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Review

Accuracy of Ultrasonography at 11–14 Weeksof Gestation for Detection of FetalStructural AnomaliesA Systematic Review

A. Cristina Rossi, MD , and Federico Prefumo, MD , PhD

OBJECTIVE: To review the literature concerning theefficacy of early ultrasonography (at 11–14 weeks of ges-

tation) to identify fetal malformations.

DATA SOURCES: A search in PubMed, MEDLINE,Embase, Cochrane Library, and ClinicalTrials.gov was per-

formed (January 2000 to December 2012). Keywordswere: fetal anatomy, fetal echocardiography, nuchal trans-

lucency, fetal structural anomalies, fetal malformations,prenatal diagnosis, prenatal screening, and first-trimester

ultrasonography.

METHODS OF STUDY SELECTION: Inclusion criteriawere: fetal anatomy examination at early ultrasonogra-

phy and diagnosis of fetal malformations confirmed by

postnatal or postmortem examination. Data abstractedwere: sample size, location of structural defect, ultra-

sound modality, presence of multiple defects, and studypopulation. Pooled detection rate was calculated foreach malformation and compared with x2. Differences

were considered statistically significant if P ,.05.

TABULATION, INTEGRATION, AND RESULTS: From1,203 articles, 19 were included. Overall, we pooled

78,002 fetuses undergoing ultrasonography at 11–14weeks, of which 996 were malformed, leading to preva-

lence of malformation of 12 per 1,000. The overall detec-tion rate was 472 of 957 (51%). The highest detection rate

was achieved for neck anomalies (92%), whereas limbs

(34%), face (34%), and genitourinary anomalies (34%)were associated with the lowest detection rate. At

14 weeks of gestation or less, fetal echocardiographydetected 53% of congenital heart disease compared with

43% by complete scan (P 5.040). The use of Doppler did

not improve the detection rate for congenital heartdefects (52% compared with 44%, respectively; P 5.11).

Multiple defects were identified more frequently thanisolated malformations (60% compared with 44%;P 5.005). The detection rate was higher combining trans-abdominal and transvaginal techniques (62%) than either

abdominal (51%) or transvaginal (34%; P ,.001). Detec-

tion rate was higher in women at high risk (65%) than

unselected population (50% P 5.001).

CONCLUSION: Because of the natural history of fetal

defects and the late development of some organ sys-tems, a number of fetal malformations remain unde-

tected by early ultrasonography.

(Obstet Gynecol 2013;122:1160–7)

DOI: 10.1097/AOG.0000000000000015

First-trimester ultrasonography is widely performedto assess the risk of chromosomal abnormalities in

unselected populations by measuring the fetal nuchaltranslucency thickness between 11 and 14 weeks of gestation. Because substantial advances in magnifica-tion imaging and signal processing increased the abil-

ity to visualize fetal anatomy, there was great concernon the feasibility to diagnose a wide range of fetalanomalies at the time of nuchal translucency scanby transvaginal, transabdominal, or transvaginal andtransabdominal ultrasonography.1–3 In the last few years, several studies encouraged the early diagnosisof major anomalies after demonstrating the associa-tion of increased nuchal translucency thickness witha number of structural defects in fetuses having bothnormal and abnormal karyotype.4–6 The ability toreassure high-risk women with normal examinations

From the Department of Obstetrics and Gynecology, University of Bari, Bari, and the Maternal-Fetal Medicine Unit, Department of Obstetrics and Gynecology,University of Brescia, Brescia, Italy.

Presented at the 17 th International Conference of Prenatal Diagnosis, June 2 – 5,2013, Lisbon, Portugal.

Corresponding author: A. Cristina Rossi, MD, Via Celentano, 42, 70121 Bari,Italy; e-mail: [email protected].

Financial Disclosure

The authors did not report any potential conflicts of interest.

© 2013 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.

