The rate of twin pregnancies in the United States has stabilized at 32 per 1000 births in 2006. Aside from determining chorionicity, first-trimester screening and second-trimester ultrasound scanning should ascertain whether there are structural or chromosomal abnormalities. Compared with singleton births, genetic amniocentesis–related loss at <24 weeks of gestation for twin births is higher (0.9% vs 2.9%, respectively). Selective termination for an anomalous fetus is an option, although the pregnancy loss rate is 7% at experienced centers. For singleton and twin births for African American and white women, approximately 50% of preterm births are indicated; approximately one-third of these births are spontaneous, and 10%

1. Twins: prevalence, problems, and preterm births
Suneet P. Chauhan, MD; James A. Scardo, MD; Edward Hayes, MD; Alfred Z. Abuhamad, MD; Vincenzo Berghella, MD
On October 10, 2009, there was an
article entitled, “21st Century Ba-
bies: The Gift of Life, and Its Price,”
which started with 2 succinct sentences:
“Scary. Like aliens.” The article could
have been dismissed easily were it not
published in The New York Times and
were the topic something other than
twins.1
Because this article is the first in a
series called “21st Century Babies: The
Twins Dilemma,” twinning will be a part
of patient lexicon and a source of con-
cern. Thus, a review of antepartum com-
plicationswithtwinpregnanciesisuseful
not only for the concerned patient but
also because recent publications on the
topic may influence our practice.
A Google search with the word “twin”
yields 116,000,000 results in 0.21 sec-
onds; a PubMed search with the words
“twin pregnancy” found 24,982 publica-
tions (November 12, 2009). Therefore,
although it is not feasible to summarize
the voluminous literature on this topic,
this review article will focus on: twin
birth rate, common antenatal problems,
andpretermbirths,whicharethebaneof
modern obstetrics.
Twin birth rate
In the United States, between 1980 and
2006, the twin rate climbed 101% (Fig-
ure 1). There were 68,339 twins born in
1980; 27 years later, 137,085 twins were
born.2
The twinning rates have also in-
creased in Austria, Finland, Norway,
Sweden, Canada, Australia, Hong Kong,
Israel, Japan, and Singapore.3
There are
multiple causes for the change in the rate
of twin pregnancies: use of assisted re-
productive techniques (ARTs) and non-
ART procedures,4
maternal age, ethnic-
ity, variation among the 50 states, and a
decreasing rate of triplets and higher or-
der multiple gestation.2
Approximately 1% of infants born in
the United States in 2006 were conceived
with the use of ARTs and account for
18% of the multiple births nationwide.
Of 54,566 infants who were born with
the use of ARTs, 48% were multiple birth
deliveries. The International Committee
for Monitoring Assisted Reproductive
Technology5
analyzed ARTs for the year
2002 from 53 countries. For conven-
tional in vitro fertilization and intracyto-
plasmic sperm injection, the overall twin
rate was 26%. In the United States, the
twin rate was 32%; in Latin America, it
was 25%; in Europe, it was 23%; in Asia
and the Middle East, it was 22%, and in
Australia/New Zealand, it was 21%.
The rate of twin pregnancies varies by
maternal age and ethnicity (Figure 2).
Between 1980 and 2006, twin birth rates
rose 27% for mothers Ͻ20 years (com-
pared with 80% for women in their 30s)
and 190% for mothers who were Ն40
years old. In 2006, 20% of births to
women 45-54 years old were twins, com-
pared with approximately 2% of births
to women 20-24 years old. Twin birth
rates were essentially unchanged among
the 3 largest racial groups for 2005-2006:
non-Hispanic white (36.0 per 1000
births in 2006), non-Hispanic black
(36.8 per 1000 births), and Hispanic
(21.8 per 1000 births). Since 1990, rates
have risen 57% for non-Hispanic white
and 38% and 21% for non-Hispanic black
and Hispanic women, respectively.2
The rate of twin pregnancies also var-
ies among the states (Figure 3). In 2004-
2006, the rate of twin pregnancies in the
United States was 32.2 per 1000 live
births, with Ͻ25% being 29.5 per 1000
live births; median, 31.8 per 1000 live
births, and Ͼ75% being 34.0 per 1000
live births. In Connecticut, Massachu-
setts, and New Jersey, 4% of all births
were twins. In contrast, Ͻ2.5% of births
to New Mexico residents were twin
pregnancies.2
The likelihood of twin pregnancies is
also increasing because the rate of trip-
From the Aurora Health Care and Center for
Urban Population Health, Milwaukee, WI
(Dr Chauhan); Spartanburg Regional
Medical Center, Spartanburg, SC (Dr
Scardo); Women’s Center at Aurora Bay
Care Medical Center, Greenbay, WI (Dr
Hayes); Eastern Virginia Medical School,
Norfolk, VA (Dr Abuhamad); Thomas
Jefferson Medical School, Philadelphia, PA
(Dr Berghella).
Received Jan. 12, 2010; revised April 12,
2010; accepted April 19, 2010.
Reprints not available from the authors.
Authorship and contribution to the article is
limited to the 5 authors indicated. There was
no outside funding or technical assistance with
the production of this article.
0002-9378/$36.00
© 2010 Mosby, Inc. All rights reserved.
doi: 10.1016/j.ajog.2010.04.031
The rate of twin pregnancies in the United States has stabilized at 32 per 1000 births in
2006. Aside from determining chorionicity, first-trimester screening and second-trimester
ultrasound scanning should ascertain whether there are structural or chromosomal ab-
normalities. Compared with singleton births, genetic amniocentesis–related loss at Ͻ24
weeks of gestation for twin births is higher (0.9% vs 2.9%, respectively). Selective termi-
nation for an anomalous fetus is an option, although the pregnancy loss rate is 7% at
experienced centers. For singleton and twin births for African American and white women,
approximately 50% of preterm births are indicated; approximately one-third of these births
are spontaneous, and 10% of the births occur after preterm premature rupture of mem-
branes. From 1989-2000, the rate of preterm twin births increased, for African American
and white women alike, although the perinatal mortality rate has actually decreased. As
with singleton births, tocolytics should be used judiciously and only for a limited time (Ͻ48
hours) in twin births. Administration of antenatal corticosteroids is an evidence-based
recommendation.
