1. Fetal Diagnosis & Counseling of Pregnancy Options
Brian L Shaffer, MD

2. Overview What is prenatal (fetal) diagnosis?
Options Available for Fetal Diagnosis
Screening
Diagnostic
Pictures, Examples
Options for Pregnancy Management
Termination
Continuation
Hospice
Adoption
The primary objectives of this hour are to talk about what options are currently available for fetal diagnosis – including screening methods & diagnostic techniques, highlighting the differences between the two – and giving some examples – and ending with a discussion about how we go about counseling patients & families regarding the options for pregnancy management – including termination or continuation of pregnancy.
At the very end, I’d like to show a brief (6 minute) video-clip highlighting the experiences of two couples who have chosen continuation of affected pregnancies.
This talk is intended to be relatively informal, so please feel free to ask questions or make additional comments at any time.

3. What is a Birth Defect? “Congenital anomaly”
Any abnormality of structure and/or function present at birth
> 4,000 different known birth defects ranging from minor to serious
Minor may be cosmetic only
Serious abnormalities lead to mental or physical disabilities or even death
Birth defects are the leading cause of infant mortality & significant cause of premature death, chronic illness and long-term disability

4. What is the Risk of Having a Fetus with an Abnormality?
Overall risk – ~ 4%
Worldwide - 6 million affected babies born/year
U.S ,000 affected babies born/year
Most common abnormalities
Congenital Heart Disease -- 8/1000
Trisomy 21 – 1/700
Neural Tube Defect -- 1/1000
Cystic fibrosis – 1/3000
So, what is the risk of having a fetus with an abnormality?
The overall risk is 2 to 4 %
Which means that worldwide – approximately 6 million affected babies are born each year
And in the US – approximately 150,000 affected babies are born each year
The most common abnormalities include congenital heart defects, Trisomy 21, and neural tube defects in that order

5. History of prenatal diagnosis
Family history
Ultrasound (US)
Introduced in the 1950s
Amniocentesis
First done in 1877 (for polyhydramnios)
First done for chromosomal studies in 1966
Common since the 1970s
Chorionic villus sampling (CVS)
First done in 1968
Greater acceptance in 1980s-90s
Rapid expansion of serum & US screening options, wide-spread use – 1990s to present
Just to provide some perspective on the field of fetal screening and diagnosis…..It really is a reasonably new field.
The use of ultrasound for fetal diagnosis was just introduced in the 1950s…. And while the first amniocentesis was performed in the late 1800s, the first time that it was used to do a karyotype on a fetus was in just 40 years ago.
Chorionic villus sampling was introduced shortly after amnio It wasn’t really until the 1950s that US and amniocentesis began to be

6. What Can Be Done Prior to Conception?
Identify women/couples at risk
Family history: birth defects or genetic dz
Medications: Coumadin, Accutane
Exposures: smoking, EtOH, drugs
Refer to genetic counselor
Consider carrier testing
Cystic Fibrosis, Sickle Cell, Tay-Sachs
Folate -  risk of NTD
So, how do we go about assessing one’s risk of having a baby with an abnormality, or making a diagnosis of a fetal abnormality?
Ideally, we talk to women & couples prior to pregnancy. Preconceptionally, it’s nice if we can identify those at greatest risk

7. What Options During pregnancy?
Screening vs. diagnostic testing
Provide information early
Personal decision
Factors that may be considered
Desire to terminate if an abnormality is found
Desire to have as much information for preparation
Delivery planning

8. Goal of Prenatal Screening & Diagnosis
To provide a safe & efficacious means of identifying affected pregnancies for those women or couples who wish to exercise reproductive choice or to plan for the care of an affected child

9. What is a Screening Test?
A test done to identify a disease or defect by the application of tests, examinations or other procedures
Provides individual RISK ASSESSMENT
Ads:  number of procedures done for diagnosis & therefore,  procedure-related complications
Disads: not diagnostic, may miss target

10. What is a Diagnostic Test?
A test that will definitively identify a disease or defect
Prenatal diagnostic test
Chromosomal abnormality (aneuploidy), gene change (Sickle cell)
Ads: DEFINITIVE ANSWER
Disads: Risks associated with the diagnostic procedure

11. What Screening Tests Are Available?
Ultrasound
1st trimester – weeks
Serum analytes: PAPP-A, free ß-hCG
Ultrasound evaluation of nuchal translucency
2nd trimester – weeks
Serum analytes: AFP, uE3, hCG, inhibin A
“non invasive” prenatal diagnosis
Maternal Serum – cell free DNA

12. Screening Options Test When Done Detection Rates 1st trimester
(NT + 2 serum)
10-14 weeks
T %
T18 – 80%
Ultrasound
18-20 weeks
T %; T %
NTD %
Quadruple screen
(4 serum analytes)
15-21 weeks
T %; T %
NTD %
*Integrated screen
(1st trimester screen + quadruple screen)
T %
T %
NTD -- 80%
Maternal serum
>7 weeks
T21 - >99%
Other aneuploidy?

