E.Keshavarz MD Assistant Professor of Radiology - PowerPoint Presentation

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E.Keshavarz MDAssistant Professor of RadiologyShahid beheshty university

IUGR

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Hyperplasia <16 wk

Hypertrophy

Hyperplasia

&

Hypertrophy

16 – 32 wk15 – 20 g/day

5 g/day

32 wk30-35g/day

Normal growth on a cellular level is not homogeneous but rather follows a pattern that shift over time from

rapid cellular duplication

to

rapid cellular enlargement.

The effects of stimuli that restrict growth may depend in part on when in the sequence of cellular events they occur.

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Why do we search for and worry about the poorly grown fetus?Growth-restricted fetuses have a 6 to 10

fold increased risk of

perinatal

mortality / 20% still birth and those who survive ; 50% have significant short- or long-term morbidity :

intrapartum fetal distress , hypoglycemia ,

hypocalcemia, meconium aspiration pneumonia abnormal neurologic development & IVH In Adulthood : Coronary heart disease – HTN – DM type2- Dyslipidemia – Stroke

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DEFINITIONLOW BIRTH WEIGHT < = 2500gm 1/3 SGA 2/3 Preterm

1/3 IUGR (30%)

2/3 Constitutionally ( 70%)

IUGR fetuses are usually SGA, but

some will be appropriate for gestational age (AGA).

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1-The first group consists of constitutionally small but (70%)otherwise normal fetuses. 2-The second group consists of fetuses with aneuploidy,

nonaneuploid

syndromes, or viral

infection.

3-The third group consists of fetuses with

placental (disease. (15%

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Near term:18% to 25% of umbilical venous flow shunts through the ductus venosus to reach the right atrium in this high-velocity stream

55%

reaches the dominant

left hepatic lobe

and 20% the

right liver lobes. The differences in direction and velocity of blood streams entering the right atrium ensures that nutrient-rich blood is distributed to the left ventricle, myocardium, and brain while low-nutrient venous return is distributed to the placenta for reoxygenation and waste exchange. This process of blood distribution is referred to as “preferential streaming”.

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UV : ligamentum teresDV: ligamentum venosum

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Initial weight gain is due to longitudinal growth and muscle bulk and therefore correlates with glucose and amino acid transport. 80% of fetal fat gain is accrued after 28 weeks’ gestation, providing essential body stores in preparation to extrauterine

life. From 32 weeks onward, fat stores increase from 3.2% of fetal body weight to 16%, accounting for the significant reduction

.

in body water content

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Very small for gestational age (VSGA; <3rd percentile), Small for gestational age (SGA; <10th percentile), Appropriate for gestational age (AGA; 10th-90th percentile) large for gestational age (LGA; >90th percentile) The ponderal index :[(birthweight (g) / crown heel length)3 ] × 100 has a high accuracy for the identification of IUGR and

macrosomia

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After 20 weeks’ gestation a lag of the symphyseal-fundal height of 4 cm (2-3 cm) or more suggests growth restriction.

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In the case that the LMP is uncertain or not known and early ultrasound (before 13 weeks) has not been performed, ultrasound biometry performed before the 20th gestational week will be associated with a margin of error of 7-10 days.The accuracy of a single US measurement for the detection of GA decrease as gestational ages increases.

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The ossification centers of various longs bones are most commonly used in practice. Although their presence does not give an exact GA assessment, it can reassure the clinician that the pregnancy is relatively late into the third trimester .The distal femoral epiphysis is never seen before 28 w, and 100% at 36 w .The proximal tibial epiphysis is never seen before 34 w, and 100% at 39 w.PHE is seen after 37-38 weeks.

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combined diameters of the DFE and PTE were > 11 mm and of similar size (DFE greater than or equal to 1mm larger than the PTE) / visible PHE : fetal lung maturity.

DFE

was seen at

33

weeks in most fetuses often appearing 2-3 weeks earlier in females (29-30 weeks) than males. when the DFE was greater than or equal to 7 mm the gestational age was greater than or equal to 37 weeks. when the

PTE was identified, the fetus was at least 35 weeks.

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Maternal causes of fetal growth restriction Vascular disease such as hypertensive disorders of pregnancyDiabetic vasculopathy CRFCollagen vascular diseaseThrombophilia.

Poor maternal weight gain is a long recognized

risk factor for IUGR

Maternal

prepregnancy

weight and weight gain in pregnancy are .two of the most important variables contributing to

birthweight

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AFV assessment provides an indirect assessment of renal/vascular status. Traditional FHR variables are frequently abnormal by this time. Reduction of global fetal activity and loss of fetal coupling (absence of heart rate reactivity and fetal breathing movements) are typically observed at a mean pH of between 7.10 and 7.20.

