Antenatal Surveillance Ahmet Baschat, MD Professor Head, Section of Fetal Therapy Dep. of Ob/Gyn, Reprod. Sciences University of Maryland School of Medicine Antenatal surveillance • AIM: to prevent compromise & stillbirth • REQUIREMENTS – – – – – Know limitations of surveillance tests Recognize specific maternal risk factors Understand progression of maternal disease Understand progression of fetal disease Physical evaluation of the fetus • PRINIPAL DECISIONS: – Is delivery indicated ? – Are steroids indicated ? – When should the patient be seen again ? Two important principles • The need for intervention is based on the balance of fetal risks versus neonatal risks • The monitoring interval has to be based on the speed of clinical progression Pathways of deterioration adaptation Not Fetal condition every condition produces the same clinical findings with INTERVENTION fetal compromise… acidemia hypoxemia » alterations fetal heart rate pattern » declining amniotic fluid volume compromise » decrease in dynamic variables » alterations in regional blood flow Stillbirth Surveillance tests • Maternal history and risk factors • Fetal physical examination • Anatomy • Size • Proportion • Growth • Amniotic fluid volume • Biophysical variables • Heart rate parameters • Cardiovascular parameters Maternal risk factors • • • Current pregnancy – specific referral – Hypertension – Pre-eclampsia – Gestational Diabetes Prior pregnancy – Pre-eclampsia – Stillbirth / Losses – Abruption Medical Illness – Hypertension – Diabetes – Lupus – Thrombophilia • Recognition of maternal risk factors is essential because it determines which tests should be performed and at which frequency. • A thorough history and physical examination should form part of the initial assessment of the patient. • Additional laboratory studies may be indicated to clarify diagnoses and prognoses. Fetal risk factors • Chromosomal abnormalities, fetal syndromes and viral infections mimic many potentially treatable fetal conditions. • Detailed anatomic survey is therefore essential – Features of aneuploidy • Multiple malformations • Multiple markers • Abnormal growth – Features of Syndromes • Recognized combinations of physical abnormalities – Viral infection • Echogenicities in organs • Fluid accumulation in body cavities • Abnormal growth • These differential diagnoses must be considered at each visit. Fetal size • BPD • HC • TCD • Fetal size is measured by – Head size • Biparietal diameter (BPD) • Head circumference (HC) • Cerebellar diameter (TCD) – Body size • Abdominal circumference (AC) • AC – Skeletal size • Femur length (FL) • Humerus length (HL) • FL • HL • SEFW – Estimated fetal weight (EFW) • Composite varieble • Assessment of size requires reference ranges and knowledge of gestational age. Fetal proportion Percentile • Measurements of fetal symmetry: – Head to abdomen ratios • (HC/AC) Percentile • (TCD/AC) – Head to Femur ratio (BPD/FL) – Femur to abdomen ratio (FL/AC) 25 5 • 20 Gestational age 40 – Early growth delay – Skeletal dysplasia 25 5 Percentile 20 Gestational age Symetrical small Asymmetrical – small abdomen 25 5 20 Gestational age 40 Asymmetrically abnormal size: Asymmetrical – short bones – Trisomy 40 – Syndromes • Symmetrically abnormal size – Severe growth delay – Aneuploidy – Viral infection Fetal growth Percentile • Growth is dynamic: single and serial measurements at >14 day intervals are needed. AC = abnormal AC AC AC AC AC AC 25 AC 5 20 AC – Continued growth along reference ranges is most likely normal. = normal • Abnormal head growth can indicate aneuploidy or viral infection AC • Abdominal circumference: single best measure of fetal nutrient status. AC AC Gestational age – measurements that fall off the curve are likely abnormal. 