Obstetrics in Family Medicine: A Practical Guide (Current Clinical Practice) 2nd ed.

6. Intrauterine Growth Restriction

Paul Lyons¹

(1)

Department of Family Medicine, University of California, Riverside, Riverside, CA, USA

Background

Risk Factors

Fetal-Genetic Factors

Uterine-Environmental Factors

Maternal Factors

Toxic Exposures

Constitutional Factors

Complications of Growth Restriction

Antenatal Tracking and Diagnosis

Screening for Risks

Diagnosis

Management

Risk Reduction

Key Points

1.

2.

3.

Background

Fetal growth is among the most important of parameters monitored during the course of prenatal care. Although the majority of pregnancies proceed with no complications in fetal growth, a small number will show evidence of growth restriction. A variety of conditions are associated with or increase the risk for intrauterine growth restriction (IUGR). These factors are summarized in Table 6.1.

Table 6.1

Risk factors for intrauterine growth restriction (IUGR)

IUGR is defined as fetal weight below the tenth percentile and an abdominal girth below the 2.5 percentile for gestational age. As this definition implies, accurate fetal dating is critical to the diagnosis. At term, this corresponds to a birth weight of 2500 g (~5.5 lb). By this definition, approximately 5 % of all US infants demonstrate evidence of IUGR, accounting for approximately 175,000 infants annually in the United States.

Risk Factors

Factors associated with IUGR can be categorized into five categories: fetal genetic, uterine environmental, maternal, toxic exposures, and constitutional factors.

Fetal-Genetic Factors

A variety of genetic conditions are associated with restricted fetal growth and account for approximately 10 % of all cases. Early fetal growth is predominantly driven by growth in the number of fetal cells, cellular hyperplasia. This process is strongly influenced by genetic and fetal factors. As such early growth restriction is predominantly associated with fetal-genetic factors. Such conditions as Down syndrome (trisomy 21) and Turner’s syndrome are associated with an increased risk for IUGR. Structural growth defects such as anencephaly, achondroplasia, osteogenesis imperfecta, and renal and gastrointestinal (GI) defects are all associated with an increased risk of IUGR.

Uterine-Environmental Factors

Abnormalities of the uterine environment may also contribute to growth restriction. Congenital infections such as cytomegalovirus, toxoplasmosis, or rubella are associated with restricted fetal growth. Although these infections can cause significant fetal growth restriction, they are a relatively uncommon cause of IUGR, <5 %. Fetal urinary tract outflow obstruction with concomitant oligohydramnios can be associated with IUGR. Placental abnormalities (placenta previa, abruption, placental malformation) and multiple gestations can both alter the uterine environment and therefore lead to growth restriction. The structure of the uterus itself may also contribute to growth restriction. Uteroplacental insufficiency is most commonly associated with late-onset growth restriction.

Maternal Factors

Growth in pregnancy is fundamentally reliant on a balance between fetal needs (especially nutrition and oxygen) and maternal ability to meet those needs. Maternal health and nutrition contribute significantly to fetal growth and a number of maternal factors can be associated with decreased fetal growth. Although specific maternal factors may not always be identified, a pregnant patient with a past history of IUGR is approximately twice as likely to have subsequent IUGR compared to those without such a history. Following the period of cellular hyperplasia, fetal growth is augmented by cellular hypertrophy. Growth restriction due to decreased cellular hypertrophy may be more responsive to correction of nutritional imbalances.

Underlying maternal diseases such as diabetes, hypertension, GI, and vascular disease are all associated with an increased risk for IUGR. Hypertension is associated with decreased placental perfusion resulting in decreased delivery of both oxygen and nutrients. GI disease with significant malabsorption will result in decreased delivery of nutrients to the fetus and may contribute to subsequent IUGR. It should be noted that less significant nutritional defects may not result in diminished fetal growth as nutrients are delivered preferentially to the fetus.

Fetal growth is dependent on adequate fetal oxygenation and delivery of necessary nutrients. Adequate delivery is dependent, in turn, on adequate vascular function. Maternal vascular disease associated with a number of diseases impairs maternal–fetal perfusion and therefore is associated with increased risk of IUGR. Such maternal conditions as diabetes mellitus, peripheral vascular disease associated with tobacco use, collagen vascular disease, and pregnancy complications such as pre-eclampsia can all decrease maternal–fetal perfusion, thus increasing the risk of IUGR.

Toxic Exposures

The use of toxic substances (tobacco, alcohol, and illicit drugs) has been associated with decreased fetal growth. Of these, tobacco use is by far the most common risk factor for diminished fetal growth. Pregnant patients who smoke approximately double the risk of IUGR, a risk that is proportional to the quantity of cigarettes smoked. Discontinuation of smoking before or during pregnancy is associated with reduction or elimination of this risk. Both alcohol and illicit drug use (especially heroin and cocaine) are associated with diminished fetal growth. Fetal alcohol syndrome infants are generally small for gestational age.