Key words: amniocentesis, perinatal mortality rate, preterm birth, twins
www.AJOG.org Obstetrics Reviews
OCTOBER 2010 American Journal of Obstetrics & Gynecology 305

2. lets and higher-order gestations is de-
creasing. Thus, twin pregnancies consti-
tute a greater proportion of multiple
pregnancies. In 1989, for example, there
were 110,670 twin deliveries, which con-
stituted 93.6% of 118,296 multiple
births; in 2006, the corresponding num-
bers were 137,085 twin pregnancies and
95.4%. During these 9 years, the rate of
triplets and higher-order gestations de-
creased by 29%.2
The rapid rise, however, in twin rates
over the last several decades may have
ended. From 1935-1980, the twinning
rate declined. After that, there has been a
steady increase: in 1980, the twin rate
was 18.9 per 1000 births; in 1990, it was
22.6 per 1000 births, and in 2000, it was
29.3 per 1000 births (Figure 1). The rate
reached 32 per 1000 births in 2004 and
has stabilized since then; the rate was
32.1 per 1000 births in 2006.2
To summarize, the rate of twin preg-
nancies varies in the United States for
several reasons and has stabilized, de-
spite the recent alarm by public press.1
Identification of chorionicity
and anomaly
Because of risks that are associated with
monochorionicity, an important aspect
of first-trimester ultrasound scans in
twin gestation is the determination of
chorionicity. It has been demonstrated
that chorionicity is best determined by
sonography in the first or early second
trimester. In a single large tertiary cen-
ter,6
the sensitivity, specificity, and posi-
tive and negative predictive values of
prediction of monochorionicity at Յ14
weeks was found to be 89.8%, 99.5%,
97.8%, and 97.5%, respectively. If only 1
placenta is visualized, the presence of an
extension of chorionic tissue from the
fused dichorionic placentas suggests
dichorionicity. If only 1 placenta is visu-
alized, the absence of an extension of
chorionic tissue into the intertwin mem-
brane suggests monochorionicity. In
monochorionic twin pregnancies, the
absence of an intertwin membrane sug-
gests monoamniotic gestation. Mono-
chorionic diamniotic twin gestation is
associated with a 10-15% risk of twin-to-
twin transfusion syndrome.7
Although
monoamnionicity is somewhat protec-
tive against the development of twin-to-
twin transfusion syndrome, monoamni-
otic gestations are associated with a 6%
incidence of twin-to-twin transfusion.8
Because of the breadth of the topic, this
article will not address risks, associa-
tions, or management of unique aspects
of monochorionic gestations, namely
FIGURE 1
Twin deliveries and birth rate: United States, 1980-2006
50,000
100,000
150,000
1980
1985
1990
1995
2000
2005
Years
#Twins/year
15
20
25
30
35
Twins/1,000births
Twins/year Twins/1,000 births
Chauhan. Twins: prevalence, problems, and preterm births. Am J Obstet Gynecol 2010.
FIGURE 2
Twin birth rate, based on maternal ethnicity and age
0
50
100
150
200
< 15 15-17 18-19 20-24 25-29 30-34 35-39 40-44 45-54
Years of age
Twins/1,000livebirths
250
Non-Hispanic white
All races
Hispanic
Non-Hispanic black
Open circles denote non-Hispanic African American; light gray line denotes non-Hispanic white; solid
black line denotes all races; and open squares denote Hispanic.
Chauhan. Twins: prevalence, problems, and preterm births. Am J Obstet Gynecol 2010.
Reviews Obstetrics www.AJOG.org
306 American Journal of Obstetrics & Gynecology OCTOBER 2010

3. twin-to-twin transfusion syndrome and
monoamnionicity.
In addition to the determination of
chorionicity and amnionicity, the goal of
sonographic examination with twin ges-
tations is to identify anomalies and/or
syndromes. This should allow for the
modification of pregnancy management
in efforts to optimize outcome for
mother and newborn infants or to iden-
tify risk factors that may suggest a need
for active or prophylactic therapy to de-
crease the likelihood of adverse preg-
nancy outcome. Depending on the se-
verity and/or lethality of the identified
anomalies or syndromes, pregnancy
managementoptionsinclude(1)contin-
ued conservative management, (2) ter-
mination of pregnancy in efforts to de-
crease maternal morbidity and death,
especially in cases in which lethal syn-
dromes are suspected, (3) selective re-
duction to prevent the birth of an ad-
versely affected child and/or to optimize
likelihood of survival for an apparently
normal fetal sibling, or (4) placental
(vascular) and/or fetal and/or neonatal
therapy in efforts to optimize outcome
for 1 or both the neonates.
Risks that are associated with selective
termination of dichorionic twin preg-
nancies with structural, chromosomal,
and Mendelian anomalies are known for
centers with experience. Evans et al9
re-
ported on 345 cases of selective termina-
tion with twins, of whom 7% delivered at
Ͻ24 weeks of gestation and 93% ended
in a viable singleton. Unlike multifetal
reduction for multifetal pregnancies, in
which outcomes are related to experi-
ence,10
over 15 years, termination for an
anomalous fetus was not associated with
improvement in losses or prematurity.
