The New Prenatal Screening Tests
St. Paul’s Hospital CME Conference
for Primary Physicians
November 22, 2007
Ken Seethram, MD, FRCSC, FACOG
Obstetrics and Gynecology
pacificfertility.ca
Disclosure statement
I have no financial relationship with
pharmaceutical or medical ultrasound
corporations associated with prenatal
screening and/or diagnosis.
..wow, things have changed
Objectives
I.
To make you current with 2007/08 guidelines
from ACOG and SOCG with regards to
Prenatal screening options
II.
Help fully understand all options in order to
better undertake counseling
III.
Help understand how and when to get your
patients screened once their options are
known
Outline
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Definitions
Background and Evolution
Second Trimester Serum Screening
First Trimester Screening
Combined Screening
Guidelines
Final words and resources
Quick Definitions
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DR = Detection rate:
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FPR = False positive rate:
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the rate at which a test will pick up the problem. This
is accuracy, not reliability
the chance that the screening tool will be positive
when the condition is absent
Screen positive:
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the literature term to describe the number of times the
test will be positive (either truly or falsely)
Background
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What are we screening for?
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Aneuploidy: majority of which is Trisomy 21,
with T18, T13, and monosomy X (45X)
Secondary screening benefits?
Dating the pregnancy
 Anatomy evaluation, placental evaluation,
twins, early anomalies
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Evolution of screening
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1887 – John Langdon Down presented
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1930’s – first association made with maternal
age and risk of major malformations
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due to egg age, declining quality of spindle
mechanism: nondisjunction at meiosis I prior to
fertilization – aneuploidy results
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late 1970’s – age was first put to use to triage
women for amniocentesis
Evolution of screening
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Age 35 became the ‘high risk age’
at which the rate of aneuploidy was equal to
the rate of amniocentesis/CVS related
miscarriage.
 Therefore, maternal age was the first screening
tool.
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Bad news: it’s the worst screening tool,
with only 30-40% detection rate
Today: don’t use age 35 as a cut-off
1980’s – 2nd Trimester serum
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AFP
Total hCG
Unconjugated estriol
uE3
Triple marker
screen (TMS)
Inhibin A
Quad Screen
(TMS/Quad = multiple marker scrg test, maternal serum screen)
TMS and Quad Screening
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Nothing really has
changed with multiple
marker screening tools
Uses 2-4 biochemical
markers to adjust the age
related risks
Problem - specificity
drops as disease
prevalence increases
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i.e. Many false positive’s
DR
FPR
TMS
<72%
7-25%
Quad
77%
5.2%
What has evolved in the first trimester?
(11-14 weeks)
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Nuchal Translucency (NT)
Serum biochemistry
Nasal Bone (NB)
Tricuspid regurgitation (TR)
Frontomaxillary facial angle (FMF Angle)
The First Trimester - NT
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US measurement, 1114w: spine to skin
Fetal Medicine
Foundation
Aneuploidy - a change in
extracellular matrix and
potential for
cardiac/lymphatic
changes causing
increased NT
Congenital hearts, others
What has evolved in the first trimester?
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Nuchal Translucency (NT)
Serum biochemistry
Nasal Bone (NB)
Tricuspid regurgitation (TR)
Frontomaxillary facial angle (FMF Angle)
PAPP-A & free beta hCG
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Serum biochemistry
Free beta hCG (different than TMS/Quad)
 PAPP-A (Preg Assoc. plasma protein-A)
 relative levels are used to predict T21, T13,
T18
 Low PAPP-A –
 may be associated with a poorly developing
placenta
 Evolving method of screening for placental
disease (IUGR, PIH)
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What has evolved in the first trimester?
