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he association of crown-rump length discordance in twinestations with adverse perinatal outcomes

udy Tai, MD; William A. Grobman, MD, MBA

BJECTIVE: The purpose of this study was to evaluate the associationetween the crown-rump length (CRL) difference in twin gestations anddverse pregnancy outcome.

TUDY DESIGN: Women with a first trimester ultrasound scan of a twinregnancy who delivered between June 2000 and March 2006 at North-estern Memorial Hospital were identified. The association between theifference in CRLs and pregnancy outcomes was explored.

ESULTS: For the 178 twins who were eligible for the study, the

rived from the first ultoi: 10.1016/j.ajog.2007.06.024

n birthweights was 9.3%. Twins with a CRL difference of �85thercentile (11.1%) were more likely to have discordant birth-eights and to have at least 1 of the pair be small-for-gestationalge, be admitted to the special care nursery, and have perinatalorbidity.

ONCLUSION: CRL differences of �85th percentile are associatedith several measures of adverse perinatal outcome.

edian difference in CRLs was 4.2% and the median difference

ite this article as: Tai J, Grobman WA. The association of crown-rump length discordance in twin gestations with adverse perinatal outcomes. Am J Obstetynecol 2007;197:369.e1-369.e4.

he twin birth rate in the UnitedStates has increased approximately

0% over the past 20 years and now ac-ounts for almost 3% of all births.1 Al-hough twins represent a minority ofirths, they account for a disproportion-te share of perinatal morbidity andeaths.1 One cause that frequently is as-ociated with perinatal morbidity andeath in twins is intrauterine growth ab-ormalities, namely intrauterine growthestriction and third-trimester twiniscordance.1,2

Although growth discordance in thehird trimester has been associated withdverse perinatal outcome, the implica-ions of twin discordance that are de-ected in the first trimester of pregnancyemain less well understood.3-8 There areelatively few articles that have assessedhis phenomenon; those articles that ex-st have not reached uniform conclu-

sions. In some cases, the degree ofcrown-rump length (CRL) differencehas been correlated with the amount ofdifference of the subsequent birth-weights, although in other studies thiscorrelation has not been found. Also, al-though very large differences in CRLhave been associated with aneuploidyand anatomic abnormalities, the clinicaloutcomes of euploid fetuses without ma-jor congenital anomalies, but with differ-ences in CRL, are not well described.

The objective of this study was to de-termine how the difference in the first-trimester CRL of twins is related to sub-sequent growth abnormalities andadverse perinatal outcome.

MATERIALS AND METHODSWomen who received a first trimester ul-trasound scan of a twin pregnancy be-tween 7 and 14 weeks of gestation andsubsequently delivered between June2000 and March 2006 at NorthwesternMemorial Hospital were identified. Onlypregnancies with 2 fetal heartbeatspresent at time of the first-trimester ul-trasound scan were included. If womenhad �1 ultrasound scan during this timeperiod, the CRL measurements were de-

tion that was performed. Fetuses withknown chromosomal or major congeni-tal anomalies were excluded from furtheranalysis, as were women who underwentfirst- or second-trimester pregnancy ter-mination. Also excluded were those preg-nancies that were monoamniotic.

Maternal charts were reviewed to as-certain antenatal and intrapartum char-acteristics. Chorionicity was assignedaccording to the ultrasonographic ap-pearance of the twin pregnancy at thefirst-trimester ultrasound examinationand confirmed by pathologic report.Birthweights, Apgar score at 1 and 5minutes, and arterial and venous bloodgases, when available, were recorded.Neonatal charts were further abstractedto ascertain the length of the neonatalhospital admission, admission to thespecial care nursery, and the presence ofmajor morbidities, which includedrespiratory distress syndrome, intraven-tricular hemorrhage, patent ductus arte-riosus, necrotizing enterocolitis, culture-proved sepsis, and neonatal death.

