Antenatal Surveillance

Ahmet Baschat, MD

ProfessorHead, Section of Fetal TherapyDep. of Ob/Gyn, Reprod. SciencesUniversity 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

Fetal condition

hypoxemia

Stillbirth

compromise

acidemia

» alterations fetal heart rate pattern

» alterations in regional blood flow

» decrease in dynamic variables

» declining amniotic fluid volume

INTERVENTION

Not every condition produces the same clinical

findings with fetal compromise…

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

• AC

• FL• HL• SEFW

• Fetal size is measured by– Head size

• Biparietal diameter (BPD)

• Head circumference (HC)

• Cerebellar diameter (TCD)

– Body size• Abdominal circumference

(AC)

– Skeletal size• Femur length (FL)

• Humerus length (HL)

– Estimated fetal weight (EFW)• Composite varieble

• Assessment of size requires reference ranges and knowledge of gestational age.

Fetal proportion• Measurements of fetal

symmetry:– Head to abdomen ratios

• (HC/AC)

• (TCD/AC)

– Head to Femur ratio (BPD/FL)

– Femur to abdomen ratio (FL/AC)

• Asymmetrically abnormal size:– Early growth delay

– Skeletal dysplasia

– Trisomy

– Syndromes

• Symmetrically abnormal size– Severe growth delay

– Aneuploidy

– Viral infection

Gestational age

Percentile

20 40

255

Gestational age

Percentile

20 40

255

Gestational age

Percentile

20 40

255

Symetrical small

Asymmetrical – small abdomen Asymmetrical – short bones

Fetal growth• Growth is dynamic: single

and serial measurements at >14 day intervals are needed.– Continued growth along

reference ranges is most likely normal.

– measurements that fall off the curve are likely abnormal.

• Abnormal head growth can indicate aneuploidy or viral infection

• Abdominal circumference: single best measure of fetal nutrient status.

• Skeletal growth abnormality: important marker for skeletal dysplasia.

Gestational age

Percentile

20 40

25

5 AC

AC

AC

AC= normal

AC

AC

AC

AC

AC

AC

AC

AC

= abnormal

Amniotic fluid volume• 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

After 14 wks a measure of

- fetal urine production

- placental fluid exchange

Amniotic fluid volume

• ↑ fluid – polyhydramnios– Maternal diabetes

– Tracho-esophageal fistula

– Choanal atresia

– Aneuploidy

– Viral infection

– Tachycardia

– Twin-twin transfusion

• 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 – oligohydramnios

– Rupture of membranes

– Placental insufficiency

– Viral infection

– Aneuploidy

– Urinary obstruction

– 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:– Zoom to the area of

interest

– Apply color Doppler • Narrow color box

• Adjust velocity scale

– Apply pulsed wave gate• Adjust gate to cover

vessel

• Adjust velocity scale

• Adjust filter

– 3-5 uniform waveforms

– No fetal activity

12

34

5

Velocitysystolic peak velocity

end-diastolic peak velocity

atrial systolic peak velocity a

diastolic peak velocity

Dsystolic peak velocity

S

TAMX

TAMX

S

D

Pulsatility index

(S-D)TAMX

TimePulsatility index

(S-a)TAMX

Doppler ultrasound• 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

• 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• Relationship of systole

and diastolic velocity and waveform characteristics depend on– Input pressure

– Vascular resistance

• Vascular resistance may be altered due to– Changes in vessel tone

– Structural vascular change

S

D Input pressure

Vessel tone Vascular histology

Peripheral resistance

AutoregulationMCARenalHepaticAdrenalCoronarie

sSplenic

VasoconstrictionDA after Indomethaci

n

Failed placentationUmbilical

arteriesUterine arteries

Venous Doppler• Venous Doppler gives

information about forward cardiac function– Compliance

– Relaxation

– Contractility

– Afterload

• All vessels have the same waveform– Systolic peak

– Diastolic peak

– Atrial systole

• Clinically most studied– Ductus venosus

– Inferior vena cava

– Umbilical vein

S

D

A

Contractility

Afterload

60 - 70%

Placenta

Compliance

The placenta• A two compartment

nutrient, fluid and gas exchange organ

• Maternal compartment – Uterine artery Doppler.

• Fetal compartment – Umbilical artery Doppler.

• Maturation of the vasculature is observed in both compartments,– Loss of uterine artery

notch

– Appearance of umbilical diastolic velocity

– Successive decline in Pulsatility index in both vessels

• Gestational age is important for assessing waveforms

Maternal compartment

Fetal compartment

11 weeks

11 weeks

24 weeks

24 weeks

40 weeks

40 weeks

500-600 ml/min.

250 ml/Kg/min.

