Christine Pecci, MD University of California, San Francisco Annual - - PowerPoint PPT Presentation

Christine Pecci, MD University of California, San Francisco Annual Review in Family Medicine December 5-6, 2016

A family physician’s approach

The Menu

Genetic disorders and loss

 Two-thirds of unrecognized SAb  Half of recognized 1st trimester losses  5% stillbirths

ACOG Practice Bulletin Number 162, May 2016

Chromosomal Abnormalities

50% 15% 5% 12% 18%

0.4 % of births

Trisomy 21 Trisomy 18 Trisomy 13 Sex Chromosomes Other Obstetrics and Gynecology, Clinical Expert Series ; Dashe July 2016

Apples, oranges and other things

 Chromosome numbers

 extra or missing chromosome  extra set of chromosome (triploidy)

 Chromosome structure

 deletion, duplication, translocation

 Single gene mutations  Neural tube defects  Major fetal anomalies (some associated with

aneuploidy)

What kind of testing does your patient want, if any?

Screening? Diagnosis?

Listen to your patient

“Counseling for aneuploidy

screening has become a conversation”

Dashe, Jodi MD Aneuploidy Screening in Pregnancy Obstetrics and Gynecology July 2016

Risk based on age

1979 Amniocentesis should be

• ffered to >35

Dashe, Jodi MD Obstet Gyn 2016

Evolution of Screening

1977

• MSAFP

1987

• Triple

Screen 1992

• NT

1996

• Quad

Screen 2003

• First

trimester Screening

2007 ACOG statement Screening and diagnostic tests should be offered to all women 2011 Introduction of cf DNA

What kind of testing does your patient want, if any? Diagnostic CVS Amnio Screening None

Diagnostic Procedures

Procedure Chorionic Villus Sampling Amniocentesis Gestational Age 10-13 weeks 15-20 weeks or later Turnaround time 5-7 day turnaround 7-10 day turnaround Procedure loss rate 0.22% 0.1%

Listen to your patient

“Counseling for aneuploidy

screening has become a conversation”

Dashe, Jodi MD Aneuploidy Screening in Pregnancy Obstetrics and Gynecology July 2016

What kind of testing does your patient want, if any? Diagnostic Screening None

What kind of testing does your patient want, if any? Diagnostic Screening The Menu! None

The Menu

1st trimester 2nd trimester Combined Ultrasound Cell-free DNA

Options for screening

First Trimester Second Trimester hcg + PAPP-A hcg + AFP + estradiol + inhibin 11-14 wks 15-22 wks Can be combined w NT Anatomy scan AFP in 2nd trimester for NTD Includes AFP

• 1st trimester screening gives the patient early results
• 2nd trimester screening good for late entry to care
• DON’T do both independently
• CAN do combined (7 serum markers + NT)

Combined 1st and 2nd trimester screening

 Sequential testing

Stepwise

 high risk offered diagnostic testing after 1st trimester  Others get results after second trimester

Contingent

 highest risk offered diagnostic testing after 1st tri  lowest risk reassured- no further testing  Others get results after 2nd trimester

 Integrated testing

Cell-free DNA

 Circulating DNA fragments placental in origin from

apoptotic troploblasts

 Can be done anytime after 9-10 wks gestation  Available in 7-10 days  Best for trisomy 21 and 18 but also screens for trisomy

13 and sex chromosome aneuploidies

 Gender  Can be used as primary or secondary screening

AJOG June 2016 SMFM Consult Series

Dashe, Jodi MD Obstet Gyn 2016

Limitations of cfDNA

 4-8% indeterminate

 occurs 10% in women >250 lbs

 Not for multiple gestation  Does not detect some genetics abnormalities picked

up by traditional testing

 Placenta and fetus do not always have the same

chromosomal complement

 Placental mosaicism can occur

Discussing results

 A “positive” or a “negative” screen needs to be

interpreted with your patient

 Reflects the lab’s chosen threshold

 Positive predictive value

 likelihood that a patient with a positive screening result

has an affected fetus.

 Negative predictive value

 likelihood of a patient with a negative screening test

who does not have the disease

 Look at the exact risk and interpret this individually

according to your patient’s threshold (values)

Disease Present Disease Absent Screen Positive

True positive False positive

Screen Negative

False negative True Negative

PPV = TP/TP+FP NNV=FN/FN+TN

How does US fit into screening?

Ultrasound

 Gestational Age  Number of fetuses  Major and minor findings  90% of babies born with congenital anomalies are

born to women with no risk factors

Major Structural Anomalies

 CV, neuro, GI, GU  25-30% of 2nd trimester fetuses with T21 have a major

anomaly that can be detected

 Trisomy 13 and 18- majority have major  If major anomaly seen, offer diagnostic test

Minor “Soft” US markers

 Nuchal thicknesss  Absent or hypoplastic nasal bone  Echogenic intracardiac focus  Echogenic bowel  Pyelectasis  Shorted femur or humerus  Soft markers present in at least 10% of normal fetuses

and can be transient

Screening desired Early entry 11-14 weeks Serum screening +/- NT (+/- combined) Late entry 15-22 weeks Ultrasound Quad screen cfDNA

What is her risk + what are her values? Is diagnostic testing indicated? Offer serum and US screening Low risk (traditional); High risk (cfDNA) Discuss results and decide on whether to pursue diagnostic testing

Don’t make management decisions without diagnostic test

Resources

 Aneuploidy Screening in Pregnancy

 Jodi S. Dashe. MD  OB GYN volume 128 (1); July 2016 181-194

 Seminars in Perinatology 2016

 Screening for fetal aneuploidy  Ultrasound screening

 ACOG Practice Bulletins May 2016

 Prenatal Diagnostic Testing for Genetic Disorders  Screening for fetal aneuploidy

 https://www.perinatalquality.org/Vendors/NSGC/NIPT/