Noninvasive Diagnosis by Doppler Ultrasonography of Fetal Anemia Due to Maternal Red-Cell Alloimmunization
Giancarlo Mari, M.D., Russell L. Deter, M.D., Robert L. Carpenter, M.D., Feryal Rahman, M.D., Roland Zimmerman, M.D., Kenneth J. Moise, M.D., Karen F. Dorman, R.N., M.S., Avi Ludomirsky, M.D., Rogelio Gonzalez, M.D., Ricardo Gomez, M.D., Utku Oz, M.D., Laura Detti, M.D., Joshua A. Copel, M.D., Ray Bahado-Singh, M.D., Stanley Berry, M.D., Juan Martinez-Poyer, M.D., Sean C. Blackwell, M.D., for The Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses
Background Invasive techniques such as amniocentesis and cordocentesisare used for diagnosis and treatment in fetuses at risk foranemia due to maternal red-cell alloimmunization. The purposeof our study was to determine the value of noninvasive measurementsof the velocity of blood flow in the fetal middle cerebral arteryfor the diagnosis of fetal anemia.
Methods We measured the hemoglobin concentration in blood obtainedby cordocentesis and also the peak velocity of systolic bloodflow in the middle cerebral artery in 111 fetuses at risk foranemia due to maternal red-cell alloimmunization. Peak systolicvelocity was measured by Doppler velocimetry. To identify thefetuses with anemia, the hemoglobin values of those at riskwere compared with the values in 265 normal fetuses.
Results Fetal hemoglobin concentrations increased with increasinggestational age in the 265 normal fetuses. Among the 111 fetusesat risk for anemia, 41 fetuses did not have anemia; 35 had mildanemia; 4 had moderate anemia; and 31, including 12 with hydrops,had severe anemia. The sensitivity of an increased peak velocityof systolic blood flow in the middle cerebral artery for theprediction of moderate or severe anemia was 100 percent eitherin the presence or in the absence of hydrops (95 percent confidenceinterval, 86 to 100 percent for the 23 fetuses without hydrops),with a false positive rate of 12 percent.
Conclusions In fetuses without hydrops that are at risk becauseof maternal red-cell alloimmunization, moderate and severe anemiacan be detected noninvasively by Doppler ultrasonography onthe basis of an increase in the peak velocity of systolic bloodflow in the middle cerebral artery.
Source Information
From the Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Conn. Other authors were Russell L. Deter, M.D., and Robert L. Carpenter, M.D., Baylor College of Medicine, Houston; Feryal Rahman, M.D., King Faisal Hospital and Specialist Centre, Riyadh, Saudi Arabia; Roland Zimmerman, M.D., Klinik und Poliklinik für Geburtshilfe, Universitätsspital, Zurich, Switzerland; Kenneth J. Moise, Jr., M.D., and Karen F. Dorman, R.N., M.S., University of North Carolina, Chapel Hill; Avi Ludomirsky, M.D., Pennsylvania Hospital, Philadelphia; Rogelio Gonzalez, M.D., and Ricardo Gomez, M.D., Universidad Católica de Chile, Sótero del Río Hospital, Santiago, Chile; Utku Oz, M.D., Laura Detti, M.D., Joshua A. Copel, M.D., and Ray Bahado-Singh, M.D., Yale University School of Medicine, New Haven, Conn.; and Stanley Berry, M.D., Juan Martinez-Poyer, M.D., and Sean C. Blackwell, M.D., Wayne State University, Hutzel Hospital, Detroit.
Address reprint requests to Dr. Mari at the Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar St., P.O. Box 208063, New Haven, CT 06520-8063, or at giancarlo.mari{at}yale.edu.
Lockwood, C. J., Nadel, A. S., King, M. E., Roberts, D. J.
(2009). Case 16-2009 -- A 32-Year-Old Pregnant Woman with an Abnormal Fetal Ultrasound Study. NEJM
360: 2225-2235
[Full Text]
Weisz, B, Rosenbaum, O, Chayen, B, Peltz, R, Feldman, B, Lipitz, S
(2009). Outcome of severely anaemic fetuses treated by intrauterine transfusions. Arch. Dis. Child. Fetal Neonatal Ed.
94: F201-F204
[Abstract][Full Text]
Gajjar, K., Spencer, C.
(2009). Diagnosis and management of non-anti-D red cell antibodies in pregnancy. The Obstetrician and Gynaecologist
11: 89-95
[Abstract][Full Text]
To, M., Kidd, M., Maxwell, D.
(2009). Prenatal diagnosis and management of fetal infections. The Obstetrician and Gynaecologist
11: 108-116
[Abstract][Full Text]
Vaisbuch, E., Romero, R., Kusanovic, J. P., Erez, O., Mazaki-Tovi, S., Gotsch, F., Kim, C. J., Kim, J.-S., Yeo, L., Hassan, S. S.
(2009). Three-Dimensional Sonography of Placental Mesenchymal Dysplasia and Its Differential Diagnosis. J Ultrasound Med
28: 359-368
[Abstract][Full Text]
de Laat, M. W. M., Manten, G. T. R., Nikkels, P. G. J., Stoutenbeek, P.
(2009). Hydropic Placenta as a First Manifestation of Twin-Twin Transfusion in a Monochorionic Diamniotic Twin Pregnancy. J Ultrasound Med
28: 375-378
[Full Text]
Abourazzak, S., Hajjaj, S., Hakima, C., Bouharrou, A., Hida, M.