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Nuchal Translucency (NT)
Serum biochemistry
Nasal Bone (NB)
Tricuspid regurgitation (TR)
Frontomaxillary facial angle (FMF Angle)
Nasal Bone (NB)
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60-70% of T21 absent
Nasal bone
99% of euploid
fetuses have Nasal
bone
tremendous increase
in detection rates of
FTS. High learning
curve
The First Trimester – TR, FMF,
Ductus Venosus
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Tricuspid Regurge, DV, and FMF angle
are somewhat experimental and not wide
clinically used outside of research settings
First Trimester Screening (FTS
performance)
Criteria
DR
FPR
Age + NT Alone
75%
5-10%
83-85%
5%
92-95%
3-5%
Age + NT +
hCG / PAPP-A
Age + NT +
hCG/PAPP-A +
Nasal Bone
Screening Strategies
First Trimester
Screening
Second
Trimester
Screening
Combined
Screening
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Serum integrated
Integrated
Sequential
Contingency
Screening Strategies
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Serum Integrated Pregnancy Screening
(SIPS)
 1st TM PAPP-A + Quad (SURUSS trial, 2003)
 Results disclosed at 17/18w
Integrated Pregnancy Screening (IPS)
 1st TM PAPP-A + NT + TMS/Quad
 Same as SIPS but with NT
 Results disclosed at 17/18w
 SURUSS and FASTER trials 2003/2005
Screening Strategies
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Sequential screening model
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IPS but disclosed after 1st, and then 2nd TM
People may opt for testing after 1st TM
Contingency Screening models
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FTS done - <1:1000, no further testing
If risks >1:50, CVS offered
If risks 1:50-1:999 
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quad offered or
Nasal bone contingency: offer NB to intermediate group
Probably best for high DR’s in population based screening
Which test is best?
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How does each model perform…
DR
FPR
Weeks
Trial
NT+NB+Serum
92-95%
3-5%
11-14
FMF
Serum
integrated
88%
5%
17-18w
SURUSS
Fully
Integrated
93%
96%
92%
5%
5%
5%
17-18w
17-18w
17-18w
SURUSS
FASTER
Meta
Sequential
95%
5%
13-18w
FASTER
5%
85%
finished in
1st TM
Cuckle
2.5%
90%
finished in
1st TM
RCT
Contingency
Nasal Bone
Contingency
91-92%
90%
Best performance
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For a first trimester result:
FTS with NT + NB + serum
 Contingency screening programs
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For a combined result:
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IPS/Contingency screening programs
For Late entry
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Quad screen
What do the guidelines say?
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ACOG released similar guidelines in
January 2007, and SOGC in February
Basics:
Triple screening is no longer good enough
 Don’t use age as a screening tool
 Aim for highest DR’s and lowest FPR’s in any
method
 Consent and review all options
 Quality assurance important in FTS programs
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Quality Assurance?
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Image and data audit
Initial certification, and on-going audit
FMF UK/USA
NTQR?
Importance on program based screening:
Pre/post test counseling
 Lab and clinical QA
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ACOG
Regardless of which screening tests you
decide to offer your patients, information about
the detection and false-positive rates,
advantages, disadvantages, limitations, and
risks and benefits of diagnostic procedures,
should be available to patients so they can
make informed decisions.
SOGC
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All women regardless of age, should be offered
consented screening for the most significant
aneuploidies, and a second trimester sonogram
for dating, growth and anomalies
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2008 Minimum standard: 75% DR, 5% FPR
Amnio/CVS can be offered to women over age
40, without screening, but screening should still
be offered.
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SOGC
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The practice of using solely the previous
cut-off of maternal age of 35 or over at the
estimated date of delivery (EDD) to
identify at-risk pregnancies should be
abandoned
What’s the best test?
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One size does not fit all
 As long as the definitive diagnosis involves an
invasive procedure which can cause
miscarriage of a normal pregnancy, there is
simply no substitute to explaining all the
options, their benefits, and risks
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best screen is the one which will service
patient’s needs for time of results, and action
depending on the results
Current Western Canada options
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Alberta
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Edmonton/Calgary – FTS programs, provincially
insured
British Columbia
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TMS program (does not yet comply with SOGC)
SIPS for women over age 38
IPS for women over age 40
Private centre's for FTS with or without NB (complies)
MOH investigating new options
FMF Accredited FTS Centre's,
BC
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BCWH (block funding for special groups)
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IPS (over age 40), SIPS (over age 38)
Prior aneuploidy, Twins
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Pacific Ctr for Reproductive Medicine ($495)
 FTS - NT + NB + serum + genetic counseling
 o-s-c-a-r modeling after FMF
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Genesis Fertility Centre ($495)
 FTS - NT + serum + genetic counseling
Resources
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www.fetalmedicine.com
www.earlyriskassessment.com
www.mfmedicine.com
www.genesis-fertility.com
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www.pacificfertility.ca
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