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OBSTETRICS

Fibroid tumors are not a risk factor for adverse

outcomes in twin pregnancies
Molly J. Stout, MD; Anthony O. Odibo, MD, MSCE; Anthony L. Shanks, MD; Ryan E. Longman, MD;
George A. Macones, MD, MSCE; Alison G. Cahill, MD, MSCI
OBJECTIVE: Uterine fibroid tumors have been associated with adverse

outcomes in singleton pregnancies. We aimed to estimate risk for adverse obstetric outcomes that are associated with fibroid tumors in twin
pregnancies.
STUDY DESIGN: A retrospective cohort study of twin pregnancies with

1 fibroid tumor on second trimester ultrasound examination. Outcomes included small-for-gestational-age fetal growth, preterm delivery, preterm rupture of membranes, abruption, preeclampsia, and intrauterine fetal death. Univariable and multivariable analyses were used
to evaluate the impact of fibroid tumors on outcomes in twin pregnancies compared with twin pregnancies without fibroid tumors.
RESULTS: Of 2378 nonanomalous twin pregnancies, 2.3% had fibroid

tumors. Twin pregnancies with fibroid tumors were no more likely to

have small-for-gestational-age growth (40.0% vs 36.0%; adjusted

odds ratio, 1.1; 95% confidence interval, 0.72.0) or preterm delivery

at 34 weeks gestation (25.0% vs 24.0%; adjusted odds ratio, 1.0;
95% confidence interval, 0.51.9) than twin pregnancies without fibroid tumors. Other adverse outcomes were no more likely to occur in
twin pregnancies with fibroid tumors than in twin pregnancies without
fibroid tumors. Post hoc power calculations suggested 97% power to
detect 2-fold differences in small for gestational age and preterm delivery at 34 weeks gestation.
CONCLUSION: In contrast to data that suggest an increased risk for ad-

verse outcomes in singleton pregnancies with fibroid tumors, twin pregnancies with fibroid tumors do not appear to be at increased risk for
complications compared with those pregnancies without fibroid
tumors.
Key words: fibroid tumor, preterm birth, twin pregnancy

Cite this article as: Stout MJ, Odibo AO, Shanks AL, et al. Fibroid tumors are not a risk factor for adverse outcomes in twin pregnancies. Am J Obstet Gynecol
2013;208:68.e1-5.

terine fibroid tumors are the most

common benign tumor of the female reproductive tract and occur in 2050% of reproductive age women. As
women age, fibroid tumors become increasingly common, and by menopause
the incidence of fibroid tumors may be as
high as 70-80%.1 Fibroid tumors may influence the entire spectrum of reproductive function from alterations in fertility,
conception, and implantation events2,3
to later pregnancy outcomes, such as
preterm birth or need for cesarean delivery. Several observational studies have
investigated the impact of fibroid tumors

on obstetric outcomes in singleton pregnancies with conflicting results. In a cohort of women with singleton pregnancies from our institution, we found a
positive association between fibroid tumors and multiple adverse obstetric outcomes that included malpresentation,
placenta previa, preterm birth, and intrauterine fetal death.4
Given the trend for women to delay
childbearing and the high prevalence
of fibroid tumors in reproductive age
women, the question of whether fibroid
tumors influence obstetric outcomes is
not infrequent for obstetric providers. In

addition, the incidence of twin pregnancies has risen 47% since 1990 and currently accounts for approximately 32 per
1000 births in 2009.5,6 All previous investigations, which include the one from
our institution, estimated the risk for adverse outcomes only among singleton
gestations, which left obstetric providers
to extrapolate the impact of fibroid tumors in twin pregnancies from singleton
studies. Thus, we aimed to investigate
whether women with twin pregnancies
and fibroid tumors are also at increased
risk for adverse obstetric outcomes.

M ATERIALS AND M ETHODS

From the Department of Obstetrics and Gynecology, Washington University School of Medicine in
St. Louis, St. Louis, MO.
Received Aug. 11, 2012; revised Sept. 17, 2012; accepted Oct. 17, 2012.
Supported by NICHD T32 (grant number 5 T32 HD055172-02) and Washington University CTSA
grant number UL1 RR024992.
The authors report no conflict of interest.
Presented at the 59th Annual Scientific Meeting of the Society for Gynecologic Investigation, San
Diego, CA, March 21-24, 2012.
Reprints: Molly J. Stout, MD, 660 S. Euclid Ave., Box 8064, St. Louis, MO 63110.
[email protected].
0002-9378/$36.00 2013 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2012.10.879

68.e1

American Journal of Obstetrics & Gynecology JANUARY 2013

This is a retrospective cohort study of all

consecutive viable twin gestations who
presented for routine second-trimester
anatomic ultrasound examination between 1990 and 2007 at Washington
University Medical Center. This analysis
was performed with the large institutional perinatal database and was approved by the Washington University
School of Medicine human studies review board.

