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1. Definition -Ankita
2. Etiology:
a. Placental factors -Rimpi
b. Maternal factors -Maitri
c. Fetal factors (including genetic perspectives) -Chetali
3. Clinical diagnosis of IUGR -Ankita
4. Non-clinical diagnosis of IUGR
• Non-invasive
a. USG for fetal growth parameter -Rimpi
b. Fetal echocardiography -Maitri
c. Doppler – colour-Velocimetry -Chetali
• Invasive:
a) Cordocentesis -Ankita
b) Placental biopsy -Rimpi
c) Chorion-villus sampling -Maitri
5. Fetal Therapy
a. Bed rest, Maternal nutrition -Ankita
b. Oxygen/Aspirin -Rimpi
c. β mimetic, IGF, A.N.P -Maitri
d. Fetal Nutrition & Supplement
e. Mechanical Treatment
f. Status of induction of pulmonary maturity -Chetali
6. Issues regarding decision making
a. Early onset IUGR (Timing & method of delivery)
-Maitri
b. Late onset IUGR (Timing & method of delivery)
-Chetali
7. SFD Baby - Rimpi
FETAL GROWTH RESTRICTION
INTRODUCTION:
The growth of fetus in utero reflects a delicate
equilibrium between the mother, the placenta, and the fetus.
Fetal growth restriction is not a single disease entity, but
rather a physical sign that may result from a broad variety
of pathogenic mechanisms. Fetal growth restriction otherwise
known as intra uterine growth restriction (IUGR) is defined
as a pathologic decrease in rate of fetal growth and
ultimately results in a fetus that does not achieve its
inherent growth potential, putting it at risk for increased
perinatal morbidity and mortality. Small for gestational age
is conceptually not the same entity as FGR. It is defined as
a fetus that has failed to achieve a specific and arbitrary
anthropometric or weight threshold by a specific gestational
age. SGA: New born with birth weight less than the 10th
percentile for their gestational age and less than 2500 gms.
Both terminologies attempt to identify fetus that are small
for reasons other than being preterm.
Fallacy: Is the variation in birth weight for gestational
age standards. SGA and IUGR do not separate normal and
healthy fetuses that have a weight below the 10th percentile
from those who are small because of intrauterine
malnutrition.
CLASSIFICATION:
* Intrinsic IUGR: Fetuses are small because of fetal
condition such as intrauterine infection or chromosomal
abnormality.
* Extrinsic IUGR: Growth failure is caused by an element
outside of fetus such as a) Placental condition or b)
Maternal disease
* Combined IUGR: Both extrinsic and intrinsic factors
acting in conjunction to bring about growth failure.
* Idiopathic IUGR: cause of fetal growth failure is
unknown.
TYPES:
TYPE-I TYPE-II
Symmetric (33%) Asymmetric (55%)
Growth of both fetal abdomen and head are proportionally
decreased There is disproportionate decrease in size of
fetal abdomen with respect to fetal head. Also called head
sparing type.
Normal HC/AC Increased HC/AC
Etiology: Early insult Late insult
Genetic, infective pathology, substance abuse, cigarette
smoking (impairs cellular hyperplasia leading to long
periods of subnormal growth) Placental vascular
insufficiency
(Impairs cellular hypertrophy with increased risk of
perinatal hypoxia and hypoglycemia)
Risk for long-term neuro-developmental dysfunction
resulting from a deficit in total number of brain cells.
Long term prognosis good
Normal Ponderal Index Low PI
Although this division is conceptually attractive whether
this classification is useful in defining etiology or in
predicting outcome is less clear
NORMAL INTRAUTERINE GROWTH PATTERN:
• Stage-I (hyperplasia): 4-20 weeks gestation rapid
mitosis & increase of DNA content.
• Stage-II (hyperplasia & hypertrophy): 20-28 weeks
declining mitosis & increase in cell size.
• Stage-III (hypertrophy): 28-40 weeks rapid increase in
cell size with peak velocity at 33 weeks gestation, rapid
accumulation of fat, muscle & connective tissue. 95% of
fetal weight gain occurs during last 20 weeks of gestation.
PLACENTAL FACTORS
1) Small Placenta
2) Premature aging of placenta
3) Abruptio placenta
4) Placenta previa
5) Chronic villitis, vasculitis
6) Chorioamnionitis
7) Chorioangioma, hemangioma, placental cysts
8) Circumvallate placenta
9) Twin to twin transfusion (Placental Anastomosis)
10) Umbilical cord complications- single umbilical artery –
true knots, velamentous cord insertion
11) Amniotic bands
12) Repeated first trimester bleeding
PATHOPHYSIOLOGY OF PLACENTAL INSUFFICIENCY
Normal Placentation- the number of spiral arteries
supplying the placental bed is fixed relatively early in
pregnancy. In order to accommodate necessary blood flow the
spiral arteries undergo following changes mediated by
trophoblastic invasion.
1) In the I- trimester- decidual segments of the arteries
undergo degeneration of internal elastic lamina–denudation
of smooth muscle & elastin in the inner and outer media,
which are replaced by hyaline & fibrin.
