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Down syndrome screening in the

United States in 2001 and 2007: a
survey of maternal-fetal medicine
specialists
Peter Benn
American Journal of Obstetrics and Gynecology

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Research www. AJOG.org

GENETICS
Down syndrome screening in the United States in 2001
and 2007: a survey of maternal-fetal medicine specialists
Yu Ming Victor Fang, MD; Peter Benn, DSc; Winston Campbell, MD;
Jay Bolnick, MD; Anne Marie Prabulos, MD; James F. X. Egan, MD

OBJECTIVE: The purpose of this study was to determine changes in
screening and performance of invasive diagnostic procedures for
Down syndrome between 2001 and 2007.
STUDY DESIGN: The Society for Maternal-Fetal Medicine members
completed a survey in 2007 regarding screening tests and diagnostic
procedures for Down syndrome. With the use of descriptive statistics,
the ␹2 test, and the Student t test, responses from 2007 were compared
with responses from a similar 2001 survey.
RESULTS: Performance of first-trimester screening more than doubled
from 2001-2007 (43.1% in 2001, 97.3% in 2007; P ⬍ .0001). Be-
tween 2001 and 2007, the use of the quad screen increased 10-fold
(8.5% in 2001, 85.6% in 2007; P ⬍ .0001). There was an estimated
20% decrease in invasive diagnostic procedures that were performed
in risk-positive women (53.7% in 2001, 34.2% in 2007; P ⬍ .0001).
In 2007, the average fetal loss rates that were quoted by maternal-fetal
medicine specialists after chorionic villous sampling was 1:160 and
after an amniocentesis was 1:493.
CONCLUSION: Down syndrome screening evolved from 2001-2007,
with an increasing emphasis on first-trimester screening. With more
efficacious screening, the number of invasive procedures has declined.
Key words: amniocentesis, chorionic villous sampling, Down
syndrome, first-trimester screening, quad screen

Cite this article as: Fang YMV, Benn P, Campbell W, et al. Down syndrome screening in the United States in 2001 and 2007: a survey of maternal-fetal medicine
specialists. Am J Obstet Gynecol 2009;201:97.e1-5.

O ver the past decade, dramatic ad-

vances have been made in Down
syndrome screening. The addition of
inhibin-A to the triple screen (quad
screen) has improved the efficacy of
the second-trimester serum screen.1,2
Increasingly, second-trimester ultra-
sound scans have been used to detect
major anomalies and minor markers
that are associated with Down syn-
From the Division of Maternal-Fetal
Medicine, Department of Obstetrics and
Gynecology (Drs Fang, Campbell, Bolnick,
Prabulos, and Egan), and the Department of
Genetics and Developmental Biology (Dr
Benn), University of Connecticut School of
Medicine, Farmington, CT.
Presented at the 28th Annual Meeting of the
Society for Maternal–Fetal Medicine, Dallas,
TX, Jan. 28-Feb. 2, 2008.
Received Oct. 22, 2008; revised Dec. 20,
2008; accepted Feb. 26, 2009.
Reprints not available from the authors.
Authorship and contribution to the manuscript
is limited to the 6 authors indicated. There was
no outside funding or technical assistance with
the production of this article.
0002-9378/$36.00
© 2009 Mosby, Inc. All rights reserved.
doi: 10.1016/j.ajog.2009.02.029
drome to modify a woman’s a priori
risk on the basis of her age and/or se-
rum screen.3 Screening with nuchal
translucency (NT) measurement and
pregnancy-associated plasma protein
A (PAPP-A) levels and human chori-
onic gonadotropin levels have been
validated.2,4,5 First- and second-tri-
mester integrated or stepwise sequen-
tial tests have a higher sensitivity and
lower false-positive rate when com-
pared with any screening test per-
formed in either the first or second tri-
mester alone.2
Women today have more options for
Down syndrome screening than ever be-
fore, and the specific screening tests and
diagnostic procedures continue to
evolve. The objective of our study there-
fore was to determine what changes have
occurred in the first- and second-trimes-
ter Down syndrome screening practices
of the members of the Society for Mater-
nal-Fetal Medicine (SMFM) in the
United States between 2001 and 2007.
The specific loss rates that were quoted
to patients and risk thresholds that
were used in screening, along with
practice patterns for the performance
of invasive diagnostic procedures, were
also assessed.
M ATERIALS AND M ETHODS
In April 2007, a single mailing of a survey
of first- and second-trimester screening
practice patterns for the antenatal diag-
nosis of Down syndrome was sent to
1756 members of the SMFM in the
United States. The name and address of
each member was obtained from a pur-
chased mailing list through the SMFM.
This survey was a revised and updated
version of a similar survey that was sent
in 2001.3 Respondents were asked to
complete the survey and return their
completed anonymous responses in an
enclosed, stamped envelope. The survey
asked a total of 29 questions: 2 questions
were related to practice demographics; 8
questions inquired about the perfor-
mance, certification, and practice pat-
terns regarding first-trimester screening;
1 question queried first- and second-tri-
mester screening strategies; 2 questions
concerned second-trimester serum
screens; 7 questions asked about practice
patterns, specific markers that were used,
and risk modification after a second-tri-
mester ultrasound evaluation; and 9
questions related to practice patterns
and patient counseling about invasive
diagnostic procedures. The first- and
second-trimester screening strategies

