Antenatal

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Antenatal

• David Watson TTH
• 2009

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Down Syndrome Screening

• Rationale
• Common chromosome abnormality 1/500
• Moderate degree of intellectual impairment (IQ
  40)
• Screening tests have high sensitivity
• Median age of women with trisomy 21 pregnancy
  28-29 years of age
• Increased individual risk increases with maternal
  not paternal age

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Maternal Age risk

• Maternal age Chance of Down syndrome
• 12 weeks birth
• 20 1 in 1070 1 in 1530
• 25 1 in 950 1 in 1350
• 30 1 in 630 1 in 900
• 32 1 in 460 1 in 660
• 34 1 in 310 1 in 450
• 35 1 in 250 1 in 360
• 36 1 in 200 1 in 280
• 38 1 in 120 1 in 170
• 40 1 in 70 1 in 100
• 42 1 in 40 1 in 55
• 44 1 in 20 1 in 30

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Maternal age-related risk for chromosomal
abnormalities
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Gestational age-related risk for chromosomal
abnormalities. The lines represent the relative
riskaccording to the risk at 10 weeks of
gestation
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Down Syndrome ScreeningWhat is recommended

• Explain difference between screen and diagnostic
  test
• Sensitivity and specificity
• Compare different tests
• Risks of prenatal diagnosis
• Psychological implications of prenatal screen and
  diagnosis
• Implications of a child with Down Syndrome
• Detection of other aneuploidy and implications
• Timing of results
• Information about termination

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Down Syndrome ScreeningWhat is recommended

• Explain difference between screen and diagnostic
  test
• Sensitivity and specificity T/T F-, T-/T-
  F
• Compare different tests
• Risks of prenatal diagnosis
• Psychological implications of prenatal screen and
  diagnosis
• Implications of a child with Down Syndrome
• Detection of other aneuploidies and implications
• Timing of results
• Information about termination

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History Screening

• Maternal Age gt35 or 37 or 40 years offer
  amniocentesis or CVS

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History Screening

• Maternal Age gt35 years amniocentesis or CVS
• MA Second Trimester biochemistry Triple test

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History Screening

• Maternal Age gt35 years amniocentesis or CVS
• MA Second Trimester biochemistry Triple test
• MA First Trimester Nuchal translucency

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NT alone

• 200,868 pregnancies, including 871 fetuses with
  trisomy 21, have demonstrated that increased
  nuchal translucency can identify 76.8 of fetuses
  with trisomy 21, which represents a
  false-positive rate of 4.2.

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History Screening

• Maternal Age gt35 years amniocentesis or CVS
• MA Second Trimester biochemistry Triple test
• MA First Trimester Nuchal translucency
• MA First trimester NT and first trimester
  biochemistry

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NT First trimester biochemistry

• fetal nuchal translucency was combined with
  maternal serum freeß-human chorionic
  gonadotrophin and pregnancy-associated plasma
  protein-A in prospective studies in a total of
  44,613 pregnancies, including 215 fetuses with
  trisomy 21, the detection rate was 87.0 for a
  false-positive rate of 5.0.

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History Screening

• Maternal Age gt35 years amniocentesis or CVS
• MA Second Trimester biochemistry Triple test
• MA First Trimester Nuchal translucency
• MA First trimester NT and first trimester
  biochemistry Combined first trimester screen
• MA First trimester NT and first trimester
  biochemistry and first trimester markers (nasal
  bone, TR, DV a wave, Maxillary angle)

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Nasal bone alone

• 15,822 pregnancies, which included 397 fetuses
  with trisomy 21, have demonstrated that the
  absence of the nasal bone can identify 69.0 of
  trisomy 21 fetuses, which represents a
  false-positive rate of 1.4

