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Sender's message: Quad screen/unexplained afp or HCG
elevation
Comment in:
First- and second-trimester evaluation of
risk for Down syndrome.
Ball
RH, Caughey
AB, Malone
FD, Nyberg
DA, Comstock
CH, Saade
GR, Berkowitz
RL, Gross
SJ, Dugoff
L, Craigo
SD, Timor-Tritsch
IE, Carr
SR, Wolfe
HM, Emig
D, D'Alton
ME; First
and Second Trimester Evaluation of Risk (FASTER) Research
Consortium.
Department of Obstetrics, Gynecology, and Reproductive
Sciences, UCSF, San Francisco, CA 94143-0132, USA. fetus@surgery.ucsf.edu
OBJECTIVE: To investigate the differences in costs and
outcomes of Down syndrome screening using data from the First
and Second Trimester Evaluation of Risk (FASTER) Trial.
METHODS: Seven possible screening options for Down syndrome
were compared: 1) Triple Screen-maternal serum alpha
fetoprotein, estriol, and hCG; 2) Quad-maternal serum alpha
fetoprotein, estriol, hCG, and Inhibin A; 3) Combined First-nuchal
translucency, pregnancy-associated plasma protein A (PAPP-A),
free beta-hCG; 4) Integrated-nuchal translucency, PAPP-A, plus
Quad; 5) Serum Integrated-PAPP-A, plus Quad; 6) Stepwise
Sequential-Combined First plus Quad with results given after
each test; and 7) Contingent Sequential-Combined First and
only those with risk between 1:30 and 1:1,500 have Quad
screen. The detection rates for each option were used given a
5% false-positive rate except for Contingent Sequential with a
4.3% false-positive rate. Outcomes included societal costs of
each screening regimen (screening tests, amniocentesis,
management of complications, and cost of care of Down syndrome
live births), Down syndrome fetuses identified and born, the
associated quality-adjusted life years, and the incremental
cost-utility ratio. RESULTS: Based on the screening results
derived from the 38,033 women evaluated in the FASTER trial,
the Contingent Sequential screen dominated (lower costs with
better outcomes) all other screens. For example, the
Contingent Sequential cost 32.3 million dollars whereas the
other screens ranged from 32.8 to 37.5 million dollars. The
Sequential strategy led to the identification of the most Down
syndrome fetuses of all of the screens, but at a higher cost
per Down syndrome case diagnosed ($719,675 compared with
$690,427) as compared with the Contingent Sequential. Because
of the lower overall false-positive rate leading to fewer
procedure-related miscarriages, the Contingent Sequential
resulted in the highest quality-adjusted life years as well.
The Contingent Sequential remained the most cost-effective
option throughout sensitivity analysis of inputs, including
amniocentesis rate after positive screen, rate of therapeutic
abortion after Down syndrome diagnosis, and rate of
procedure-related miscarriages. CONCLUSION: Analysis of this
actual data from the FASTER Trial demonstrates that the
Contingent Sequential test is the most cost-effective. This
information can help shape future policy regarding Down
syndrome screening.
Publication Types:
- Comparative Study
- Evaluation Studies
- Research Support, N.I.H., Extramural
PMID: 17601890 [PubMed - indexed for MEDLINE]
-
Second-trimester prediction of severe
placental complications in women with combined elevations in
alpha-fetoprotein and human chorionic gonadotrophin.
Alkazaleh
F, Chaddha
V, Viero
S, Malik
A, Anastasiades
C, Sroka
H, Chitayat
D, Toi
A, Windrim
RC, Kingdom
JC.
Department of Obstetrics and Gynaecology, Maternal-Fetal
Medicine Division Placenta Clinic, University of Toronto,
Toronto, Ontario, Canada.