JULY 2009 American Journal of Obstetrics & Gynecology 97.e1

Research Genetics www.AJOG.org

certain cutoff values from first-trimester est increase in the percentage of respon-
TABLE 1 test. The criteria for offering an invasive dents from private practice group prac-
Practice settings of respondentsa diagnostic test and the specific preg- tices (15.8% in 2001, 22.8% in 2007; P ⫽
Practice nancy loss rates that were quoted after an .03). The practice settings of respondents
setting 2001 (%)b 2007 (%)c invasive test were derived from ques- from both years are listed in Table 1.
University tions in which the respondents were In 2007, 100% of maternal-fetal med-
..................................................................................................
Group 46.8 45.1 given several specific numeric estimates icine specialists in the United States who
..................................................................................................
and asked to choose the one they use. If responded replied that they screened for
Solo 3.4 2.0
........................................................................................................... their estimate was not represented Down syndrome, compared with 97.5%
Community among the choices, they were directed to in 2001 (P ⬍ .0001). The number of re-
..................................................................................................
Group 23.7 18.0 write in their specific numeric response. spondents who performed first-trimes-
..................................................................................................
Solo 3.6 4.5 A copy of the 2007 survey is available in a ter screening more than doubled from
...........................................................................................................
companion article.6 Survey responses 43.1% in 2001 to 97.3% in 2007 (P ⬍
Private practice
.................................................................................................. were closed in July 2007. The responses .0001; Table 2). Specialists who used NT
Group 15.8 22.8 from 2007 were compared with the re- measurement as part of first-trimester
..................................................................................................
Solo 6.8 7.7 sponses from the 2001 survey with the screening doubled (48.5% in 2001,
...........................................................................................................
a
P ⫽ .03; b n ⫽ 532/1638; c n ⫽ 444/1756. use of the ␹2 test for categoric variables, 96.6% in 2007; P ⬍ .0001); specialists
Fang. Down syndrome screening: 2001 and 2007. and the Student t test for continuous who used human chorionic gonadotro-
Am J Obstet Gynecol 2009.
variables. For questions that were not pin and PAPP-A serum analytes in first-
asked in the 2001 survey, descriptive sta- trimester screening more than tripled
were defined as combined screening: tistics are reported. Because some re- from 2001-2007 (27.9% in 2001, 94.9%
first-trimester NT, PAPP-A, and beta spondents did not answer all questions, in 2007; P ⬍ .0001).
human chorionic gonadotropin; no sec- the denominator for each question in ei- The use of nasal bone in the modifica-
ond-trimester screen. For stepwise se- ther year was based on the number of tion of risk for Down syndrome was not
quential screening, the results were given responses to that question. Institutional assessed in our 2001 survey. In 2007, 235
immediately after first-trimester testing; review board approval was obtained for of 445 respondents (52.8%) reported
the final risk was then calculated from this study. that they used absent or decreased nasal
first- and second-trimester results. For bone measurements in either the first or
integrated screening, the single risk was second trimester for modification of
given after first- and second-trimester R ESULTS Down syndrome risk. Of these 235 re-
screens were combined; first-trimester A total of 991 responses from 2001 and spondents, 25.1% reported using absent
results were not revealed. For indepen- 2007 were received from 46 states, Wash- nasal bone in the first trimester; 27.2%
dent screening, the first- and second-tri- ington, DC, Puerto Rico, and the Virgin reported using decreased nasal bone
mester risks were evaluated indepen- Islands. Of these, 543 of 1638 responses length measurements in the second tri-
dently and not combined. For (32%) were from 2001, and 448 of 1756 mester, and 47.7% reported that they
contingency screening, invasive testing responses (26%) were from 2007. Signif- used absent or decreased nasal bone in
was offered; no further testing was done, icant changes were noted in the practice both the first and second trimesters for
or second-trimester screen was based on settings from 2001-2007, with the great- modification of Down syndrome risk.
In 2007, of the specialists who per-
TABLE 2 formed first-trimester NT screening, 330
First-trimester screening of 422 specialists (78.2%) replied that
they were certified to perform this mea-
Variable 2001 (%)a 2007 (%)b P value surement. Of those who were certified,
Perform first-trimester screen 43.1 97.3 ⬍ .0001 322 specialists (97.9%) had taken an NT
..............................................................................................................................................................................................................................................
Use pregnancy-associated plasma protein 27.9 c
94.9 ⬍ .0001 certification course. One hundred eleven
A and human chorionic gonadotropin of the members (34%) were certified
serum analytes in first-trimester screens through the SMFM; 143 respondents
..............................................................................................................................................................................................................................................
Ultrasound findings used in first trimester (43.7%) were certified through the Fetal
for screening Medicine Foundation; 69 respondents
.....................................................................................................................................................................................................................................
Nuchal translucency 48.5 96.6 ⬍ .0001 (21%) were certified through both, and 4
.....................................................................................................................................................................................................................................
Anomalies 23.6 50.0 ⬍ .0001 respondents (1.3%) were certified
.....................................................................................................................................................................................................................................
through other agencies. Of those who
Biometry (crown rump length) 14 41.3 ⬍ .0001
.............................................................................................................................................................................................................................................. were certified, 305 specialists (93.8%) re-
a
n ⫽ 543; b n ⫽ 448; c For use of pregnancy-associated plasma protein A and human chorionic gonadotropin serum sponded that their practice participated
analytes in first-trimester screens: n ⫽ 537.
Fang. Down syndrome screening: 2001 and 2007. Am J Obstet Gynecol 2009.
in continued quality assurance for NT
scans.

