Intrauterine Growth Retardation

Vol.1 No.8

by Giancarlo Mari, M.D.

Assistant Professor Department of Obstetrics and Gynecology
The Yale University School of Medicine

Editors Note: The subject of Intrauterine Growth Retardation is a very important topic of concern,
for if not recognized, it can lead to a severely compromised fetus as well as fetal and/or neonatal
demise. Dr. Mari is a recognized, world authority on the diagnosis of IUGR by the techniques
described here.

Definition of IUGR

The term intrauterine growth restriction (IUGR) is the most common generic term that is used to
describe the fetus with a birthweight at or below the 10th percentile for gestational age and sex.
This term is often erroneously used as synonymous of small for gestational age (SGA). The IUGR
fetus is a fetus that does not reach his potential of growth; whereas the SGA fetus is a fetus who
reaches his potential of growth. In other words, a fetus who has a potential of growth at the 50th
percentile but because of maternal, fetal, or placental disorders occurring alone or in combination,
becomes growth restricted (birthweight < 10th percentile) is a IUGR fetus and he is at risk for
adverse perinatal outcome. A fetus with a potential of growth at the 7th percentile who reaches his
potential of growth (7th percentile) is not a IUGR fetus but a SGA fetus. He is a normal small fetus
and he is not at risk for adverse perinatal outcome.

The two components that are necessary to define a IUGR fetus are:

a) birthweight < 10th percentile;

b) pathologic process that inhibits expression of the normal intrinsic growth potential.

The two components that are necessary to define a SGA fetus are:

a) birthweight < 10th percentile;

b) absence of pathologic process.

Incidence

The incidence of SGA fetuses in the population is approximately 7%. Ten to fifteen percent of the
SGA fetuses are IUGR fetuses.

Etiology

Both maternal and paternal race have a measurable effect on the fetal size, and, therefore an
indirect effect on the incidence of SGA. These racial influences can have an impact on clinical
practice. The application of a fetal growth curve derived from one population applied to a different
population can result in over- or underestimation of the true incidence of SGA. Birthweight and fetal
growth rates tend to be least among population of Asiatic extraction and greatest in populations of
Nordic extractions. These racial differences can be quite dramatic, and at term the mean birthweight
may vary as much as 1400 grams. The lowest mean birthweight has been noted in Africa (New
Guinea- Lumi's tribe: mean birthweight = 2400 grams); whereas the largest mean birthweight has
been noted in the Caribbean (Aguilla; mean birthweight = 3880 g).

IUGR may be considered the consequence of a disease process within one or more of the three
compartments that sustain and regulate fetal growth - the maternal compartment, the placenta, or
the fetus. In table I the most common causes of IUGR are reported.

Diagnosis of the risk of IUGR

Pregnancies at risk for IUGR may be diagnosed on the basis of previous history (low fetal birth
weight in earlier pregnancies, etc.), associated disorders (autoimmune diseases, high blood pressure,
etc.), and toxic habits (smoker, etc). Previous history of IUGR is the most important risk factor. In
pregnancies with an increased risk, fetal growth should be closely monitored.

Diagnosis of presumed or suspected IUGR

This is perhaps the most important and the most difficult diagnosis to make, when we consider that
most of the pregnancies are free of any associated conditions that would alert obstetricians to the
possibility of IUGR. The discrepancy between gestational age and the size of the uterus is the most
clearly indicative sign of IUGR. Therefore, basic screening for IUGR should be done using serial
symphysis fundal height (SFH), reserving ultrasound biometrical data for those cases in which the
SFH fell below the 5th percentile.

Diagnosis of probable IUGR

The diagnosis of IUGR is based on biometrical parameters recorded during ultrasound scanning. In
order to reduce misreadings to a minimum, gestational age should be precisely determined. The
most used biometrical parameters are the biparietal diameter, head circumference, abdominal
circumference, head/abdominal circumference ratio, length of femur and humerus, estimated fetal
weight.

Fetal hemodynamics in growth restriction

IUGR is in most of the cases secondary to uteroplacental insufficiency. Much of the understanding of
this phenomenon is derived from animal research. However, the advent of pulsed and color Doppler
ultrasonography has allowed us to obtain non-invasive hemodynamic measurements from several
vascular beds of the uterine, placental and fetal circulation in humans.

Doppler ultrasound

Doppler ultrasound give us information on the vascular resistance and, indirectly on the blood flow.
Three indices are considered related to the vascular resistance: S/D ratio (systolic/diastolic ratio),
resistance index (RI = systolic velocity - diastolic velocity/systolic velocity), and pulsatility index
(systolic velocity - diastolic velocity/mean velocity).

Uterine circulation

The main uterine artery is the most commonly analyzed vessel. In normal pregnancy the S/D ratio or
RI values significantly decrease with advancing gestation until 24 to 26 weeks. In the absence of this
physiologic decrease, a higher incidence of hypertensive diseases and/or IUGR has been widely
documented.
Umbilical artery

In the normal fetus, the pulsatility index decreases with advancing gestation. This reflects a decrease
of the placental vascular resistance. In fetuses with IUGR there is an increase of the pulsatility index
secondary to the decrease, absence or reversal of end- diastolic flow. The changes of these
waveforms are thought to be indicative of increased placental resistance. The absent or reversed
end-diastolic flows are strongly associated with an abnormal course of pregnancy and a higher
incidence of perinatal complications, when compared to fetuses with IUGR but characterized by the
presence of end-diastolic flow.