OBJECTIVE: The purpose of this study was to determine the
ability of uterine artery Doppler and placental ultrasound to
identify adverse clinical outcomes attributable to severe
placental dysfunction in women with second-trimester
unexplained elevated maternal serum screening of
alpha-fetoprotein and human chorionic gonadotropin. STUDY
DESIGN: Fifty singleton pregnancies with elevated
alpha-fetoprotein (3.5 multiples of median [range 2.1 to
10.5]) and human chorionic gonadotropin (5.3 multiples of
median [range 2.5 to 21.7]) and a normal fetal anatomical
ultrasound were prospectively evaluated with placental
ultrasound and uterine artery Doppler at referral between 19
and 23 weeks' gestation. RESULTS: Abnormalities in both
placental ultrasound and uterine artery Doppler (n = 24)
predicted preterm delivery less than 32 weeks from any cause
(n = 24) (75% sensitivity, 75% positive predictive value;
likelihood ratio positive 3.3 [1.6 to 6.8]), intrauterine
fetal death (n = 12) (100% sensitivity, 50% positive
predictive value; likelihood ratio positive 3.1 [2.0 to 5.0]),
and intrauterine growth restriction with absent/reversed
end-diastolic flow (n = 17) (sensitivity 94%, positive
predictive value 67%, likelihood ratio positive 3.9 [2.0 to
6.2]) . Ischemic-thrombotic pathology was present in 88% of
placentas examined (n = 32). CONCLUSION: Uterine artery
Doppler and placental morphology identified most pregnancies
with combined abnormal maternal serum screening destined to
result in extremely premature delivery and/or perinatal death.
Abnormal maternal serum screening reports could include a
recommendation for placental ultrasound testing when no fetal
explanation has been identified.
PMID: 16522419 [PubMed - indexed for MEDLINE]
-
-
Comment in:
Screening for Down syndrome: practice
patterns and knowledge of obstetricians and gynecologists.
Cleary-Goldman
J, Morgan
MA, Malone
FD, Robinson
JN, D'Alton
ME, Schulkin
J.
Division of Maternal-Fetal Medicine, Columbia University
Medical Center, New York, New York 10032, USA. jec32@columbia.edu
OBJECTIVE: To assess obstetricians' practice patterns and
knowledge regarding screening for Down syndrome. METHODS: A
questionnaire was mailed to 1,105 American College of
Obstetricians and Gynecologists Fellows and Junior Fellows in
2004. RESULTS: Sixty percent of questionnaires were returned.
Statistical analyses were limited to the 532 practicing
obstetricians. Greater than 80% felt their training and
experience qualified them to counsel patients about genetic
issues in pregnancy. However, 45% rated their residency
training regarding prenatal diagnosis as barely adequate or
nonexistent. American College of Obstetricians and
Gynecologists publications were rated by 86% as an important
source of information on genetic counseling. Seventy-eight
percent of practitioners counsel all obstetric patients about
risks for fetal aneuploidy, and 67% provide counseling for
heritable genetic abnormalities. Although the majority (99%)
offer second-trimester Down syndrome screening, only 55% also
offer first-trimester screening for Down syndrome. Almost one
half (49%) use the quad screen, and 6% offer integrated first-
and second-trimester screening. The majority (88%) routinely
offer amniocentesis to patients who are at elevated risk for
genetic abnormalities, whereas 44% also offer chorionic villus
sampling. Few (2%) perform chorionic villus sampling.
CONCLUSION: Most obstetricians manage patients at risk for
fetal genetic abnormalities according to American College of
Obstetricians and Gynecologists educational materials. This
survey identified deficiencies related to Down syndrome
screening, including a limited number of practitioners
performing chorionic villus sampling and physicians' own
perception that training regarding genetic counseling should
be improved. Educational strategies are needed to address
these deficiencies before first-trimester screening programs
are widely implemented. LEVEL OF EVIDENCE: III.
Publication Types:
- Comparative Study
- Research Support, U.S. Gov't, P.H.S.
PMID: 16394034 [PubMed - indexed for MEDLINE]
-
Predicting the result of additional
second-trimester markers from a woman's first-trimester marker
profile: a new concept in Down syndrome screening.
Maymon
R, Cuckle
H, Jones
R, Reish
O, Sharony
R, Herman
A.
Department of Obstetrics and Gynecology, Assaf Harofe Medical
Center, Zerifin and Sackler Faculty of Medicine, Tel Aviv
University, Israel. intposgr@post.tau.ac.il
OBJECTIVE: To describe a method for deciding whether an
individual's first-trimester Down syndrome screening test
result justifies further testing in the second trimester.
METHODS: Statistical modelling was used to estimate the
distribution of second-trimester marker profiles for a given
first-trimester profile and hence the probability of a final
positive result, using a 1 in 250 term cut-off. A multi-variate
log Gaussian model was used with published parameters. Markers
were maternal serum pregnancy-associated plasma protein-A and
free beta-human chorionic gonadotrophin (hCG) at 10 weeks,
nuchal translucency at 11 weeks, and second-trimester maternal
serum alpha-fetoprotein, total hCG, unconjugated estriol and
inhibin-A. To illustrate the method, the model was applied to
a published series of 24 Down syndrome and 367 unaffected
pregnancies. RESULTS: Modelling predicts that for 63% Down
syndrome and 0.4% unaffected pregnancies having
first-trimester tests, there is a 50% or more probability of a
final positive result. A step-wise sequential screening policy
based on immediate prenatal diagnosis for those with high
probability and second-trimester testing for the remainder
would have a 90% detection rate and 1.7% false-positive rate.
