Postgraduate Training Course in Reproductive Health 2004

Doppler ultrasound in high risk pregnancies
(Protocol for a Cochrane  Systematic Review)

Dr. Cristiane Barbieri, MD
Department of Obstetrics and Gynaecology of the Center for Integral Attention to Women’s Health (CAISM)
State University of Campinas (UNICAMP), Brazil

See also presentation

BACKGROUND

Doppler  ultrasound has  been used in almost every medical discipline to study  blood flow in diseases where an alteration of this dynamic system is anticipated. Until this development the only way to study circulation was the invasive technique of angiography. With the availability of this technique, it has been possible to study the circulation patterns and their pathologies non-invasively.  The first Doppler ultrasound report using continuous wave assessment of umbilical artery flow was published in 1977 (Fitzgerald 1977). With the same systems, in 1983, Campbell published the assessment of the utero-placental circulation and that high resistance waveforms were obtained in pre-eclampsia (Campbell 1983) (Berkowitz 1988). Subsequently these studies were done with colour Doppler and in many centers this has become an important screening technique to predict women at risk of pre-eclampsia.  In the colour Doppler imaging, a real-time, two-dimensional flow imaging technique utilizes an auto-correlation processor for the detection of a moving target. With this method, color is assigned to flow direction. Customarily, flow towards the Doppler transducer is displayed in red and flow away from it is shown in blue. The structures that do not move are presented in basic gray-scale image. Color flow imaging facilitates the detection of small vessels and slow blood-flow velocity.  With the use of colour Doppler, in 1987, it was possible to study the middle cerebral artery in fetuses and compare to umbilical artery pulsatility index (PI) ratio to demonstrate centralization of the fetal circulation (Wladimiroff 1987). Centralization indicates a high resistance in the feto-placental circulation and the study of the middle cerebral artery shows inadequate cerebral perfusion.
The Doppler studies in Obstetrics and gynecology made a significant advance following describing waveforms in the ductus venosus, which is now recognized as a key examination to predict right heart failure in the hypoxic fetus and an important indicator of imminent fetal demise (Kiserud 1991). Ductus venosus leads directly into the vena cava; allows some blood rich in oxygen and nutrients to be pumped out of the body without passing through the capillary beds in the kidney. The presence of reversed flow in the ductus venosus is an ominous sign. The relationship between abnormal uterine artery Doppler velocimetry and pre-eclampsia, intra-uterine growth retardation and adverse pregnancy outcome is well established (Aquilina 1996). Maternal hypertensive disorders are often associated with inadequate blood supply through the placenta.
Pre-eclampsia occurs more commonly during first pregnancies, with twins or triplets, in very young or older women, and when a woman has had pre-eclampsia in previous pregnancies. In general, about 5-10 % of women get this condition during their first pregnancy, while about 7% of women who have previously had children develop pre- eclampsia with subsequent pregnancies (WHO 1988).
Doppler measurements can be obtained from the umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV) and uterine arteries. The pulsatility index (PI) and resistance index (RI) are used for the arteries and the peak velocity index (PVI) is used for the veins.  Abnormal umbilical artery Doppler flow velocimetry is defined as a pulsatility index (PI) >2 standard deviations (SD) above the mean for gestational age and / or absence or reversal of end-diastolic flow. Umbilical artery Doppler reflects downstream placental vascular resistance, correlated with intrauterine growth restriction and the multisystem effects of placental deficiency. Abnormalities are progressive, with reduction, loss and finally a reversal of diastolic flow.  When blood flow in the umbilical arteries become abnormal, the differentiation of fetus status requires Doppler information from systemic vessels, as middle cerebral artery and ductus venosus. The middle cerebral artery is the vessel of choice to assess the fetal cerebral circulation because it is easy to identify. When the fetus is hypoxic, the cerebral arteries tend to become dilated in order to preserve the blood flow to the brain. In the middle cerebral artery, the systolic to diastolic (A/B)  ratio will decrease (due to an increase in diastolic flow) in the presence of chronic hypoxic insult to the fetus. This increase in blood flow can be evidenced by Doppler ultrasound of the middle cerebral artery. This effect has been called "brain sparing effect" and is demonstrated by a lower value of the pulsatility index. In fetuses with intrauterine growth restriction (IUGR) a pulsatility index below the normal range indicates a greater risk of adverse perinatal outcome. The brain sparing effect may be temporary, as reported during prolonged hypoxemia in animal experiments, and the overstressed human fetus can also lose the brain sparing effect. The disappearance of the brain sparing effect is a critical event for the fetus, and appears to precede fetal death.

