Small for Gestational Age (SGA) & Fetal Growth Restriction (FGR)

1. Topic Overview (Clinical Overview)

Summary

Small for Gestational Age (SGA) refers to a fetus or neonate with an Estimated Fetal Weight (EFW) or birthweight below the 10th percentile for gestational age. [1] It is a descriptive term based purely on size, not pathology. The critical clinical distinction is that not all SGA babies are "growth restricted" – approximately 50-70% are constitutionally small (healthy parents, healthy baby, genetically small). [2] Fetal Growth Restriction (FGR), previously termed Intrauterine Growth Restriction (IUGR), is the pathological subset where the fetus has failed to reach its genetic growth potential due to an underlying cause, most commonly placental insufficiency. [3]

This distinction is the cornerstone of clinical management because true FGR carries a 5-10 fold increased risk of stillbirth, whereas constitutional SGA does not. [4] The Delphi consensus definition (2016) provides standardised criteria distinguishing early-onset (less than 32 weeks) from late-onset (≥32 weeks) FGR, incorporating Doppler parameters alongside biometry. [5]

Key Facts

Clinical Pearls

"SGA is a size. FGR is a disease." Always ask: Is this baby constitutionally small (healthy), or is something pathologically restricting growth?

The Doppler Cascade: As placental function fails, Dopplers deteriorate in a predictable sequence: Umbilical Artery (resistance increases) → Middle Cerebral Artery (vasodilation/"brain sparing") → Ductus Venosus (A-wave reversal = cardiac dysfunction) → CTG abnormalities → Stillbirth. [6]

Customised vs Population Centiles: A baby at the 8th centile for a tall Scandinavian woman is very different from one at the 8th centile for a petite South Asian woman. Customised centile charts (GROW) account for maternal ethnicity, height, weight, and parity, improving detection of pathologically small babies by 30-40%. [7]

The 3rd Centile Rule: Any fetus below the 3rd customised centile should be considered FGR until proven otherwise, regardless of Doppler findings.

Why This Matters Clinically

Unrecognised FGR is a leading preventable cause of stillbirth. The UK Confidential Enquiry into Stillbirths found that 43% of stillbirths had evidence of FGR, of which over one-third were not detected antenatally. [8] The "Saving Babies' Lives" care bundle specifically targets the detection and management of FGR through standardised symphysis-fundal height measurement, customised growth charts, and protocolised surveillance. Early identification enables appropriate monitoring and timely delivery, transforming outcomes from tragedy to survival.

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2. Definitions and Terminology

International Consensus Definitions (Delphi 2016) [5]

The Delphi consensus established standardised definitions to harmonise research and clinical practice:

Early-Onset FGR (less than 32 weeks) - Requires:

• EFW or AC less than 3rd percentile, OR
• EFW or AC less than 10th percentile + UA AEDF, OR
• EFW or AC less than 10th percentile + UA PI > 95th percentile + Uterine Artery PI > 95th percentile

Late-Onset FGR (≥32 weeks) - Requires:

• EFW or AC less than 3rd percentile, OR
• At least 2 of the following:
  • EFW or AC less than 10th percentile
  • AC or EFW crossing centiles > 2 quartiles
  • CPR less than 5th percentile or UA PI > 95th percentile

Symmetric vs Asymmetric Growth Restriction

Constitutional SGA vs Pathological FGR

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3. Epidemiology

Incidence and Prevalence

Risk Factors (RCOG GTG 31 Classification) [10]

Major Risk Factors (RR > 2.0) - Warrant Serial USS + Doppler Surveillance:

Minor Risk Factors (RR 1.5-2.0) - Consider Increased Surveillance:

Pregnancy-Specific Risk Factors:

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4. Aetiology and Pathophysiology

Classification of Causes

1. Fetal Causes (Symmetric SGA - 15-20%):

• Chromosomal abnormalities: Trisomy 18, Trisomy 13, Triploidy, Turner syndrome
• Genetic syndromes: Russell-Silver syndrome, Seckel syndrome, Cornelia de Lange syndrome
• Congenital malformations: Congenital heart disease, Neural tube defects
• Congenital infections (TORCH): CMV (most common), Toxoplasma, Rubella, Varicella, Malaria