Modelling also predicts 8.0% Down syndrome and 89% unaffected
pregnancies with probabilities below 3%. A contingent
screening policy restricting second-trimester testing to those
with 3-49% probabilities would have an 88% detection rate and
1.4% false-positive rate. CONCLUSION: Predicting the
probability of a positive final result from the
first-trimester marker profile has potential utility, either
as a decision aide for individual women or as a formal part of
screening policy in selecting a subset of women for
second-trimester testing. Copyright 2005 John Wiley &
Sons, Ltd
Publication Types:
- Research Support, Non-U.S. Gov't
PMID: 16231324 [PubMed - indexed for MEDLINE]
-
Comment in:
First-trimester or second-trimester
screening, or both, for Down's syndrome.
Malone
FD, Canick
JA, Ball
RH, Nyberg
DA, Comstock
CH, Bukowski
R, Berkowitz
RL, Gross
SJ, Dugoff
L, Craigo
SD, Timor-Tritsch
IE, Carr
SR, Wolfe
HM, Dukes
K, Bianchi
DW, Rudnicka
AR, Hackshaw
AK, Lambert-Messerlian
G, Wald
NJ, D'Alton
ME; First-
and Second-Trimester Evaluation of Risk (FASTER) Research
Consortium.
Columbia University College of Physicians and Surgeons, New
York, USA. fmalone@rcsi.ie
BACKGROUND: It is uncertain how best to screen pregnant women
for the presence of fetal Down's syndrome: to perform
first-trimester screening, to perform second-trimester
screening, or to use strategies incorporating measurements in
both trimesters. METHODS: Women with singleton pregnancies
underwent first-trimester combined screening (measurement of
nuchal translucency, pregnancy-associated plasma protein A [PAPP-A],
and the free beta subunit of human chorionic gonadotropin at
10 weeks 3 days through 13 weeks 6 days of gestation) and
second-trimester quadruple screening (measurement of
alpha-fetoprotein, total human chorionic gonadotropin,
unconjugated estriol, and inhibin A at 15 through 18 weeks of
gestation). We compared the results of stepwise sequential
screening (risk results provided after each test), fully
integrated screening (single risk result provided), and serum
integrated screening (identical to fully integrated screening,
but without nuchal translucency). RESULTS: First-trimester
screening was performed in 38,167 patients; 117 had a fetus
with Down's syndrome. At a 5 percent false positive rate, the
rates of detection of Down's syndrome were as follows: with
first-trimester combined screening, 87 percent, 85 percent,
and 82 percent for measurements performed at 11, 12, and 13
weeks, respectively; with second-trimester quadruple
screening, 81 percent; with stepwise sequential screening, 95
percent; with serum integrated screening, 88 percent; and with
fully integrated screening with first-trimester measurements
performed at 11 weeks, 96 percent. Paired comparisons found
significant differences between the tests, except for the
comparison between serum integrated screening and combined
screening. CONCLUSIONS: First-trimester combined screening at
11 weeks of gestation is better than second-trimester
quadruple screening but at 13 weeks has results similar to
second-trimester quadruple screening. Both stepwise sequential
screening and fully integrated screening have high rates of
detection of Down's syndrome, with low false positive rates.
Copyright 2005 Massachusetts Medical Society.
Publication Types:
- Clinical Trial
- Comparative Study
- Multicenter Study
- Research Support, N.I.H., Extramural
- Research Support, U.S. Gov't, P.H.S.
PMID: 16282175 [PubMed - indexed for MEDLINE]
-
Uterine artery Doppler velocimetry for the
detection of adverse obstetric outcomes in patients with
elevated mid-trimester beta-human chorionic gonadotrophin.
Barkehall-Thomas
A, Wilson
C, Baker
L, ni
Bhuinneain M, Wallace
EM.
