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wins: prevalence, problems, and preterm births
uneet P. Chauhan, MD; James A. Scardo, MD; Edward Hayes, MD; Alfred Z. Abuhamad, MD; Vincenzo Berghella, MD
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n October 10, 2009, there was anarticle entitled, “21st Century Ba-

ies: The Gift of Life, and Its Price,”hich started with 2 succinct sentences:

Scary. Like aliens.” The article couldave been dismissed easily were it notublished in The New York Times andere the topic something other than

wins.1 Because this article is the first in aeries called “21st Century Babies: Thewins Dilemma,” twinning will be a partf patient lexicon and a source of con-ern. Thus, a review of antepartum com-lications with twin pregnancies is usefulot only for the concerned patient butlso because recent publications on theopic may influence our practice.

A Google search with the word “twin”ields 116,000,000 results in 0.21 sec-nds; a PubMed search with the wordstwin pregnancy” found 24,982 publica-ions (November 12, 2009). Therefore,lthough it is not feasible to summarizehe voluminous literature on this topic,his review article will focus on: twinirth rate, common antenatal problems,nd preterm births, which are the bane ofodern obstetrics.

rom the Aurora Health Care and Center forrban Population Health, Milwaukee, WI

Dr Chauhan); Spartanburg Regionaledical Center, Spartanburg, SC (Dr

cardo); Women’s Center at Aurora Bayare Medical Center, Greenbay, WI (Drayes); Eastern Virginia Medical School,orfolk, VA (Dr Abuhamad); Thomas

efferson Medical School, Philadelphia, PADr Berghella).

eceived Jan. 12, 2010; revised April 12,010; accepted April 19, 2010.

eprints not available from the authors.

uthorship and contribution to the article isimited to the 5 authors indicated. There waso outside funding or technical assistance withhe production of this article.

002-9378/$36.002010 Mosby, Inc. All rights reserved.

Aoi: 10.1016/j.ajog.2010.04.031

win birth raten the United States, between 1980 and006, the twin rate climbed 101% (Fig-re 1). There were 68,339 twins born in980; 27 years later, 137,085 twins wereorn.2 The twinning rates have also in-reased in Austria, Finland, Norway,weden, Canada, Australia, Hong Kong,srael, Japan, and Singapore.3 There are

ultiple causes for the change in the ratef twin pregnancies: use of assisted re-roductive techniques (ARTs) and non-RT procedures,4 maternal age, ethnic-

ty, variation among the 50 states, and aecreasing rate of triplets and higher or-er multiple gestation.2

Approximately 1% of infants born inhe United States in 2006 were conceivedith the use of ARTs and account for8% of the multiple births nationwide.f 54,566 infants who were born with

he use of ARTs, 48% were multiple birtheliveries. The International Committee

or Monitoring Assisted Reproductiveechnology5 analyzed ARTs for the year002 from 53 countries. For conven-ional in vitro fertilization and intracyto-lasmic sperm injection, the overall twinate was 26%. In the United States, thewin rate was 32%; in Latin America, itas 25%; in Europe, it was 23%; in Asia

nd the Middle East, it was 22%, and in

The rate of twin pregnancies in the United2006. Aside from determining chorionicity,ultrasound scanning should ascertain whenormalities. Compared with singleton birthsweeks of gestation for twin births is highernation for an anomalous fetus is an optionexperienced centers. For singleton and twinapproximately 50% of preterm births are indare spontaneous, and 10% of the births ocbranes. From 1989-2000, the rate of preteand white women alike, although the perinwith singleton births, tocolytics should be ushours) in twin births. Administration of anrecommendation.

Key words: amniocentesis, perinatal morta

ustralia/New Zealand, it was 21%. a

OCTOBER 2010 Am

The rate of twin pregnancies varies byaternal age and ethnicity (Figure 2).

etween 1980 and 2006, twin birth ratesose 27% for mothers �20 years (com-ared with 80% for women in their 30s)nd 190% for mothers who were �40ears old. In 2006, 20% of births toomen 45-54 years old were twins, com-ared with approximately 2% of birthso women 20-24 years old. Twin birthates were essentially unchanged amonghe 3 largest racial groups for 2005-2006:on-Hispanic white (36.0 per 1000irths in 2006), non-Hispanic black36.8 per 1000 births), and Hispanic21.8 per 1000 births). Since 1990, ratesave risen 57% for non-Hispanic whitend 38% and 21% for non-Hispanic blacknd Hispanic women, respectively.2

The rate of twin pregnancies also var-es among the states (Figure 3). In 2004-006, the rate of twin pregnancies in thenited States was 32.2 per 1000 liveirths, with �25% being 29.5 per 1000

ive births; median, 31.8 per 1000 liveirths, and �75% being 34.0 per 1000

ive births. In Connecticut, Massachu-etts, and New Jersey, 4% of all birthsere twins. In contrast, �2.5% of births

o New Mexico residents were twinregnancies.2

The likelihood of twin pregnancies is

tes has stabilized at 32 per 1000 births in-trimester screening and second-trimesterthere are structural or chromosomal ab-

enetic amniocentesis–related loss at �24% vs 2.9%, respectively). Selective termi-lthough the pregnancy loss rate is 7% aths for African American and white women,ted; approximately one-third of these birthsafter preterm premature rupture of mem-

twin births increased, for African Americanl mortality rate has actually decreased. Asjudiciously and only for a limited time (�48atal corticosteroids is an evidence-based

rate, preterm birth, twins

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ets and higher-order gestations is de-reasing. Thus, twin pregnancies consti-ute a greater proportion of multipleregnancies. In 1989, for example, there