The loss rate also was not influenced by
thegestationalageoftheprocedure,even
when done at Ͼ24 weeks of gestation,
and by the indication for selective
termination.9
For many reasons, the likelihood of
aneuploidy is higher in twin pregnancies
than in singleton pregnancies. In dizy-
gotic gestations, the background risk for
each twin is the same as it would be in a
singleton gestation for that mother;
however, the number of fetuses results in
a 2-fold increase in risk for that gestation
when compared with singleton pregnan-
cies. Because ARTs are often used in
older women, the risk of aneuploidy
should be approximately twice her age-
related risk, unless donor oocytes are
used. In monozygous twins, the risk of
both twins being affected should be sim-
ilar to that of a singleton gestation.
First-trimester screening for aneu-
ploidy in twin pregnancies has many nu-
ances that limit its capabilities as a
screening tool.11
Although monochorio-
nicity has been associated with increased
FIGURE 3
Twin births (2004-2006) by state by percentile
Texas
Utah
Montana
California
Arizona
Idaho
Nevada
Oregon
Iowa
Colorado
Kansas
Wyoming
New Mexico
Illinois
Ohio
Missouri
Florida
Minnesota
Nebraska
Georgia
Oklahoma
Alabama
Washington
Arkansas
South Dakota Wisconsin
North Dakota
Virginia
Maine
New York
Indiana
Louisiana
Michigan
Kentucky
Tennessee
Pennsylvania
North Carolina
Mississippi
South Carolina
West Virginia
Vermont
Maryland
New Jersey
New Hampshire
Massachusetts
Connecticut
Delaware
Hawaii
Alaska
Twin births by percentile
(Number per 1,000 live births)
< 25th percentile (24.3-28.9)
26-74th percentile (29.5-33.9)
> 75th percentile (34-44.2)
Chauhan. Twins: prevalence, problems, and preterm births. Am J Obstet Gynecol 2010.
www.AJOG.org Obstetrics Reviews
OCTOBER 2010 American Journal of Obstetrics & Gynecology 307

4. nuchal translucency,12
nuchal translu-
cency alone has been shown to be an ef-
fective marker for aneuploidy in twin
gestations.11,12
The addition of serum
biochemistry to age and nuchal translu-
cency measurementintwingestationhas
a very high sensitivity for detecting tri-
somy 18 or 21. In that series of 535 sets,
maternal (or egg donor) age alone was
associated with a 33% detection rate for
trisomy 18 or 21. The addition of nuchal
translucency increased the sensitivity to
83%; combined age and nuchal translu-
cency and biochemistry (free or total
beta human chorionic gonadotropin
and pregnancy-associated pregnancy
protein A) increased sensitivity to 100%.
The authors did acknowledge that, with
larger numbers, the combined detection
rate would be Ͻ100%.11
As alluded to earlier, early diagnosis is
important to minimize the complica-
tions that are associated with interven-
tion. Chorionic villus sampling (CVS) is
the standard first-trimester approach to
the confirmation of suspected aneu-
ploidy. CVS is performed by 2 general
approaches: transabdominal vs transcer-
vical, depending on operator experience
and placental location/accessibility. In
the hands of experienced clinicians, first-
trimester CVS has been found to be at
least as safe and effective as second-tri-
mester amniocentesis for prenatal diag-
nosis in twin gestations. De Catte et al13
summarized the outcomes of CVS with 3
earlier studies14-16
and their own experi-
ence with 262 cases. Overall outcomes of
614 twins who had CVS were known.
The likelihood of total loss was 4.6%
(95% confidence interval [CI], 3.5–6.0).
Furthermore, Ferrara et al17
confirmed
that CVS does not increase the preg-
nancy loss rate before multifetal preg-
nancy reduction.
Compared with singleton pregnan-
cies, twin pregnancy is associated with an
increased incidence of anomalies,18,19
al-
though the rate of anomalies in dizygotic
twins is not likely increased per twin.
Hardin et al,18
for example, compared
the prevalence of cardiovascular defects
in 56,709 California twin pairs with sin-
gleton pregnancies. They categorized
cardiac anomalies into 16 groups; twins
had a higher incidence for all 16 catego-
ries. For 7 of the cardiovascular catego-
ries, the prevalence was 2 times higher
for twin pregnancies than singleton
pregnancies. Like-sex twins, a proxy for
monozygosity, had a higher prevalence
of cardiac defects than unlike sex twins.
Bahtiyar et al19
reviewed the literature
and noted that congenital heart defects
were prevalent significantly more among
monochorionic, diamniotic twins than
the general population (relative risk
[RR], 9.18; 95% CI, 5.51–15.29). Ven-
tricular septal defects are the most fre-
quent heart defects.
Fortunately, detection of anomalies in
twin gestation does not seem to be com-
promised by its multifetal nature. Ed-
wards et al20
confirmed a sensitivity of
82% and negative predictive value of
98% for anatomic surveys among 245
consecutive twins, with a 4.9% preva-
lence of anomalies. Among 495 mono-
chorionic twins, Sperling et al21
reported
severe structural abnormalities in 2.6%;
two-thirdsoftheabnormalitieswerecar-
diac.Withfirst-trimesternuchaltranslu-
cency and anatomy scan at Ͻ20 weeks of
gestation, 83% of anomalies and aneu-
ploidy were detected. Earlier reports on
detection of congenital anomalies in
twinpregnanciesnotedalowerdetection
rate. In 1991, Allen et al22
reported that,
among 157 pair of twins (314 newborn
infants), anomalies occurred in 9.5%.
