To Doppler or not to Doppler Ivica Zalud, MD, PhD Community Collaborations: Obstetrics, Genetics and Ultrasound December 14-15, 2018

Objectives Describe Doppler technique in different blood vessels Discuss Doppler role in IUGR fetuses Understand the value of Doppler in fetal anemia Present Doppler frontiers

The Doppler Effect

Doppler Ultrasound

Color Doppler

3D Doppler

Clinical Applications Common applications (IUGR) Other applications (fetal anemia) New applications 3D Doppler

Doppler in IUGR Doppler meta analysis has shown that the use of the UA Doppler reduces the number of: antenatal admissions: 44% inductions of labor: 29% C/S for NRFS: 52% perinatal mortality: 38% Alfirevic Z, Neilson JP ACOG 1995;172;1379-87

Umbilical Artery Low impedance circulation S/D index (A/B index) Placental insertion has least impedance Intervene for absent or reversed EDF

UA Doppler – reversed diastolic flow This is an advanced stage of fetal compromise, associated with increased perinatal morbidity and mortality.

MCA Doppler Most accessible cerebral vessel Carries 80% of cerebral flow Excellent reproducibility

MCA Doppler Normal Abnormal – fetal hypoxia

Venous Circulation Central: ductus venosus, hepatic veins, IVC – characteristic pulsations Peripheral: portal veins, umbilical vein – no pulsations

Ductus venosus turbulence (DV) Umbilical vein DV IVC

Normal Fetus IVC Doppler DV Doppler

Hypoxic Fetus IVC Doppler DV Doppler

Uterine Circulation Low impedance circulation in pregnancy S/D or RI – standard indices Low EDF & notching – abnormal findings Associated with elevated MS AFP & hCG

Uterine Artery Abnormal waveforms: IUGR Pre-eclampsia FHR abnormalities

IUGR Challenge: Diagnose true IUGR Identify markers of morbidity Intervene in a timely fashion

middle cerebral artery ductus venosus. Berkley E, Chauhan SP, Abuhamad A. Doppler assessment of the fetus with intrauterine growth restriction. Am J Obstet Gynecol. 2012 Apr;206(4):300-8. Relevant studies in English identified using PubMed (US National Library of Medicine, 1983 through 2011) which describe the peripartum outcomes of IUGR according to Doppler assessment of: umbilical arterial middle cerebral artery ductus venosus.

Randomized and quasi-randomized studies Berkley E, Chauhan SP, Abuhamad A. Doppler assessment of the fetus with intrauterine growth restriction. Am J Obstet Gynecol. 2012 Apr;206(4):300-8. Randomized and quasi-randomized studies UA Doppler significantly decreases the likelihood (1.2% vs 1.7%; RR, 0.71; 95% confidence interval, 0.52-0.98). labor induction cesarean delivery perinatal deaths Antepartum surveillance with UA Doppler should be started when the fetus is viable and IUGR is suspected.

Berkley E, Chauhan SP, Abuhamad A Berkley E, Chauhan SP, Abuhamad A. Doppler assessment of the fetus with intrauterine growth restriction. Am J Obstet Gynecol. 2012 Apr;206(4):300-8. Although Ductus venous, MCA and other vessels have some prognostic value for IUGR fetuses, there is a lack of randomized trials showing benefit. Doppler studies of vessels other than the UA, as part of assessment of fetal well-being in pregnancies complicated by IUGR, should be reserved for research protocols.

Delivery The optimal timing of delivery depends on the underlying etiology of the growth restriction (if known) as well as the estimated gestational age. The patient makes informed decision

GRIT Trial BJOG 2003;110:27–32 Lancet 2004;364:513–20 AJOG 2011;204:34.e1–34.e9 The only published randomized trial to assess the timing of delivery of the early preterm (<34 weeks) IUGR fetus. Pts whose OBs were uncertain whether delivery would be beneficial, were randomized: early delivery group (delivery within 48 hours) or expectant management group (with antepartum surveillance until it was felt that delivery should not be delayed any longer).

GRIT Trial BJOG 2003;110:27–32 Lancet 2004;364:513–20 AJOG 2011;204:34.e1–34.e9 The rates of betamethasone administration were the same in both groups. Perinatal survival was similar. At the 6–12-year follow-up there were no differences in cognitive, language, behavior, or motor abilities of the children born to women in the early-delivery group versus those in the expectant management group.

DIGIT Trial In the Disproportionate Intrauterine Growth Intervention Trial at Term, women with singleton gestations at or beyond 36 weeks with suspected IUGR were randomized: undergo delivery or expectant management with delivery only if some other indication arose. BMJ 2010;341:c7087.

DIGIT Trial There were no differences in composite neonatal outcome between these two groups. The study cohort was not large enough to determine whether individual outcomes, such as perinatal death, were affected by the different management approaches. BMJ 2010;341:c7087.