ISSN: 0029-7844/13

1160 VOL. 122, NO. 6, DECEMBER 2013 OBSTETRICS & GYNECOLOGY

http://clinicaltrials.gov/http://clinicaltrials.gov/

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and the possibility to terminate pregnancy in cases of detection of lethal malformations earlier in gestationled to the modern trend of shifting prenatal diagnosisto the earliest possible gestational age so that earlierdecisions on further management are allowed. How-ever, research about the effectiveness of early ultraso-nography in the diagnosis of structural defects has

produced conflicting results, which made question-able to what extent structural congenital abnormalitiescould be detected by the routine scanning of fetalanatomy combined with nuchal translucency mea-surement.7 Other disadvantages associated with earlyprenatal diagnosis consist of the high experiencerequired and high costs in terms of time and equip-ment.8

Our objective was to review current literatureconcerning the diagnostic accuracy of first-trimesterand early second-trimester ultrasonography in thedetection of fetal structural defects. We further

explored whether the effectiveness of early ultraso-nography is associated with location of structuraldefects, the presence of risk factors for fetal anomalies,and number of malformations per fetus.

SOURCESA search in PubMed, Medline, Embase, Clinical-Trials.gov, and the Cochrane Library was performedto find relevant publications that analyzed the accu-racy of ultrasonography in the assessment of fetalanatomy in the first trimester (11–14 weeks of gesta-tion). Because ultrasound equipment improved the

resolution of fetal images during the last decade,9–11

the search included articles that were published from January 2000 to December 2012. Keywords were:fetal anatomy, fetal echocardiography, nuchal trans-lucency, fetal structural anomalies, fetal malforma-tions, prenatal diagnosis, prenatal screening, andfirst-trimester ultrasonography. Two authors indepen-dently reviewed the articles by following theMeta-analysis Of Observational Studies in Epidemiol-ogy (MOOSE) guidelines.12 We used the QualityAssessment of Diagnostic Accuracy Studies to assess

the quality of the studies included in the analysis(http://www.bris.ac.uk/quadas/ , accessed July 5, 2013).Quality Assessment of Diagnostic Accuracy Studies isa tool for use in systematic reviews to evaluate the risk of bias and applicability of primary diagnostic accuracystudies. It consists of four domains: patient selection,index test, reference standard, and flow and timing.Each domain is assessed in terms of risk of bias, whichis summarized as “low,” “high,” or “unclear.” The first three domains are also assessed in term of applicabilityusing the same summary outcomes.13,14

Discordance between the two authors was solvedby consensus. Statistical analysis was performed withx2 to compare detection rates according to the ultra-sound technique, the use of Doppler, the presence of multiple defects, and the presence of risk factors forfetal malformation. Differences were considered sta-tistically significant if P ,.05 (GraphPrism).

STUDY SELECTIONInclusion criteria were fetal anatomy examinationperformed at 11–14 weeks of gestation; visualizationof the brain, face, thorax, abdomen, urinary tract, limbs,and four cardiac chambers with outflow tract, cardiacsitus, interventricular septum; confirmation of the earlydiagnosis of fetal malformations by postnatal or post-mortem examination; and data reported exactly in ta-bles and text. Exclusion criteria were omitting at least one of the inclusion criteria, data reported in graphs orpercentage, case reports, reviews, personal communica-

tion, and non-English language publications.Data abstracted from each article were: sample size,

presence or absence of risk factors for fetal malforma-tions, location and type of structural defects, ultrasoundmodality (transabdominal, transvaginal, or transabdomi-nal and transvaginal approach), and presence of isolatedor multiple defects. Risk factors for fetal malformationswere defined as a family history of inherited malforma-tions, increased nuchal translucency, maternal age olderthan 35 years, and abnormal karyotype.

Tricuspid regurgitation and ventricular discrep-ancy were not considered as structural malformations,

because the former is recognized to be compatiblewith normal finding 15 and the latter is highly subjec-tive. When data were missing, an effort was made tocontact the corresponding author.

We calculated the pooled detection rate of eachmalformation and compared it according to theultrasound technique (transvaginal compared withtransabdominal compared with combined transvagi-nal and transabdominal ultrasonography), associatedcompared with isolated defects, and high- comparedwith low-risk factors for fetal malformations. With

regard to congenital heart defects, we further com-pared detection rates of targeted echocardiographywith complete anatomy assessment and investigatedwhether Doppler assessment improved the accuracyof 11–14 weeks of gestation ultrasonography in diag-nosing congenital heart defects.