2) 2nd Phase (16-18 weeks) -extension of trophoblastic
invasion into the myometrial segment of spiral arteries
Placental insufficiency:
-Reduction in villi & stem capillaries
-Decrease in parenchyma & increase in stroma
-Clumps of syncitial villi forming knots in the intervillous
space
-Trophoblastic invasion restricted to decidual segments
-Myometrial segments remain intact and responsive to
vasoconstrictors
-Acute atherosis of stem villi-- lipid necrosis of
myometrium & smooth muscle cells
-Hyperplastic proliferation of the remaining smooth muscle
cells resulting in narrowing of the lumen.
MATERNAL FACTORS:
1) Constitutionally Small Mothers:
a) Small women typically have small babies.
b) If woman begins pregnant weighing less than 100 pounds,
the risk of delivering a small for gestational age infant is
increased at least 2 fold.
c) Reduced intrauterine growth of the mother is a risk
factor for reduced intrauterine growth of her children.
2) Maternal Vascular disease:
a) E.g. Chronic hypertension, preeclampsia, renal disease,
diabetes, collagen vascular disease like SLE, cyanotic heart
disease, severe anemia as can be seen with sickle cell
anemia, chronic pulmonary disease such as asthma.
b) In case of preeclampsia, there is a deficient
trophoblastic invasion.
c) Incidence of fetal growth retardation is increased 2 to 3
fold in hypertensives disorders of pregnancy.
d) In case of pregestational diabetes, the risk of fetal
growth restriction increases with increasing severity &
duration of the disease.
e) This may be due to damage in the microcirculation that is
associated with diabetes.
f) Affection of microcirculation could risk the development
of PIH & cause severe IUGR.
g) Collagen vascular disease such as SLE is frequently
associated with fetal growth restriction with an increase of
more than 8 folds that of general incidence of IUGR.
3) Maternal Habits:
a) Cigarette smoking is the most important preventable
cause. The reduction in foetal growth is between 150 to 400
gm at term. Carbon monoxide exposure causes decrease in
foetal hemoglobin oxygen carrying capacity. Nicotine
releases catecholamines. This could cause repetitive
episodes of reduced maternal perfusion of the placenta.
Placental abruption also has been reported to occur more
frequently among them.
a) Tobaccos chewing gravidas & passive smoker also have
reduced foetal weight. This is because decreased
intervillous blood flow, the effect of carbon monoxide &
thiocyanate on the fetus, decreased prostacyclin production.
b) Maternal alcohol ingestion is another well recognized
cause of IUGR & it has synergistic effect with smoking.
c) The chronic ingestion of heroin, morphine, Cocaine &
other additive substances is frequently associated with
IUGR.
4) Maternal malnutrition:
a) Major cause of IUGR
b) Lack of weight gain in the 2nd trimester is strongly
correlated with decreased birth weight.
c) The human foetus behaves as a parasite & its growth rate
is not affected except in extreme states of severe dietary
deprivation.
5) Maternal Medication:
a) The use of certain medication during pregnancy is
associated with IUGR babies. E.g.
• Cancer chemotherapeutic agents, warfarin
• Anticonvulsants like phenytoin
• Folic acid antagonists.
FOETAL FACTORS INCLUDING GENETIC PERSPECTIVES:
1) Chromosomal abnormalities:
• Frequency 10% may be as high as 38%
• Majority have symmetric measurements
• Most common are karyotype abnormalities
A) Trisomy 21.
• Foetal growth restriction generally mild
• After first trimester growth of all long bones lag behind.
• Shortened femur length and hypoplasia of middle phalanx
documented with increased frequency.
B) Trisomy-18:
• Significant restriction of growth
• As early as first trimester
• Upper extremity more severely affected than lower.
• Visceral organs growth may be abnormal.
C) Trisomy –13:
• Mild growth restriction
D) Trisomy- 16-
• Usually lead to spontaneous abortions.
• Affect the placenta called confined placental mosaicism
lead to placental insufficiency.
• Placentas of foetal autosomal trisomies have reduced
number of small muscular arteries in tertiary stem villi.
II) CONGENITAL ANOMALIES:
• Potter’s syndrome
• Cardiac anomalies
• Primarily disorders of cartilage and bone
• Osteogenesis imperfecta
• Chondrodystrophies
III) MULTIFETAL GESTATION:
• Up to 21% affected
• More common with monochorionic placentation
• Causes
- Abnormal placentation
- Decreased placental size
- Abnormal placental vascular Anastomosis
IV) INFECTIONS:
A) Rubella: Causes capillary endothelial damage, decreases
number of normalized cells, reduces cell division rate.
B) Cytomegalovirus: Decreases cell number because of
cytolysis and localized organ necrosis.
C) Possibly- Toxoplasmosis,
-Varicella zoster
-Tuberculosis
-Malaria
-Syphilis
CLINICAL DIAGNOSIS
MEDICAL OBSTERIC HISTORY
Age
Parity
Occupation
Income
Personal history
Past history
EXAMINATION
Vitals
Weight gain
Height
Uterine fundal height
Abdominal circumference
EBW
Liquor.
ANTEPARTUM SURVEILLANCE OF IUGR FETUS: -
Non stress test
Fluid volume
PRENATAL DIAGNOSIS:
MATERNAL HISTORY:
Age: < 17 Yrs Or > 35 Yrs.
