Case 22. Intrauterine Growth Restriction

 A 32-year-old primigravida is seen in your office at 33 weeks’ gestation for a routine prenatal visit. Her gestational age (GA) was calculated by her last normal menstrual period, which was consistent with an ultrasound performed at 8 weeks’ gestation. Her pregnancy has been uneventful to date, although she has continued to smoke one pack or more of cigarettes daily. She states that she has been feeling normal fetal movement and no uterine contractions. On examination, her height is 5 ft 6 in., her weight is 118 lb (53.5 kg), and her blood pressure (BP) is 90/60 mm Hg. Her fundal height is 26 cm. On ultrasound, you note a single pregnancy with an estimated fetal weight of 900 g, which is at the third percentile for gestational age.

» What is the most likely diagnosis?

» What other important items should be noted on the ultrasound?

» What is the next step in the management of this patient?

» What are potential complications of the patient’s disorder?

ANSWERS TO CASE 22:

Intrauterine Growth Restriction

Summary: This is a 32-year-old woman at 33 weeks’ gestation, who continues to smoke cigarettes during pregnancy, showing a growth-restricted fetus by ultrasound.

 Most likely diagnosis: Intrauterine growth restriction (IUGR), likely due to

cigarette smoking.

 Other ultrasound items: (a) Determine whether this is symmetric or asymmetric IUGR, and (b) assess the amniotic fluid.

 Next step: Evaluate fetal well-being.

 Potential complications: Preterm birth, fetal stress, intrauterine demise.

ANALYSIS

Objectives

1. Describe the definition and risk factors for IUGR.

2. Understand signs in pregnancy that may indicate a growth-restricted fetus.

3. Be able to evaluate a patient with suspected IUGR.

4. Develop a plan of management for a patient whose fetus is growth restricted.

Considerations

This gravida’s main risk for IUGR is that she is a smoker. Although there is overlap,

once IUGR is diagnosed, the fetal ultrasound parameters are broadly categorized

as symmetric (head affected) or asymmetric (head spared) IUGR. By comparing

the relative measurements of the head circumference (H C) as compared to the

abdominal circumference (AC) and femur length (FL), this determination can be

made. In general, factors that affect the head growth include chromosomal abnormalities, and severe and early intrauterine infections (such as TORCH [TOxoplasmosis, Rubella, Cytomegalovirus, Herpes] infections). In situations of relative

hypoxia or a decrease in nutrients provided to the fetus, the fetus will tend to preserve blood flow to the brain and heart, preserving H C, while losing growth on the

AC and FL. The most common cause of asymmetric IUGR is a maternal vascular

disorder such as hypertensive disease, smoking, or illicit drug use. The most common cause of symmetric “IUGR” is a constitutionally small baby with no adverse

problems. H owever, estimated weight of less than 5th percentile, or 3rd percentile,

is more likely a true growth restriction. After an attempt is made to determine symmetric versus asymmetric IUGR, fetal assessment should be undertaken to assess

risk of fetal death. Biophysical profile, assessment of amniotic fluid volume, and

Doppler flow studies of the umbilical artery are helpful. In the case of this patient,

if the ultrasound parameters suggest asymmetric IUGR (eg, H C: 33 weeks,

AC: 26 weeks, FL: 27 weeks), then cigarette smoking can be assumed to be the

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culprit provided there are no other risk factors (see Table 22– 1). The decision for

delivery depends on gestational age, severity of the IUGR, possibility of reversible

causes, and findings on the fetal assessment (risk of fetal death). If the fetal testing

for this patient is reasonably reassuring (eg, BPP shows 10/ 10 with normal amniotic fluid), then a careful observation with once or twice weekly fetal testing may

be adopted. Repeat ultrasound for fetal growth in 3 weeks can help to evaluate the

severity of the process. In other words, no growth at all after 3 weeks indicates a

profound IUGR, whereas normal interval growth may indicate a constitutionally

small baby or an underlying process that is not as severe.

APPROACH TO:

IUGR

DEFINITIONS

IUGR: The most commonly used definition is a birthweight less than the 10th

percentile for GA.

ASSYMETRIC IUGR: Preservation of the H C while the AC and FL lag behind.

SYMMETRIC IUGR: All parameters including the H C are small.

BIOPHYSICAL PROFILE:Combination of ultrasound criteria and NST to assess

for fetal well-being conducted over 30 minutes. Fetal breathing, movement, tone,

and amniotic fluid are assessed.

DOPPLER FLOW STUDIES:Using ultrasound to assess for flow through vessels.

With IUGR, Doppler flow in the umbilical artery is helpful.

