Doppler U/S better than amnio for Rh+ pregnancy

In the management of Rh-alloimmunized pregnancies, Doppler ultrasonography (U/S) of the middle cerebral artery is superior to amniocentesis in predicting fetal anemia and is a safe alternative for monitoring such pregnancies, according to a study in the July 13 issue of the New England Journal of Medicine.

Dick Oepkes, MD, of Leiden University Medical Center in Leiden, the Netherlands, and colleagues compared the accuracy of Doppler U/S and amniocentesis in assessing 165 fetuses, 74 of which had severe anemia.

The researchers found that Doppler U/S had superior sensitivity (88% vs. 76%), specificity (82% vs. 77%) and accuracy (85% vs. 76%) compared to amniocentesis.

Commentary by Kenneth J. Moise, Jr., MD, Upjohn Distinguished Professor of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of North Carolina School of Medicine, Chapel Hill.

Red cell alloimmunization in pregnancy continues to occur despite the widespread use of Rhesus immune globulin. US birth certificates from 2003 indicate that 6.8 per 1,000 live births are complicated by this disease.¹ In approximately 10% of cases, the maternal anti-D titer is high enough to cause severe fetal anemia (hemolytic disease of the fetus/newborn; HDFN), necessitating intrauterine transfusion.

Since the sentinel work of Bevis and Liley in the early 1960s to indirectly determine the degree of fetal anemia through the measurement of the amniotic fluid bilirubin (DOD₄₅₀), many investigators have looked for a noninvasive method of assessing the severity of HDFN.^2,3 Ultrasound has been used to assess the size of the fetal liver and spleen-two organs that respond to fetal anemia as sites of extramedullary hematopoiesis. Additional ultrasonographic parameters including the umbilical venous diameter, placental thickness, and amniotic fluid volume have also been evaluated. More recently, blood velocities in various fetal vessels have been measured using Doppler to see if changes could accurately reflect the degree of fetal anemia. None of these measurements was able to reliably predict the severity of HDFN.

In 1990, one researcher reported an association between the peak velocity in the middle cerebral artery (MCA) and fetal hemoglobin.⁴ However, it wasn't until a landmark study done 10 years later that a threshold of 1.5 multiples of the median (MoM's) for the peak MCA velocity was established for the detection of moderate-to-severe fetal anemia.⁵ The false-positive rate in this study was 12%; but more importantly no cases of significant fetal anemia were missed when the MCA was <1.5 MoM's.

The Oepkes et al. study further supports the value of MCA Doppler as compared to amniocentesis for DOD₄₅₀.⁶ In 165 patients with severe fetal anemia, Doppler was both more sensitive and specific than amniocentesis in detecting fetal disease. The negative predictive value for MCA Doppler was 89% as compared to 80% with amniocentesis. This would indicate that the Doppler is better at determining which fetus is not anemic.

All new diagnostic techniques require a learning curve when they move from the research arena to the bedside. Improvements in color Doppler imaging have allowed the sonographer to easily visualize the fetal circle of Willis. The pulsed Doppler gate can then be placed at the origin of the MCA from the internal carotid artery. Angle correction software should not be used; evaluation of the MCA more proximate to the maternal abdominal wall is preferred; however, the contralateral MCA will yield similar results. Studies can be started as early as 18 weeks' gestation and should be repeated every week. If the rise in the peak velocities after three serial studies is minimal, repeat examinations can be spaced to every 2 weeks.