Combined first trimester screening for fetal chromosomal abnormalities in University Hospital Centre of Split

Cilj istraživanja: Cilj ovog istraživanja je prikazati rezultate i istražiti uspješnost kombiniranog testa probira na kromosomopatije ploda u KBC Split. Materijali i metode: Provedeno je presječno retrospektivno istraživanje. Uključene su sve trudnice u kojih je proveden kombinirani test probira u Klinici za ženske bolesti i porode KBC Split od 1. siječnja 2011. do 31. prosinca 2017. godine. Podatci su prikupljeni iz digitalne arhive Zavoda za medicinsko laboratorijsku dijagnostiku i arhive Klinike za ženske bolesti i porode. Promatrani su sljedeći podatci: a) godina izvođenja kombiniranog testa, b) životna dob ispitanica, c) navršeni tjedan trudnoće, d) vrijednosti beta podjedinice humanog korionskog gonadotropina (β-hCG) iz periferne krvi majke, e) vrijednost proteina A udruženog s trudnoćom (engl. pregnancy associated protein A; PAPP-A) iz periferne krvi majke, f) vrijednost ultrazvučnog biljega nuhalne prozirnosti, g) vrijednosti a priori rizika od kromosomopatija ploda po životnoj dobi trudnice, h) vrijednosti rizika od kromosomopatija ploda izračunatog kombiniranim testom, i) indikacija za izvođenje amniocenteze (RACZ), j) prethodna provedenost kombiniranog testa u žena kojima je odobren prekid trudnoće iz eugeničkih ili medicinskih razloga, k) prethodna provedenost kombiniranog testa u žena koje su rodile dijete s kromosomopatijom. Rezultati: Udio probirnih testova na kromosomopatije ploda u ukupnom broju porođaja iznosio je 27,28%, a među njima je većinu činio kombinirani test (81,89%). Kombiniranom testu u istraživanom razdoblju pristupilo je 6898 trudnica. Najveći broj trudnica pripadao je dobnoj skupini od 30 do 35 godina (39,99%). Kombinirani test provodio se između 10. i 14. tjedna trudnoće, najviše u 12. tjednu (48,93%). Porastom životne dobi trudnice statistički se značajno povećava broj a priori visokorizičnih trudnica za trisomiju 21 po životnoj dobi, kao i po rezultatima kombiniranog testa (P<0,001). Broj a priori visokorizičnih trudnica za trisomiju 21 po životnoj dobi (1457 trudnica) značajno je veći od broja visokorizičnih trudnica po rezultatima kombiniranog testa (239 trudnica) (P<0,001). Od 1457 a priori visokorizičnih trudnica za trisomiju 21 po životnoj dobi, visoki je rizik potvrđen kombiniranim testom u njih 118. Kombiniranim je testom iz skupine a priori niskorizičnih trudnica za trisomiju 21 po životnoj dobi (mlađe od 36 godina) pronađena 121 visokorizična trudnica koja probirom po životnoj dobi ne bi bila detektirana. Porastom životne dobi trudnice statistički se značajno povećava prosječna vrijednost a priori rizika od trisomije 21 po životnoj dobi trudnice, kao i po rezultatima kombiniranog testa (P<0,001). Prosječna vrijednost a priori rizika od trisomije 21 po životnoj dobi veća je od rizika izračunatog kombiniranim testom. Postoji pozitivna korelacija između vrijednosti a priori rizika od trisomije 21 po životnoj dobi i rizika izračunatog kombiniranim testom probira (r=0,377, P<0,001). U 11 od 48 (22,92%) majki djece rođene s kromosomopatijim tijekom trudnoće izveden je kombinirani test. U 10 od 40 (25%) žena kojima je odobren pobačaj iz eugeničkih razloga zbog kromosomopatije ploda rizičan kombinirani test bio je indikacija za RACZ. Kombiniranim testom uspješno je detektirano 17 od navedene 21 trudnoća s kromosomopatijom. Uz fiksnu graničnu vrijednost od 1:250, procijenjena osjetljivost kombiniranog testa za ispitivanu populaciju iznosi 81% uz specifičnost od 96,8% (AUC=0,929, 95% CI 0,859-1,000, P<0,001). Zaključak: Kombiniranim testom u KBC Split uspješno se postiže osnovni cilj probirnih metoda na kromosomopatije ploda – pronalaženje visokorizičnih trudnica među ženama mlađima od 36 godina. Moguće je i dio a priori visokorizičnih trudnica za trisomiju 21 (36 godina i starije) svrstati u niskorizične i tako smanjiti broj RACZ i spontanih pobačaja kao neizbježnih komplikacija invazivnih zahvata prenatalne dijagnostike.Objective: The aim of this study is to present the results, as well as to