FIGURE 1Twin deliveries and birth rate: Unit

50,000

100,000

150,000

1980

1985

1990

# T

win

s/ye

ar

Twins/year

hauhan. Twins: prevalence, problems, and preterm births. A

FIGURE 2Twin birth rate, based on maternal

0

50

100

150

200

< 15 15-17 18-19 20-24

Y

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ins

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pen circles denote non-Hispanic African Americlack line denotes all races; and open squares dhauhan. Twins: prevalence, problems, and preterm births. A

06 American Journal of Obstetrics & Gynecology

ere 110,670 twin deliveries, which con-tituted 93.6% of 118,296 multipleirths; in 2006, the corresponding num-ers were 137,085 twin pregnancies and

States, 1980-2006

1995

2000

2005

ars

15

20

25

30

35

Tw

ins/

1,00

0 b

irth

s

Twins/1,000 births

Obstet Gynecol 2010.

hnicity and age

5-29 30-34 35-39 40-44 45-54

s of age

Non-Hispanic white

All races

Hispanic

ack

light gray line denotes non-Hispanic white; solidte Hispanic.Obstet Gynecol 2010.

o

OCTOBER 2010

5.4%. During these 9 years, the rate ofriplets and higher-order gestations de-reased by 29%.2

The rapid rise, however, in twin ratesver the last several decades may havended. From 1935-1980, the twinningate declined. After that, there has been ateady increase: in 1980, the twin rateas 18.9 per 1000 births; in 1990, it was2.6 per 1000 births, and in 2000, it was9.3 per 1000 births (Figure 1). The rateeached 32 per 1000 births in 2004 andas stabilized since then; the rate was2.1 per 1000 births in 2006.2

To summarize, the rate of twin preg-ancies varies in the United States foreveral reasons and has stabilized, de-pite the recent alarm by public press.1

dentification of chorionicitynd anomalyecause of risks that are associated withonochorionicity, an important aspect

f first-trimester ultrasound scans inwin gestation is the determination ofhorionicity. It has been demonstratedhat chorionicity is best determined byonography in the first or early secondrimester. In a single large tertiary cen-er,6 the sensitivity, specificity, and posi-ive and negative predictive values ofrediction of monochorionicity at �14eeks was found to be 89.8%, 99.5%,7.8%, and 97.5%, respectively. If only 1lacenta is visualized, the presence of anxtension of chorionic tissue from theused dichorionic placentas suggestsichorionicity. If only 1 placenta is visu-lized, the absence of an extension ofhorionic tissue into the intertwin mem-rane suggests monochorionicity. Inonochorionic twin pregnancies, the

bsence of an intertwin membrane sug-ests monoamniotic gestation. Mono-horionic diamniotic twin gestation isssociated with a 10-15% risk of twin-to-win transfusion syndrome.7 Although

onoamnionicity is somewhat protec-ive against the development of twin-to-win transfusion syndrome, monoamni-tic gestations are associated with a 6%

ncidence of twin-to-twin transfusion.8

ecause of the breadth of the topic, thisrticle will not address risks, associa-ions, or management of unique aspects

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win-to-twin transfusion syndrome andonoamnionicity.In addition to the determination of

horionicity and amnionicity, the goal ofonographic examination with twin ges-ations is to identify anomalies and/oryndromes. This should allow for the

odification of pregnancy managementn efforts to optimize outcome for

other and newborn infants or to iden-ify risk factors that may suggest a needor active or prophylactic therapy to de-rease the likelihood of adverse preg-ancy outcome. Depending on the se-erity and/or lethality of the identifiednomalies or syndromes, pregnancyanagement options include (1) contin-

ed conservative management, (2) ter-ination of pregnancy in efforts to de-

rease maternal morbidity and death,specially in cases in which lethal syn-romes are suspected, (3) selective re-

FIGURE 3Twin births (2004-2006) by state b

Utah

Montan

California

Arizona

Idaho

Nevada

Oregon

C

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Washington

Alaska


uction to prevent the birth of an ad- w

ersely affected child and/or to optimizeikelihood of survival for an apparentlyormal fetal sibling, or (4) placentalvascular) and/or fetal and/or neonatalherapy in efforts to optimize outcomeor 1 or both the neonates.