Maternal-Fetal Medicine Unit, Monash University Medical
Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia.
a.barkehallthomas@southernhealth.org.au
AIM: The aim of this study is to review the clinical
usefulness of Doppler velocimetry of the uterine artery for
the detection of adverse obstetric outcome in a population of
women with elevated mid-trimester serum beta-human chorionic
gonadotrophin (betahCG). METHODS: Women with an unexplained
elevated mid-trimester betahCG level (> or = 4.0 multiples
of the median) are offered uterine artery Doppler assessment
at 22-24 weeks of gestation. We have audited the clinical
usefulness of this practice by reviewing the prevalence of the
adverse outcomes of gestational hypertension, intrauterine
growth restriction (IUGR) and preterm birth and the predictive
capacity of the test when applied to this subgroup of
high-risk patients. RESULTS: Sixty-two women had an elevated
serum betahCG and underwent Doppler study of uterine artery
flow velocity waveform. Notching afforded better predictive
utility for any outcome than the resistance index alone or in
combination with notching. For a composite adverse outcome of
any or all of gestational hypertension, birthweight < or =
10th centile, and preterm delivery, the presence of a uterine
notch alone had sensitivity of 30.7% and specificity of 93.8%.
For the identification of severe fetal growth restriction
(< 5th centile) and/or preeclampsia, the presence of a
notch offered a sensitivity of 50%, specificity of 96.3%, a
positive likelihood ratio of 13.5, and a negative likelihood
ratio of 0.5. CONCLUSIONS: The identification of uterine
artery notching by means of Doppler ultrasound as a component
of the surveillance of women with unexplained elevated betahCG
levels significantly improves the prediction of preeclampsia
and/or severe IUGR, although the low prevalence of 13% of
these adverse outcomes limits the usefulness of the test in
routine clinical practice.
Publication Types:
PMID: 16026398 [PubMed - indexed for MEDLINE]
-
-
Quad screen as a predictor of adverse
pregnancy outcome.
Dugoff
L, Hobbins
JC, Malone
FD, Vidaver
J, Sullivan
L, Canick
JA, Lambert-Messerlian
GM, Porter
TF, Luthy
DA, Comstock
CH, Saade
G, Eddleman
K, Merkatz
IR, Craigo
SD, Timor-Tritsch
IE, Carr
SR, Wolfe
HM, D'Alton
ME; FASTER
Trial Research Consortium.
Department of Obstetrics and Gynecology, University of
Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Lorraine.Dugoff@uchsc.edu
OBJECTIVE: To estimate the effect of second-trimester levels
of maternal serum alpha-fetoprotein (AFP), human chorionic
gonadotrophin (hCG), unconjugated estriol (uE3), and inhibin A
(the quad screen) on obstetric complications by using a large,
prospectively collected database (the FASTER database).
METHODS: The FASTER trial was a multicenter study that
evaluated first- and second-trimester screening programs for
aneuploidy in women with singleton pregnancies. As part of
this trial, patients had a quad screen drawn at 15-18 6/7
weeks. We analyzed the data to identify associations between
the quad screen markers and preterm birth, intrauterine growth
restriction, preeclampsia, and fetal loss. Our analysis was
performed by evaluating the performance characteristics of
quad screen markers individually and in combination. Crude and
adjusted effects were estimated by multivariable logistic
regression analysis. Patients with fetal anomalies were
excluded from the analysis. RESULTS: We analyzed data from
33,145 pregnancies. We identified numerous associations
between the markers and the adverse outcomes. There was a
relatively low, but often significant, risk of having an
adverse pregnancy complication if a patient had a single
abnormal marker. However, the risk of having an adverse
outcome increased significantly if a patient had 2 or more
abnormal markers. The sensitivity and positive predictive
values using combinations of markers is relatively low,
although superior to using individual markers. CONCLUSION:
These data suggest that components of the quad screen may
prove useful in predicting adverse obstetric outcomes. We also
showed that the total number and specific combinations of
abnormal markers are most useful in predicting the risk of
adverse perinatal outcome.
Publication Types:
- Multicenter Study
- Research Support, N.I.H., Extramural
- Research Support, U.S. Gov't, P.H.S.
PMID: 16055573 [PubMed - indexed for MEDLINE]
-
-
Second trimester serum markers.
Canick
JA, MacRae
AR.
