Amniocentesis is a prenatal diagnostic method that analyzes the composition of amniotic fluid using various laboratory techniques. Fetal cells present in the amniotic fluid can be used for cytogenetic and molecular genetic testing. Enzymatic analysis of the amniotic fluid facilitates screening for congenital hereditary metabolic diseases, while pathogen detection in the fluid can aid in determining the presence of intrauterine infections. Clinically, amniocentesis is commonly utilized for prenatal diagnosis of genetic disorders and the detection of intrauterine pathogens.
Indications
These include:
- Prenatal diagnosis of genetic disorders and screening for hereditary metabolic diseases.
- Prenatal diagnosis of intrauterine pathogenic infections.
Clinical Applications
Prenatal Diagnosis of Genetic Disorders and Screening for Hereditary Metabolic Diseases
Chromosomal and Genomic Disorders
Through cell culture from amniotic fluid, conventional chromosome karyotype analysis can diagnose chromosomal numerical or structural abnormalities. Chromosomal microarray analysis (CMA) enables high-resolution, genome-wide detection of small structural variants such as microdeletions and microduplications that conventional karyotyping may miss. Single Nucleotide Polymorphism (SNP) array can identify genomic loss of heterozygosity (LOH) and uniparental disomy (UPD). Techniques such as fluorescence in situ hybridization (FISH) and quantitative PCR are typically employed for targeted diagnosis of common chromosomal and genomic disorders.
Single-Gene Disorders
Fetal DNA extracted from amniotic fluid cells can be analyzed using various genetic testing technologies, including Sanger sequencing, MLPA, quantitative PCR, DNA methylation assays, long-fragment PCR, and high-throughput sequencing. Over 3,000 single-gene disorders can now be diagnosed prenatally. Common examples include thalassemia, phenylketonuria, hemophilia A and B, Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA), and fragile X syndrome.
Screening for Hereditary Metabolic Disorders
Enzymatic analysis of amniotic fluid can diagnose abnormalities or deficiencies in specific proteins or enzymes caused by genetic mutations. Hereditary metabolic diseases involving enzymatic activity loss often lead to substrate accumulation or depletion of metabolic products, resulting in a series of biochemical consequences. For example, measuring the activity of hexosaminidase A can diagnose familial dysautonomia associated with lipid storage disorders. Similarly, measuring galactose-1-phosphate uridylyltransferase levels can aid in diagnosing galactosemia.
Prenatal Diagnosis of Intrauterine Infections
When maternal infections with pathogens such as Toxoplasma gondii, cytomegalovirus, or rubella virus are suspected, quantitative analysis of viral DNA or RNA in amniotic fluid can assist in detecting fetal intrauterine infections. Amniotic fluid culture provides reliable evidence for diagnosing intrauterine bacterial infections. Additionally, Gram staining of amniotic fluid smears, measurement of glucose levels, white blood cell counts, and interleukin-6 assays can serve as supplementary diagnostic tools for prenatal detection of chorioamnionitis.