Marital status: Single mothers / unwanted pregnancies
Education level: Low educational level.
Family problems
Occupation: Strong physical work and intellectual stress.
Environmental factors: Urban environment, economic
depression, migration, culture.
Parity: Mainly when the intergenesic period is less than 2
years & in precocious primigravida, history of IUGR baby in
previous pregnancy.
Personal Habits: Smoking as in active and/or passive
smoking.
Alcohol, which provokes irreversible damage, mental
deficiency & malformations have been reported.
Drugs: Cytostatic medications, propylthiouracil, heroine,
propranolol, anticonvulsants, prednisone.
History of maternal vascular disease: Chronic hypertension
Preeclampsia
Renal disease
Diabetes
Collagen vascular disease
Cyanotic heart diseases
Sickle cell disease
GENERAL EXAMINATION: -
Built & nutrition: Height: low (< 1.50m)
Weight: starting pregnancy underweight and with inadequate
gain during the same.
Measurement of fundal height:
1. Measurement of fundal height is an excellent screening
tool for IUGR.
2. Sensitivity may reach 95% when precise gestational dates
are available.
3. Measured from symphysis pubis to superior aspect of
uterine fundus.
4. Between 20-34 weeks the uterine fundal height in cms.
roughly coincides with weeks of gestation.
5. While this measurement is useful it is fraught with
potential measurement problems in women who are overweight
and the inability of the physician to identify the top of
uterus for proper measurement.
6. Patients’ bladder should be evacuated prior to the
examination.
7. Inference – If the measurement is 4 cm less than the
expected height inappropriate fetal growth is suspected.
(According to Williams Obstetrics 2 cm less than the
expected is worrisome)
8. Difficulty:
• If uterine fundus is deviated to one side measurement
taken in middle will be inaccurate
• Maternal obesity
• Breech / transverse presentation
• Uncertain dates
• Uterine anomalies such as fibroids / twins / hydramnios
• This screening method can identify < 50% of fetus with
IUGR.
Positive Roll Over Test:
• Is predictive of IUGR
• Is defined as a rise in diastolic blood pressure of 20 mm
Hg or more with a position change from the left lateral
recumbent to supine.
AMNIOTIC FLUID VOLUME:
• Oligohydramnios is frequently associated with IUGR
especially asymmetric IUGR and may reflect decreased renal
blood flow and urine output.
• It occurs in about 16% of IUGR pregnancies.
POSITIVE PREDICITIVE VALUES:
• Fundal height 20-60%
• Roll over test 22%
• Decreased amniotic fluid volume 55%
DIAGNOSIS OF FGR BY USG
It is very important, non-invasive, easily available
accurate method for the diagnosis and confirmation of FGR.
1) ESTIMATED FETAL WEIGHT-
Fetal weight estimation is within 5-10% of the true fetal
weight. Also the method requires precise knowledge of the
gestational age. Fetal weight estimation is valuable in the
diagnosis of small fetuses but do not differentiate between
FGR and small but healthy babies. This method has
sensitivity of 87% and specificity of 87% when the estimated
fetal weight is below the 10th percentile for the
gestational age.
2) FETAL PONDERAL INDEX-
It is gestational age independent and gives a constant
value throughout the second part of pregnancy. PI=Estimated
Fetal Weight/(Femur length)3 PI value 8.325+/- 2.5 (2SD).
Value of 7 or less than 7 strongly suggest fetal
malnutrition
3) ESTIMATED GESTATIONAL AGE-
Estimating the gestational age of the fetus by averaging
routine fetal measurements. The difference between the USG
derived and clinically estimated gestational age (only if
the gestational age is reliable) gives a quantitative idea
of fetal growth impairment
4) BIPARIETAL DIAMETER-
- Serial measurements of BPD demonstrate 2 distinct
patterns of impaired fetal growth.
• SLOW GROWTH PROFILE- Fetuses which show continuous BPD
growth during the entire pregnancy but measurements remain
at all times below the 10th percentile for the gestational
age.
• LATE FLATTENING PROFILE: Fetuses that exhibit normal
BPD growth during the first two trimesters of pregnancy
followed by arrest of growth during the last trimester.
These are the true FGR.
But sensitivity & specificity is too low since
- Head is one of the last organ to be affected by fetal
malnutrition
- Late in pregnancy fetal head enters the pelvis and undergo
moulding process.
5) ABDOMINAL CIRCUMFERENCE-
The best single measurement is AC. Serial AC value
plotted over a graph that is linear from 15 weeks of
gestation that is 1 cm in 2 weeks correctly identified most
FGR babies. Negative predictive value- 99%. Therefore
finding a normal AC practically rules out that the baby is
small
6) HEAD TO ABDOMEN RATIO
The ratio compares the most preserved organ in the
malnourished fetus, the brain with the most compromised, the
liver. AC is measured at the level of bifurcation of hepatic
vein in the center of the liver. HC is measured at the level
of thalamii. It is important to diagnose the type of IUGR.