Department of Pathology and Laboratory Medicine, Women and
Infants Hospital, Brown Medical School, Providence, RI 02905,
USA. jcanick@wihri.org
Prenatal screening for Down syndrome in the early second
trimester with multiple maternal serum markers has been
available for more than 15 years. The multiple marker
combination with the highest screening performance currently
available is alpha-fetoprotein (AFP), unconjugated estriol
(uE3), human chorionic gonadotropin (hCG), and inhibin A,
together with maternal age (so-called quad marker test). With
this combination, a detection rate of 80% at a 5% false
positive rate is achieved. Inhibin A, the newest addition to
second trimester serum screening, is an alpha-beta subunit
hormone of placental origin, and is measured using a
monoclonal two-site ELISA validated for use in prenatal
screening. Quality control parameters for inhibin A
measurement are acceptable and are monitored through the
proficiency testing program administered by the College of
American Pathologists. Research into other possible second
trimester screening markers has included studies on the
maternal urine and serum levels of an hCG variant,
hyperglosylated hCG (h-hCG; invasive trophoblast antigen).
Recent data indicate that h-hCG is similar to hCG itself,
although its measurement in maternal urine may improve the
performance of the established serum marker combinations. With
the introduction of first trimester screening markers and
their use in an integrated first and second trimester marker
approach to screening, and with the fact that many women do
not seek prenatal care until the early second trimester,
prenatal screening for Down syndrome using second trimester
serum markers remains a major resource in obstetrical care.
Publication Types:
PMID: 16104669 [PubMed - indexed for MEDLINE]
-
Elevated second-trimester free beta-hCG as
an isolated finding and pregnancy outcomes.
Brajenović-Milić
B, Tislarić
D, Zuvić-Butorac
M, Bacić
J, Petrović
O, Ristić
S, Mimica
M, Kapović
M.
Department of Biology, School of Medicine, University of
Rijeka, Rijeka, Croatia. bojana@mamed.medri.hr
OBJECTIVE: To investigate the relationship between unexplained
elevated second-trimester free beta-human chorionic
gonadotropin (beta-hCG) levels and pregnancy complications as
well as adverse pregnancy outcomes. METHODS: The study cohort
comprised 2,110 non-smoking women with chromosomal and
structurally normal fetuses at low-risk for both Down's
syndrome (risk <1:250) and neural tube defects (maternal
serum alpha-fetoprotein <2.0 MoM). A free beta-hCG value of
> or =2.0 MoM was used to define the populations with
elevated levels of free beta-hCG. Descriptive statistics, chi2
test, Fisher's exact test, and logistic regression analysis
were used for statistical analysis, and p < 0.05 was
considered statistically significant. RESULTS: The mean
maternal age of the study group was significantly lower than
in controls (27.9 +/- 4.3 and 30.6 +/- 5.1 years,
respectively, p < 0.05), while the proportion of
primigravidas was significantly higher compared to that of
controls (p < 0.05). After adjustment of the 2 groups
according to maternal age and parity, we observed an increased
incidence of preeclampsia among women with elevated free beta-hCG
levels in relation to controls (p < 0.05). However, a
logistic regression analysis demonstrated that the free beta-hCG
level was not a predictor of the occurrence of preeclampsia.
No significant relationship was found with the incidence of
gestational diabetes, oligohydramnios, polyhydramnios,
pregnancy-related hypertension, intrauterine growth
retardation, preterm delivery, spontaneous abortion and
stillbirths (p > 0.05). 2004 S. Karger AG, Basel.
PMID: 15539871 [PubMed - indexed for MEDLINE]
-
The C677T methylenetetrahydrofolate
reductase variant and third trimester obstetrical
complications in women with unexplained elevations of maternal
serum alpha-fetoprotein.
Björklund
NK, Evans
JA, Greenberg
CR, Seargeant
LE, Schneider
CE, Chodirker
BN.
Department of Biochemistry & Medical Genetics, University
of Manitoba, Winnipeg, Canada. umbjork1@cc.UManitoba.CA
INTRODUCTION: The C677T MTHFR variant has been associated with
the same third trimester pregnancy complications as seen in
women who have elevations of maternal serum alpha-fetoprotein
(MSAFP). We hypothesized that these women with third trimester
pregnancy complications and MSAFP elevations would have an
increased frequency of the variant compared to an abnormal
study control group (women with MSAFP elevations without
pregnancy complications) as well as to normal population
controls. METHODS: Women who had unexplained elevations of
MSAFP in pregnancy were ascertained retrospectively. The
frequency of the C677T MTHFR variant among those women with
unexplained elevations of MSAFP who had experienced later
pregnancy complications was compared to that of women with
unexplained elevations of MSAFP without complications as well
as to that of the previously established Manitoba frequency.
