1. Achiron R, Barkai G, Katznelson MB, and Mashiach S. Fetal Lateral Ventricle Choroid Plexus Cysts: the Dilemna of Amniocentesis. Obstet Gynecol (1991) 78:815-818.
2. Twining P, Zuccollo J, Clewes J, Swallow J. Fetal Choroid Plexus Cysts: A Prospective Study and Review of the Literature. British J Radiology (1991) 64:98-102.
3. Platt LD, Carlson DE, Medearis AL, Walla CA. Fetal Choroid Plexus Cysts in the Second Trimester of Pregnancy: A Cause for Concern. Am J Obstet Gynecol (1991)164:652-6.
4. Benacerraf BL. Harlow B, Frigoletto FT. Are Choroid Plexus Cysts an Indication for Second Trimester Amniocentesis. Am J Obstet Gynecol (1990) 62:1001-1006.

These four papers add to the current controversy regarding the association of choroid plexus cysts (CPC) of the fetal lateral ventricle and the occurrence of trisomy 18. The paper by Achiron and colleagues is a relatively unselected cohort study that determines that the incidence of CPC in their Israeli population is 0.6%. Two of their 30 fetuses with CPC's had trisomy 18. The authors make a number of assumptions regarding the occurrence of CPC's in the second trimester fetuses with trisomy 1 8 and estimate a figure of 25 of 38 fetuses from the literature or about 66%. Taking this figure, as well as the prevalence of trisomy 18 in newborns, and the frequency of CPC's in the general population, the authors calculate that the risk of trisomy 18 in a fetus with a CPC is 3.3%. Allowing for the assumption that about 70% of fetuses with trisomy 18 will have other anomalies on ultrasound, the authors estimate that the risk of trisomy 18 in a fetus with no other anomalies at ultrasound is about 1%. Since this figure is higher than the usual risk estimated for a woman of 35 years of age, the authors recommend amniocentesis in second trimester diagnosed cases of CPC. Twinning's study is also a relatively unselected cohort which showed a yield of one fetus with trisomy 18 in 19 who had a CPC. One other case in their series had trisomy 21. These authors emphasize the frequency of other anomalies on ultrasound in fetuses with trisomy 18 and recommend amniocentesis only when there are other anomalies or when the cysts are greater than 13 mm. and bilateral. The paper by Platt and colleagues recommends routine amniocentesis in cases of second trimester detected CPC. Their cohort is more selected, and detects 3 cases of trisomy 18 out of 62 that have an amniocentesis. In the discussion at the end of the paper, the authors recommend that we "inform our patients of this relationship and offer an amniocentesis and whether the couple accepts the recommendation is entirely up to them." In contrast to the opinions of Platt and Achiron, Benaceraf, et al take the opposite position. These authors basically performed a case control study looking for the frequency of CPC's in patients diagnosed with trisomy 18 fetuses through their amniocentesis and ultrasound program. Six of 21(28.6%) fetuses imaged in the second trimester between 13.5 and 18 weeks had a CPC.
These authors used this figure (which was lower than the figures proposed by Achiron) and took the prevalence of trisomy 18, the frequency of CPC's in second trimester fetuses in general, and the occurrence of other anomalies on ultrasound in trisomy 18 and estimated that only one fetus with trisomy 18 would be detected for every 477 normal fetuses with CPC's (assuming no other sonographic abnormality). Because of this low-positive predictive value in fetuses with CPC and no other anomalies on ultrasound, the authors felt that amniocentesis was not indicated in this situation.

Comment:
CPC's were first described on a prenatal ultrasound in 1984 inS fetuses who were normal. Since that time, a number of case reports and series have appeared suggesting some association between the presence of second trimester CPC and chromosome abnormalities, especially trisomy 18. In these series, about half of all CPC's detected are bilateral. Some are loculated and complex and the mean size is about 6 to 7 mm. Eighty to 94% resolve by 24 weeks of pregnancy depending upon the series. CPC's appear to be normal variants of histogenesis of the choroid plexus. Thus, like other phenotypic variations, it is biologically plausible to say that they occur with increased frequency in individuals with trisomy 18 or trisomy 21.

Taken together 31 cases of trisomy 18 with CPC in prenatal ultrasound have been reported in the literature since 1985. These cases either occurred as individual case reports, in small series, or in the epidemiologic cohort studies. Eleven prospective investigations have occurred but only 4 of them are unselected. The other studies have some degree of selection bias due to their referral system. These four studies include the ones cited above by Achiron and Twinning, as well as 2 other studies (Ostlere, et al and Camurri) (see citations below).

These four series involve second trimester scans on over 24,000 pregnancy resulting in 159 CPC's, an incidence of 0.7%. Seven of these 159 or 4.4% had trisomy 18. This figure of CPC in ultrasound represents an emperic estimate of the occurrence of trisomy 18. However, this figure may still be too high given publication bias. This concept involves the notion that there is a tendency for investigators to report only their positive findings and thus, the negative studies rarely occur in such analyses. The theoretical risk of trisomy 18 in second trimester CPC's discussed above (papers of Achiron and Benacerrof) could also be used as an estimation of risk. However, these authors make a number of assumptions about figures in their studies: the crucial figure is the frequency of CPC's in second trimester fetuses with trisomy 18. This particular figure is probably somewhere between the 28.6% estimated by Benacerrof and the 66% estimated by Achiron; a precise figure, however, is not available. The risk, then, of trisomy 18 in a second trimester fetus with a CPC is somewhere between 0.9 and 5% depending on one's approach and assumptions. It is, however, also of note, that about 70-80% of second trimester fetuses with trisomy 18 will have one or more other ultrasound detected defects. Thus, the occurrence of trisomy 18 in a fetus with a CPC and otherwise normal ultrasound, is between 1 and 400 and 1% depending upon the chosen assumptions and figures. Despite the limitations of small numbers, selection bias in most of the cohorts and publication bias, this editor would lean toward the figure of 1% and feel that the presentation of the option of amniocentesis is warranted. In regards to the issue of bilateral ity or size of the cyst, there is a tendency in the cases of trisomy 18 for the cyst to be bilateral and larger than 10mm but the numbers are too small to factor these issues into the equation. As in all cases of reproductive risk counseling, this information would need to be presented to the family and the final choice would be up to them.