Clinical Genetics IV: The Practice of Prenatal Diagnosis

Lecture 29

December 3(Monday), 2001

Required Reading: Principles of Medical Genetics

Gelerhter TD, Collins FS, Ginsburg D

1998 Williams and Wilkins

Pages: 297-307


    • Know that all couples face a nearly 3% risk that their child will be born with a medical problem or birth defect that will require intervention.

    • Understand that prenatal tests are used specifically and selectively. There is no 100% guarantee of a healthy baby even if when prenatal tests are done (such as cytogenetic analysis and ultrasounds) and are completely normal.

    • The use of non-directive genetic counseling in prenatal diagnoses, selective terminations, and assisted reproductive technologies is extremely important.

    • Understand that ethnocultural, moral, and/or religious backgrounds that may strongly influence an individual’s or couple’s choice surrounding prenatal diagnosis, selective termination of a pregnancy, and the use of reproductive technologies. Appreciate the difficult decisions that individuals, couples and families must face when encountering situations where pregnancy termination is being considered or presented as an option.

    • Examine your own moral/religious/cultural beliefs regarding challenging and complex issues surrounding prenatal diagnosis and available options. Make an effort to understand the potential biases you may bring to a genetic counseling session where these issues are discussed. Find ways to address your feelings and concerns regarding these issues prior to meeting with your patients to avoid introducing personal biases.

    • Understand the grief process associated with unanticipated pregnancy loss due to genetic causes or due to pregnancy termination that couples might face. Be aware of the important role a physician or other health care worker can play in helping individuals/couples/families cope with that grief. Specifically, understand the importance of providing individuals with education information about their fetus and the disorder, address why this may have happened without implying blame, provide for "remembrances" of their fetus (photographs, clips of hair, a chance to hold their fetus), access to support groups/counseling, and general information about recurrence risk. An autopsy and further genetic studies may be needed to understand the cause of fetal demise and the parents should understand the need for these studies and plans for follow-up counseling should be made. It is important to raise the issue of burial of the fetus and/or memorial services as some individuals/couples desire and benefit from these services. It is usually not helpful to suggest that couples make immediate decisions about having future pregnancies at the acute time of the loss. For instance, the time of a pregnancy loss or termination would not be the ideal time to recommend various sterilization procedures to avoid having future pregnancies or, at the other extreme, to suggest they ‘forget about this loss’ and try to have another baby as soon as possible. It is usually most helpful to see individuals/couples back after the loss/termination to discuss future family planning issues, more details about recurrence risks, and reproductive options.

    • Know that some couples undergo preconception genetic counseling and evaluation prior to becoming pregnant in order to determine their risks and prepare for future prenatal testing if desired. Understand this concept and the utility of such counseling.

    • Understand the variable effects of prenatal diagnosis that results in pregnancy termination on gene frequency and disease frequency. In general, selective terminations of fetuses with later adult-onset autosomal diseases that have a low mutation rate and high reproductive fitness could have a significant effect on gene frequency whereas selective termination of fetuses with autosomal recessive disorders which are lethal in childhood would only effect the gene frequency if carriers would also decide to have less children, reducing the chance of having other carriers.


    • Be able to generally describe the major kinds of prenatal diagnostic techniques. Know the indications, applications, benefits and limitations of the different types of prenatal diagnostic techniques.

    • Be able to describe the general differences between the commonly applied techniques of amniocentesis and chorionic villus sampling (CVS).

    • Know that CVS can be done earlier in the pregnancy (generally 9-12 weeks gestation) than amniocentesis (generally 16-20 weeks gestation) and the risk of fetal loss during CVS is relatively low, 1% or less. Risks from amniocentesis are even lower about .5% or slightly less. Thus since the risks are not dramatically different, many women prefer CVS since that can be done earlier providing results that may help them decide whether or not to terminate a pregnancy.