Antenatal ultrasonography detected only
39% of all major anomalies, 55% of non-
cardiac anomalies, and 69% of major
anomalies for which routine prenatal
management would be altered. For de-
tection of cardiac anomalies, their ultra-
sound protocol was limited to a 4-cham-
ber view, and they detected no major
cardiac lesions. Thus, it is understand-
able why the American College of
Obstetrics and Gynecology (ACOG)
practice bulletin23
on ultrasonography
recommends that, as part of cardiac
screening examination, the views of the
outflow tracts should be obtained, if
technically feasible. Twins should have
fetal echocardiograms, especially if they
are monochorionic24
or a result of as-
sisted reproduction.25
Importantly, if discordant anomaly is
noted, the likelihood of adverse outcome
for the normal twin is increased. Sun et
al26
used the 1995-1997 matched multi-
ple births dataset from the United States
and noted that 1 fetus had an anomaly in
2.5% of the cases and both fetuses had
anomalies in 1.0%. They identified 3307
twins and matched them with 12,813
nonanomalous twins. Compared with
the control subject, the presence of an
anomalous cotwin significantly in-
creased the risk of (1) preterm birth at
Ͻ32weeksofgestation(oddsratio[OR],
1.85; 95% CI, 1.65–2.07), (2) birth-
weight Ͻ1500 g (OR, 1.88; 95% CI 1.67–
2.12), (3) small for gestational age (10%
vs 12%; OR, 1.21; 95% CI, 1.07–1.36),
(4) fetal death (OR, 3.75; 95% CI, 2.61–
5.38), (5) neonatal death (OR, 2.08; 95%
CI 1.47–2.94), and (6) infant death (OR,
1.97; 95% CI,1.49–2.61).
In summary, once twin pregnancies
are detected, sonographic examination
should be done to determine chorionic-
ity, first trimester screening should be
done to identify fetuses with aneuploidy,
targeted ultrasound should be done for
the detection of major anomalies, and fe-
tal echocardiography should be done for
identification of congenital heart defect.
As recommended by the ACOG practice
bulletin on ultrasonography in pregnan-
cy,23
every patient should be informed
about the limitation of the detection of
all major birth defects. If 1 fetus has a
major structural or chromosomal ab-
normality, selective termination should
be discussed.
Genetic amniocentesis
Compared with singleton pregnancies,
twin pregnancies are at higher risk for
fetal anomalies and for chromosomal
abnormalities. Rodis et al27
calculated
that a 33-year-old woman with twins has
an equivalent risk of a child with Down
syndromeasa35-year-oldwomanwitha
singleton infant. Thus, the importance
of genetic amniocentesis with twins can
be seen.
Among the 6 publications that re-
ported on loss rate after genetic amnio-
centesis with twins, the needle gauge var-
ied, but all investigators used 2 separate
needle insertions (Table 1).28-33
Al-
though the rate of loss at Ͻ24 weeks of
gestation varied from 0.4-4.1%, the cu-
mulative experience with Ͼ1700 amnio-
Reviews Obstetrics www.AJOG.org
308 American Journal of Obstetrics & Gynecology OCTOBER 2010

5. centesesindicatesthatthefetallossrateis
2.9% (95% CI, 2.3–3.8) or 1 per 34 (95%
CI, 26–43). It is noteworthy that a sys-
tematic review that summarized the re-
sults of 29 articles calculated that, for sin-
gleton pregnancies who undergo genetic
amniocentesis, the loss rate at Ͻ24 weeks
of gestation is 0.9% (95% CI, 0.6–1.3)
or 1 per 111 procedures (95% CI, 76–
111).34
The differential loss rate between
singleton and twin pregnancies may re-
sult from the fact that the spontaneous
loss rate at Ͻ24 weeks of gestation is
higher with multiples. Only 3 of these re-
ports provided data for twins who were
treatedatasimilartimewhodidnothave
a genetic amniocentesis.28-30
For the
twins who did not have the invasive pro-
cedure, the overall loss rate was 1.1%
(95% CI, 0.6–2.0). A comparison of
spontaneous loss rate vs after loss rate
genetic amniocentesis indicates that the
fetal losses are approximately 160%
higher after the procedure (1.1% vs
2.9%; Table 1). It should be noted that
loss subsequent to genetic amniocentesis
is similar among twins who are con-
ceived spontaneously or with ART and
those who had undergone multifetal
reduction.35
Subtypes of preterm birth
and perinatal death
Undeniably twin pregnancies are more
likely to be delivered preterm (Ͻ37
weeks of gestation) than singleton preg-
nancies, although its magnitude may be
underappreciated.2
In 2006, of the
137,085 twins who were delivered in the
United States, approximately 60% of the
twins were preterm (78,824 infants) and
weighed Ͻ2500 g (82,799 infants). Ap-
proximately 1 in 10 twins was born at
Ͻ32 weeks of gestation (n ϭ 16,597 in-
fants) or weighed Ͻ1500 g (n ϭ 13,983;
Figure 4). As Ananth et al36
noted that,
with the exception of France and Fin-
land, most industrialized countries have
noted a temporal increase in prematu-
rity. The increase in preterm births is
multifactorial but can be categorized
into 3 groups: medically indicated be-
cause of maternal-neonatal outcomes,
after spontaneous onset of preterm
labor, and after premature rupture of
membranes.
A comparison of the causes of preterm
births for singleton vs twin pregnancies
is instructive, especially when the data
are separated by ethnicity. Using the data
from National Center for Health Statis-
tics, Ananth et al36,37
provided such data
(singleton pregnancies for the year 2000
and twin pregnancies for the years 1999-
2002). For singleton and twin pregnan-
cies for African American and white
women, approximately 50% of preterm
births were indicated; one-third of the
births were spontaneous, and 10% of the
births occurred after preterm premature
rupture of membranes (Figure 5). Per-
haps because the data do not lend them-
selves to detailed information on the
cause of indicated delivery, the investiga-
tors did not provide the specific reasons
clinicians were compelled to perform the
delivery prematurely.
The perinatal mortality (PNM) rates
with preterm birth vary based on plural-
ity, ethnicity, and the subtypes of prema-
turity (Figure 6). With the exception of
singleton and white pregnancies, the
PNM rate is highest when preterm deliv-
ery follows premature rupture of mem-
branes. Consistently for singleton and
twin pregnancies for African American
and white women, the PNM rate is low-
est when preterm birth results from
spontaneous labor. Within the same eth-
nicity, the total preterm PNM rate is sig-
nificantly less for twin than for singleton
pregnancies.
