Intrauterine Growth Restriction (IUGR) / Fetal Growth Restriction (FGR)

Definition

• Not every SGA newborn has pathological IUGR because some are constitutionally small.
• Not every fetus diagnosed with FGR will be born SGA.

Symmetric versus Asymmetric IUGR

Diagram: Pattern of growth restriction

SYMMETRIC IUGR                         ASYMMETRIC IUGR

Early fetal insult                      Late placental insufficiency
        ↓                                        ↓
Reduced cell multiplication             Reduced nutrient and oxygen supply
        ↓                                        ↓
All body parameters reduced             Brain-sparing response
        ↓                                        ↓
HC ↓  AC ↓  FL ↓                         AC ↓↓↓   HC relatively normal
        ↓                                        ↓
Proportionately small fetus             Thin, wasted fetus with relative
                                        preservation of head size

Causes of IUGR

1. Maternal causes

• Chronic hypertension
• Pre-eclampsia
• Chronic renal disease
• Maternal cardiac disease
• Chronic pulmonary disease
• Gastrointestinal disease
• Systemic lupus erythematosus
• Vascular diabetes mellitus
• Maternal malnutrition
• Micronutrient deficiency
• Low pre-pregnancy BMI
• Maternal age <16 years or >35 years
• Smoking
• Alcohol intake
• Opioid or cocaine abuse
• Chronic infections:
  • Malaria
  • Tuberculosis
  • Urinary tract infection
• Maternal hypoxemia:
  • High altitude
  • Cyanotic heart disease
  • Severe pulmonary disease
• Low socioeconomic status
• Assisted reproductive technology
• Previous SGA baby or previous IUGR baby

2. Fetal causes

• Chromosomal abnormalities:
  • Trisomy 13
  • Trisomy 18
  • Microdeletion syndromes
• Monogenic disorders
• Major congenital malformations:
  • Congenital diaphragmatic hernia
  • Tracheoesophageal fistula
  • Abdominal wall defects
  • Neural tube defects
• Congenital infections:
  • TORCH infections
• Multiple pregnancy
• Monochorionic twins
• Exposure to radiation

3. Placental and cord causes

• Small placenta
• Reduced placental surface area
• Villous placentitis
• Placental infarction
• Placental tumors:
  • Chorioangioma
  • Hydatidiform mole
• Placental abruption
• Mesenchymal dysplasia
• Twin-to-twin transfusion syndrome
• Velamentous cord insertion
• True knot of cord
• Placental mosaicism

4. Endocrine causes

• Fetal insulin deficiency
• Insulin-like growth factor-1 deficiency

Diagnosis of FGR

Clinical suspicion

• Maternal risk factors for placental insufficiency
• Fundal height smaller than expected for gestational age
• Reduced fetal movements
• Previous pregnancy with FGR or stillbirth

Ultrasound diagnosis

• Estimated fetal weight (EFW) <10th percentile suggests SGA/FGR.
• Abdominal circumference (AC) <10th percentile suggests SGA/FGR.
• Severe FGR is usually considered when EFW or AC is <3rd percentile.
• Serial ultrasound is important to assess growth velocity.
• A fall in fetal growth centiles is concerning even if the measurement remains above the 10th percentile.

Doppler evaluation

• Umbilical artery Doppler
• Middle cerebral artery Doppler
• Cerebroplacental ratio
• Ductus venosus Doppler in severe early-onset FGR, depending on protocol and expertise

Important Doppler findings

Antenatal Management of IUGR

1. Confirm diagnosis

• Perform detailed fetal biometry:
  • AC
  • EFW
  • Head circumference
  • Femur length
• Assess amniotic fluid volume.
• Perform umbilical artery Doppler.
• Assess MCA Doppler and cerebroplacental ratio where used.
• Repeat growth scans serially.

2. Identify the cause

• Detailed anomaly scan.
• Consider fetal karyotype/genetic testing in early-onset or symmetric IUGR.
• TORCH testing if congenital infection is suspected.
• Maternal assessment for:
  • Hypertension
  • Diabetes
  • Renal disease
  • Autoimmune disease
  • Thrombophilia where clinically appropriate
  • Nutritional deficiency
  • Substance use

3. Correct reversible maternal factors

• Optimize maternal nutrition.
• Treat maternal anemia and micronutrient deficiency.
• Control hypertension and diabetes.
• Treat infection.
• Stop smoking, alcohol and recreational drugs.
• Advise rest only when clinically indicated. Routine bed rest is not a treatment for FGR.

4. Aspirin

• Low-dose aspirin is used for prevention in women at high risk of pre-eclampsia or placental insufficiency.
• It is most useful when started early in pregnancy.
• It does not reverse established severe FGR.

5. Antenatal corticosteroids

• Usually when delivery before 34 weeks is anticipated.
• May also be considered in selected pregnancies at later gestations according to local protocol.
• Magnesium sulfate may be used for fetal neuroprotection when very preterm delivery is expected.