40 • Skeletal growth abnormality: important marker for skeletal dysplasia. Amniotic fluid volume After 14 wks a measure of - fetal urine production - placental fluid exchange • Amniotic fluid index – Sum of 4 quadrant vertical pockets – Allows trend-analysis • Subjectively reduced fluid – Maximum pocket < 3 cm – No fetal bladder filling – Empty fetal stomach – Restricted fetal movement – Flexed fetal position – Uterine molding around fetus – Deceleration with movement – Deceleration with transducer pressure – increased uterine contractility • Single vertical pocket < 2cm Amniotic fluid volume • Fluid volume is determined by the relative rate of production (urination) and removal (fetal intake). • If conditions co-exist dynamics may appear normal (i.e. placental insufficiency and maternal diabetes. • ↑ fluid – polyhydramnios • ↓ fluid – oligohydramnios – Maternal diabetes – Rupture of membranes – Tracho-esophageal fistula – Placental insufficiency – Choanal atresia – Viral infection – Aneuploidy – Aneuploidy – Viral infection – Urinary obstruction – Tachycardia – Twin-twin transfusion – Twin-twin transfusion Doppler ultrasound • This standardized approach to the Doppler examination of every vessel is essential in order to achieve reproducible and reliable results: 21 34 – Zoom to the area of interest – Apply color Doppler • Narrow color box 5 • Adjust velocity scale – Apply pulsed wave gate • Adjust gate to cover vessel • Adjust velocity scale • Adjust filter – 3-5 uniform waveforms – No fetal activity Doppler ultrasound Velocity systolic peak velocity end-diastolic peak velocity systolic peak velocity Pulsatility index S (S- D) TAMX TAMX S diastolic peak velocity Continuous trace of the waveform from start to the beginning of the next • In venous vessels automatic tracing software should not be used because the triphasic waveform is not appropriately analyzed D Time Pulsatility index (S- a) TAMX D TAMX atrial systolic peak velocity • a • The Pulsatility index is recommended for arterial vessels • The Pulsatility index for veins is recommended for venous vessels • Reference ranges should be used to interpret the Doppler values Arterial Doppler S • D Input pressure Peripheral resistance Relationship of systole and diastolic velocity and waveform characteristics depend on – Input pressure – Vascular resistance • Vessel tone Vascular histology Autoregulation Failed placentation MCA Umbilical arteries Renal Uterine arteries Hepatic Adrenal Coronaries Splenic Vasoconstriction DA after Indomethacin Vascular resistance may be altered due to – Changes in vessel tone – Structural vascular change Venous Doppler • S D Venous Doppler gives information about forward cardiac function – Compliance – Relaxation – Contractility Compliance A – Afterload • Contractility Afterload All vessels have the same waveform – Systolic peak – Diastolic peak – Atrial systole • Clinically most studied – Ductus venosus 60 - 70% Placenta – Inferior vena cava – Umbilical vein The placenta Maternal compartment A two compartment nutrient, fluid and gas exchange organ • Maternal compartment – Uterine artery Doppler. 11 weeks • 24 weeks 500-600 ml/min. 40 weeks 12 m2 24 weeks 11 weeks • – Umbilical artery Doppler. • 40 weeks Maturation of the vasculature is observed in both compartments, – Loss of uterine artery notch – Appearance of umbilical diastolic velocity 250 ml/Kg/min. – Successive decline in Pulsatility index in both vessels • Fetal compartment Fetal compartment Gestational age is important for assessing waveforms The placenta Uterine artery Umbilical artery • Abnormal trophoblast invasion: – High uterine artery PI – Persistent uterine artery notch • Abnormal villous vascular tree – Umbilical artery Doppler. • Fetal compartment – 30% abnormal villous vasculature – high umbilical artery PI. – 50% abnormal villous vasculature – absent umbilical artery end-diastolic velocity – 70% abnormal villous vasculature – reversed umbilical artery end-diastolic velocity • Risk for hypoxemia / acidemia proportional to decrease in umbilical end-diastolic flow Middle cerebral artery • Branch of the circle of Willis – Use parietal bone window – Parallel to wings of sphenoid – Proximal part recommended – Insonate at 0 degrees • Two parameters are of importance in this vessel • Decreased pulsatility index in – Fetal hypoxemia – Fetal hypertension – Both are indistinguishable by the waveform. • Increased peak systolic velocity (0 degree insonation) in – Fetal anemia – Increased paCO2 Ductus venosus • Is the primary shunt regulating nutrient flow to the liver and heart • Can be imaged in a saggital or abdominal transverse view. • From the first trimester on the a-wave should be antegrade • Pulsatility index for veins significantly decreases with advancing gestation. Umbilical vein • Examine in the straight abdominal portion or cord • 90% of fetuses have constant flow from 12 weeks on. • Pulsations can be – Monophasic – Biphasic – Triphasic • Monophasic pulsations are relevant if central veins are abnormal • Multiphasic pulsations