Prenatal screening is performed during pregnancy by specific investigations.
Indications for prenatal diagnosis:
- Maternal age over 35 years;
- A child with chromosomal abnormality in history;
- One parent carrier of genetic structural abnormalities;
- Mother carrying a recessive X-linked disease;
- Monogenic diseases in history;
- Parents are carriers of recessive genes, which can be detected by prenatal diagnosis;
- Family history of neural tube defect;
- Screening tests at risk;
- Abnormal fetal ultrasound;
- After in vitro fertilization procedures or intracytoplasmic injection of spermatozoon in egg, which can predispose to chromosomal abnormalities.
The purpose of prenatal diagnosis is to detect birth defects with chromosomal, monogenic, genomic and multifactorial etilogy.
In practice, prenatal screening is used to determine biochemical markers, ultrasound measurements and signs which can highlight genetic abnormalities.
Methods Of Prenatal Diagnosis
- Non-invasive: ultrasound, Doppler ultrasound, biochemical screening, analysis of fetal cells from maternal blood.
- Invasive: chorionic villi biopsy, amniocentesis, cordocentesis.
Chorionic Villi Sampling (CVS)
An early diagnosis (between 10-12 weeks of gestation) is possible using chorionic villi sampling (CVS). This is done under ultrasound control, transabdominal or transcervical and allows the study of biopsied material.
Cells taken from CVS can be subjected to:
- Molecular genetic testing – allows diagnosis of monogenic genetic disorders;
- Biochemical tests – allows diagnosis of metabolic disorders;
- Fetal karyotype – allows diagnosis of chromosomal abnormalities;
Disadvantages of the technique: the possibility of contamination with maternal cells, leading to false positive results of mosaicism, reason why amniocentesis is often necessary for diagnosis.
- Abortion: 1/50-1/100;
- Abnormalities of limbs due to amputations of embryonic buds by vacuuming.
Amniocentesis consists of transabdominal aspiration of amniotic fluid (10-20 ml) under ultrasound guidance.
Depending on the moment when is performed, amniocentesis is:
- Standard (15-18 weeks gestation);
- Early (11-14 weeks of gestation) as an alternative to CVS;
- Late (in the last trimester of pregnancy) used to diagnose Rh isoimmunization diseases. Can also be used as a treatment in case of polihidroamnios.
Analyses performed from amniotic fluid:
- Cytogenetic examination- fetal karyotype;
- Polymerase chain reaction (PCR), Fluorescence in situ hybridization (FISH) – for a rapid diagnosis of numeric chromosomal abnormalities;
- Alpha-fetoprotein dosage – in suspicion of neural tube defects;
- Acetylcholinesterase dosage (elevated in neural tube defects);
- Biochemical tests – to diagnose metabolic diseases;
- Molecular genetic testing – to diagnose monogenic diseases.
Indications for amniocentesis:
- Establishing the genetic sex, in case of a family history of X-linked disease;
- Karyotype for diagnosis of a aneuploidy;
- Diagnosis of metabolic diseases: errors in lipid metabolism, familial hypercholesterolemia, mucopolysaccharidosis, homocystinuria, galactosemia, glicogenoze, Lesh-Nyhan disease;
- Molecular diagnosis for monogenic diseases: thalassemia, hemophilia, phenylketonuria, Duchenne disease, fragile X syndrome, osteogenesis imperfecta;
- Abortion: 1/100-1/400;
- Rh immunization.
Analysis is made from fetal umbilical cord blood collected after week 18 of gestation. Can be determined:
- Accurate diagnosis in case of mosaicism detected by amniocentesis;
- Diagnosis of hematologic diseases: haemoglobinopathies (thalassemia, sickle cell anemia), hemophilia;
- Diagnosis of fetal infection;
- Diagnosis of chromosomal abnormalities with instability;
- Blood group incompatibility (in case of confirmation blood transfusion is possible);
- Fetal hydrops.
- Rh immunization;
- Abortion: 3% -5% of cases;
- Fetal death;
- Premature birth.