RESULTS: Women who had complications of pregnancy and an
unexplained MSAFP elevation had a higher allele frequency for
the C677T MTHFR variant (q = 0.36,) compared to women with
MSAFP elevations and normal pregnancy outcomes (q = 0.25, OR
1.73 95% CI 1.25-2.37, p = 0.03). The frequency was also
higher than that of the population controls (q= 0.25, OR 1.70
95% CI 1.11-2.60, p = 0.007). The frequency in women with
MSAFP elevations without pregnancy complications was not
significantly different from that of the population controls
(p = 0.41). CONCLUSION: Women with unexplained elevations of
MSAFP and who experience complications in later pregnancy are
more likely to have one or two alleles of the C677T MTHFR
variant.
Publication Types:
- Research Support, Non-U.S. Gov't
- Validation Studies
PMID: 15352998 [PubMed - indexed for MEDLINE]
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-
Comment in:
An outcomes analysis of five prenatal
screening strategies for trisomy 21 in women younger than 35
years.
Biggio
JR Jr, Morris
TC, Owen
J, Stringer
JS.
Department of Obstetrics and Gynecology, Division of
Maternal-Fetal Medicine and Reproductive Genetics, University
of Alabama at Birmingham, Ala, USA.
OBJECTIVE: This study was undertaken to examine the
cost-effectiveness and procedural-related losses associated
with 5 prenatal screening strategies for fetal aneuploidy in
women under 35 years old. STUDY DESIGN: Five prenatal
screening strategies were compared in a decision analysis
model: triple screen: maternal age and midtrimester serum
alpha-fetoprotein, human chorionic gonadotropin (hCG), and
unconjugated estriol; quad screen: triple screen plus serum
dimeric inhibin A; first-trimester screen: maternal age, serum
pregnancy-associated plasma protein A and free beta-hCG and
fetal nuchal translucency at 10 to 14 weeks' gestation;
integrated screen: first-trimester screen plus quad screen,
but first-trimester results are withheld until the quad screen
is completed when a composite result is provided; sequential
screen: first-trimester screen plus quad screen, but the
first-trimester screen results are provided immediately and
prenatal diagnosis offered if positive; later prenatal
diagnosis is available if the quad screen is positive. Model
estimates were literature derived, and cost estimates also
included local sources. The 5 strategies were compared for
cost, the numbers of Down syndrome fetuses detected and live
births averted, and the number of procedure-related euploid
losses. Sensitivity analyses were performed for parameters
with imprecise point estimates. RESULTS: In the baseline
analysis, sequential screening was the least expensive
strategy ($455 million). It detected the most Down syndrome
fetuses (n=1213), averted the most Down syndrome live births
(n=678), but led to the highest number of procedure-related
euploid losses (n=859). The integrated screen had the fewest
euploid losses (n=62) and averted the second most Down
syndrome live births (n=520). If fewer than 70% of women
diagnosed with fetal Down syndrome elect to abort, the quad
screen became the least expensive strategy. CONCLUSION:
Although sequential screening was the most cost-effective
prenatal screening strategy for fetal trisomy 21, it had the
highest procedure-related euploid loss rate. The patient's
perspective on detection versus fetal safety may help define
the optimal screening strategy.
PMID: 15042005 [PubMed - indexed for MEDLINE]
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-
Multiple-marker screening in human
immunodeficiency virus-positive pregnant women: Screen
positivity rates with the triple and quad screens.
Yudin
MH, Prosen
TL, Landers
DV.
Department of Obstetrics, Gynecology, and Reproductive
Sciences, University of Pittsburgh School of Medicine, Magee-Womens
Research Institute, and Pittsburgh Development Center,
Pittsburgh, Pa., USA.
OBJECTIVE: The study was undertaken to determine the
screen-positive rates of multiple-marker screening tests in
pregnant women who are positive for human immunodeficiency
virus (HIV) at our institution for open neural tube defects
and aneuploidy, for both triple (alpha-fetoprotein, human
chorionic gonadotropin [hCG], unconjugated estriol) and quad
(alpha-fetoprotein, hCG, unconjugated estriol, inhibin A)
screens, and to compare these rates with a matched control
group. STUDY DESIGN: A 1:1 matched case-control study was
performed comparing multiple marker screening test results in
34 HIV-positive women with age- and race-matched HIV-negative
controls. Individual serum markers and screen positive rates
for both the triple and quad screens were compared among the
cases and controls. RESULTS: In each group, there were 19
women with triple screens and 15 with quad screens. Serum hCG
multiples of the median were significantly higher in the
HIV-positive compared with the HIV-negative women (P=.033).