Table 22–1 • SELECTED LIST OF RISK FACTORS FOR IUGR

Maternal factors:

• Hypertensive disease (chronic hypertension or preeclampsia)

• Renal disease

• Cardiac and respiratory diseases

• Underweight and/or poor pregnancy weight gain

• Significant anemia

• Substances: cocaine, tobacco

Uterine/placental factors:

• Abruptio placenta

• Placenta previa

• Infection

Fetal factors:

• Multiple gestation

• Aneuploidy

• Congenital syndromes

• Structural fetal malformations

• Infection

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END-DIASTOLIC FLOW: The flow through the umbilical artery measured by

Doppler ultrasound. Reverse end-diastolic flow is associated with a high stillbirth

rate within 48 hours. Absent end-diastolic flow has a moderately high stillbirth

risk, and in some settings can be closely observed.

CLINICAL APPROACH

Diagnosis

By definition, 10% of infants in a population will have a birthweight less than the

10th percentile. This designation notes that while defining a pathologic condition

using a 10th-percentile cutoff makes statistical sense, it may not be clinically relevant. The clinical challenge of greatest relevance: distinguishing the small-buthealthy fetus from the one who is compromised. Bernstein and Gabbe elegantly

define the IUGR fetus as one who suffers morbidity and/ or mortality associated with

the failure to reach growth potential. This is in contrast to a fetus that is constitutionally small. When a patient has had an early ultrasound establishing the gestational age, then a “dating error” is not a consideration. In those patients who present

with late prenatal care, the possibility of wrong dates is likely (eg, menstrual history

suggests 36 weeks but ultrasound measures 30 weeks). A repeat ultrasound in

2 to 3 weeks showing adequate interval growth is highly suggestive of a dating

error, whereas lagging growth suggests IUGR.

Symmetric or Asymmetric

Early insults to fetal growth are thought to more commonly manifest as symmetric IUGR. Symmetric IUGR may be caused by aneuploidy or early transplacental

infection. On the other hand, asymmetric IUGR describes a pattern with a relatively smaller abdominal circumference in comparison to the fetal head circumference, and it is thought to reflect a more recent insult to fetal growth. An example

of this type of situation occurs in association with hypertension developing late in

the pregnancy. The patterns may ultimately merge in the setting of long-standing

complications, such as preexisting hypertension.

The excess morbidity and mortality in the setting of IUGR are significant. An

early study of infants born between 38 and 42 weeks with a birthweight between

1500 and 2500 g found that perinatal morbidity and mortality were up to 30 times

greater than that seen in infants born between the 10th and the 90th percentile.

Expert commentary on this study offered the following perspective:“An infant with

a weight of 1250 g at 38 to 42 weeks’ gestation has a greater perinatal mortality risk

than one born with similar weight at 32 weeks.”

Some of the neonatal morbidities associated with IUGR include increased

meconium aspiration, necrotizing enterocolitis, hypoglycemia, respiratory distress,

hypothermia, and thrombocytopenia.

It has been suggested that IUGR has long-term consequences, beyond those

seen in the immediate postnatal period. The Barker hypothesis states that undernutrition during fetal life—a time of great developmental plasticity—increases the

risk of adult-onset coronary artery disease, type II diabetes, stroke, and hypertension (H TN ). This increased morbidity is thought to be secondary to the allocation

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of energy to one trait (such as brain growth) at the expense of allocation to traits

such as tissue repair processes.

Risk Factors and Etiology

There are many risk factors for IUGR, which may be divided into three broad categories: maternal, uterine/ placental, and fetal (see Table 22– 1).

Maternal factors include H TN, cardiac disease, respiratory diseases, renal disease, anemia, toxic habits, and malnutrition. H TN—whether antecedent to pregnancy or first appearing during pregnancy—places the fetus at risk for IUGR. Cardiac and respiratory diseases may impact oxygenation, and maternal oxygenation,

in turn, is associated with IUGR. Gravidas with severe anemia are at increased risk

of having a fetus with IUGR. Toxic habits, such as drug and tobacco use, are potentially the most modifiable risk factors for IUGR. Evidence suggests that advanced

maternal age is a risk for IUGR.

Uterine/ placental factors include abruptio, placenta previa, and infection.

Abruptio is more common in women with H TN, as well as in those who smoke.

Cocaine use is a risk factor for abruption. Toxoplasmosis, herpes, and parvovirus

have all been associated with IUGR. Early-onset IUGR (< 20 weeks) is associated

with cytomegalovirus.