Risks that are associated with selectiveermination of dichorionic twin preg-ancies with structural, chromosomal,nd Mendelian anomalies are known forenters with experience. Evans et al9 re-orted on 345 cases of selective termina-ion with twins, of whom 7% delivered at

24 weeks of gestation and 93% endedn a viable singleton. Unlike multifetaleduction for multifetal pregnancies, inhich outcomes are related to experi-

nce,10 over 15 years, termination for annomalous fetus was not associated withmprovement in losses or prematurity.he loss rate also was not influenced by

he gestational age of the procedure, even

ercentile

Texas

Iowa

do

Kansas

o

IllinoisO

Missouri

Minnesota

Nebraska

Oklahoma

Alabama

Arkansas

South Dakota Wisconsin

North Dakota

Indiana

Louisiana

Michigan

Kentuck

Tennessee

Mississippi

Hawaii


hen done at �24 weeks of gestation, n

OCTOBER 2010 Am

nd by the indication for selectiveermination.9

For many reasons, the likelihood ofneuploidy is higher in twin pregnancieshan in singleton pregnancies. In dizy-otic gestations, the background risk forach twin is the same as it would be in aingleton gestation for that mother;owever, the number of fetuses results in2-fold increase in risk for that gestationhen compared with singleton pregnan-

ies. Because ARTs are often used inlder women, the risk of aneuploidyhould be approximately twice her age-elated risk, unless donor oocytes aresed. In monozygous twins, the risk ofoth twins being affected should be sim-

lar to that of a singleton gestation.First-trimester screening for aneu-

loidy in twin pregnancies has many nu-nces that limit its capabilities as acreening tool.11 Although monochorio-

Florida

gia

Virginia

Maine

New York

Pennsylvania

North Carolina

outh Carolina

t Virginia

Vermont

Maryland

New Jersey

New Hampshire

Massachusetts

Connecticut

Delaware

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)

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uchal translucency,12 nuchal translu-ency alone has been shown to be an ef-ective marker for aneuploidy in twinestations.11,12 The addition of serumiochemistry to age and nuchal translu-ency measurement in twin gestation hasvery high sensitivity for detecting tri-

omy 18 or 21. In that series of 535 sets,aternal (or egg donor) age alone was

ssociated with a 33% detection rate forrisomy 18 or 21. The addition of nuchalranslucency increased the sensitivity to3%; combined age and nuchal translu-ency and biochemistry (free or totaleta human chorionic gonadotropinnd pregnancy-associated pregnancyrotein A) increased sensitivity to 100%.he authors did acknowledge that, with

arger numbers, the combined detectionate would be �100%.11

As alluded to earlier, early diagnosis ismportant to minimize the complica-ions that are associated with interven-ion. Chorionic villus sampling (CVS) ishe standard first-trimester approach tohe confirmation of suspected aneu-loidy. CVS is performed by 2 generalpproaches: transabdominal vs transcer-ical, depending on operator experiencend placental location/accessibility. Inhe hands of experienced clinicians, first-rimester CVS has been found to be ateast as safe and effective as second-tri-

ester amniocentesis for prenatal diag-osis in twin gestations. De Catte et al13

ummarized the outcomes of CVS with 3arlier studies14-16 and their own experi-nce with 262 cases. Overall outcomes of14 twins who had CVS were known.he likelihood of total loss was 4.6%

95% confidence interval [CI], 3.5– 6.0).urthermore, Ferrara et al17 confirmedhat CVS does not increase the preg-ancy loss rate before multifetal preg-ancy reduction.Compared with singleton pregnan-

ies, twin pregnancy is associated with anncreased incidence of anomalies,18,19 al-hough the rate of anomalies in dizygoticwins is not likely increased per twin.ardin et al,18 for example, compared

he prevalence of cardiovascular defectsn 56,709 California twin pairs with sin-leton pregnancies. They categorizedardiac anomalies into 16 groups; twins
ad a higher incidence for all 16 catego- f

ies. For 7 of the cardiovascular catego-ies, the prevalence was 2 times higheror twin pregnancies than singletonregnancies. Like-sex twins, a proxy foronozygosity, had a higher prevalence

f cardiac defects than unlike sex twins.ahtiyar et al19 reviewed the literaturend noted that congenital heart defectsere prevalent significantly more amongonochorionic, diamniotic twins than

he general population (relative riskRR], 9.18; 95% CI, 5.51–15.29). Ven-ricular septal defects are the most fre-uent heart defects.Fortunately, detection of anomalies in

win gestation does not seem to be com-romised by its multifetal nature. Ed-ards et al20 confirmed a sensitivity of2% and negative predictive value of8% for anatomic surveys among 245onsecutive twins, with a 4.9% preva-ence of anomalies. Among 495 mono-horionic twins, Sperling et al21 reportedevere structural abnormalities in 2.6%;wo-thirds of the abnormalities were car-iac. With first-trimester nuchal translu-ency and anatomy scan at �20 weeks ofestation, 83% of anomalies and aneu-loidy were detected. Earlier reports onetection of congenital anomalies inwin pregnancies noted a lower detectionate. In 1991, Allen et al22 reported that,mong 157 pair of twins (314 newbornnfants), anomalies occurred in 9.5%.ntenatal ultrasonography detected only9% of all major anomalies, 55% of non-ardiac anomalies, and 69% of majornomalies for which routine prenatalanagement would be altered. For de-

ection of cardiac anomalies, their ultra-ound protocol was limited to a 4-cham-er view, and they detected no majorardiac lesions. Thus, it is understand-ble why the American College ofbstetrics and Gynecology (ACOG)ractice bulletin23 on ultrasonographyecommends that, as part of cardiaccreening examination, the views of theutflow tracts should be obtained, ifechnically feasible. Twins should haveetal echocardiograms, especially if theyre monochorionic24 or a result of as-isted reproduction.25