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Using the 10th percentiles as cut-offs, the AC has a higher sensitivity (98% vs. 85%) but lower positive predictive value than the SEFW (36% vs. 51%). Its sensitivity is further enhanced by serial measurements at least

14 days apart (3 weeks)

.

The fetal AC is related to hepatic glycogen storage and liver size, therefore correlating closely with the nutritional state. .

HC/AC ratio is approximately

1 at 32 to 34 weeks’ gestation falls below 1 after 34 weeks’ gestation .

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However, both the sensitivity and the positive predictive value of the HC/AC ratio for growth restriction does not equal either the AC percentile, or the SEFW.The FL/AC ratio is 22 at all gestational ages from 21 weeks .An FL/AC ratio

greater than 23.5

suggests IUGR.

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Approximately 70% of infants with a birthweight below the 10th percentile are constitutionally small .The remaining 30% consist of infants who are truly growth restricted and are at risk for increased perinatal morbidity and mortality.

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When the cut-off for an abnormal birthweight is adjusted to the 3rd percentile as suggested by Usher and McLean, the proportion of truly growth-restricted infants identified increases while some with milder forms of IUGR will be missed .

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Fetal growth as opposed to fetal size is a dynamic processThe recommended interval between ultrasound evaluations of fetal growth is 3 weeks, as shorter intervals increase the likelihood of a false-positive .diagnosis

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If gestational age is known, ultrasound assessment of fetal growth based on the HC, AC, FL, and SEFW can be performed. If gestational age is unknown, measurements of the FL/AC ratio and single amniotic fluid pocket have to be used because they are independent of gestational age

.

Up to 96% of fetuses with fluid pockets less than 1 cm may be growth restricted.

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DOPPLER

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Uterine artery doppler

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Umbilical a.Doppler

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Middle cerebral artery

Place the Doppler sample volume in the proximal mid portion of the middle cerebral artery to record the pulsed Doppler waveform

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Clinically, most physicians measure the resistance index (RI) or the pulsatility index (PI)Resistance index (RI): S-D/SPulsatility index (PI) : S-D/Mean flow

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Erythropoietin production in the fetus, as in the adult, is stimulated by the presence of anemia. Elevated blood or amniotic fluid erythropoietin levels may be of help in identifying growth-restricted fetuses at risk for long-term morbidity. An increase in the cord blood glycine

/

valine

ratio

is a .specific response to intrauterine starvation

Invasive Testing

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Although fetal erythropoietin and amino acid levels are of academic interest, they currently add little to the contemporary clinical management of the IUGR fetus.

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FIRST TRIMESTER RISK ASSESSMENT

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The history of delivery of a growth-restricted infant in the first pregnancy is associated with a 25% risk of delivering a second infant below the 10th percentile. After two pregnancies complicated by IUGR, there is a

4

fold

increase in the risk of a subsequent growth-restricted infant.

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A range of first trimester serum analytes that are associated with early abnormalities in placenta angiogenesis and development have been identified in the past years. These show significant differences in their distribution among pregnancies at risk of developing early-onset preeclampsia or fetal growth restriction prior to 34 weeks’ gestation. Of these markers a decrease in the pregnancy-associated protein A (PAPP-A)

or the placental growth factor

(PLGF)

have shown the most consistent predictive performance. The advantage of PAPP-A is the current commercial availability as part of the integrated first trimester screen for

aneuploidy. In this setting a decrease in the PAPP-A

below 0.8 is associated with an increased risk for subsequent placental dysfunction.Maternal Serum Analytes

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At least four hormone/protein markers measured in the maternal sera during the early second trimester are associated with subsequent IUGR. These include serum estriol, human placental

lactogen

,

human chorionic

gonadotrophin, and α-fetoprotein

(AFP). Elevated MSAFP or hCG levels in the second trimester are considered as markers of abnormal placentation and have been associated with an increased risk for IUGR.second trimester elevated MSAFP, “flat” oral glucose tolerance, and abnormal second trimester uterine artery Doppler

velocimetry as important risk factors for IUGR.

