Schechter, in 1987, was the first author to note a hyperechoic focus within the left ventricular chamber that was associated with the chordae tendinae . In a 1994 review of three fetuses with sonographic and pathologic correlation, Brown et. al.  found that EIF represents papillary muscle mineralization within the fetal heart.
Bromley et. al. in 1995 reported a 4.9% incidence of EIF among 1334 patients studied. They also found that 18% of fetuses with trisomy 21 had an EIF and that sonographic identification of an EIF had a fourfold increase risk of trisomy 21 . Petrikovsky et. al. in 1995 reported a 3.6% incidence of EIF in 1139 patients, all of whom had a normal karyotype. The subjects in this study were not stratified by ethnic origin. Interestingly, the echogenic focus was present in all infants who underwent echocardiographic examination within the first three months of life . In 1996, the same author failed to find any correlation between unusually appearing echogenic foci and adverse perinatal outcome .
Bromley et. al., in 1997, incorporated maternal age and the presence of EIF in the sonographic scoring index for the detection of trisomy 21 . The same group in 1998 reported a 4.8% incidence of aneuploidy in 290 fetuses that had an EIF. In that study the incidence of aneuploidy in patients less than 35 years old was 3.6%. Only one of the 14 aneuploid fetuses had an echogenic intracardiac focus as the only sonographic marker, and this occurred in a woman older than 35 years . Bromley, in 2002, reported similar findings focusing on the likelihood ratios (LR). With an isolated finding of EIF, there was a non-significant LR of 1.4 (95%CI 0.6 – 4.3) as compared to controls .
Smith-Bindman et. al., in a 2001 meta-analysis (a total of 56 studies describing 1930 fetuses with Down syndrome and 130,365 unaffected fetuses were included) of second trimester ultrasound to detect Down syndrome determined that when ultrasonographic markers were observed without associated fetal structural malformations, sensitivity for each one was low (range, 1%–16%), and most fetuses with such markers had normal outcomes . Of the 5 studies in the meta-analysis that specifically looked at EIF there were a total of 5948 patients, 7.3% of whom had EIF.
In 2000, Shipp et. al.  reported on EIF and its correlation to maternal race. They reported a 30.4% prevalence of EIF in Asian patients. There, however, were only 46 (489 total patients) patients in the Asian cohort of their study. Additionally, there was no stratification of Asian patients into various geographic origins. So, it is not known whether they were mainly Japanese or mainly composed of patients of other Asian origin. The current study focuses on Japanese patients only and with a larger sample (148 vs. 49).
A recent meta-analysis by Sotiriadis, et. al , evaluated all comers races with eleven studies for a total of 51,831 pregnancies. Positive and negative likelihood ratios for an isolated finding of EIF were 5.4 and 0.81, respectively. Specificity was approximately 96%. However, a weakness of this meta-analysis is that many of the studies selected were of high risk subjects. In 2001, Nyberg  evaluated the ultrasound findings in 186 fetuses with trisomy 21 and 8728 controls. EIF was the most common marker found among affected fetuses after exclusion of major anomalies (7.1%). The positive LR for an isolated finding if EIF was 1.8. It is not clear why this is significantly lower than that found in the meta-analysis by Sotiriadis as it appears they both evaluated subjects of similar risk. The most likely explanation is the data from the meta-analysis more likely represents the true population given the larger numbers.
Limitations of the current study include a small sample size, the retrospective nature of the review, and the use of a meta-analysis sample that may not be truly representative of the general population. In general, studies of EIF are limited by factors such as technique, experience, and equipment. Our preliminary results revealed no increase in the incidence of aneuploidy despite an increased incidence of EIF. As there is not conclusive evidence in the literature that links isolated EIF to an increased risk of aneuploidy in low risk populations. Caution should be exerted when counseling these patients regarding these findings until there is general expert consensus or conclusive scientific evidence regarding this issue.