Research Article| Volume 152, ISSUE 1, P3-12, September 2010

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Systematic review and meta-analysis of the test accuracy of ductus venosus Doppler to predict compromise of fetal/neonatal wellbeing in high risk pregnancies with placental insufficiency



      To evaluate the test accuracy of ductus venosus Doppler for prediction of compromise of fetal/neonatal wellbeing.

      Study design

      The search strategy employed searching of electronic databases (Medline, Embase, Cochrane library, Medion) from inception to May 2009, hand searching of journal and reference lists, contact with experts. Two reviewers independently selected articles in which the results of ductus venosus Doppler were associated with the occurrence of compromise of fetal/neonatal wellbeing. There were no language restrictions applied. Data were extracted on study characteristics, quality and results to construct 2 × 2 tables. Likelihood ratios for positive and negative test results, sensitivity, specificity and their 95% confidence intervals were generated for the different indices and thresholds.


      Eighteen studies, testing 2267 fetuses met the selection criteria, all performed in a high risk population with placental insufficiency in second/third trimester. Meta-analysis showed moderate predictive accuracy. The best result was for the prediction of perinatal mortality, positive likelihood ratio 4.21 (95% CI 1.98–8.96) and negative likelihood ratio 0.43 (95% CI 0.30–0.61). For prediction of adverse perinatal outcome the results were positive likelihood ratio 3.15 (95% CI 2.19–4.54) and negative likelihood ratio 0.49 (95% CI 0.40–0.59).


      Abnormal ductus venosus Doppler showed moderate predictive accuracy for compromise of fetal/neonatal wellbeing overall and perinatal mortality in high risk pregnancies with placental insufficiency.


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        • Hay Jr., W.W.
        • Catz C.S.
        • Grave G.D.
        • Yaffe S.J.
        Workshop summary: fetal growth: its regulation and disorders.
        Pediatrics. 1997; 99: 585-591
        • McIntire D.D.
        • Bloom S.L.
        • Casey B.M.
        • Leveno K.J.
        Birth weight in relation to morbidity and mortality among newborn infants.
        N Engl J Med. 1999; 340: 1234-1238
        • Taylor D.J.
        • Howie P.W.
        Fetal growth achievement and neurodevelopmental disability.
        Br J Obstet Gynaecol. 1989; 96: 789-794
        • Rich-Edwards J.W.
        • Colditz G.A.
        • Stampfer M.J.
        • et al.
        Birthweight and the risk for type 2 diabetes mellitus in adult women.
        Ann Intern Med. 1999; 130: 278-284
        • Barker D.J.
        The developmental origins of chromic adult disease.
        Acta Paediatr Suppl. 2004; 93: 26-33
        • Duley L.
        • Henderson-Smart D.J.
        • Meher S.
        • King J.F.
        Antiplatelet agents for preventing pre-eclampsia and its complications.
        Cochrane Database Syst Rev: Reviews. 2007;
        • Coomarasamy A.
        • Frisk N.
        • Gee H.
        • Robson S.
        The investigation and management of the small for gestational age fetus. Guideline No 31 Nov 2002.
        RCOG, London2003
        • Baschat A.A.
        • Gembruch U.
        • Weiner C.P.
        • Harman C.R.
        Qualitative venous Doppler waveform analysis improves prediction of critical perinatal outcomes in premature growth-restricted fetuses.
        Ultrasound Obstet Gynecol. 2003; 22: 240-245
        • Baschat A.A.
        • Cosmi E.
        • Bilardo C.M.
        • et al.
        Predictors of neonatal outcome in early-onset placental dysfunction.
        Obstet Gynecol. 2007; 109: 253-261
        • Morris R.K.
        • Khan K.S.
        • Coomarasamy A.
        • Robson S.C.
        • Kleijnen J.
        The value of predicting restriction of fetal growth and compromise of its wellbeing: systematic quantitative overviews (meta-analysis) of test accuracy literature.
        BMC Pregnancy Childbirth. 2007; 7 (Article Number: 3)
      1. Cochrane Methods Diagnostic Test Accuracy: Handbook for DTA reviews; 2009

