Disorders of fetal development, growth disorders

Disorders of fetal development and growth represent a broad group of conditions arising from abnormal prenatal development of the fetus. These include both congenital developmental defects (structural or functional abnormalities) and fetal growth disorders (failure to reach genetically determined growth potential). These conditions may result from genetic factors, environmental influences, placental dysfunction, or their combination.

Introduction

Abnormal fetal development may manifest either as:

• Structural or functional anomalies (congenital defects), or
• Quantitative deviations in growth (growth restriction or overgrowth).

Clinical severity ranges from mild cosmetic abnormalities to conditions incompatible with life. These disorders are classified under Template:MKN.

Congenital developmental defects

Congenital developmental defects are deviations from normal prenatal development exceeding the variability of the general population and potentially pathological for the individual. They may affect both structure and function and arise from abnormal ontogenetic development.

Classification

According to mechanism:

• Malformations – abnormal development from the beginning (e.g., congenital heart defects, neural tube defects).
• Disruptions – secondary damage to previously normal tissue (e.g., amniotic band syndrome).
• Deformations – mechanical forces affecting normal tissue (e.g., clubfoot in oligohydramnios).
• Dysplasias – abnormal cellular organization (e.g., osteogenesis imperfecta).

According to complexity:

• Isolated defects
• Sequences (e.g., Potter sequence)
• Associations (e.g., VACTERL)
• Syndromes (e.g., Down syndrome)

Fetal growth disorders

Fetal growth restriction (FGR, also IUGR – intrauterine growth restriction) is a condition in which the fetus does not reach its genetically determined growth potential due to a pathological process.

The most common cause is placental insufficiency. FGR is associated with significantly increased perinatal morbidity and mortality.

Forms

• Early FGR (<32 weeks)
  • Severe placental insufficiency
  • Abnormal Doppler findings
  • Strong association with preeclampsia
  • High morbidity and mortality

• Late FGR (≥32 weeks)
  • Milder placental dysfunction
  • Often normal Doppler findings
  • Lower acute mortality but significant long-term impact
  • Diagnostic difficulty

Pathophysiology

Fetal hypoxia leads to centralization of circulation:

• Preferential perfusion of brain and heart
• Reduced perfusion of kidneys → oligohydramnios
• Reduced hepatic perfusion → impaired glycogen storage
• Risk of cardiac failure (abnormal ductus venosus flow)

Risk factors

• Fetal: chromosomal abnormalities, congenital defects, infections, multiple pregnancy
• Maternal: smoking, malnutrition, hypertension, preeclampsia, diabetes, autoimmune diseases
• Placental: vascular abnormalities, abruption, cord anomalies
• Uterine: structural abnormalities

Consequences

• Perinatal: fetal death
• Neonatal: respiratory distress, hypoglycemia, hypothermia, NEC, neurological damage
• Long-term: cognitive delay, cerebral palsy
• Adult life: metabolic syndrome, hypertension, cardiovascular disease

Diagnosis

• Ultrasound biometrics: BPD, HC, AC, FL
• EFW (estimated fetal weight) compared to percentiles
• Doppler ultrasound:
  • a. umbilicalis
  • a. cerebri media
  • ductus venosus
  • aa. uterinae

Diagnostic criteria are based on percentile thresholds and abnormal flow indices.

Etiology

The causes of fetal developmental and growth disorders are multifactorial:

Genetic

• Chromosomal aberrations (e.g., Down syndrome)
• Monogenic disorders (e.g., achondroplasia)
• Multifactorial inheritance

Environmental (teratogens)

Biological

• Viruses (rubella, CMV, HIV)
• Bacteria (syphilis)
• Parasites (toxoplasmosis)

Chemical

• Drugs (thalidomide, warfarin, antiepileptics)
• Alcohol (fetal alcohol syndrome)
• Industrial toxins

Physical

• Ionizing radiation
• Hyperthermia
• Mechanical factors

Maternal and placental factors

• Placental insufficiency (key in FGR)
• Maternal diseases (diabetes, hypertension)
• Lifestyle (smoking, drugs)

Prenatal diagnosis

Prenatal diagnostics includes methods for detecting abnormalities in the fetus:

Non-invasive

• Screening programs (1st and 2nd trimester)
• Ultrasound (including targeted fetal echocardiography)
• Maternal serum markers

These are generally safe.

Invasive

• Amniocentesis
• Chorionic villus sampling
• Cordocentesis

Used for genetic and molecular analysis when risk is increased.

Clinical management

Management depends on severity and type of disorder:

• Prevention of modifiable risk factors (e.g., smoking)
• Regular prenatal monitoring
• Timely diagnosis
• Optimal timing of delivery (especially in FGR)
• Postnatal care and possible surgical correction

In severe cases incompatible with life, pregnancy termination may be considered according to legislation.

Examples

• Congenital defects: neural tube defects, congenital heart defects
• Growth disorders: fetal growth restriction, macrosomia
• Chromosomal syndromes: Down, Turner, Klinefelter

Externí odkazy

• MKN-10 klasifikace
• ICBDSR
• EUROCAT