2. Placental Causes (Asymmetric SGA - 60-70%):

• Primary placental insufficiency
• Pre-eclampsia spectrum disorders
• Placental abruption (chronic)
• Placenta praevia
• Circumvallate placenta
• Single umbilical artery
• Velamentous cord insertion

3. Maternal Causes (10-15%):

• Vascular disease (Chronic HTN, Diabetes with vasculopathy, SLE, APS)
• Malnutrition and eating disorders
• Substance use (Smoking, Alcohol, Cocaine, Heroin)
• Hypoxic conditions (Severe anaemia, Cyanotic heart disease, High altitude)
• Medications (Antiepileptics, Warfarin, Immunosuppressants)

4. Constitutional (50-70% of all SGA):

• Small parental size
• Female sex
• Ethnic variation

The Placental Insufficiency Cascade

The pathophysiology of placental-mediated FGR follows a well-characterised sequence: [6,11]

Stage 1 - Abnormal Placentation:

• Poor trophoblast invasion of spiral arteries (1st/2nd trimester)
• Failure of physiological conversion of spiral arteries to low-resistance vessels
• Retained spiral artery musculature → vasoconstriction potential
• Results in high-resistance uteroplacental circulation

Stage 2 - Chronic Hypoxia and Nutrient Restriction:

• Reduced uteroplacental blood flow
• Decreased oxygen and nutrient delivery
• Preferential use of glucose for essential organs (brain, heart, adrenals)
• Liver glycogen depletion → reduced abdominal circumference (first sign)

Stage 3 - Fetal Adaptation (Brain Sparing):

• Hypoxia triggers peripheral vasoconstriction
• Vasodilation of cerebral vessels (reduced MCA PI)
• Blood flow redistributed to brain, heart, and adrenals
• "Sacrificed" organs: kidneys, gut, skin, muscle
• Clinical consequence: Oligohydramnios (reduced renal perfusion)

Stage 4 - Cardiovascular Decompensation:

• Prolonged hypoxia → myocardial dysfunction
• Increased cardiac afterload from peripheral vasoconstriction
• Ductus venosus flow abnormality (absent/reversed A-wave)
• Umbilical vein pulsations (late, ominous)

Stage 5 - Terminal Deterioration:

• CTG abnormalities: reduced variability, decelerations, sinusoidal pattern
• Metabolic acidosis
• Stillbirth if undelivered

Doppler Flow Physics in FGR

Umbilical Artery (UA):

• Measures placental vascular resistance

• 60% of placental vascular bed must be obliterated for AEDF

• Raised PI → AEDF → REDF reflects progressive placental destruction
• REDF indicates > 70% placental destruction - critical hypoxia [11]

Middle Cerebral Artery (MCA):

• Normally high resistance (high PI) - brain doesn't "steal" blood
• In hypoxia: cerebral vasodilation → reduced PI (less than 5th percentile)
• "Brain sparing" = survival response, not reassurance

Cerebro-Placental Ratio (CPR = MCA PI / UA PI):

• More sensitive than individual Dopplers
• Low CPR (less than 5th percentile or less than 1.0) indicates redistribution
• Predictive of adverse outcome even with normal individual values [12]

Ductus Venosus (DV):

• Shunts oxygenated blood from umbilical vein to heart
• Absent/reversed A-wave indicates myocardial dysfunction
• Strong predictor of perinatal death within 1-2 weeks [6]

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5. Clinical Presentation and Detection

Antenatal Detection Methods

1. Symphysis-Fundal Height (SFH) Measurement:

Serial Plotting is Superior to Single Measurement:

• Single SFH: Sensitivity 27%
• Serial SFH on customised chart: Sensitivity 48-76% [7]

Actions on Abnormal SFH:

• SFH less than 10th centile or > 90th centile → USS within 3 weeks
• SFH less than 3rd centile → USS within 48 hours
• Two static measurements (no growth in 2-3 weeks) → USS within 48 hours

2. Ultrasound Biometry:

Red Flags on USS:

3. Risk Factor Screening at Booking:

• Identify high-risk women (see Risk Factors above)
• Stratify into surveillance pathways
• Consider prophylactic aspirin if eligible

Ultrasound Timing Recommendations (RCOG) [10]

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6. Doppler Assessment (Key Investigation)

Umbilical Artery (UA) Doppler

The cornerstone of FGR surveillance - measures placental vascular resistance.