        • Deeks J.
        Systematic reviews in health care: systematic reviews of diagnostic and screening tests.
        BMJ. 2001; 323: 157-162
        • Irwig L.
        • Tosteton A.
        • Gatsonis C.
        • et al.
        Guidelines for meta-analyses evaluating diagnostic tests.
        Ann Intern Med. 1994; 120: 667-676
        • Khan K.S.
        • Dinnes J.
        • Kleijnen J.
        Systematic reviews to evaluate diagnostic tests.
        Eur J Obstet Gynecol Reprod Biol. 2001; 95: 6-11
        • Whiting P.
        • Rutjes A.W.
        • Reitsma J.B.
        • Bossuyt P.M.
        • Kleijnen J.
        The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews.
        BMC Med Res Methodol. 2003; 3: 25
        • Whiting P.F.
        • Weswood M.E.
        • Rutjes A.W.
        • Reitsma J.B.
        • Bossuyt P.N.
        • Kleijnen J.
        Evaluation of QUADAS, a tool for the quality assessment of diagnostic accuracy studies.
        BMC Med Res Methodol. 2006; 6: 9
        • Bossuyt P.M.
        • Reitsma J.B.
        • Bruns D.E.
        • et al.
        Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD.
        BMJ. 2003; 326: 41-44
        • Lijmer J.G.
        • Mol B.W.
        • Heisterkamp S.
        • et al.
        Empirical evidence of design-related bias in studies of diagnostic tests.
        JAMA. 1999; 282: 1061-1066
        • Rutjes A.W.
        • Reitsma J.
        • Di N.
        • Smidt N.
        • van Rijn J.
        • Bossuyt P.M.
        Evidence of bias and variation in diagnostic accuracy studies.
        CMAJ. 2006; 174: 469-476
        • Whiting P.
        • Rutjes A.W.
        • Dinnes J.
        • Reitsma J.
        • Bossuyt P.M.
        • Kleijnen J.
        Development and validation of methods for assessing the quality of diagnostic accuracy studies.
        Health Technol Assess. 2004; 8: iii
        • Honest H.
        • Khan K.S.
        Reporting of measures of accuracy in systematic reviews of diagnostic literature.
        BMC Health Serv Res. 2002; 2: 4
        • Jaeschke R.
        • Guyatt G.H.
        • Sackett D.L.
        Users’ guides to the medical literature. III. How to use an article about a diagnostic test. B. What are the results and will they help me in caring for my patients? The Evidence-Based Medicine Working Group.
        JAMA. 1994; 271: 703-707
        • Sankey S.
        • Weissfeld L.
        • Fine M.
        • Kapoor W.
        An assessment of the use of the continuity correction for sparse data in meta analysis.
        Commun Stat Simul Comput. 1996; 25: 1031-1056
        • Reitsma J.B.
        • Glas A.S.
        • Rutjes A.W.
        • Scholten R.J.
        • Bossuyt P.M.
        • Zwinderman A.H.
        Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews.
        J Clin Epidemiol. 2005; 58: 982-990
        • Van Houwelingen H.
        • Zwinderman K.
        • Stijnen T.
        A bivariate approach to meta-analysis.
        Stat Med. 1993; 12: 2273-2284
        • Van Houwelingen H.
        • Arends L.
        • Stijnen T.
        Advanced methods in meta-analysis: multivariate approach and meta-regression.
        Stat Med. 2002; 21: 589-624
        • Song F.
        • Khan K.S.
        • Dinnes J.
        • Sutton A.J.
        Asymmetric funnel plots and publication bias in meta-analyses of diagnostic accuracy.
        Int J Epidemiol. 2002; 31: 88-95
        • Deeks J.J.
        • Macaskill P.I.L.
        The performance of tests of publication bias and other sample size effects in sytematic reviews of diagnostic test accuracy was assessed.
        J Clin Epidemiol. 2005; 58: 882-893
        • Zamora J.
        • Abraira V.
        • Muriel A.
        • Khan K.
        • Coomarasamy A.
        Meta-Disc: a software for meta-analysis of test accuracy data.
        BMC Med Res Methodol. 2006; 6: 31
        • Habord R.
        Metandi: Stata module for meta-analysis of diagnostic accuracy.
        • Alves S.
        • Francisco R.P.
        • Miyadahira S.
        • Krebs V.
        • Vaz F.
        • Zugaib M.
        Ductus venousus Doppler and postnatal outcomes in fetuses with absent or reversed end-diastolic flow in the umbilical arteries.
        Eur J Obstet Gynecol Repro Biol. 2008; 141: 100-103
        • Baschat A.A.
        • Guclu S.
        • Kush M.L.
        • Gembruch U.
        • Weiner C.P.
        • Harman C.R.
        Venous Doppler in the prediction of acid–base status of growth-restricted fetuses with elevated placental blood flow resistance.
        Am J Obstet Gynecol. 2004; 191: 277-284
        • Baschat A.A.
        • Galan H.L.
        • Bhide A.
        • et al.