Importantly, if discordant anomaly isoted, the likelihood of adverse outcome

or the normal twin is increased. Sun et m

OCTOBER 2010

l26 used the 1995-1997 matched multi-le births dataset from the United Statesnd noted that 1 fetus had an anomaly in.5% of the cases and both fetuses hadnomalies in 1.0%. They identified 3307wins and matched them with 12,813onanomalous twins. Compared with

he control subject, the presence of annomalous cotwin significantly in-reased the risk of (1) preterm birth at32 weeks of gestation (odds ratio [OR],

.85; 95% CI, 1.65–2.07), (2) birth-eight �1500 g (OR, 1.88; 95% CI 1.67–.12), (3) small for gestational age (10%s 12%; OR, 1.21; 95% CI, 1.07–1.36),4) fetal death (OR, 3.75; 95% CI, 2.61–.38), (5) neonatal death (OR, 2.08; 95%I 1.47–2.94), and (6) infant death (OR,.97; 95% CI,1.49 –2.61).In summary, once twin pregnancies

re detected, sonographic examinationhould be done to determine chorionic-ty, first trimester screening should beone to identify fetuses with aneuploidy,argeted ultrasound should be done forhe detection of major anomalies, and fe-al echocardiography should be done fordentification of congenital heart defect.s recommended by the ACOG practiceulletin on ultrasonography in pregnan-y,23 every patient should be informedbout the limitation of the detection ofll major birth defects. If 1 fetus has aajor structural or chromosomal ab-

ormality, selective termination shoulde discussed.

enetic amniocentesisompared with singleton pregnancies,

win pregnancies are at higher risk foretal anomalies and for chromosomalbnormalities. Rodis et al27 calculatedhat a 33-year-old woman with twins hasn equivalent risk of a child with Downyndrome as a 35-year-old woman with aingleton infant. Thus, the importancef genetic amniocentesis with twins cane seen.Among the 6 publications that re-

orted on loss rate after genetic amnio-entesis with twins, the needle gauge var-ed, but all investigators used 2 separateeedle insertions (Table 1).28-33 Al-

hough the rate of loss at �24 weeks ofestation varied from 0.4-4.1%, the cu-
ulative experience with �1700 amnio-

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enteses indicates that the fetal loss rate is.9% (95% CI, 2.3–3.8) or 1 per 34 (95%I, 26 – 43). It is noteworthy that a sys-

ematic review that summarized the re-ults of 29 articles calculated that, for sin-leton pregnancies who undergo geneticmniocentesis, the loss rate at �24 weeksf gestation is 0.9% (95% CI, 0.6 –1.3)r 1 per 111 procedures (95% CI, 76 –11).34 The differential loss rate betweeningleton and twin pregnancies may re-ult from the fact that the spontaneousoss rate at �24 weeks of gestation isigher with multiples. Only 3 of these re-orts provided data for twins who werereated at a similar time who did not have

genetic amniocentesis.28-30 For thewins who did not have the invasive pro-edure, the overall loss rate was 1.1%95% CI, 0.6 –2.0). A comparison ofpontaneous loss rate vs after loss rateenetic amniocentesis indicates that theetal losses are approximately 160%igher after the procedure (1.1% vs.9%; Table 1). It should be noted thatoss subsequent to genetic amniocentesiss similar among twins who are con-eived spontaneously or with ART andhose who had undergone multifetaleduction.35

ubtypes of preterm birthnd perinatal deathndeniably twin pregnancies are more

TABLE 1Amniocentesis with twin pregnanc

Variable Country

Twinpregnancyamniocentesis

Yukobowichet al28b

Israel 476

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

Tóth-Pál etal29

Hungary 155

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

Millaire etal30

Canada 134

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

Delisle etal31

British Columbia 233

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

Cahill etal32

United States 311

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

Daskalakiset al33

Greece 442

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

TOTAL 1751...................................................................................................................a Data presented as percentage (95% confidence interval); b R

Chauhan. Twins: prevalence, problems, and preterm birth

ikely to be delivered preterm (�37 b

eeks of gestation) than singleton preg-ancies, although its magnitude may benderappreciated.2 In 2006, of the37,085 twins who were delivered in thenited States, approximately 60% of the

wins were preterm (78,824 infants) andeighed �2500 g (82,799 infants). Ap-roximately 1 in 10 twins was born at32 weeks of gestation (n � 16,597 in-

ants) or weighed �1500 g (n � 13,983;igure 4). As Ananth et al36 noted that,ith the exception of France and Fin-

and, most industrialized countries haveoted a temporal increase in prematu-ity. The increase in preterm births isultifactorial but can be categorized

nto 3 groups: medically indicated be-ause of maternal-neonatal outcomes,fter spontaneous onset of pretermabor, and after premature rupture of

embranes.A comparison of the causes of preterm

irths for singleton vs twin pregnanciess instructive, especially when the datare separated by ethnicity. Using the datarom National Center for Health Statis-ics, Ananth et al36,37 provided such datasingleton pregnancies for the year 2000nd twin pregnancies for the years 1999-002). For singleton and twin pregnan-ies for African American and whiteomen, approximately 50% of pretermirths were indicated; one-third of the

dle Secondpuncture

Loss at<24 wkgestation, n

Loss rate,%a

Yes 13 2.7 (1.6–4.6)