The difference in CRL (CRL�) wascalculated as the difference in the twinCRLs divided by the CRL of the largertwin and expressed as a percentage. Sim-ilarly, the difference in birthweight(BW�) was calculated as the differencein birthweights divided by the birth-

rom the Department of Obstetrics andynecology, Feinberg School of Medicine,orthwestern University, Chicago, IL.

resented at the 27th Annual Clinical Meetingf the Society for Maternal–Fetal Medicine,an Francisco, CA, Feb. 5-10, 2007.

eprints not available from the authors.

002-9378/$32.002007 Mosby, Inc. All rights reserved.

ipwam

Cw

Key words: crown-rump length, discordance, twins

rasound examina- w

OCTOBER 2007 America

eight of the larger twin and expressed

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3

s a percentage. Birthweight discordanceas defined as a BW� of �20%. Small-

or-gestational age birthweight was de-ned as a birthweight of �10th percen-

ile for gestational age.1 Compositeerinatal morbidity was defined as the oc-urrence of any of the following events:espiratory distress syndrome, intraven-ricular hemorrhage grade 3 or 4, necro-izing enterocolitis, culture-proved sep-is, or perinatal death. Continuousariables were evaluated with the Stu-ent t or Mann-Whitney U test, based onormality of the data as assessed by theolmogorov-Smirnov test; categoricariables were evaluated with either theisher exact test or chi-square analysis, asppropriate. All tests were 2-tailed; arobability value �.05 was used to de-ne statistical significance. Statisticalnalysis was performed with Minitab 13oftware (Minitab, Inc, State College,A) and Stata 9 software (StataCorp,ollege Station, TX). This investigation

eceived approval from the Institutionaleview Board of Northwesternniversity.

FIGUREROC for prediction ofdiscordant birthweight byCRL�

ai. The association of crown-rump length discordance in twinestations with adverse perinatal outcomes. AJOG 2007.

TABLE 1Demographic characteristics strati

Characteristic

Maternal age (y)*...................................................................................................................

Gestational age at initial ultrasonographicexamination (wk)†

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

Monochorionic (n)...................................................................................................................

* Data presented as mean � SD.†

Data are presented as median (interquartile range).

69.e2 American Journal of Obstetrics & Gynecol

ESULTSne hundred seventy-eight women met

nclusion criteria. In 6 pregnancies, thereas previable death of both twins, andirthweights were not obtained. Forhese cases and for the 3 pregnanciesith an intrauterine fetal death of 1 twin

ong before delivery of the cotwin, birth-eight discordance was not calculated.hese pregnancies were included in eval-ation of CRL� with other pregnancyutcomes, as applicable. Thus, the 6reviable deaths were not considered inhe analysis of a outcome such as “neo-atal intensive care unit” admission butere analyzed with regard to the com-osite adverse outcome, which includedeath. No neonates were found to haveny major congenital anomaly or wereiagnosed with a chromosomalbnormality.

The median CRL� of the 178 twins inhe study was 4.2% (interquartile range,.9%-8.3%); the median BW� of the 168wins with birthweight available was.3% (interquartile range, 3.9%-16.4%).he median CRL�s of monochorionicnd dichorionic twin gestations wereimilar (3.6% [interquartile range,.0%-8.3%] vs 5.1% [interquartileange, 2.0%-8.3%], respectively; P �18). The CRL� was significantly corre-ated with BW� (r � 0.43; P � .001). TheRL� was further evaluated in relation

o birthweight discordance through theonstruction of a receiver operatingharacteristic (ROC) curve. This ROCurve (Figure) had an area under theurve of 0.72 and revealed the 85th per-entile of CRL� (11.1%) to be an opti-al point of demarcation to predict sub-

equent birthweight discordance. Thus,CRL� of �11% was further used to as-

d by CRL� >11%L � > 11%� 29)

CRL � < 11%(n � 149) P value

0 � 4.1 33.2 � 5.3 .35..................................................................................................................