97.e2 American Journal of Obstetrics & Gynecology JULY 2009

www.AJOG.org Genetics Research

Tables 3 and 4 list changes in the use

of second-trimester Down syndrome TABLE 3
screening tests from 2001-2007 and the Second-trimester screening modalities
various Down syndrome screening strat- Variable 2001 (%)a 2007 (%)b P value
egies that were used in 2007. The use of Type of second-trimester analyte used ⬍ .0001
.....................................................................................................................................................................................................................................
the quad screen had increased 10-fold Maternal serum alpha-fetal protein only 3.6 0.9
during this time period (8.5% in 2001, .....................................................................................................................................................................................................................................
Triple screen 73.6 10.3
85.6% in 2007; P ⬍ .0001). There were .....................................................................................................................................................................................................................................

significant increases in the rates of spe- Quad screen 8.5 85.6

..............................................................................................................................................................................................................................................
cialists who screened for Down syn- Screen with second-trimester ultrasound 91.5 98.2 ⬍ .0001
drome with a second-trimester ultra- findings
..............................................................................................................................................................................................................................................
sound scan (91.5% in 2001, 98.2% in Use of second-trimester ultrasound findings 65.9 85.1 ⬍ .0001
2007; P ⬍ .0001) and those who used a to adjust Down syndrome risk
..............................................................................................................................................................................................................................................
second-trimester ultrasound scan to ad- Average risk reduction for “normal” 49.6 c
51.5 c
NS
just a woman’s a priori Down syndrome ultrasound findings
..............................................................................................................................................................................................................................................
risk based on her age and/or her serum NS, not significant.
screen (65.9% in 2001, 85.1% in 2007; P a
n ⫽ 543; b n ⫽ 443; c n ⫽ 277 for 2001; 341 for 2007.
⬍ .0001). The frequency of use of spe- Fang. Down syndrome screening: 2001 and 2007. Am J Obstet Gynecol 2009.
cific second-trimester ultrasound mark-
ers that were used in the modification of
nosis of fetal aneuploidy (Table 5). would not terminate. A comparable
Down syndrome risk was reported pre-
Reasons that were chosen by the respon- number of specialists in both surveys re-
viously in a companion article.6 The av-
dents for the perceived decline in inva- plied that they would perform a midtri-
erage risk reduction after a “normal” sec-
sive testing are listed in Table 6. If the mester amniocentesis for definitive diag-
ond-trimester sonogram remained at
reason for the perceived decline was not nosis in low-risk women because of
approximately 50% in both years (Table
one of the choices in the survey, many maternal anxiety (Table 5).
3: P ⫽ not significant).
respondents filled in “other” reasons In 2007, 60.7% of the specialists re-
In 2007, SMFM members in the
that they believed contributed to the de- plied that their risk threshold for offering
United States used many different types
cline in invasive procedures. Foremost a CVS in the first trimester was a Down
of first- and second-trimester screening
among the “other” reasons for avoiding syndrome risk of 1:270 (n ⫽ 359; range,
strategies, with combined testing being