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

Yes 6 3.9 (1.8–9.1)

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

Yes 4 3.0 (1.1–7.4)

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

ention Yes 1 0.4 (0.1–2.3)

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

Yes 9 2.9 (1.5–5.4)

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

Yes 18 4.1 (2.5–6.7)

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

51 2.9 (2.3–3.8).........................................................................................................................

ted loss rate within 4 weeks of birth.

m J Obstet Gynecol 2010.

irths were spontaneous, and 10% of the 1

OCTOBER 2010 Am

irths occurred after preterm prematureupture of membranes (Figure 5). Per-aps because the data do not lend them-elves to detailed information on theause of indicated delivery, the investiga-ors did not provide the specific reasonslinicians were compelled to perform theelivery prematurely.The perinatal mortality (PNM) ratesith preterm birth vary based on plural-

ty, ethnicity, and the subtypes of prema-urity (Figure 6). With the exception ofingleton and white pregnancies, theNM rate is highest when preterm deliv-ry follows premature rupture of mem-ranes. Consistently for singleton andwin pregnancies for African Americannd white women, the PNM rate is low-st when preterm birth results frompontaneous labor. Within the same eth-icity, the total preterm PNM rate is sig-ificantly less for twin than for singletonregnancies.The remarkable finding by Ananth et

l36,37 is that, despite the increase in theate of prematurity in the United States,here is a concomitant decrease in PNMates among African American and whiteomen among twin and singleton preg-ancies. In 2 separate publications,nanth et al36,37 reported the trends inreterm births for twin and singletonregnancies in the United States from

in pregnancyth noniocentesis, n

Loss with noamniocentesis, n

Loss rate,%a

77 3 0.6 (0.2–1.8)

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

92 7 2.4 (1.1–4.8)

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

48 2 0.8 (0.2–2.8)

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

— —

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

— —

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

— —

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

17 12 1.1 (0.6–2.0)..................................................................................................................

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erinatal mortality rates (Figure 7). Forheir analysis, they had 1,172,405 pre-erm twin live births and 46,375,578 pre-erm singleton pregnancies. Over 11ears, the rate of preterm births in-reased for African American and white

FIGURE 4Preterm births in 2006: twin vs sin

11%

2%

58%

12%

Del <37 weeks

Singleto

OR, 7.68 (95% CI, 7.51-7.78)

OR, 10.83 (95% CI, 10.71-10.95)

Del <32 weeks

W, birthweight; CI, confidence interval; Del, delivery; OR, odds rata derived, with permission, from Martin et al.2


FIGURE 5Data are based on ethnicity and suof preterm births: singleton vs twin

56% 58%

35% 32%

9% 10%

Singletons (AA) Twins (AA)

Med Indicated

A, African American; med, medically; PROM, premature ruptureata derived, with permission, from Ananth et al.36,37



win pregnancies and for white singletonregnancies; however, it decreased forfrican American twin singletons. TheNM rate decreased for all 4 groups dur-

ng the 11 years (Figure 7). The reasonor the decrease in the PNM rate is that

ton

7%

1%

60%

10%

Twins

OR, 21.94 (95% CI, 21.68-22.19)

OR, 10.21 (95% CI, 10.01-10.41)

BW <2500 g BW <1500 g


pes

53%62%

38%30%

9% 8%

Singletons (W) Twins (W)

p PTB PROM

embranes; Sp PTB, spontaneous preterm birth; W, white.


a

OCTOBER 2010

edically indicated preterm births aressociated with a favorable reduction inNM rates.

reterm labor: prediction,revention, and managementegardless of the temporal trend, therediction, prevention, and manage-ent of preterm birth are important and

hould be evidence based. Transvaginalervical length or fetal fibronectin (fFN)evel can be used to differentiate thoseregnancies that are likely to vs not likelyo deliver prematurely.

Fox et al38 described their experienceith routinely obtaining, from 22-32eeks, fFN and measuring transvaginal

ervical length. Overall, among 155 twinregnancies, of which 64% were the re-ults of in vitro fertilization, the rate ofirth at �37 weeks of gestation was 53%,t �34 weeks of gestation was 16%, and28 weeks of gestation was 4%. The rate

f spontaneous preterm birth was signif-cantly higher when either fFN was pos-tive or cervical length was �20 mm, butt was the highest when both tests werebnormal (Table 2). It is noteworthyhat, if the fFN is negative and cervicalength is at least 20 mm, almost 90% ofhe pregnancies will deliver at �34 weeksf gestation. Conversely, if both fFN andervical length are abnormal, �50% ofhe pregnancies will deliver at �34 weeksf gestation.Routine use of the diagnostic tests in

win pregnancies should not be expectedo decrease the actual rate of pretermirths. Matter of fact, the use of cervical

ength could increase the duration of an-epartum admission without concomi-ant improvement in neonatal outcome.