7 (9.9-12.7) 11.7 (10.4-12.6) .96

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

(24.1%) 36/146 (24.7%) .95..................................................................................................................

s

ogy OCTOBER 2007

ess the relation between this extreme ofRL� and other patient characteristicsnd adverse pregnancy outcomes.

There did not appear to be any relationetween a CRL� of at least 11% and anyemographic characteristic of the pa-ients. As Table 1 shows, there were noifferences in maternal age, gestationalge at first trimester ultrasonographicxamination, or chorionicity, after strat-fication of the study group by thisRL�.Conversely, a CRL� �11% was asso-

iated with a significantly increasedisk of continued discordant twinrowth, because these twins were sig-ificantly more likely to be deliveredith discordant birthweights (Table). The association of a CRL� of ateast 11% with discordant birthweightas evident regardless of chorionicity,ecause this association was present inoth monochorionic and dichorionicwin subgroups after stratification.ixty-seven percent of monochorionicwins with a CRL� of at least 11% hadiscordant birthweights; the frequencyf birthweight discordance was only.1% among those with a CRL� �11%P � .01). With respect to dichorionicwins, those twins with a CRL� of ateast 11% had a 41% probability ofirthweight discordance, althoughnly 7.6% of those twins with a CRL�11% had this birthweight discor-

ance (P � .01).Multiple other adverse outcomesere also increased in twins with aRL� of at least 11%. Those twins withCRL� in this range were at increased

isk of at least 1 twin being growth re-tricted at birth. Moreover, there wasvidence that these growth abnormali-ies had ramifications for perinatalealth. Those twins with a CRL� of11% were significantly more likely to

equire admission to the neonatal in-ensive care unit and to experience ateast 1 of the adverse outcomes in theomposite perinatal morbidity mea-ure. The test characteristics of a CRL�f at least 11% as a predictor of selecteddverse neonatal outcomes are pre-

fieCR(n

34..........

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.........

7.........

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OMMENThere has been relatively little informa-

ion regarding the pregnancy outcomesf women with twins who were exam-

ned in the first trimester with differ-nces in their CRL.4-8 The informationhat does exist has focused on 2 out-omes: birthweight discordance or theresence of a fetus with a chromosomalr anatomic abnormality. Several au-hors, for example, have found that twinsith large CRL�s were more likely toave birthweight discordance.4,6,8 Kalisht al7 also demonstrated, in a populationf dichorionic twins, that only those withCRL� of �90th percentile (in their

tudy population a difference in CRL of10%) were more likely to include a fe-

us with a chromosomal or anatomic

TABLE 2Pregnancy outcomes stratified byOutcome

Gestational age at delivery (wk)...................................................................................................................

Delivery at �37 wk (n)...................................................................................................................

Twin-twin transfusion syndrome (n/N)*...................................................................................................................

Birthweight discordance (n/N)...................................................................................................................

Small-for-gestational age (n)†...................................................................................................................

Birthweight discordance and at least 1 fetussmall-for-gestational age (n/N)

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

Perinatal death (n)†...................................................................................................................

Apgar �7 at 5 min (n)†...................................................................................................................

Arterial pH �7.0 (n/N)†...................................................................................................................

Neonatal intensive care unit admission (n)†...................................................................................................................

Composite perinatal morbidity (n)†...................................................................................................................

* Frequency for the monochorionic population only.† Based on the occurrence in at least 1 fetus within the twin

TABLE 3The test characteristics of a CRL�

Birthweight discordance...................................................................................................................

Small-for-gestation age*...................................................................................................................

Neonatal intensive care...................................................................................................................

Unit admission*...................................................................................................................

Composite perinatal...................................................................................................................

Morbidity*...................................................................................................................

