Prenatal screening for Down syndrome

First-trimester biochemical screening

The basis for early detection of chromosomal abnormalities is combined screening, which is mandatory at 11–14 weeks of gestation. It includes a standardized ultrasound examination and maternal serum analysis for specific proteins.

Pregnancy with a fetus having Down syndrome presents a characteristic biochemical profile:

• Free β-subunit of hCG (β-hCG) — levels are significantly higher than normal for the gestational age. Quantitative determination of serum β-hCG is the method of choice due to its high sensitivity and specificity. Normally, hCG increases up to the 15th–17th week (peaking at 10–11 weeks), but in pathology, its concentration is excessive.
• PAPP-A (Pregnancy-Associated Plasma Protein-A) — levels are below normal. This pregnancy-associated plasma protein A is synthesized by the syncytiotrophoblast. It appears in the blood from the 5th week and progressively increases, but its deficiency at 11–14 weeks indicates a high risk of genetic mutations.

The combination of ultrasound and biochemistry detects up to 90% of fetuses with Down syndrome. Special computer software for individual risk calculation is used to improve diagnostic efficiency.

Confounding factors and second-trimester markers

It is important to understand that abnormal levels of PAPP-A and β-hCG are not absolutely specific solely for congenital fetal pathology. Biochemical screening results can be influenced by:

• Maternal body weight.
• Extragenital diseases (diabetes mellitus, liver pathology).
• Obstetric complications (preeclampsia, Rh incompatibility, threatened abortion, missed miscarriage).
• Multiple pregnancy and placental pathologies (hypoplasia, hyperplasia, cysts, tumors, placental abruption sites).

If a patient missed the first screening, diagnostics are supplemented in the second trimester (at 16–18 weeks). During this period, unconjugated (free) estriol, produced by the fetoplacental complex, is evaluated. In Down syndrome, its concentration in maternal blood is reliably decreased. Alpha-fetoprotein can also be tested at this time, but its reliable elevation is characteristic of neural tube defects and anterior abdominal wall defects rather than Down syndrome.

Non-invasive and preimplantation diagnosis

Modern obstetrics employs high-precision methods that do not require penetration into the uterine cavity and amniotic fluid:

• Non-invasive prenatal testing (NIPT). Available from the 10th week of pregnancy. The method is based on isolating and assessing the risk of chromosomal abnormalities through the analysis of cell-free fetal DNA, which freely circulates in the pregnant woman's bloodstream.
• Preimplantation genetic diagnosis. Possible exclusively within in vitro fertilization (IVF) programs. For genetic testing of gene or chromosomal mutations, a biopsy of one or both polar bodies of the oocyte, or cells of the embryo itself (blastomeres, trophectoderm cells) is performed before transfer into the uterine cavity.

Invasive methods and associated anomalies

Definitive confirmation of the diagnosis requires cytogenetic examination of tissues of fetal origin. Indications for invasive intervention for karyotyping at 11–14 weeks include: ultrasound soft markers, decreased PAPP-A, elevated β-hCG, and a calculated individual risk greater than 1 in 250 (threshold value).

Depending on the gestational age and laboratory capabilities, different approaches are used:

1. Chorionic villus sampling — performed at 8–12 weeks.
2. Amniocentesis — sampling of amniotic fluid at 16–22 weeks (early amniocentesis is possible at 13–14 weeks).
3. Cordocentesis — puncture of the umbilical cord, performed from the 18th week.

These methods allow the diagnosis of all forms of chromosomal pathology. It should be noted that Down syndrome (trisomy 21) is very frequently accompanied by severe combined developmental anomalies. Specifically, when karyotyping patients with congenital heart defects (CHD), chromosomal abnormalities are detected in more than a third of cases, and trisomy 21 is one of the most characteristic.

Class and exam questions

What else to study on this topic

• Ultrasound markers of fetal chromosomal pathology in the 1st trimester
• Methods for calculating individual genetic risk
• Technique of amniocentesis and chorionic villus sampling
• Diagnosis of neural tube defects (the role of alpha-fetoprotein)
• Impact of maternal extragenital pathology on screening results

Other topics in the "Obstetrics" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.