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Noninvasive Techniques to Detect Fetal Anemia Due to Red Blood Cell Alloimmunization: A Systematic Review

Divakaran, T. G. MD; Waugh, J. MBBS; Clark, T. J. MBBS; Khan, K. S. MSc; Whittle, M. J. MD; Kilby, M. D. MD


OBJECTIVE To estimate, in maternal red blood cell alloimmunization, the diagnostic value of fetal ultrasonography and Doppler blood flow velocity in the evaluation and prediction of fetal anemia.

METHODS Literature from 1970 to 2000 was identified using general bibliographic databases (MEDLINE and EMBASE), the Cochrane Library and relevant specialist register of the Cochrane Collaboration, and by checking reference lists of known primary and review articles. Studies were selected if the accuracy of the fetal ultrasound parameters or Doppler studies of blood flow in the fetal vessels was estimated compared with a reference standard (fetal hemoglobin). The diagnostic tests evaluated were ultrasound measurement of the fetal spleen perimeter and Doppler studies of blood velocity estimates in the umbilical vein, ductus venosus, middle cerebral artery, thoracic aorta, and umbilical vessel combined with the thoracic aorta. Study selection, quality assessment, and data abstraction were performed independently and in duplicate. Data from the selected studies were abstracted as 2 × 2 tables comparing the diagnostic test result with the reference standard. Diagnostic accuracy was expressed as likelihood ratios.

RESULTS The review included eight primary studies with 362 pregnancies affected by red cell alloimmunization. Prospective patient recruitment and complete population details were reported in half of the selected studies (four of eight). Only one study reported masking the diagnostic test results to clinicians. The diagnostic test performance varied widely according to the type of the test evaluated and the cutoff level used to define fetal anemia, which varied from study to study. The diagnostic test study of highest methodological quality reported a positive likelihood ratio of 8.45 (95% confidence interval 4.69, 15.56) and negative likelihood ratio of 0.02 (95% confidence interval 0.001, 0.25) for maximum middle cerebral artery Doppler velocity.

CONCLUSION The literature reporting noninvasive techniques to predict fetal anemia is methodologically poor and a standard approach to the evaluation of these techniques is lacking. A recommendation for practice cannot be generated without further rigorous research.

Recommendations for practice cannot be generated from the available research as studies reporting noninvasive techniques to predict fetal anemia are methodologically poor and lack a standardized approach to the evaluation of these techniques.

Department of Fetal Medicine and Division of Reproduction and Child Health, Birmingham Women's Hospital, University of Birmingham, Edgbaston, Birmingham, United Kingdom.

Address reprint requests to: Mark D. Kilby, MD, Reader and Clinical Consultant in Fetal Medicine, Division of Reproductive and Child Health, Department of Fetal Medicine, Birmingham Women's Hospital, University of Birmingham, Edgbaston, Birmingham B15 2TG, United Kingdom; E-mail:

Received November 8, 2000. Received in revised form March 15, 2001. Accepted March 23, 2001.

© 2001 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.