Williams Manual of Pregnancy Complications, 23 ed.

CHAPTER 38. Fetal Growth Restriction

Infants who are small-for-gestational age (SGA) are often designated as suffering from intrauterine growth restriction. It is estimated that from 3 to 10 percent of infants are growth restricted. In the past, infants who were SGA were designated as suffering from intrauterine growth retardation. To avoid undue alarm in parents to whom the term “retardation” implies abnormal mental function, the term fetal growth restriction is now preferred.

DEFINITION

Table 38-1 shows the percentiles of birth weight for each week of gestation between 20 and 44 weeks. Small-for-gestational-age (SGA) infants are generally considered to be those whose weights are below the 10th percentile for their gestational age. Not all infants with birth weights less than the 10th percentile, however, are pathologically growth restricted; some are small simply because of constitutional factors. Indeed, 25 to 60 percent of infants conventionally diagnosed to be SGA are, in fact, appropriately grown when determinants of birth weight such as maternal ethnic group, parity, weight, and height are considered. A definition of SGA that is based upon birth weight below the 5th percentile has also been proposed. Normal fetal growth standards are sometimes based on mean values with normal limits defined by ±2 standard deviations. This definition would limit SGA infants to 3 percent of births instead of 10 percent. In fact, most poor outcomes are in those infants with birth weights that are below the 3rd percentile (Figure 38-1). Most recently, individual fetal growth potential has been proposed in place of a population-based cutoff. In this model, a fetus that is less than its individual optimal size at a given gestational age would be considered growth restricted.

TABLE 38-1. Smoothed Percentiles of Birth Weight (g) for Gestational Age in the United States Based on 3,134,879 Singleton Live Births

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FIGURE 38-1 Relationship between birth weight percentile and perinatal mortality and morbidity observed in 1560 small-for-gestational age fetuses. A progressive increase in both mortality and morbidity is observed as birth weight percentile falls. (Reproduced, with permission, from Cunningham FG, Leveno KJ, Bloom SL, et al (eds). Williams Obstetrics. 23rd ed. New York, NY: McGraw-Hill; 2010. Data from Manning FA: Intrauterine growth retardation. In: Fetal Medicine. Principles and Practice. Norwalk, CR: Appleton and Lange; 1995, p. 317, with permission.)

MORTALITY AND MORBIDITY

As shown in Figure 38-1, fetal growth restriction is associated with increased mortality and morbidity. Fetal demise, birth asphyxia, meconium aspiration, and neonatal hypoglycemia and hypothermia are all increased, as is the prevalence of abnormal neurological development. This is true for both term and preterm infants.

Postnatal growth and development of the growth-restricted fetus depends on the cause of restriction, nutrition in infancy, and the social environment. Infants with growth restriction due to congenital, viral, chromosomal, or maternal constitutional factors remain small throughout life. Those infants with inutero growth restriction due to placental insufficiency will often have catch-up growth after birth and approach their inherited growth potential when provided with an optimal environment. Similarly, neurodevelopmental outcome of the growth-restricted fetus is influenced by postnatal environment. Such infants born to families of higher socioeconomic status demonstrate fewer developmental problems during follow-up.

ACCELERATED MATURATION

There have been numerous reports describing accelerated fetal pulmonary maturation in complicated pregnancies associated with growth restriction. Although this concept pervades modern perinatal thinking, there is little clinical information to substantiate that pregnancy complications convey a fetal advantage.

SYMMETRICAL VERSUS ASYMMETRICAL FETAL GROWTH RESTRICTION

By dividing growth-restricted fetuses into the subtypes “symmetrical,” meaning proportionately small, and “asymmetrical,” referring to those with disproportionately lagging abdominal growth (compared to head size), generalizations about the potential pathophysiology of fetal growth restriction are implied. For example, an early insult due to chemical exposure, viral infection, or inherent cellular development abnormality caused by aneuploidy could theoretically result in proportionate reduction in both head and body size. This has been termed symmetrical growth restriction. Conversely, a late pregnancy insult such as placental insufficiency associated with hypertension could theoretically result in diminished glucose transfer and hepatic storage. Therefore, fetal abdominal circumference—which reflects liver size—would be reduced. Simultaneously, it is proposed that there is preferential shunting of oxygen and nutrients to the brain, which allows normal brain and head growth. This sequence of events can theoretically result in asymmetrical growth restriction with an abnormally increased relative brain size compared with the small liver (abdominal circumference). Recognition of symmetrical and asymmetrical patterns of impaired fetal growth has prompted considerable interest in the antepartum diagnosis of these two forms because the pattern may potentially reveal the cause.