Detection rate was calculated as number of malformations detected by 11–14 weeks of gestationultrasonography divided by the number of malforma-tions detected at birth or postnatal or postmortemexaminations.

VOL. 122, NO. 6, DECEMBER 2013 Rossi and Prefumo First-Trimester Ultrasonography 1161

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RESULTSFrom 1,203 articles, 19 were included, of whichnine articles described a complete survey of fetalanatomy,6,10,16–22 nine articles assessed fetal heart only,8,15,23–29 and one article reported fetal anatomyexamination except cardiac assessment 30 (Fig. 1).

The Quality Assessment of Diagnostic Accuracy

Studies assessment (Table 1) demonstrates that only11 of 19 included studies had a low risk of bias regard-ing patient selection. This was the result of the inclu-sion of high-risk women in a significant number of studies, mainly based on increased nuchal translu-cency measurements. In 18 of 19 studies, the protocolfor ultrasound examination was clearly defined, lead-ing to a low risk of bias in the index test domain. Theidentification of structural abnormalities must oftenrely on different types of clinical and instrumentalassessment, postmortem or after birth. We consideredthis to be normal in the diagnosis of structural abnor-

malities, but still the reference standard was not satis-factorily described in three of 19 studies. Finally, only13 of 19 had a low risk of bias in the flow and timing domain as a result of insufficient details on follow-upand exclusions (Fig. 2). The applicability was gener-ally satisfactory. We only considered one study25 to

have high concerns of applicability in the index test domain as a result of the use of high-frequency trans-abdominal probes, which are not widely available inmost clinical settings.

Characteristics of the studies are summarized inTable 2. Overall, we pooled 78,002 fetuses undergo-ing ultrasonography at 11–14 weeks of gestation, of

which 996 were malformed, leading to prevalence of malformation of 12 per 1,000.The overall detection rate of early ultrasonogra-

phy was 501 of 996 (51%). With regard to location of fetal malformation, the highest detection rate wasobserved for neck anomalies (24/26 [92%]) followedby anomalies of the abdomen (96/109 [88%]), brainand spine (81/158 [51%]), heart (201/418 [48%]),limbs (36/105 [34%]), genitourinary tract (40/116[34%]), and face (8/23 [34%]). Other types of malfor-mations were associated with a detection rate of 15 of 41 (36%). Box 1 groups the types of malformation

according to their detection rates.Fetal heart assessment was performed by echo-

cardiography alone in 224 (53%) and included incomplete anatomy examination in 194 (47%) fetuses.The Doppler technique was applied in 210 (50%)cases. The detection rate of congenital heart defects

Potentially relevant observational

studies concerning

the accuracy of first/early

second trimester ultrasound

for the detection of

fetal malformations

N=1,203

Observational studies

retrieved for more

detailed evaluation

n=798

Potentially appropriate

observational studies

to be included in

the meta-analysis

n=32


with usable information

included in the

meta-analysis

n=19


in which complete anatomy

survey was performed

n=9


in which anatomy survey

was performed, except

for echocardiography

n=1

Excluded: n=407

Not published during

the study period, 1999–2009

Excluded: n=766

Based on title or abstract

(case reports, reviews,

personal communications)

Excluded: n=13

Did not meet the

inclusion criteria

Observational studies in

which only echocardiography

was performed

n=9

Fig. 1. Steps for meta-analysis.

Rossi. First-Trimester Ultrasonography.Obstet Gynecol 2013.

1162 Rossi and Prefumo First-Trimester Ultrasonography OBSTETRICS & GYNECOLOGY

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was higher after echocardiography (118/224 [53%])than complete ultrasonography (83/194 [43%];P 5.040), but the use of Doppler did not improvethe accuracy (Doppler: 109/210 [52%] compared withno Doppler: 92/208 [44%]; P 5.11).

In 748 of 996 (75%) malformed fetuses, it wasspecified if malformations were isolated or multiple.The former occurred in 670 of 748 (89%) fetuses and

the latter were described in 78 of 748 (11%) fetuses.Detection rates of isolated and multiple malforma-tions were 293 of 670 (44%) and 47 of 78 (60%),respectively (P 5.005).