    • The risks of fetal loss associated with percutaneous umbilical blood sampling (PUBS) or fetal blood sampling are higher than amniocentesis or CVS. The risks are relatively low if done later in the pregnancy (when the umbilical vessel is bigger) but this is at a time when pregnancy termination is no longer a potential option. For this reason, some individuals might accept the higher rate of loss (approximately 2%) associated with this technique during the early-mid second trimester in order to obtain a relatively rapid diagnosis.

    • Cytogenetic studies on amniocytes and trophoblasts generally take 10-14 days, as they must be cultured before cytogenetic analysis can be done. DNA tests from CVS samples often do not require culturing and can be done often within 3-5 days if it is a PCR based test. Fetal blood cell cytogenetic analysis and DNA analyses can be done in 3-5 days.

    • PUBS may be the best way to detect a disorder for which other biochemical, molecular, or cytogenetic studies are not yet available. Although there has been some progress in detecting fetal cells in maternal blood specimens, this is not yet state-of-the-art for most prenatal tests.

    • Understand the potential utility and limitations of fetal ultrasounds in evaluating a fetus for structural birth defects.

    • Know the difference between screening tests and more definite genetic tests.

    • Understand that "AFP screening" is routinely done during most pregnancies and elevated measurements of maternal alpha fetal protein may indicate a neural tube abnormality and therefore requires further evaluation. Know that other factors such as wrong gestational dates, fetal death, and multiple gestations may cause erroneous elevations of serum AFPs. A lower than normal AFP screen can be associated with chromosomal trisomies such as Down syndrome but this is not very specific or sensitive. Use of AFP screening along with screening of other metabolites including unconjugated estriol and human chorionic gonadotropin increases the sensitivity of the screen and is reported to pick up approximately 60% of infants with Down syndrome. Because serum AFP screening alone and/or the "triple screen" is not even close to 100% specific or 100% sensitive it is imperative that these tests be recognized as only screening tests and that more definitive studies (e.g. detailed ultrasounds for elevated AFP levels and chromosome analyses if trisomy is being considered) must be done in order to establish or disprove a suspected diagnosis.

    • Understand that the cytogenetic, biochemical, and molecular techniques used in prenatal diagnosis are generally similar to standard techniques but have different specimen requirements and, oftentimes, different urgency associated with the testing. Pregnancy terminations are legal only up to 24 weeks gestation in most states. Additionally, many couples note that termination is emotionally harder at later dates.

    • Understand the importance of good prenatal care — avoidance of known teratogens AND the use of vitamin supplementation to reduce birth defects. Specifically, known about the importance of taking FOLIC ACID to reduce neural tube defects as well as other birth defects. All women of child bearing age should who are at "risk" of becoming pregnant should have an adequate intake of folic acid PRIOR to and during pregnancy.


    • Understand that a variety of assisted reproductive technologies are available for couples to consider including (but not limited to): artificial insemination (donor sperm), sex selection based on sperm sorting followed by assisted reproductive techniques to achieve pregnancy, donor ovum with or without surrogate parenting, in-vitro fertilization, and even preimplantation diagnosis.

    • Know that preimplantation diagnosis means that fertilization takes place in vitro and DNA tests are performed on single cells of very early embryos (4-16 cell stage). If the cell does not have the mutation being tested for, the embryo it was derived from is allowed to implant in a uterus prepared for pregnancy.

    • Know that in-vitro fertilization techniques can result in multiple fetuses and that selective termination of some fetuses is sometimes done to increase the chances of having healthy babies born near term.

    • Know that new technologies that have reproductive potential are being developed. Know what the issues are surrounding somatic cell mammalian cloning by nuclear transfer. Understand that this technique of taking the nucleus from an adult somatic cell and implanting it into an enucleated egg that is allowed to implant in an appropriate uterine environment has resulted in the birth of rodent and sheep clones. Know that worldwide discussions are taking place regarding potential applications of similar methods of human cloning.