Browsing by Subject "TRISOMY-21"

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  • Teder, Hindrek; Paluoja, Priit; Rekker, Kadri; Salumets, Andres; Krjutškov, Kaarel; Palta, Priit (2019)
    Non-invasive prenatal testing (NIPT) enables accurate detection of fetal chromosomal trisomies. The majority of publicly available computational methods for sequencing-based NIPT analyses rely on low-coverage whole-genome sequencing (WGS) data and are not applicable for targeted high-coverage sequencing data from cell-free DNA samples. Here, we present a novel computational framework for a targeted high-coverage sequencing-based NIPT analysis. The developed framework uses a hidden Markov model (HMM) in conjunction with a supplemental machine learning model, such as decision tree (DT) or support vector machine (SVM), to detect fetal trisomy and parental origin of additional fetal chromosomes. These models were developed using simulated datasets covering a wide range of biologically relevant scenarios with various chromosomal quantities, parental origins of extra chromosomes, fetal DNA fractions, and sequencing read depths. Developed models were tested on simulated and experimental targeted sequencing datasets. Consequently, we determined the functional feasibility and limitations of each proposed approach and demonstrated that read count-based HMM achieved the best overall classification accuracy of 0.89 for detecting fetal euploidies and trisomies on simulated dataset. Furthermore, we show that by using the DT and SVM on the HMM classification results, it was possible to increase the final trisomy classification accuracy to 0.98 and 0.99, respectively. We demonstrate that read count and allelic ratio-based models can achieve a high accuracy (up to 0.98) for detecting fetal trisomy even if the fetal fraction is as low as 2%. Currently, existing commercial NIPT analysis requires at least 4% of fetal fraction, which can be possibly a challenge in case of early gestational age (35 kg/m2). More accurate detection can be achieved at higher sequencing depth using HMM in conjunction with supplemental models, which significantly improve the trisomy detection especially in borderline scenarios (e.g., very low fetal fraction) and enables to perform NIPT even earlier than 10 weeks of pregnancy.
  • Chen, An; Tenhunen, Henni; Torkki, Paulus; Heinonen, Seppo; Lillrank, Paul; Stefanovic, Vedran (2017)
    Introduction Nowadays, an important decision for pregnant women is whether to undergo prenatal testing for aneuploidies and which tests to uptake. We investigate the factors influencing women's choices between non-invasive prenatal testing (NIPT) and invasive prenatal tests in pregnancies with elevated a priori risk of fetal aneuploidies. Methodology This is a mixed-method study. We used medical data (1st Jan 2015-31st Dec 2015) about women participating in further testing at Fetomaternal Medical Center at Helsinki University Hospital and employed Chi-square tests and ANOVA to compare the groups of women choosing different methods. Multinomial logistic regressions revealed the significant clinical factors influencing women's choice. We explored the underlying values, beliefs, attitudes and other psychosocial factors that affect women's choice by interviewing women with the Theory of Planned Behavior framework. The semi-structured interview data were processed by thematic analysis. Results Statistical data indicated that gestational age and counseling day were strong factors influencing women's choice. Interview data revealed that women's values and moral principles on pregnancy and childbirth chiefly determined the choices. Behavioral beliefs (e.g. safety and accuracy) and perceived choice control (e.g. easiness, rapidness and convenience) were also important and the major trade-offs happened between these constructs. Discussion Values are the determinants of women's choice. Service availability and convenience are strong factors. Medical risk status in this choice context is not highly influential. Choice aids can be developed by helping women to identify their leading values in prenatal testing and by providing lists of value-matching test options and attributes.
  • Äyräs, Outi; Rahkola-Soisalo, Päivi; Kaijomaa, Marja; Tikkanen, Minna; Paavonen, Jorma; Stefanovic, Vedran (2019)
    Objective: To bring new accuracy to the prognosis of outcomes of euploid fetuses with an extremely high risk in the first-trimester combined screening when compared to the low-risk group. Study design: The data included pregnancies with a trisomy 21 risk >= 1:50 in the combined first-trimester screening but normal fetal chromosomes. The control group had a risk value Results: The study comprised 483 women (161 cases and 322 controls). The mean follow-up time of children born alive was 61.4 months. An adverse outcome was detected in 11.8% of the cases and in 5.9% of the controls. After adjusting the values of mothers age, parity, and smoking habit the odds ratio for an adverse outcome was 2.1 (95% CI: 1.0-4.5, p = 0.05) for cases. When evaluating the effect of 1 SD increase in MOM of PAPP-A or 1 SD decrease in MOM of NT or beta-hCG to any adverse outcome, 1 SD increase in PAPP-A MOM decreased the risk of adverse outcome by OR 0.48 (95% CI: 0.3 - 0.8, p = 0.05) while the others were not significant. Conclusion: Euploid fetuses with a high risk in the combined first-trimester screening have a twofold risk for adverse outcomes when compared to those with a low risk. (C) 2019 Elsevier B.V. All rights reserved.
  • Vuorenlehto, Leena; Hinnelä, Kaisa; Äyräs, Outi; Ulander, Veli-Matti; Louhiala, Pekka; Kaijomaa, Marja (2021)
    Objective To study women's apprehensions, understanding and experiences of counselling concerning a screen-positive result in screening for fetal chromosomal defects. Methods A questionnaire study including different steps of the prenatal screening process was carried out in Helsinki University Hospital. Women's experiences concerning counselling immediately after a screen-positive result and during further examinations in the Fetal Medicine Unit (FMU) were analyzed. Results 143 women filled in the questionnaire. Less than half of the women considered the primary counselling after a screen-positive result to be explicit (43.9%) and sufficient (43.1%). In the FMU, 88.3% and 89.8% of women were satisfied with the explicitness and sufficiency of counselling. Most women (75%) experienced worry before further examinations but less than half (45%) had considered their personal values concerning diagnostic tests. Half (50.5%) of women expected the worry to continue even if diagnostic tests turn out normal. Most (81%) women were aware that diagnostic tests are voluntary and were confident (85.3%) with their decision to participate. Conclusions After a screen-positive result, women have unanswered questions, experience anxiety and confusion. The possibility of an abnormal screening result is not seriously considered beforehand. To enable an informed consent for prenatal screening, improvements in prescreening counselling during the first visits of antenatal care need to be made.