There was no difference in screen positive rates between the
cases and controls using the triple screen, but there was a
significantly higher overall screen positive rate in the
HIV-positive group when the quad screen was used (33% vs 7%,
P=.046). CONCLUSION: There is a significantly higher rate of
overall quad screen positivity on multiple-marker screening
among HIV-positive women compared with a matched control
group.
PMID: 14586337 [PubMed - indexed for MEDLINE]
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Unexplained elevated maternal serum
alpha-fetoprotein and/or human chorionic gonadotropin and the
risk of adverse outcomes.
Chandra
S, Scott
H, Dodds
L, Watts
C, Blight
C, Van
Den Hof M.
Department Obstetrics and Gynecology, University of Alberta,
Edmonton, Canada. schandra@cha.ab.ca
OBJECTIVE: The study was undertaken to determine the risks of
adverse obstetric outcomes in pregnant women with unexplained
elevations of maternal serum alpha-fetoprotein (MSAFP) and/or
human chorionic gonadotropin (hCG) and to determine whether
these risks vary by prepregnancy risk status. STUDY DESIGN:
All women who underwent double-marker screening (MSAFP+hCG)
between 1994 and 2000 and were delivered of an infant in Nova
Scotia, Canada, during this period were identified from a
hospital serum screening database and a provincial perinatal
database. Patients with inaccurate dating, major structural
anomalies, or chromosomal abnormalities were excluded. The
primary outcomes studied were preeclampsia, abruptio placentae,
fetal growth restriction, fetal death, and preterm birth.
Women with medical or previous obstetric complications were
designated high risk. Logistic regression, controlling for
confounding factors, was used to estimate the relative risks (RRs)
and 95% CI for elevated levels of MSAFP and/or hCG and each of
the outcomes. RESULTS: Among the 14,374 women who met the
study criteria, 5,789 were designated high risk. Except for
abruptio placentae, unexplained elevated MSAFP or elevated hCG
levels were independently associated with all the outcomes in
both high- and low-risk women. Elevated screening values were
associated with increased risk of abruptio placentae among
low-risk women only. Particularly large RRs were seen for
fetal death in both high- and low-risk women (RR=4.9, 95% CI
2.7-8.7 for elevated MSAFP or hCG in high- and low-risk women
combined). CONCLUSION: Unexplained elevated levels of MSAFP
and/or hCG are associated with an increased risk of most
pregnancy complications. Increased antenatal surveillance of
these patients is important regardless of prepregnancy risk
status.
Publication Types:
- Research Support, Non-U.S. Gov't
PMID: 14526312 [PubMed - indexed for MEDLINE]
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Comment in:
Incorporation of inhibin-A in
second-trimester screening for Down syndrome.
Benn
PA, Fang
M, Egan
JF, Horne
D, Collins
R.
Division of Human Genetics, Department of Pediatrics,
University of Connecticut Health Center, 263 Farmington
Avenue, Farmington, CT 06030-6140, USA. benn@nso1.uchc.edu
OBJECTIVE: To evaluate the efficacy of the second-trimester
quadruple test (maternal serum alpha-fetoprotein, unconjugated
estriol, human chorionic gonadotropin, and inhibin-A) in
prenatal screening for Down syndrome. METHODS: All quadruple
tests performed on singleton pregnancies over a 32-month
period were reviewed. The sensitivity and false-positive rates
were compared with the theoretic rates predicted by the
screening model when applied to a population of women with the
same maternal age distribution. RESULTS: Twenty-three thousand
seven hundred four women with unaffected pregnancies and 45
women with Down syndrome-affected pregnancies received the
quadruple test. Mean analyte values for both unaffected and
affected pregnancies were similar to those expected. The
sensitivity of the quadruple test, which was based on
ascertainment of all viable affected pregnancies in the
screened population, was 85.8%. This sensitivity did not
significantly differ from an expected 83.8% (P =.8). The
initial false-positive rate, 9.0%, was significantly below
that expected (9.9%) (P =.002) and was further reduced to 8.2%
after correction for major gestational age errors. The
positive predictive value of the quadruple test was one in 51.
Women with an affected pregnancy and a positive test result
(true positives) generally had very high risks (median 1:22)
relative to women with false-positive results (median risk
1:111). CONCLUSION: The quadruple test meets or exceeds
performance expectations and appears to represent an
improvement over the widely used triple test.
