cases and controls
in the HCCSCA is the definition of exposure and to de-
termine its diagnostic criteria. The diagnosis of LP was
based on the personal manual and ultrasound examina-
tion of pregnant women by obstetrician. In general the
size of uterine leiomyoma and their types (intramural,
subserosal, submucosal, pedunculated, etc) was given in
the prenatal maternity logbook but unfortunately these
data were not copied out. Pregnant women with dys-
functional uterine bleeding, endometrial polyp, endome-
triosis, etc were excluded from the study.
Gestational time was calculated from the first day of
the last menstrual period. Beyond birth weight (g) and
gestational age at delivery (wk), the rate of low birth-
weight (< 2500 g) and large birth weight (4000 or more
g) newborns, in addition the rate of preterm births (< 37
weeks) and postterm birth (42 or more weeks) were
analyzed on the basis of discharge summaries of inpa-
tient obstetric clinics. The critical period of most major
CAs is in the second and/or third gestational month.
Drug treatments and folic acid/multivitamin supple-
ments were also evaluated. The latter may indicate the
level of pregnancy care, and indirectly may show the
socio-economic status and the motivation of mothers to
prepare and/or to achieve a healthy baby. In addition it is
necessary to consider folic acid and folic acid-containing
multivitamins in the evaluation of preventable CAs
[15-18]. Other potential confounding factors included
maternal age, birth order, marital and employment stat-
us which had a good correlation with the level of educa-
tion and income, thus was regarded at the indicator of
socioeconomic status [19], and high fever related dis-
eases such as influenza.
We used SAS version 8.02 (SAS Institute Ins., Cary,
North Carolina, USA) for statistical analyses as the fifth
step of the HCCSCA. The occurrence of LP was com-
pared in the two study groups and the crude odds ratios
(OR) with 95% confidence intervals (CI) were calcu-
lated. Contingency tables were prepared for the main
study variables. The prevalence of other maternal dis-
eases, drug intakes and pregnancy supplements used
during pregnancy were compared between the group of
case and control mothers with LP. We compared the
prevalence of LP during the study pregnancy in specific
CA groups including at least 2 cases with the frequency
of LP in their all matched control pairs. Crude and ad-
justed OR with 95% CI were evaluated in conditional
logistic regression models. We examined confounding
variables by comparing the OR for LP in the models
with and without inclusion of the potential confounding
variables. Finally, maternal age (< 20 yr, 20-29 yr, and
30 yr or more), birth order (first delivery or one or more
previous deliveries), employment status, influenza-
common cold (yes/no), and use of folic acid supplement
(yes/no) were included in the models as potential con-
As it appeared at the preliminary evaluation of LP, two
groups could be differentiated: 1) prospectively and
medically recorded LP in the prenatal maternity logbook,
and 2) LP based on retrospective maternal information in
the questionnaire. However, the diagnosis of leiomyoma
can be frequently questioned without medical record in
the latter group and in general it was not possible to dif-
ferentiate the leiomyoma with myomectomy before the
study pregnancy. Thus, only the first group, i.e. medi-
cally recorded LP was evaluated.
The case group consisted of 22,843 malformed new-
borns or fetuses (“informative offspring”), of whom 39
(0.15%) had mothers with medically recorded leio-
myoma during the study pregnancy. However, of these
39 pregnant women, 5 (12.8%) had previous myomec-
tomy due to leiomyoma. The total number of births in
Hungary was 2,146,574 during the study period between
F. Bánhidy et al. / HEALTH 2 (2010) 566-574
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1980 and 1996. Thus the 38,151 controls represented
1.8% of all Hungarian births, and among those controls,
82 were born to mothers with medically recorded leio-
myoma. Of these 82 control mothers, 11 (13.4%) had
previous myomectomy. Our objective was to evaluate
the possible association of leiomyoma during the study
pregnancy with pregnancy complications and adverse
birth outcomes, therefore 34 case mothers (0.15%) and
71 control mothers (0.19%) with leiomyoma, i.e. LP
were evaluated. Surgical intervention due to LP during
the study pregnancy was not recorded in the prenatal
maternity logbook and in the discharge summaries of
these 105 pregnant women with LP. The number of
pregnant women with previous myomectomy of leio-
myoma was too small, thus these pregnant women were
excluded from this analysis.