AEDF/REDF Evidence:

• AEDF: 40% stillbirth risk if undelivered; perinatal mortality OR 4.0 [11]
• REDF: 70% stillbirth risk within 1 week if undelivered
• Median time from AEDF to abnormal CTG: 7 days
• Median time from REDF to abnormal CTG: 2-3 days

Middle Cerebral Artery (MCA) Doppler

Detects fetal brain-sparing response to hypoxia.

Cerebroplacental Ratio (CPR)

MCA PI divided by UA PI - highly sensitive composite marker. [12]

Clinical Pearl: CPR can be abnormal even when both MCA and UA PI are individually normal. Always calculate CPR in SGA assessment.

Ductus Venosus (DV) Doppler

Late-stage marker of cardiovascular decompensation. [6]

FGR Staging Model (Figueras/Gratacos Classification) [5]

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7. Investigations

Baseline Investigations on FGR Diagnosis

Maternal:

Fetal:

TORCH Screening Indications

Consider TORCH serology when:

• Symmetrical FGR (head and abdomen proportionally small)
• Intracranial calcifications
• Ventriculomegaly
• Echogenic bowel
• Hepatosplenomegaly
• Hydrops

Genetic Testing Indications

Consider invasive testing (amniocentesis/CVS for karyotype and microarray) when:

• EFW less than 3rd centile before 28 weeks
• Symmetrical FGR
• Any structural anomaly identified
• Polyhydramnios with SGA (paradoxical - suggests swallowing issue)
• Multiple anomalies

Common Chromosomal Causes of FGR:

• Trisomy 18 (Edwards): Severe early FGR, clenched hands, rocker-bottom feet
• Trisomy 13 (Patau): Holoprosencephaly, polydactyly, cardiac defects
• Triploidy: Severe early FGR, hydatidiform changes in placenta
• Turner syndrome (45,X): Cystic hygroma, cardiac defects

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8. Management

Management Algorithm (Based on RCOG GTG 31) [10]

┌─────────────────────────────────────────────────────────────────────────┐
│           SGA DETECTED ON ULTRASOUND (less than 10th Percentile)                  │
├─────────────────────────────────────────────────────────────────────────┤
│                                                                          │
│  STEP 1: Establish Cause                                                 │
│  ├── Screen for Pre-eclampsia (BP, Urine Protein, Bloods)               │
│  ├── Detailed Anatomy Scan                                               │
│  ├── Consider TORCH serology if symmetrical/anomalies                    │
│  └── Consider Karyotype if less than 28w, severe, symmetrical, anomalies          │
│                                                                          │
│  STEP 2: Check Umbilical Artery Doppler                                  │
│                                                                          │
│  ├── UA Doppler NORMAL ───────────────────────────────────────────────  │
│  │       ↓                                                               │
│  │   Likely Constitutional SGA                                           │
│  │   • Serial Growth Scans every 2-4 weeks                               │
│  │   • Standard antenatal care                                           │
│  │   • Plan delivery 40+0 - 41+0 weeks                                   │
│  │                                                                       │
│  └── UA Doppler ABNORMAL (PI > 95th, AEDF, REDF) ──────────────────────  │
│          ↓                                                               │
│      FGR CONFIRMED                                                       │
│                                                                          │
│  STEP 3: Stage and Surveillance                                          │
│  ├── Stage I (High PI only): Weekly scans. Deliver 37+0 weeks           │
│  ├── Stage II (AEDF or low MCA PI): Twice weekly scans/CTG. 34+0 weeks  │
│  └── Stage III/IV (REDF/DV abnormal/CTG abnormal): Admit. Daily CTG.    │
│                                                                          │
│  STEP 4: Antenatal Steroids                                              │
│  ├── Betamethasone 12mg IM x 2 doses 24h apart, OR                      │
│  └── Dexamethasone 6mg IM x 4 doses 12h apart                           │
│      → Give if delivery anticipated less than 34+6 weeks                          │
│                                                                          │
│  STEP 5: Magnesium Sulphate Neuroprotection                              │
│  └── 4g IV loading dose if delivery anticipated less than 32 weeks               │
│                                                                          │
│  STEP 6: Delivery Planning                                               │
│  ├── Mode: Vaginal if tolerating; CS if fetal compromise                │
│  └── Neonatology counselling for preterm/severe FGR                     │
│                                                                          │
└─────────────────────────────────────────────────────────────────────────┘

