Fetal Growth Restriction

Fetal growth restriction (FGR), also known as intrauterine fetal growth restriction (IUGR), is an estimated fetal weight (EFW) or abdominal circumference < 10th percentile for gestational age. The term small for gestational age (SGA) is sometimes erroneously used interchangeably with FGR. However, SGA refers to babies born with a birth weight < 10th percentile for gestational age. Defining FGR is challenging because each fetus has a different growth potential that may not be accounted for. The most commonly recognized classifications for FGR are symmetrical or asymmetrical. Symmetrical FGR occurs when all parts of the fetus are equally small and is typically the result of a complication early in pregnancy. Asymmetrical FGR occurs when there is disproportionately lagging growth in different body parts; most commonly, the fetus will have a normal size head and a small body. The causes of FGR can be broadly grouped into maternal, fetal, and placental. Fetal growth restriction is diagnosed by ultrasonography and confirmed by weight at birth. Management is often targeted to the underlying etiology, if known. Depending on the etiology, these fetuses may be at increased risk for complications such as preterm birth, intrauterine fetal death, and neurologic sequelae. Close surveillance and delivery planning by a skilled provider is crucial.

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Overview

Definition

Fetal growth restriction (FGR) is the term used to describe fetuses with an estimated fetal weight (EFW) or abdominal circumference < 10th percentile for gestational age.

  • The definition given above is the most common one; however, defining FGR is challenging because the individualized growth potential of each fetus may not be accounted for.
  • Larger fetuses who have not reached their growth potential will not be identified and may be at equal risk of adverse outcomes. 
  • Fetal growth is regulated by multiple factors and varies by: 
    • Race
    • Maternal factors
    • Paternal factors 
  • Establishing definitions and growth curves that address individualized fetal growth potential is an ongoing challenge.

Epidemiology

  • The incidence of FGR varies among populations; it appears to be more prevalent in underdeveloped nations.
    • In developed countries: approximately 4%–8%
    • In developing countries: approximately 6%–30%
    • The true prevalence is difficult to determine, as it depends on which definition is used. 
  • Occurs in all age groups, but the incidence may be higher in extremes of maternal age
  • Can occur at any gestational age
  • Associated with increased morbidity and mortality

Classification

The most commonly recognized classifications of FGR are as follows:

Symmetrical FGR:

  • All parts of the fetus (such as height, weight, and head circumference) are equally affected
  • Accounts for approximately 20%–30% of cases of FGR
  • Typically caused by a problem that started early in pregnancy
  • Most often related to aneuploidy, malformations, or fetal infection

Asymmetrical FGR:

  • Weight is most affected, with relative preservation of the head circumference
  • Accounts for 70%–80% of cases of FGR
  • Typically the result of a problem that began later in pregnancy
  • Most often a result of placental dysfunction

Other less commonly used classifications include:

  • Early FGR: describes FGR occurring at < 32 weeks 
  • Late FGR: describes FGR occurring at ≥ 32 weeks

Etiology

Many potential causes and risk factors contribute to FGR.

Maternal

  • Hypertension
  • Pregestational diabetes
  • Substance abuse:
    • Tobacco
    • Alcohol
    • Cocaine
    • Narcotics
  • Autoimmune disorders:
    • Lupus
    • Antiphospholipid antibody syndrome
    • Thyroid disease
  • Multiple gestation
  • Cyanotic heart disease
  • Sickle cell disease
  • High altitude (> 10,000 feet)
  • Restrictive pulmonary disease
  • Chronic renal disease
  • Malabsorption/malnutrition
  • Extremes of maternal age

Fetal

  • Teratogen exposure:
    • Cyclophosphamide
    • Valproic acid
    • Warfarin
  • Structural abnormalities:
    • Gastroschisis
    • Congenital heart disease
  • Genetic disorders:
    • Trisomy 13
    • Trisomy 18
  • Fetal infection:
    • Malaria (most common infectious cause worldwide)
    • Cytomegalovirus
    • Rubella
    • Toxoplasmosis
    • Syphilis
    • Varicella zoster
    • Herpes simplex

