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

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.

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

What is the Risk of Having a Fetus with an Abnormality? Overall risk – ~ 4% Worldwide - 6 million affected babies born/year U.S. - 150,000 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

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 1966 --- 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

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

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

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

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

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

What Screening Tests Are Available? Ultrasound 1st trimester – 10-14 weeks Serum analytes: PAPP-A, free ß-hCG Ultrasound evaluation of nuchal translucency 2nd trimester – 15-21 weeks Serum analytes: AFP, uE3, hCG, inhibin A “non invasive” prenatal diagnosis Maternal Serum – cell free DNA

Screening Options Test When Done Detection Rates 1st trimester (NT + 2 serum) 10-14 weeks T21 -- 83% T18 – 80% Ultrasound 18-20 weeks T21 -- 60%; T18 -- 85% NTD -- 70-98% Quadruple screen (4 serum analytes) 15-21 weeks T21 -- 75-80%; T18 -- 60% NTD -- 80-90% *Integrated screen (1st trimester screen + quadruple screen) T21 -- 92% T18 -- 90% NTD -- 80% Maternal serum >7 weeks T21 - >99% Other aneuploidy?

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

What Diagnostic Tests Are Available? Chorionic villus sampling – 10-13 weeks Amniocentesis – > 15 weeks Fetal Blood Sampling – rarely done Ultrasound

Chorionic Villus Sampling 10-13 weeks Trophoblasts cultured Advantages Early diagnosis Disadvantages Loss rate 0.5-1% 1% risk of confined placental mosaicism http://www.pennhealth.com/health_info/pregnancy/000242.htm

Amniocentesis > 15 weeks Remove 15-20 ml of amniotic fluid Amniocytes cultured Advantages Can test AFP levels. Disadvantages Loss rate 0.1-0.5% Later diagnosis

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

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%

How is Ultrasound Used for Screening & Diagnosis?

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

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

1st Trimester US What Can We See? Multiple Gestation

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

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

Anencephaly http://i.b5z.net/i/u/909479/i/med_sketch500.gif http://www.obgyn.net/us/cotm/0006/Anencephaly%205.jpg

Neural Tube Defects

Gastrochisis

Bilateral Cleft Lip & Palate

Club Foot & Polydactyly

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.

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 (http://www.birthdefects.org/) Multidisciplinary clinics : Pediatric surgeons, Cardiologists, Neonatologists Delivery planning

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

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

Nondirective counseling I cannot overemphasize the importance of this concept

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;332:909-912

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

http://video. on. nytimes. com/index. jsp http://video.on.nytimes.com/index.jsp?auto_band=x&rf=sv&fr_story=79cf26acead199fa0a000074e41deda20072c923

Thank You!

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.

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

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."

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

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