Conservative Management: Surveillance Frequency

Pharmacological Interventions

1. Antenatal Corticosteroids:

2. Magnesium Sulphate (Neuroprotection): [13]

3. Aspirin Prophylaxis (Prevention): [14]

Timing of Delivery

Evidence Base - GRIT and TRUFFLE Studies: [6,15]

The balance between risks of ongoing intrauterine hypoxia vs iatrogenic prematurity.

TRUFFLE Study Key Findings: [6]

• DV-based timing (await DV changes) vs CTG-based timing
• DV approach allowed 4 days longer gestation without increased adverse outcome
• DV reversal = indication for delivery regardless of CTG
• Supports DV as delivery timing marker for early-onset FGR

Mode of Delivery

Intrapartum Considerations for FGR:

• Continuous CTG mandatory (fetal reserve limited)
• Low threshold for CS if CTG abnormal
• Avoid prolonged second stage
• Paediatric/neonatal team present at delivery
• Delayed cord clamping (30-60 seconds) if baby in good condition

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9. Neonatal Complications

Immediate Neonatal Complications [16]

Hypoglycemia Management Protocol

Definition: Blood glucose less than 2.6 mmol/L

Risk Period: Highest in first 24 hours

Monitoring Schedule for SGA Neonates:

• Pre-feed glucose at: Birth, 2h, 4h, 8h, 12h, 24h
• Continue until 3 consecutive normal values > 2.6 mmol/L

Polycythemia Management

Definition: Venous haematocrit (Hct) > 65%

Symptoms: Plethora, lethargy, hypoglycemia, feeding difficulty, respiratory distress

Partial Exchange Formula: Volume (mL) = Blood Volume × (Observed Hct - Desired Hct) / Observed Hct

• Use normal saline as replacement fluid

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10. Long-Term Outcomes

Catch-Up Growth [17]

Neurodevelopmental Outcomes [17,18]

Neuroprotective Factors:

• Magnesium sulphate if delivery less than 32 weeks
• Optimal delivery timing (not too early, not too late)
• Breast milk feeding
• Early intervention services

Metabolic Programming: Barker Hypothesis (DOHaD) [19,20]

The "Developmental Origins of Health and Disease" paradigm explains why SGA babies face increased cardiometabolic risk in adulthood.

Theory:

• Fetal undernutrition triggers adaptive responses ("thrifty phenotype")
• Permanent epigenetic changes alter metabolism
• Programmed for caloric efficiency (survival advantage in utero)
• Mismatch with postnatal caloric abundance → metabolic disease

Long-Term Risks in Adults Born SGA:

Clinical Implications for Follow-Up:

• Counsel parents about long-term risks
• Healthy lifestyle from childhood (avoid obesity)
• Annual BP monitoring from young adulthood
• Screening for diabetes in adulthood (earlier than population average)
• Awareness for GPs about increased cardiovascular risk

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11. Special Populations

SGA in Multiple Pregnancy [10]

Key Differences from Singletons:

• Twins are normally smaller than singletons at term
• Population singleton charts over-diagnose SGA in twins
• Twin-specific growth charts should be used

Chorionicity Considerations:

Selective FGR (sFGR) in MCDA Twins:

• Definition: One twin SGA, weight discordance > 25%
• Classification (by UA Doppler of smaller twin):
  • "Type I: Normal Dopplers → Often good outcome"
  • "Type II: AEDF/REDF → Poor outcome; complex management"
  • "Type III: Intermittent AEDF/REDF → Variable outcome"
• Management options: Expectant, Laser ablation, Cord occlusion, Early delivery

SGA with Pre-eclampsia

Shared Pathophysiology:

• Same underlying placental disease (defective trophoblast invasion)
• Often coexist; FGR may precede or accompany pre-eclampsia
• sFlt-1/PlGF ratio can help distinguish placental disease from essential hypertension

Key Management Points:

• Always screen for pre-eclampsia when FGR detected (BP, urine protein, bloods)
• Delivery indication may be maternal (severe hypertension, HELLP) rather than fetal
• Pre-eclampsia may accelerate fetal deterioration
• Aspirin 150mg from 12 weeks prevents up to 60% of preterm pre-eclampsia

Previous Stillbirth

Risk of Recurrence:

• 2-4 times increased risk of SGA/FGR in subsequent pregnancy
• Higher if previous stillbirth was due to FGR/placental cause

Management of Subsequent Pregnancy:

• Consultant-led care from booking
• Aspirin 150mg from 12-36 weeks
• Uterine artery Doppler at 20-24 weeks (if abnormal → high-risk pathway)
• Serial growth scans from 24-26 weeks, every 2 weeks
• Customised growth charts
• Low threshold for intervention
• Earlier delivery often planned (37-38 weeks even if normal findings) for parental reassurance
• Psychological support and bereavement midwife involvement

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12. Prevention

Primary Prevention Strategies

Secondary Prevention (Detection)

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13. Guidelines Summary

Key Guidelines

Landmark Trials

1. GRIT Study (2004) - Growth Restriction Intervention Trial [15]

• Question: Early vs Delayed delivery in severe FGR 24-36 weeks
• Finding: No significant difference in death or disability at 2 years
• Impact: Supports individualised decision-making; neither extreme is optimal

2. TRUFFLE Study (2015) - Trial of Umbilical and Fetal Flow in Europe [6]

• Question: Best parameter for timing delivery in early-onset FGR
• Finding: DV-based timing allowed pregnancy prolongation without increased adverse outcome
• Impact: Supports DV Doppler for delivery timing in severe preterm FGR

3. ASPRE Trial (2017) - Aspirin for Pre-eclampsia Prevention [14]

• Finding: Aspirin 150mg at night from 12-36 weeks reduced preterm pre-eclampsia by 62%
• Impact: Also reduced SGA rates; Changed UK practice to 150mg (not 75mg)

4. STRIDER Trials (2018-2021) - Sildenafil in FGR [21]

• Finding: No benefit; Some harm signal (increased pulmonary hypertension in neonates in Dutch trial)
• Impact: Sildenafil NOT recommended for FGR treatment

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14. Exam Scenarios (Common Vivas)

Scenario 1: Early-Onset Severe FGR

Stem: 28-week scan shows EFW less than 3rd percentile. UA Doppler shows AEDF. What is your management?

Model Answer: "This is a case of early-onset severe FGR with absent end-diastolic flow, indicating significant placental insufficiency. My management would be:

1. Immediate: Admit for inpatient monitoring. Exclude pre-eclampsia (BP, urine protein, bloods including LFTs, FBC, urate).

2. Steroids: Administer betamethasone 12mg IM now and repeat in 24 hours for fetal lung maturity.

3. Neuroprotection: Consider magnesium sulphate 4g IV loading dose given delivery may occur less than 32 weeks.

4. Surveillance: Twice-daily CTG, twice-weekly Doppler assessment including MCA and ductus venosus.

5. Investigations: Detailed anatomy scan if not done; consider amniocentesis for karyotype/microarray given severity and early onset.

6. Counselling: Discuss prognosis with parents and neonatology team. Balance prematurity risks vs ongoing intrauterine hypoxia.

7. Delivery timing: Aim for 32-34 weeks if stable. Deliver earlier if REDF develops, DV becomes abnormal, or CTG deteriorates. The TRUFFLE study supports DV-based timing in this scenario.

8. Mode: Likely caesarean section as fetus is unlikely to tolerate labour with AEDF."

Scenario 2: Constitutional SGA

Stem: 36-week scan shows EFW 8th percentile. Both parents are of small stature. UA Doppler normal. MCA normal. CPR > 1.0. What is your diagnosis and plan?