6. Fetal surveillance

• Maternal fetal movement monitoring.
• Non-stress test/cardiotocography.
• Biophysical profile where indicated.
• Serial umbilical artery Doppler.
• Frequency depends on severity:

FGR with normal umbilical artery Doppler
            ↓
Umbilical artery Doppler every 1-2 weeks
            ↓
Weekly fetal surveillance after viability

Severe FGR or raised umbilical artery resistance
            ↓
Weekly Doppler and closer surveillance

Absent end-diastolic flow
            ↓
Doppler 2-3 times per week
            ↓
Frequent CTG and consideration of admission

Reversed end-diastolic flow
            ↓
Hospitalize
            ↓
Corticosteroids + intensive CTG surveillance
            ↓
Consider delivery based on gestation and fetal condition

Timing of Delivery

Risk of continuing pregnancy
stillbirth + hypoxia + acidosis
                versus
Risk of prematurity
RDS + IVH + NEC + sepsis + neurodevelopmental problems

General approach

• Deliver earlier if there is:
  • Severe oligohydramnios
  • No interval fetal growth
  • Non-reassuring NST/CTG
  • Abnormal biophysical profile
  • Severe pre-eclampsia or maternal deterioration
  • Absent/reversed end-diastolic flow in the umbilical artery
  • Abnormal ductus venosus Doppler
• In uncomplicated late-onset FGR with reassuring surveillance, delivery is commonly planned near term.
• With major Doppler abnormalities, delivery may be required much earlier after corticosteroid cover, according to gestational age and fetal condition.

Simplified delivery guide

Management Flowchart

Suspected fetal growth restriction
                ↓
Detailed fetal biometry
AC and EFW percentile
Amniotic fluid assessment
Umbilical artery Doppler
MCA Doppler / CPR where available
                ↓
Is AC or EFW <3rd percentile,
or is Doppler abnormal?
                ↓
        ┌────── Yes ──────┐
        ↓                 ↓
Detailed etiological       Assess for maternal disease,
work-up                    placental insufficiency and
- Anomaly scan             fetal compromise
- Genetic testing          ↓
- TORCH testing if needed  Treat reversible factors
- Maternal evaluation      ↓
                           Steroids if delivery <34 weeks expected
                           ↓
                           Serial surveillance
                           NST / CTG / BPP / Doppler
                           ↓
             Is there severe Doppler abnormality,
             oligohydramnios, no growth, or non-reassuring testing?
                           ↓
                 ┌──── Yes ────┐
                 ↓             ↓
          Deliver in a         Continue surveillance
          hospital with        until planned delivery
          neonatal support     near term
                 ↓
      Postnatal monitoring and neonatal care

Intrapartum Management

• Deliver in a facility with neonatal resuscitation and NICU support.
• Continuous electronic fetal heart-rate monitoring during labour.
• Low threshold for caesarean delivery if fetal compromise is suspected.
• Induction of labour may be possible in selected late-onset FGR with reassuring fetal monitoring.
• Caesarean delivery is often preferred in severe FGR with absent/reversed end-diastolic flow or fetal distress.

Postnatal Management

1. Anticipate perinatal depression

• FGR babies have increased risk of:
  • Birth asphyxia
  • Meconium aspiration
  • Need for resuscitation

2. Prevent hypothermia

• Use radiant warmer.
• Encourage skin-to-skin care when stable.
• Maintain warm chain.
• Poor subcutaneous fat makes these babies prone to rapid heat loss.

3. Prevent and treat hypoglycemia

• Feed early, preferably within 30 minutes to 1 hour after birth.
• Give frequent feeds, often every 2-3 hours.
• Monitor blood glucose.
• Give IV dextrose if feeding does not correct hypoglycemia.

4. Feeding support

• Early breastfeeding.
• Frequent feeds.
• Expressed breast milk if direct breastfeeding is ineffective.
• Fortified feeds or supplementation if necessary.

5. Screen for polycythemia

• Chronic intrauterine hypoxia increases erythropoietin production.
• Check hematocrit if clinically indicated.
• Watch for hyperviscosity symptoms.

6. Other neonatal screening

• Thrombocytopenia or neutropenia
• Jaundice
• Sepsis when suspected
• Congenital infection evaluation in symmetric IUGR
• Dysmorphism and congenital anomaly assessment

7. Long-term follow-up

• Growth monitoring.
• Developmental surveillance.
• Neurodevelopmental assessment.
• Monitor for later cardiovascular and metabolic risk.

High-Yield Exam Points

• SGA is a postnatal diagnosis.
• IUGR/FGR is an antenatal diagnosis.
• Symmetric IUGR is early, global and commonly due to chromosomal disorders or congenital infection.
• Asymmetric IUGR is late, due mainly to placental insufficiency, with head sparing.
• AC is the earliest and most sensitive biometric parameter affected in placental insufficiency.
• Umbilical artery Doppler is central to surveillance of placental FGR.
• Absent/reversed end-diastolic flow indicates severe placental insufficiency.
• Low MCA resistance indicates brain-sparing.
• Ductus venosus abnormality suggests advanced fetal compromise.
• Major neonatal complications are:
  • Hypoglycemia
  • Hypothermia
  • Polycythemia
  • Perinatal asphyxia
  • Feeding difficulty
  • Thrombocytopenia
  • Hyperbilirubinemia