Placental

  • Placenta abruption
  • Placental masses:
    • Chorioangioma
    • Hemangioma
  • Placental mosaicism
  • Single umbilical artery

Clinical Presentation and Diagnosis

Clinical presentation

  • Often asymptomatic
  • May present with symptoms of the underlying etiology, such as hypertension or diabetes

Diagnostic evaluation

Dating:

  • Accurate knowledge of gestational age is crucial to avoid incorrect diagnosis.
  • Dating by last menstrual period is valuable if menstrual cycles are regular. 
  • Crown-rump length (CRL) measured by ultrasonography between 7 and 10 weeks of gestation is the most accurate way to date a pregnancy (± 3 days).

History and physical:

  • Fundal height 
    • Measured in centimeters between 24 and 37 weeks
    • FGR: ≥ 3 cm less than the expected height for gestational age
    • A good screening tool, but when used alone, the diagnosis is often inaccurate
  • A thorough assessment of maternal and fetal health is warranted to potentially elicit the cause.
  • Screening for maternal conditions such as:
    • 1-hour glucose-challenge test or HbA1c to screen for diabetes
    • Thyroid function testing
    • Hypertension screening
  • Screening for fetal conditions such as infection or aneuploidy may be considered based on the clinical scenario.
Fundal height measurement

Fundal height measurement:
As shown, the measuring tape is placed between the pubic symphysis and the top of the uterine fundus. The height is reported in centimeters and should match the gestational age (in weeks) within 3 cm.

Image: “Fundal Height Management” by Katrina Wittkamp/Getty Images. License: Public Domain

Ultrasonography:

  • The best way to diagnose FGR prior to delivery
  • Used to measure:
    • EFW 
    • Head circumference and biparietal diameter
    • Abdominal circumference
    • Femur length
  • Can also evaluate for:
    • Placental abnormalities
    • Oligohydramnios
Crl measurement

An ultrasound showing a crown-rump length (CRL) measurement, which is the most accurate way to date a pregnancy.

Image: “Ultrasound image of a 12-week fetus.” by hild Health, Royal Aberdeen Children’s Hospital, University of Aberdeen, Foresterhill, Aberdeen. License: CC BY 3.0

Management

General approach

Management starts with adequate treatment of the underlying cause, if identified, such as:

  • Diabetes
  • Hypertension 
  • Autoimmune conditions

Surveillance

  • Continued fetal growth and amniotic fluid volume assessment should be performed every 3–4 weeks until delivery. 
  • Doppler velocimetry of the umbilical artery: assesses the pattern and resistance of blood flow by measuring the systolic-to-diastolic ratio (S/D ratio) 
    • Normal pregnancies: The umbilical artery resistance shows gradual decline, forward diastolic flow, and a low S/D ratio.
    • Growth restriction: The S/D ratio is elevated and diastolic flow may become absent or reversed with disease progression.
  • Once- or twice-weekly monitoring with a biophysical profile or nonstress test

Delivery

  • Timing of delivery should be individualized. 
  • In cases of isolated FGR with normal antenatal testing and:
    • EFW between the 3rd and 10th percentile, the recommendation is 38–39 weeks.
    • EFW below the 3rd percentile, the recommendation is 37 weeks.

Complications

Fetal growth restriction is associated with several complications. These complications can be seen before or immediately after delivery but can also been seen months to years after.

