Objectives: To prospectively and quantitatively grade intracardiac echogenic focus/foci (ICEF) using sonographic gain reduction and to determine the association of ICEF by grade with fetal aneuploidy.
Methods: Women referred for raised maternal age (> or = 35 years), or > 18 years of age and with a Down syndrome risk > or = 1/270, increased trisomy 18 risk by second trimester serum screen or a prior aneuploid offspring were included in this institutionally approved protocol. Only pregnancies of gestational age between 14 and 24 weeks were included. All women had a targeted ultrasound and were offered fetal chromosome analysis. The classification of ICEF was made from a four-chamber view of the fetal heart. The echo amplitude of the ICEF was compared to that of the thoracic spine and categorized according to the comparative gain setting at which the image of the relevant structure disappeared: Grade O = no ICEF present, Grade 1 = ICEF image lost before thoracic spine when gain was reduced, Grade 2 = ICEF image lost at same gain setting as thoracic spine, Grade 3 = thoracic spine image lost before ICEF. The primary outcome was a prenatally or post-natally detected chromosomal abnormality.
Results: A total of 885 eligible women were examined during the 21-month study period. ICEF were seen in 29 (3.3%) fetuses: 24(83%) in the left ventricle and five (17%) in the right ventricle. A chromosome abnormality was identified in 13/671 (1.9%) fetuses without ICEF (Grade 0) and 0/21 (0%) fetuses with Grade 1 ICEF. In contrast, two of five (40%) fetuses with Grade 2 ICEF were aneuploid (P = 0.005). No Grade 3 ICEF were observed. Additional sonographic abnormalities were seen in both aneuploid fetuses with Grade 2 ICEF. Interobserver agreement on ICEF grading was noted in 50/50 (100%) examinations (kappa = 1.0).
Conclusions: Sonographic grading of ICEF is feasible and highly reliable. Grade 2 ICEF, especially when accompanied by additional sonographic markers of a chromosomal abnormality, are associated with aneuploidy significantly more frequently than Grade 1 ICEF.