Objective: To assess the value of gestational age and cardiovascular Doppler indices in predicting perinatal mortality in a multicenter cohort of early-onset intrauterine growth-restricted (IUGR) fetuses. Methods: A multicenter prospective cohort study including 157 early-onset (<34 weeks) IUGR cases with abnormal umbilical artery (UA) Doppler was conducted. Cardiovascular assessment included the ductus venosus (DV), the aortic isthmus flow index (IFI), and the myocardial performance index (MPI). Isolated and combined values to predict the risk of perinatal death were evaluated by logistic regression and by decision tree analysis, where the gestational age at delivery, UA, and middle cerebral artery (MCA) were also included as covariates. Results: Perinatal mortality was 17% (27/157). All parameters were significantly associated with perinatal death, with individual odds ratios (OR) of 25.2 for gestational age below 28 weeks, 12.1 for absent/reversed DV atrial flow, 5.3 for MCA pulsatility index <5th centile, 4.6 for UA absent/reversed diastolic end-flow, 1.8 for IFI <5th centile, and 1.6 for MPI >95th centile. Decision tree analysis identified gestational age at birth as the best predictor of death (<26 weeks, 93% mortality; 26–28 weeks, 29% mortality, and >28 weeks, 3% mortality). Between 26 and 28 weeks, DV atrial flow allowed further stratification between high (60%) and low risk (18%) of mortality. Conclusions: Gestational age largely determines the risk of perinatal mortality in early-onset IUGR before 26 weeks and later than 28 weeks of gestation. The DV may improve clinical management by stratifying the probability of death between 26 and 28 weeks of gestation.

Keywords:
Intrauterine growth restriction, Perinatal mortality, Doppler, Ductus venosus, Myocardial performance index, Aortic isthmus
1.
Gardosi J: Intrauterine growth restriction: new standards for assessing adverse outcome. Best Pract Res Clin Obstet Gynaecol 2009;23:741–749.
2.
Baschat AA, Gembruch U, Weiner CP, Harman CR: Qualitative venous Doppler waveform analysis improves prediction of critical perinatal outcomes in premature growth-restricted fetuses. Ultrasound Obstet Gynecol 2003;22:240–245.
3.
Crispi F, Bijnens B, Figueras F, Bartrons J, Eixarch E, Le Noble F, Ahmed A, Gratacos E: Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation 2010;121:2427–2436.
4.
Jang DG, Jo YS, Lee SJ, Kim N, Lee GS: Perinatal outcomes and maternal clinical characteristics in IUGR with absent or reversed end-diastolic flow velocity in the umbilical artery. Arch Gynecol Obstet 2011;284:73–8.
5.
Baschat AA, Cosmi E, Bilardo CM, Wolf H, Berg C, Rigano S, Germer U, Moyano D, Turan S, Hartung J, Bhide A, Muller T, Bower S, Nicolaides KH, Thilaganathan B, Gembruch U, Ferrazzi E, Hecher K, Galan HL, Harman CR: Predictors of neonatal outcome in early-onset placental dysfunction. Obstet Gynecol 2007;109:253–261.
6.
Hernandez-Andrade E, Crispi F, Benavides-Serralde JA, Plasencia W, Diesel HF, Eixarch E, Acosta-Rojas R, Figueras F, Nicolaides K, Gratacos E: Contribution of the myocardial performance index and aortic isthmus blood flow index to predicting mortality in preterm growth-restricted fetuses. Ultrasound Obstet Gynecol 2009;34:430–436.
7.
Morris RK, Selman TJ, Verma M, Robson SC, Kleijnen J, Khan KS: 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. Eur J Obstet Gynecol Reprod Biol 2010;152:3–12.
8.
Del Rio M, Martinez JM, Figueras F, Bennasar M, Olivella A, Palacio M, Coll O, Puerto B, Gratacos E: Doppler assessment of the aortic isthmus and perinatal outcome in preterm fetuses with severe intrauterine growth restriction. Ultrasound Obstet Gynecol 2008;31:41–47.