- SYMMETRIC FGR - refers to a growth pattern in which the
growth of both fetal head & abdomen are decreased
proportionately. It results from an early insult and is
characterized by a long period of subnormal growth. These
infants do not have perinatal asphyxia but are at a risk of
neuro-developmental dysfunction resulting from a deficit of
total number of brain cells. It is associated with infective
/genetic pathology
- ASYMMETRIC FGR- refers to the growth-retarded fetus in
whom, a disproportionate decrease in the size of the fetal
abdomen with respect to fetal head is seen. This pattern is
also known as head sparing type. It is caused by a late
insult that impairs cellular hypertrophy. It is usually
associated with progressive uteroplacental insufficiency.
Greater risk of perinatal hypoxia and neonatal hypoglycemia,
their long-term prognosis by appropriate management is good.
There is a substantial overlap between the two patterns.
Although this differentiation is conceptually attractive the
usefulness in defining etiology and predicting outcome is
less clear.
7) FEMUR TO ABDOMEN RATIO-
- This method compares femur length that is minimally
affected by fetal growth impairment with the abdominal
circumference, which is the most affected.
- Advantage: FL is easy to obtain, Not affected by
moulding/abnormal presentation and position
- FL remains constant after 20 weeks
- Normal value of FL/AC= 22+/-2 (upper limit 23.5)
- When F/A is abnormally high—fetal malnutrition
- When F/A ratio is normal--- small but healthy baby,
symmetrical FGR but it is unlikely that the baby is
suffering from severe malnutrition.
8) OLIGOHYDRAMNIOS-
- Late sign of fetal malnutrition
- Amniotic fluid volume is measured by four quadrant
technique (AFI)
- The fluid is decreased if AFI<10 and markedly decreased if
AFI<5
8) PLACENTAL GRADING
- When BPD & FL suggests less gestational age and
placental grading is high S/O FGR
9) CONGENITAL ANOMALIES
- Important etiological factors for FGR
- USG done to rule out congenital anomalies
FETAL ECHOCARDIOGRAPHY:
- Ultrasonography imaging of foetal heart & blood vessels
started with the Doppler recording of placental blood flow
and some experimental M mode studies. The most important
application of foetal echo remains in determining cardiac
structural & functional status in a pre-viable foetus.
- A careful delineation of the cardiac status may lead to
one of the three situations:
- 1) For a potentially irremediable condition such as
hypoplastic left heart syndrome (HLHS), one is likely to
take a decision for medical termination of pregnancy.
- 2) For a structural problem that is amenable to surgical
or trans-catheter intervention treatment, by & large the
decision will be to continue the pregnancy. The time & place
of delivery will be carefully planned to optimize the
neonatal outcome.
- 3) In an otherwise high-risk state, a normal foetal echo
always helps to ease the burden of the pregnancy.
- Cardiac arrhythmia is getting more & more frequently
diagnosed & assessed by fetal echo, thereby helping medical
management of this condition. Fetal echo is emerging as a
strong tool and is helping to clarify the pathogenesis of
many cardiac abnormalities.
Timing of Fetal Echo:
- The first study should ideally be done between 20-22
weeks of gestation to allow a possible decision of
termination.
- By current techniques of fetal echo, the best impression
however is found between 23-26 weeks.
- If indicated, the fetus is followed up with serial echo at
intervals of one to two weeks.
Indications:
In an ideal world each pregnancy should undergo a fetal
cardiac scan to rule out the possibility of congenital heart
defects. The following are the situations where a fetal echo
is strongly indicated:
- F/h/o congenital heart defects especially previous sib or
parents.
- Hydrops fetalis esp. the nonimmune
- Fetal cardiac arrhythmia &/or maternal collagen vascular
disease.
- Fetal somatic anomaly on USG
- Suggestion of abnormal genetic, chromosomal or syndromatic
pattern in fetus or in the family.
- Maternal condition this associated with fetal
abnormalities e.g. diabetes mellitus, polyhydroamnios,
oligohydramnios, Rh sensitization, drug exposure esp.
alcohol, narcotics, anticonvulsants.
- Any condition that indicates that the fetus is not doing
well should preferably be looked into with a fetal echo.
E.g. IUGR & unexplained diminished fetal movements.
DOPPLER FLOW VELOCIMETRY
- Deteriorating placental function triggers a sequence of
fetal protective mechanisms resulting in altered fetal
cardiac function. These cardiac vascular alterations are
mirrored by fetal arterial and venous Doppler studies.
- Indices used are:
1) S/D Ratio: Maximal systole flow velocity/ minimal end
diastolic flow velocity.
2) S-D/ S: Resistance index (Pourcelot index)
3) S-D/ Mean: Pulsatility index.
4) Percentage of reverse flow
5) Preload index: - PLI = PVA (Peak velocity in atrial
contraction)/
PVS (Peak velocity in ventricular systole)
N: 0 to 0.37
6) Cerebro-placental Ratio: Cerebral flow/ placental or
umbilical flow Normal:> 1
Doppler Sequencing Of Foetal Jeopardy:
1) Impaired endovascular trophoblastic invasion
(secondary invasion)
2) This is expressed as high resistance in uterine artery
fetal blood flow velocity waveforms (FVW) – systolic or/ and
diastolic notching can be there. Abnormal Doppler Indices
need not always be present in uterine artery in FGR.