RISK FACTORS

Constitutionally Small Mothers

Small women typically have smaller infants. Whether or not the phenomenon of a small mother giving birth to a small infant is nature or nurture is unclear, but the environment provided by the mother is more important than her genetic contribution to birth weight. In the woman of average or low weight, lack of weight gain throughout pregnancy may be associated with fetal growth restriction. If the mother is large and otherwise healthy, however, below-average maternal weight gain without maternal disease is unlikely to be associated with appreciable fetal growth restriction. Marked restriction of weight gain during the later half of pregnancy should not be encouraged.

Social Deprivation

The effect of social deprivation on birth weight is interconnected to the effects of associated lifestyle factors such as smoking, alcohol or other substance abuse, and poor nutrition. The most socially deprived mothers have the smallest infants, and a lack of psychosocial resources increases the risk of growth-restricted infants.

Maternal and Fetal Infections

Viral, bacterial, protozoan, and spirochetal infections have been implicated in up to 5 percent of cases of fetal growth restriction. The best known of these are infections caused by rubella and cytomegalovirus. Hepatitis A and B are associated with preterm delivery but may also adversely affect fetal growth. Listeriosis, tuberculosis, and syphilis have also been reported to cause fetal growth restriction. Toxoplasmosisis the protozoan infection most often associated with compromised fetal growth, but congenital malaria may produce the same result.

Congenital Malformations

One-fourth of infants with major structural anomalies have accompanying growth restriction. In general, the more severe the malformation, the more likely the fetus is to be SGA. This is especially evident in fetuses with chromosomal abnormalities or those with serious cardiovascular malformations. Karyotype abnormalities can be found in approximately 20 percent of growth-restricted fetuses without sonographically visible structural anomalies. In the presence of growth restriction and fetal anomalies, the prevalence of chromosomal abnormalities is even greater. Although postnatal growth failure is prominent in children with trisomy 21, fetal growth restriction is generally mild. In contrast to the mild and variable growth restriction that accompanies trisomy 21, fetuses with trisomy 18 are virtually always significantly growth restricted. Some degree of growth restriction is also commonly present in fetuses with trisomy 13, but it is generally not as severe as in those with trisomy 18. Significant fetal growth restriction is not seen with Turner syndrome (45,X or gonadal dysgenesis) or Klinefelter syndrome (47,XXY). Numerous inherited syndromes such as osteogenesis imperfecta and various chondrodystrophies are also associated with fetal growth restriction.

Chemical Teratogens

Any teratogen is capable of adversely affecting fetal growth. Cigarette smoking causes growth restriction as well as preterm delivery in a direct relationship with the number of cigarettes smoked per day. Narcotics and related drugs act by decreasing maternal food intake and fetal cell number. Alcohol is a potent teratogen that acts in a linear dose-related fashion. Cocaine use is also associated with poor fetal weight gain. These are considered in detail in Chapter 8.

Maternal Medical Complications

Chronic vascular disease, especially when further complicated by superimposed preeclampsia, commonly causes growth restriction. Preeclampsia itself may also cause fetal growth failure, especially when the onset is before 37 weeks. Renal disease may be accompanied by restricted fetal growth. Conditions associated with chronic uteroplacental hypoxia like chronic hypertension, asthma, and high altitude are also related to significant reductions in birth weight. Fetuses of women who reside at high altitude usually weigh less than those born to women who live at a lower altitude. Fetuses of women with cyanotic heart disease are frequently severely growth restricted. In most cases, anemia does not cause growth restriction. Exceptions include sickle-cell disease or other inherited anemias associated with serious maternal disease.

Placental and Cord Abnormalities

Chronic partial placental separation, extensive infarction, or chorioangioma are likely to cause restricted fetal growth. Marginal insertion of the cord and especially vela-mentous insertions are more likely to be accompanied by a growth-restricted fetus.

Extrauterine Pregnancy

The fetus gestated outside the uterus is usually growth restricted. Also, some maternal uterine malformations have been linked to impaired fetal growth.