(2009). Haemolytic disease of the newborn due to anti-c. BMJ Case Reports
2009: bcr0920080987-bcr0920080987
[Abstract][Full Text]
Clark, E. A. S., Lacoursiere, D. Y., Byrne, J. L. B., Ponder, R., Silver, R. M., Esplin, M. S.
(2009). Reliability of Fetal Middle Cerebral Artery Velocity Measurements: A Randomized Controlled Trial of Sonographer Training. J Ultrasound Med
28: 19-25
[Abstract][Full Text]
Tongsong, T., Wanapirak, C., Sirichotiyakul, S., Tongprasert, F., Srisupundit, K.
(2007). Middle Cerebral Artery Peak Systolic Velocity of Healthy Fetuses in the First Half of Pregnancy. J Ultrasound Med
26: 1013-1017
[Abstract][Full Text]
Steiner, L. A., Bizzarro, M. J., Ehrenkranz, R. A., Gallagher, P. G.
(2007). A Decline in the Frequency of Neonatal Exchange Transfusions and Its Effect on Exchange-Related Morbidity and Mortality. Pediatrics
120: 27-32
[Abstract][Full Text]
Dashe, J. S., Ramus, R. M., Santos-Ramos, R., McIntire, D. D., Twickler, D. M.
(2007). Middle Cerebral Artery Peak Systolic Velocity in Monochorionic and Dichorionic Twin Pregnancies. J Ultrasound Med
26: 195-200
[Abstract][Full Text]
Hershkovitz, R., Sheiner, E., Mazor, M.
(2006). Middle cerebral artery blood flow velocimetry among healthy fetuses with a single umbilical artery.. J Ultrasound Med
25: 1405-1408
[Abstract][Full Text]
Oepkes, D., Seaward, P. G., Vandenbussche, F. P.H.A., Windrim, R., Kingdom, J., Beyene, J., Kanhai, H. H.H., Ohlsson, A., Ryan, G., the DIAMOND Study Group,
(2006). Doppler ultrasonography versus amniocentesis to predict fetal anemia.. NEJM
355: 156-164
[Abstract][Full Text]
Moise, K. J. Jr.
(2006). Diagnosing hemolytic disease of the fetus--time to put the needles away?. NEJM
355: 192-194
[Full Text]
Kumar, S., Regan, F.
(2005). Management of pregnancies with RhD alloimmunisation. BMJ
330: 1255-1258
[Full Text]
Mari, G.
(2005). Middle Cerebral Artery Peak Systolic Velocity: Is It the Standard of Care for the Diagnosis of Fetal Anemia?. J Ultrasound Med
24: 697-702
[Abstract][Full Text]
Mari, G., Abuhamad, A. Z., Cosmi, E., Segata, M., Altaye, M., Akiyama, M.
(2005). Middle Cerebral Artery Peak Systolic Velocity: Technique and Variability. J Ultrasound Med
24: 425-430
[Abstract][Full Text]
Cosmi, E., Dessole, S., Uras, L., Capobianco, G., D'Antona, D., Andrisani, A., Litta, P., Ambrosini, G.
(2005). Middle Cerebral Artery Peak Systolic and Ductus Venosus Velocity Waveforms in the Hydropic Fetus. J Ultrasound Med
24: 209-213
[Abstract][Full Text]
Wong, G., Levine, D.
(2005). Increased Systolic Peak Velocity in Fetal Middle Cerebral Artery Blood Flow Shown by Doppler Sonography in Acute Fetomaternal Hemorrhage. J Ultrasound Med
24: 243-246
[Full Text]
Taslimi, M. M.
(2004). Doppler Ultrasonography in Assessment of Fetal Well-being. NeoReviews
5: e247-e251
[Full Text]
Kumar, S., O'Brien, A.
(2004). Recent developments in fetal medicine. BMJ
328: 1002-1006
[Full Text]
Mostello, D., Holcomb, W. L. Jr, Talsky, J. M., Winn, H. N.
(2004). Fetal Parvovirus B19 Infection: Doppler Studies Allow Noninvasive Treatment of Ascites. J Ultrasound Med
23: 557-560
[Full Text]
Lalicker, A., Himmelberg, J.
(2004). Middle Cerebral Artery Doppler Used to Detect Fetal Anemia. Journal of Diagnostic Medical Sonography
20: 94-99
[Abstract]
Alkalay, A. L., Galvis, S., Ferry, D. A., Simmons, C. F., Krueger, R. C. Jr
(2003). Hemodynamic Changes in Anemic Premature Infants: Are We Allowing the Hematocrits to Fall Too Low?. Pediatrics
112: 838-845
[Abstract][Full Text]
Abdel-Fattah, S A, Soothill, P W, Carroll, S G, Kyle, P M
(2002). Middle cerebral artery Doppler for the prediction of fetal anaemia in cases without hydrops: a practical approach. Br. J. Radiol.
75: 726-730
[Abstract][Full Text]
Nagey, D. A., Laks, M. P., Cohen, T., Mari, G., Zimmerman, R., Oz, U.
(2000). Noninvasive Diagnosis of Fetal Anemia by Doppler Ultrasonography. NEJM
343: 66-68
[Full Text]
Saade, G. R.
(2000). Noninvasive Testing for Fetal Anemia. NEJM
342: 52-53
[Full Text]