invasive procedures were (1) an increas- 1:50-1:360). The risk threshold for offer-
the most commonly used protocol (Ta-
ing acceptance of children with Down ing a CVS was not assessed in the 2001
ble 4). More than one type of Down syn-
syndrome, (2) the introduction of first- survey. In 2001, 77.8% of respondents
drome screening strategy was used by
trimester screening, (3) a more conser- used a risk of 1:270 (n ⫽ 517; range,
30.4% of the respondents.
vative population, (4) religious beliefs, 1:190-1:350) for offering a genetic am-
In 2007, 183 of 445 respondents
(5) infertile patients, (6) the false-posi- niocentesis; in 2007, 77.7% of respon-
(41.1%) stated that over the previous 5
tive rate of testing, and (7) patients who dents used a risk of 1:270 (n ⫽ 395;
years, they believed that the number of
chorionic villous sampling (CVS) that
was performed in their practice in- TABLE 4
creased; 257 of 445 respondents (57.7%) Types of first- and second-trimester screening strategies used in 2007
replied that the number of genetic am- Screening strategy Respondents who used screening (%)a
niocenteses that was performed in their b
Combined 56.0
practice declined. In 2007, respondents ..............................................................................................................................................................................................................................................
c
estimated that an average of 34.2% of Stepwise sequential 29.0
..............................................................................................................................................................................................................................................
d
screen-positive women in the first tri- Integrated 22.3
..............................................................................................................................................................................................................................................
mester chose CVS and that approxi- Independent e
13.6
..............................................................................................................................................................................................................................................
mately 42.8% of screen-positive women f
Contingency 11.8
in the second trimester chose an amnio- ..............................................................................................................................................................................................................................................

centesis. A follow-up question revealed Other 8.3

that, despite the increase in CVS, mater-
nal-fetal medicine specialists believed
that there was an estimated 20% decline
(53.7% in 2001, 34.2% in 2007; P ⬍
.0001) in the overall number of risk-pos-
itive women who would choose to un-
dergo an invasive test for definitive diag-
..............................................................................................................................................................................................................................................
None 4.7
..............................................................................................................................................................................................................................................
a
Some respondents used multiple screening strategies; therefore the total percentage is ⬎ 100% (n ⫽ 448); b First-trimester
nuchal translucency, pregnancy-associated plasma protein A, beta human chorionic gonadotropin; no second-trimester
screen; c Results given immediately after first-trimester test; the final risk is then calculated from first- and second-trimester
results; d Single risk given after first- and second-trimester screens are combined; first-trimester results are not revealed;
e
First- and second-trimester risks are evaluated independently and not combined; f Offer invasive testing, no further testing,
or second-trimester screen based on certain cutoff values from first-trimester test.
Fang. Down syndrome screening: 2001 and 2007. Am J Obstet Gynecol 2009.