Fetal factors include multiple pregnancy, aneuploidy, structural malformations, and infection. Multiple gestations are at increased risk of IUGR. Aneuploid

fetuses—trisomy 13, trisomy 18, and trisomy 21—are typically smaller than their

euploid siblings. Many syndromes are associated with IUGR, including Russel–

Silver syndrome, Bloom syndrome, and cretinism (hypothyroidism). Fetal structural malformations, such as gastroschisis or omphalocele, place the fetus at risk for

IUGR. As noted above, infection is also associated with IUGR.

Diagnostic Strategy

Once a diagnosis of IUGR is suspected, the clinical challenge is to distinguish

the small and sick (IUGR) fetus from the one who is small but healthy. Several

tools help make this distinction: clinical history and risk factors, fetal assessment tools such as the BPP, the amniotic fluid assessment, and Doppler studies

(see Table 22– 2).

A detailed history and physical should unearth any factors that would

increase the risk of a pathologically small fetus. In the sample patient, for

Table 22–2 • EVALUATION OF IUGR

• Detailed history and physical

• Close attention to current blood pressure and blood pressure trend

• Detailed fetal anatomic ultrasound survey

• If indicated, consider amniocentesis

• Karyotype: Increased risk of aneuploidy in the setting of IUGR

• Infectious workup (such as cytomegalovirus assessment)

• Fetal lung maturity studies depending upon the GA at presentation

• Modified or complete BPP

• Umbilical artery Doppler studies

• Antenatal corticosteroids if less than 34 weeks’ GA

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example, the low body mass index, poor weight gain, and smoking all point

toward a pathologically—rather than constitutionally—small fetus.

First- or second-trimester screening results are important, as aneuploidy is associated with IUGR. Amniocentesis is often indicated, although this will depend on

the GA at presentation. While infection is associated with IUGR, the yield of an

infectious workup after mid-gestation is low.

Decreased AFI is associated with IUGR, and may be the earliest pathological

sign detected on ultrasound. Decreased perfusion of fetal kidneys and decreased

urine output explain the low AFI. In general, pregnancies with the most severe oligohydramnios have the highest perinatal mortality rate, incidence of anomalies, and

incidence of IUGR. At the other extreme, polyhydramnios and IUGR have been

dubbed an “ominous combination.” This combination is associated with a high rate

of structural and chromosomal anomalies.

Doppler studies have proven to be a powerful tool in the evaluation of a suspected IUGR fetus. Increased resistance in the placental circulation manifests as

increased Doppler blood flow indices in the umbilical arteries. This finding has

been demonstrated by many investigators in both animal and human models.

By signaling an underlying pathology, the utilization of umbilical artery Doppler

flow measurements improves clinical outcomes. Numerous trials confirm that the

use of Doppler flow measurements can significantly reduce both perinatal death and

unnecessary induction of labor (iatrogenic preterm birth of the small-but-healthy

fetus). Absence or reversal of end-diastolic flow in the umbilical artery is suggestive

of poor fetal condition. Conversely, normal flow is rarely associated with significant

morbidity.

Management

Treatment of the fetus with suspected IUGR will depend upon the clinical circumstances, particularly the gestational age. In general, pregnancies of < 34 weeks’

GA should receive a course of antenatal corticosteroids to enhance lung maturation

since preterm delivery is commonly encountered. In fact, the use of antenatal corticosteroids is associated with a 50% reduction in neonatal death, a 50% reduction in RDS, and a 33% reduction in intraventricular hemorrhage; its use is the

single most important intervention to improve neonatal outcome. Doppler studies

are very useful. Antenatal testing with BPP or modified BPP—along with a repeat

growth scan in 2 to 4 weeks—is suggested (see Table 22– 3).

Emerging Concepts

There are ongoing trials to assess whether the use of low-dose aspirin with or without

dipyridamole can improve or reduce the risk of IUGR; the speculated mechanism is

to alter the thromboxane-to-prostacyclin ratio. To date, the results are inconclusive.

CASE CORRELATION

 See also Case 19 (Parvovirus Infection in Pregnancy) to see how Doppler is

used to assess for fetal anemia (middle cerebral artery) versus growth restriction (umbilical artery).

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COMPREHENSION QUESTIONS

22.1 A 21-year-old G1P0 woman is seen for her first prenatal visit at the obstetrician’s office. Based on the LMP, the patient is 36 weeks’ gestation. On ultrasound, the measurements indicate 32 weeks for all parameters including the

H C, AC, and FL. Which of the following is the best management for this

patient?

A. Antenatal steroids for probably IUGR

B. Recommend amniocentesis for karyotype

C. Delivery in 1 week (at term)

D. Continued monitoring and repeat ultrasound

22.2 A 27-year-old G2P1 woman is at 37 weeks’ gestation supported by LMP and

a 10-week ultrasound. The estimated fetal weight is 2000 g, which is less than

the 3rd percentile for gestational age. The Doppler studies indicate the presence of forward end-diastolic flow. You recommend delivery for this patient.