The remarkable finding by Ananth et
al36,37
is that, despite the increase in the
rate of prematurity in the United States,
there is a concomitant decrease in PNM
ratesamongAfricanAmericanandwhite
women among twin and singleton preg-
nancies. In 2 separate publications,
Ananth et al36,37
reported the trends in
preterm births for twin and singleton
pregnancies in the United States from
1989-2000, along with its impact on
TABLE 1
Amniocentesis with twin pregnancies
Variable Country
Twin
pregnancy
amniocentesis
Needle
size
Second
puncture
Loss at
<24 wk
gestation, n
Loss rate,
%a
Twin pregnancy
with no
amniocentesis, n
Loss with no
amniocentesis, n
Loss rate,
%a
Yukobowich
et al28b
Israel 476 20 Yes 13 2.7 (1.6–4.6) 477 3 0.6 (0.2–1.8)
................................................................................................................................................................................................................................................................................................................................................................................
Tóth-Pál et
al29
Hungary 155 22 Yes 6 3.9 (1.8–9.1) 292 7 2.4 (1.1–4.8)
................................................................................................................................................................................................................................................................................................................................................................................
Millaire et
al30
Canada 134 22 Yes 4 3.0 (1.1–7.4) 248 2 0.8 (0.2–2.8)
................................................................................................................................................................................................................................................................................................................................................................................
Delisle et
al31
British Columbia 233 No mention Yes 1 0.4 (0.1–2.3) — — —
................................................................................................................................................................................................................................................................................................................................................................................
Cahill et
al32
United States 311 22 Yes 9 2.9 (1.5–5.4) — — —
................................................................................................................................................................................................................................................................................................................................................................................
Daskalakis
et al33
Greece 442 21 Yes 18 4.1 (2.5–6.7) — — —
................................................................................................................................................................................................................................................................................................................................................................................
TOTAL 1751 51 2.9 (2.3–3.8) 1,017 12 1.1 (0.6–2.0)
................................................................................................................................................................................................................................................................................................................................................................................
a
Data presented as percentage (95% confidence interval); b
Reported loss rate within 4 weeks of birth.
Chauhan. Twins: prevalence, problems, and preterm births. Am J Obstet Gynecol 2010.
www.AJOG.org Obstetrics Reviews
OCTOBER 2010 American Journal of Obstetrics & Gynecology 309

6. perinatal mortality rates (Figure 7). For
their analysis, they had 1,172,405 pre-
term twin live births and 46,375,578 pre-
term singleton pregnancies. Over 11
years, the rate of preterm births in-
creased for African American and white
twin pregnancies and for white singleton
pregnancies; however, it decreased for
African American twin singletons. The
PNM rate decreased for all 4 groups dur-
ing the 11 years (Figure 7). The reason
for the decrease in the PNM rate is that
medically indicated preterm births are
associated with a favorable reduction in
PNM rates.
Preterm labor: prediction,
prevention, and management
Regardless of the temporal trend, the
prediction, prevention, and manage-
ment of preterm birth are important and
should be evidence based. Transvaginal
cervical length or fetal fibronectin (fFN)
level can be used to differentiate those
pregnancies that are likely to vs not likely
to deliver prematurely.
Fox et al38
described their experience
with routinely obtaining, from 22-32
weeks, fFN and measuring transvaginal
cervical length. Overall, among 155 twin
pregnancies, of which 64% were the re-
sults of in vitro fertilization, the rate of
birth at Ͻ37 weeks of gestation was 53%,
at Ͻ34 weeks of gestation was 16%, and
Ͻ28 weeks of gestation was 4%. The rate
of spontaneous preterm birth was signif-
icantly higher when either fFN was pos-
itive or cervical length was Ͻ20 mm, but
it was the highest when both tests were
abnormal (Table 2). It is noteworthy
that, if the fFN is negative and cervical
length is at least 20 mm, almost 90% of
the pregnancies will deliver at Ͼ34 weeks
of gestation. Conversely, if both fFN and
cervical length are abnormal, Ͼ50% of
the pregnancies will deliver at Ͻ34 weeks
of gestation.
Routine use of the diagnostic tests in
twin pregnancies should not be expected
to decrease the actual rate of preterm
births. Matter of fact, the use of cervical
length could increase the duration of an-
tepartum admission without concomi-
tant improvement in neonatal outcome.
A retrospective analysis by Gyamfi et al39
compared the outcome among 184 twin
pregnancies with cervical length vs 78
pregnancies without this data. Between
the 2 groups, there was no difference in
gestational age at delivery (34.8 vs 35.3
weeks of gestation; P ϭ .35), delivery at
Ͻ28 weeks of gestation (8.2% vs 3.9%;
P ϭ .21), or delivery at Ͻ34 weeks of ges-
tation (26.1% vs 25.6%; P ϭ .94); how-
ever, there was an increase in maternal
antepartum length of stay (cervical
length at 34.5 days vs no cervical length
at 31.3 days; P Ͻ .001). It is uncertain
FIGURE 4
Preterm births in 2006: twin vs singleton
11%
2%
7%
1%
58%
12%
60%
10%
Del <37 weeks
Singletons Twins
OR, 7.68 (95% CI, 7.51-7.78)
OR, 21.94 (95% CI, 21.68-22.19)
OR, 10.21 (95% CI, 10.01-10.41)
OR, 10.83 (95% CI, 10.71-10.95)
Del <32 weeks BW <2500 g BW <1500 g
BW, birthweight; CI, confidence interval; Del, delivery; OR, odds ratio.
Data derived, with permission, from Martin et al.2
Chauhan. Twins: prevalence, problems, and preterm births. Am J Obstet Gynecol 2010.
