Doppler Ultrasonography in Obstetrical Practice China Medical University Hospital OBS & GYN department Chien Chung, Lee

Conditions That Place Fetuses at Risk for Adverse Outcomes Maternal Chronic hypertension Collagen-vascular diseases Sickle cell anemia Current substance abuse Impaired renal function Asthma Pneumonia Significant cardiac disease Seizure disorders Diabetes Acute febrile illnesses Significant anemia (hematocrit <26% Fetal Intrauterine growth restriction Congenital anomalies Fetal cardiac arrhythmias Isoimmunization Hydrops fetalis Fetal infections such as parvovirus, coxsackievirus B, syphilis, toxoplasmosis Pregnancy-related Poorly controlled gestational diabetes Multiple gestations Pregnancy-induced hypertension Cholestasis of pregnancy Premature rupture of the membranes (preterm) Unexplained elevated maternal serum alpha-fetoprotein Polyhydramnios Oligohydramnios Placental abruption Abnormal placentation Postdates Unexplained stillbirth in a prior pregnancy

General Guidelines for Antepartum Testing Indication Initiation Frequency Post-term pregnancy 41 weeks Twice a week Preterm rupture of the membranes At onset Daily Oligohydramnios 26 weeks or at onset Polyhydramnios 32 weeks Weekly Class A1 DM (well-controlled, no complications) 36 weeks Class A2 and B (well-controlled, no complications) Class A or B with poor control, Class C-R 28 weeks Chronic or pregnancy-induced hypertension 28 Weeks Steroid-dependent or poorly controlled asthma Collagen-vascular disease including antiphospholipid antibody syndrome Impaired renal function Uncontrolled thyroid disease Maternal heart disease (NYHA class III or IV) Once a week Substance abuse Prior stillbirth At 2 weeks before prior fetal death Multiple gestation Fetal growth restriction Decreased fetal movement At time of complaint Once Cholestasis

Biophysical profile for fetal assessment in high risk pregnancies (Cochrane Methodology Review) Reviewers' conclusions: At present, there is not enough evidence from randomised trials to evaluate the use of biophysical profile as a test of fetal well-being in high risk pregnancies. Alfirevic Z, Neilson JP. In: The Cochrane Library, Issue 4, 2003.

Doppler ultrasound for fetal assessment in high risk pregnancies (Cochrane Methodology Review) Reviewers' conclusions: The use of Doppler ultrasound in high risk pregnancies appears to improve a number of obstetric care outcomes and appears promising in helping to reducing perinatal deaths. Neilson JP, Alfirevic Z. . In: The Cochrane Library, Issue 4, 2003.

Type of Doppler ultrasonography used Descriptive characteristics of randomized trials evaluating the use of Doppler ultrasonography in pregnancy included in overview Reference No. of participant Perinatal deaths (%) Type of Doppler ultrasonography used AEDV (%) Controls Prespecified primary end point with sample size calculations Trudinger et al., 1987, l289 2.1 Umbilical artery, CW 4 MHz ? Gestational age at delivery McParland and Pearce, 1988 509 5.1 Umbilical and uterine arteries, PW 15.1 Death before discharge from hospital Tyrell et al., 1990 500 1.2 Umbilical and uterine arteries, CW, 4 MHz, 100 hZ 2.7 No. of days in neonatal intensive care unit, frequency of low Apgar score Hofmeyr et al., 1991 897 1.3 Umbilical artery, CW, 4 MHz, 50 Hz filter Not stated Newnham et al., 1991 545 3.3 Umbilical artery, CW, 280 Hz filter 2.9 Neonatal hospital stay Burke et al., 1992 476 1.5 Umbilical artery, CW, 4 MHz, 150 Hz filter Almstrom et al., 1992 426 0.7 Umbilical artery, PW, 3 MHz, 100 Hz filter 1.9 Biljan et al., 1992 674 Umbilical artery, CW, 4 MHz, 100 Hz filter No. of antenatal tests per patient, duration of antenatal stay Johnstone et al., 1993 2329 Umbilical artery, CW, 4 MHz, 60-80 Hz filter? Pattison et al., 1994 212 6.6 9.4 Perinatal mortality Neales et al 467 5.3 Umbilical artery, CW, 4 MHz 6.4 Nienhuis and Hoogland 150S 3.4 Umbilical artery, PW, 50 Hz filter

