stephanie cooper md frcsc
Download
Skip this Video
Download Presentation
Stephanie Cooper, MD FRCSC

Loading in 2 Seconds...

play fullscreen
1 / 41

Stephanie Cooper, MD FRCSC - PowerPoint PPT Presentation


  • 259 Views
  • Uploaded on

Beyond Aneuploidy - Prediction of Adverse Obstetrical Outcomes with First Trimester Screening: PAPP-A . Stephanie Cooper, MD FRCSC. Prenatal Screening.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Stephanie Cooper, MD FRCSC' - adamdaniel


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
stephanie cooper md frcsc
Beyond Aneuploidy-

Prediction of Adverse Obstetrical Outcomes with First Trimester Screening: PAPP-A

Stephanie Cooper, MD FRCSC

prenatal screening
Prenatal Screening

Sensitive and accessible prenatal screening for aneuploidy and open neural tube defects is a standard recognized in the 2007 SOGC Clinical Practice Guidelines on Prenatal Screening for Fetal Aneuploidy

slide3
“All pregnant women in Canada, regardless of age, should be offered, through an informed consent process, a prenatal screening test for the most common clinically significant aneuploidies”

SOGC- Clinical Practice GuidelinesPrenatal Screening for Aneuploidy (2007)

why is early prediction of adverse outcomes important
Why is early prediction of adverse outcomes important?
  • Alberta has highest rate of preterm birth and low birth weight in Canada
  • Preeclampsia is the 2nd most common cause of maternal death worldwide and most common cause of iatrogenic prematurity
  • Strategies to identify risk factors and interventions that may improve pregnancy outcome in this group is a priority
where it all starts
Where it all starts

The pathologic changes of preeclampsia, IUGR (and in some cases of preterm labour) occur as early as the first trimester, long before clinical manifestations are observed

where it all starts1
Where it all starts

Early placental cells invade maternal spiral arteries transforming them from small muscular arterioles to large vessels of low resistance.

where it all starts2
Where it all starts
  • In pregnancies destined for preeclampsia and IUGR, the cytotrophoblasts infiltrate the decidual portion of the spiral arteries, not the myometrial portion.
  • The vessels remain narrow leading to hypoperfusion
slide12
A detectable maternal humeral response to inadequate placentation might predict those pregnancies at risk
papp a
PAPP-A
  • PAPP-A is a protease for IGFBP-4
  • IGF binding proteins inhibit the action of IGFs, which play a key role in regulating fetal growth and trophoblastic invasion of the decidua
papp a1
PAPP-A

PAPP-A levels in the first trimester

of pregnancy are predictive

of a range of adverse outcomes*

“Additional monitoring should occur in such circumstance*”

“Screening reports should highlight such cases with increased risk*”

*Smith et al. JAMA 2004: 2249-2252, Dugoff et al. Am J ObstetGynecol 2004; 191:1446-51, Krantz et al. Am J ObstetGynecol 2004; 191:1446-51, Spencer et al. PrenatDiagn 2005: 25:949-953

However, as prospective data assessing PAPP-A as a screening tool in a low risk population is limited, the finding of low PAPP-A in women undergoing FTS presents a clinical management dilemma

slide17
Uterine Artery Doppler
  • Impaired trophoblastic invasion of maternal spiral arteries is associated with increased impedance to flow in uterine arteries
  • Uterine artery Doppler ultrasound can assess blood flow for adequate or reduced perfusion
uterine artery doppler
Uterine Artery Doppler

Combining uterine artery Doppler at 22-24 weeks with low

PAPP-A (10-14 weeks)improves detection

of hypertension than by either marker in isolation.

Spencer et al. PrenatDiagn 2005: 25:949-953

sogc clinical practice guideline
SOGC Clinical Practice Guideline

“Uterine artery Doppler may be performed at the time of the 17-22 weeks ...in women with the following risk factors”:

  • Previous early onset gestational hypertension
  • Placental abruption
  • IUGR
  • Stillbirth
  • Pre-existing hypertension
  • Gestational hypertension
  • Pre-existing renal disease
  • Long standing IDDM with end organ involvement
  • Abnormal maternal serum screening (hCG or AFP >2.0 MOM)
  • Low PAPP-A

Fetal Health Surveillance: Antepartum and Intrapartum Consensus Guidelines. JOCG Sept 2007

slide21
Association between first trimester maternal

serum pregnancy associated plasma protein-A (PAPP-A) and adverse pregnancy outcome

Cooper S, Johnson JM, Metcalfe A,

Connors G, Pollard J, Simrose R, Jones D

Roggensack A, Krause R, Lange I

Division of Maternal Fetal Medicine

Department of Obstetrics and Gynecology

University of Calgary

Calgary Laboratory Services

purpose
PURPOSE

A: To assess the diagnostic accuracy of maternal serum PAPP-A <0.4 MOM (<5th %ile) at 11-13+6 weeks gestation in detecting adverse obstetrical outcomes in a low risk population.