FIGURE 5
Data are based on ethnicity and subtypes
of preterm births: singleton vs twin
56% 58% 53%
62%
35% 32% 38%
30%
9% 10% 9% 8%
Singletons (AA) Twins (AA) Singletons (W) Twins (W)
Med Indicated Sp PTB PROM
AA, African American; med, medically; PROM, premature rupture of membranes; Sp PTB, spontaneous preterm birth; W, white.
Data derived, with permission, from Ananth et al.36,37
Chauhan. Twins: prevalence, problems, and preterm births. Am J Obstet Gynecol 2010.
Reviews Obstetrics www.AJOG.org
310 American Journal of Obstetrics & Gynecology OCTOBER 2010

7. whether their findings would have been
valid had they obtained fFN measure-
ments in conjunction with cervical
length. So, fFN and cervical length can be
used to ascertain which twin pregnancies
will deliver prematurely, although im-
provement in peripartum outcomes
should not be expected.
Of twin gestations with symptoms of
preterm labor, approximately 22-29% of
the pregnancies will deliver within 7
days.39,40
Thus, the first goal with symp-
tomatic patients should be to identify
those who will deliver prematurely. Such
identification avoids unnecessary thera-
peutic interventions like unwarranted
hospitalization and medical treatment.
The usefulness of fFN in the evaluation
of twin gestations with symptoms of pre-
term labor is not related to its ability to
predict who will deliver in the next 14
days (19% positive predictive value; 95%
CI, 7–39%), but rather the test’s ability
to determine who is not going to deliver
during the timeframe (97% negative
predictive value; 95% CI, 89–100). The
negative predictive value of fFN is simi-
lar for singleton and twin pregnancies
with symptoms of preterm labor.40
Fuchs et al41
reported on the inverse
relationship between cervical length and
likelihood of delivery of twin pregnan-
cies within a week of the onset of symp-
toms: 80% of the pregnancies delivered
when the cervical length was 0-5 mm;
46% of the pregnancies delivered when
the cervical length was 6-10 mm; 29% of
the pregnancies delivered when the cer-
vical length was 11-15 mm; 21% of the
pregnancies delivered when the cervical
length was 16-20 mm; 7% of the preg-
nancies delivered when the cervical
length was 21-25 mm, and none of the
pregnancies delivered when the cervical
length was at least 25 mm. Undeniably,
randomized trials are needed to deter-
mine whether the knowledge of fFN and
cervical length influences outcome among
twin pregnancies, as it did in the trial re-
ported by Ness et al.42
While awaiting the
results of these randomized trials, we
should be cognizant of the ACOG prac-
tice bulletin on the management of pre-
term labor.43
They recommend that ei-
ther cervical ultrasound examination or
fFN or both diagnostic tests should be
FIGURE 6
Data are based on ethnicity and perinatal mortality
rates with preterm births: singleton vs twin
71
76
43
5351
49
44
33
41
31
29
25
10
100
Singletons (AA) Twins (AA) Singletons (W) Twins (W)
PNM/1000births
PROM Med Ind Sp PTB
AA, African American; Med Ind, medically indicated; PNM, perinatal mortality rate; PROM, premature rupture of membranes; Sp PTB,
spontaneous preterm birth; W, white.
Data derived, with permission, from Ananth et al.36,37
Chauhan. Twins: prevalence, problems, and preterm births. Am J Obstet Gynecol 2010.
FIGURE 7
Trend in the rate of preterm births and perinatal mortality for twin
and singleton births in the United States: 1989-2000
9%
-15%
-37%
-27%
22%
14%
-41%
-30%
-50%
-30%
-10%
10%
30%
AA White
PTB-Twins PTB-Singletons PNM-Twins PNM-Singletons
AA, African American; PNM, perinatal mortality rate; PTB, preterm birth.
Data derived, with permission, from Ananth et al.36,37
Chauhan. Twins: prevalence, problems, and preterm births. Am J Obstet Gynecol 2010.
www.AJOG.org Obstetrics Reviews
OCTOBER 2010 American Journal of Obstetrics & Gynecology 311

8. used to determine which patients do not
need tocolytics. Until there are publica-
tions to the contrary, this recommenda-
tion is applicable to twin and singleton
pregnancies.
Considering the increased likelihood
of preterm births among twin preg-
nancies, it is reasonable to determine
whether it can be prevented. One of the
more common interventions that have
been tried in the past was the use of pro-
phylactic oral betamimetics to reduce
the incidence of preterm birth in twin
gestations. From a Cochrane database,
Yamasmit et al44
reviewed 5 randomized
trials with 344 twin pregnancies. This in-
tervention has not been proved to reduce
the incidence of birth at Ͻ37 weeks of
gestation (RR, 0.85; 95% CI, 0.65–1.10)
or delivery at Ͻ34 weeks of gestation
(RR, 0.47; 95% CI, 0.15–1.50). It also has
not been shown to change the neonatal
outcomes of low birthweight (RR, 1.19;
95% CI, 0.77–1.85) or neonatal mortal-
ity rates (RR, 0.80; 95% CI, 0.35–1.82).
Therefore, in light of these findings, the
use of prophylactic tocolysis should not
be undertaken.
Progesterone has been shown to de-
crease the incidence of recurrent pre-
term delivery in a singleton gestation.45
A systematic review by Dodd et al46
iden-
tified only 2 randomized trials that as-
sessed the use of progesterone vs placebo
for multiple pregnancy. Depending on
the outcome of interest, the number of
participants varied between 154 and
1280.Theauthorsconcludedthattheuse
of progesterone in multiple gestations
does not decrease the likelihood of birth
at Ͻ37 weeks of gestation (RR, 1.01; 95%
CI, 0.92–1.12), birthweight Ͻ2500 g
(RR, 0.94; 95% CI, 0.86–1.02), respira-
tory distress (RR, 1.13; 95% CI,
0.86–1.48), intraventricular hemor-
rhage grade 3 or 4 (RR, 1.20; 95% CI,
0.40–3.54), necrotizing enterocolitis
(RR, 0.77; 95% CI, 0.17–3.42), neonatal
sepsis (RR, 0.95; 95% CI, 0.55–1.63), and
perinatal death (RR, 1.95; 95% CI,
0.37–10.33).