Proportional effect of Doppler ultrasonography on number of dead babies (stillbirths and neonates) when used in high-risk pregnancies. Meta-analysis shows that clinical action guided by Doppler ultrasonography reduced the odds ratio of perinatal death by 38%

Effects of Doppler ultrasonography on perinatal outcomes in high-risk pregnancies. Post hoc analysis. The 16% reduction in the number of elective deliveries, 31% reduction in fetal distress in labor, and 87% reduction in hypoxic encephalopathy in the Doppler group reached statistical significance.

Conditions for Doppler ultrasound Pregnancies complicated by IUGR Pregnancies in which the fetus is at risk for anemia Multiple gestations Pregnancies treated with prostaglandin inhibitors to monitor the ductus arteriosus Fetal echocardiograms

Doppler Flow Velocity in the First Trimester Comparison of endometrial thickness, RI, & gestational age between groups Retained tissue Not retained tissue P Gestational age 10.0(3.3) 7.6(2.0) 0.001 Endometrial thickness(mm) 19.5(1.8) 10.2(7.0) RI 0.38(0.16) 0.59(0.12) Alcazar JL, Ortiz CA. Eur J Obstet Gynecol Reprod Biol. 2002 Apr 10;102(1):83-7.

Doppler Flow Velocity in Uterine Artery Resistance falls and notching is lost on the placental side first, and asymmetry may remain until term. If notching persists contralaterally, there may be relative placental deficiency, but the ipsilateral uterine artery is more reliable. Bewley et. al. Br J Obstet Gynaecol 1989;96:1040–6

Successful placental invasion removes intimal muscle and renders vessels with minimal resistance, no elastic property, and vigorous diastolic flow . In successful pregnancies, Doppler studies show that this remodelling is rapid, with the loss of notching by 12 weeks and low resistance indices by 20 weeks or sooner

Normal midtrimester uterine artery, increased diastolic flow. Normal uterine artery at 12 weeks shows relatively high resistance, absent notching. Normal midtrimester uterine artery, increased diastolic flow. Normal third trimester uterine artery, very low resistance. High resistance with persistent notching may be normal in first trimester, not in this 24-week gestation. Very high resistance, marked notching, absent diastolic velocities in a woman with pre-eclampsia, and severe intrauterine growth restriction (IUGR) at 28 weeks. abnormal placentation is already determined by 20 weeks in worst cases; persistent notching is the best discriminator there is a graded relationship between the severity of notching and the severity of complication screening women at high risk (thrombophilia, hypertension, past history of either pre-eclampsia or IUGR) at 12-14 weeks, using bilateral notching to initiate low-dose aspirin therapy, is highly effective; a significant reduction in rates of all hypertensive disorders and fetal complications included an 80% reduction in proteinuric pre-eclampsia 4.7 versus 23.3% in placebo-treated controls

Doppler Flow Velocity in Umbilical Artery Normal umbilical artery at 18 weeks shows relatively high resistance, but consistent diastolic flow. Normal umbilical artery at 36 weeks, low resistance, generous diastolic flow. High resistance, diastolic velocity low. Absent end-diastolic velocity (AEDV). Reversed diastolic velocity (REDV) in severe intrauterine growth restriction (IUGR).

Doppler Flow Velocity in Umbilical Artery Fetuses with absent end-diastolic velocity of the umbilical artery all died in utero within 3 weeks (median 7 days). Madazli R, Uludag S, Ocak V. Acta Obstet Gynecol Scand 2001; 80:702 With advancing gestation, umbilical arterial Doppler waveforms demonstrate a progressive rise in the end-diastolic velocity and a decrease in the impedance indices. When the high-pass filter is either turned off or set at the lowest value, end-diastolic frequencies may be detected from as early as 10 weeks and in normal pregnancies they are always present from 15 weeks.