3) This altered deicidal circulation leads to impaired
uteroplacental perfusion, which causes decreased oxygen
perfusion.
4) The placental tertiary arteries decrease in number. Until
the reduction is more than 50%, umbilical blood flow can be
maintained. There- fore umbilical artery FVW is not
sensitive to fetal hypoxemia, hypoxia or partly
decompensated respiratory acidosis. It can only determine
fetal acidosis with sensitivity ranging near 100%. It still
identifies fetal acidosis well ahead of gross changes in
biophysical profile.
5) There is increased placental vascular resistance and
reduced fetal oxygenation.
6) Resultant fetal hypoxemia causes peripheral
vasoconstriction. Which when worsened is expressed as
umbilical artery impedance (High S/D ratio)
7) The right ventricular after load increase and reduction
in fetal perfusion of substrate and oxygen
8) This fetal hypoxemia causes dilatation of ductus venosus
and vasoconstriction of hepatic microcirculation.
9) Amplitude of flow in microcirculation: Amplitude of flow
in ductus venous is increased and is the earliest and most
sensitive sign of fetal hypoxemia. Normally ductus venosus
distributes 50% of umbilical blood directly into inferior
vena cava (IVC). Such blood flow ensures the supply of
oxygenated blood to coronary and cerebral circulation.
During hypoxemia this fraction increases up to 70% and less
blood is circulated in liver through portal system. Hence
less hepatic glycogen deposition lead to reduced abdominal
circumference of FGR fetus. A 50% decrease in umbilical
blood flow is associated with 75% decrease in hepatic blood
flow. The mechanism responsible could be accounted by active
relaxation of ductus venosus or vasoconstriction in hepatic
circulation.
10) Streaming of more blood through ductus venous across the
foramen ovale and resultant increase in left ventricular
pre-load.
11) There is cerebral vasodilatation and increase blood flow
(low S/D ratio in middle cerebral artery). Myocardial blood
flow is also similarly increased. Thus, brain and heart are
perfused with oxygenated blood even in fetal hypoxemia. The
normal fetal cerebral circulation is of high impedance low
flow. Even in second hall of pregnancy normal S/D of middle
cerebral artery is very high in the range of 2.8 to 3. The
cerebroplacental ratio (CPR) compare the resistance to blood
flow in umbilical artery and middle cerebral artery. It is
the most powerful parameter of assessment of FGR and
hypoxemia. It takes into account the placental disturbances
due to vascular disease and cerebral response to placental
resistance. CPR value is heart rate independent and has
significant cut off value of 1. (CPR is normal if it is > 1
12) Increased cerebral flow decrease the left ventricular
after load. Fetus even though hypoxemic, is maintained in
the compensated phase by the ventricular contractile force.
13) Superior vena cava venous return greatly increases
cerebral flow. This deoxygenated blood from the cerebral
region in large volume reaches the right atrium and ejected
into right ventricle, increasing right ventricular preload.
At this stage ductus venosus may reveal decreased amplitude
and absent or reverse flow during arterial contraction.
Concurrently AEDV or reversed flow develops in umbilical
artery. Reduced oxygenation causes vasoconstriction of
ductus arteriosus and pulmonary trunk. Hence the right
ventricular blood cannot be properly pumped into descending
aorta and placenta for oxygenation. This stagnation leads to
recirculation of deoxygenated blood into cerebral
circulation. Increased flow of this deoxygenated blood
causes cerebral congestion and edema leading to vascular
impendence in middle cerebral artery (high S/D ratio)
14) This deoxygenated blood recirculated in vasorum causes
myocardial ischemia
15) Combined with increase right ventricular load the
myocardial ischemia leads to cardiac failure and poor
contractile force.
16) This is evidenced by absent or reverse flow in ductus
venous and IVC and appearance of pulsations in umbilical
vein.
17) Cardiac dilatation and tricuspid regurgitation are other
signs of failure.
CORDOCENTESIS
UMBLICAL CORD BLOOD SAMPLING:
Aim:
• To make rapid determination of fetal karyotype when
chromosomal defect is suspected.
• To assess degree of fetal hypoxia & acidosis.
• To assess Cytogenetic, Biochemical, Metabolic, Endocrine
and Hematological status
Limitations:
- In most series of FGR fetuses, incidence of chromosomal
anomalies has been <10% (which can be detected by targeted
ultrasound)
- Doppler velocimetry results are found to correlate better
with the level of fetal acidosis precluding the need for
cord blood study.
- Fetal loss rates within 2 weeks of sampling were 1,7, 14 &
25% in groups: Normal /Abnormal / Growth retarded / hydropic
fetus respectively.
- Babies frequently develop prolonged, severe bradycardias
requiring emergency caesarean delivery.
Inference:
- 19% Chromosomal defects were detected.
They included:
Triploidy
Trisomy 21
Trisomy 18
Trisomy 13
Aneuploidus
Deletions or translocations
- Triploidies encountered in second trimester &
Aneuploidus, deletions and translocations found in third
trimester group.
- Triploidy is associated with the most severe from of early
onset growth retardation and that majority of fetuses die
before third trimester of pregnancy.