Maternal Serum Analytes

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First trimester: decreased PAPP-A & PLGFSecond trimester: Increased BHCG/MSAFP and inhibin A

decreased

estriol

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Maternal Doppler Velocimetry

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Abnormal uterine artery flow velocity waveforms are a manifestation of delayed trophoblast invasion that are highly associated with gestational hypertensive disorders, IUGR, and fetal demise.In women with hypertensive disorders the presence of an elevated uterine artery systolic/diastolic (S/D) ratio (>2.6) and/or

diastolic notching

increased the risk for IUGR and stillbirth .

various cut-offs to define an abnormal test result. These include

S/D ratios above 2.18 at 18 weeks, RI above 0.58

at 18-24 weeks, PI above 1.45 at 22-24 weeks, or the presence of notches. Uterine artery

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The presence of a normal uterine artery flow velocity waveform bears a high negative predictive value, with a likelihood ratio of 0.5 and 0.8 for the development of preeclampsia and IUGR respectively.

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Therapeutic Options

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Tobacco smoke contains a number of substances that are vasoactive and can cause vasoconstriction. IUGR cases with absent end-diastolic flow in the umbilical artery in which diastolic flow returned upon cessation of maternal smoking.Bed rest in the left lateral decubitus Dietary supplementation

Adequate diet

Maternal

hyperoxygenation

: administration of 55% oxygen by face mask or 2.5 L/min by nasal prong. Prolongation of pregnancy from the first recognition of the fetal condition ranged from 9 days to 5 weeks. However, fetal growth velocity was not improved. In addition, fetuses subjected to oxygen therapy had more hypoglycemia, thrombocytopenia, and disseminated intravascular coagulation compared to controls. The primary role of maternal

hyperoxygenation lies in the safe short-term prolongation of pregnancy to allow the administration of corticosteroids to reduce the risk of RDS and IVH.

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Maternal hyperalimentation : only plays a role in patients where malnutrition has been established as the underlying cause of growth delay.Maternal volume expansion : In a small group of centrally monitored women with abnormal placental Doppler studies, they noted that volume expansion was associated with reappearance of umbilical artery end-diastolic velocities and a significant improvement of neonatal survival .

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Low-dose aspirin :Although the overall safety of aspirin has been documented in a large patient population, concerns about a possible association with abdominal wall defects have been raised with administration in the early first trimester .Also bleeding risk is increased. So low dose aspirin in 12-34 weeks is recommended.Corticosteroids : enhancing lung maturation and preventing IVH .(A transient decrease in the middle cerebral artery blood flow resistance has been reported 48 hours after betamethasone

administration

)

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A “reactive” NST exhibits two 15-beat accelerations above the baseline maintained for 15 seconds in a 30-minute monitoring period.prior to 32 weeks’ gestation—greater than 10 beats/minute accelerations sustained for more than 10 seconds; between 32 to 36 weeks’ gestation—greater than 15 beats/minute accelerations sustained for more than 15 seconds; and after 36 weeks’ gestation—greater than 20 beats/minute accelerations sustained for more than 20 seconds.Many growth-restricted fetuses with a normal heart rate tracing can have low-normal pO2 values, but acidemia

is virtually excluded by a reactive NST

.

Fetal Heart Rate Analysis

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Doppler Ultrasound

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“Early” responses : loss of 30% of villi hypoxemia-NL PH“Late” responses : loss of 60-70% of villi

acidemia

Final

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Mild placental vascular disease when umbilical artery end-diastolic velocity is still present. A decrease in the cerebral/placental Doppler ratio provides an early and sensitive marker of redistribution of cardiac output, often preceding overt growth delay by up to 2 weeks .

The nadir of cerebral blood flow resistance is typically reached after a median of

2 weeks

and is followed by an increase in aortic blood flow impedance.

Early cardiovascular responses are considered compensatory because they occur at a time when cardiac function is normal and are typically accompanied by preferential perfusion of vital organs and the placenta.

While the fetus may be hypoxemic, the risk for acidemia is low.“Early” responses to placental insufficiency

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In growth-restricted fetuses with an elevated Doppler index in the umbilical artery, brain sparing in the presence of normal venous Doppler parameters is typically associated with hypoxemia but a normal pH.

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Uterine artery notchingDecreased, absent, or reversed umbilical artery end-diastolic velocity Elevation of blood flow resistance in the thoracic aorta and iliac art (Hind limb reflex) Decrease in the

cerebroplacental

Doppler ratio.

(

Brain sparing ) Centralization :

redistribution of cardiac output in favor of the left ventricle and placental perfusion Increased Doppler resistance in peripheral pulmonary arteries ( right ventricular output bypasses the lungs to reach the placenta.) Decrease in the splenic artery Doppler index (facilitating an increase in red cell mass) Decreased Doppler resistance in the

celiac axis (blood flow augmentation in the hepatic (Liver sparing) and splenic arteries )

Adrenal sparing (as part of the fetal stress response ) Increased SMA Doppler resistance (gut as a nonessential organ )

Increased Doppler resistance in the

renal arteries

.