FACTORS AFFECTING UMBILICAL ARTERY DOPPLER FLOW VELOCITY WAVEFORMS Gestational age EDFV ratio increases with advancing gestational age Fetal heart rate EDFV decreases with decreasing fetal heart rate Fetal breathing movements Increases variability in the measurements Site of measurement EDFV is higher near the placental insertion than near the umbilical cord insertion into the fetal abdomen Equipment used : continuous Doppler versus pulsed Doppler Continuous Doppler is more a “blind technique” compared with pulsed Duplex Doppler, allowing 2D real time ultrasound User experience Reliability increases with increasing experience Radius of the umbilical artery Decreasing radius (vasoconstriction) increases EDFV Impedance to pulsatile flow propagation Increasing vascular impedance increases EDFV Downstream vascular resistance within the microcirculation Increasing vascular resistance decreases EDFV Angle of the fetal Doppler insonation Best if less than 45˚; <15˚ for MCA absolute peak systolic flow velocity

Diagnostic efficacy of umbilical arterial Doppler in IUGR Author DI Prevalence Sensitivity Specificity PPV Fleischer S/D>3.0 16.8 78 83 49 Aruidini PI>1SD 30.7 60.8 73 50 Berkowitz S/D>3.0 25 55 92 73 Divon S/D>3.0 35.4 49 94 81 Gaziano S/D>4.0 9.4 79 66 79 Ott S/D>3.0 10.4 59 84 29 Maulik S/D>2.9 12.3 75 71 27 Lowery S/D>4.0 22.6 65 66 24 Lee S/D>3.0 15 91.7 68.7 84.6 While umbilical artery Doppler velocimetry studies are not recommended as an independent antepartum testing modality, it can be extremely useful in differentiating the growth restricted fetus from a constitutionally small fetus. Studies suggest that additional antenatal surveillance is unnecessary in fetuses with suspected growth restriction when the umbilical artery Doppler study is normal.

Middle cerebral artery Doppler waveforms Normal flow of the Middle Cerebral Artery in 1º trimester Normal flow of the Middle Cerebral Artery in 2º and 3º trimester

Middle cerebral artery Doppler waveforms (A) Normal middle cerebral artery (MCA) at term - normal peak systolic velocity (58 cm/s), high resistance, low end-diastolic velocity. (B) ‘Brain sparing’ MCA - lower peak, much higher diastolic velocity suggests cerebrovasodilation. (C) Anemic fetus with retained high resistance, elevated peak systolic velocity (77 cm/s).

Doppler Flow Velocity in Ductus venosus

The upper panel represents the venous waveform, correlated with the EKG in the lower panel. A = atrial systole, S = ventricular systole, D = early ventricular diastole. The colored portions of the waveform represent the Tamx for atrial systole (gold), ventricular systole (red), and early ventricular diastole (blue). The yellow arrows represent the measurement of the peak velocity for ventricular systole and early ventricular diastole. The black arrow represents the peak velocity for atrial systole.

(A) Ductus venosus (DV) Doppler waveforms at 12 weeks gestation. (B) At 12 weeks gestation, an abnormal a-wave (a), correctly predicted anomalous pulmonary and systemic venous return, proven by fetal echocardiography at 24 weeks. (C) DV at 26 weeks, with 4-phase waveform. (1) atrial contraction (2) ventricular systole, (3) return (ascent) of the annulus (called the y-descent of the DV waveform), & (4) diastole. (D) Normal waveform from the middle hepatic vein which, is only a few millimeters from the DV.

Doppler Flow Velocity in IUGR

Progressive changes in Doppler parameters in IUGR fetuses delivered for an abnormal Biophysical Profile Score.

Vessel Impedance to flow Hemodynamic changes occurring in fetal arterial vessels during hypoxemia and acidemia induced by uteroplacental insufficiency Vessel         Impedance to flow   Descending aorta Increased Renal artery Femoral artery Peripheral pulmonary artery Mesenteric arteries Cerebral arteries Decreased Adrenal arteries Splenic arteries Coronary arteries

Fetal Systemic Vascular Responses in IUGRA/REDV, absent or reversed end-diastolic velocities HARMAN: Clin Obstet Gynecol, 46(4).December 2003.931-946

Aortic isthmus blood velocity waveform a) normal blood flow pattern in an uncomplicated pregnancy b) antegrade net blood flow (antegrade/retrograde ratio of 2.0) c) retrograde net blood flow with a corresponding value of 0.54 in pregnancies complicated by placental insufficiency. In the sagittal view of the fetus, the aortic arch and the location of the aortic isthmus (white triangle) are shown.