Prescription drug use may also be associated with decreased fetal growth. Folic acid is a critical component in fetal development. Supplementation with folate is recommended during the preconception and early prenatal course. Drugs that inhibit folic acid metabolism may result in decreased fetal growth among other complications. The use of warfarin for anticoagulation has also been associated with IUGR.

Constitutional Factors

Small mothers are more likely to have small infants. Although these infants are small for gestational age, they are otherwise healthy. If no maternal, fetal, or uterine factors can be identified, these infants are generally healthy and normal but small. There is some variation in size based on birth order and gender. First infants are slightly smaller, on average, than subsequent infants; female infants are somewhat smaller, on average, than male infants.

Complications of Growth Restriction

Although not all small babies have complications, IUGR represents the second leading cause of perinatal morbidity and mortality after prematurity. Infants with a birth weight below 2500 g have a mortality rate of 5–30 times that of infants weighing more than 2500 g. IUGR (or associated underlying disease processes) is associated with an increased risk for pre-eclampsia, preterm labor/delivery, stillbirth, fetal electrolyte abnormalities, hypoglycemia, and aspiration. Long-term consequences associated with IUGR include increased risk for learning, behavioral, and developmental abnormalities.

Antenatal Tracking and Diagnosis

Every prenatal visit includes assessment of fetal growth either indirectly or directly. A general approach to tracking fetal growth is presented in Fig. 6.1. Indirect measures of fetal growth include maternal weight gain, fundal height, and age-appropriate landmarks (e.g., fetal heart tones heard with handheld Doppler at approximately 10–12 weeks’ gestation). Direct measures of fetal growth can be obtained with obstetrical ultrasound. Interpretation of these markers depends on accurate pregnancy dating. Parameters for establishing gestational age and estimated date of delivery (EDD) are covered in Chap. 3. In addition to assessing markers of fetal growth, all patients should be screened for risk factors that may contribute to an increased risk for IUGR.

Fig. 6.1

Tracking fetal growth

Screening for Risks

The first prenatal visit will include a comprehensive historical review of the patient’s, patient’s family, and paternal risk factors. Particular note should be made of prior obstetrical history, including infant size at delivery, prior history of genetic abnormalities including neural tube defects and Down syndrome, and multiple gestations. The mother’s history should be reviewed for chronic disease such as hypertension, cardiovascular disease, renal disease, diabetes mellitus (including prior macrosomic infants with or without a known diagnosis of diabetes mellitus), GI disease, and nutritional status. The note should be made of alcohol, tobacco, or illicit drug use.

Physical examination at the first prenatal visit should include assessment of uterine size (and comparison of this finding to estimated gestational age). If appropriate, fetal heart tones should be documented at this visit. Initial laboratory studies that may contribute to risk screening would include protein or glucose on urinalysis and evidence of cytomegalovirus, herpes, rubella, and/or toxoplasmosis.

Each subsequent visit will include interval updates for each of these risk factors. Patients should be screened for changes in nutritional status, toxic substance use, medications, or new exposures. Each prenatal visit will include documentation of blood pressure, maternal weight, fundal height, and fetal heart rate. Particular attention should be paid to fundal height measurement as this can be a significant clue to growth abnormalities. Fundal height (measured symphysis pubis to top of fundus) in centimeters should be equal to gestational age in weeks (±2 cm).

At 15–20 weeks’ gestation, patients should be offered α-fetoprotein (or triple test) screening. Also, in this time period many patients will undergo obstetrical ultrasound examination. Key parameters on ultrasound include biparietal diameter, head circumference, abdominal girth, estimated fetal weight, and amniotic fluid index (AFI). Routine screening for gestational diabetes is performed at 24–28 weeks’ gestation but may be performed earlier in patients with increased risk.

Patients who show abnormalities in any of these parameters should be considered at increased risk for IUGR with appropriate follow-up and diagnostic testing when indicated.

Diagnosis

Diagnosis of IUGR requires correlation of gestational age with ultrasonographic measurements of fetal growth. The accuracy of the diagnosis is ultimately dependent on the accuracy of each of these components. IUGR must also be understood to be a growth phenomenon; a single static measurement may be suggestive but is not diagnostic. Serial measurements are generally required to diagnose IUGR.

