Abstract
Aim: Non-invasive prenatal test (NIPT) has become widespread over the years with higher probabilities of detection and fewer false positives with regard to traditionally used screening techniques. We aimed to document the experience of introducing this kind of equipment intoiclinical practice, evaluate its impact on the detection of fetal-aneuploidies, analyze the demographic characteristics of females undergoing 1.trimester fetal-aneuploidy screening testing with those choosing the NIPT, and assess elements influencing cfDNA fetal fraction.
Materials and Methods: Our research was designed as an observational, retrospective research of 406 pregnant females who underwent fetal-aneuploidy screening in the course of pregnancy, from January 2019 to April 2023. Some patients had the 1.trimester fetal-aneuploidy screening test between 11-13.weeks, while another group of patients chose to undergo the NIPT at their own request. Any abnormalities in trisomy 13,18,21 were reported in the NIPT results. Maternal age, parity, history of miscarriage, presence of hypertension, fetal anomaly detected on ultrasound were questioned.
Results: The average age of females who chose the 1.trimester fetal-aneuploidy screening test was 31.17±4.00, and that of those who chose NIPT was 32.84±5.09, and it was seen to be significantly higher in the NIPT group (p<0.01). The history of miscarriage in patients undergoing NIPT was significantly higher with regard to the other group (p=0.027). The presence of pregestational diabetes mellitus and hypertension in patients who underwent NIPT was found to be significantly higher than the other group (p=0.016, p=0.024 respectively). Age and BMI have a statistically significant negative connection versus cfDNA fetal fraction (p<0.01, r=-0.506) (p<0.01, r=-0.509).
Conclusion: Our study showed that the area of prenatal aneuploidy screening was greatly impacted by the introduction of NIPT, which replaced the 1.trimester screening test and decreased the number of intrusive testing. Our findings may be used as a reference for prenatal treatment and can offer clinics useful information when integrating NIPT into the prenatal screening flow.
References
- Yüreğir ÖÖ, Büyükkurt S, Koç F, Pazarbaşı A. Prenatal (Doğum Öncesi) Tanı. Aktd. 2012; 21(1).
- Nussbaum RL MR, Willard HF. Principles of Clinical Cytogenetics Thompson and Thompson Genetics, in Medicine Sixth Edition. Philadelphia: W.B. Saunders Company.2001;307-8.
- (KOSIS) KSIS. Basic demographic information of the nation. In: WaFA Moh, editor. Seoul, South Korea. 2016.
- Bianchi DW, Chiu RWK. Sequencing of Circulating Cell-free DNA during Pregnancy. N Engl J Med. 2018 Aug 2;379(5):464-473. doi: 10.1056/NEJMra1705345. PMID: 30067923; PMCID: PMC10123508.
- (KOSIS) KSIS. Prevalence of congenital anomalies in newborns. In: WaFA Moh, editor. Seoul, South Korea. 2006.
- Oepkes D, Page-Christiaens GC, Bax CJ, Bekker MN, Bilardo CM, Boon EM, et al. Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part I-clinical impact. Prenat Diagn. 2016; 36(12): 1083-90.
- Balkan M, Erdemoğlu M, Alp MN, Budak T. Patau Sendromlu Bir Prenatal Tanı Olgu Sunumu. Diclemedj. Haziran 2008;35(2):145-148.
- Yenilmez ED, Tuli A. İnvaziv Olmayan Bir Prenatal Tanı Yöntemi; Maternal Plazmadaki Serbest Fetal DNA. Arşiv Kaynak Tarama Dergisi. 2013; 22(3):317-34.
- Fuchs F, Riis P. Antenatal sex determination. Nature.1956; 18(177).
- Antonarakis SE, Skotko BG, Rafii MS., et al. Down syndrome. Nat Rev Dis Primers. 2020; 6(9).
- Norton ME, Brar H, Weiss J, Karimi A, Laurent LC, Caughey AB, et al. Non-Invasive Chromosomal Evaluation (NICE) Study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012; 207(2).
- Nicolaides KH, Syngelaki A, Ashoor G, Birdir C, Touzet G. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. Am J Obstet Gynecol. 2012; 207(5).
- Ashoor G, Syngelaki A, Wagner M, Birdir C, Nicolaides KH. Chromosome-selective sequencing of maternal plasma cell-free DNA for first-trimester detection of trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012; 206(4).
- Van-Opstal D, Srebniak MI, Polak J, de-Vries F, Govaerts LC, Joosten M, et al. False Negative NIPT Results: Risk Figures for Chromosomes 13, 18 and 21 Based on Chorionic Villi Results in 5967 Cases and Literature Review. PLoS One. 2016; 11(1).
- Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock CH, Bukowski R, et al. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med. 2005; 353(19): 2001-11.
- Nicolaides KH. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat Diagn. 2011; 31(1): 7-15.
- Norton ME, Baer RJ, Wapner RJ, Kuppermann M, Jelliffe-Pawlowski LL, Currier RJ. Cell-free DNA vs sequential screening for the detection of fetal chromosomal abnormalities. Am J Obstet Gynecol. 2016; 214(6): 727.
- Committee Opinion No. 640: Cell-Free DNA Screening for Fetal Aneuploidy. Obstet Gynecol. 2015; 126(3).
- Gregg AR, Skotko BG, Benkendorf JL, Monaghan KG, Bajaj K, Best RG, et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016; 18(10): 1056-65.
- Wang E, Batey A, Struble C, Musci T, Song K, Oliphant A. Gestational age and maternal weight effects on fetal cell-free DNA in maternal plasma. Prenat Diagn. 2013; 33(7): 662-6.
- Norton ME, Jacobsson B, Swamy GK, Laurent LC, Ranzini AC, Brar H, et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. 2015; 372(17): 1589-97.
- Palomaki GE, Kloza EM, Lambert-Messerlian GM, van den Boom D, Ehrich M, Deciu C, et al. Circulating cell free DNA testing: are some test failures informative? Prenat Diagn. 2015; 35(3): 289-93.
- Platt LD, Janicki MB, Prosen T, Goldberg JD, Adashek J, Figueroa R, et al. Impact of noninvasive prenatal testing in regionally dispersed medical centers in the United States. Am J Obstet Gynecol. 2014; 211(4).
- Committee Opinion No. 545: Noninvasive prenatal testing for fetal aneuploidy. Obstet Gynecol. 2012; 120(6): 1532-4.
Abstract
Amaç: Non-invaziv prenatal test (NIPT), geleneksel olarak kullanılan tarama yöntemlerinden daha üstün saptama oranları ve düşük yanlış pozitiflik oranlarıyla yıllar içinde yaygınlaşmıştır. Çalışmamızda, bu teknolojinin fetal anöploidilerin saptanmasına yönelik yaklaşımlarımıza etkisini raporlamak, 1. Trimester fetal anöploidi taraması yapılanların özelliklerini, NIPT testini seçenlerle karşılaştırmak ve serbest DNA fetal fraksiyonunu etkileyen faktörleri değerlendirmek amaçlanmıştır.
Gereç ve Yöntem: Çalışmamız, Ocak 2019-Nisan 2023 arasında prenatal dönemde fetal anöploidi taraması yapılan 406 gebeye ilişkin gözlemsel, retrospektif bir çalışma olarak tasarlandı. Hastaların bir bölümü 11-13.hafta arasında 1. trimester fetal anöploidi tarama testi yaptırmış olup, bir grup hasta ise kendi isteğiyle NIPT yaptırmıştır. NIPT sonuçlarında trizomi 13,18 ve 21 kromozomlarındaki olası bir anomali rapor edildi. Anne yaşı, gebelik sayısı, abortus öyküsü, hipertansiyon varlığı, ultrasonda saptanmış fetal anomali varlığı gibi demografik veriler çalışmada sorgulandı.
Bulgular: 1. trimester fetal anöploidi taraması testini seçen kadınların ortalama yaşı 31,17±4,00, NIPT’i seçenlerin ise 32,84±5,09 olarak saptanmış olup, NIPT grubunda anlamlı yüksek saptanmıştır (p<0.01). NIPT yapılan hastalarda abortus öyküsü, diğer gruba göre anlamlı şeklide yüksek olduğu tespit edilmiştir (p=0.027). NIPT yapılan hastalarda pregestasyonal diabetes mellitus ve hipertansiyon varlığı, diğer gruba göre anlamlı yüksek saptanmıştır (p=0.016, p=0.024 sırasıyla). Yaş ve vücut kitle indeksi ile hücre dışı serbest DNA fetal fraksiyonunu arasında sırasıyla negatif yönlü bir ilişki saptanmıştır (p<0.01, r=-0,506) (p<0.01, r=-0,509).
Sonuç: NIPT uygulamasının, 1. trimester fetal anöploidi taraması testlerinin yerini alarak ve invaziv testleri azaltarak doğum öncesi anöploidi taraması alanını önemli ölçüde etkilediğini göstermiştir. Çalışmamız, NIPT’nin prenatal tarama akışına entegrasyonu sürecinde kliniklere pratik bilgiler sunabilir ve doğum öncesi bakımda referans bilgiler verebilir.
References
- Yüreğir ÖÖ, Büyükkurt S, Koç F, Pazarbaşı A. Prenatal (Doğum Öncesi) Tanı. Aktd. 2012; 21(1).