Obstetrics

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Ultrasound examinations were performed by dedicated obstetric and gynecologic sonographers with final interpretation and diagnoses made by Maternal
Fetal Medicine attending physicians. Fetal number, chorionicity, placental location, fetal anatomy, and maternal anatomy are recorded routinely as part of
second-trimester anatomic surveys. Gestational age was determined by the best
data available from the last menstrual
period that was consistent with ultrasound dating (5 days in the first trimester or 14 days in the second trimester). If last menstrual period was
unknown or inconsistent with ultrasound dating, the pregnancy was dated
according to the earliest ultrasound data
available. Chorionicity is assigned on the
basis of the evaluation of fetal genders,
placental masses, visualization of the intersection of fetal membranes with placental masses (lambda sign), and
thickness of fetal membranes. If chorionicity was determined at an earlier ultrasound examination, repeat examination
of the routine markers of chorionicity, as
appropriate for gestational age, was performed to confirm that the findings were
consistent with previous documentation. Maternal anatomy, which included
presence, location, and sizes of the 6 largest or most clinically relevant fibroid tumors were documented according to
recommendations of the American Institute of Ultrasound in Medicine.7 Fibroid size routinely is measured in 3 dimensions. In addition, fibroid location
within the uterus and relative to placental location is documented routinely.
Twin pregnancies with 1 fibroid tumors were compared with twin pregnancies without fibroid tumors. Obstetric
outcomes were collected prospectively as
the pregnancies continued through the
study period and were entered into the
perinatal database by trained obstetric
research coordinators. Primary outcomes included preterm delivery and
small-for-gestational-age (SGA) infants
in 1 or both twins (defined as birthweight 10th percentile for gestational
age according to the Alexander growth
standard8). Other outcomes that were
evaluated included placenta previa, placental abruption (defined clinically by

the obstetric provider and documented

in the medical record), preeclampsia
(defined according to criteria established
by the American College of Obstetricians
and Gynecologists9), and intrauterine fetal death at 20 weeks of gestation. Pregnancies that were complicated by major
fetal anomalies in either fetus were
excluded.
Descriptive statistics were used to calculate the incidence of fibroid tumors in
the cohort of twin pregnancies. Baseline
maternal characteristics were compared
between women with and without fibroid tumors with chi-square or Fisher
Exact tests, as appropriate. Univariable
analysis was performed for obstetric outcomes of interest to obtain relative risks
with 95% confidence intervals. Backward stepwise logistic regression was
used to control for pertinent confounding variables. The likelihood ratio test
was used to assess the impact of removal
of covariates from the model. If there
were 10 observations for any cell, multivariable logistic regression was not
performed to avoid the potential for
misleading estimates of risk. Stratified
analysis according to chorionicity and fibroid size was also performed. All outcomes were considered at the level of the
pregnancy (not at the level of each individual fetus); therefore, paired analysis
was not used. All statistical analyses were
performed using STATA software (version 10, Special Edition; StataCorp, College Station, TX).

R ESULTS
There were a total of 2445 women with
twin pregnancies in the cohort. Of those,
67 women (2.7%) were excluded because of major fetal anomalies, which left
2378 women in the final nonanomalous
cohort that was examined for obstetric
outcomes. Of 2378 women with nonanomalous twin pregnancies, 55 women
(2.3%) had fibroid tumors, and 2323
women (97.7%) did not. Of the 55 pregnancies with fibroid tumors, 51 of the fibroid tumors (92.7%) were 6 cm in
greatest dimension, and 4 fibroid tumors
(7.3%) were 6 cm.
Women with twin pregnancies that
were complicated by fibroid tumors