Another approach to decrease prema-
ture births is to reinforce the cervix with
a cerclage in multiple gestations. The
placement of a cerclage was examined
both as a prophylactic intervention and
when a short cervix is noted on ultra-
sound examination. The use of history-
indicated (prophylactic) cerclage for
ovulation-induced twin gestations (n ϭ
50) in a randomized trial did not de-
crease the rate of prematurity signifi-
cantly (45% with cerclage vs 48% with-
out suture) or neonatal mortality (18%
vs 15% for suture vs no suture, respec-
tively).47
More importantly, when cer-
clage was used in asymptomatic woman
with twin gestations and short cervical
length on transvaginal ultrasound exam-
ination, it significantly increased the risk
of delivery at Ͻ35 weeks of gestation
(75% in the cerclage group and 36%
without suture; RR, 2.15; 95% CI, 1.15–
4.01).48
Thus, cerclage of asymptomatic
short cervical length should be avoided
for twin gestations.
Otherprophylacticinterventions,which
have been examined in multiple gesta-
tions to prevent preterm delivery, are
bed rest and home uterine monitoring.
Crowther,49
in 2001, summarized the re-
sults of 6 trials with hospitalization and
bed rest. The summary, which involved
Ͼ600 patients and 1400 newborn in-
fants, noted that the intervention did not
decrease the rate of preterm birth or
perinatal mortality. Paradoxically, bed
rest significantly (OR, 1.84; 95% CI,
1.01–3.34) increased the risk of preterm
birth at Ͻ34 weeks of gestation in
asymptomatic twin gestations. Similarly
a lack of efficacy was also shown with the
use of home uterine monitoring for twin
gestations. Because home uterine moni-
toring has not been shown to be benefi-
cial in the prevention of preterm birth in
TABLE 2
Spontaneous preterm birth among twin pregnancies
Variable
Gestational week
<28 <30 <32 <34 <37
Negative fetal fibronectin level: 135 births, % 2.1 2.9 4.5 Ͻ11.5 46
................................................................................................................................................................................................................................................................................................................................................................................
Positive fetal fibronectin level: 20 births, % 27.3 21.4 35 55 95
................................................................................................................................................................................................................................................................................................................................................................................
P value .005 .017 Ͻ .001 .001 Ͻ .001
................................................................................................................................................................................................................................................................................................................................................................................
Transvaginal cervical length Ն20 mm: 129 births, % 2.3 3 4.7 11.9 46.8
................................................................................................................................................................................................................................................................................................................................................................................
Transvaginal cervical length Ͻ20 mm: 26 births, % 25 15.8 26.9 36 83.3
................................................................................................................................................................................................................................................................................................................................................................................
P value .008 .42 .002 .006 .001
................................................................................................................................................................................................................................................................................................................................................................................
Negative fetal fibronectin level and transvaginal cervical length Ն20 mm:
120 births, %
1.6 2.4 4.2 10.3 43
................................................................................................................................................................................................................................................................................................................................................................................
Either positive fetal fibronectin level or transvaginal cervical length Ͻ20 mm:
24 births, %
13.3 9.5 8.3 26.1 77.3
................................................................................................................................................................................................................................................................................................................................................................................
Positive fetal fibronectin level and transvaginal cervical length Ͻ20 mm: 11
births, %
50 33.3 54.5 54.5 100
................................................................................................................................................................................................................................................................................................................................................................................
P value Ͻ .001 .001 Ͻ .001 Ͻ .001 Ͻ .001
................................................................................................................................................................................................................................................................................................................................................................................
Data derived, with permission, from Fox et al.38
Chauhan. Twins: prevalence, problems, and preterm births. Am J Obstet Gynecol 2010.
Reviews Obstetrics www.AJOG.org
312 American Journal of Obstetrics & Gynecology OCTOBER 2010

9. multiple gestations, its use should be
abandoned.50
Thus, the following treat-
ment modalities have no role in the pre-
vention of preterm births with twin
gestations: bed rest and oral tocolytics;
cerclage and progesterone injections.
One of the most difficult aspects of
caring for multiple gestations is the lack
of proven intervention once preterm la-
bor has been diagnosed. The use of toco-
lytics for the treatment of preterm labor
has not been shown to decrease the inci-
dence of delivery within 7 days of treat-
ment, perinatal or neonatal death, or the
neonatal complications of respiratory
distress syndrome, necrotizing entero-
colitis, or cerebral palsy. This lack of
proven efficacy,51
the amplification of
side-effects, and the increased risk of
pulmonary edema with tocolytics in
multiple gestations52
lead ACOG to
comment that they should be used judi-
ciously in this population.53
In contrast to the unproven efficacy of
tocolytics, the use of antenatal cortico-
steroids (ACS) has been shown54
to de-
crease the incidence of neonatal death
(RR, 0.69; 95% CI, 0.58–0.81), respira-
tory distress syndrome (RR, 0.66; 95%
CI, 0.43–0.69), intraventricular hemor-
rhage (RR, 0.54; 95% CI, 0.43–0.69), ne-
crotizing enterocolitis (RR, 0.46; 95%
CI, 0.29–0.74), and systemic infections
within the first 48 hours of life (RR, 0.56;
95% CI, 0.38–0.58). Although none of
the studies specifically addressed use in
multiple gestations, the National Insti-
tutes of Health recommends that all
women in preterm labor, regardless of
the number of fetuses, be given a course
of ACS.55
Although ACS does improve neonatal
outcome significantly, it should not be
administered repeatedly. A retrospective
study by Murphy et al56
compared the
use of prophylactic ACS in twin gesta-
tions beginning at 24 weeks of gestation
and given every 2 weeks (n ϭ 136) with
the standard approach in women who
were at immediate risk of preterm deliv-
ery (n ϭ 902). The prophylactic ap-
proach was shown not to offer a signifi-
cant reduction in respiratory distress
syndrome (13% vs 11%; adjusted OR,
0.69; 95% CI, 0.33–1.46) and was associ-
ated with exposing a large number of ba-
bies to unnecessary treatment that ad-
versely affects growth. Therefore, the
repeated administration of ACS should
be avoided in favor of those pregnancies
that are at immediate risk for preterm
births.