Doppler studies of uterine artery blood flow in the second trimester may be useful in predicting pre-eclampsia and/or IUGR (Campbell 1986, 1993). In normal pregnancy the systolic/diastolic ratio or RI values significantly decrease with advancing gestation until 24 to 26 weeks. In the absence of this physiologic decrease, a higher incidence of hypertensive diseases and/or IUGR has been widely documented. Many indices have been devised but only two are in regular clinical use. These are the resistance index (RI), also known as the Pourcelot index and the pulsatility index (PI), also known as the Gosling index. An advantage of these waveform indices is that they consist of ratios of Doppler shift frequencies and thus are independent of transmit frequency and Doppler angle. Doppler ultrasound of the umbilical artery is more helpful than other tests of fetal wellbeing (Harman 2003), namely cardiotocography and biophysical profile score in distinguishing between the normal small fetus and the ‘sick’ small fetus (Soothil 1993). Using cardiotocography for fetal surveillance, despite a low false-negative rate, estimates of false-positive rates range from 50 to 80 % (Black 1997). It is possible to use other methods for monitoring fetus in case of IUGR, such as biophysical profile, which can complete the cardiotocography results using the amniotic fluids levels and fetal movement during the exam (Manning 1980) (Vintzileos 1987).

At 22-24 weeks gestation if the fetus is measurably small by ultrasound, several Doppler patterns may occur. The umbilical artery may still have a normal pulsatility index (resistance index or S/D ratio), the middle cerebral artery may have either a normal or abnormal pulsatility index. The second possibility is when the umbilical artery has an abnormal pulsatility index and the middle cerebral artery has either a normal or abnormal value of pulsatility index. The other possibility occurs when both umbilical artery and the middle cerebral artery have an abnormal value of pulsatility index. In this case, there is a severe utero-placental insufficiency. The fetus needs to be monitored very closed. Oligohydramnios may be present at any stage of the above process. Ductus venosus reverse flow and umbilical veins pulsation are present continuously. The fetus starts to lose the brain sparing effect and the biophysical profile becomes abnormal (Gagnon 2003).
This sequence of events applies to a IUGR in cases of insufficiency placental circulation and not to the fetuses who have other causes such as smoking, abruption, and toxic drug exposure who may have a different pathology.

Since the first report of Doppler ultrasound evaluating high-risk pregnancies in 1977, the fetal arterial system has been extensively studied to determine if abnormal waveforms identify fetuses at increased risk of perinatal mortality.
Recent meta-analysis of randomized controlled trials suggests that incorporation of umbilical artery Doppler waveform analysis into management protocols for high risk pregnancies significantly decreases perinatal mortality (Neilson 1999). Other investigators suggested that the time period between identification of an abnormal  umbilical artery Doppler waveform and the development of fetal distress and/or death varies widely – from days to weeks. Studies show that there is a wide variability in the interval between detection of umbilical absent or reverse end-diastolic flow velocities and occurrence of heart rate decelerations (Kurkinen-Räty 1997). Therefore, the challenge is to identify fetuses at greatest risk for adverse perinatal outcome when abnormal umbilical artery waveforms are present.

The effects of Doppler ultrasound in high-risk pregnancies on obstetrical care and fetal outcomes were systematically reviewed (Neilson 2003). The use of Doppler in pregnancies complicated by hypertension or presumed impaired fetal growth was associated with a trend in reduction of perinatal deaths.
The safety of Doppler ultrasound remains a concern. In particular the use of pulsed Doppler involves the use of higher intensities compared to diagnostic ultrasound, and may cause significant tissue heating and other thermal effects. These thermal effects depend on the presence of a tissue/air interface and may therefore not be clinically significant in obstetric ultrasound examinations (Barnett 1995).
It is worth emphasizing that, screening is only worthwhile if an effective preventive treatment is available. If we could identify the 'at-risk' fetus using the Doppler ultrasound in order to apply clinical interventions, it could result in reduced perinatal deaths and unnecessary obstetric interventions. In many cases, the management consists of early delivery when the fetus is mature or specific interventions for conditions such as pre-eclampsia.

OBJECTIVES

To evaluate the benefits and possible harms of the use of Doppler ultrasound screening in high risk pregnancies.

CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW

Types of studies

Randomized controlled trials of Doppler ultrasound as a clinical technique to improve pregnancy outcome in high risk pregnancies.

Types of participants

Women with pregnancies deemed by the investigators to be  at 'high-risk'. The definitions of 'high-risk' are likely to include hypertensive disorders of pregnancy, including pre-eclampsia and intrauterine growth restriction. Women with multiple pregnancies are reviewed separately and will not be included in this review.

Types of interventions

Doppler ultrasound of the umbilical artery and/or middle cerebral artery and/or ductus venosus.
The study of the pulsatility index (PI), resistance index (RI) and systolic/diastolic (S/D) ratio of the umbilical and uterine arteries, middle cerebral artery during pregnancy.
All routine Doppler ultrasound versus no Doppler :

  • Umbilical artery Doppler versus no Doppler/ concealed Doppler examinations

  • Uterine artery Doppler versus no Doppler/ concealed Doppler examinations

  • Umbilical and uterine artery Doppler versus no Doppler/ concealed Doppler examinations

  • Umbilical artery Doppler and ductus venosus Doppler versus no Doppler / concealed Doppler

  • Umbilical artery Doppler and middle cerebral artery versus no Doppler/ concealed Doppler

  • Doppler ultrasound and other monitoring methods versus other method only.