Of 34 case mothers, 30 (88.2%), while of 71 control
mothers, 60 (84.5%) had diagnosed LP in the first visit
of prenatal maternity clinic, thus the onset of this patho-
logical condition was before conception. The so-called
new-onset LP occurred in 4 case mothers and 11 control
mothers diagnosed after the fourth gestational month.
Table 1 summarizes the characteristics of mothers
with and without LP as reference. This comparison indi-
cates a much higher mean maternal age (due to the larger
proportion of women with the age group of 30 and more
years) in women with LP. However, the mean birth order
was only higher in control mothers with LP, but some-
what lower in case mothers with LP than case mothers
without LP. Mean pregnancy order (previous birth +
recorded miscarriages) was also evaluated, and the dif-
ference between birth and pregnancy order was some-
what higher in pregnant women with LP in both case
mothers and control mothers and these data may indicate
a higher rate of miscarriages in previous pregnancies.
The proportion of unmarried pregnant women was larger
in the groups of LP, while LP was more frequently re-
corded in the prenatal maternity logbooks of profes-
sional pregnant women. In the group of case mothers,
the proportion of managerial women was also larger.
Among pregnancy supplements (Table 1), the use of
folic acid and iron was similar between mothers with or
without LP, but these supplements were used more fre-
quently by control mothers. However, medicinal prod-
ucts containing calcium were used more frequently by
mothers with LP, and a much higher rate of case mothers
were treated with vitamin E.
Of 2,640 case mothers visited at home, only 4 had LP
and one was smoker during the study pregnancy. Of
2,636 mothers without LP, 576 (21.9%) smoked. Of 800
control mothers visited at home, 152 (19.0%) smoked
during the study pregnancy.
Acute maternal diseases (e.g. influenza) did not occur
more frequently in mothers with LP. Among chronic
diseases, the prevalence of diabetes mellitus and epi-
lepsy was similar in the study groups, but essential hy-
pertension (19.0% vs. 7.0%, OR with 95% CI: 3.1,
1.9-5.1), haemorrhoids (18.1% vs. 3.9%, OR with 95%
CI: 5.4, 3.3-8.8) and constipation (7.6% vs. 2.1%, OR
with 95% CI: 3.9, 1.9-8.1) were more frequent in 105
women with LP than in 60,889 mothers without LP.
The incidences of pregnancy complications are shown
in Table 2, because they were different in case and con-
trol mothers with LP. Threatened abortion, placental
disorders (mainly abruption placentae) and anaemia oc-
curred more frequently in case mothers with LP than in
case mothers without LP. However, LP did not associate
with a higher rate of threatened abortion, placental dis-
orders and anaemia in control mothers. Thus LP and
fetal defects may have some causal association with the
higher risk of certain pregnancy complications, such as
placental disorders. Unexpectedly the incidence of
threatened preterm delivery was not significantly higher
in case and control mothers with LP.
There was some difference in the distribution and fre-
quency of drugs used by mothers with LP explained by
the higher use of antihypertensive (methyldopa, metop-
rolol, nifedipine) drugs (12.4% vs. 2.6%) and the usual
treatment of threatened abortion with allylestrenol
(21.0% vs. 14.5%) and diazepam (25.7% vs. 11.3%) in
Hungary. In addition the use of hydroxyprogesterone
(5.7% vs. 1.2%) and human chorionic gonadotropin
(2.9% vs. 0.3%) was more frequent in 105 pregnant
women with LP than in 60,889 pregnant women without
Birth outcomes are shown in case and control new-
borns (Table 3) but statistical testing was used only in
controls because CAs may have a more drastic effect for
these variables in cases than LP itself. (There was no
difference in the sex ratio of the study groups, and twin
did not occur among newborns of mothers with LP.) The
mean gestational age at delivery was somewhat (0.1 wk
in cases and 0.2 wk in controls) longer, the rate of pre-
term birth was higher in controls but lower in cases.
There was no difference in the rate of postterm births
among study groups. However, these differences were
not significant. The mean birth weight was 159 and 95 g
larger in cases and controls of mothers with LP and these
differences were significant. However, these differences
were not reflected in the rate of low birthweight new-
borns because there was no difference in their rates be-
tween cases and controls born to mother with or without
LP. There was a higher proportion of large birthweight
newborns of both cases and controls but this difference
was significant only in cases (OR with 95% CI: 3.0,
F. Bánhidy et al. / HEALTH 2 (2010) 566-574
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Table 1. Maternal characteristics of women with or without leiomyoma in pregnancy (LP).