- 2nd trimester most severely asymmetrically small fetuses
are chromosomally abnormal.
- Growth retarded fetuses are hyperlacticaemic
- In SGA erythropoetin concentration increased in response
to tissue hypoxia & is associated with macrocytosis and
erythroblastosis
- Severely growth retarded fetuses are thrombocytopenic &
leukopenic as a result of tissue hypoxia & deficiency of
essential nutrients.
CHORION VILLI SAMPLING (CVS)
- It is a procedure for prenatal genetic diagnosis.
- It is performed between 9 & 12 weeks.
- Chorionic villi for antenatal diagnosis can be obtained
by:
I) Trans cervical catheter aspiration
II) Trans abdominal needle aspiration
III) Trans vaginal aspiration
I) Trans-cervical catheter aspiration:
- CVS starts with a real-time ultrasound examination.
- The position of uterus, number of gestational sacs,
gestational age of foetus, presence of foetal heart
activity, localization of the chorion frundosum are
determined.
Advantages:
1) Genetic diagnosis is achieved at an early gestational
age.
2) Comfortable for the patient.
3) Technically simple.
Disadvantages:
1) It has a slightly higher risk of foetal loss
2) Chromosome composition of the chorionic villous is
occasionally different from the chromosome composition of
foetal cells.
3) Enzyme composition of chorionic villous cells may be
different from the fetal cells.
4) It is difficult if placenta is fundal.
Contraindications:
1. Positive N. gonorrhea culture of cervix
2. Active genital herpes
3. Active bleeding
4. Maternal coagulopathy
5. Cervical stenosis
6. Severe cervicitis
7. Uterine myomata
8. IUD inside the pregnant uterus.
II) Trans-abdominal CVS:
The need to obtain chorionic villi from patients who had
contraindications to the performance of Tran cervical CVS &
the need to reduce the potential risk of infection
associated with the vaginal procedure.
Advantages:
- 1) Minimal risk of infection
- 2) Does not cause vaginal bleeding
- 3) Can be performed in 2nd & 3rd trimester
Disadvantages:
- The amount of tissue obtained is less
- Greater discomfort
- Difficult to performs if placenta is posterior
- Technically more difficult.
III) Trans Vaginal CVS:
- There are some patients in whom trans abdominal &
trans-cervical CVS are difficult to perform because of
extreme uterine retroversion, presence of myomas, or
placental localization.
MATERNAL NUTRITION
- The most common cause of FGR is impaired nutrient
supply to the fetus.
- Fetal growth depends on adequate maternal fuel supply and
a maternal vascular tree that can deliver these fuels to the
fetoplacental unit.
- Adequate perfusion of uteroplacental bed and adequate
delivery of amino acids, lipids and carbohydrates are
necessary for normal fetal growth.
- Weight gain in women with normal pre pregnancy body mass
index should be at least 11.29 kg to prevent preterm births
& fetal growth restriction.
Energy Needs: -
• 36 k cal /kg
• Increase 10-15% over pre-pregnant state
• Proteins: Additional 10-12 gm for fetal
growth.
• Minerals: Calcium: 1000gm –fetal skeletal
Tissue, muscle action, blood
coagulation
Iron: 30mg
• Vitamins: Folic acid: 1mg, Vitamin C: 70 mg, Vitamin A:
6000 IU
BED REST:
Results in decreased blood flow to the periphery and
increase in blood flow to uteroplacental circulation that
contributes to improved fetal growth. However there is no
striking paucity of data validating these assumptions. Hard
and strenuous work should be avoided specially in first
trimester and last 6 weeks. On an average patient should be
in bed for about 10 hours.
MATERNAL HYPEROXYGENATION THERAPY:
It has been proved that in IUGR baby’s acidosis and
decreased oxygen saturation is found in umbilical artery.
Maternal hyper-oxygenation with 55% oxygen administered at a
rate of 8L/min around the clock in gestational age of 26-34
weeks in FGR fetuses with oligohydramnios and abnormal
umbilical artery Doppler studies. Po2 is increased from 21.2
mm Hg –27.7mm Hg. PCo2 decreased from 43.7 mm Hg - 38 mm Hg.
O2 saturation is increased from 57% to 71.8%. pH is
increased from 7.31—7.34. Although there is not much
difference in birth weight the mortality significantly
decreased from 68-85% to 20-29 %
ASPIRIN:
Role of aspirin is yet to be proven. The dose recommended
is low dose aspirin 1-2mg/kg/day. It inhibits the
cyclooxygenase pathway, decreases TXA2 but does not alter
PGI2 in low dose. TXA2 & PGI2 ratio is altered in favour of
PGI2. This leads to vasodilatation in uteroplacental bed.
There is insufficient evidence to recommend for or against
the routine use of aspirin.
Side effects include Congenital Heart disease (associated
with aspirin) use in 1st trimester. However no causal links
has been established between aspirin & birth defects. An
occasional increased risk of maternal bleeding, abruption,
and post partum hemorrhage has been reported. Aspirin use
needs very careful proper counseling.