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History Screening

• Maternal Age gt35 years amniocentesis or CVS
• MA Second Trimester biochemistry Triple test
• MA First Trimester Nuchal translucency
• MA First trimester NT and first trimester
  biochemistry
• MA First trimester NT and first trimester
  biochemistry and first trimester markers (nasal
  bone others)
• MA First trimester NT and first trimester
  biochemistry and first trimester markers (nasal
  bone) and second trimester biochemistry
  Integrated test

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History Screening

• Maternal Age gt36 years amniocentesis or CVS
• MA Second Trimester biochemistry Triple test
• MA First Trimester Nuchal translucency
• MA First trimester NT first trimester
  biochemistry
• MA First trimester NT first trimester
  biochemistry and first trimester markers (nasal
  bone others)
• MA First trimester NT first trimester
  biochemistry /- first trimester markers and
  second trimester biochemistry Integrated test
• MA First trimester NT first trimester
  biochemistry and next test contingent on results
  from earlier testing Contingent test (nasal
  bone)

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Contingent Testing

• Combined first trimester result in three groups
• 1. Low risk lt1/1000 exit testing here
• 2. High risk gt1/100 Offer invasive testing
• 3. Intermediate risk 1/100 1/1000 proceed to
  next stage of testing with first trimester
  markers Nasal Bone, TR, DV a wave, Maxillary
  angle
• Advantage 97 sensitivity with 3 false positive

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NT Biochem Nasal bone

• It has been estimated that first-trimester
  screening by a combination of sonography and
  maternal serum testing can identify 97 of
  trisomy 21 fetuses, which represents a
  false-positive rate of 3, or that the detection
  rate can be 91, which represents a
  false-positive rate of 0.5

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Detection rate Trisomy 21
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Calculate Trisomy 21 risk

• Background maternal age related risk
• Risk increases with maternal not paternal age
• Previous aneuploidy?
• Risk increases if previous affected baby
• Nuchal translucency
• increases risk if greater than median NT for CRL
• Nuchal translucency measure increases with bigger
  CRL
• First trimester Biochemistry
• Risk increases with low PAPPA and high BHCG
• High Risk if Trisomy 21 more likely than 1/300

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Nuchal translucency measurement in 326 trisomy 21
fetuses plotted on the normal range
forcrownrump length (95th and 5th centiles)
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What is a normal NT?

• Fetal NT increases with crown-rump length
• 96,127 pregnancies
• Median and 95th percentile at a crown-rump length
  of
• 45 mm were 1.2 and 2.1 mm
• 84 mm were 1.9 and 2.7 mm
• 99th percentile did not change with crown-rump
  length and was approximately 3.5 mm

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Maternal age-related risk for trisomy 21 at 12
weeks of gestation and the effect of fetal
nuchal translucency thickness
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First trimester biochemistry
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Number of pregnancies withnuchal translucency
(NT) thickness above the 95th centile and an
estimated risk for trisomy 21, based onmaternal
age and fetal nuchal translucency and crown-rump
length, of 1 in 300 or more
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INCREASED NUCHAL TRANSLUCENCY WITHNORMAL
KARYOTYPE
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Down Syndrome ScreeningWhat is recommended

• Explain difference between screen and diagnostic
  test
• Sensitivity and specificity T/T F-, T-/T-
  F
• Compare different tests
• Risks of prenatal diagnosis
• Psychological implications of prenatal screen and
  diagnosis
• Implications of a child with Down Syndrome
• Detection of other aneuploidies and implications
• Timing of results
• Information about termination

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Risks of Prenatal Diagnosis

• Most high risk results are false positives,
• 5 screened population will offered invasive
  testing much less than with age based screening
  (15)
• CVS
• 11-13 weeks
• Trans-abdominal not TV (yet)
• 1 fetal loss rate (1/50 1/100 or 1-2)
• Possible to have suction TOP if results before
  13-14 weeks

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Risks of Prenatal Diagnosis

• Amniocentesis
• 16 -17 weeks
• 1 fetal loss rate ( 1 0.5 or 1/100 1/200)
• One randomized trial 1 miscarriage rate
• If termination of pregnancy induction of labour
• 20W0D birth and ideal to have done before 20
  weeks