Case mothers Control mothers
Va ri ab le s
without with without with
(N = 22,809) (N = 34) (N = 38,080) (N = 71)
Maternal age, yr. No. % No. % No. % No. %
– 19 2,506 11.0 0 0.0 3,277 8.6 0 0.0
20 – 29 15,580 68.3 13 38.2 25,777 72.4 25 35.2
30 – 4,723 20.7 21 61.8 7,226 19.0 46 64.8
Mean, S.D. 25.5 ± 5.3 32.1 ± 6.0 25.4 ± 4.9 31.9 ± 5.7
Birth order (parity)
1 10,691 46.9 17 50.0 18,175 47.7 34 47.9
2 or more 12,118 53.1 17 50.0 19,905 52.3 37 52.1
Mean, S.D. 1.9 ± 1.1 1.8 ± 1.0 1.7 ± 0.9 1.9 ± 1.1
Pregnancy order
1 9,493 41.6 14 41.2 16,296 42.8 24 33.8
2 or more 13,316 58.4 50 58.8 21,784 57.2 47 66.2
Mean, S.D. 2.1 ± 1.4 2.1 ± 1.2 1.9 ± 1.2 2.2 ± 1.2
Categorical No. % No. % No. % No. %
Unmarried 1,265 5.5 4 11.8 1,467 3.9 5 7.0
Employment status
Professional 1,969 8.6 8 23.5 4,399 11.6 24 33.8
Managerial 5,083 22.3 14 41.2 10,249 26.9 16 22.5
Skilled worker 6,493 28.5 8 23.5 11,886 31.2 22 31.0
Semiskilled worker 4,196 18.4 1 2.9 6,159 16.2 2 2.8
Unskilled worker 1,775 7.8 1 2.9 2,187 5.7 0 0.0
Housewife 2,404 10.5 2 5.9 2,351 6.2 3 4.2
Others 889 3.9 0 0.0 849 2.2 4 5.6
Pregnancy supplements
Iron 14,721 64.5 21 61.8 26,722 70.2 49 69.0
Calcium 1,798 7.9 5 14.7 3,570 9.4 13 18.3
Folic acid 11,263 49.4 16 47.1 20,736 54.5 39 54.9
Vitamin B6 2,010 8.8 3 8.8 4,080 10.7 6 8.5
Vitamin D 6,093 26.7 8 23.5 10,131 26.6 19 26.8
Vitamin C 908 4.0 4 11.8 1,681 4.4 4 5.6
Vitamin E 1,410 6.2 8 23.5 2,281 6.0 6 8.5
Multivitamin 1,328 5.8 2 5.9 2,501 6.6 8 11.3
F. Bánhidy et al. / HEALTH 2 (2010) 566-574
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Table 2. Incidence of pregnancy complications in women with or without leiomyoma in pregnancy (LP).
Case mothers Control mothers
without with without with
(N = 22,809) (N = 34) (N = 38,080)(N = 71)
Pregnancy complications
No. % No. %
Comparison of
cases with or
without LP
OR with 95% CI
No. % No. %
Comparison of
controls with or
without LP
OR with 95% CI
Comparison be-
tween case and
control mothers
with LP
Threatened abortion 3,483 15.3 14 41.23.9 (2.0 7.7) 6,49417.116 22.51.4 (0.8 – 2.5) 2.4 (0.9 – 5.8)
Nausea-vomiting, severe 1,739 7.6 3 8.81.2 (0.4 – 3.8)3,84910.16 8.50.8 (0.4 – 1.9) 1.0 (0.2 – 4.5)
Preeclampsia–eclampsia 6672.9 3 8.83.2 (0.9 – 10.5)1,1563.0 2 2.80.9 (0.2 – 3.8) 3.3 (0.5 – 21.0)
Pregnancy related renal diseases 3371.5 1 2.92.0 (0.3 – 14.8)4901.32 2.82.2 (0.5 – 9.1) 1.0 (0.1 – 11.9)
Placental disorders* 2941.3 2 5.94.8 (1.1 20.1) 5921.61 1.40.9 (0.1 – 6.5) 4.4 (0.4 – 50.0)
Polyhydramnios 2110.9 0 0.00.0 1900.5 1 1.42.8 (0.4 – 20.6) –
Threatened preterm delivery** 2,601 11.4 5 14.71.3 (0.5 – 3.5)5,43714.310 14.11.0 (0.5 – 1.9) 1.1 (0.3 – 3.3)
Anemia 3,233 14.2 9 26.52.2 (1.0 4.7) 6,34516.713 18.31.1 (0.6 – 2.0) 1.6 (0.6 – 4.2)
Others*** 2881.3 1 2.92.4 (0.3 – 17.4)6741.81 1.40.8 (0.1 – 5.7) 2.1 (0.1 – 35.0)
*incl. placenta praevia, premature separation of
**incl. cervical incompetence as well
***e.g. trauma, poisoning, blood isoimmunisation
Bold numbers show significant associations
Table 3. Birth outcomes of cases and controls born to mothers with or without leiomyoma in pregnancy (LP).