The study of the Doppler ultrasound in high risk pregnancies can be done after the first trimester once and/or more Doppler examinations during pregnancy.
Types of outcome measures
All outcome measures:

  • Perinatal outcome: preterm delivery

  • Obstetrics interventions: elective cesarean section or emergency cesarean section

Neonatal outcome:

  • acute neonatal problems,

  • neonatal morbidity (Apgar score and admission to the neonatal intensive care unit)

METHODS OF THE REVIEW

The review will use the search strategy developed for the Cochrane Pregnancy and Childbirth Group as a whole.

REFERENCES

  1. Aquilina J, Harrington K. Pregnancy hypertension and uterine artery Doppler ultrasound. Curr Opin Obstet Gynecol. 1996 Dec;8(6):435-40. Review. [PubMed]

  2. Barnett SB. Ultrasound safety in obstetrics : What are the concerns? Ultrasound Quarterly. 1995 ; 13(4) :228-39.

  3. Berkowitz GS, Mehalek KE, Chitkara U, Rosenberg J, Cogswell C, Berkowitz RL. Doppler umbilical velocimetry in the prediction of adverse outcome in pregnancies at risk for intrauterine growth retardation. Obstet Gynecol. 1988 May;71(5):742-6. [PubMed]

  4. Black RS, Campbell S. Cardiotocography versus Doppler. Ultrasound Obstet Gynecol. 1997 Mar;9(3):148-51.[PubMed]

  5. Campbell S, Diaz-Recasens J, Griffin DR, Cohen-Overbeek TE, Pearce JM, Willson K, Teague MJNew doppler technique for assessing uteroplacental blood flow. Lancet. 1983 Mar 26;1(8326 Pt 1):675-7. [PubMed]

  6. Campbell S, Pearce JM, Hackett G, Cohen-Overbeek T, Hernandez C. Qualitative assessment of uteroplacental blood flow: early screening test for high-risk pregnancies. Obstet Gynecol. 1986 Nov;68(5):649-53.[PubMed]

  7. Campbell S, Soothill P. Detection and management of intrauterine growth retardation : a British approach. In : Chervenak FA, Isaacson GC, Campbell S, editors. Ultrasound in obstetrics and gynaecology, vol 2. Boston : Little, Brown and Company, 1993 : 1431-5.

  8. FitzGerald DE, Drumm JE. Non-invasive measurement of human fetal circulation using ultrasound: a new method. Br Med J. 1977 Dec 3;2(6100):1450-1. [PubMed]

  9. Gagnon R, Van den Hof M; Diagnostic Imaging Committee, Executive and Council of the Society of Obstetricians and Gynaecologists of Canada. The use of fetal Doppler in obstetrics. J Obstet Gynaecol Can. 2003 Jul;25(7):601-14; quiz 615-6.[PubMed]

  10. Harman CR, Baschat AA. Comprehensive assessment of fetal wellbeing: which Doppler tests should be performed? Curr Opin Obstet Gynecol. 2003 Apr;15(2):147-57. [PubMed]

  11. Kiserud T, Eik-Nes SH, Blaas HG, Hellevik LR. Ultrasonographic velocimetry of the fetal ductus venosus. Lancet. 1991 Dec 7;338(8780):1412-4.[PubMed]

  12. Kurkinen-Räty M, Kivelä A, Jouppila P. The clinical significance of an absent end-diastolic velocity in the umbilical artery detected before the 34th week of pregnancy. Acta Obstet Gynecol Scand. 1997 May;76(5):398-404. [PubMed]

  13. Manning FA, Platt LD, Sipos L. Antepartum fetal evaluation: development of a fetal biophysical profile. Am J Obstet Gynecol. 1980 Mar 15;136(6):787-95. [PubMed]

  14. Neilson JP, Alfirevic Z. Doppler ultrasound for fetal assessment in high risk pregnancies. Cochrane Database Syst Rev. 2000;(2):CD000073. [PubMed]

  15. Soothill PW, Ajayi RA, Campbell S, Nicolaides KH. Prediction of morbidity in small and normally grown fetuses by fetal heart rate variability, biophysical profile score and umbilical artery Doppler studies. Br J Obstet Gynaecol. 1993 Aug;100(8):742-5. [PubMed]

  16. Vintzileos AM, Bors-Koefoed R, Pelegano JF, Campbell WA, Rodis JF, Nochimson DJ, Kontopoulos VG.  The use of fetal biophysical profile improves pregnancy outcome in premature rupture of the membranes. Am J Obstet Gynecol. 1987 Aug;157(2):236-40. [PubMed]

  17. Wladimiroff JW, vd Wijngaard JA, Degani S, Noordam MJ, van Eyck J, Tonge HM. Cerebral and umbilical arterial blood flow velocity waveforms in normal and growth-retarded pregnancies. Obstet Gynecol. 1987 May;69(5):705-9.[PubMed]

  18. [No authors listed]. Geographic variation in the incidence of hypertension in pregnancy. World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy. Am J Obstet Gynecol. 1988 Jan;158(1):80-3. [PubMed]

 

 

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