Each year,
approximately 20 percent of the almost 4 million infants in the United States
are born at the low and high extremes of fetal growth. Although most
low-birthweight infants are preterm, approximately 3 percent are term
Lin and
Santolaya-Forgas (1998) have divided cell growth into three consecutive phases.
The initial phase of
hyperplasia occurs in the first 16 weeks and is characterized by a rapid
increase in cell number. The second phase, which extends up to 32 weeks,
includes both cellular hyperplasia and hypertrophy. After 32 weeks, fetal
growth is by cellular hypertrophy, and it is during this phase that most fetal
fat and glycogen deposition takes place
The corresponding fetal-growth rates during
these three phases are 5 g/day at 15 weeks, 15 to 20 g/day at 24 weeks, and 30
to 35 g/day at 34 weeks
For
example, there is considerable evidence that insulin and insulin-like growth
factor-I (IGF-I) and II (IGF-II) have a role in the regulation of fetal growth
and weight gain
Fetal-Growth
Restriction
Low-birthweight infants who are small-for-gestational age are often
designated as having fetal-growth restriction. The term fetal-growth
retardation has been discarded because "retardation" implies abnormal
mental function, which is not the intent. It is estimated that 3 to 10 percent of infants are
growth restricted.
In 1963, Lubchenco and co-workers published detailed comparisons of
gestational ages with birthweights in an effort to derive norms for expected
fetal size at a given gestational week. Battaglia and Lubchenco (1967) then
classified small-for-gestational-age (SGA) infants as those whose
weights were below the
10th percentile for their gestational age.
Because of
these disparities, other classifications have been developed. Seeds (1984)
suggested a definition based on birthweight below the 5th percentile. Usher and
McLean (1969) suggested that fetal-growth standards should be based on mean
weights-for-age with normal limits defined by ±2 standard deviations. This
definition would limit SGA infants to 3 percent of births instead of 10 percent.
Normative
data for fetal growth based on birthweight vary with ethnic and regional
differences. For example, infants born to women who reside at high altitudes
are smaller than those born to women who live at sea level.
example, a
fetus with a birthweight in the 40th percentile may not have
achieved its genomic growth potential for a birthweight in the 80th
percentile. The rate or velocity of fetal growth can be estimated by
serial sonographic anthropometry. Reports suggest that a diminished growth
velocity is related to perinatal morbidity.
Economides
and Nicolaides (1989a) found that the major cause of hypoglycemia in SGA
fetuses was reduced supply rather than increased fetal consumption or diminished
fetal glucose production. These fetuses had hypoinsulinemia along with
hypoglycemia.
By
comparison, Economides and colleagues (1989b) measured the glycine:valine ratio in cord blood from
growth-restricted fetuses and found ratios similar to those observed in older
children with kwashiorkor. Moreover, protein deprivation correlated with
fetal hypoxemia. Economides and associates (1990) then measured plasma
triglyceride concentrations in SGA fetuses and compared those with the
concentrations of appropriately grown fetuses. Growth-restricted fetuses demonstrated
hypertriglyceridemia that was correlated with the degree of fetal hypoxemia.
They hypothesized that hypoglycemic, growth-restricted fetuses mobilize adipose
tissue and that hypertriglyceridemia is the result of lipolysis of their fat stores.
Elevated plasma concentrations of
interleukin-10, placental atrial natriuretic peptide, and endothelin-1, as well
as a defect in epidermal growth factor function, have also been described in
growth-restricted fetuses.
In animals, chronic reduction in nitric oxide—an endothelium-derived,
locally acting vasorelaxant—has been shown to result in diminished fetal growth
(Diket and associates, 1994). Conversely, Giannubilo and co-workers (2008)
showed that placenta-induced nitric oxide synthase was significantly increased
in growth restriction, possibly representing an adaptive response to placental
insufficiency.
Risk is increased threefold at 26 weeks
compared with only a 1.13-fold increased risk at 40 weeks.
Symmetrical
versus Asymmetrical Growth Restriction
Campbell and Thoms (1977) described the use of the sonographically
determined head-to-abdomen circumference ratio (HC/AC) to
differentiate growth-restricted fetuses. Those who were symmetrical were
proportionately small, and those who were asymmetrical had
disproportionately lagging abdominal growth.
The onset or etiology of a particular fetal insult has been
hypothetically linked to either type of growth restriction. In the instance of symmetrical growth restriction,
an early insult could result in a relative decrease in cell number and size.
For example, global insults such as from chemical exposure, viral infection, or cellular
maldevelopment with aneuploidy may cause a proportionate reduction of
both head and body size.
Asymmetrical growth
restriction might follow a late pregnancy insult such as
placental insufficiency from hypertension. Resultant diminished glucose
transfer and hepatic storage would primarily affect cell size and not number,
and fetal abdominal circumference—which reflects liver size—would be reduced.
Such somatic growth restriction is proposed to result from preferential
shunting of oxygen and nutrients to the brain, which allows normal brain and
head growth—so-called brain sparing. The fetal brain is normally relatively large
and the liver relatively small. Accordingly, the ratio of brain weight to liver
weight during the last 12 weeks—usually about 3 to 1—may be increased to 5 to 1
or more in severely growth-restricted infants.
