o_1977r8vv9vk1ts2ms0kd8pksa.pdf

162 D. Ley, K. MarsÏ—l
striatum (globus pallidus and putamen). The striatum
samples information from the entire cortex through
spiny neurons, enormously rich in glutaminergic synapses.
Repeated asphyxia in fetal sheep causing hypotension
and acidosis resulted in neuronal loss primarily
in the striatum [16]. The reason for preferential
neuron loss in the striatum may partly be due to
its localization in an arterial border zone making it
vulnerable in a state of circulatory compromise.
Furthermore, perhaps most importantly, the spiny
neurons will be at risk from the high levels of noxious
glutamine released during hypoxia/ischemia in
this area. IUGR is, as previously mentioned, associated
with fetal hypoxia and circulatory changes.
One may speculate that the increased frequency of
minor neurological dysfunction observed in children
with IUGR may be due to damage induced by ischemia
in the striatal area.
IUGR and Cardiovascular Morbidity
An increasing body of studies have appeared on the
relationship between suboptimal fetal growth and
morbidity in adulthood. An early study on Swedish
male army conscripts suggested that being born SGA
may be a predictor of raised blood pressure in early
adult life [17]. Epidemiological surveys of men born
in Britain during the first three decades of the 19th
century have shown an inverse relationship between
weight at birth and blood pressure in adult age [18].
Morbidity in cardiovascular disease and incidence of
non-insulin-dependent diabetes have further been
demonstrated to relate to low birth weight [19, 20].
Barker and coworkers have speculated that changes in
fetal blood flow and in activities of substances engaged
in the regulation of fetal growth such as insulin
and insulin-like growth factor I (IGF-I) may permanently
affect vessel wall structure and have persisting
effects on metabolism [21]. An increased vulnerability
to maternal glucocorticoid levels in the growth-restricted
fetus has also been suggested as a mechanism
that may alter vasoregulatory mechanisms during fetal
life and lead to subsequent hypertension [22].
Results from prospective postnatal studies have not
been as convincing as those derived from large populations
studied retrospectively. No inverse correlation
was found between size at birth and blood pressure
at 8 years of age in a cohort of 616 prematurely delivered
children. On the contrary, blood pressure decreased
with decreasing birth weight for gestational
age [23]. Williams et al. [24] observed a weak inverse
association between blood pressure and birth weight
for gestational age in children at 7 years of age, but
when the same cohort was analyzed at 18 years of
age, the relationship had disappeared. In a Dutch
study, a U-shaped relationship was shown between
birth weight for gestational age and blood pressure at
4 years of age, implying an increase in blood pressure
in children with both low and high birth weight for
gestational age [25].
Postnatal Implications
of Abnormal Fetal Blood Flow
Abnormal flow velocity waveform in the umbilical artery
has been shown in a large number of studies to
be associated with adverse outcome of pregnancy and
high perinatal mortality rate [26, 27]. A multicenter
European study [28] differentiated the outcome according
to the presence, absence, or reversal of the
end-diastolic flow in the umbilical artery. The odds
ratio for perinatal mortality was 4.0 with absent enddiastolic
flow and 10.6 with reversed end-diastolic
flow when compared with high-risk pregnancies with
positive end-diastolic flow in the umbilical artery.
The experience from descriptive studies has been
used to design randomized controlled trials, which
showed that the use of Doppler velocimetry as a
method of fetal surveillance in high-risk pregnancies
leads to a significant decrease of perinatal mortality
[29]. The Doppler method became a method of
choice for monitoring fetal health in pregnancies with
complications caused by placental dysfunction. The
changes of blood velocities recorded from the fetal
descending aorta using Doppler ultrasound have been
shown to parallel those found in the umbilical artery
[30].
Neonatal Outcome
Several studies have been published on the association
between abnormal fetal blood flow and shortterm
perinatal outcome. Absent or reverse end-diastolic
flow (AREDF) in the umbilical artery or fetal
descending aorta has been associated with an increased
neonatal mortality and increased morbidity
in terms of cerebral intraventricular hemorrhage and
necrotizing enterocolitis (NEC) [31±34]. The relationship
between abnormal fetal aortic velocities and necrotizing
enterocolitis in the neonate is supported by
the study by Kempley et al. [35], who found decreased
velocities in the superior mesenteric artery in
SGA infants who had absent end-diastolic velocities
in the aorta during fetal life.
McDonnell et al. [36] performed a case-control
study of AREDF, matching for gestational age and
pregnancy complications in 61 pairs of infants. They
found that AREDF was associated with a higher degree
of growth restriction, thrombocytopenia, and
NEC. A more recent case-control study of umbilical
AREDF, including 36 pairs of infants, matching for