Intrauterine Growth Retardation

Aka: Intrauterine Growth Retardation, Intrauterine Growth Restriction, Fetal Growth Retardation, Fetal Growth Restriction, Small for Gestational Age, IUGR

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II. Definitions

  1. Fetal Growth Restriction or Intrauterine Growth Retardation (IUGR)
    1. Estimated fetal weight (ACOG) or abdominal circumference (MFM) < 10% for Gestational age
  2. Severe Fetal Growth Restriction or IUGR
    1. Estimated fetal weight <3%
  3. Small for Gestational Age (SGA)
    1. Newborn with birth weight <10% for Gestational age

III. Epidemiology

  1. Affects up to 10% of pregnancies

IV. Causes: Fetal

  1. Genetic Causes
    1. Trisomy 13, Trisomy 18, Trisomy 21
    2. Cornelia de Lange Syndrome
    3. Fanconi Anemia
  2. Major Congenital Abnormalities
    1. Anencephaly
    2. Congenital Heart Disease
    3. Diaphragmatic Hernia
    4. Omphalocele
    5. Transesophageal Fistula

V. Causes: Maternal Chronic Disease

  1. Cardiovascular Disease
    1. Coronary Artery Disease
    2. Congestive Heart Failure
    3. Congenital Heart Disease
    4. Hypertensive Disorders of Pregnancy (e.g. Preeclampsia)
  2. Lung Disease
    1. Uncontrolled Severe Asthma
      1. Bracken (2003) Obstet Gynecol 102:739-52 [PubMed]
    2. Chronic Obstructive Lung Disease (COPD)
    3. Cystic Fibrosis
  3. Miscellaneous Conditions
    1. Systemic Lupus Erythematosus (or other Collagen vascular disease)
    2. Inflammatory Bowel Disease (Crohn Disease, Ulcerative Colitis)
    3. Severe Anemia including Sickle Cell Disease
    4. Chronic Diabetes Mellitus
      1. Second most common cause of IUGR (Tobacco Abuse is first)
    5. Renal Insufficiency

VI. Causes: Pregnancy Related Conditions

  1. Assisted Reproduction
  2. Socioeconomic factors (e.g. decreased maternal nutrition)
  3. Uterine Fibroids (or other uterine abnormalities limiting Intrauterine Growth)
  4. Infectious Disease
    1. TORCH Virus
      1. Toxoplasmosis
      2. Syphilis
      3. Rubella
      4. Cytomegalovirus (CMV)
      5. Herpes Simplex Virus (HSV)
    2. Listeria
    3. Tuberculosis
    4. HIV Infection
    5. Malaria
    6. Varicella
  5. Multiple Gestation
  6. Prior history of Small for Gestational Age infant
  7. Short interval between pregnancies
  8. Illicit Drugs
    1. Maternal Tobacco Abuse
      1. Most common preventable cause of IUGR
      2. Birth weight reduced 200 grams if mother smokes
    2. Maternal Alcohol Use (e.g. Fetal Alcohol Syndrome)
      1. No amount of Alcohol is safe!
    3. Cocaine
    4. Tobacco
    5. Opioids (Heroin, Methadone)
  9. Medications
    1. Antithrombotic Medications
    2. Cyclophosphamide
    3. Valproic Acid
    4. Phenytoin
  10. Placental Abnormalities
    1. Placental Abruption
    2. Placental Infarcts
    3. Abnormal placenta implantation
  11. Umbilical Cord Abnormalities
    1. Marginal Cord Insertion
    2. Two vessel cord (Single Umbilical Artery)

VII. Types

  1. Fetal asymmetry does not predict complications
    1. IUGR is now classified by onset before or after 32 weeks
  2. Early onset Fetal Growth Restriction (<32 weeks gestation) accounts for 20-30% of cases
    1. Previously described as Symmetric Intrauterine Growth Retardation
    2. More severe and progressive
    3. Associated with decreased umbilical artery flow in 70%
    4. Associated with perinatal death in 7%
    5. Associated with Preeclampsia inm 35% of cases
    6. Chromosome or genetic abnormalities in 20% of cases
  3. Late onset Fetal Growth Retardation (>32 weeks gestation)
    1. Previously described as Asymmetric Intrauterine Growth Retardation (70-80% of cases)
    2. Less severe than early onset
    3. Abnormal umbilical artery in <10%
    4. Rare perinatal death
    5. Associated with Preeclampsia in 12% of cases