Of the 996 malformed fetuses, 181 (18%) pre-sented risk factors for fetal structural anomalies and815 (82%) were unselected. The detection rate of fetalmalformations by 11–14 weeks of gestation ultraso-nography was higher in women at high risk (118/181 [65%]) than an unselected population (404/815[50%]; P ,.001).

The ultrasound technique was transabdominal in

694 (71%), transvaginal in 131 (13%), and combined in150 (16%) cases (unreported in 21 women; 2%). Thehighest detection rate was higher combining the twotechniques (93/150 [62%]) than either transabdominal

Table 1. Risk of Bias Regarding Patient Selection

Reference Patient Selection Index Test Reference Standard Flow and Timing

Souka 2001 High Low Low UnclearMcAuliffe 2005* Low Low Low LowTaipale 2003 Low Low Low UnclearAbu-Rustum 2010 Low Low Low UnclearChen 2004 Unclear Low Unclear Low

Cane 2007 Low Low Unclear UnclearEbrashy 2010 Low Low High UnclearOztekin 2009 Low Low Low LowSyngelaki 2011 Low Low Low LowRustico 2000 Low Low Low LowHuggon 2000 High Low Low HighBecker 2006 Low Low Low LowHaak 2002 High Low Low LowLombardi 2007 Low Low Low LowLopes 2003 High Low Low LowMcAuliffe 2005† High Low Low LowSimpson 2000 High Low Low LowSmreck 2006 Unclear Low Low LowCedergren 2006 Low Unclear Low Low

* Reference 20.† Reference 27.

B A

Q u a l i t y A s s e s s m e n t o f D

i a g n o s t i c A c c u r a c y

S t u d i e s – 2 d o m a i n

Flow and timing

Reference standard

Index test

Patient selection

0 20 40 60 80 100Proportion of studies with low, high, or unclear

risk of bias (%)

Low

Proportion of studies with low, high, or unclear

concerns regarding applicability (percent)

60 80 100

Reference standard

Index test

Patient selection

Low High Unclear

High Unclear

Fig. 2. Flow and timing domain of bias. A. Proportion of studies with low, high, or unclear risk of bias. B. Proportion of studies with low, high, or unclear concerns regarding applicability.

Rossi. First-Trimester Ultrasonography. Obstet Gynecol 2013.


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(353/694 [51%]) or transvaginal ultrasonography (44/131 [34%]; P ,.001).

The detection rate increased from 11 to 14 weeksof gestation at diagnosis (Fig. 3).

CONCLUSIONThis review shows that ultrasound examination from11 to 14 weeks of gestation can detect approximatelyhalf of fetal malformations. In addition, all but two

cases of cystic hygroma were identified. In contrast,anomalies of the face were less likely to be determined(34%). Anomalies of kidneys and bladder wereresponsible for the highest interstudy variability,because the detection rate ranged widely acrossstudies from 0% to 100%. Our review calculated that congenital heart defects were the most commonanomalies in the study population and detected inthe first trimester in 45% of affected fetuses. Of note,the assessment of fetal heart by targeted echocardiog-raphy was more accurate (53%) than by complete

ultrasonography (43%) for the detection of cardiacabnormalities. It may be speculated that when atten-tion and concentration from the operator are focusedon the fetal heart rather than the whole anatomy, theaccuracy of early echocardiography is enhanced. Inaddition, the use of Doppler examination did not improve the detection of congenital heart defects.