retrospective analysis by Gyamfi et al39

ompared the outcome among 184 twinregnancies with cervical length vs 78regnancies without this data. Betweenhe 2 groups, there was no difference inestational age at delivery (34.8 vs 35.3eeks of gestation; P � .35), delivery at28 weeks of gestation (8.2% vs 3.9%;� .21), or delivery at �34 weeks of ges-

ation (26.1% vs 25.6%; P � .94); how-ver, there was an increase in maternalntepartum length of stay (cervicalength at 34.5 days vs no cervical length

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hether their findings would have beenalid had they obtained fFN measure-ents in conjunction with cervical

ength. So, fFN and cervical length can besed to ascertain which twin pregnanciesill deliver prematurely, although im-rovement in peripartum outcomeshould not be expected.

Of twin gestations with symptoms ofreterm labor, approximately 22-29% ofhe pregnancies will deliver within 7ays.39,40 Thus, the first goal with symp-omatic patients should be to identifyhose who will deliver prematurely. Suchdentification avoids unnecessary thera-eutic interventions like unwarrantedospitalization and medical treatment.he usefulness of fFN in the evaluationf twin gestations with symptoms of pre-erm labor is not related to its ability toredict who will deliver in the next 14ays (19% positive predictive value; 95%I, 7–39%), but rather the test’s ability

o determine who is not going to deliveruring the timeframe (97% negativeredictive value; 95% CI, 89 –100). Theegative predictive value of fFN is simi-

ar for singleton and twin pregnanciesith symptoms of preterm labor.40

Fuchs et al41 reported on the inverseelationship between cervical length andikelihood of delivery of twin pregnan-ies within a week of the onset of symp-oms: 80% of the pregnancies deliveredhen the cervical length was 0-5 mm;6% of the pregnancies delivered whenhe cervical length was 6-10 mm; 29% ofhe pregnancies delivered when the cer-ical length was 11-15 mm; 21% of theregnancies delivered when the cervical

ength was 16-20 mm; 7% of the preg-ancies delivered when the cervical

ength was 21-25 mm, and none of theregnancies delivered when the cervical

ength was at least 25 mm. Undeniably,andomized trials are needed to deter-ine whether the knowledge of fFN and

ervical length influences outcome amongwin pregnancies, as it did in the trial re-orted by Ness et al.42 While awaiting theesults of these randomized trials, wehould be cognizant of the ACOG prac-ice bulletin on the management of pre-erm labor.43 They recommend that ei-her cervical ultrasound examination or
FN or both diagnostic tests should be
FIGURE 6Data are based on ethnicity and perinatal mortalityrates with preterm births: singleton vs twin

7176

43

535149

44

33

41

3129

25

10

100

Singletons (AA) Twins (AA) Singletons (W) Twins (W)

PN

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1000

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ths

PROM Med Ind Sp PTB

A, African American; Med Ind, medically indicated; PNM, perinatal mortality rate; PROM, premature rupture of membranes; Sp PTB,pontaneous preterm birth; W, white.ata derived, with permission, from Ananth et al.36,37

hauhan. Twins: prevalence, problems, and preterm births. Am J Obstet Gynecol 2010.

FIGURE 7Trend in the rate of preterm births and perinatal mortality for twinand 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

A, African American; PNM, perinatal mortality rate; PTB, preterm birth.ata derived, with permission, from Ananth et al.36,37

hauhan. Twins: prevalence, problems, and preterm births. Am J Obstet Gynecol 2010.

OCTOBER 2010 American Journal of Obstetrics & Gynecology 311

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sed to determine which patients do noteed tocolytics. Until there are publica-

ions to the contrary, this recommenda-ion is applicable to twin and singletonregnancies.Considering the increased likelihood

f preterm births among twin preg-ancies, it is reasonable to determinehether it can be prevented. One of theore common interventions that have

een tried in the past was the use of pro-hylactic oral betamimetics to reducehe incidence of preterm birth in twinestations. From a Cochrane database,amasmit et al44 reviewed 5 randomized

rials with 344 twin pregnancies. This in-ervention has not been proved to reducehe incidence of birth at �37 weeks ofestation (RR, 0.85; 95% CI, 0.65–1.10)r delivery at �34 weeks of gestationRR, 0.47; 95% CI, 0.15–1.50). It also hasot been shown to change the neonatalutcomes of low birthweight (RR, 1.19;5% CI, 0.77–1.85) or neonatal mortal-ty rates (RR, 0.80; 95% CI, 0.35–1.82).herefore, in light of these findings, these of prophylactic tocolysis should note undertaken.Progesterone has been shown to de-

rease the incidence of recurrent pre-erm delivery in a singleton gestation.45

TABLE 2Spontaneous preterm birth among

Variable

Negative fetal fibronectin level: 135 births, %...................................................................................................................

Positive fetal fibronectin level: 20 births, %...................................................................................................................

P value...................................................................................................................

Transvaginal cervical length �20 mm: 129 b...................................................................................................................

Transvaginal cervical length �20 mm: 26 bir...................................................................................................................

P value...................................................................................................................