Publication Types:
PMID: 12636947 [PubMed - indexed for MEDLINE]
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Elevated maternal serum hCG in the second
trimester increases prematurity rate and need for neonatal
intensive care in primiparous preeclamptic pregnancies.
Heikkilä
A, Makkonen
N, Heinonen
S, Kirkinen
P.
Department of Obstetrics and Gynecology, University Hospital
of Kuopio, Kuopio, Finland.
OBJECTIVE: This study was designed to investigate the
association between the serum concentrations of maternal
second trimester human chorionic gonadotropin (hCG) and the
severity of preeclampsia. METHODS: At Kuopio University
Hospital, a total of 487 preeclamptic primiparas had undergone
maternal serum screening for Down's syndrome between January
1993 and December 1998. Of these, 37 women had unexplained
elevated serum hCG concentrations [> 2.5 multiples of the
median (MoM)], whereas the remaining 450 preeclamptic women
had normal hCG results. Pregnancy characteristics and outcome
measures in these groups were evaluated using logistic
regression. RESULTS: Elevated midtrimester hCG concentrations
were associated with higher rates of low-birth-weight infants,
preterm delivery, and need for neonatal intensive care. The
adjusted odds ratios was 2.11 [95% confidence interval (CI):
1.03-4.32], 2.08 (95% CI: 1.10-4.30), and 2.27 (95% CI:
1.14-4.51), respectively. CONCLUSIONS: In primiparous
preeclamptic pregnancies, an elevated maternal serum hCG
concentration is a marker of early-onset and severe disease
with significant maternal and perinatal morbidity. This
finding, in turn, reinforces the association between elevated
hCG concentrations and placental damage in early pregnancy.
Elevated maternal serum hCG levels identify a subgroup of
preeclamptic patients who deserve more intensive observation.
PMID: 12044318 [PubMed - indexed for MEDLINE]
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Estimates for the sensitivity and
false-positive rates for second trimester serum screening for
Down syndrome and trisomy 18 with adjustment for
cross-identification and double-positive results.
Benn
PA, Ying
J, Beazoglou
T, Egan
JF.
Division of Human Genetics, Department of Pediatrics,
University of Connecticut Health Center, 263 Farmington
Avenue, Farmington, CT 06030-6140, USA. Benn@nso1.uchc.edu
Second trimester screening for fetal Down syndrome and trisomy
18 is available through separate protocols that combine the
maternal age-specific risk and the analysis of maternal serum
markers. We have determined the extent to which additional
Down syndrome affected pregnancies may be identified through
trisomy 18 screening, and the extent to which additional cases
of trisomy 18 may be screen-positive for Down syndrome. The
combined false-positive rate, taking into consideration those
pregnancies that are screen-positive by both protocols, has
also been determined. Sensitivity and false-positive rates
were determined by computer simulation of results that
incorporated previously published statistical variables into
the model. Using second trimester risk cut-offs of 1:270 for
Down syndrome and 1:100 for trisomy 18, it was found that few
additional cases of Down syndrome are identified through
trisomy 18 screening. However, approximately 6-10% of trisomy
18 affected pregnancies will be screen-positive for Down
syndrome but screen-negative for trisomy 18. For women aged 40
or more, the false-positive rate for trisomy 18 exceeds 1% and
approximately half of these cases will also be screen-positive
for Down syndrome. For a population with maternal ages
equivalent to that in the United States in 1998, after
adjusting for the cross-identification, the sensitivity for
three-analyte trisomy 18 screening is 78%. If this testing is
performed in conjunction with Down syndrome "triple"
screening, the Down syndrome sensitivity is 75% and the
combined false-positive rate is 8.5%. If the three-analyte
trisomy 18 screening is performed with the Down syndrome
"quad" screen, the trisomy 18 sensitivity remains at
78%, the Down syndrome sensitivity is 79%, and combined
false-positive rate is 7.5%. Sensitivity and false-positive
rates are also provided for other widely used Down syndrome
and trisomy 18 risk cut-offs. Sensitivity and false-positive
rates that take into consideration cross-identification and
double-positives should be helpful for pre-test counseling and
the evaluation of serum screening programs. Copyright 2001
John Wiley & Sons, Ltd.
Publication Types:
- Research Support, Non-U.S. Gov't
PMID: 11180240 [PubMed - indexed for MEDLINE]
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