* Based on the occurrence in at least one fetus within the tw

NPV, negative predictive value; PPV, positive predictive value.

nomaly. This association was alsoound in the study by Salomon et al.5

We chose to assess the relationship be-ween the CRL difference in euploid andnatomically normal twin gestations andubsequent pregnancy outcome. This re-ationship has not been well explorednd is potentially important for patientounseling, because parents of a twinregnancy with discordant CRLs, butithout evident aneuploidy or anatomic

bnormality, will desire other prognosticnformation. We have confirmed thathe difference in first-trimester CRL isorrelated with differences in birth-eight and that large differences in theRLs are associated with eventualrowth discordance and growth restric-ion in the third trimester and with twin-

L� >11%CRL � >11% (n � 29)

35.6 (32.2-37.5).........................................................................................................................

19 (65.5%).........................................................................................................................

3/7 (43.9%).........................................................................................................................

13/28 (46.4%).........................................................................................................................

19 (65.5%).........................................................................................................................

9/28 (31.0%)

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

2 (6.9%).........................................................................................................................

5 (17.2%).........................................................................................................................

2/19 (10.5%).........................................................................................................................

17 (58.6%).........................................................................................................................

14 (48.3%).........................................................................................................................

nancy.

11% as a predictor of selected advnsitivity Specificity

% 90%.........................................................................................................................

% 90%.........................................................................................................................

% 89%.........................................................................................................................

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

% 88%.........................................................................................................................

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

regnancy.

OCTOBER 2007 America

win transfusion syndrome in monocho-ionic gestations. We have also showedhat larger CRL differences are associ-ted with adverse perinatal outcomes,hich are represented by the increased

requency of perinatal morbidity andeonatal intensive care unit admission.We have used a CRL� of �85th per-

entile to identify the group that is at riskf adverse outcome. There is nothing,owever, that is inherently pathologicbout the 85th percentile; it was used be-ause, on the basis of the ROC analysis, its a cutoff that adequately balances sen-itivity and specificity. Indeed, other in-estigators have used other cutoffs. Forxample, Kalish et al6 used ROC analysiso determine that a CRL� of �90th per-entile was best for the prediction of dis-

L � <11% (n � 149) P value

4 (34.0-38.0) .31..................................................................................................................

(56.4%) .36..................................................................................................................

36 (8.3%) .04..................................................................................................................

141 (7.8%) �.001..................................................................................................................

143 (38.5%) �.01..................................................................................................................

141 (6.4%) �.001

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

(5.4%) .67..................................................................................................................

138 (6.5%) .06..................................................................................................................

111 (3.6%) .21..................................................................................................................

143 (35.0%) .02..................................................................................................................

(24.2%) �.01..................................................................................................................

e neonatal outcomesPPV NPV

46% 92%..................................................................................................................

66% 62%..................................................................................................................

59% 65%..................................................................................................................

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

48% 76%..................................................................................................................

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

CRCR

36.......... .........

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55/......... .........

9/

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8......... .........

9/......... .........

4/......... .........

50/......... .........

36......... .........

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54......... .........

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SMFM Meeting Papers www.AJOG.org

3

ordant third-trimester growth. Yet, inheir study population, the 90th percen-ile was a CRL� of 10%, which is a dif-erence quite similar to our finding of1% as the optimal discriminator. Also,e have used a percentage difference aspposed to the absolute difference inRL. It should be noted that we did an-lyze the absolute difference for its asso-iation with adverse outcomes (data nothown), but the absolute difference wasot as good as the percentage differencet the prediction of these neonatal out-omes. This is not surprising, given thathe absolute size of the CRL changes overuch a wide range during the gestationalges under study.