Research

were, on average, more likely to be of advanced maternal age, have gestational diabetes mellitus, report alcohol use, have
had a previous cesarean delivery, have
lower parity, and have fewer living children compared with women with twin
pregnancies without fibroid tumors (Table 1). However, twin pregnancies with
fibroid tumors had similar prevalence of
black women compared with twin
pregnancies without fibroid tumors. In
addition, smoking during pregnancy,
gestational age at study ultrasound examination, monochorionicity, previous
birth of a neonate who weighed 5
pounds, and previous preterm birth did
not differ between twin pregnancies with
fibroid tumors and twin pregnancies
without fibroid tumors.
Pregnancy outcomes are shown in Table 2. Women with twin pregnancies and
fibroid tumors were no more likely to
deliver preterm at 37 weeks gestation
(71.4% vs 62.3%; adjusted odds ratio
[OR], 1.2; 95% confidence interval [CI],
0.72.3), 34 weeks gestation (25.0% vs
24.0%; adjusted OR, 1.0; 95% CI, 0.5
1.9), 28 weeks gestation (7.1% vs
6.7%; relative risk [RR], 1.0; 95% CI,
0.4 2.9), or 24 weeks gestation (3.8%
vs 3.4%; RR, 1.0; 95% CI, 0.3 4.1) compared with twin pregnancies without fibroid tumors. Similarly, twin pregnancies with and without fibroid tumors had
statistically similar risk for preterm premature rupture of membranes (5.7% vs
11.6%; RR, 0.5; 95% CI, 0.21.5). There
was no difference in risk for placental abruption or preeclampsia in twin pregnancies with or without fibroid tumors.
There were no cases of twin pregnancies with placenta previa; therefore, no
meaningful comparisons can be made
regarding the impact of fibroid tumors
on this outcome.
Fetal outcomes are shown in Table 3.
There was no increase in the risk for SGA
in twin pregnancies in the presence of
fibroid tumors relative to twins in the absence of fibroid tumors (40.0% vs 36.0%;
adjusted OR, 1.1; 95% CI, 0.72.0), even
after adjustment for advanced maternal
age and alcohol use. In addition, there
was no increase in the risk for intrauterine fetal death in twin gestations with fibroid tumors compared with those ges-

JANUARY 2013 American Journal of Obstetrics & Gynecology

68.e2

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Obstetrics

tations without (3.6% vs 3.7%; RR, 0.9;

95% CI, 0.23.5). However, given the
rarity of fetal death, no adjusted analysis
could be performed reliably.
Given the known association between
chorionicity and pregnancy outcomes,
we examined obstetric and fetal outcomes that were associated with fibroid
tumors that had been stratified by chorionicity. The results remain the same
with no increased risk for adverse outcomes associated with fibroid tumors in
either monochorionic or dichorionic
twin pregnancies. Obstetric outcomes
were then examined and stratified by
large (6 cm) and small (6 cm) fibroid
size that had been measured in the largest dimension. No differences were observed in the cohort with only small fibroid tumors compared with the cohort
with no fibroid tumors. Because there
were only 4 cases of fibroid tumors 6
cm, it was difficult to draw meaningful
conclusions. However, it is noteworthy
that none of the 4 twin pregnancies with
large fibroid tumors were complicated
by the most severe obstetric outcomes of
SGA, intrauterine fetal death, or delivery
at 28 weeks.

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TABLE 1

Baseline demographic characteristics of twin

pregnancies with and without fibroid tumors
Characteristic

Fibroid tumor No fibroid tumor

(n 55)
(n 2323)
P value

Advanced maternal age: 35 y, %

60.0

24.7

.01

Black race, %

29.1

23.0

.33

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
a

Gravidity, n

2.4 1.5

2.6 1.6

2.02.8

2.62.7

0.6 1.0

1.0 1.2

0.40.9

1.01.1

.14

.....................................................................................................................................................................................................................................

Range

..............................................................................................................................................................................................................................................
a

Parity, n

.01

.....................................................................................................................................................................................................................................

Range

..............................................................................................................................................................................................................................................
2

Body mass index 30 kg/m , %

27.1

20.9

.30

..............................................................................................................................................................................................................................................

Current smoker, %

7.3

10.6

.4

Alcohol use during pregnancy, %

21.8

12.3

.03

Current diagnosis of gestational diabetes

mellitus, %

17.6

6.1

.01

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

..............................................................................................................................................................................................................................................

Preexisting diabetes mellitus, %

1.8

1.2

.65

Current diagnosis of chronic hypertension, %

5.5

2.8

.28

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

Gestational age at study ultrasound

examination, wka

19.8 1.7

19.7 1.6

.6

.....................................................................................................................................................................................................................................