BETA- MIMETICS:
These agents have been employed for tocolysis. One of the
effects is stimulation of myometrium adenylate cyclase,
which results in myometrial relaxation. These consequently
results in decreased resistance to uterine blood flow &
increase uterine perfusion. Similarly, a direct vasodilator
effect on the uterine arteries may results in increased
uterine perfusion. This may theoretically benefit in
treatment of IUGR. However, recent studies could not
demonstrate enhanced foetal growth associated with
Beta-agonist administration.
ATRIAL NATRIURETIC PEPTIDE (ANP):
It is an endogenous peptide synthesized in the right
atrium that has diuretic, natriuretic & vasodilator effects.
The biologic effects of ANP are thought to be mediated
through the stimulation of guanylate cyclase, resulting in
increased intracellular concentration of cyclic guanosine
monophosphate. This peptide has been reported to dilate the
placental vasculature in late pregnancy. Recent studies
support the administration of ANP as a novel measure for
treatment of IUGR. Infusion of ANP has resulted in 26%
increase in blood flow to the placenta. An 80% reduction in
number of ANP receptors in IUGR has been observed;
suggesting that pertubation of ANP receptor physiology may
be associated with IUGR.
INSULIN LIKE GROWTH FACTOR (IGF):
It has a direct effect on placental carbohydrate
metabolism thereby facilitating transfer of substrate to the
fetus & foetal growth. This may explain how maternal
IGF-1administration reverses maternal constraint of foetal
growth in FGR. Short-term IGF-1 infusions improved the
placental carbohydrate metabolism, but have no effect on
foetal oxygenation.
FOETAL THERAPY-
I) FOETAL NUTRITIONAL SUPPLEMETNATION:
Nutrients like sugar proteins, amino acids and lactate in
amniotic fluid are swallowed, digested and absorbed by the
fetus which provides 10-30 calories per day and 0.2-0.3 gm
proteins per kg per day in the third trimester. Absorption
of nutrients may occur through placenta, foetal membranes
and umbilical cord. Trans amniotic foetal feeding (TAFF)
with a 10% dextrose solution, amino acids and lipids has
been tried. It has been observed that when fetal oxygenation
is impaired TAFF might not be of any use in treatment of
FGR. The trophic factors on the gastro-intestinal tract
present in amniotic fluid are gastrin and epidermal growth
factor (EGF). It has been suggested that EGF must be an
important constituent of TAFF. The relevance of these data
to clinical practice remains to be determined.
II) MECHANICAL THERPAY:
A novel approach is intermittent abdominal decompression.
A negative pressure of 70mm Hg is applied for 30 seconds
every minute for 30 minutes twice daily. This is thought to
increase blood flow to placental intervillous space.
III) STATUS OF INDUCTION OF PULMONARY MATURITY:
The growth-retarded foetus is thought to be stressed and
responds to this stress by secreting endogenous
corticosteroids that enhance pulmonary maturity. But
recently the validity of these data is questioned.
EARLY ONSET –IUGR:
The usual causes for early onset FGR before 32 weeks of
gestation are:
- Chromosomal anomalies
- Congenital anomalies
- Intrauterine infection
- Only when these are excluded the probability of:
Uteroplacental dysfunction
Nearly 20% fetuses with early onset FGR have a
chromosomal abnormality. Using serology, a viral agent can
be identified in nearly 5% cases. Foetal infection is most
suspected when a severely FGR foetus has normal blood gas
levels, normal karyotype & abnormal platelet or WBC count.
Screening for toxoplasmosis, rubella, cytomegalovirus,
herpes & other viral agents is recommended. Since USG &
color Doppler studies can identify nearly 90% of chromosomal
anomalies & 65% of all structural anomalies. Major causes of
early onset FGR can be sorted out at ultrasound study
itself. The normal fetuses otherwise showing early onset FGR
should be considered to suffer from uteroplacental
dysfunction. They are to be managed conservatively with
regular Doppler studies or BPP. The pregnancy could be
continued at least until 36 weeks if Doppler is normal.
Development of AEDV with venous Doppler abnormality, REDF or
severe oligohydramnios will be an indication for delivery.
Fetal response to maternal hyper oxygenation may be
predictive of which fetus may develop hypoxia
Timing & Method Of Delivery: Chromosomally normal FGR
foetus with a gestational age of > 36 weeks should be
delivered electively. There is no need for prior
documentation of foetal pulmonary maturity. Oligohydramnios
at >36weeks is an indication for immediate delivery because
of the risk of a cord accident. Failure of growth is also an
indication for delivery. As age advances, delivery in the
absence of frank fetal distress becomes a more desirable
option. The mode of delivery is governed by the underlying
etiology, evidence of acidemia & gestational age. As long as
ductus venosus flow velocity is normal, vaginal delivery
under intrapartum monitoring is quite acceptable. Unless
there is an abnormal CTG or a malpresentation, normal but
small fetuses should be allowed to go into labour. Growth
restricted fetuses without evidence of hypoxemia can be also
managed in same way. In case of acidemia, LSCS is ideal.
Acidemia is presumed when there is REDF, reverse flow in
ductus venosus, significant reverse flow in inferior vena
cava, cerebral dilatation or repetitive late deceleration &
these fetuses are not suited for vaginal delivery. A trial
of labour should be considered first with continuous fetal
heart rate monitoring. Thick meconium is an indication for
LSCS as lethal meconium aspiration can occur before
delivery.