Case mothers Control mothers
without LP with LP without LP with LP
Va ri ab le s
(N = 22,809) (N = 71) (N = 38,080) (N = 71)
Quantitative Mean S.D. Mean S.D Mean S.D. Mean S.D. t = p =
Gestational age, wk** 38.6 3.2 38.7 2.4 39.4 2.0 39.6 2.2 0.9 0.37
Birth weight, g* 2,977 705 3,136 752 3,275 511 3,370 575 2.1 0.03
Categorical No. % No. % No. %. No. % OR with 95% CI
Preterm birth* 3,760 16.5 5 14.7 3,487 9.2 9 12.7 1.6 0.8 – 3.2
Postterm birth* 573 2.5 1 2.9 3,854 10.1 8 11.3 1.1 0.6 – 2.4
Low birthweight** 4,622 20.3 7 20.6 2,163 5.7 4 5.6 0.8 0.2 – 2.5
Large birthweight** 1,169 5.1 5 14.7 2,865 7.5 7 9.9 1.4 0.7 – 3.0
*adjusted for maternal age, birth order and maternal socio-economic status
**adjusted for maternal age, birth order, maternal socio-economic status and gestational age
Bold numbers show significant association
At the estimation of possible higher risk for CAs, the
occurrence of LP during the entire pregnancy of mothers
who had cases with different CAs was compared with
the occurrence of LP in the mothers of all matched con-
trols (Table 4). (We supposed that 4 case and 11 control
mothers with the diagnosis of LP after the fourth gesta-
tional month might have some effect for the uterus dur-
ing the critical period of most major CAs, i.e. during the
second and third gestational month.) There was no
higher risk for total CA and any CA group, including
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Table 4. Estimate the association between women with leimyoma in pregnancy (LP) and different CAs in their offspring using all
matched controls as reference.
Entire pregnancy Crude Adjusted
Study groups Grand total No.
No. % OR 95% CI OR 95% CI
Controls 38,151 71 0.2 reference reference
Isolated CAs
Neural-tube defects 1,203 2 0.2 0.9 0.2 – 3.6 0.6 0.1 – 3.3
Cleft lip ± palate 1,374 3 0.2 1.2 0.4 – 3.7 0.8 0.2 – 3.4
Cleft palate only 601 2 0.3 1.8 0.4 – 7.3 3.5 0.3 – 39.1
Hypospadias 3,038 9 0.3 1.6 0.8 – 3.2 1.3 0.5 – 3.3
Undescended testis 2,051 3 0.1 0.8 0.2 – 2.5 1.1 0.3 – 4.8
Cardiovascular CAs 4,479 6 0.1 0.7 0.3 – 1.7 0.9 0.3 – 2.4
Clubfoot 2,424 4 0.2 0.9 0.3 – 2.4 0.6 0.2 – 2.1
Limb deficiencies 548 3 0.5 3.0 0.9 – 9.4 1.4 0.3 – 6.0
Other isolated CAs 5,776 2** 0.0 0.2 0.0 – 0.8 0.2 0.0 – 0.8
Multiple CAs 1,349 0 0.0 0.0 0.0 – 0.0 – –
Total 22,843 34 0.1 0.8 0.5 – 1.2 0.7 0.5 – 1.1
*ORs adjusted for maternal age and employment status, use of folic acid during pregnancy, and birth order
**torticollis, branchial cyst
clubfoot (i.e. typical manifestation of postural deforma-
tion due to fetal malposition).
We examined the possible association between LP and
pregnancy complications, in addition birth outcomes.