Range

19.320.2

19.619.8

19.6

23.0

..............................................................................................................................................................................................................................................

Monochorionic gestation, %

.56

..............................................................................................................................................................................................................................................

Previous preterm birth, %

1.8

6.6

.14

Spontaneous abortions, n

0.3 0.6

0.4 0.7

.58

0.20.5

0.30.4

0.6 1.0

1.0 1.2

..............................................................................................................................................................................................................................................
a
.....................................................................................................................................................................................................................................

Range

..............................................................................................................................................................................................................................................
a

Living children, n

.03

.....................................................................................................................................................................................................................................

C OMMENT
This cohort of twin pregnancies suggests
that those pregnancies with fibroid tumors do not have significantly increased
risk for adverse obstetric outcomes compared with twin pregnancies without fibroid tumors. Specifically, we found no
increased risk for preterm birth, preterm
premature rupture of membranes, placental abruption, SGA, or intrauterine fetal death when we compared them
with twin pregnancies without fibroid
tumors.
Multiple studies have investigated the
impact of fibroid tumors on pregnancy
outcomes in singleton gestations.10-16
However, no previous studies have commented on the impact of fibroid tumors
in twin pregnancies, which left providers
to extrapolate associations from studies
of singletons. A retrospective cohort of
64,000 singleton pregnancies from our
institution found an increased risk for
placenta previa, placental abruption,
68.e3

0.40.9

0.91.0

Previous cesarean delivery, %

Range

1.8

1.4

.01

Previous birth of neonate weighing 5 lbs, %

7.3

7.3

.98

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
a

Data are given as mean SD.

Stout. Fibroid tumors in twin pregnancies. Am J Obstet Gynecol 2013.

preterm birth, and intrauterine fetal

death in women with fibroid tumors
compared with those women without fibroid tumors.4 In a retrospective cohort
study of 100,000 patients, Sheiner et
al12 reported an increased risk for abruption and preterm labor in singleton pregnancies with fibroid tumors. Qidwai et
al14 evaluated a cohort of 15,000 pregnancies that underwent second-trimester ultrasound examination and found
an increased risk for preterm delivery
and placenta previa that was associated
with fibroid tumors, but no increased
risk for preterm rupture of membranes
or abruption. However, both studies included only singleton pregnancies. Ex-

American Journal of Obstetrics & Gynecology JANUARY 2013

clusion of multiple gestations in these

studies was appropriate because the
increased risk for complications that
are associated with multiple gestations
would likely confound the interpretation
of complications that were associated
specifically with fibroid tumors in cohorts that were primarily singletons.
However, given mounting data that
fibroid tumors are associated with
increased obstetric risk in singleton
pregnancies, the question remained
whether twin pregnancies with fibroid
tumors were also at increased risk for
complications.
Given the negative findings of this
study, one interpretation is that the out-

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TABLE 2

Pregnancy-related adverse outcomes for twin pregnancies with (n 55) and without (n 2323) fibroids
Fibroid
tumor, %

Outcome

No fibroid
tumor, %

Unadjusted relative
risk (95% CI)

Adjusted odds
ratio (95% CI)

P value

Delivery at 37 wk gestation

71.4

62.3

1.1 (1.01.4)

1.2 (0.72.3)

Delivery at 34 wk gestation

25.0

24.0

1.0 (0.71.6)

1.0 (0.51.9)

.80

Delivery at 28 wk gestation

7.1

6.7

1.0 (0.42.7)

NA

.9

Delivery at 24 wk gestation

3.8

3.4

1.0 (0.34.1)

NA

.9

Preterm premature rupture of membranes

5.7

11.6

0.5 (0.21.5)

NA

.2

Placenta previa

0.8

NA

NA

.52

Abruption

1.9

1.9

1.0 (0.17.3)

NA

.98

19.2

20.0

1.0 (0.51.7)

0.9 (0.41.9)

.69

.17

................................................................................................................................................................................................................................................................................................................................................................................
b
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
c

Preeclampsia

................................................................................................................................................................................................................................................................................................................................................................................

CI, confidence interval; NA, not applicable.

a

Adjusted for advanced maternal age, tobacco use, previous preterm birth; b Adjusted for previous preterm birth; c Adjusted for parity, body mass index.