Model Answer: "This is likely constitutional SGA rather than pathological FGR based on:

• Small parental size (strong genetic component)
• Normal umbilical artery Doppler
• Normal MCA Doppler
• Normal cerebroplacental ratio

My management:

1. Reassurance: Explain to parents that baby is likely healthy but genetically small
2. Surveillance: Continue standard antenatal care with serial SFH
3. Follow-up scan: Consider repeat growth scan in 2-3 weeks to confirm appropriate growth velocity (tracking centile)
4. Delivery: Plan delivery at 40+0 to 41+0 weeks unless clinical concern develops
5. Intrapartum: Vaginal delivery with standard care is appropriate
6. Neonatal: Routine postnatal care with standard hypoglycemia prevention (early feeding)"

Scenario 3: Brain Sparing

Stem: 32-week scan shows EFW 5th percentile, UA PI raised but positive diastolic flow, MCA PI less than 5th percentile ("brain sparing"). What does this mean and how would you manage?

Model Answer: "This represents Stage II FGR with evidence of fetal redistribution ('brain sparing'). The low MCA PI indicates cerebral vasodilation in response to chronic hypoxia - the fetus is prioritising brain perfusion.

Management:

1. Escalate surveillance: Twice-weekly Doppler and CTG
2. Steroids: Administer if not already given (delivery likely before 35 weeks)
3. Monitor for progression: Watch for development of AEDF, REDF, or DV abnormality
4. Planned delivery: Aim for 34 weeks if stable
5. Neonatology involvement: Counsel parents about prematurity outcomes
6. Continue maternal monitoring: Regular pre-eclampsia screening"

Scenario 4: High-Risk History at Booking

Stem: A woman at booking visit has a history of previous stillbirth at 34 weeks attributed to undiagnosed FGR. What is your plan for this pregnancy?

Model Answer: "This woman is at high risk of recurrent FGR (RR 2-4). My plan:

1. Prophylaxis: Aspirin 150mg at night from 12 weeks to 36 weeks
2. First trimester: Combined pre-eclampsia screening; Consider PAPP-A/PlGF
3. 20-week scan: Detailed anatomy plus uterine artery Dopplers (abnormal predicts higher risk)
4. Serial growth scans: Starting at 24-26 weeks, every 2 weeks with Doppler
5. Customised growth charts: Use GROW software for accurate assessment
6. Delivery planning: Consider earlier delivery (37-38 weeks) even if normal, given psychological factors and residual risk
7. Psychological support: Bereavement midwife involvement; additional scans for reassurance if needed
8. Consultant-led care: Throughout pregnancy"

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15. Triage and Referral

When to Refer / Admit

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16. Quality Markers and Audit Standards

Saving Babies' Lives Care Bundle v2 Standards

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17. Patient Information and Counselling

What Does "Small for Gestational Age" Mean?

Your baby is measuring smaller than expected for how far along you are in your pregnancy. This is common – about 1 in 10 babies measure this way. There are two main reasons:

1. Constitutionally Small: Your baby is healthy but genetically small, often because you or your partner are smaller in stature. These babies do very well.

2. Growth Restricted: Your baby isn't growing as well as they should, often because the placenta isn't working as efficiently. These babies need extra monitoring.

Is My Baby Okay?

We need to do extra tests to find out which group your baby is in. The most important test is a Doppler scan that looks at blood flow in the umbilical cord. If the blood flow is normal, it's very reassuring.

What Tests Will I Have?

1. Ultrasound scans to measure your baby's size
2. Doppler scans to check blood flow in the cord and baby's brain
3. CTG (heart rate monitoring) if we're concerned
4. Blood and urine tests to check for pre-eclampsia

Will My Baby Need to Be Born Early?

Some babies need to be delivered early if the tests show they're not coping well inside the womb. Your doctor will discuss the right timing with you. It's a balance between keeping baby inside to grow and getting them out for safety.

What Should I Look Out For?

Please monitor your baby's movements. If you notice baby moving less than usual, contact the hospital immediately. Do not wait until the next day.

After Birth

Your baby may need extra checks for low blood sugar and temperature in the first day or two. Most SGA babies do very well. Some may have a slightly increased risk of health problems later in life (diabetes, high blood pressure), so a healthy lifestyle from childhood is especially important.