Umbilical vein

The umbilical vein has a continuous pattern following the first trimester. The presence of umbilical
vein pulsations is associated to an increased risk of adverse perinatal outcome.

Ductus venosus

The presence of reversed flow in the ductus venosus is an ominous sign. Goncalves et al observed 5
fetuses with reverse flow velocity waveforms at the ductus venosus and all the fetuses died in utero.
In 18 other fetuses with abnormal umbilical and middle cerebral artery waveforms, but without
reverse flow in the ductus venosus, no deaths occurred.

Fetal cerebral circulation

The middle cerebral artery is the vessel of choice to assess the fetal cerebral circulation because it is
easy to identify, has a high reproducibility, and it provides information on the brain sparing effect.
Additionally, it can be studied easily with an angle of zero degrees between the ultrasound beam
and the direction of blood flow and, therefore, information on the true velocity of the blood flow
may be obtained.

Brain sparing effect

Animal and human experiments have shown that there is an increase in blood flow to the brain in
the IUGR fetus. This increase in blood flow can be evidenced by Doppler ultrasound of the middle
cerebral artery. This effect has been called "brain sparing effect" and is demonstrated by a lower
value of the pulsatility index. In IUGR fetuses with a pulsatility index below the normal range there is
a greater incidence of adverse perinatal outcome. The brain sparing effect may be transient, as
reported during prolonged hypoxemia in animal experiments, and the overstressed human fetus can
also lose the brain sparing effect. The disappearance of the brain sparing effect is a very critical
event for the fetus, and appears to precede fetal death. Unfortunately, to demonstrate this concept,
it is necessary to perform a longitudinal study on severely IUGR fetuses up to the point of fetal
demise. This has been confirmed in a few fetuses in situations where obstetrical intervention was
refused by the parents. If these information's are confirmed on a larger number of fetuses, the study
of the middle cerebral artery may have tremendous implication for determining the proper timing of
delivery.

Based on our personal experience, there are several phases of utero-placental insufficiency that may
reflect changes in fetal hemodynamics.

Severe utero-placental insufficiency

A) The substrate for the development of uteroplacental insufficiency may be laid down as early as
the time of the implantation. However, no effect is seen on growth or Doppler until 20-24 weeks
gestation. These fetuses do not have signs of growth restriction or abnormal Doppler ultrasound
prior to this period.

B) At 22-24 weeks gestation if the fetus is measurably small by ultrasound, several Doppler patterns
may occur. 1) The umbilical artery may still have a normal pulsatility index (resistance index or S/D
ratio); the middle cerebral artery may have either a normal or abnormal pulsatility index.

2) The umbilical artery has an abnormal pulsatility index; the middle cerebral artery has either a
normal or abnormal value of pulsatility index.

3) The umbilical artery and the middle cerebral artery have both an abnormal value of pulsatility
index.

The fetus needs to be monitored very closely. Bed rest and oxygen therapy may be useful; however,
if both vessels have an abnormal value at this early gestational age, it is very likely that the process
will deteriorate and the chance of a delivery at term is remote.

C) The pulsatility index of the umbilical artery may increase and the pulsatility index of the middle
cerebral artery may decrease. The other fetal vessels may still appear normal and the only Doppler
abnormalities are the umbilical artery and middle cerebral artery. The fetus starts to show signs of
IUGR. The biophysical profile is normal.

At this time the lack of fetal growth, and/or the development of preeclampsia/eclampsia, or a
persistent abnormal biophysical profile may interrupt the process with delivery of the fetus. These
fetuses are at lower risk for the development of respiratory distress syndrome and intraventricular
hemorrhage. We have reported that IUGR fetuses with brain sparing effect are less likely to develop
IVH. The reason is not completely understood. However, production of steroids with stress may play
an important role in this process.

If the fetus is not delivered, the process continues.

D) At this time tricuspid regurgitation may appear, ductus venosus reverse flow and umbilical vein
pulsations may be present intermittently. The biophysical profile may still appear normal.

E) Ductus venosus reverse flow and umbilical vein pulsations are present continuously. The fetus
starts to lose the brain sparing effect. The biophysical profile becomes abnormal.

F) Fetal demise.

The time interval between E and F is variable (from 6-12 hours to 2 weeks). Oligohydramnios may be
present at any stage of the above process.

This theory applies to a specific, common IUGR and not to the fetuses who have other causes such as
smoking, abruption, and toxic drug exposure who may have a different pathology.

Mild utero-placental insufficiency

Uteroplacental insufficiency starts either at, or after the implantation. However, no effect is seen on
Doppler and growth until 26-32 weeks gestation. The umbilical artery and the middle cerebral artery
waveforms may be abnormal. However, the process is not severe enough to stop fetal growth
completely or to deteriorate as above. These cases may be followed with outpatient monitoring and
they often deliver at term.

Conclusion

Fetuses with IUGR show evident modifications of Doppler parameters in the uteroplacental and fetal
circulation. At present, the condition of fetuses with IUGR can accurately be assessed by sequential
studies of Doppler waveforms from different vascular areas. There are, however, still many
uncertainties concerning the relationships between the Doppler changes and the metabolic situation
of the fetus and therefore, on the optimal timing of delivery to prevent an intrauterine injury.

Next Journal Article