Coronary artery blood velocity waveform of a growth-restricted 32 week fetus (heart sparing effect).

Alfred Abuhamad et al. Contemporary Ob/Gyn May 1, 2003;48:56-73

Evaluation of fetal intrapartum hypoxia by middle cerebral & umbilical artery Doppler velocimetry with simultaneous cardiotocography & pulse oximetry Siristatidis C, Salamalekis E, Kassanos D, Loghis C, Creatsas G Arch Gynecol Obstet. 2003 Nov 5 During active labor the fetus maintains oxygen supply to the brain by redistributing blood flow. In cases of hypoxia this is feasible for only 2 min.

Spectral Doppler waveform of an A-A anastomosis with characteristic bidirectional, pulsatile flow.

Systematic Doppler Evaluation HARMAN: Clin Obstet Gynecol, Volume 46(4).December 2003.931

Which Doppler Tests Should be Performed? Uterine arteries depict maternal vascular effects of the invading placenta Umbilical artery Doppler reflects downstream placental vascular resistance Middle cerebral artery changes begin when the redistribution of cardiac output reflects rising placental resistance precordial veins illustrate fetal cardiac function

DIFFERENTIAL DIAGNOSIS OF OLIGOHYDRAMNIOS PPROM --- normal renal vessels, normal umbilical flow & normal filling of the bladder. Bilateral renal agenesis or dysplasia --- umbilical artery Doppler is normal, but no renal vessels & no bladder filling Severe hypoxia with IUGR --- fetal measurements are small for gestation, fetal heart looks dilated & the bowel is echogenic. Doppler demonstrates the presence of two renal arteries and absent or reversed end-diastolic frequencies in the umbilical arteries

Deficient placentation defined by notched uterine arteries Increased umbilical artery resistance with progression to AEDV/REDV Declining CPR, brain-sparing MCA As the arteriovenous ratio decline, ductus venosus abnormality begins Abnormal biophysical variables emerge Oligohydramnios and abnormal (non-reactive) fetal heart rate tracing Loss of fetal breathing movements, body movements and fetal tone

1. Umbilical artery Doppler should be available for assessment of the fetal-placental circulation in pregnant women with suspected severe placental insufficiency. (I-A) 2. Depending on other clinical factors, reduced, absent, or reversed umbilical artery end-diastolic flow is an indication for enhanced fetal surveillance or delivery. If delivery is delayed to enhance fetal lung maturity with maternal administration of glucocorticoid, intensive fetal surveillance until delivery is suggested for those fetuses with reversed end-diastolic flow. (II-1B) 3. Umbilical artery Doppler should not be used as a screening tool in healthy pregnancies, as it has not been shown to be of value in this group. (I-A) 4. Umbilical venous double pulsations, in the presence of abnormal umbilical artery Doppler waveforms, necessitate a detailed assessment of fetal health status. (II-3B) 5. Measurement of the fetal middle cerebral artery Doppler peak systolic flow velocity is a predictor of moderate or severe fetal anemia and can be used to avoid unnecessary invasive procedures in pregnancies complicated with red blood cell isoimmunization. (II-1A) 6. Since inaccurate information concerning fetal Doppler studies could lead to inappropriate clinical decisions, it is imperative that measurements be undertaken and interpreted by expert operators who are knowledgeable about the significance of Doppler changes and who practise appropriate techniques. (II-1A) THE USE OF FETAL DOPPLER IN OBSTETRICS Society of Obstetricians and Gynaecologists of Canada. No. 130, July 2003

Conclusion No single diagnostic modality can provide information complete enough to adequately address the complex nature of IUGR and its interacting fetal compensations and compromises Management decisions based on Doppler data are gestational age dependent

Thank You For Your Attention! The relative simplicity of the nipple stimulation test may make the CST more desirable to patients and physicians and could be used as a first line screening test instead of the more commonly used NST and BPP. Of all the antepartum testing modalities described in this chapter, none can be described as the best one to use. Each test has certain pros and cons that need to be carefully evaluated in the clinical context in which it is used.