Post-term Pregnancy Management Recomendations

Fetal Growth Restriction - Williams 23th Review

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.

Definition

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 40^th percentile may not have achieved its genomic growth potential for a birthweight in the 80^th 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 5^th 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 < 5^th 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 < 5^th 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