9.
Turan S, Turan OM, Berg C, Moyano D, Bhide A, Bower S, Thilaganathan B, Gembruch U, Nicolaides K, Harman C, Baschat AA: 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.
10.
Alves SK, Francisco RP, Miyadahira S, Krebs VL, Vaz FA, Zugaib M: Ductus venosus Doppler and postnatal outcomes in fetuses with absent or reversed end-diastolic flow in the umbilical arteries. Eur J Obstet Gynecol Reprod Biol 2008;141:100–103.
11.
Bilardo CM, Wolf H, Stigter RH, Ville Y, Baez E, Visser GH, Hecher K: Relationship between monitoring parameters and perinatal outcome in severe, early intrauterine growth restriction. Ultrasound Obstet Gynecol 2004;23:119–125.
12.
Figueras F, Benavides A, Del Rio M, Crispi F, Eixarch E, Martinez JM, Hernandez-Andrade E, Gratacos E: Monitoring of fetuses with intrauterine growth restriction: longitudinal changes in ductus venosus and aortic isthmus flow. Ultrasound Obstet Gynecol 2009;33:39–43.
13.
Rizzo G, Capponi A, Vendola M, Pietrolucci ME, Arduini D: Relationship between aortic isthmus and ductus venosus velocity waveforms in severe growth restricted fetuses. Prenat Diagn 2008;28:1042–1047.
14.
Fouron JC: The unrecognized physiological and clinical significance of the fetal aortic isthmus. Ultrasound Obstet Gynecol 2003;22:441–447.
15.
Cruz-Martinez R, Figueras F, Tenorio V, Valsky DV, Arranz A, Crispi F, Hernández-Andrade E, Gratacos E: Combination of the aortic isthmus with ductus venosus improves the prediction of neurological damage in early-onset intrauterine growth restricted fetuses. Ultrasound Obstet Gynecol 2010;36:40.
16.
Crispi F, Hernandez-Andrade E, Pelsers MM, Plasencia W, Benavides-Serralde JA, Eixarch E, Le Noble F, Ahmed A, Glatz JF, Nicolaides KH, Gratacos E: Cardiac dysfunction and cell damage across clinical stages of severity in growth-restricted fetuses. Am J Obstet Gynecol 2008;199:254.e1–254.e8.
17.
Figueras F, Meler E, Iraola A, Eixarch E, Coll O, Figueras J, Francis A, Gratacos E, Gardosi J: Customized birthweight standards for a spanish population. Eur J Obstet Gynecol Reprod Biol 2008;136:20–24.
18.
Baschat AA, Weiner CP: Umbilical artery Doppler screening for detection of the small fetus in need of antepartum surveillance. Am J Obstet Gynecol 2000;182:154–158.
19.
Arduini D, Rizzo G: Normal values of pulsatility index from fetal vessels: a cross-sectional study on 1,556 healthy fetuses. J Perinat Med 1990;18:165–172.
20.
Del Rio M, Martinez JM, Figueras F, Lopez M, Palacio M, Gomez O, Coll O, Puerto B: Reference ranges for Doppler parameters of the fetal aortic isthmus during the second half of pregnancy. Ultrasound Obstet Gynecol 2006;28:71–76.
21.
Hecher K, Campbell S, Snijders R, Nicolaides K: Reference ranges for fetal venous and atrioventricular blood flow parameters. Ultrasound Obstet Gynecol 1994;4:381–390.
22.
Hernandez-Andrade E, Figueroa-Diesel H, Kottman C, Illanes S, Arraztoa J, Acosta-Rojas R, Gratacos E: Gestational-age-adjusted reference values for the modified myocardial performance index for evaluation of fetal left cardiac function. Ultrasound Obstet Gynecol 2007;29:321–325.
23.