Which of the following is the best reason for your recommendation?

A. A fetal weight of 2000 g correlates with a high survival in the nursery

B. IUGR carries a significant risk of fetal death

C. The Doppler studies indicate a concern for continuing the pregnancy

D. With delivery, further diagnostic studies such as karyotype and viral

studies can be conducted

Table 22–3 • SUGGESTED GUIDELINES FOR TIMING OF DELIVERY IUGR

Gestational Age Circumstances for Delivery

Term (37+ weeks): (risk of

prematurity low)

Deliver since risks of prematurity are low

32-36 weeks (prematurity risks

intermediate)

• Severe hypertension despite therapy

• Absence of growth over 2-4 weeks

• Nonreassuring fetal testing

• Absent or reversal of end-diastolic flow on Doppler studies

<32 weeks (prematurity

risks high)

• Reverse end-diastolic flow

•   Persistent nonreassuring fetal testing despite measures to 

optimize placental perfusion

• Significant or ominous fetal testing results

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22.3 An 18-year-old G1P0 woman at 38 weeks’ gestation confirmed by a 12-week

ultrasound has a fundal height of 34 cm. The patient has gained 20 lbs during the pregnancy. She denies smoking or alcohol or illicit substance use. H er

BP is 110/ 70 mm H g. Which of the following is the best management of this

patient?

A. Perform a basic ultrasound study

B. Schedule for delivery since the patient has reached a term gestational age

C. Schedule biophysical profile and Doppler studies for this patient

D. Send her urine for a drug screen and consider ordering serum TORCH

titers

ANSWERS

22.1 D. This patient presents for her first prenatal visit at 36 weeks’ gestation.

Although the baby measures small on ultrasound, there is a strong likelihood of wrong dates. Thus, rather than presume IUGR, this patient should

be monitored with fetal surveillance such as BPP each week and a repeat

ultrasound in 3 weeks to assess for interval growth. Normal growth would

confirm wrong dates. In contrast, lack of growth would suggest IUGR.

22.2 B. Doppler flow showing forward diastolic flow is normal. Ominous signs

would be reverse end-diastolic flow or absent end-distolic flow. The most

concerning complication of IUGR is fetal death. The reason for delivery at

term is to avoid stillbirth or other complications.

22.3 A. The first step in evaluating size less than dates is to perform an ultrasound

for fetal weight. Sometimes due to the fetal position, or fetal head descending

into the maternal pelvis, the fundal height may be decreased. If the ultrasound demonstrates fetal weight less than the 10th percentile, then further

management may be contemplated.

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CLINICAL PEARLS

» In general, the diagnosis of IUGR is made by the estimated fetal weight of 

less than the 10th percentile for gestational age.

» It is often helpful to categorize the IUGR as asymmetric (head sparing) or 

symmetric (head affected).

» Causes of symmetric IUGR include fetal chromosomal abnormalities, congenital syndromes, or severe fetal infections.

» Causes of asymmetric IUGR include maternal vascular disorders such as 

hypertensive disease.

» Antenatal corticosteroid use prior to delivery of an infant of <34 weeks’ 

gestation is associated with dramatically improved outcome.

» Delivery is typically indicated when IUGR is coupled with oligohydramnios due to the greatly increased risk of fetal death.

» Umbilical artery Doppler is a useful tool in distinguishing the constitutionally small fetus from the pathologically small fetus. The use of

Doppler has been shown to significantly reduce perinatal death and

unnecessary preterm delivery.

» Timing of delivery is based on the clinical circumstances. Hypertension,

the absence of growth over a 2- to 4-week period, and nonreassuring 

testing typically trigger delivery.

» When the Doppler flow reveals reverse end-diastolic umbilical artery

flow, there is a high perinatal death within 48 hours, and usually delivery 

is performed.

» Absent end-diastolic flow is also worrisome although the risk for fetal

death is not as ominous.

REFERENCES

American College of Obstetricians and Gynecologists. Fetal growth restriction. Practice Bulletin 124,

May 2013.

Chamberlain PF, Manning FA, Morrison I, H arman CR, Lange IR. Ultrasound evaluation of amniotic

fluid volume. The relationship of marginal and decreased amniotic fluid volumes to perinatal outcome. Am J Obstet Gynecol. 1984;150(3):245-249.

Miller J, Turan S, Baschat AA. Fetal growth restriction. SeminPerinatol. 2008;32(4):274-280.

Ott W J. Diagnosis of IUGR: comparison of ultrasound parameters. Am J Perinatol. 2002;19(3):

133-137.