JULY 2009 American Journal of Obstetrics & Gynecology 97.e3

Research Genetics www.AJOG.org

TABLE 5
Frequency of use and quoted risk of invasive procedures
Variable 2001 2007 P value
Overall estimate of risk-positive women who chose a 53.7% (n ⫽ 522) 34.2% (n ⫽ 404) ⬍ .0001
definitive test
................................................................................................................................................................................................................................................................................................................................................................................
Mean pregnancy loss rate quoted
.......................................................................................................................................................................................................................................................................................................................................................................
Chorionic villous sampling
..............................................................................................................................................................................................................................................................................................................................................................
Mean ⫾ SD N/A 1:160 ⫾ 122 N/A
..............................................................................................................................................................................................................................................................................................................................................................
Median N/A 1:100 N/A
.......................................................................................................................................................................................................................................................................................................................................................................
Amniocentesis
..............................................................................................................................................................................................................................................................................................................................................................
Mean ⫾ SD 1:243 ⫾ 82.9 1:493 ⫾ 460 ⬍ .0001
..............................................................................................................................................................................................................................................................................................................................................................
Median 1:200 1:300 ⬍ .0001
................................................................................................................................................................................................................................................................................................................................................................................
Would perform an amniocentesis in a low-risk 91.9% (n ⫽ 543) 93% (n ⫽ 442) NS
woman for anxiety
................................................................................................................................................................................................................................................................................................................................................................................
N/A, not applicable; NS, not significant SD, standard deviation.
Fang. Down syndrome screening: 2001 and 2007. Am J Obstet Gynecol 2009.

range, 1:190-1:1600). In 2007, the aver- tween 2001 and 2007 (Table 2). This sig- combination of ultrasonographic and
age procedure-related loss rate that was nificant increase is most likely caused by biochemical markers in the second tri-
quoted by maternal-fetal medicine the results of recent studies that indicate mester improves Down syndrome
members after a CVS procedure was that first-trimester screening has an effi- screening performance, when compared
1:160 (range, 1:50-1:1600). The average cacy that is comparable to screening in with either ultrasonography or second-
pregnancy loss rate after a CVS proce- the second trimester, while providing the trimester serum markers alone.7
dure was not assessed in the 2001 survey. patient with the potential for earlier di- Our study highlights the fact that
The mean quoted pregnancy loss rate af- agnosis and safer treatment options.2,4,5 SMFM members in the United States use
ter an amniocentesis was cut in half from Our results also indicate that the quad a wide variety of first- and second-tri-
1:243 in 2001 to1:493 in 2007 (P ⬍ .0001; screen has now replaced the triple screen mester strategies for Down syndrome
Table 5). as the second-trimester serum test of screening (Table 4). A single screening
choice. The quad screen has a higher sen- strategy has not been generally adopted.
C OMMENT sitivity and a lower false-positive rate for The wide variation in screening methods
Our study documents the significant the detection of Down syndrome, com- is also noted in the use of the “genetic
changes that have occurred in Down pared with the triple screen.2 Significant sonogram” in the second trimester. Use
syndrome screening practices among increases were also noted in the number of the genetic sonogram as a screening
maternal-fetal medicine specialists in the of specialists who would screen for tool increased from 77.9% in 2001 to
United States between 2001 and 2007. Down syndrome using a second-trimes- 88.3% in 2007, but the use of specific
Our results indicate that, in 2007, all ma- ter ultrasound scan (genetic sonogram) markers (such as cardiac defects, nuchal
ternal-fetal medicine specialists screened and in the number who would adjust a fold thickness, major anomalies, echo-
for Down syndrome. The percentage of woman’s Down syndrome risk on the genic bowel, shortened long bones, pyel-
respondents who performed first-tri- basis of the sonographic findings.6 This ectasis, ventriculomegaly, intracardiac
mester screening more than doubled be- trend will most likely continue as the echogenic focus, and nasal bone) re-
mains variable.6 The use of an assort-
TABLE 6 ment of strategies with varied nomencla-
Reasons for the decline in invasive testing from 2001-2007 ture and markers makes it difficult for
clinicians to interpret these tests and for
Reason 2001 (%) 2007 (%) P value
patient counseling. Ball et al8 have sug-
Younger or older patients 8.1 4.0 ⬍ .007
.............................................................................................................................................................................................................................................. gested a cohesive national strategy re-
Serum screening 22.3 40.2 ⬍ .0001 garding prenatal diagnosis and screening
..............................................................................................................................................................................................................................................
Genetic sonogram 38.3 33.5 NS for Down syndrome. A more uniform
..............................................................................................................................................................................................................................................
Other 7.6 9.6 NS strategy for screening that would be used
.............................................................................................................................................................................................................................................. by most clinicians would simplify the
NS, not significant.
Fang. Down syndrome screening: 2001 and 2007. Am J Obstet Gynecol 2009.
screening process, would make the re-
sults easier to interpret, and could make