        Doppler and biophysical assessment in growth restricted fetuses: distribution of test results.
        Ultrasound Obstet Gynecol. 2006; 27: 41-47
        • Bilardo C.M.
        • Wolf H.
        • Stigter R.H.
        • et al.
        Relationship between monitoring parameters and perinatal outcome in severe, early intrauterine growth restriction.
        Ultrasound Obstet Gynecol. 2004; 23: 119-125
        • Carvalho F.H.
        • Moron A.F.
        • Mattar R.
        • et al.
        Ductus venosus Doppler velocimetry in the prediction of acidemia at birth: which is the best parameter?.
        Prenat Diag. 2005; 25: 1212-1216
        • Cosmi E.
        • Ambrosini G.
        • D’Antona D.
        • Saccardi C.
        • Mari G.
        Doppler, cardiotocography, and biophysical profile changes in growth-restricted fetuses.
        Obstet Gynecol. 2005; 106: 1240-1245
        • Del R.M.
        • Martinez J.M.
        • Figueras F.
        • et al.
        Doppler assessment of the aortic isthmus and perinatal outcome in preterm fetuses with severe intrauterine growth restriction.
        Ultrasound Obstet Gynecol. 2008; 31: 41-47
        • Figueras F.
        • Martinez J.M.
        • Puerto B.
        • Coll O.
        • Cararach V.
        • Vanrell J.A.
        Contraction stress test versus ductus venosus Doppler evaluation for the prediction of adverse perinatal outcome in growth-restricted fetuses with non-reassuring non-stress test.
        Ultrasound Obstet Gynecol. 2003; 21: 250-255
        • Figueras R.F.
        • Bennasar M.
        • Eixarch E.
        • et al.
        Arterial, venous and intracardiac parameters in growth-restricted fetuses: Associations with adverse perinatal outcome.
        Ultrasound Rev Obstet Gynaecol. 2004; 4: 179-185
        • Gramellini D.
        • Piantelli G.
        • Verrotti C.
        • Fieni S.
        • Chiaie L.D.
        • Kaihura C.
        Doppler velocimetry and non stress test in severe fetal growth restriction.
        Clin Exp Obstet Gynecol. 2001; 28: 33-39
        • Hofstaetter C.
        • Gudmundsson S.
        • Dubiel M.
        • Marsal K.
        Ductus venosus velocimetry in high-risk pregnancies.
        Eur J Obstet Gynecol Repro Biol. 1996; 70: 135-140
        • Hung J.H.
        • Fu C.Y.
        • Hung J.
        Combination of fetal Doppler velocimetric resistance values predict acidemic growth-restricted neonates.
        J Ultrasound Med. 2006; 25: 957-962
        • Manogura A.
        • Turan O.
        • Kush M.L.
        • et al.
        Predictors of necrotising enterocolitis in preterm growth-restricted neonates.
        Am J Obstet Gynecol. 2008; 198: 638.e1-638.e5
        • Muller T.
        • Nanan R.
        • Rehn M.
        • Kristen P.
        • Dietl J.
        Arterial and ductus venosus Doppler in fetuses with absent or reverse end-diastolic flow in the umbilical artery: correlation with short-term perinatal outcome.
        Acta Obstet Gynecol Scand. 2002; 81: 860-866
        • Ozcan T.
        • Sbracia M.
        • d’Ancona R.L.
        • Copel J.A.
        • Mari G.
        Arterial and venous Doppler velocimetry in the severely growth-restricted fetus and associations with adverse perinatal outcome.
        Ultrasound Obstet Gynecol. 1998; 12: 39-44
        • Schwarze A.
        • Gembruch U.
        • Krapp M.
        • Katalinic A.
        • Germer U.
        • Axt-Fliedner R.
        Qualitative venous Doppler flow waveform analysis in preterm intrauterine growth-restricted fetuses with ARED flow in the umbilical artery—correlation with short-term outcome.
        Ultrasound Obstet Gynecol. 2005; 25: 573-579
        • Turan S.
        • Turan O.M.
        • Berg C.
        • et al.
        Computerized fetal heart rate analysis. Doppler ultrasound and biophysical profile score in the prediction of acid–base status of growth-restricted fetuses.
        Ultrasound Obstet Gynecol. 2007; 30: 750-756
        • Stroup D.F.
        • Berlin J.A.
        • Morton S.C.
        • et al.
        Meta-analysis of observational studies in epidemiology: a proposal for reporting.
        JAMA. 2000; 283: 2008-2012
        • Zwinderman A.H.
        • Bossuyt P.M.
        We should not pool diagnostic likelihood ratios in systematic reviews.
        Stat Med. 2008; 27: 687-697
        • Deeks J.
        • Altman D.G.
        Diagnostic tests: likelihood ratios.
        BMJ. 2004; 329: 168-169
        • Diemart A.
        • Hecher K.
        Severely abnormal flow patterns in the ductus venosus in the presence of otherwise normal fetal Doppler parameters in two cases of severe intrauterine growth restriction.
        Ultrasound Obstet Gynecol. 2009; 34: 605-608