13. What if the Screen is Abnormal?
Discussion with patient and her family
Discussion with primary provider
Referral to genetic counselor
Detailed anatomical US
50% of T21 fetuses have a normal US!
Offer diagnostic testing

14. What Diagnostic Tests Are Available?
Chorionic villus sampling – weeks
Amniocentesis – > 15 weeks
Fetal Blood Sampling – rarely done
Ultrasound

15. Chorionic Villus Sampling
10-13 weeks
Trophoblasts cultured
Advantages
Early diagnosis
Disadvantages
Loss rate 0.5-1%
1% risk of confined placental mosaicism

16. Amniocentesis > 15 weeks Remove 15-20 ml of amniotic fluid
Amniocytes cultured
Advantages
Can test AFP levels.
Disadvantages
Loss rate %
Later diagnosis

17. ACOG’s Stance on Prenatal Screening & Diagnosis
All women should be offered aneuploidy screening before 20 weeks, regardless of maternal age
All women should have the option of invasive testing regardless of age
Primary provider should be able to discuss the detection rates, false positive rates, disadvantages & limitations
ACOG Practice Bulletin #77: Screening for Fetal Chromosomal Abnormalities

18. Fetal Blood Sampling (Cordocentesis)
Removal of blood from umbilical cord
Rarely done
Done when diagnostic information can not be obtained through amniocentesis, CVS, US or the results of these tests were inconclusive
Performed after 17 weeks
Potential indications: suspected fetal infection, anemia, thrombocytopenia
Loss rate - 2%

19. How is Ultrasound Used for Screening & Diagnosis?

20. 1st Trimester US What Can We See?
Markers of Aneuploidy & Congenital Heart Disease
 Nuchal translucency
Absent nasal bone
Tricuspid regurgitation

21. 1st Trimester US What Can We See?
Normal Fetus
Anencephaly

22. 1st Trimester US What Can We See?
Multiple Gestation

23. 2nd Trimester Ultrasound What Can We See?
Lethal anomalies
Anencephaly
Skeletal dysplasias
Renal agenesis
Moderate to severe anomalies
Congenital diaphragmatic hernia
Heart defects
Neural tube defects
Gastroschisis, Omphalocele

24. 2nd Trimester Ultrasound What Can We See?
Relatively minor abnormalities
Cleft lip/palate
Club foot
Polydactyly

25. Anencephaly http://i.b5z.net/i/u/909479/i/med_sketch500.gif

26. Neural Tube Defects

27. Gastrochisis

28. Bilateral Cleft Lip & Palate

29. Club Foot & Polydactyly

30. What Happens Once a Diagnosis is Made?
Breaking the bad news…..
Difficult
US technologists often the 1st to recognize - awkward for them & patient
Acknowledge concern
“Ruined the pregnancy for me”
As prenatal testing becomes increasingly sophisticated and routine, more parents are learning devastating news before their babies are born. In many ways, the ability to diagnose a fatal condition has raced ahead of the ability to care for these families and their babies.

31. Breaking the Bad News …. Present all of the facts
Survival, morbidity, quality of life
Show empathy & compassion at all times
Allow the couple time to process the information
Provide them with additional resources
Genetic counselor
Social work
Literature, websites (
Multidisciplinary clinics : Pediatric surgeons, Cardiologists, Neonatologists
Delivery planning

32. Breaking the Bad News…..
Do not let them leave your office without having all of their immediate questions answered & addressed
Encourage them to bring additional support people as needed
Offer to meet with them again at anytime

33. What Are The Options for Management?
Termination by D&C or D&E
Termination by induction of labor
Can be done anytime after 15 weeks
Always done after 24 weeks
Allows parents to spend time with fetus
Allows complete autopsy
Continuation of the pregnancy
Preparation, adoption, delivery planning

34. Nondirective counseling
I cannot overemphasize the importance of this concept

35. Do Fetuses Feel Pain? Hotly debated
Neuroanatomical system complete by 26 weeks
A developed neuroanatomical system is necessary but not sufficient for pain experience
Pain experience also requires development of the mind to accommodate the subjectivity of pain
Unclear
May consider cord/intracardiac injection of KCl prior to termination or induction
Important neurobiological developments occur at 7, 18, and 26 weeks gestation and are the proposed periods for when a fetus can feel pain. The subjective experience of pain cannot be inferred from anatomical developments because these developments do not account for subjectivity and the conscious contents of pain.
Derbyshire SWG BMJ 2006;332:

