Electronic letters to:

Research:
Jeltsje S. Cnossen, MD, Rachel K. Morris, MD, Gerben ter Riet, MD PhD, Ben W.J. Mol, MD PhD, Joris A.M. van der Post, MD PhD, Arri Coomarasamy, MD, Aeilko H. Zwinderman, MSc PhD, Stephen C. Robson, MD, Patrick J.E. Bindels, MD PhD, Jos Kleijnen, MD PhD, and Khalid S. Khan, MD
Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis
CMAJ 2008; 178: 701-711 [Abstract] [Full text] [PDF]
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[Read eLetter] Doppler ultrasonography for predicting pre-eclampsia
Agustin Conde-Agudelo   (18 March 2008)

Doppler ultrasonography for predicting pre-eclampsia 18 March 2008
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Agustin Conde-Agudelo
Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Baltimore, MD, and Detroit, MI,

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Re: Doppler ultrasonography for predicting pre-eclampsia

condeagu{at}hotmail.com Agustin Conde-Agudelo

Agustín Conde-Agudelo, MD, MPH and Marshall Lindheimer, MD

We enjoyed Cnossen and colleagues’ systematic review of uterine artery Doppler ultrasonography to predict pre-eclampsia.[1] Authors conclude 2nd trimester increased pulsatility index with notching is the best predictor of pre-eclampsia, strongly recommending routine use of these Doppler indices in clinical practice. However, this recommendation derives from but two studies, one in low risk (n=1757), the other in high- risk women (n=351). As pre-eclampsia’s incidence is relatively low (0.4%- 6.7%), screening tests require high likelihood ratios to adequately predict the disease’s probability with positive test results, and very low likelihood ratios to confidently exclude the disorder with negative test results.[2] Increased pulsatility index with notching produced sufficiently positive likelihood ratios (21.0) in high risk women, but was inadequate in low risk populations (7.5), and, importantly, negative likelihood ratios were quite poor for either population (high-risk, 0.59; low risk, 0.82). We also have methodological concerns. Firstly, a valid meta-analysis should be examined for heterogeneity before considering pooling the results of primary studies into summary estimates with enhanced precision.[3] There is no indication in the review that heterogeneity of results between studies was formally tested using statistical tests and/or graphical approaches. Secondly, there is a substantial possibility of publication bias in this area of research,[4] and again there is no indication that this was assessed. Finally, although pooling of sensitivities and specificities instead of likelihood ratios have recently been encouraged [5] we are skeptical concurring with others [6] that sensitivities and specificities are inappropriate for meta- analyses, as they do not behave independently when pooled from primary studies to generate separate averages. We, therefore, suggest the authors’ conclusions are premature. Doppler ultrasonography, useful for monitoring high risk pregnancies, should not currently be recommended for routine screening to predict pre-eclampsia.

REFERENCES

1. Cnossen JS, Morris RK, ter Riet G, et al. Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis. CMAJ 2008;178:701-11.

2. Conde-Agudelo A, Villar J, Lindheimer M. World Health Organization systematic review of screening tests for preeclampsia. Obstet Gynecol 2004;104:1367-91.

3. Lijmer JG, Bossuyt PM, Heisterkamp SH. Exploring sources of heterogeneity in systematic reviews of diagnostic tests. Stat Med 2002;21:1525-37.

4. Song F, Khan KS, Dinnes J, Sutton AJ. Asymmetric funnel plots and publication bias in meta-analyses of diagnostic accuracy. Int J Epidemiol 2002;31:88-95.

5. Zwinderman AH, Bossuyt PM. We should not pool diagnostic likelihood ratios in systematic reviews. Stat Med 2008;27:687-97.

6. Shapiro DE. Issues in combining independent estimates of the sensitivity and specificity of a diagnostic test. Acad Radiol 1995;2:S37–S47.

AFFILIATIONS

Dr Conde-Agudelo: Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Baltimore, Maryland, and Detroit, Michigan

Dr Lindheimer: Department of Obstetrics & Gynecology and Medicine, The University of Chicago, Chicago, Illinois

Conflict of Interest:

None declared