The mitral gap at 11 + 0 to 13 + 6 weeks: marker of trisomy 21 or artifact?

OBJECTIVES To investigate the possible association between a particular pulsed Doppler waveform pattern, mitral gap, and trisomy 21 at 11 + 0 to 13 + 6 weeks. METHODS We performed two studies. The first was a retrospective analysis of pulsed Doppler velocity waveforms of the mitral valve inflow, recorded during specialist fetal echocardiography in 291 chromosomally normal and 144 trisomy 21 fetuses with a nuchal translucency (NT) thickness of 3.5 mm or more. We examined each waveform in each trace to determine whether there was a gap between the E-wave (early diastolic filling) and A-wave (atrial contraction) in the waveform across the mitral valve. We also examined each trace that contained at least one waveform with a mitral gap and, first, noted the order of waveforms with a mitral gap relative to those without and, second, measured the A-wave peak velocity in a representative waveform with a mitral gap and in one without. The second study was a prospective investigation in which Doppler velocity waveforms of the mitral valve inflow were assessed in 227 singleton pregnancies immediately before chorionic villus sampling. RESULTS A mitral gap was observed in 16 (5.5%) of the chromosomally normal and in 25 (17.4%) of the trisomy 21 fetuses. The incidence of mitral gap was significantly associated with the presence of cardiac defects but not with thickness of NT. The median number of waveforms per recorded image was 6 (range, 3-7) and in 32 (78%) of the 41 traces with a mitral gap only one or two of the waveforms was abnormal. The abnormal waveforms were in the middle or at the end of the trace in 95% of cases and had a lower mean A-wave peak velocity than did the normal waveforms (mean difference 3.7 cm/s; 95% CI, 0.3-7.0 cm/s; P = 0.03). In a prospective study of 10 normal fetuses we could produce a mitral gap deliberately by moving the sample volume out of the center of flow in the atrioventricular valve. In the prospective study of 227 pregnancies undergoing chorionic villus sampling a mitral gap was observed in 26/197 (13.2%) in which the fetal karyotype was subsequently found to be normal, 4/20 (20%) with trisomy 21 and 1/10 with other chromosomal defects. CONCLUSIONS At 11 + 0 to 13 + 6 weeks, a mitral gap may be more common in fetuses with trisomy 21 than in fetuses with a normal karyotype. However, it is possible that a mitral gap does not reflect an underlying hemodynamic abnormality, but is rather the result of suboptimal positioning of the Doppler sample volume as the fetus moves during acquisition.