Use of Doppler ultrasonography to predict pre-eclampsia
=======================================================

* Gerben ter Riet, MD PhD
* Jeltsje S. Cnossen MD
* Joris A.M. van der Post, MD PhD
* Ben W. Mol, MD PhD
* Rachel K. Morris MD
* Khalid S. Khan MD

*   © 2008 Canadian Medical Association or its licensors

[Six of the authors respond:]

We thank Agustín Conde-Agudelo and Marshall Lindheimer for giving us the opportunity to clarify the interpretation of our findings. We regret that they interpreted our words as a strong recommendation for routine use of Doppler ultrasonography in clinical practice. In the abstract we stated that “a pulsatility index, alone or combined with notching, is the most predictive Doppler index. These indices should be used in clinical practice.”1 Our intention was not to recommend the routine use of Doppler ultrasonography but rather to emphasize that if it is used then the pulsatility index, alone or combined with notching, is the best choice.

More generally, we do not think that firm clinical recommendations should be made on the basis of what might be called early-phase diagnostic studies or meta-analyses thereof.2 A more formal economic modelling analysis on this topic, although still hampered by the use of early-phase diagnostic studies only, showed that the routine use of Doppler ultrasonography cannot currently be considered cost-effective.3

Conde-Agudelo and Lindheimer raise 3 methodologic concerns. First, the statistical test for heterogeneity has bad statistical properties, making such tests virtually superfluous. Although the *I*2 statistic is an improvement,4 we agree with its inventors that “quantification of heterogeneity is only one component of a wider investigation of variability across studies, the most important being diversity in clinical and methodological aspects.”5 We carefully dealt with methodologic diversity using predefined stratified analyses. Second, funnel-plot asymmetry may be caused by at least 6 different mechanisms, of which publication bias is just 1. This is why experts in the field now prefer the term small-study bias. Without firm criteria to distinguish the sources for the asymmetry, interpretation of such plots remains speculative.6,7 Finally, the nonindependence of sensitivity and specificity is a phenomenon for which the bivariate method explicitly accounts.8 In conclusion, we concur with Conde-Agudelo and Lindheimer that it is still too early to recommend routine use of Doppler ultrasonography to predict a pregnant woman's risk of developing pre-eclampsia and intrauterine growth restriction.

## Footnotes

*   **Competing interests:** None declared.

## REFERENCES

1.  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.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czo5OiIxNzgvNi83MDEiO3M6NDoiYXRvbSI7czoyMToiL2NtYWovMTc5LzEvNTMuMi5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

2.  2. Fryback DG, Thornbury JR. The efficacy of diagnostic imaging. Med Decis Making 1991;11:88-94.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NToic3BtZG0iO3M6NToicmVzaWQiO3M6NzoiMTEvMi84OCI7czo0OiJhdG9tIjtzOjIxOiIvY21hai8xNzkvMS81My4yLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

3.  3. Meads CA, Cnossen JS, Meher S, et al. Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness literature with economic modelling. Health Technol Assess 2008;12:1-270.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=19049692&link_type=MED&atom=%2Fcmaj%2F179%2F1%2F53.2.atom) 

4.  4. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:1539-58.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1002/sim.1186&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=12111919&link_type=MED&atom=%2Fcmaj%2F179%2F1%2F53.2.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000176016900005&link_type=ISI) 

5.  5. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.
    
    [FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjEyOiIzMjcvNzQxNC81NTciO3M6NDoiYXRvbSI7czoyMToiL2NtYWovMTc5LzEvNTMuMi5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

6.  6. Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 2005;58:882-93.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/j.jclinepi.2005.01.016&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=16085191&link_type=MED&atom=%2Fcmaj%2F179%2F1%2F53.2.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000231543200004&link_type=ISI) 

7.  7. Ioannidis JP, Trikalinos TA. The appropriateness of asymmetry tests for publication bias in meta-analyses: a large survey. CMAJ 2007;176:1091-6.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czoxMDoiMTc2LzgvMTA5MSI7czo0OiJhdG9tIjtzOjIxOiIvY21hai8xNzkvMS81My4yLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

8.  8. Reitsma JB, Glas AS, Rutjes AW, et al. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews.J Clin Epidemiol 2005;58:982-90.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/j.jclinepi.2005.02.022&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=16168343&link_type=MED&atom=%2Fcmaj%2F179%2F1%2F53.2.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000232209000003&link_type=ISI)