Estimation of gestational age is based on the last menstrual period, key developmental markers (such as heartbeat), and sonographic data. Sonographic data can be useful for three purposes: (a) estimation of gestational age, (b) identification of structural or developmental abnormalities, and (c) measurement of fetal growth parameters. The most accurate ultrasound parameters for estimating gestational age vary with the age of the fetus. Crown–rump length is most accurate in early pregnancy; biparietal diameter and head circumference are most accurate for second trimester evaluation. Third trimester estimates are decreasingly accurate but head circumference may be most accurate. The increased sophistication of obstetrical ultrasounds has yielded images capable of remarkable anatomic detail. Cardiac, renal, GI, and neurological anomalies may all be detected on ultrasound examination. Patients with suspected IUGR should undergo ultrasound examination with particular attention paid to detailed anatomic survey.

In addition to the parameters mentioned here, abdominal girth is particularly helpful in measuring fetal growth. Abdominal girth reflects subcutaneous fat that, in turn, is a marker for adequate fetal nutrition. IUGR is often associated with an oligohydramnios (decreased amniotic fluid) that can be measured via the AFI. The AFI is the sum of the largest fluid pocket in each of the four quadrants. IUGR with oligohydramnios is associated with increased morbidity compared with IUGR alone.

Although not diagnostic of IUGR, measurement of fetal vascular flow, Doppler velocimetry, can provide additional clinical information regarding fetal well-being. Blood flow is measured in the umbilical artery and the ratio of systolic to diastolic flow is calculated. Peak systolic frequency shift/end-diastolic frequency shift (S/D) ratios of 1.8–2.0 are normal. S/D ratios >3.0 indicate a pregnancy at high risk for adverse outcomes. Measurement of flow can also be measured in the middle cerebral artery and the ductus venosus.

Management

Risk Reduction

Although early identification and management can reduce the morbidity associated with IUGR, risk reduction remains a critical component of management. Ideally, such risk evaluation and reduction would begin in the preconception period with identification of pre-existing risk factors. For patients with a strong history of genetic abnormalities, genetics counseling may be indicated prior to conception. Identification of pre-existing medical conditions and nutritional deficits may also contribute to a reduction in the risk for IUGR. Although the benefits of such management in IUGR have not been well established, control of blood pressure, euglycemia prior to conception, and nutritional augmentation, among others, are recommended. Patients who smoke should be counseled to discontinue smoking; alcohol use should also be discontinued. The use of illicit drugs should be identified and cessation should be counseled. For many patients, pregnancy may represent a compelling reason to reduce or discontinue the use of toxic substances with benefit to both the mother and fetus.

Infectious risks for IUGR should be reviewed with the patient and reduction of exposure counseled. Toxoplasmosis is associated with raw or undercooked meat and cat feces. Patients should be counseled concerning exposure to those with varicella and rubella. If patients are seen in the preconceptual period, immune status should be documented for varicella and rubella. Vaccinations for both are available and should be administered to nonimmune patients who do not plan to become pregnant in the subsequent 3 months.

With diagnosis of IUGR, management involves three basic tasks: (a) identification and modification (when possible) of underlying etiology, (b) monitoring for anticipated or possible complications, and (c) evaluation of risks and benefits of continued pregnancy versus early delivery. Identification of the potential etiology is similar to preconception evaluation. The benefits of intervention are not well documented but management of medical conditions such as hypertension and diabetes, augmentation of nutritional status, and reduction or elimination of tobacco, alcohol, and illicit drug use are recommended.

Complications associated with IUGR include prenatal and perinatal complications such as increased risk of hypoxia, metabolic acidosis, preterm labor, pre-eclampsia, and surgical delivery. Neonatal complications include aspiration, apnea, intubation, sepsis, hypoglycemia, electrolyte abnormalities (especially hypocalcemia), seizure, and death. Careful intrapartum monitoring is critical to early identification and management of these potential complications.

In patients with documented IUGR, careful assessment of fetal growth and well-being is critical to determining the timing and manner of delivery. Weekly prenatal visits are recommended, with careful monitoring of fetal status with review of fetal movement and kick counts. As noted, serial measurements (every 2–6 weeks) of fetal growth are important for the diagnosis as well as for tracking. Antenatal fetal monitoring may also include nonstress testing, contraction stress testing, and/or biophysical profile measurements at least weekly. Amniotic fluid should be measured via AFI once weekly.

Management of IUGR requires individualized assessment and decision-making. Timing of delivery should balance the benefits of further fetal maturity against the risks of continued exposure to an intrauterine environment that is less than optimal. Evidence of fetal maturity (well-documented gestational age of 38 weeks’ gestation or documentation of fetal lung maturity) or significant fetal stress should prompt delivery. For infants with reassuring antenatal monitoring and without evidence of maturity, the benefits of intrauterine development may outweigh the risks of early delivery. Delivery should be planned for a facility that is experienced with and capable of managing the high-risk infants of a pregnancy complicated by IUGR. Management of perinatal complications in the infant is best managed by an experienced neonatologist.