- Nussbaum RL MR, Willard HF. Principles of Clinical Cytogenetics Thompson and Thompson Genetics, in Medicine Sixth Edition. Philadelphia: W.B. Saunders Company.2001;307-8.
- (KOSIS) KSIS. Basic demographic information of the nation. In: WaFA Moh, editor. Seoul, South Korea. 2016.
- Bianchi DW, Chiu RWK. Sequencing of Circulating Cell-free DNA during Pregnancy. N Engl J Med. 2018 Aug 2;379(5):464-473. doi: 10.1056/NEJMra1705345. PMID: 30067923; PMCID: PMC10123508.
- (KOSIS) KSIS. Prevalence of congenital anomalies in newborns. In: WaFA Moh, editor. Seoul, South Korea. 2006.
- Oepkes D, Page-Christiaens GC, Bax CJ, Bekker MN, Bilardo CM, Boon EM, et al. Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part I-clinical impact. Prenat Diagn. 2016; 36(12): 1083-90.
- Balkan M, Erdemoğlu M, Alp MN, Budak T. Patau Sendromlu Bir Prenatal Tanı Olgu Sunumu. Diclemedj. Haziran 2008;35(2):145-148.
- Yenilmez ED, Tuli A. İnvaziv Olmayan Bir Prenatal Tanı Yöntemi; Maternal Plazmadaki Serbest Fetal DNA. Arşiv Kaynak Tarama Dergisi. 2013; 22(3):317-34.
- Fuchs F, Riis P. Antenatal sex determination. Nature.1956; 18(177).
- Antonarakis SE, Skotko BG, Rafii MS., et al. Down syndrome. Nat Rev Dis Primers. 2020; 6(9).
- Norton ME, Brar H, Weiss J, Karimi A, Laurent LC, Caughey AB, et al. Non-Invasive Chromosomal Evaluation (NICE) Study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012; 207(2).
- Nicolaides KH, Syngelaki A, Ashoor G, Birdir C, Touzet G. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. Am J Obstet Gynecol. 2012; 207(5).
- Ashoor G, Syngelaki A, Wagner M, Birdir C, Nicolaides KH. Chromosome-selective sequencing of maternal plasma cell-free DNA for first-trimester detection of trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012; 206(4).
- Van-Opstal D, Srebniak MI, Polak J, de-Vries F, Govaerts LC, Joosten M, et al. False Negative NIPT Results: Risk Figures for Chromosomes 13, 18 and 21 Based on Chorionic Villi Results in 5967 Cases and Literature Review. PLoS One. 2016; 11(1).
- Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock CH, Bukowski R, et al. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med. 2005; 353(19): 2001-11.
- Nicolaides KH. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat Diagn. 2011; 31(1): 7-15.
- Norton ME, Baer RJ, Wapner RJ, Kuppermann M, Jelliffe-Pawlowski LL, Currier RJ. Cell-free DNA vs sequential screening for the detection of fetal chromosomal abnormalities. Am J Obstet Gynecol. 2016; 214(6): 727.
- Committee Opinion No. 640: Cell-Free DNA Screening for Fetal Aneuploidy. Obstet Gynecol. 2015; 126(3).
- Gregg AR, Skotko BG, Benkendorf JL, Monaghan KG, Bajaj K, Best RG, et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016; 18(10): 1056-65.
- Wang E, Batey A, Struble C, Musci T, Song K, Oliphant A. Gestational age and maternal weight effects on fetal cell-free DNA in maternal plasma. Prenat Diagn. 2013; 33(7): 662-6.
- Norton ME, Jacobsson B, Swamy GK, Laurent LC, Ranzini AC, Brar H, et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. 2015; 372(17): 1589-97.
- Palomaki GE, Kloza EM, Lambert-Messerlian GM, van den Boom D, Ehrich M, Deciu C, et al. Circulating cell free DNA testing: are some test failures informative? Prenat Diagn. 2015; 35(3): 289-93.
- Platt LD, Janicki MB, Prosen T, Goldberg JD, Adashek J, Figueroa R, et al. Impact of noninvasive prenatal testing in regionally dispersed medical centers in the United States. Am J Obstet Gynecol. 2014; 211(4).
- Committee Opinion No. 545: Noninvasive prenatal testing for fetal aneuploidy. Obstet Gynecol. 2012; 120(6): 1532-4.
Details
| Primary Language | English |
|---|---|
| Subjects | Obstetrics and Gynaecology |
| Journal Section | Research Articles |
| Authors | |
| Publication Date | December 9, 2024 |
| Submission Date | June 11, 2024 |
| Acceptance Date | September 14, 2024 |
| Published in Issue | Year 2024 |