The finding in the present study thathe median CRL� of monochorionicwins is similar to that of dichorionicwins was also noted by Sebire et al.4 Inontrast to our data, however, that studyemonstrated an association betweenhe CRL� and subsequent birthweightiscordance only in the dichorionic sub-roup. One potential reason for the dif-erence in findings is that Sebire et al an-lyzed the association using the medianRL� and we have used a categoricRL� variable. Also, the present study

ncorporated ultrasound informationhat was ascertained as early as 7 weeks ofestation; the study of Sebire et al4 (andf Kalish et al7) did not use ultrasoundata from pregnancies that were before0 weeks of gestation.Northwestern Memorial Hospital is a

ertiary care center, and this characteris-

ic raises the possibility that the results 2

69.e4 American Journal of Obstetrics & Gynecol

hat were derived from this study popu-ation are not generalizable to other twinopulations. However, the medianRL� and the frequency of birthweightiscordance are similar to findings thatave been described by other investiga-ors. Moreover, characteristics of thetudy population (such as the frequencyf preterm birth, monochorionicity, andiscordant twin birthweights) are simi-

ar to that expected in the general popu-ation.9-11 Although the frequency ofmall-for-gestational-age birthweightppears higher than expected, this find-ng is explained by the fact that we ascer-ained this outcome on the basis of sin-leton nomograms, because theseomograms have been shown to be moreredictive of adverse perinatal outcomeshan twin-specific nomograms.12,13

This study provides information thatan be used to counsel women who areonfronted with CRL discordance in therst trimester of pregnancy. In someense, the information may be viewed aseassuring, because CRL discordance isot associated inevitably with adverseregnancy outcome. Those twins withiscordant CRLs still had a �50%hance of not having significant perina-al morbidity. Nevertheless, the risk ofdverse outcomes is increased, and careroviders should be cognizant of thisssociation. f

EFERENCES. MacDorman MF, Minino AM, Strobino DM,uyer B. Annual summary of vital statistics-

001. Pediatrics 2002;110:1037-52. G

ogy OCTOBER 2007

. Powers WF, Kiely JL. The risks of confrontingwins: a national perspective. Am J Obstet Gy-ecol 1994;170:456-61.. Hollier LM, McIntire DD, Leveno KJ. Out-ome of twin pregnancies according to intrapairirthweight differences. Obstet Gynecol 1999;4:1006-10.. Sebire NJ, D’Ercole C, Soares W, Nayar R,icolaides K. Intertwin disparity in fetal size inonochorionic and dichorionic pregnancies.bstet Gynecol 1998;91:82-5.. Salomon LJ, Cavicchioni JP, Bernard JP,uyme M, Ville Y. Growth discrepancy in twins

n the first trimester of pregnancy. Ultrasoundbstet Gynecol 2005;26:512-6.. Kalish RB, Chasen ST, Gupta M, Sharma G,erni S, Chervenak FA. First trimester predic-

ion of growth discordance in twin gestations.m J Obstet Gynecol 2003;189:706-9.. Kalish RB, Gupta M, Perni SC, Berman S,hasen ST. Clinical significance of first trimesterrown-rump length disparity in dichorionic twinestations. Am J Obstet Gynecol 2004;191:437-40.. Bartha JL, Ling Y, Kyle P, Soothill PW. Clini-al consequences of first trimester growth dis-ordance in twins. Eur J Obstet Gynecol Re-rod Biol 2005;119:56-9.. O’Brien WF, Knuppel RA, Scerbo JC, RattanK. Birthweight in twins: an analysis of discor-ance and growth retardation. Obstet Gynecol986;67:483-6.0. Martin JA, Hamilton BE, Stuton PD, Ven-ura SJ, Menacker F, Munson ML. Births: finalata for 2002. Natl Vital Stat Rep 2003;52:-102.1. Wenstrom KD, Syrop CH, Hammitt DG, vanoorhis BJ. Increased risk of monochorionic

winning associated with assisted reproduction.ertil Steril 1993;60:510-4.2. Alexander GR, Himes JH, Kaufman RB,or J, Kogan M. A United States national ref-

rence for fetal growth. Obstet Gynecol996;87:163-8.3. Hamilton EF, Platt R, Morin L, Usher R,ramer M. How small is too small? Am J Obstet

ynecol 1998;179:682-5.