Delivery: NICHD, SMFM, ACOG Existing data and expert consensus, a joint conference of the NICHD , SMFM and ACOG suggested the following two timing strategies: 1) Delivery at 38 0/7–39 6/7 weeks of gestation in cases of isolated fetal growth restriction Obstet Gynecol 2011;118:323–33.

Delivery: NICHD, SMFM, ACOG 2) Delivery at 34 0/7–37 6/7 weeks of gestation in cases of IUGR with additional risk factors for adverse outcome oligohydramnios abnormal umbilical artery Doppler maternal risk factors comorbidities Obstet Gynecol 2011;118:323–33.

Delivery: NICHD, SMFM, ACOG 3) Delivery before 34 weeks At a center with a NICU and, ideally, after consultation with a maternal–fetal specialist. Corticosteroids should be administered before delivery (improved preterm neonatal outcomes). For cases in which delivery occurs before 32 weeks of gestation, magnesium sulfate should be considered for fetal and neonatal neuroprotection Obstet Gynecol 2011;118:323–33.

TERM IUGR Mode of delivery Based entirely on standard obstetric practice No evidence to support routine C/S Consideration for C/S if non-reassuring antepartum testing with an unfavorable cervix Labor induction with or without cx ripening Continuous electronic fetal monitoring FHR monitor: Increased risk for decreased variability and late decelerations Meconium Optimum: Tertiary care centers with MFM and NICU available

Evidence –based national guidelines for management of suspected fetal growth restriction: comparison, consensus and controversy McCowan LM et all. Am J Obstet Gynecol 2018:S855-868

McCowan LM et all. Am J Obstet Gynecol 2018:S855-868

McCowan LM et all. Am J Obstet Gynecol 2018:S855-868

McCowan LM et all. Am J Obstet Gynecol 2018:S855-868

McCowan LM et all. Am J Obstet Gynecol 2018:S855-868

Cerebroplacental Ratio (CPR) G.DeVore AJOG July 2015;213:5-15 Emerging as important predictor of adverse pregnancy outcome Abnormal CPR in AGA fetuses or late IUGR (>34 weeks) Higher incidence of distress in labor (more c/s) Lower cord pH Increased NICU admissions

Cerebroplacental Ratio (CPR) G.DeVore AJOG July 2015;213:5-15 Abnormal CPR in early IUGR (<34 weeks) Lower GA at birth Lower mean BW and lower BW centile Higher c/s rate for distress in labor Higher rate of 5 min Apgar <7 Increased rate of neonatal acidosis Increased rate of NICU admissions Higher rate of adverse neonatal outcome Greater incidence of perinatal death

Doppler & Fetal Anemia Anemia: Why MCA? Increased cardiac output Decreased blood viscosity Increased blood velocity Peak systolic velocity of MCA Why MCA? Increased blood flow to brain in anemic fetus MCA lends itself to insonation angle close to zero Low inter- and intra-observer variability

Doppler & Fetal Anemia MCA PSV: Moderate to severe anemia: Parvo virus Sensitivity 100% FPR 12% Mari C et al. NEJM 2000;342:9 Parvo virus Sensitivity 94.1% Specificity 93.3% ACOG 2002

New Applications Umbilical artery notching: JUM 2002;21:857 Cord entanglement True knot Cord stricture Velamentous insertion Tight nuchal cords Abnormal cord coiling JUM 2002;21:857

Placenta - 3D Doppler

Vascularization Index (VI) VI = measures % of color pixels in ROI that represent flow

Flow Index (FI) & Vascularization Flow Index (VFI) FI = measures intensity of color pixels in ROI VFI = combines % of color pixels and intensity in ROI (0-100 normalized)

3-D Calculations Measurement Measurement Measurement 60 degrees

Pre-eclampsia, IUGR, placenta accreta

Placental vasculature: 3D power Doppler angiography and 3D color Doppler imaging Campbell S. Ultrasound Obstet Gynecol 2007;30(6):917-20. 

Evaluation of the utero-placental circulation by 3D Doppler ultrasound in the second trimester of normal pregnancy Significant difference among placental VI, FI and VFI related to gestational age at the time of the ultrasound exam. The same was true for spiral arteries ultrasound measurements. (F=0.219; P=0.954) Placental vascular indices slowly increased indicating progressive development of vascular network and increase in the volume blood flow. Zalud I, Shaha S: J Matern Fetal Neonat Med 2007;20:299–305.

3D Doppler of the placenta and spiral arteries: Influence of maternal age and parity Zalud I, Shaha S: J Clin Ultrasound. 2008 May 2. The parity influenced all placental 3D Doppler indices (larger indices in multipara). Maternal age influenced the spiral arteries volume (larger volume in patients younger than 25).

Placenta Accreta: 3D Doppler

Small is the new big… Are you ready for the future?

? 4D Doppler

Conclusions Doppler ultrasound is integral part in management of IUGR, fetal anemia and placental abnormalities. 3D Doppler is a unique technique that enables assessment of vascular signals within the whole investigated area. Homodynamic changes included in the process of placentation are one of the most exciting topics in the investigation of human development.

Mahalo Nui Loa! Thank you!