Stout. Fibroid tumors in twin pregnancies. Am J Obstet Gynecol 2013.

comes are rare, and, with the fixed number of patients in the cohort, we were not
powered to detect a significant difference. However, a post hoc power calculation was performed that revealed that
we had 99% and 97% power to detect a 2-fold increased risk for SGA and
preterm birth at 34 weeks gestation, respectively. Thus, we argue that the negative findings in this study are not attributable to a type 2 error. Instead, a more
probable explanation is that twin pregnancies are surveyed more frequently
with growth ultrasound examinations
and antenatal testing; thus, the risks for
adverse outcomes that are seen in singleton cohorts with fibroid tumors may be
avoided in twin gestations. At our institution, twins generally are treated with
ultrasound examination for fetal growth
every 2-4 weeks. Antenatal testing with
nonstress tests or biophysical profiles are
used in twin pregnancies at 32-34 weeks
gestation or earlier if an indication arises
(for example preeclampsia or twin-twin

transfusion syndrome).17 Thus, we propose that one interpretation of our findings may be that testing routinely, when
applied to fetal well-being in twins and
planned earlier deliveries in twins, may
be mitigating adverse effects that could
be attributable to fibroid tumors that are
detected in singleton cohorts. The singleton cohort from our institution demonstrated a slightly increased risk for
preterm birth that was associated with
fibroid tumors in contrast to no increased risk for preterm birth that was
demonstrated in this cohort of twins.4
We propose that the multiple risk factors
that increase the risk for preterm birth in
twins, relative to singletons generally (eg,
uterine distension, indicated preterm
delivery), likely blunt the mild effect of
fibroid tumors on the risk for preterm
birth that is demonstrated in the singleton cohort.
Our study has several limitations.
First, although this was a large cohort of
twin pregnancies that were available for

investigation, the number of twin pregnancies with fibroid tumors was small
enough that further stratification by fibroid size would yield unstable results
with wide confidence intervals and
therefore was not performed. Second,
the location of the fibroid tumor within
the uterine wall was not known. However, we previously demonstrated that
the location of fibroid tumors with respect to the placenta does not matter and
that pregnancies with a directly subplacental fibroid tumor have similar risks as
pregnancies with a fibroid tumor distant
from the placenta.4 Third, ascertainment
of fibroid tumors based on ultrasound
examination during pregnancy may be
imperfect. We propose that ultrasound
examination is the most clinically relevant tool. Furthermore, the most likely
direction for ascertainment bias in an ultrasound diagnosis is misclassification of
patients with fibroid tumors as control
subjects or missing a fibroid that is present. This misclassification would bias

TABLE 3

Fetal adverse outcomes for twin pregnancies with and without fibroids
Outcome
Intrauterine growth restriction

Fibroid
tumor, %

No fibroid
tumor, %

Unadjusted relative
risk (95% CI)

Adjusted odds
ratio (95% CI)
a

P value

40.0

36.0

1.1 (0.81.5)

1.1 (0.72.0)

.6

3.6

3.7

0.9 (0.23.5)

NA

.9

................................................................................................................................................................................................................................................................................................................................................................................

Intrauterine fetal death

................................................................................................................................................................................................................................................................................................................................................................................

NA, not applicable.

a

Adjusted for advanced maternal age and alcohol use.

Stout. Fibroid tumors in twin pregnancies. Am J Obstet Gynecol 2013.

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our results toward the null. Last, this

study included pregnancies at 20 weeks
of gestation; therefore, no conclusions regarding the impact of fibroid tumors earlier in pregnancy can be made.
Generalizability of this observational
cohort should be considered because this
population represents the wide spectrum of patients that is typical of an
urban tertiary care referral center.
Strengths of our study include the large
cohort size of twin pregnancies that facilitated comparisons with adequate
power and the ability to perform adjusted analysis for some outcomes. Furthermore, this is the first investigation on
the impact of fibroid tumors specifically
in twin pregnancies.
In summary, this investigation suggests that twin pregnancies with fibroid
tumors are not at increased risk for adverse obstetric outcomes beyond that
which exists for twin gestations without
fibroid tumors. Specifically, adverse outcomes that previously were demonstrated in cohorts of singleton pregnancies with fibroid tumors are not seen in
this cohort of twin pregnancies with fibroid tumors. Screening strategies that
are already in place for women with twin
pregnancies do not need to be altered

68.e5

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based on the presence or absence of fibroid tumors.
f
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