The previously found higher risk of threatened abortion
and placental disorders particularly abruption placentae
was found [4-6,8,20], but this risk was significant only
in the mothers of cases with CA, but not in the mothers
of controls without CA in our study. Birth outcomes
showed controversial pattern: the previously reported
somewhat higher rate of preterm birth was confirmed
(e.g. [9]), but only in controls without CA and this in-
crease was not significant. On the other hand, there was
a larger mean birth weight of cases and controls born to
mothers with LP, but it does not associate with a lower
risk of low birthweight. In fact cases had a higher rate of
large birthweight. There was no higher risk of total and
any CA group.
The secondary findings of the study confirmed the
well-known fact that LP is more frequent in elder preg-
nant women (e.g. [8]). The advance maternal age may
explain the higher prevalence of essential hypertension,
haemorrhoids and constipation. Previously the higher
rate of anaemia (mostly iron deficiency) in women with
LP due to abnormal menstruation and haemorrhoids
(frequently with bleeding) was not frequently mentioned.
However, it is worth mentioning that these associations
achieved the significant level only in case mothers thus
this study suggests that case mothers with LP (i.e. having
a malformed fetus) had a higher risk of pregnancy com-
The higher mean maternal age did not associate with a
higher mean birth order, and the difference between birth
and pregnancy order was somewhat larger in women
with LP likely due to the higher rate of previous miscar-
riages [21].
The high use of vitamin E (particularly in case moth-
ers), human chorionic gonadotropin and hydroxypro-
gesterone may indicate some infertility problem in
women affected with leiomyoma.
The prevalence of LP ranged from 0.1-3.9% in previ-
ous epidemiological studies [4,6,20,22,23], while this
prevalence was 0.15-0.19% in our study, i.e. near to the
lower level of this range. A similar lower prevalence
(0.37%) was found in another population-based material
[8]. Of course, the prevalence is determined by the age
distribution of women and the diagnostic criteria, in ad-
dition underreporting might occur if a woman did not
have a sonographic examination, or the diagnosis was
F. Bánhidy et al. / HEALTH 2 (2010) 566-574
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
not reported in the prenatal maternity logbook.
The unexpected finding of the study is the larger mean
birth weight, and a somewhat higher rate of large birth-
weight newborns of pregnant women with LP. Coronado
et al. [8] reported a higher rate of low birthweight new-
borns and prolonged labor. Our data were not appropri-
ate to evaluate the latter, but newborns had larger birth
weight. Women with LP had a better socioeconomic
status but this confounder was considered at the calcula-
tion of adjusted mean birth weight. Obviously these
pregnant women at high risk had also a special prenatal
medical management but it did not associate with a
higher level of folic acid supplementation. Thus further
studies are needed to check the efficacy of recent medi-
cal management of women with LP and to explain some
unexpected findings in this study.
The strengths of the HCCSCA are that is a popula-
tion-based and large data set including 105 women with
prospectively and medically recorded LP in prenatal
maternity logbook, furthermore medically recorded ges-
tational age at delivery and birth weight in an ethnically
homogeneous Hungarian (Caucasian) population. Addi-
tional strengths include the matching of cases to controls
without CAs; available data for potential confounders,
and finally that the diagnosis of medically reported CAs
was checked in the HCAR [11] and later modified, if
necessary, on the basis of recent medical examination
within the HCCSCA [10].
However, this data set also has limitations. 1) There is
underreporting of LP in our data set. 2) The occurrence
of previous surgical and other medical management in
women with leiomyoma was not checked in validation
studies, only the medically recorded data in the prenatal
maternity logbook were evaluated 3) The size of LP was
not recorded thus there was no chance to estimate the
dose-effect relation. 4) The occurrence of previous mis-
carriages could be estimated only on the basis of differ-
ence of birth and pregnancy order in the data set of the
HCCSCA, in addition the higher risk of women with LP
was supported by the higher rate of vitamin E and hy-
droxyprogesterone treatment. 5) The lifestyle data were
known only in the subsamples of pregnant women vis-
ited at home because previous validation study indicated
the unreliability of maternal information regarding their
smoking and drinking habit [24].
In conclusion, a higher occurrence of threatened abor-
tion and placental disorders was found in the mothers of
cases with CA, but not in the mothers of controls with-
out CA. There was larger mean birth weight of babies
born to mothers with LP and it associated with a higher
rate of large birthweight in cases. A higher risk of CAs
was not found among the offspring of pregnant women
with LP. Thus the pregnancy of women with uterine
leiomyoma does not to be discouraged if they wish to
have babies, but they need specific and high medical
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