VIII. Diagnosis: Level 2 Obstetric Ultrasound

  1. Indications: Exam Findings Suggestive of IUGR
    1. Poor Maternal Weight gain
      1. Most sensitive indicator for IUGR
    2. Fundal Height less than expected for Gestational age (fundal height <3 cm below Gestational age)
      1. Follow serial fundal height measurements at every visit after 24 weeks
      2. Fundal heights may be inaccurate due to body habitus, Multiple Gestation, Uterine Fibroids
  2. Indications: History Findings increasing IUGR Risk (see causes above)
    1. Tobacco Abuse (most significant individual risk)
    2. Poor Nutrition
    3. Illicit Drug Use
    4. Alcohol Abuse
    5. Minimal to no Prenatal Care
    6. Traumatic stress
    7. Prior pregnancy with IUGR or infant SGA
    8. Maternal chronic disease
  3. IUGR Test Sensitivity
    1. Detection rate in-utero: 70%
  4. Level 2 Obstetric Ultrasound (Detailed Anatomy Survey) Interpretation
    1. Estimated Fetal Weight and Abdominal Circumference <10% consistent with IUGR
    2. Head Circumference to Abdominal Circumference ratio
      1. Most useful in assessing Asymmetric IUGR
    3. Consider repeat Level 2 Ultrasound in 4 weeks if initial Ultrasound does not meet IUGR criteria

IX. Evaluation: Confirmed IUGR

  1. Maternal-Fetal Medicine Consultation recommended in all cases of IUGR
  2. Cardiocartography
  3. Umbilical Artery Doppler End-Diastolic Velocity (EDV)
    1. Normal EDV
      1. Estimatated Fetal Weight <3% for Gestational age (Severe Fetal Growth Restriction)
        1. MFM-directed monitoring
        2. Target delivery at 37 weeks
      2. Estimatated Fetal Weight >3% for Gestational age
        1. MFM-directed monitoring
        2. Target delivery at 38-39 weeks
    2. Decreased EDV
      1. MFM-directed monitoring
      2. Target delivery at 37 weeks
    3. Absent EDV
      1. MFM-directed disposition (consider admission)
      2. Target delivery at 33-34 weeks
    4. Reversed EDV
      1. Emergent Hospital Admission
      2. Target delivery at 30-32 weeks
  4. Chromosome MIcroarray analysis
    1. Obtained by Cell-Free DNA (non-invasive) or Chorionic Villus Sampling or Amniocentesis (invasive)
    2. False Positive Rate: 5%
    3. Indications
      1. Unexplained Early Onset Growth Restriction <32 weeks gestation
      2. Ultrasound structural abnormality
      3. Polyhydramnios
  5. Fetal Assessment monitoring of growth restriction ongoing after 24 weeks (at least every 3-4 weeks)
    1. Biophysical Profile or Non-Stress Test twice weekly
    2. Serial Obstetric Ultrasounds for growth
    3. Umbilical Artery Doppler End-Diastolic Velocity every 1-2 weeks (every 4 weeks if consistently normal)

X. Management: Prenatal

  1. Address risk factors
    1. Tobacco Cessation
    2. Eliminate other negative habits
    3. Ensure adequate maternal weight gain
    4. Maximize Prenatal Care
    5. Reduce environmental stressors
  2. Maternal-Fetal Medicine Consultation Indications
    1. Maternal-Fetal Medicine Consultation recommended in all cases of IUGR
    2. Poor Nonstress Test
    3. Decreasing Biparietal diameter
    4. Oligohydramnios
    5. Abdominal circumference 4 weeks less than BPD
  3. Management based on Maternal-Fetal Medicine and objective data
    1. See Umbilical Artery Doppler End-Diastolic Velocity (EDV) as above
    2. Fetal Assessment monitoring as above

XI. Management: Small for Gestational Age Infants and Children

  1. Target 30% growth by 4 months, and 50% by age 7 years
  2. Follow weight, length and Head Circumference
    1. Obtain at least every three months for the first year, and then every 6 months
  3. Consult endocrinology for length <3% in those under age 2 years
  4. Monitor Developmental Milestones (cognitive, psychomotor)
  5. Annual Blood Pressure Monitoring starting at age 3 years

XII. Complications: Peripartum Risks of IUGR

  1. Meconium Aspiration
  2. Intrauterine Asphyxia
  3. Polycythemia
  4. Hypoglycemia
  5. Intraventricular Hemorrhage
  6. Hypoxic Ischemic Encephalopathy
  7. Necrotizing Enterocolitis
  8. Bronchopulmonary Dysplasia
  9. Late onset Neonatal Sepsis
  10. Persistent Pulmonary Hypertension
  11. Neonatal Jaundice
  12. Temperature Instability

XIII. Complications: Longterm Risks of IUGR

  1. Cerebral Palsy
  2. Developmental Delay
  3. Growth Delay
  4. Learning Disorder
  5. Cardiovascular Disease
  6. Impaired Insulin Resistance

XIV. Prevention

  1. No medications (e.g. Heparin, Vitamins) appear to reduce the risk of IUGR during pregnancy
  2. Aspirin prophylaxis is only effective in Preeclampsia to reduce IUGR risk

XV. References

  1. Gabbe (1996) Obstetrics, Churchill, p. 863-886
  2. Ahluwalia (2001) Obstet Gynecol 97:649-56 [PubMed]
  3. Westby (2021) Am Fam Physician 104(5): 486-92 [PubMed]

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