Negative fetal fibronectin level and transvagin120 births, %...................................................................................................................

Either positive fetal fibronectin level or transva24 births, %...................................................................................................................

Positive fetal fibronectin level and transvaginabirths, %...................................................................................................................

P value...................................................................................................................

Data derived, with permission, from Fox et al.38

Chauhan. Twins: prevalence, problems, and preterm birth

systematic review by Dodd et al46 iden- o


ified only 2 randomized trials that as-essed the use of progesterone vs placeboor multiple pregnancy. Depending onhe outcome of interest, the number ofarticipants varied between 154 and280. The authors concluded that the usef progesterone in multiple gestationsoes not decrease the likelihood of birtht �37 weeks of gestation (RR, 1.01; 95%I, 0.92–1.12), birthweight �2500 g

RR, 0.94; 95% CI, 0.86 –1.02), respira-ory distress (RR, 1.13; 95% CI,.86 –1.48), intraventricular hemor-hage grade 3 or 4 (RR, 1.20; 95% CI,.40 –3.54), necrotizing enterocolitisRR, 0.77; 95% CI, 0.17–3.42), neonatalepsis (RR, 0.95; 95% CI, 0.55–1.63), anderinatal death (RR, 1.95; 95% CI,.37–10.33).Another approach to decrease prema-

ure births is to reinforce the cervix withcerclage in multiple gestations. The

lacement of a cerclage was examinedoth as a prophylactic intervention andhen a short cervix is noted on ultra-

ound examination. The use of history-ndicated (prophylactic) cerclage forvulation-induced twin gestations (n �0) in a randomized trial did not de-rease the rate of prematurity signifi-antly (45% with cerclage vs 48% with-

in pregnanciesGestational w

<28 <

2.1.........................................................................................................................

27.3 2.........................................................................................................................

.005.........................................................................................................................

, % 2.3.........................................................................................................................

% 25 1.........................................................................................................................

.008.........................................................................................................................

ervical length �20 mm: 1.6

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

al cervical length �20 mm: 13.3

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

rvical length �20 mm: 11 50 3

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

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m J Obstet Gynecol 2010.

ut suture) or neonatal mortality (18% c

OCTOBER 2010

s 15% for suture vs no suture, respec-ively).47 More importantly, when cer-lage was used in asymptomatic womanith twin gestations and short cervical

ength on transvaginal ultrasound exam-nation, it significantly increased the riskf delivery at �35 weeks of gestation75% in the cerclage group and 36%ithout suture; RR, 2.15; 95% CI, 1.15–.01).48 Thus, cerclage of asymptomatichort cervical length should be avoidedor twin gestations.

Other prophylactic interventions, whichave been examined in multiple gesta-ions to prevent preterm delivery, areed rest and home uterine monitoring.rowther,49 in 2001, summarized the re-

ults of 6 trials with hospitalization anded rest. The summary, which involved600 patients and 1400 newborn in-

ants, noted that the intervention did notecrease the rate of preterm birth orerinatal mortality. Paradoxically, bedest significantly (OR, 1.84; 95% CI,.01–3.34) increased the risk of pretermirth at �34 weeks of gestation insymptomatic twin gestations. Similarlylack of efficacy was also shown with these of home uterine monitoring for twinestations. Because home uterine moni-oring has not been shown to be benefi-

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ial in the prevention of preterm birth in

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ultiple gestations, its use should bebandoned.50 Thus, the following treat-ent modalities have no role in the pre-

ention of preterm births with twinestations: bed rest and oral tocolytics;erclage and progesterone injections.

One of the most difficult aspects ofaring for multiple gestations is the lackf proven intervention once preterm la-or has been diagnosed. The use of toco-

ytics for the treatment of preterm laboras not been shown to decrease the inci-ence of delivery within 7 days of treat-ent, perinatal or neonatal death, or the

eonatal complications of respiratoryistress syndrome, necrotizing entero-olitis, or cerebral palsy. This lack ofroven efficacy,51 the amplification ofide-effects, and the increased risk ofulmonary edema with tocolytics inultiple gestations52 lead ACOG to

omment that they should be used judi-iously in this population.53

In contrast to the unproven efficacy ofocolytics, the use of antenatal cortico-teroids (ACS) has been shown54 to de-rease the incidence of neonatal deathRR, 0.69; 95% CI, 0.58 – 0.81), respira-ory distress syndrome (RR, 0.66; 95%I, 0.43– 0.69), intraventricular hemor-

hage (RR, 0.54; 95% CI, 0.43– 0.69), ne-rotizing enterocolitis (RR, 0.46; 95%I, 0.29 – 0.74), and systemic infectionsithin the first 48 hours of life (RR, 0.56;5% CI, 0.38 – 0.58). Although none ofhe studies specifically addressed use in

ultiple gestations, the National Insti-utes of Health recommends that allomen in preterm labor, regardless of

he number of fetuses, be given a coursef ACS.55

Although ACS does improve neonatalutcome significantly, it should not bedministered repeatedly. A retrospectivetudy by Murphy et al56 compared these of prophylactic ACS in twin gesta-

ions beginning at 24 weeks of gestationnd given every 2 weeks (n � 136) withhe standard approach in women whoere at immediate risk of preterm deliv-