Mari G, Deter RL, Carpenter RL, Rahman F, Zimmerman R, Moise KJ Jr, Dorman KF, Ludomirsky A, Gonzalez R, Gomez R, Oz U, Detti L, Copel JA, Bahado-Singh R, Berry S, Martinez-Poyer J, Blackwell SC: Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative group for Doppler assessment of the blood velocity in anemic fetuses. N Engl J Med 2000;342:9–14.
24.
Rizzo G, Capponi A, Talone PE, Arduini D, Romanini C: Doppler indices from inferior vena cava and ductus venosus in predicting ph and oxygen tension in umbilical blood at cordocentesis in growth-retarded fetuses. Ultrasound Obstet Gynecol 1996;7:401–410.
25.
Ruskamp J, Fouron JC, Gosselin J, Raboisson MJ, Infante-Rivard C, Proulx F: Reference values for an index of fetal aortic isthmus blood flow during the second half of pregnancy. Ultrasound Obstet Gynecol 2003;21:441–444.
26.
Van Mieghem T, Gucciardo L, Lewi P, Lewi L, Van Schoubroeck D, Devlieger R, De Catte L, Verhaeghe J, Deprest J: Validation of the fetal myocardial performance index in the second and third trimesters of gestation. Ultrasound Obstet Gynecol 2009;33:58–63.
27.
Del Rio M, Martinez JM, Figueras F, Bennasar M, Palacio M, Gomez O, Coll O, Puerto B, Cararach V: Doppler assessment of fetal aortic isthmus blood flow in two different sonographic planes during the second half of gestation. Ultrasound Obstet Gynecol 2005;26:170–174.
28.
Hernandez-Andrade E, Lopez-Tenorio J, Figueroa-Diesel H, Sanin-Blair J, Carreras E, Cabero L, Gratacos E: A modified myocardial performance (Tei) index based on the use of valve clicks improves reproducibility of fetal left cardiac function assessment. Ultrasound Obstet Gynecol 2005;26:227–232.
29.
Report of the national high blood pressure education program working group on high blood pressure in pregnancy. Am J Obstet Gynecol 2000;183:S1–S22.
30.
Robertson MC, Murila F, Tong S, Baker LS, Yu VY, Wallace EM: Predicting perinatal outcome through changes in umbilical artery Doppler studies after antenatal corticosteroids in the growth-restricted fetus. Obstet Gynecol 2009;113:636–640.
31.
Baschat AA: Doppler application in the delivery timing of the preterm growth-restricted fetus: another step in the right direction. Ultrasound Obstet Gynecol 2004;23:111–118.
32.
Cruz-Martinez R, Figueras F, Hernandez-Andrade E, Oros D, Gratacos E: Changes in myocardial performance index, aortic isthmus and ductus venosus in term, small-for-gestational age fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2011;38:400–405.
33.
Cruz-Martinez R, Figueras F, Benavides-Serralde A, Crispi F, Hernandez-Andrade E, Gratacos E: Sequence of changes in myocardial performance index in relation with aortic isthmus and ductus venosus Doppler in fetuses with early-onset intrauterine growth restriction. Ultrasound Obstet Gynecol 2011;38:179–184.
34.
Makikallio K: Is it time to add aortic isthmus evaluation to the repertoire of Doppler investigations for placental insufficiency? Ultrasound Obstet Gynecol 2008;31:6–9.
35.
Fouron JC, Gosselin J, Amiel-Tison C, Infante-Rivard C, Fouron C, Skoll A, Veilleux A: Correlation between prenatal velocity waveforms in the aortic isthmus and neurodevelopmental outcome between the ages of 2 and 4 years. Am J Obstet Gynecol 2001;184:630–636.
36.
Figueras F, Cruz-Martinez R, Sanz-Cortes M, Arranz A, Illa M, Botet F, Costas-Moragas C, Gratacos E: Neurobehavioral outcomes in preterm, growth-restricted infants with and without prenatal advanced signs of brain-sparing. Ultrasound Obstet Gynecol 2011;38:288–294.
© 2012 S. Karger AG, Basel
2012
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.