indicate abnormally high venous pressure • Clinical applications: – Fetal growth restriction – Twin-twin transfusion – Hydrops Abnormal veins • The following are abnormal – Decreased a-wave – Decreased D-wave – Decreased v-trough Constant • These abnormalities produce an increase in the Pulsatility index for veins • Absent or reversed flow during the a-wave gives a simple visual assessment of abnormal ductus venosus flow Umbilical vein Fetal behavior 1st trimester 2nd trimester Behavioral states 3rd trimester Stable constellation of activity Cyclicity Rest activity cycles Vibroacoustic Coupling Glucose & breathing Movement & FHR • Breathing movement Activity Fetal behavior develops sequentially: – Isolated activity – Coupling of behavior Gross body movement – Rest activity cycles – Behavioral states • Movement frequency is determined by gestational age and behavioral state Fetal tone & movement • Fetal tone can be assessed by examining flexionextension of the extremities and/or the trunk. • Absence can be explained by – Fetal hypoxemia – Fetal acidemia – Fetal rest – Neuromuscular block – CNS abnormality • Best interpreted in the context of a full biophysical profile score Fetal breathing • Chest movement, diaphragm movement and hiccups count • Absence can be explained by – Fasting state – Fetal hypoxemia – Fetal acidemia – Fetal rest – Neuromuscular block – CNS abnormality • Absence of fetal breathing should prompt re-evaluation after maternal food intake. Fetal heart rate cerebral cortex VMC RAS • A record of autonomic regulation of intrinsic cardiac activity and its modulation by regulatory centers. ANS – Vasomotor center (VMC) – Reticular activating system (RAS) – Autonomic nervous system (ANS) CVS Heart BP = CO x • Analyzed visually by – Baseline heart rate – Reactivity peripheral resistance – Variability – Periodic changes stroke volume x HR • Computerized analysis – Short term variation (ms) Fetal heart rate • Reactivity virtually excludes hypoxemia • Causes of non-reactivity – Gestational age – Behavioral state – Hypoxemia / Acidemia – Medications • Variable decelerations – Cord compression • Late decelerations – >8 torr drop in paO2 – Hypoxemia • Short term variation <3.5 ms – Hypoxemia – Abnormal brain development Biophysical profile score For each component presence = 2 points, absence = 0 points Tone Movement Breathing Amniotic fluid Heart rate at least one episode of active limb, trunk or hand extension with return to flexion • – Amniotic fluid index – Reactive FHR • – Equivocal (PNM=7-10/1000) • 8 with oligohydramnios at least one episode of at least 30 seconds duration (includes hiccups) at least 2 acceleration of - 10 beat x 10 sec (24-28 weeks) - 15 beat x 15 sec (28-34 weeks) - 20 beats x 20 sec (>34 weeks) Manning et al., Am J Obstet Gynecol 1982 Composite score of 5 variables – Normal = 10, 8 (PNM=1/1000) at least 3 discrete body/limb movements (active continuous considered as single movement) at least one single vertical pocket >2 cm Modified BPS • 6 – Abnormal (PNM=12-300/1000) • 6 with oligohydramnios • 4,2,0 • Score of 4 – immediate retesting for 30 min • Persistent score of 4, or less – immediate delivery 0 FHR parameter s LTV <30 reakti v STV <3.5 biophysical parameters Breathing Doppler Parameter Tone & Movement Δ pH -2 -4 -6 pH < 7.20 -8 pH < 7.10 abnormal cCTG und Ductus venosus comparable pH -10 NST cCTG* AFV biophysical parameter = closer relationship with pH FBM FGM Tone AEDV TAO DAO MCA CPR Akalin-Sel et al., Arduini et al., Bilardo et al., Guzman et al,, Hecher et al,, Nicolaides et al., Ribbert et al., Rizzo et al., Soothill et al., Visser et al., Weiner et al. DV Summary Tests provide specific information Fetal anatomy – differential diagnosis Fetal growth – placental performance Amniotic fluid – volume status / placental transfer Uterine Doppler – trophoblast invasion Umbilical Doppler – vascular exchange area MCA Doppler – pCO2, Hgb, Oxygen, Hypertension Venous Doppler – rhythm, forward cardiac function Dynamic variables – Maturation, Behavioral state, pO2 FHR variables – CNS, PNS, pO2 Specific conditions require specific tests… Pathways of deterioration adaptation Not Fetal condition every condition produces the same clinical findings with INTERVENTION fetal compromise… acidemia hypoxemia » alterations fetal heart rate pattern » declining amniotic fluid volume compromise » decrease in dynamic variables » alterations in regional blood flow Stillbirth Integrated fetal testing • Every surveillance test has advantages and disadvantages • Integrated fetal testing combines different tests as needed – Distinguishing false positives from true positives – Detect different avenues of fetal deterioration • Examples of integrated testing – Biophysical profile score – Fetal Apgar Score – Integrated fetal testing management Fetal growth restriction FGR before 34 weeks * * * CIRCULATORY COMPROMISE Ductus venosus CIRCULATORY DECOMPENSATION PLACENTA – BASED Umbilical artery GROWTH DELAY BPS Middle cerebral artery CIRCULATORY COMPENSATION Delayed maturation of FHR control DEVELOPMENTAL DELAY Increased baseline variation decrease / loss Decreased variation / variability Decreased reactivity ABNORMAL DECLINING declining amniotic fluid volume BPS ACTIVITY declining global activity Loss of breathing Loss of movement Delayed behavioral maturation Loss of tone Δ pH 0 -2 * HYPOXEMIA ACIDEMIA STILLBIRTH -4 Baschat 2008 FGR after 34 weeks Ductus venosus PLACENTA – BASED GROWTH DELAY Umbilical artery Middle cerebral artery Nonreactive heart rate declining amniotic fluid volume Loss of breathing Δ pH 0 -2 -4 ? STILLBIRTH Baschat 2008 Approach to the fetus with small biometry Anatomy abnormal Likely diagnosis Aneuploidy Syndrome normal Amniotic fluid increased Viral infection normal or decreased elevated index Absent / reversed end-diastolic velocity Umbilical artery Doppler normal Middle cerebral artery Doppler decreased index IUGR due to placental insufficiency normal Cerebroplacental ratio decreased ratio normal normal repeat examination at 14 days Constitutionally small fetus The principal decisions The monitoring interval Early stages require less frequent monitoring Disease acceleration = ↑ monitoring frequency New onset brain sparing Oligohydramnios UA – AEDV / REDV Abnormal DV Doppler Which thresholds to base delivery on ? Early gestation = high threshold Late gestation = low threshold Severe ↑ ↓ UA PI Cerebroplacental Doppler ratio UA A-REDV Brain sparing Abnormal DV index DV RAV – UV pulsations Progressive ↑ ↓ UA PI Cerebroplacental Doppler ratio Brain sparing UA A-REDV Abnormal DV index DV RAV – UV pulsations 27 day latency 30 weeks delivery 38 day latency / 33.4 weeks delivery ↓ ↑ Mild CPR UA PI 46 day latency / 35.3 weeks delivery 27 29 31 33 35 37 39 Gestational weeks Turan OM et al., Ultrasound Obstet Gynecol 2008 After diagnosis of FGR: -Weekly UA Doppler -Severe deteriorates within 2 weeks -Progressive deteriorates over next 2 weeks - If no change over 4 weeks – probably mild Turan OM et al., Ultrasound Obstet Gynecol 2008 100 90 1%/day in utero N=642 Overall mortality = 130 (21%) Intact survival = 352 (54%) 80 2% / day in utero 70 60 Percent 50 Neonatal survival 40 Intact survival 30 20 10 0 24 25 26 27 28 29 30 31 32 Baschat et al., Obstet Gynecol 2007 Prospective Stillbirth rate 2.5 prospective stillbirth rate Risk / 1000 ongoing pregnancies prospective perinatal mortality rate 2 Favor delivery for singletons 1.5 1 0.5 0 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 Kahn et al., Obstet Gynecol, 2002 • If Fetal growth restriction is observed at 38 weeks the statistical benefit of delivery outweighs the risk of continuing pregnancy Divon et al., 1989, AJOG • • • • Clinical trial IUGR fetuses with A/REDF Daily BPS Delivery for – – – – BPS of 4 or less Oligohydramnios maternal status documented lung maturity • No stillbirths, no acidemia at birth Cosmi et al., 2005, Obstet. Gynecol • 145 idiopathic IUGR; delivery for BPS or CTG • Two groups of fetuses – – – complete deterioration of all Doppler parameters Abnormal BPS / CTG with maintained Dopplers No differences in perinatal outcome • Predictors of outcome – UA REDV – DV REDV – Birthweight • Even with DV A/REDV up to 8 days normal BPP ! Combined tests – hypothetical modeling 100 Percent ongoing pregnancies 80 modified BPP & AREDV DV RAV or UV Pulsations and absent movement or fluid 11/17 stillbirths prevented 12/ 24 Acidemia prevented 28.0 weeks delivery GA 18/29 stillbirths prevented 17/30 Acidemia prevented 29.3 weeks delivery GA 15% increase in survival 60 Abnormal BPP alone 19/29 stillbirths prevented 18/30 Acidemia prevented 28.5 weeks delivery GA 8% increase in survival 40 20 0 24 25 26 27 28 Gestational week 29 30 31 32 Baschat et al., AJOG 2007 Intervention triggers TRUFFLE individualize