The natural history of fetal malformations playsa very important role in the diagnosis of fetal structural

anomalies with early ultrasonography, because themanifestation of structural defects in the second tri-mester represents an important limitation of earlyultrasonography. For instance, the diagnosis of hydro-cephalus in the first trimester is very unlikely as a result of the physiologically large proportions of the lateralventricles to the calvarium. Similarly, indirect signs of spina bifida such as the lemon sign, effaced cisterna magna, and small cerebellum have been described asuseful markers in the evaluation of spinal defects.31

However, because these cranial signs are not visible

Table 2. Characteristics of Each Study

First Author YearStudy

PopulationType of

ExaminationSample

SizeGestational Age at

Ultrasonography (wk)*UltrasoundTechnique

AdditionalExamination

Rustico 2000 Unselected Echocardiography 4,785 13–14 Transvaginal Not performedSimpson 2000 High risk Echocardiography 211 12–14 NA Not performedHaak 2002 High risk Echocardiography 37 12.5 (11–14) Transvaginal Not performedHuggon 2003 High risk Echocardiography 227 12 (10–13) Transabdominal Transvaginal

Lopes 2003 High risk Echocardiography 275 11–14 Transvaginal TransvaginalChen 2004 High risk Complete

anatomy survey1,609 13.4 (12–14) Transabdominal Transvaginal

Taipale 2004 Unselected Completeanatomy survey

4,789 13–14 Transvaginal Transabdominal

McAuliffe 2005 High risk Echocardiography 144 13.5 (11–16) Transabdominal TransvaginalMcAuliffe 2005 Unselected Complete

anatomy survey300 11–14 Transabdominal Transvaginal

Smreck 2006 Unselected Echocardiography 2,165 11–13 Transvaginal+transabdominal

Not performed

Cedergren 2006 Unselected Completeanatomy survey

2,708 11–14 Transabdominal Not performed

Souka 2006 Unselected Completeanatomy survey

1,148 11–14 Transvaginal+transabdominal

Not performed

Becker 2006 Unselected Completeanatomy survey


Not performed

Lombardi 2007 Unselected Echocardiography 627 12.6 (12–13) Transabdominal Not performedDane 2007 Unselected Complete

anatomy survey1,290 12 (11–14) Transvaginal

+transabdominalNot performed

Oztekin 2009 Unselected Completeanatomy survey

1,085 11–14 NA NA

Ebrashy 2010 Unselected completeanatomy survey


Not performed

Syngelaki 2011 Unselected completeanatomy survey

44,859 11–13 Transabdominal Transvaginal

Abu-Rustum 2010 Unselected Completeanatomy survey

1,370 11–13 Transabdominal Transvaginal

* Data are range or median (range).N/A, not available.


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in the first trimester, the sensitivity of detection of spina bifida with early ultrasonography is unlikely to be ashigh as in the second trimester. In addition, a normalappearance of cardiac anatomy at any time of preg-nancy does not exclude heart defects that may developwith advancing gestational age and can be detected

later in pregnancy or even postnatally.

29

In a very largerandomized study, Saltvedt et al7 reported that theantenatal detection rate of major fetal malformationsat 12–14 weeks of gestation was lower than the detec-

tion rate at 15–22 weeks of gestation (38% and 47%,respectively). Similarly, Westin et al32 observed that theidentification of cardiac defects was similar betweenearly and late ultrasonography (11% and 15%, respec-tively), although this report was affected by very low sensitivity. In the series of McAuliffe et al,20 a completeanatomy survey was successful in only 33% of fetuses

undergoing early ultrasonography. On the other hand,early ultrasound screening might be more accuratethan second-trimester ultrasonography for the detec-tion of fetal anomalies associated with oligohydramniosor anhydramnios, resulting in poor examination of fetalanatomy. From approximately 1,000 malformed fe-tuses, we were able to identify what the fetal malforma-tions are that are more easily diagnosed by earlyultrasonography, because their detection rate is 100%and which ones that could be diagnosed (detection rategreater than 50%). In this review, there are defects that can be seen with high sensitivity (approaching 100%),

medium (detection between 50% and 100%), and low sensitivity (less than 50%). As well, some anomalies arenot detected before 14 weeks of gestation.

The accuracy of early ultrasonography can becompromised by the transient or embryologic find-ings that resolve spontaneously throughout gestation.For example, midgut rotation is a physiologic finding up to 13 weeks of gestation, small ventricular defectscommonly undergo spontaneous closure during intra-uterine life,33 and hydronephrosis is regarded as tran-sient anomaly in the first trimester.34–36 Patientsshould be counselled that in some cases, the early

diagnosis of most fetal malformations needs furtherconfirmation in a later gestational period.