36. When A Family Decides to Continue the Pregnancy
Offer support without judgment
Continued, regular prenatal care
Social work
Local & online support groups
Perinatal hospice organizations
Encourage them to make plans for delivery
Birth plan, support people
Surgical intervention for fetal distress
Encourage them to make plans for after delivery
Neonatal resuscitation or interventions?
Neonatologist
20-40% of famillies opt to carry the pregnancy to term
40 perinatal hospice programs have been started in the US in the last decade
Often associated with hospitals, hospice nurses, social workers - birthing classes, guidance on how to tell other children in the family that the new baby will not be growing up with them
If the newborn lives beyond a few days, the hospice staff teaches the family how to take care of the baby at home
Helps to give families control over an event that could otherwise cruch them. Goal is to help ease the isolation many families face in dealing with profound grief
Need to make decisions regarding intervention intrapartum, intervention post-delivery, ie intubation, feeding tubes, IV fluids, and surgery

37. http://video. on. nytimes. com/index. jsp

38. Thank You!

40. Preimplantation Genetic Diagnosis
Alternative to conventional prenatal diagnosis
Diagnose cytogenetic or single gene disorders prior to embryo implantation
Biopsy of 1-2 cells from an in vitro embryo
Allows couples to avoid intrauterine transfer of affected embryos
For PGD, the early embryo is examined after IVF for inherited diseases or to determine the sex of the embryo for sex-related genetic disorders. The process starts with a basic IVF. When the embryo is at the 6- to 8-cell stage, 1-2 cells (blastomeres) are removed and sent to the genetic laboratory for diagnosis using either polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH) techniques, depending on which disease is being sought. The unaffected embryos are then transferred into the mother's uterus.
In certain situations in which the genetic problem is only with the female, a polar body can be removed from the eggs and tested before fertilization.

41. Preimplantation Genetic Diagnosis
Advantages
Avoid pregnancy termination
Avoid procedure related pregnancy loss
Improve ongoing pregnancy rates
Disadvantages
Must undergo IVF
Expensive
Can only be done for anomalies associated with cytogenetic or single gene disorders

42. ACOG’s Opinion
"All women, regardless of age, should have the option of invasive testing. A woman's decision to have an amniocentesis or CVS is based on many factors, including the risk that the fetus will have a chromosomal abnormality, the risk of pregnancy loss from an invasive procedure, and the consequences of having an affected child if diagnostic testing is not done. Studies that have evaluated women's preferences have shown that women weight these potential outcomes differently. The decision to offer invasive testing should take into account this preference sand should not be solely age based. The differences between screening and diagnostic testing should be discussed with all women. Thus, maternal age of 35 years alone should no longer be used as a cutoff to determine who is offered screening versus who is offered invasive testing."

43. Multifetal Pregnancy Reduction & Selective Termination
Goal of MPR is to reduce the risk of complications associated with higher order pregnancies by decreasing the number of fetuses in the gestation
Goal of ST is to prevent the survival of a severely impaired fetus of a multiple pregnancy in which the fetuses are discordant for anomalies
Prenatal diagnosis employs a variety of techniques to determine the health and condition of an unborn fetus. Without knowledge gained by prenatal diagnosis, there could be an untoward outcome for the fetus or the mother or both. Congenital anomalies account for 20 to 25% of perinatal deaths. Specifically, prenatal diagnosis is helpful for:
Managing the remaining weeks of the pregnancy
Determining the outcome of the pregnancy
Planning for possible complications with the birth process
Planning for problems that may occur in the newborn infant
Deciding whether to continue the pregnancy
Finding conditions that may affect future pregnancies
There are a variety of non-invasive and invasive techniques available for prenatal diagnosis. Each of them can be applied only during specific time periods during the pregnancy for greatest utility. The techniques employed for prenatal diagnosis include:
Ultrasonography
Amniocentesis
Chorionic villus sampling
Fetal blood cells in maternal blood
Maternal serum alpha-fetoprotein
Maternal serum beta-HCG
Maternal serum estriol

44. How Can Prenatal Diagnosis Be Useful?
Managing the remaining weeks of the pregnancy
Determining the outcome of the pregnancy
Planning for possible complications with the birth process
Planning for problems that may occur in the newborn infant
Deciding whether to continue the pregnancy
Finding conditions that may affect future pregnancies