STV < 3.5 msec STV < 4 msec DV - RAV DV PI > 3SD UA - REDV UA-AEDV Biophysical profile score < 6 Integrated fetal testing score < 8 Greatest survival benefit / day in utero Periviability 24 26 Steroids beneficial 29 32 Not well delineated 34 Baschat 2008 Maternal Diabetes 140 mg/dl 130 Increased insulin resistance GLUCOSE 120 110 Higher postprandial glucose 100 90 80 Lower fasting glucose 70 60 250 IU / ml 200 INSULIN Non-pregnant Pregnant Potential risk to develop diabetes in pregnancy 150 100 50 0 Risks of worsening glycemic control in existing diabetes Diagnosis Current pregnancy Duration Fasting sugar <105 mg% >105 mg% 1’ sugar <140 mg% >140 mg% Therapy Diet > Age 20 Age 10-19 Age <10 <10 years 10-19 years >20 years Insulin Insulin Vascular risks Whites Class A 1 Benign NephroRetinopathy pathy A 2 B C D Cardiac R H F Macrosomia Pregnancy risks Proliferative Retinopathy IUGR Fetal death Anomalies PIH / PET Maternal Mortality Surveillance in diabetes • Signs of glycemiamediated risks • Signs of vascularmediated risks – Macrosomia – IUGR – Polyhydramnios – Abnormal uterine artery Dopplers – Myocardial thickening Monitor fluid & FHR Monitor like IUGR Once / twice weekly Once / twice weekly Empiric monitoring based on GA Start monitoring in the presence of above signs Anti Ro/La antibodies A E MV AAO • Anti Ro/La (SSA/SSB) autoantibodies of the IgG class can pass the placenta from 12 weeks on. • In the fetal circulation they can lead to irreversible destruction of the myocardium and conduction tissue. • Doppler measurement of the PR-interval allows detection of a first degree heart block (>130 ms). • Therapeutic Dexamthasone can prevent progression to complete heart block Fetal SVT Reappearance of normal venous pattern Cardioversion • The risk of hydrops is related to the rise in central venous pressure that occurs when triphasic venous flow is lost. • The earliest sign of therapy success is the reappearance of triphasic venous flow • This is followed by cardioversion to normal heart rate… • And finally resolution of post SVT cardiomyopathy Resolution of cardiomyopathy Monochorionic pregnancies Surveillance in monochorionic twins • Surveillance should integrate the following information: – Growth dynamics – Fetal volume status • Amniotic fluid index • Bladder filling – Vascular parameters • Umbilical artery Doppler • Middle cerebral artery Doppler • Venous Doppler – Biophysical parameters (esp. in growth restriction) Anemia - pathophysiology Alterations in blood flow dynamics Detectable elevation of blood flow velocity Doppler correlates with fetal hemoglobin value Middle cerebral artery Fetal anemia Mari et al., Obstet Gynecol 2002 » Prediction of fetal anemia » sensitivity 100 % (86-100), false +ve rate 12% » responds to correction of anemia » retains sensitivity to time repeat transfusions » Correlation improves with degree of anemia » Utility in other conditions associated with anemia » Parvovirus infection » TTTS » Non-immune hydrops Mari et al., NEJM 2000; Detti et al., AJOG 2001 , Stefos et al., AJOG 2002, Cosmi et al., AJOG 2002; Ohkuchi et al., UOG 2002, Hernandez-Andrade UOG 2004 Fetal hydrops Hydrops pathophysiology Abnormal preload Alterations in forward cardiac function Doppler gives diagnostic / prognostic thresholds Anemiarelated issues Prognosis MCA PSV Structural problems >70 % mortality Cardiac disease Venous Doppler Doppler in Hydrops Critical diagnostic tool Prognostic assessment Allows for monitoring of potentially treatable lesions – CCAM, Sacrococcygeal Teratoma Post-dates pregnancy 2.5 prospective stillbirth rate • Correct routine first trimester ultrasound dating almost halves rates of postterm inductions. • In properly dated pregnancies 3 % go beyond 42 weeks • Risks of stillbirth are related to placental ageing. • No specific sequence of progression has been described to direct surveillance • Rapid decline of amniotic fluid volume is typical Risk / 1000 ongoing pregnancies prospective perinatal mortality rate 2 Favor delivery for singletons 1.5 1 0.5 – Twice weekly surveillance 0 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 Kahn et al., Obstet Gynecol, 2002 • Induction at 41 weeks decreases stillbirth rate significantly. Conclusion Surveillance should be disease specific Testing frequency should be based on disease acceleration Intervention thresholds should be based on intrauterine versus neonatal risks