According to our review, the presence of associ-ated anomalies appears to increase the accuracy of early ultrasonography, because early detection of fetalanomalies increased from 44% in fetuses with isolatedmalformations to 60% when fetuses were affected withmultiple anomalies. This finding obviously indicatesthat an isolated defect can be missed easier thanmultiple defects.

We also found that the presence of maternal risk

factors for fetal structural abnormalities may influencethe accuracy of early ultrasound examination. Inparticular, we obtained a sensitivity of 65% in womenat high risk and 50% in low-risk women. Noteworthy,in the reviewed articles, the operators were not blinded to the presence or absence of risk factors forfetal anomalies. Therefore, the awareness of theultrasonographer is higher when the a priori proba-bility for anomalies is high. Transvaginal ultrasonog-raphy has the advantage of higher resolution and isgenerally more useful for women with high body mass

Box 1. Detection Rate of Fetal Malformations inthe First Trimester

100% detection rateAcrania, anencephaly, ectopia cordis, encephalocele

50–99% detection rateCystic hygroma, double-outlet right ventricular flow,

Fallot, gastroschisis, omphalocele, holoprosencephaly,hypoplastic left heart syndrome, limb reduction, mega-cystis, polydactyly, septal defects, transposition of greatvessels, valvular disease

1–49% detection rateSpina bifida, hydrocephalus, skeletal dysplasia, facial

cleft, Dandy-Walker, aortic coarctation, arthrogryposis

0% detection rateCorpus callosum agenesia, bladder exstrophy, con-

genital cyst adenomatoid malformation, cerebellar

hypoplasia, duodenal atresia, hydronephrosis, renalagenesia, duplex kidneys, bowel obstruction, extra-lobar sequestration

100

90

80

70

60

50

40

30

20

10

011 12 13 14

F r e q

u e n c y ( % )

Gestational age (weeks)

Fig. 3. Detection rates from 11–14 weeks of gestation.

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indexes as compared with transabdominal ultrasonog-raphy. The use of transvaginal technique also in-creases the successful examination of the fetalanatomy from 72% to 86% of cases and allows bettervisualization of the face, kidneys, and bladder.37 Forthe four-chamber and three-vessel view, the additionof transvaginal approach enhances successful evalua-

tion rates by approximately 5%.

37

However, thereduced probe flexibility in obtaining different scan-ning plans limits the accuracy of transvaginal ultraso-nography.15 Our review shows that a combination of both of the approaches may improve the visualizationof fetal anatomy compared with either technique.

Gestational age at the time of examination couldbe helpful in the choice of the ultrasound technique.Smreck et al38 reported that transvaginal echocardiog-raphy was superior to the transabdominal routebetween 10 and 13 weeks of gestation, both methodswere similar to each other at 14 weeks of gestation,

and the transabdominal echocardiography was moreaccurate than the transvaginal approach at 15 weeksof gestation. We observed a trend for improved detec-tion rate by time, although this increment did not reach a significant difference.

Caution should be exerted in interpreting ourresults. Different protocols, various definitions of “major” and “minor” malformations, different opera-tors’ skills, local differences in the prevalence of var-ious conditions, and differences in follow-up timemight have contributed to interstudy heterogeneity.In our opinion, standard criteria should be established

to optimize the accuracy of early ultrasonography fordetecting fetal malformations. We were also unable tofind data concerning interobserver variability, whichmay represent an important factor to assess sensitivityof early ultrasonography in the diagnosis of some de-fects such as small interventricular defects and dispro-portion of the cardiac chambers. Finally, we did not find studies about maternal anxiety when fetal malfor-mations are suspected in the first trimester but requireconfirmation in the second trimester.

In conclusion, detailed examination of fetal anat-

omy during the routine 11–

14 weeks of gestation scancan provide a comprehensive assessment of fetal anat-omy and can detect approximately half of major struc-tural defects in both low- and high-risk pregnancies.Detection rate markedly increases at 13–14 weeks of gestation compared with 11 weeks of gestation. How-ever, because of the late development of some organsystems and the delayed onset of a significant numberof major anomalies in the second and third trimester,it is very unlikely that the early scan may replacesecond-trimester ultrasonography.

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