97.e4 American Journal of Obstetrics & Gynecology JULY 2009

www.AJOG.org
screening more acceptable to both phy-
sicians and patients.
With the introduction of first-trimes-
ter NT screening, the American College
of Obstetricians and Gynecologists has
recommended specific training and on-
going quality assessment to achieve opti-
mal NT measurement for Down syn-
drome risk assessment.9 Our study
indicates that most maternal-fetal medi-
cine specialists in the United States who
perform first-trimester NT screening are
certified and that most practices that
perform first-trimester NT screening
participate in continuous quality assur-
ance. Proper training and continued
monitoring of quality control should re-
sult in the most efficacious Down syn-
drome screening process.
As the sensitivity of screening tests in-
creases and the false-positive rate de-
clines, most of our respondents believed
that over the past 5 years, the overall
number of invasive diagnostic proce-
dures that were performed in their prac-
tice has decreased. This finding is consis-
tent with those of Benn et al,10 who
documented a 50% reduction in invasive
testing in northern Connecticut from
1870 tests in 1990 to 878 tests in 2002,
despite an increase in the percentage of
advanced maternal age from 12.5% in
1990 to 21.7% in 2002. Although the am-
niocentesis rate was reduced by ⬎ 50%,
the antenatal detection of Down syn-
drome remained at approximately 49%
throughout the study, with a nonsignifi-
cant increase in detection.10 Although
improved screening explains some of
this decline, patient autonomy also ap-
pears to play a role.
With the introduction of first-trimes-
ter screening, the number of CVS proce-
dures that are performed has increased.
The increasing emphasis on first-trimes-
ter screening may further increase the
demand for CVS in the coming years.
Currently, only a limited number of ma-
ternal-fetal medicine fellowship pro-
grams in the United States provide ap-
propriate training for the performance
of CVS.11 Appropriate training for the
performance of this procedure may need
to be expanded to meet this growing
demand.
Recent studies that have examined
the pregnancy loss rates after CVS and
amniocentesis that was performed un-
der continuous ultrasound guidance
have challenged the traditionally
quoted fetal loss rate of 1.0% for CVS
and 0.5% for amniocentesis.12,13 Our
study indicates that, in 2007, the aver-
age fetal loss rate that was quoted by
SMFM members after a CVS or an am-
niocentesis is lower than the tradition-
ally quoted risk (Table 5). A recent
study at a single institution found that
the loss rates for both CVS and amnio-
centesis decreased over time,12 which
suggests that the fetal loss rate that is
quoted should be institution specific or
based on the experience of the physi-
cian who performed the procedure.
Further studies are necessary to clarify
whether the fetal loss rates after a CVS
or an amniocentesis are similar, be-
cause this may influence which proce-
dure a screen-positive patient decides
to undergo.
A limitation of our study was that, al-
though statistically significant differ-
ences were noted when the results from
2001 and 2007 were compared, com-
pleted surveys were received from a mi-
nority of SMFM members. Because this
was an anonymous survey and no iden-
tifiers were included in the survey, we did
not have the ability to track who re-
turned the completed surveys.
Over the past decade, Down syndrome
screening has undergone dramatic
changes. As the newer screening tests are
introduced throughout the United
States, we anticipate an increasing em-
phasis on first-trimester screening and
diagnosis, along with an increasing reli-
ance on ultrasound scanning to identify
fetuses who are at risk for Down
syndrome. f centesis. Obstet Gynecol 2006;108:1067-72.
JULY 2009 American Journal of Obstetrics & Gynecology
Genetics Research
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97.e5