Is a Genetic Amniocentesis Indicated for Isolated Choroid Plexus Cyst or Echogenic Cardiac Focus?

Abstract & Commentary

By John C. Hobbins, MD, Professor and Chief of Obstetrics, University of Colorado Health Sciences Center, Denver, is Associate Editor for OB/GYN Clinical Alert.

Dr. Hobbins reports no financial relationship to this field of study.

Synopsis: Genetic amniocentesis is not warranted when isolated choroid plexus cysts or echogenic cardiac foci are noted on prenatal ultrasound.

Source: Ouzounian JG, et al. Isolated choroid plexus cyst or echogenic cardiac focus on prenatal ultrasound: is genetic amniocentesis indicated? Am J Obstet Gynecol. 2007;196 (6): 595.e1-595.e3

Aside from advanced maternal age, two of the most common reasons for referral for a genetic sonogram are fetal choroid plexus cysts (CPCs) and echogenic intracardiac foci (EIFs). Likelihood ratios for Down syndrome with EIF vary appreciably in the literature, as do likelihood ratios for trisomy 18 with CPCs. Since both findings are quite common, it has become extremely important to find data that will put these findings in proper perspective when they are "isolated," especially in patients at low risk for either trisomy 21 (T21) or trisomy 18 (T18).

In a recent report, data were culled from a California Kaiser Permanente database from 1998 to 2004. During this time, 515 patients were noted to have fetuses with isolated EIF (240 or 46.6%) and/or CPCs (275 or 53.4%). Those with risk factors (AMA, elevated risk for aneuploidy by second trimester biochemistry) were analyzed separately. Since Kaiser is a closed system, the authors were able to obtain amniocentesis and birth data on all patients getting care within the study period.

Of the 515 patients with EIF/CPC, 429 (83.3%) were isolated and in low-risk mothers. Eighty-six (16.7%) had risk factors and/or other ultrasound findings. Thirty-six percent of the former group and 43.3% in the latter group had amniocenteses. In those having amnios with risk factors, 2 had fetuses with T18. In the low-risk group, none of the amnio patients were positive for aneuploidy. Of the 20,122 live births recorded during the study period, there were 27 infants with aneuploidy, all of whom had T21. None of these had isolated CPCs or EIFs. Therefore, isolated CPC/EIF had a positive predictive value of 0% in a low-risk population. The authors concluded that their study had the statistical power to detect a difference in outcome when isolated EIF or CPCs were found and that "amniocentesis does not appear to be warranted in low-risk patients with isolated CPCs or EIFs."

Commentary

It is clear that there is an association between EIF and T21, as well as between CPC and T18. However, Bromley and others have shown no association between CPCs and T21. Likelihood ratios have been derived for both EIF and CPCs based on the percentage of fetuses with aneuploidy that have had them and the prevalence of the findings in an accompanying normal population of fetuses. These positive likelihood ratios have varied from 1.5 up to 7. The problem is that even in studies where the findings were judged to be "isolated," (especially in the older studies) one wonders what isolated really meant. Were other markers for T21 and T18 really evaluated or did the search only involve major abnormalities? Also, in some cases, how diligent were the sonologists/sonographers in investigating other signs when the patients were about to have an amniocentesis?

An EIF represents an increase in density in the papillary muscles, generally, in the left ventricle, and the brightness can vary according to the patient's body habitus, the frequency of the transducer used, and the angle at which the heart is approached. At least one quarter of patients referred to us do not have an echogenic focus that is as bright as adjacent bone. Also, the prevalence of this finding depends upon the population studied. For example, one study shows up to 15% of Asian fetuses will have EIFs. CPCs vary in size between simply a mottled appearance of the plexus to some that measure over 5 mm, and often some disappear by the time they get to us. However, CPCs have little meaning once other signs of T18 have been excluded, since it is extremely rare for a fetus with this condition to not have at least 2 and up to 8 abnormal findings. Also, the quad screen is an excellent exclude of T18 despite statements in the literature (and in some laboratory reports) that the sensitivity is only 60% for this condition. However, this is at a screen positive rate of 0.5%. If the bar is set at 5%, then over 90% of fetal T18 will be screened in.

So, the take home message is that if a CPC or EIF is found, a diligent attempt should be made to look for other markers for Down syndrome (with an EIF) or T18 (with CPC), and if none is found, and the patient is in a low-risk category, the likelihood is no greater than her pre-scan risk. Also, under these circumstances the risk for T18 is most likely less than the risk of amniocentesis (see Jan. '07 OB/GYN Clinical Alert on amniocentesis risk).