SUMMARY OF VASCULAR RESPONSES IN IUGR FETUSES

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loss or reversal of umbilical artery end-diastolic velocityChanges in venous doppler indicesAlthough the development of abnormal venous blood flows has been documented in many veins, the precordial veins, including the ductus

venosus

, the

inferior vena cava

, and the umbilical vein, are typically utilized in clinical practice .

Incidences of intrauterine hypoxia ranging from 50% to 80% in fetuses with absent end-diastolic flow have been reported. “Late” responses to placental insufficiency

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The magnitude of forward flow during the atrial systole varies considerably in individual veins and reversal may be physiologic in the inferior vena cava and hepatic veins but is always abnormal in the ductus .

venosus

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IVCThe inferior vena cava shows the typical

triphasic

pattern with systolic and diastolic peaks .

The a-wave may be reversed under physiologic conditions .

An abnormal inferior vena cava flow velocity waveform shows a relative decrease in forward flow during the first trough, the D-wave, and the a-wave .

Under extreme circumstances there may be reversed flow during the first trough .

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DVDuctus

venous has

antegrade

blood flow throughout the cardiac cycle with forward velocities during the S-, D-, and a-waves .

A decrease in

atrial systolic forward velocities (*) is the first sign of abnormality .With marked elevation of central venous pressure blood flow may reverse during atrial systole .

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Abnormal venous Doppler parameters are the strongest Doppler predictors of stillbirth. Even among fetuses with severe arterial Doppler abnormalities (e.g., AEDV or REDV), the risk of stillbirth is largely confined to those fetuses that have abnormal venous Dopplers.

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Cardiac dilatation with holosystolic tricuspid insufficiency .Complete fetal inactivity .Short-term variation below 3.5 msec. Spontaneous “cardiac” late decelerations of the fetal heart rate .

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Normal umbilical venous flow velocity .

Monophasic

umbilical venous pulsations (

*) may be observed with moderate elevations of placental blood flow resistance and/or

oligohydramnios

.Retrograde propagation of increased central venous pressure first results in biphasic and then triphasic pulsations .

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Absence or reverse A-wave in DV.Biphasic/Triphasic UV pulsation.Ominous venous doppler findings

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Fetal Doppler assessment that is based on the umbilical artery alone is NO longer appropriate, particularly in the setting of early onset IUGR prior to 34 weeks. Incorporation of middle cerebral artery and venous Doppler provide the best prediction of acid–base status, risk of stillbirth, and the anticipated rate of progression.

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Arterial redistribution and brain sparing (early stage)are not associated with a significant rise in major neonatal complications. In contrast, a 2 SD elevation of the ductus venosus

Doppler index is associated with

a 3-fold increase

in neonatal complications .The neonatal mortality rate in fetuses with absent or reverse umbilical artery end-diastolic velocity ranges from

5% to 18% when the venous Doppler indices are normal. Elevation of the ductus venosus Doppler index greater than 2 SDs doubles this mortality rate

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DV S/a ratio >95th percentile :8UmA REDF :6PA PSV abnormal :5-9Ao PSV abnormal :6DV reverse flow :3

IVC abnormal:4

DV abnormal :4

UV pulsations :4

BPS <6 :1

Brain sparing

Absence UAEDV

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Once brain sparing is established, the next level of deterioration occurs when umbilical artery end-diastolic velocity is lost.This may happen after several weeks, the anticipation of such deterioration may require twice weekly rather than weekly testing.

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Elevations of precordial venous Doppler indices also precede sudden deterioration of the BPS by a median of 1 week in fetuses with elevated umbilical artery blood flow resistance.Therefore,

three-times weekly or even daily

testing may be necessary in such fetuses.

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In pregnancies in which umbilical artery end-diastolic velocity is lost within the first 2 weeks of diagnosis, deterioration to venous Doppler and biophysical abnormalities within 4 weeks is common. If umbilical artery end-diastolic is maintained for longer periods, deterioration may not occur for 6 weeks after diagnosis.

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1-The first group consists of constitutionally small but (70%)otherwise normal fetuses. 2-The second group consists of fetuses with aneuploidy,

nonaneuploid

syndromes, or viral

infection.

3-The third group consists of fetuses with

placental (disease. (15%

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First trimester screeningmeasurement of the uterine artery pulsatility index (PI) at 11-13 weeks' gestation in combination with maternal history(inc) mean arterial pressure

(inc)

serum PAPP-A

(dec…>inc) placental growth factor (PLGF)

(dec…>inc)

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“Early” responses : loss of 30% of villi hypoxemia-NL PH“Late” responses : loss of 60-70% of villi

acidemia

Final

Diagnosis

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