As one of my end-post promises, I wanted to return to the issue of dealing with ‘abnormal results’ that return with first trimester aneuploidy screening. Again, this is not a straightforward discussion. One of the first issues that has to be addressed is what constitutes an ‘abnormal result?’ Remember, this is not a diagnostic test, it is a screening test, and the result that comes back does not necessarily mean the baby has or does not have the condition for which it is being screened. It provides a risk estimate that is, albeit, generally better than that provided by ‘age alone’ counseling because specific data related to the pregnancy (fetal measurements; pregnancy-specific serum analytes; maternal characteristics and risk factors) are included in the actual risk assessment. Even then, there is not a ‘normal’ or ‘abnormal’ result (although some organizations have elected to classify results as either “risk positive” or “risk negative”) and, to some degree, because the result sits somewhere along a continuum, the risk assessment result needs to be interpreted within the context of the patient’s own risk tolerance. Some folks play nickels in Las Vegas and others hundred dollar chips. Still, as providers, we need to offer some guidance to the patient. It is not fair to place the entire burden of decision-making related to this very complex issue on the patient alone, although, in the end the final decision as to what they do with the information given to them is their decision. The goal should be to make them feel comfortable about their choices.
There are several steps that I take with patients when presenting their screening assessment results. First, I reiterate that we (me and our genetic counselors) are there to provide them with information, review the test results, review their options for further fetal evaluation, answer their questions, and help them to decide what the best course of action is for them, reminding them up front that we will not tell them what to do. In fact, I make it quite clear that I do not care what they do! I then present the risk assessment results and compare this to their age-related risks. I also remind them that this screening test is most successful at diagnosing trisomies 21, 18, and 13, that it may pick up some other, but not all, chromosomal abnormalities, and that it may also miss a small percentage of those abnormalities it is most reliable in detecting. Before I ask for any decisions on their part, I review the risks and benefits of other screening and diagnostic options and suggest that they use this information to help balance the decision-making process.
With regard to the diagnostic options, I focus on two procedures, chorionic villus sampling and amniocentesis, reserving a discussion about percutaneous umbilical cord sampling, or cordocentesis, for special circumstances. I explain the differences in techniques (CVS as a transcervical, or transabdominal, placental biopsy and amniocentesis as a transabdominal technique, sampling 20-30cc of the amniotic fluid with a thin needle) and the risks of pregnancy complications related to the procedures. For counseling purposes, I have stuck with a 1% risk for CVS over the years and have drifted from the classic counseling of 1 in 200-300 risk for amniocentesis to less than 1 in 1000 (which our own experience and recent publications would support). I also explain the options and limitations of rapid (48-72 hr) diagnostic techniques (such as fluorescent in situ hybridization, or FISH) and always suggest these be considered when a specific chromosomal abnormality is highly suspected. I always conclude this part of the discussion with a statement to the effect that they have the option for an invasive diagnostic test, regardless of the risk assessment results, and that the choice depends on their risk tolerance and their ‘need to know’ or need to get more information. I emphasize that these latter questions should take priority over the question of what they would actually do with the information once they had it. The reason I can state that with confidence is that, over the years, it has become quite clear to me that many people DO NOT KNOW what they might do (regardless of age, race, religious, ethnic, spiritual, or socioeconomic background), even with a documented fetal chromosomal abnormality, until they are actually faced with that decision.
I then ask if they have any questions and I always get the response, “Doctor, what would you do if you were in our position?” I can then answer that honestly by telling them that “I am not in your situation and I don’t know what I would do if I were. But, I can give you some general guidelines based on counseling that is offered in other places around the country and the world.” Many institutions routinely recommend CVS when the first trimester risk is greater than 1 in 100. If the pregnancy is beyond the gestational age at which the institution will do a CVS when the result comes back, then an amniocentesis at about 16 weeks is offered.
If the risk is less than 1 in 270 (in the range of the risk of a 35 year old woman to have a baby with Down Syndrome and also the risk range typically quoted for amniocentesis), we currently offer maternal serum ?-fetoprotein (MSAFP) screening only at about 16 weeks and a ‘targeted’ ultrasound examination at 18-20 weeks. The MSAFP screening can provide information about risks for certain fetal abnormalities, such as neural tube defects and abdominal wall defects (usually readily detected at the time of ‘targeted’ ultrasound alone), but of equal importance may suggest, if the results are abnormal, an abnormality of placentation that could put the pregnancy at increased risk for complications and might warrant a change in our recommendations for follow-up.
If the risk falls between 1 in 100 and 1 in 270, amniocentesis is generally offered and if the patient is averse to this, then the second approach outlined above is recommended. Many women will choose the latter approach because, during their counseling, we also inform them that a completely ‘normal’ targeted ultrasound probably reduces their a priori risk (based on the combined first trimester screening result) for aneuploidy by 60-80%., thereby placing them below the risk of a 35 year old woman without the need for an invasive diagnostic study. Indeed, we have found that one of the primary advantages of first trimester screening and midtrimester screening, coupled with ultrasound, is that we have found ourselves performing far fewer invasive procedures than we have done in the past (putting fewer pregnancies at risk from that standpoint).
I want to make it clear. At present, there is no uniform approach (‘standard of care’) to management of the results obtained by first trimester screening. This is the approach we have chosen and, it may change next week, or be very different from that offered at other institutions. The important things are to provide a reliable service within the constraints of the diagnostic capabilities available locally and to make the patient feel comfortable with the decision they make for additional screening, a diagnostic study, or no follow-up at all.