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Down Syndrome ScreeningWhat is recommended

• Explain difference between screen and diagnostic
  test
• Sensitivity and specificity T/T F-, T-/T-
  F
• Compare different tests
• Risks of prenatal diagnosis
• Psychological implications of prenatal screen and
  diagnosis
• Implications of a child with Down Syndrome
• Detection of other aneuploidies and implications
• Timing of results
• Information about termination

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Down Syndrome ScreeningWhat is recommended

• Explain difference between screen and diagnostic
  test
• Sensitivity and specificity T/T F-, T-/T-
  F
• Compare different tests
• Risks of prenatal diagnosis
• Psychological implications of prenatal screen and
  diagnosis
• Implications of a child with Down Syndrome
• Detection of other aneuploidies and implications
• Timing of results
• Information about termination

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Down Syndrome ScreeningWhat is recommended

• Explain difference between screen and diagnostic
  test
• Sensitivity and specificity T/T F-, T-/T-
  F
• Compare different tests
• Risks of prenatal diagnosis
• Psychological implications of prenatal screen and
  diagnosis
• Implications of a child with Down Syndrome
• Detection of other aneuploidies and implications
• Timing of results
• FISH (21,18,13,X and Y 2-3 days)
• Full Karyotype CVS 2 weeks. Amniocentesis 3
  weeks
• Culture failure 1/200, Placental mosaicism
  1/200
• Terminate on FISH?
• Information about termination

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Down Syndrome ScreeningWhat is possible?

• Ask about screen or diagnostic test Queensland
  policy on Down Syndrome Screening 2009, RANZCOG
• Detection rates (Sensitivity) and stress second
  trimester morphology is not a screening test for
  Down Syndrome (poor detection rate)
• Compare one or two different tests depending on
  gestation
• Risks of prenatal diagnosis false positive and
  invasive testing loss rate of 1
• Psychological implications of prenatal screen and
  diagnosis
• Implications of a child with Down Syndrome
• Detection of other aneuploidies and implications
• Timing of results
• Information about termination All if required

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Second Trimester Morphology

• 19-20 weeks with 20 weeks better if overweight
• No obvious structural anomalies
• Soft signs or markers
• Structural anomalies that may be associated with
  aneuploidy ( or not associated with aneuploidy)

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Soft Markers

• Definition Normal variants in anatomy
• Present in 1-17 of normal fetuses
• Prevalance may be higher in aneuploid fetus
• Most fetuses with Down Syndrome dont have
  markers at 20 weeks
• Increased nuchal fold
• Absent or small nasal bone
• Echogenic bowel
• Pyelectasis
• Ventriculomegaly
• Shortened long bones (humerus, femur)
• Echogenic intracardiac focus
• Choroid plexus cysts
• Single Umbilical artery

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Nuchal fold 6 mm
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Absent nasal bone
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Soft Markers

• Increased Nuchal Fold
• gt6mm
• 40 Trisomy 21 and 1-2 normal fetuses
• LR 9-11
• Absent or Hypoplastic nasal bone
• lt3mm 16/40 or lt4.5mm 20/40
• 60 Trisomy 21, 1.4 normal
• LR 20-40

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Pyelectasis 4 mm
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Hypoplasia 5th metacarpal
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Hyperechoic bowel
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Echogenic intracardiac focus
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Likelihood Ratios of Isolated Markers

• None 0.5-1.0
• Nuchal fold 9-11
• Bright bowel 3-5
• Short humerus 2.5
• Short femur 2.2
• EIF 2
• Pyelectasis 1.5

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The Scoring Index (USA)

• Sonographic Finding Score
• Major anomaly 2
• Nuchal fold 6 mm 2
• Short femur 1
• Short humerus 1
• Pyelectasis 4 mm 1
• Hyperechoic bowel 1
• Echogenic intracardiac focus 1
• Age gt34 1

