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Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis

From the Departments of General Practice (Cnossen, ter Riet, Bindels), of Obstetrics and Gynaecology (Cnossen, Mol, van der Post) and of Clinical Epidemiology and Biostatistics (Zwinderman), Academic Medical Center, Amsterdam, the Netherlands; the Horten Center (ter Riet), University of Zurich, Zurich, Switzerland; the Department of Obstetrics and Gynaecology (Morris, Coomarasamy, Khan), Birmingham Women's Hospital, Birmingham, United Kingdom; the School of Surgical and Reproductive Sciences (Robson), Newcastle University, Newcastle upon Tyne, United Kingdom; and Kleijnen Systematic Reviews Ltd (Kleijnen), Westminster Business Centre, Nether Poppleton, York, United Kingdom

Correspondence to: Dr. Jeltsje S. Cnossen, Department of General Practice, Academic Medical Center, Meibergdreef 15, 1100 DD, Amsterdam, The Netherlands; fax +31-20-5669186; j.s.cnossen{at}amc.uva.nl

Background: Alterations in waveforms in the uterine artery are associated with the development of pre-eclampsia and intrauterine growth restriction. We investigated the predictive accuracy of all uterine artery Doppler indices for both conditions in the first and second trimesters.

Methods: We identified relevant studies through searches of MEDLINE, EMBASE, the Cochrane Library and Medion databases (all records to April 2006) and by checking bibliographies of identified studies and consulting with experts. Four of us independently selected studies, extracted data and assessed study validity. We performed a bivariable meta-analysis of sensitivity and specificity and calculated likelihood ratios.

Results: We identified 74 studies of pre-eclampsia (total 79 547 patients) and 61 studies of intrauterine growth restriction (total 41 131 patients). Uterine artery Doppler ultrasonography provided a more accurate prediction when performed in the second trimester than in the first-trimester. Most Doppler indices had poor predictive characteristics, but this varied with patient risk and outcome severity. An increased pulsatility index with notching was the best predictor of pre-eclampsia (positive likelihood ratio 21.0 among high-risk patients and 7.5 among low-risk patients). It was also the best predictor of overall (positive likelihood ratio 9.1) and severe (positive likelihood ratio 14.6) intrauterine growth restriction among low-risk patients.

Interpretation: Abnormal uterine artery waveforms are a better predictor of pre-eclampsia than of intrauterine growth restriction. A pulsatility index, alone or combined with notching, is the most predictive Doppler index. These indices should be used in clinical practice. Future research should also concentrate on combining uterine artery Doppler ultrasonography with other tests.

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