Antiphospholipid Antibody Syndrome

Two classes of antiphospholipid antibodies have been associated with fetal growth restriction—anticardiolipin antibodies and lupus anticoagulant. These are considered in detail in Chapter 54.

Multiple Fetuses

Pregnancies with two or more fetuses are more likely to be complicated by diminished growth of one or both fetuses compared with normal singletons.

DIAGNOSIS OF FETAL GROWTH RESTRICTION

Early confirmation of gestational age, attention to maternal weight gain, and careful measurement of uterine fundal growth throughout pregnancy will serve to identify many cases of abnormal fetal growth. If the fundal height measurement is more than 2 to 3 cm below the expected height, inappropriate fetal growth may be suspected. Identification of risk factors, including a previously growth-restricted fetus, should raise the possibility of recurrence during the current pregnancy. In women with significant risk factors, consideration should be given to serial sonography. An initial dating examination in the first trimester followed by a second examination at 32 to 34 weeks should serve to identify many cases of growth restriction.

Identification of the inappropriately growing fetus remains a challenge. This is underscored by the fact that such identification is not always possible even in the nursery. Regardless, there are both simple clinical techniques and more complex technologies that may prove useful in helping to diagnose fetal growth restriction.

Doppler Velocimetry

Abnormal umbilical artery Doppler velocimetry, characterized by absent or reversed end-diastolic flow signifying increased impedance, has been uniquely associated with fetal growth restriction (see Chapter 9). An example of this is shown in Figure 38-2. The use of Doppler velocimetry in the management of fetal growth restriction has been recommended as a possible adjunct to other fetal evaluation techniques such as nonstress tests or biophysical profiles.

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FIGURE 38-2 Umbilical arterial Doppler velocimetry studies, ranging from normal to markedly abnormal. A. Normal velocimetry pattern with a systolic-to-diastolic (S/D) ratio of <30. B. The diastolic velocity approaching zero reflects increased placental vascular resistance. C. During diastole, arterial flow is reversed (negative S/D ratio), which is an ominous sign that may precede fetal demise. (Reproduced, with permission, from Cunningham FG, Leveno KJ, Bloom SL, et al (eds). Williams Obstetrics. 23rd ed. New York, NY: McGraw-Hill; 2010.)

MANAGEMENT

Once a growth-restricted fetus is suspected, efforts should be made to confirm the diagnosis and, if so, to determine if the fetus has anomalies or is in poor condition. The timing of delivery is crucial, and the clinician must often weigh the risks of fetal death against the hazards of preterm delivery.

Growth Restriction Near Term

Prompt delivery is likely to afford the best outcome for the fetus that is growth restricted at or near term. Assuming that the fetal heart rate pattern is reassuring, vaginal delivery may be attempted. Unfortunately, such fetuses often tolerate labor less well than their appropriately grown counterparts, and cesarean delivery is often necessary. Importantly, uncertainty about the diagnosis of fetal growth restriction should preclude intervention until fetal lung maturity is ensured. Expectant management can be guided using antepartum fetal surveillance techniques described in Chapters 9 and 12.

Growth Restriction Remote from Term

When a growth-restricted fetus is diagnosed prior to 34 weeks, and amnionic fluid volume and antepartum fetal surveillance are normal, observation is recommended. A sonographic search is made for fetal anomalies. Sonography is repeated at intervals of 2 to 3 weeks. As long as there is continued growth and fetal evaluation remains normal, pregnancy is allowed to continue until fetal maturity is achieved; otherwise, delivery is affected. At times, amniocentesis for assessment of pulmonary maturity may be helpful in clinical decision making.

Labor and Delivery

Throughout labor, spontaneous or induced, those fetuses suspected of being growth restricted should be monitored for evidence of compromise, manifested by fetal heart rate abnormalities. Fetal growth restriction is commonly the result of insufficient placental function as a consequence of faulty maternal perfusion, ablation of functional placenta, or both. These conditions are likely to be aggravated by labor.

The fetus is at risk of being born hypoxic and having aspirated meconium. It is essential that care for the newborn be provided immediately by someone who can skillfully clear the airway below the vocal cords, especially of meconium, and ventilate the infant as needed. The severely growth-restricted newborn is particularly susceptible to hypothermia and may also develop other metabolic derangements such as hypoglycemia, polycythemia, and hyperviscosity.


For further reading in Williams Obstetrics, 23rd ed.,

see Chapter 38, “Fetal Growth Disorders.”