LATE ONSET IUGR (>32 WEEKS):
Most frequent etiology is mild to moderate uteroplacental
dysfunction which is defined as inadequate supply of
nutrient and oxygen to support normal aerobic growth of
foetus. Foetal chromosomal and structural anomalies should
be ruled out. Indications for delivery are 1) Oligohydramnios at less than 36 weeks. 2) REDF after 32
weeks of gestation 3) AEDF after 34 weeks. 4) Abnormal
venous Doppler: Low flow during arterial contraction, absent
or reverse flow in ductus venosus, High diastolic flow in
middle cerebral artery. With AEDF at less than 34 weeks the
fetus should be followed preferably by venous Doppler study
or by BPP. Any abnormality in either is an indication for
delivery. Sonographic assessment of growth rate is done.
Absent growth is an indication for delivery. Hospitalization
for bed rest and prophylactic or therapeutic administration
of aspirin to women at risk is controversial. Conservative
management is recommended for otherwise normal but small
fetuses with Doppler profile and BPP normal. They usually
demonstrate a slow but fixed velocity of growth. Spontaneous
onset of labour at term and vaginal delivery is preferred.
Even induction of labour at or near term has not been proved
advantageous.
Timing Of Delivery: Chromosomally normal FGR foetus with
gestational age > 36 weeks should be delivered electively.
Oligohydramnios at > 36 weeks.
Mode Of Delivery: this is governed by underlying etiology,
evidence of acidemia and gestational age. If ductus venosus
flow velocity is normal, vaginal delivery under intrapartum
monitoring is acceptable. A FGR foetus is allowed to labour
as long as complicating factors like abnormal CTG or
malpresentation are not present. Whenever termination is
indicated LSCS is ideal whenever there is good evidence of
acidemia. Acidemia is presumed with REDF, reverse flow in
ductus venosus or inferior vena cava, cerebral dilatation,
repetitive late deceleration
ISSUES REGARDING DECISION MAKING MANAGEMENT
Upon suspicion of IUGR, it is recommended for mother to
do daily fetal movement counts. Obtain twice weekly non
stress tests. Obtain fetal ultrasound every 2-3 weeks to
assess: Fetal growth, Amount of amniotic fluid, Biophysical
profile. Make a diagnosis then begin regular antepartum
fetal surveillance. 34 weeks gestation is appropriate for
most at risk patient. 26-28 weeks is appropriate for
high-risk maternal conditions such as chronic hypertension.
EARLY ONSET IUGR- (before 32 weeks)
- Classify IUGR by etiology.
- Determine IUGR type
- Treat maternal condition-- improve nutrition, reduce
stress
- Encourage maternal rest
- Evaluate growth scans & umbilical artery Doppler velocity
every 3 weeks unless 36 weeks or severe oligohydramnios
develops
- Consider hospitalization if AFI less than 2.5 percentile
with normal umbilical Doppler velocity (UAD)
- Absent umbilical end diastolic flow (AEDF) or reversed
umbilical artery end-diastolic flow.
- Determine IUGR type: symmetric vs. asymmetric
Consider delivery of:
- Anhydramnios (no pockets of fluid that are clear of cord
loops at 30 weeks gestation or beyond.
- Repetitive fetal heart rate decelerations
- Lack of growth over 3 week period and mature lung studies
- Abnormal UAD (AEDF OR REDF)
LATE ONSET IUGR- (32 WEEKS OR GREATER)
- Classify IUGR
- Determine IUGR type
- Treat maternal condition reduce stress improve nutrition
- Encourage maternal rest in lateral position
- Growth scans and UAD every 3 weeks
- Each week do full biophysical profile & non stress test
Consider hospitalization if AFI less than or equal to 5
cm
Consider delivery if Oligohydramnios (AFI < 5 cm) at 36
weeks or greater, Oligohydramnios at less than 36 weeks
gestation should be combined with other indication of fetal
status such as UAD, Abnormal UAD at 36 weeks or greater,
REDF after 32 weeks, AEDF after 34 weeks,
If AEDF at less than 34 weeks BPP twice weekly.
- ADEF+ Abnormal NST
- AEDF + OLIGO HYDRAMNIOS
- Abnormal BPP-
- Poor fetal growth: If no growth on three week serial
growth scans,
- Anhydramnios
- Repetitive fetal heart rate deceleration
DECISION MAKING:
The ideal strategy of management of FGR with depend on:
1) Gestational age
2) Underlying etiology
3) Probability of intact extra uterine survival
4) Level of expertise
5) Available technology
Doppler velocimetry –Best fetal surveillance technique
for predicting hypoxemia/academia
COMPLICATIONS OF SFD baby:
Related to perinatal asphyxia and acidosis
1) Persistent fetal circulation
2) Meconium aspiration syndrome
3) Hypoxic insults including ischemic encephalopathy
Related to metabolic alterations
1) Hypoglycemia
2) Hypocalcaemia
3) Hyperviscosity
4) Hyperglycemia
5) Hypothermia
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