One single rescue course of ACS
should be given among twins who have
received betamethasone 12 mg, intra-
muscularly, twice, 24 hours apart. If at
least 14 days have elapsed and delivery is
likely at Ͻ33 weeks of gestation, then a
single rescue dose should be adminis-
tered. This recommendation is based on
the randomized trial by Garite et al57
that
involved 437 patients, with 577 newborn
infants, 24% of whom (141; 1 fetal death
before randomization) were from twin
gestations. Compared with the patients
who received placebo, patients who re-
ceived the rescue dosage had a significant
reduction in composite perinatal neona-
tal morbidity (64% vs 44%; P ϭ .02) and
significantly decreased rate of respira-
tory distress syndrome, ventilator sup-
port, and surfactant use.
In summary, although there are diag-
nostic tests to identify those pregnancies
that will deliver prematurely, these tests
do not decrease the rate of preterm birth.
There are no known treatments to de-
crease the likelihood of preterm birth.
Tocolyticsshouldbeusedeithertotrans-
fer a patient to a tertiary center or to
ensure ACSs are administered. Pro-
longed tocolytic use should be avoided,
as should repeated administration of
corticosteroids.
Comment
Twins are a source of awe and delight to
parents, fascination and photo opportuni-
ties to the press,1
and challenge and trepi-
dation to clinicians.58,59
Compared with
singleton pregnancies, twin pregnancies
are more likely to be complicated by hy-
pertensive disorders, gestational diabetes
mellitus, anemia, preterm birth, ante- and
postpartum hemorrhage, and maternal
death.60
The newborn infants from twin
pregnancies are more likely to have anom-
alies,26
intrauterine growth restriction,61
handicap, and cerebral palsy. The average
cost for singleton deliveries is $9,845 and
for twins is $37,947.60
Thus, continued
understanding of twin pregnancies is
important.
This review of the literature on twin
gestations, although limited to common
problems, was notable for 4 findings.
First, the rate for twin gestations has sta-
bilized for now. For 2004, 2005, and
2006, there have been approximately 32
twin gestations per 1000 births (Figure
1). Second, the sonographic evaluations
of twin gestations should be limited not
only to the identification of the chorio-
nicity but also aneuploidy with first-
trimester screening and anomaly with
first- and second-trimester ultrasound
examinations. Because anomalies and
aneuploidies are more common with
twin pregnancies than with singleton
pregnancies,26,27
it is important that cli-
nicians who have experience in detecting
these abnormalities evaluate these pa-
tients. If need be, parents who are ex-
pecting twins should be offered and re-
ferred for CVS, genetic amniocentesis,
and selective reduction.
Third, we found that the rate of pre-
term births is significantly higher for
twin pregnancies than for singleton
pregnancies (Figure 4). Although this
has been known, findings from the na-
tional data provide not only unequivocal
evidence but also the magnitude to
which this occurs. Data from the United
States also are available for the analysis of
causes for preterm birth (Figure 5) and
associated perinatal mortality rates (Fig-
ure 6). But what is most captivating is
that, although the rate for preterm birth
has increased, the associated perinatal
mortality rate has actually decreased.
Thefactthatthisconclusionisbasedona
population-based, retrospective cohort
study comprised of 46,375,578 women
and 1,172,405 twins in the United States
is staggering.36,37
It will be beneficial if
other countries can confirm the findings
reported by Ananth et al36,37
and if fu-
ture studies can ascertain what precisely
decreased the perinatal mortality rate. It
will also be useful to understand whether
the overall perinatal mortality rate, not
just for preterm births, has also de-
creased in the United States.
Fourth, the findings focus on the man-
agement of preterm labor with twin ges-
tations. Clinicians should be cognizant
www.AJOG.org Obstetrics Reviews
OCTOBER 2010 American Journal of Obstetrics & Gynecology 313

10. ofthefactsthat,withtwins,pretermcon-
tractions are common, that the benefit of
tocolytics is limited although the com-
plications rate is higher, and that the pre-
term birth-related perinatal mortality
rate has been lowered. Whenever feasi-
ble, clinicians should use diagnostic tests
(transvaginal cervical length or fFN) to
differentiate true vs false preterm labor.
The use of tocolytics should be limited to
(1) either the cervical length is Ͻ2.5 cm
or fFN is positive or both, (2) the test
results have been evaluated, (3) 48 hours
have elapsed since the first dosage of cor-
ticosteroid was administered, or (4) the
patient has been transferred to a tertiary
center. As with singleton pregnancies,43
there is no justification for prolonged to-
colytics with twin pregnancies.
In conclusion, there are several reas-
suring findings with twin pregnancies.
The rate of twin pregnancies is not in-
creasing in the United States; although
the preterm birth rate is high, the associ-
ated perinatal mortality rate is decreas-
ing. Future studies should focus on im-
proving the detection of birth defects
and of abnormal growth and on antepar-
tum testing to improve the outcomes for
twin pregnancies with medical or obstet-
ric complications. f
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