ry (n � 902). The prophylactic ap-roach was shown not to offer a signifi-ant reduction in respiratory distressyndrome (13% vs 11%; adjusted OR,.69; 95% CI, 0.33–1.46) and was associ-
ted with exposing a large number of ba- f
ies to unnecessary treatment that ad-ersely affects growth. Therefore, theepeated administration of ACS shoulde avoided in favor of those pregnancieshat are at immediate risk for pretermirths.One single rescue course of ACS

hould be given among twins who haveeceived betamethasone 12 mg, intra-uscularly, twice, 24 hours apart. If at

east 14 days have elapsed and delivery isikely at �33 weeks of gestation, then aingle rescue dose should be adminis-ered. This recommendation is based onhe randomized trial by Garite et al57 thatnvolved 437 patients, with 577 newbornnfants, 24% of whom (141; 1 fetal deathefore randomization) were from twinestations. Compared with the patientsho received placebo, patients who re-

eived the rescue dosage had a significanteduction in composite perinatal neona-al morbidity (64% vs 44%; P � .02) andignificantly decreased rate of respira-ory distress syndrome, ventilator sup-ort, and surfactant use.In summary, although there are diag-

ostic tests to identify those pregnancieshat will deliver prematurely, these testso not decrease the rate of preterm birth.here are no known treatments to de-rease the likelihood of preterm birth.ocolytics should be used either to trans-

er a patient to a tertiary center or tonsure ACSs are administered. Pro-onged tocolytic use should be avoided,s should repeated administration oforticosteroids.

ommentwins are a source of awe and delight toarents, fascination and photo opportuni-ies to the press,1 and challenge and trepi-ation to clinicians.58,59 Compared withingleton pregnancies, twin pregnanciesre more likely to be complicated by hy-ertensive disorders, gestational diabetesellitus, anemia, preterm birth, ante- and

ostpartum hemorrhage, and maternaleath.60 The newborn infants from twinregnancies are more likely to have anom-lies,26 intrauterine growth restriction,61

andicap, and cerebral palsy. The averageost for singleton deliveries is $9,845 and
or twins is $37,947.60 Thus, continued t
OCTOBER 2010 Am

nderstanding of twin pregnancies ismportant.

This review of the literature on twinestations, although limited to commonroblems, was notable for 4 findings.irst, the rate for twin gestations has sta-ilized for now. For 2004, 2005, and006, there have been approximately 32win gestations per 1000 births (Figure). Second, the sonographic evaluationsf twin gestations should be limited notnly to the identification of the chorio-icity but also aneuploidy with first-

rimester screening and anomaly withrst- and second-trimester ultrasoundxaminations. Because anomalies andneuploidies are more common withwin pregnancies than with singletonregnancies,26,27 it is important that cli-icians who have experience in detecting

hese abnormalities evaluate these pa-ients. If need be, parents who are ex-ecting twins should be offered and re-

erred for CVS, genetic amniocentesis,nd selective reduction.

Third, we found that the rate of pre-erm births is significantly higher forwin pregnancies than for singletonregnancies (Figure 4). Although thisas been known, findings from the na-ional data provide not only unequivocalvidence but also the magnitude tohich this occurs. Data from the Unitedtates also are available for the analysis ofauses for preterm birth (Figure 5) andssociated perinatal mortality rates (Fig-re 6). But what is most captivating is

hat, although the rate for preterm birthas increased, the associated perinatalortality rate has actually decreased.he fact that this conclusion is based on aopulation-based, retrospective cohorttudy comprised of 46,375,578 womennd 1,172,405 twins in the United Statess staggering.36,37 It will be beneficial ifther countries can confirm the findingseported by Ananth et al36,37 and if fu-ure studies can ascertain what preciselyecreased the perinatal mortality rate. Itill also be useful to understand whether

he overall perinatal mortality rate, notust for preterm births, has also de-reased in the United States.

Fourth, the findings focus on the man-gement of preterm labor with twin ges-
ations. Clinicians should be cognizant

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f the facts that, with twins, preterm con-ractions are common, that the benefit ofocolytics is limited although the com-lications rate is higher, and that the pre-erm birth-related perinatal mortalityate has been lowered. Whenever feasi-le, clinicians should use diagnostic teststransvaginal cervical length or fFN) toifferentiate true vs false preterm labor.he use of tocolytics should be limited to

1) either the cervical length is �2.5 cmr fFN is positive or both, (2) the testesults have been evaluated, (3) 48 hoursave elapsed since the first dosage of cor-icosteroid was administered, or (4) theatient has been transferred to a tertiaryenter. As with singleton pregnancies,43

here is no justification for prolonged to-olytics with twin pregnancies.

In conclusion, there are several reas-uring findings with twin pregnancies.he rate of twin pregnancies is not in-reasing in the United States; althoughhe preterm birth rate is high, the associ-ted perinatal mortality rate is decreas-ng. Future studies should focus on im-roving the detection of birth defectsnd of abnormal growth and on antepar-um testing to improve the outcomes forwin pregnancies with medical or obstet-ic complications. f

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Twins prevalence, problems, and preterm births ajog2010