Intrauterine growth restriction

Intrauterine growth restriction (IUGR) is defined as lower than normal fetal growth characterized by an estimated fetal weight below the 10^th percentile for a given gestational age. There are two types of IUGR: asymmetrical and symmetrical. Asymmetrical IUGR is caused by extrinsic influences (most commonly placental insufficiency) that affect the fetus in the later stages of gestation and symmetrical IUGR is caused by intrinsic influences (e.g., early intrauterine infections, aneuploidy) that affect the fetus in the early stages of gestation. IUGR is diagnosed with serial ultrasound, which demonstrates decreased fetal growth and oligohydramnios. Typical manifestations of asymmetrical IUGR are a normal fetal head size with a disproportionately small body and limbs, while symmetrical IUGR typically manifests with a global growth restriction of the head and body and can lead to an increased risk of neurologic sequelae. Treatment should address the underlying cause. Regular nonstress test (NST), contraction stress test (CST), and biophysical profile (BPP) are recommended to closely monitor fetal status and placental development. Labor induction or cesarean delivery should be considered if the infant is close to term or if there are signs of nonreassuring fetal status.

• Second leading cause of perinatal morbidity and mortality following preterm birth worldwide
• Occurs in ∼ 10% of pregnancies

Epidemiological data refers to the US, unless otherwise specified.

Maternal causes

• Substance use (e.g., alcohol, cigarettes, cocaine, heroin)
• Teratogenic drugs: ACE inhibitors, carbamazepine, phenytoin, warfarin
• Systemic diseases resulting in placental insufficiency (see below)

Uteroplacental causes

• Placental insufficiency (most common cause in the US) ^[1]
  • Definition: A disorder of the fetomaternal circulation that causes inadequate blood flow to the placenta and impaired substance exchange (e.g., oxygen) between the mother and fetus, leading to metabolic compromise of the fetus.
  • Causes and risk factors
    • Maternal conditions (smoking during pregnancy, diabetes mellitus with vasculopathy, chronic hypertension, severe anemia, anorexia nervosa, antiphospholipid syndrome, SLE, sickle cell disease)
    • Pregnancy-related conditions (preeclampsia, Rh incompatibility)
  • Clinical features: depend on the underlying cause
  • Complications: IUGR, placental abruption, preterm labor, stillbirth, Potter sequence, oligohydramnios
• Placenta previa
• Multiple gestations
• Placental abruption
• Umbilical artery thrombosis/extensive infarction ^[2]
• Uterine malformations (e.g., fibroids)

Fetal factors

• Genetic abnormalities in the fetus (e.g., aneuploidy)
• Cyanotic congenital heart defects ^[3]
• Early intrauterine infections (TORCH)

Asymmetrical IUGR is the most common manifestation of IUGR (∼ 70%), has a late onset, and is usually due to maternal systemic disease (e.g., hypertension) that results in placental insufficiency. Symmetrical IUGR is less common (∼ 30%) and is usually due to a genetic disorder (e.g., aneuploidy), congenital heart disease, or early intrauterine TORCH infection that affects the fetus early in gestation.

References:^[1][3][4]

Recent studies show that symmetry of body proportions alone can not reliably indicate intrinsic or extrinsic etiology, therefore the terms “symmetrical” and “asymmetrical” for IUGR are advised not to be used anymore. For exam purposes and because it is still used in some resources, we are covering the division. ^[5]

Asymmetrical IUGR

Caused by extrinsic factors, which affect the fetus in the later stages of gestation (i.e., third trimester).

• Impaired function of the uteroplacental unit (see placental function) → insufficient transplacental delivery of oxygen and nutrients to the fetus and impaired return of carbon dioxide and fetal metabolic waste products from the fetus to the mother's circulation
  • Effect on fetal development
    • Fetal hypoxia and hypoglycemia → shunting of blood flow to vital fetal organs (brain, heart, and adrenal glands) bypassing other organs (e.g., liver, muscle, fat tissue)
    • Fetal switch to anaerobic glycolysis → metabolic acidosis → lactic acid accumulates → progressive damage to vital fetal organs (e.g., brain, myocardium) → permanent damage, possibly fetal death
  • Effect on maternal factors
    • Decreased placental growth (↓ placental surface area) → further impairs placental function
    • ↑ Risk of preeclampsia, preterm labor, vaginal bleeding ^[6]

Symmetrical IUGR

Caused by intrinsic factors (e.g., genetic abnormalities, infections), which affect the fetus in the early stages of gestation.

Reference:^[7]

Fetal signs

• Small for gestational age (or with a birth weight below 10^th percentile) ^[3]
• Decreased or absent fetal movements ^[8]
• Asymmetrical IUGR: disproportionate growth restriction
  • The dimensions of the head are normal while the body and limbs are thin and small.
• Symmetrical IUGR: global growth restriction
  • The entire body is proportionally small.
  • The circumference of the head is proportional to the rest of the fetal body.
  • ↑ Risk of neurologic sequelae ^[9]

Maternal signs

• Mostly asymptomatic
• Decreased symphysis-fundal height
  • Measured between 24 and 36 weeks of gestation ^[10]
  • Fundal height at least 3 cm less than gestational age in weeks is a sign of IUGR.
• Small uterus (e.g., a smaller abdomen than in previous pregnancies)
• Possible vaginal bleeding (e.g., placental abruption); preterm labor

• Serial ultrasonography
  • Decreased fetal growth: fetal weight below the 10^thpercentile of a given gestational age, as estimated on ultrasound
  • Small placenta
  • Oligohydramnios
  • Further assessment of the placenta (e.g., diagnosis of placenta previa and/or calcifications can be a sign of chronic placental impairment) ^[11]
• Doppler velocimetry of the umbilical artery: reduced or reversed diastolic flow; ↑ systolic/diastolic ratio
• Nonstress test: late decelerations of the fetal heartbeat, bradycardia
• Biophysical profile
  • Oligohydramnios; (AFI < 5)
  • Absent fetal breathing movements
  • Decreased fetal movement and tone
  • A score ≤ 4 indicates fetal hypoxia and/or placental insufficiency.; In this case, labor should be induced. ^[6][12]

Constitutionally small fetus

• Definition: estimated fetal weight < 10^th percentile without an identified underlying condition
• Predisposing factors ^[13]
  • Low maternal height
  • Low maternal weight before/in early pregnancy
  • Asian descent ^[14]
  • Parity
  • Fetal female sex
• Diagnosis
  • Assessment of fetal growth using customized growth charts ^[15]
  • Doppler velocimetry of the umbilical artery: normal systolic/diastolic ratio ^[16]
• Prognosis: constitutionally small fetuses are not at increased risk for adverse perinatal outcomes

The differential diagnoses listed here are not exhaustive.

• Treatment of the underlying condition (e.g., treatment of hypertension in pregnancy, gestational diabetes mellitus)
• Close monitoring; of fetal status and placental development (NST, CST, BPP)
• If there are signs of nonreassuring fetal status; or deterioration of maternal vital signs (e.g., pre-eclampsia), induce labor or perform immediate cesarean delivery.
• If the infant is < 34 weeks gestation and close to delivery, administer steroids 48 hours before inducing labor.

• Stillbirth
• Preterm labor
• Low birth weight; (< 2500 g) with ↑ risk of sudden infant death syndrome
• Perinatal asphyxia
• Hypoglycemia, hypocalcemia
• Hypothermia
• Possibly motor and neurological disabilities

We list the most important complications. The selection is not exhaustive.