Rani kombinirani probir i neinvazivni prenatalni testovi u prenatalnom probiru kromosomopatija

master's thesis

• Title (english): First trimester combined screening and non-invasive prenatal testing in prenatal screening for chromosomal abnormalities
• Author: Tea Škrobo
• Mentor: Trpimir Goluža (mentor)
• Committee member: Vesna Elveđi-Gašparović (predsjednik povjerenstva)
• Committee member: Dinka Pavičić Baldani (član povjerenstva)
• Committee member: Trpimir Goluža (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2024-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Gynecology and Obstetrics

Abstract

Kromosomopatija je promjena u strukturi ili broju kromosoma koja može uzrokovati različite kliničke posljedice. Abnormalnosti broja kromosoma dijele se na poliploidije i aneuploidije, gdje dolazi do gubitka ili dobitka jednog kromosoma. Identifikacija ovih abnormalnosti je ključna za preventivne strategije, genetsko savjetovanje i odgovarajuće liječenje. Najčešći test koji se nudi je rani kombinirani probir u prvom tromjesečju. On uključuje detaljni ultrazvuk za mjerenje udaljenosti tjeme-trtica i nuhalne translucencije fetusa u razdoblju od 11. do 13. tjedna gestacije, uz serumski probir slobodnog beta-humanog korionskog gonadotropina (βhCG) i proteina A povezanog s trudnoćom (PAPP-A) između 8. i 13. tjedna gestacije. Iako rani kombinirani probir ima stopu detekcije od 90 %, glavni problem je relativno visoka stopa lažno pozitivnih rezultata, gdje bi 1 od 20 (5 %) pacijentica bila nepotrebno zabrinuta. S pojavom neinvazivnog prenatalnog testiranja (NIPT) vrlo je izgledno da će upravo ono zamijeniti klasični rani probir, a neke zemlje su ga već uvele u svoj nacionalni probirni program. Radi se o tehnici koja analizira kratke fragmente slobodne fetalne DNK uzduž cijelog genoma kako bi se identificirale kromosomske abnormalnosti poput Patauovog (T13), Edwardsovog (T18) i Downovog sindroma (T21). Zahvaljujući napretku masovnog paralelnog sekvenciranja, NIPT je značajno smanjio upotrebu invazivnih metoda poput amniocenteze i biopsije korionskih resica te postaje ključan probirni test zbog svoje jednostavnosti, neinvazivnosti i niskog rizika. Međutim, ovi testovi se često provode bez adekvatnog genetičkog savjetovanja te su katkad pogrešno interpretirani kao dijagnostički testovi, a zapravo su testovi probira. Neovisno o tome, uvođenje neinvazivnog prenatalnog testiranja predstavlja značajan napredak u identifikaciji kromosomopatija, omogućujući precizniju dijagnostiku i unaprjeđujući skrb za trudnice i nerođene potomke.

Abstract (english)

Chromosomopathy is a change in the structure or number of chromosomes that can cause various clinical consequences. Numerical chromosomal abnormalities can be polyploidies or aneuploidies, involving the loss or gain of a single chromosome. Identifying these abnormalities is crucial for preventive strategies, genetic counselling, and appropriate treatment. The most common test offered is the combined first trimester screening. It includes detailed ultrasound to measure the crown-rump length and nuchal translucency of the fetus between the 11th and 13th weeks of gestation, combined with serum screening of free beta-human chorionic gonadotropin (βhCG) and pregnancy-associated plasma protein A (PAPP-A) between the 8th and 13th weeks of gestation. Although early combined screening has a detection rate of 90 %, the main issue is the relatively high rate of false positive results, where 1 out of 20 (5 %) patients would be unnecessarily concerned. With the emergence of non-invasive prenatal testing (NIPT), it is very likely that it will replace traditional early screening, and some countries have already incorporated it into their national screening programs. This technique analyses cell-free DNA fragments across the whole genome to identify chromosomal abnormalities such as Patau (T13), Edwards (T18), and Down syndrome (T21). Thanks to the advancement of massive parallel sequencing, NIPT has significantly reduced the use of invasive methods such as amniocentesis and chorionic villus sampling and will probably become a key screening test due to its simplicity, non-invasiveness, and low risk. However, these tests are often performed without adequate genetic counselling and are sometimes wrongly interpreted as diagnostic tests, when in fact they are screening tests. Nonetheless, the introduction of non-invasive prenatal testing represents a significant advancement in the identification of chromosomal abnormalities, enabling more precise diagnosis and improving care for pregnant women and their unborn children.

• Keywords: Downov sindrom; metode probira; NIPT; prenatalna dijagnostika; slobodna cirkulirajuća DNK; trisomija
• Keywords (english): Down syndrome; screening methods; NIPT; prenatal diagnosis; cell-free circulating DNA; trisomy
• Language: croatian
• URN:NBN: urn:nbn:hr:105:500543
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-07-01 12:58:08