B: To determine if the addition of UA Doppler pulsatility index (PI) at 18 and 22 weeks gestation improves the predictive accuracy of low first trimester PAPP-A in the detection of adverse obstetrical outcomes.

methods part a
METHODS- Part A

TYPE OF STUDY

  • Prospective, non-intervention, matched cohort study

INCLUSION CRITERIA

  • All pregnant women attending for FTS at single site with:
    • Live singleton gestations at 11-13+6 weeks
    • Able to provide informed consent

EXCLUSION CRITERIA

  • Pregnancies with chromosomal or structural abnormalities

LOW PAPP-A

NORMALS

“Normal” PAPP-A (> 0.4 MOM)

Matched by independent reviewer to

cases (2:1) for ethnicity, age, FTS date

Followed to pregnancy outcome

Low PAPP-A (< 0.4 MOM’s)

No interventions specific to low PAPP-A

(patients and physicians ‘blinded’)

Followed to pregnancy outcome

methods part b
METHODS: Part B

TYPE OF STUDY

  • Prospective cohort study

INCLUSION CRITERIA

  • All pregnant women attending FTS February- Oct 2007 with:
    • Live singleton gestations at 11-13+6 weeks
    • PAPP-A < 0.4 MOM
    • Agreeing to additional pregnancy surveillance
    • Provided informed consent

EXCLUSION CRITERIA

  • Pregnancies with chromosomal or structural abnormalities

Additional surveillance & management as clinically indicated

primary outcomes
Primary Outcomes

PRIMARY OUTCOMES ( A&B)

  • Manual in-patient chart review at 3 hospital sites
  • Low Birth Weight (LBW) (<2500 grams)
  • Preterm Delivery (PTB) (< 37 weeks gestation)
  • Pre-eclampsia1 (PIH)
  • Small for gestational age (SGA) (< 10th%ile)
  • SOGC Clinical Practice Guidelines. Diagnosis, evaluation and management
  • of hypertension in pregnancy. JOGC March 2008
statistical analysis
Statistical Analysis

Part A:

Chi square tests were used to compare outcomes (LBW, PTB, PIH and SGA) between groups

Logistic regression was used to determine if low PAPP-A predicts negative outcomes

Part B:

Logistic regression analysis was used to compare outcomes in low PAPP-A patients with positive and negative UA Doppler at both gestational age groups

results part a
RESULTS: Part A

March 2006 – December 2006:

3815 women completed FTS

Low PAPP-A (< 0.4 MOM) n= 198 (5.6%)

Eligible patients with complete obstetrical outcomes n=150 (80%), matched to 300 controls

Demographics

Low PAPP-A group representative of controls:

Average Age: 32 yrs (31% ≥ 35, 4.6% > 40 yrs)

87%: High school +/- University

35%: Primiparous

18%: Non-English speaking (ESL)

slide28
RESULTS : Part A

Incidence (%) of Adverse Outcomes

results part a1
RESULTS: Part A

PAPP-A as a predictor of adverse outcomes

slide30
RESULTS : Part A

PAPP-A: Test performance for adverse outcomes

results
RESULTS

PAPP-A: Test performance for any adverse outcome using cut-offs 0.2 MOM- 0.4 MOM

conclusions part a
CONCLUSIONS- Part A

Low PAPP-A is a significant predictor of adverse obstetrical outcomes

This association would support pregnancy monitoring and surveillance

However, the predictive value of low PAPP-A for these outcomes is weak

Therefore the clinical utility of isolated low PAPP-A as a predictor of adverse obstetrical outcomes is limited

Further study is needed to determine if adjunctive biochemical and ultrasound markers can better identify risk

results part b
RESULTS- Part B
  • January - October 2007;
    • 5359 women completed FTS
    • Low PAPP-A (< 0.4 MOM) n= 289 (5.3%)
    • Patients consenting to ongoing surveillance, n= 229 (79%)
    • Complete obstetrical outcomes, n= 202 (89%)
slide34
RESULTS

Uterine artery Doppler as a predictor of adverse outcomes in low PAPP-A patients

+ uterine artery Doppler = PI > 1.45

slide35
RESULTS

22 Week Uterine Artery Doppler: test performance for adverse outcomes

slide36
RESULTS

18 Week Uterine Artery Doppler: test performance for adverse outcomes

results summary
RESULTS: SUMMARY
  • A positive uterine artery Doppler (PI >1.45) at 18 weeks in low PAPP-A patients was found to significantly predict SGA but not found to significantly predict PTB, PIH or LBW
  • A positive uterine artery Doppler (PI >1.45) at 22 weeks in low PAPP-A patients was found to significantly predict PTB, SGA and LBW but notPIH
conclusions 18 w
CONCLUSIONS- 18 w
  • Uterine artery Doppler at 18 weeks was found to have good specificity and a strong negative predictive value, however, there was a high rate of false positives
  • Economic analysis is required to determine the cost effectiveness of a 2 stage uterine artery Doppler protocol
conclusions 22 w
CONCLUSIONS- 22 w
  • Due to small sample size, we are unable to conclude if uterine artery Doppler at 22 weeks can accurately predict the risk of adverse outcomes in low PAPP-A patients
  • At present, clinical judgement is advised
    • Consider third trimester ultrasound for fetal growth and well-being
  • Future studies are required to verify our findings
  • Larger sample sizes
  • Additional ultrasound and biochemical markers should be evaluated in low PAPP-A patients
slide40
But most importantly, clinical assessment and judgment

of the maternal-fetal unit as a whole can never be forgotten

ad