These
researchers concluded that asymmetrical fetal-growth restriction represented
significantly disordered growth, whereas symmetrical growth restriction more
likely represented normal, genetically determined small stature.
a woman
begins pregnancy weighing less than 100 pounds, the risk of delivering an SGA
infant is increased at least twofold.
concluded
that the environment provided by the recipient mother was more important than
the genetic contribution to birthweight.
Poor
maternal nutrition and social deprivation.
Mechanisms
affecting fetal growth appear to be different with each. Cytomegalovirus is associated with direct cytolysis
and loss of functional cells. Rubella infection causes vascular
insufficiency by damaging the endothelium of small vessels, and it also reduces
cell división. Hepatitis
A and B are associated with preterm delivery but may also adversely
affect fetal growth (Waterson, 1979). Listeriosis, tuberculosis, and syphilis have
also been reported to cause fetal-growth restriction. Paradoxically, with
syphilis, the placenta is almost always increased in weight and size due to
edema and perivascular inflammation (Varner and Galask, 1984). Toxoplasmosis
is the protozoan infection most often associated with compromised fetal growth.
In a study
of more than 13,000 infants with major structural anomalies, 22 percent had
accompanying growth restriction.
According to Droste (1992), significant
fetal-growth restriction is not seen with Turner syndrome (45,X) or Klinefelter
syndrome (47,XXY).
First-trimester
prenatal screening programs to identify women at risk for aneuploidy may
incidentally identify pregnancies at risk for fetal-growth restriction
unrelated to karyotype. In their analysis of 8012 women, Krantz and associates
(2004) identified an
increased risk for growth restriction in those with extremely low free -human
chorionic gonadotropin (-hCG) and pregnancy-associated plasma protein-A
(PAPP-A) levels despite normal chromosomes. Similar findings have also
been reported for second-trimester quad screening by the First- and
Second-Trimester Evaluation of Risk (FASTER) Trial Research Consortium
Placentary insufficiency
Reanl disease and prediabetes, multiple
fetouses
Conditions associated with chronic
uteroplacental hypoxia include preeclampsia, chronic hypertension, asthma,
smoking, and high altitude
A number of
placental abnormalities may cause fetal-growth restriction. These are discussed
further throughout Chapter 27 and include chronic placental abruption, extensive infarction,
chorioangioma, marginal or velamentous cord insertion, circumvallate placenta,
placenta previa, and umbilical artery thrombosis. Growth failure in
these cases is presumed to be due to uteroplacental insufficiency.
Two classes
of antiphospholipid antibodies—anticardiolipin antibodies and lupus
anticoagulant—have been associated with fetal-growth restriction. Pathophysiological mechanisms
appear to be caused by maternal platelet aggregation and placental thrombosis
Risk
factors, including a previous growth-restricted fetus, increase the
possibility of recurrence. Specifically, the rate of recurrence is believed to
be nearly 20 percent
1.
Femur length (FL) measurement is
technically the easiest and the most reproducible
2.
Biparietal diameter (BPD) and
head circumference (HC) measurements are dependent on the plane of section and
may also be affected by deformative pressures on the skull
3.
Abdominal circumference (AC)
measurement is more variable, but it is most commonly abnormal in cases of
fetal-growth restriction because mostly soft tissue is involved (Fig. 38-5).
An abdominal circumference within the normal
range for gestational age reliably excludes growth restriction, whereas a
measurement less than the 5th percentile is highly suggestive of
growth restriction. Despite
its accuracy, sonography used for detection of fetal-growth restriction has
false-negative findings. Dashe and colleagues (2000) studied 8400 live births
at Parkland Hospital in which fetal sonographic evaluation had been performed
within 4 weeks of delivery. They reported that 30 percent of growth-restricted
fetuses were not detected.
Doppler
Velocimetry
Abnormal umbilical artery
Doppler velocimetry—characterized by absent or reversed end-diastolic flow—has
been uniquely associated with fetal-growth restriction (see Chap. 16, Umbilical Artery). The use of Doppler velocimetry
in the management of fetal-growth restriction has been recommended as a
possible adjunct to techniques such as nonstress testing or biophysical profile.
Abnormalities in Doppler flow characterize early versus severe fetal-growth
restriction and represent the transition from fetal adaptation to failure. Early changes in
placenta-based growth restriction are detected in peripheral vessels such as
the umbilical and middle cerebral arteries. Late changes are characterized by
abnormal flow in the ductus venosus and aortic and pulmonary outflow tracts, as
well as by reversal of umbilical artery flow.
In a series of 604 neonates < 33 weeks who
had an abdominal circumference < 5th percentile, Baschat and
colleagues (2007) found that the ductus venosus Doppler parameters were the
primary cardiovascular factor in predicting neonatal outcome. These late changes are felt to reflect myocardial
deterioration and acidemia, which are major contributors to adverse perinatal
and neurological outcome. In their longitudinal evaluation of 46 growth-restricted fetuses,
Figueras and colleagues (2009) determined that Doppler flow abnormalities at
the aortic isthmus preceded those in the ductus venosus by one week.
Similarly, Towers and co-workers (2008) prospectively observed 104 fetuses with
abdominal circumference < 5th percentile. They broadly identified
two patterns of progression of Doppler abnormalities: (1) mild placental
dysfunction, which remained confined to umbilical and middle cerebral
arteries, and (2) progressive placental dysfunction, which progressed
from peripheral vessels to the ductus venosus at variable intervals depending
on gestational age. Both groups of investigators stressed that knowledge of
these patterns of progression is critical for planning subsequent fetal
surveillance and timing of delivery
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