12 m2

The placenta• 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

Umbilical artery

Uterine artery

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

• 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 veinConstant

Fetal behavior1st trimester 2nd trimester 3rd trimester

Activity

Coupling

Cyclicity

Behavioral states

Gross body movement

Breathing movement

Movement & FHR

Glucose & breathing

Vibroacoustic

Rest activity cycles

Stable constellation of activity

• Fetal behavior develops sequentially:– Isolated activity

– Coupling of behavior

– 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

flexion-extension 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.

cerebral cortex

ANS

VMC RAS

Heart CVS

BP = CO peripheral resistancex

HRxstroke volume

Fetal heart rate

• A record of autonomic regulation of intrinsic cardiac activity and its modulation by regulatory centers.– Vasomotor center (VMC)

– Reticular activating system (RAS)

– Autonomic nervous system (ANS)

• Analyzed visually by– Baseline heart rate

– Reactivity

– Variability

– Periodic changes

• 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• Modified BPS

– Amniotic fluid index

– Reactive FHR

• Composite score of 5 variables– Normal = 10, 8

(PNM=1/1000)

– Equivocal (PNM=7-10/1000) • 8 with oligohydramnios

• 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

Tone at least one episode of active limb, trunk or hand extension with return to flexion

Movement

at least 3 discrete body/limb movements (active continuous considered as single movement)

Breathing at least one episode of at least 30 seconds duration (includes hiccups)

Amniotic fluid at least one single vertical pocket >2 cm

Heart rate 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

For each component presence = 2 points, absence = 0 points

pH < 7.10

-10

Δ p

HFHR

parameters

0

-2

-4

-6

-8

NST cCTG* ToneAFV FBM FGM AEDV TAO MCA CPR DVDAO

-reaktiv

LTV <30

STV <3.5

biophysicalparameters

DopplerParameter

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.

pH < 7.20

Breathing

Tone & Movement

biophysical parameter = closer relationship with pH

abnormal cCTG und Ductus venosus comparable pH

SummaryTests provide specific information

Fetal anatomy – differential diagnosis Fetal growth – placental performance Amniotic fluid – volume status / placental transferUterine Doppler – trophoblast invasion

Umbilical Doppler – vascular exchange area

MCA Doppler – pCO2, Hgb, Oxygen, Hypertension

Venous Doppler – rhythm, forward cardiac functionDynamic variables – Maturation, Behavioral state, pO2FHR variables – CNS, PNS, pO2

Specific conditions require specific tests…

Pathways of deterioration

adaptation

Fetal condition

hypoxemia

Stillbirth

compromise

acidemia

» alterations fetal heart rate pattern

» alterations in regional blood flow

» decrease in dynamic variables

» declining amniotic fluid volume

INTERVENTION

Not every condition produces the same clinical

findings with fetal compromise…

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

Delayed behavioral maturation

BP

S

Delayed maturation of FHR control

Increased baselineDecreased variation / variabilityDecreased reactivity

variation decrease / loss

Loss of breathing

declining amniotic fluid volume

declining global activity

Ductus venosus

Umbilical artery

Middle cerebral artery

PLACENTA – BASED GROWTH DELAY

CIRCULATORY COMPENSATION

DEVELOPMENTAL DELAY

* *

DECLINING ACTIVITY

* *

CIRCULATORY DECOMPENSATION

CIRCULATORY COMPROMISE

Loss of movement

Loss of tone

ABNORMAL BPS

Δ p

H

0

- 4

- 6

- 2 HYPOXEMIA ACIDEMIA STILLBIRTH

Baschat 2008

FGR after 34 weeks

Ductus venosus

Umbilical artery

Middle cerebral artery

Nonreactive heart rate

Loss of breathing

declining amniotic fluid volume

Δ p

H

0

- 4

- 6

- 2

Baschat 2008?

PLACENTA – BASED GROWTH DELAY

STILLBIRTH

Likely diagnosis

Anatomy

Amniotic fluid

Aneuploidy

Syndrome

Viral infection

normal

normal or decreased

Umbilical artery Doppler

normal

Middle cerebral artery Doppler

normal

Cerebroplacental ratio

normal

abnormal

increased

elevated indexAbsent / reversed end-diastolic velocity

decreased index

decreased ratio

IUGR due to placental insufficiency

normal repeat examination at 14 days

Constitutionally small fetus

Approach to the fetus with small biometry

The principal decisions

The monitoring interval

Which thresholds to base delivery on ?