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18. References

1. Lee PA, Chernausek SD, Hokken-Koelega AC, Czernichow P. International Small for Gestational Age Advisory Board consensus development conference statement: management of short children born small for gestational age. Pediatrics. 2003;111(6 Pt 1):1253-1261. doi:10.1542/peds.111.6.1253

2. Figueras F, Gratacos E. Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol. Fetal Diagn Ther. 2014;36(2):86-98. doi:10.1159/000357592

3. Nardozza LM, Caetano AC, Zamarian AC, et al. Fetal growth restriction: current knowledge. Arch Gynecol Obstet. 2017;295(5):1061-1077. doi:10.1007/s00404-017-4341-9

4. Gardosi J, Madurasinghe V, Williams M, Malik A, Francis A. Maternal and fetal risk factors for stillbirth: population based study. BMJ. 2013;346:f108. doi:10.1136/bmj.f108

5. Gordijn SJ, Beune IM, Thilaganathan B, et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol. 2016;48(3):333-339. doi:10.1002/uog.15884

6. Lees CC, Marlow N, van Wassenaer-Leemhuis A, et al. 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial. Lancet. 2015;385(9983):2162-2172. doi:10.1016/S0140-6736(14)62049-3

7. Gardosi J, Francis A, Turner S, Williams M. Customized growth charts: rationale, validation and clinical benefits. Am J Obstet Gynecol. 2018;218(2S):S609-S618. doi:10.1016/j.ajog.2017.12.011

8. Draper ES, Kurinczuk JJ, Kenyon S. MBRRACE-UK Perinatal Mortality Surveillance Report, UK Perinatal Deaths for Births from January to December 2017. Leicester: The Infant Mortality and Morbidity Studies, Department of Health Sciences, University of Leicester; 2019.

9. Sharma D, Shastri S, Sharma P. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects. Clin Med Insights Pediatr. 2016;10:67-83. doi:10.4137/CMPed.S40070

10. Royal College of Obstetricians and Gynaecologists. The Investigation and Management of the Small-for-Gestational-Age Fetus. Green-top Guideline No. 31. 2nd ed. London: RCOG; 2014.

11. Baschat AA. Neurodevelopment following fetal growth restriction and its relationship with antepartum parameters of placental dysfunction. Ultrasound Obstet Gynecol. 2011;37(5):501-514. doi:10.1002/uog.9008

12. DeVore GR. The importance of the cerebroplacental ratio in the evaluation of fetal well-being in SGA and AGA fetuses. Am J Obstet Gynecol. 2015;213(1):5-15. doi:10.1016/j.ajog.2015.05.024

13. Crowther CA, Middleton PF, Voysey M, et al. Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis. PLoS Med. 2017;14(10):e1002398. doi:10.1371/journal.pmed.1002398

14. Rolnik DL, Wright D, Poon LC, et al. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017;377(7):613-622. doi:10.1056/NEJMoa1704559

15. GRIT Study Group. A randomised trial of timed delivery for the compromised preterm fetus: short term outcomes and Bayesian interpretation. BJOG. 2003;110(1):27-32. doi:10.1046/j.1471-0528.2003.02014.x

16. Sharma D, Shastri S, Farahbakhsh N, Sharma P. Intrauterine growth restriction - part 2. J Matern Fetal Neonatal Med. 2016;29(24):4037-4048. doi:10.3109/14767058.2016.1154525

17. Sacchi C, Marino C, Nosarti C, Vieno A, Visentin S, Simonelli A. Association of Intrauterine Growth Restriction and Small for Gestational Age Status With Childhood Cognitive Outcomes: A Systematic Review and Meta-analysis. JAMA Pediatr. 2020;174(8):772-781. doi:10.1001/jamapediatrics.2020.1097

18. Murray E, Fernandes M, Fazel M, Kennedy SH, Villar J, Stein A. Differential effect of intrauterine growth restriction on childhood neurodevelopment: a systematic review. BJOG. 2015;122(8):1062-1072. doi:10.1111/1471-0528.13435

19. Barker DJ. Fetal origins of coronary heart disease. BMJ. 1995;311(6998):171-174. doi:10.1136/bmj.311.6998.171

20. Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008;359(1):61-73. doi:10.1056/NEJMra0708473

21. Sharp A, Cornforth C, Jackson R, et al. Maternal sildenafil for severe fetal growth restriction (STRIDER): a multicentre, randomised, placebo-controlled, double-blind trial. Lancet Child Adolesc Health. 2018;2(2):93-102. doi:10.1016/S2352-4642(17)30173-6

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