The New Prenatal Screening Tests

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The New Prenatal Screening Tests

• St. Pauls Hospital CME Conference for Primary
  Physicians
• November 22, 2007
• Ken Seethram, MD, FRCSC, FACOG
• Obstetrics and Gynecology

pacificfertility.ca
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Disclosure statement
I have no financial relationship with
pharmaceutical or medical ultrasound corporations
associated with prenatal screening and/or
diagnosis.
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• ..wow, things have changed

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Objectives

• To make you current with 2007/08 guidelines from
  ACOG and SOCG with regards to Prenatal screening
  options
• Help fully understand all options in order to
  better undertake counseling
• Help understand how and when to get your patients
  screened once their options are known

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Outline

• Definitions
• Background and Evolution
• Second Trimester Serum Screening
• First Trimester Screening
• Combined Screening
• Guidelines
• Final words and resources

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Quick Definitions

• DR Detection rate
• the rate at which a test will pick up the
  problem. This is accuracy, not reliability
• FPR False positive rate
• the chance that the screening tool will be
  positive when the condition is absent
• Screen positive
• the literature term to describe the number of
  times the test will be positive (either truly or
  falsely)

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Background

• What are we screening for?
• 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

• 1887 John Langdon Down presented
• 1930s first association made with maternal age
  and risk of major malformations
• due to egg age, declining quality of spindle
  mechanism nondisjunction at meiosis I prior to
  fertilization aneuploidy results
• late 1970s age was first put to use to triage
  women for amniocentesis

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Evolution of screening

• 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.
• Bad news its the worst screening tool, with
  only 30-40 detection rate
• Today dont use age 35 as a cut-off

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1980s 2nd Trimester serum

• AFP
• Total hCG
• Unconjugated estriol uE3

Inhibin A
Quad Screen (TMS/Quad multiple marker scrg
test, maternal serum screen)
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TMS and Quad Screening

• 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
• i.e. Many false positives

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What has evolved in the first trimester?(11-14
weeks)

• Nuchal Translucency (NT)
• Serum biochemistry
• Nasal Bone (NB)
• Tricuspid regurgitation (TR)
• Frontomaxillary facial angle (FMF Angle)

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The First Trimester - NT

• US measurement, 11-14w spine to skin
• Fetal Medicine Foundation
• Aneuploidy - a change in extracellular matrix and
  potential for cardiac/lymphatic changes causing
  increased NT
• Congenital hearts, others

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What has evolved in the first trimester?

• Nuchal Translucency (NT)
• Serum biochemistry
• Nasal Bone (NB)
• Tricuspid regurgitation (TR)
• Frontomaxillary facial angle (FMF Angle)

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PAPP-A free beta hCG

• 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?

• Nuchal Translucency (NT)
• Serum biochemistry
• Nasal Bone (NB)
• Tricuspid regurgitation (TR)
• Frontomaxillary facial angle (FMF Angle)

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Nasal Bone (NB)

• 60-70 of T21 absent Nasal bone
• 99 of euploid fetuses have Nasal bone
• tremendous increase in detection rates of FTS.
  High learning curve

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The First Trimester TR, FMF, Ductus Venosus

• Tricuspid Regurge, DV, and FMF angle are somewhat
  experimental and not wide clinically used outside
  of research settings

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First Trimester Screening (FTS performance)
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Screening Strategies
First Trimester Screening
Second Trimester Screening

• Serum integrated
• Integrated
• Sequential
• Contingency

Combined Screening
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Screening Strategies

• 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

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Screening Strategies

• Sequential screening model
• IPS but disclosed after 1st, and then 2nd TM
• People may opt for testing after 1st TM
• Contingency Screening models
• FTS done - lt11000, no further testing
• If risks gt150, CVS offered
• If risks 150-1999 -
• quad offered or
• Nasal bone contingency offer NB to intermediate
  group
• Probably best for high DRs in population based
  screening

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Which test is best?

• How does each model perform

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Best performance

• For a first trimester result
• FTS with NT NB serum
• Contingency screening programs
• For a combined result
• IPS/Contingency screening programs
• For Late entry
• Quad screen

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What do the guidelines say?

• ACOG released similar guidelines in January 2007,
  and SOGC in February
• Basics
• Triple screening is no longer good enough
• Dont use age as a screening tool
• Aim for highest DRs and lowest FPRs in any
  method
• Consent and review all options
• Quality assurance important in FTS programs

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Quality Assurance?

• 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.

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SOGC

• 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
• 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

• 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

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Whats the best test?

• 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
• best screen is the one which will service
  patients needs for time of results, and action
  depending on the results

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Current Western Canada options

• Alberta
• Edmonton/Calgary FTS programs, provincially
  insured
• British Columbia
• 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

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FMF Accredited FTS Centre's, BC

• BCWH (block funding for special groups)
• IPS (over age 40), SIPS (over age 38)
• Prior aneuploidy, Twins
• Pacific Ctr for Reproductive Medicine (495)
• FTS - NT NB serum genetic counseling
• o-s-c-a-r modeling after FMF
• Genesis Fertility Centre (495)
• FTS - NT serum genetic counseling

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Resources

• www.fetalmedicine.com
• www.earlyriskassessment.com
• www.mfmedicine.com
• www.genesis-fertility.com
• www.pacificfertility.ca