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Summary

• Should all women be offered screening?
• Definite answer requires invasive testing in
  2009.
• Fetal cells in pap smear
• Fetal DNA in maternal circulation
• How to screen Combined NT and first trimester
  biochemistry gtgt second trimester testing
• MA NT Biochem Combined first trimester
  Screening good sensitivity (80 90) but false
  positives 5

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Alcohol

• Prevalence of drinking
• Non-pregnant
• 10 drink daily and 10 never
• 40 drink weekly (AIHW 2005)
• 50 drink at or below NHMRC 2001 level for short
  term harm 1/3 drink above harm threshold at
  least once in 12 months
• 10 above long term harm threshold (AIHW 2008)

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Pregnancy and Alcohol

• NHMRC 2001 concept of short and long term harm
• Short term accidents and injuries
• Long term alcohol related diseases
• Short term threshold
• gt6 standard drinks (10g alcohol)/day men
• gt 4 standard drinks/day women
• Long term threshold
• 4/day XY and 2/day XX

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Pregnancy and Alcohol

• 60 drink alcohol at some time in pregnancy
• 15 gt5 drinks at one occasion in 3/12 before
  pregnancy
• Most abstain from alcohol in pregnancy
• T1 T2 58 no alcohol
• T3 54 no alcohol
• Colvin 2007 Alcohol Clin Exp Res 31(2)

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Pregnancy and Alcohol

• 15 above 2001 NHMRC guidelines in T1
• 10 above 2001 NHMRC guidelines in T2 T3
• 34 drank alcohol in last pregnancy
• 24 would drink in future pregnancy
• 80 said reducing or no alcohol would benefit
  baby
• Colvin 2007 Alcohol Clin Exp Res 31(2)
• Peadon 2007 J Paed Child Health 43(7-8)

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Alcohol and high risk groups

• Non English home language
• Regional or remote location
• Aboriginal or Torres Straight race if they drink
• ATSI
• 50 drink above short term threshold ( 34)
• 20 drink above long term threshold ( 10)

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NHMRC 2009

• Non Pregnant no more than 2 standard
  drinks/day may reduce lifetime risk of harm
• Pregnancy and breast feeding No alcohol is the
  safest option

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NHMRC 2009

• Alcohol is a Teratogen
• Alcohol X placenta easily
• Associated with miscarriage, stillbirth, Preterm
  delivery at high doses
• Fetal anomalies with FASD Fetal Alcohol
  Spectrum Disorder including FAS and structural
  anomalies (agenesis of Corpus Callosum)
• ARBD (birth defects) and ARND (neurodevelopmental
  disorders) Risk is greatest with heavy or
  frequent drinking
• No safe threshold with likely risk of 1 or 2
  drinks/week low

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Alcohol and Pregnancy

• Hendersen systematic review (2007)
• 46 studies
• Low moderate alcohol 12g/week
• No real evidence of adverse pregnancy outcomes
  miscarriage, SB, PTD, IUGR, Anomalies including
  FAS, BUT quality of evidence poor and cant
  conclude safe dose is one drink/week

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Alcohol and Pregnancy

• Hendersen systematic review (2007)
• 14 studies
• Binge drinking (6 drinks one one occasion or
  multiple occasions)
• Poorer neuro-developmental outcomes with dose
  effect learning difficulties, low verbal IQ,
  behavioral problems and poor education
  performance
• No consistent evidence of adverse pregnancy
  outcomes miscarriage, SB, PTD, IUGR, Anomalies
  including FAS,

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Alcohol and Pregnancy

• Approach similar to smoking in pregnancy
• 5As
• Ask about alcohol
• Assess level of risk
• Advise
• Assist
• Arrange further support

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• Group B streptococcus
• Miscarriage management
• Poor fetal movements
• Reduced liquor volume