investigate the success rate of the combined first trimester screening for fetal chromosomal abnormalities in the University Hospital Centre of Split. Materials and methods: A retrospective cross-sectional study was carried out. The study involved all pregnant women who underwent combined first trimester screening for fetal chromosomal abnormalities in the University Hospital Centre of Split from January 1st 2011 to December 31st 2017. Relevant data was collected from the Department of Medical Laboratory Diagnostics digital archive, as well as from the Department of Gynecology and Obstetrics archive. The following data was taken into account: a) year in which the test was performed, b) age of the participants, c) gestational age, d) values of the beta subunit of human chorionic gonadotrophin (β-hCG) from the peripheral blood of the mother, e) values of the pregnancy associated protein A (PAPP-A) from the peripheral blood of the mother, f) values of the ultrasound marker nuchal translucency, g) values of a priori risk of fetal chromosomal abnormalities based on the age of the mother, h) values of risk of fetal chromosomal abnormalities calculated with the combined first trimester screening, i) indication for performing amniocentesis, j) previous implementation of the combined first trimester screening in women to whom abortion was approved for eugenic or medical reasons, k) previous implementation of the combined first trimester screening in women who bore a child with chromosomal abnormalities. Results: The amount of screenings for fetal chromosomal abnormalities in the total number of births was equivalent to 27.28%, and most of those screenings were in fact combined first trimester screenings (81.89%). A total of 6898 pregnant women underwent the combined first trimester screening in the research period. Most women were between 30 and 35 years of age (39.99%). The combined screening was performed between the 10th and the 14th week of pregnancy, mostly in the 12th week (48.93%). With the increase of a patient’s age, a statistically significant increase in the number of pregnant women who were a priori at high risk for trisomy 21 based on age, as well as on the combined test results was detected (P<0.001). The number of pregnant women who were a priori at high risk for trisomy 21 based on age (1457 pregnant women) was significantly higher than the number of those at high risk for it based on the combined screening results (239 pregnant women) (P<0.001). Out of 1457 pregnant women who were a priori at high risk for trisomy 21 based on age, the combined test led to determination of a high-risk pregnancy in 118 cases. When it comes to pregnant women who were a priori at low risk for trisomy 21 based on age (under 36 years of age), the combined test led to determination of 121 cases of high-risk pregnancies, which would not have been detected with screening based on age. With the increase of a patient’s age, a statistically significant increase in the mean value of a priori risk for trisomy 21 based on age, as well as on the combined test results was detected (P<0.001). The mean value of a priori risk for trisomy 21 based on age was higher than the one calculated with the combined first trimester screening. There was a positive correlation between the value of a priori risk for trisomy 21 based on age and the one calculated with the combined first trimester screening (r=0.377, P<0.001). A total of 11 out of 48 (22.92%) mothers of children born with chromosomal abnormalities underwent combined screening during their pregnancy. In 10 out of 40 (25%) women to whom abortion was approved for eugenic reasons related to fetal chromosomal abnormalities the high-risk combined screening was an indication for amniocentesis. The combined screening led to a successful determination of 17 of the aforementioned 21 pregnancies with chromosomal abnormalities. With the cut-off value set at 1:250, the estimated sensitivity of the combined screening for the research population was equivalent to 81%, with the specificity of 96.8% (AUC=0.929, 95% CI 0.859-1.000, P