Immediate

  • Perinatal asphyxia
  • Preterm delivery
  • Meconium aspiration
  • Low Apgar scores
  • Hypoglycemia
  • Polycythemia
  • Hyperbilirubinemia
  • Intraventricular hemorrhage
  • Impaired thermoregulation
  • Necrotizing enterocolitis
  • Respiratory failure
  • Seizures
  • Sepsis
  • Increased risk for stillbirth

Late

  • Spastic cerebral palsy
  • Neurodevelopmental abnormalities
  • Increased risk of developing chronic conditions later in life, such as:
    • Chronic hypertension
    • Ischemic heart disease
    • Type 2 diabetes
    • Obstructive lung disease

Clinical Relevance

  • Constitutionally small babies: This term is used to describe babies who are born with a birth weight < 10th percentile for their gestational age without evidence of underlying pathology. These babies are a challenge to treat in the antepartum period because it can be hard to distinguish them from growth-restricted fetuses. Therefore, the management before delivery is identical.
  • Placental abruption: complete or partial premature detachment of a normally implanted placenta before birth of the infant. Small, partial abruptions may be less dramatic and present with smaller amounts of bleeding over time (chronic abruptions), oligohydramnios, and FGR. The diagnosis is usually clinical. Management depends on the severity, but includes frequent maternal and fetal assessments and delivery if the mother or infant decompensates.
  • Patau syndrome: also known as trisomy 13. Patau syndrome is a genetic syndrome caused by the presence of 3 copies of the 13th chromosome. Findings include craniofacial and cardiac malformations, severe intellectual disability, and greatly reduced life expectancy. Most babies do not survive past 3 months. Most cases are diagnosed prenatally with the aid of maternal screening and ultrasonography. If pregnancy reaches term, it is recommended that a specialized center handle the delivery and neonatal care. 
  • Edwards syndrome: also known as trisomy 18. Edwards syndrome is a genetic condition caused by the presence of an extra chromosome 18. Many cases are detected prenatally with maternal screening and ultrasound findings. Abnormalities include FGR, overlapping fingers, typical craniofacial features, rocker bottom feet, and congenital heart defects. Trisomy 18 frequently results in fetal loss. Delivery in a specialized center is recommended for full-term pregnancies, and intervention is based on associated abnormalities.
  • Congenital TORCH infections: group of infections acquired in utero, including toxoplasmosis, syphilis, varicella-zoster virus, parvovirus B19, HIV, rubella, cytomegalovirus, and herpes simplex. These diseases can have significant consequences, such as FGR, preterm birth, congenital abnormalities, or fetal death.

References

  1. American College of Obstetricians and Gynecologists. (2021). Fetal growth restriction. ACOG Practice Bulletin Summary, number 227. Obstetrics & Gynecology 137:385–387. https://journals.lww.com/greenjournal/Abstract/2021/02000/Fetal_Growth_Restriction__ACOG_Practice_Bulletin.38.aspx
  2. Cunningham, F. G. (2018). Fetal growth disorders. In: Williams Obstetrics, 25th ed. McGraw-Hill Medical, pp. 843–886.
  3. Resnik, R., et al. (2019). Creasy and Resnik’s Maternal-Fetal Medicine: Principles and Practice. Elsevier.
  4. Gabbe, S. G. (2020). Fetal growth restriction. In: Obstetrics Normal and Problem Pregnancies, 8th ed. Elsevier, pp. 555–585.
  5. Divon, M. Y. (2021). Fetal growth restriction: screening and diagnosis. UpToDate. Retrieved September 03, 2021, from https://www.uptodate.com/contents/fetal-growth-restriction-screening-and-diagnosis
  6. Mari, G. (2021). Fetal growth restriction: evaluation and management. UpToDate. Retrieved September 3, 2021, from https://www.uptodate.com/contents/fetal-growth-restriction-evaluation-and-management
  7. Mandy, G. T. (2021). Infants with fetal (intrauterine) growth restriction. UpToDate. Retrieved September 12, 2021, from https://www.uptodate.com/contents/infants-with-fetal-intrauterine-growth-restriction
  8. Balest, A. L. (2021). Small for gestational age infant. MSD Manual Professional Version. Retrieved October 26, 2021, from https://www.msdmanuals.com/professional/pediatrics/perinatal-problems/small-for-gestational-age-sga-infant
  9. Ross, M. G. (2020). Fetal growth restriction. Medscape. Retrieved October 26, 2021, from https://emedicine.medscape.com/article/261226-overview#a4

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