What are the genetic and non-genetic causes of early onset Fetal Growth Restriction (FGR) in a pregnant woman?

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Genetic and Non-Genetic Causes of Early Onset Fetal Growth Restriction

Early-onset FGR (diagnosed <32 weeks gestation) is associated with fetal or chromosomal abnormalities in up to 20% of cases, making genetic evaluation essential, while the remaining cases are predominantly caused by placental insufficiency and maternal factors. 1

Genetic Causes

Chromosomal Abnormalities

Chromosomal abnormalities account for approximately 6.4% of early-onset FGR cases even without structural malformations. 1 The most common chromosomal causes include:

  • Triploidies and Trisomy 18 are the most frequent chromosomal abnormalities causing early and severe FGR 2
  • Chromosomal microarray analysis (CMA) provides a 4-10% incremental diagnostic yield over standard karyotyping in fetuses with early-onset growth restriction without structural malformations 1
  • When FGR is accompanied by fetal malformations or polyhydramnios, the rate of chromosomal abnormalities increases substantially 1

Submicroscopic Chromosomal Anomalies

  • 22q11.2 microduplication syndrome is a notable submicroscopic chromosomal anomaly associated with early-onset FGR 2
  • These anomalies are detected through CMA rather than standard karyotyping, emphasizing the importance of advanced genetic testing 2

Single Gene Disorders

  • Single gene disorders frequently present with early-onset FGR, often accompanied by mild ultrasound findings that may not constitute frank structural malformations 2
  • Syndromes related to abnormal genomic imprinting can cause FGR 3

Epigenetic Factors

  • Epigenetic marks have growing importance in fetal growth, representing a distinct category of genetic influence on fetal development 2

Non-Genetic Causes

Placental Factors (Most Common)

Suboptimal perfusion of the maternal-placental circulation is the most common cause of early-onset FGR, accounting for 25-30% of all cases. 1

  • Placental insufficiency results from defective placental implantation with elevated hypoxia 4
  • Anatomical, vascular, chromosomal, and morphological placental abnormalities contribute to FGR 3
  • Early FGR (<32 weeks) is associated with substantial alterations in placental implantation requiring cardiovascular adaptation 4

Maternal Factors

Maternal hypertensive disease is present in 50% of early-onset FGR cases during pregnancy and 70% at delivery, making it one of the most important independent determinants of poor outcomes. 1

Additional maternal causes include:

  • Autoimmune disorders 3
  • Severe malnutrition 3
  • Maternal lifestyle factors including smoking, alcohol, and cocaine use 3
  • Certain medications 3

Infectious Causes

Cytomegalovirus (CMV) is the primary infectious etiology to evaluate in early-onset FGR. 1

  • PCR for CMV should be performed in women with unexplained FGR who elect diagnostic testing with amniocentesis 1
  • Screening for toxoplasmosis, rubella, or herpes is not recommended in the absence of other specific risk factors 1
  • Perinatal viral or protozoan infections can cause FGR 3

Multiple Gestation

  • Multiple gestation is a recognized fetal etiology of FGR 3
  • Selective FGR in monochorionic twins represents a specific subset with distinct management considerations 5

Clinical Algorithm for Evaluation

Initial Diagnostic Workup

When early-onset FGR is diagnosed, perform a detailed obstetrical ultrasound examination (CPT code 76811) to identify structural abnormalities. 1

Genetic Testing Indications

Offer prenatal diagnostic testing with CMA when:

  • FGR is detected with fetal malformation, polyhydramnios, or both (regardless of gestational age) 1
  • Unexplained isolated FGR is diagnosed at <32 weeks gestation 1

Infectious Workup

  • Perform PCR for CMV only in women with unexplained FGR who elect amniocentesis 1
  • Do not routinely screen for toxoplasmosis, rubella, or herpes without additional risk factors 1

Maternal Evaluation

  • Monitor closely for development of hypertensive disorders of pregnancy, as this complication is highly prevalent and significantly impacts outcomes 1

Common Pitfalls

  • Failing to offer CMA in isolated early-onset FGR misses 4-10% of genetic diagnoses that standard karyotyping would not detect 1
  • Assuming all early-onset FGR without structural malformations is non-genetic overlooks the 6.4% rate of chromosomal abnormalities in this population 1
  • Over-screening for infectious etiologies without specific risk factors is not evidence-based, except for CMV testing during amniocentesis 1
  • Underestimating the role of maternal hypertension as both a cause and complication of early-onset FGR can lead to inadequate maternal monitoring 1

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

3
Research

Fetal growth restriction: the etiology.

Clinical obstetrics and gynecology, 2006

4
Research

Fetal growth restriction: current knowledge.

Archives of gynecology and obstetrics, 2017

5
Guideline

Classification and Management of Selective Fetal Growth Restriction (sFGR) in Monochorionic Twin Pregnancies

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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