Early stages require less frequent monitoring

Disease acceleration = ↑ monitoring frequency

New onset brain sparing

Abnormal DV Doppler

Oligohydramnios

UA – AEDV / REDV

Early gestation = high threshold

Late gestation = low threshold

Turan OM et al., Ultrasound Obstet Gynecol 2008

27 29 31 33 35 37 39

Degre

e o

f D

opple

r A

bn

orm

alit

y

Gestational weeks

Severe

Progressive

Mild

↑ UA PI

↓ Cerebroplacental Doppler ratio

UA A-REDVBrain sparing

Abnormal DV index

DV RAV – UV pulsations↑ UA PI

↓ Cerebroplacental Doppler ratio

Brain sparingUA A-REDV

Abnormal DV index

DV RAV – UV pulsations

↑ UA PI

↓ CPR

46 day latency / 35.3 weeks delivery

38 day latency / 33.4 weeks delivery

27 day latency30 weeks delivery

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

Neonatal survival

24 25 26 27 28 29 30 31 32

Gestational week

0

10

20

30

40

50

60

70

80

90

100Perc

en

t

Intact survival

2% / day in utero

1%/day in utero

Baschat et al., Obstet Gynecol 2007

N=642

Overall mortality = 130 (21%)

Intact survival = 352 (54%)

Prospective Stillbirth rate

0

0.5

1

1.5

2

2.5

24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43

Ris

k /

10

00

on

goin

g p

reg

nan

cie

s

prospective stillbirth rate

prospective perinatal mortality rate

Kahn et al., Obstet Gynecol, 2002

Favor delivery

for singleton

s

• 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 !

0

20

40

60

80

100

24 25 26 27 28 29 30 31 32

Perc

en

t on

goin

g p

reg

nan

cie

s

Gestational week

modified BPP & AREDV

Abnormal BPP alone

DV RAV or UV Pulsations and absent movement or fluid

19/29 stillbirths prevented18/30 Acidemia prevented28.5 weeks delivery GA8% increase in survival

18/29 stillbirths prevented17/30 Acidemia prevented29.3 weeks delivery GA15% increase in survival

11/17 stillbirths prevented12/ 24 Acidemia prevented28.0 weeks delivery GA

Combined tests – hypothetical modeling

Baschat et al., AJOG 2007

Intervention triggers

24 26 29 32 34

individualize

STV < 3.5 msec

DV - RAV

STV < 4 msec

DV PI > 3SD UA - REDV UA-AEDV

Biophysical profile score < 6

Integrated fetal testing score < 8

Periviability Steroids beneficialNot well

delineated

Greatest survival benefit / day in utero

TRUFFLE

Baschat 2008

Maternal Diabetes

Pregnant

Non-pregnant

60

70

80

90

100

110

120

130

140

0

50

100

150

200

250

8 10 12 14 16 18 20 22 24 2 4 6 8

IU /

ml

mg

/dl

GLUCOSE

INSULIN

Increased insulin resistance

Higher postprandial glucose

Lower fasting glucose

Potential risk to develop diabetes in pregnancy

Risks of worsening glycemic control in existing diabetes

Diagnosis

Fasting sugar

1’ sugar

Therapy

Whites Class

Current pregnancy

<105 mg%

<140 mg%

>105 mg%

>140 mg%

Diet Insulin

A 1 A 2

Duration

Vascular risks

Insulin

> Age 20

<10 years

B

Age 10-19

10-19 years

C

Age<10

>20 years

Benign Retinopat

hy

D

Nephro-pathy

Proliferative

Retinopathy

Cardiac

F R H

Pregnancy risks

PIH / PET

Maternal Mortality

Fetal death

Anomalies

Macrosomia IUGR

Surveillance in diabetes

• Signs of glycemia-mediated risks– Macrosomia

– Polyhydramnios

– Myocardial thickening

• Signs of vascular-mediated risks– IUGR

– Abnormal uterine artery Dopplers

Monitor fluid & FHR Monitor like IUGR

Once / twice weekly Once / twice weeklyEmpiric monitoring based on GA

Start monitoring in the presence of above signs

Anti Ro/La antibodies• 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

MV

AAO

A

E

Fetal SVT• 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

Reappearance of normal venous pattern

Cardioversion

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 - pathophysiologyAlterations 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

Cardiac disease

Structural problems

Anemia-related issues

MCA PSV

Venous Doppler

Prognosis

>70 % mortality

Doppler in Hydrops

Critical diagnostic tool

Prognostic assessment

Allows for monitoring of potentially treatable lesions – CCAM, Sacrococcygeal Teratoma

Post-dates pregnancy• Correct routine first

trimester ultrasound dating almost halves rates of post-term 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– Twice weekly

surveillance

• Induction at 41 weeks decreases stillbirth rate significantly.

0

0.5

1

1.5

2

2.5

24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43

Ris

k /

10

00

on

goin

g p

reg

nan

cie

s

prospective stillbirth rate

prospective perinatal mortality rate

Kahn et al., Obstet Gynecol, 2002

Favor delivery

for singleton

s

Conclusion

Surveillance should be disease specificTesting frequency should be based on disease acceleration

Intervention thresholds should be based on intrauterine versus neonatal risks