Objective To investigate the uptake of different components of first trimester screening (FTS) and the impact on invasive diagnostic testing (IPT) since the introduction of non-invasive prenatal testing (NIPT) at a level III center. Methods Retrospective data analysis was conducted for singleton pregnancies that presented for FTS between 01/2019–12/2019 (group 1, n = 990). Patients were categorized into three risk groups: low risk for trisomy 21 (< 1 : 1000), intermediate risk (1 : 101–1 : 1000) and high risk (≥ 1 : 100). Uptake of NIPT and IPT was analyzed for each of the risk groups. Results were compared to a previous cohort from 2012/2013 (immediately after the introduction of NIPT, group 2, n = 1178). Results Group 1 showed a significant increase in the use of NIPT as part of FTS (29.5% vs. 3.7% for group 2, p = 0.001) in all three risk groups. Overall IPT rates were lower in group 1 (8.6%) vs. group 2 (11.3%, p = 0.038), mainly due to a significant reduction of IPT in the intermediate risk group. IPT rates in the high-risk group remained stable over time. Conclusion Appropriate clinical implementation of NIPT is still currently a challenge for prenatal medicine experts. Our data suggest that widespread uptake of NIPT is becoming more common these days; however, a contingent approach might prevent redundant uptake. 相似文献
It has been shown that in non-invasive prenatal testing (NIPT) there is a small chance of a false-positive or false-negative result. This is partly due to the fact that the fetal cell-free DNA present in maternal plasma is derived from the cytotrophoblast of chorionic villi (CV), which is not always representative for the fetal karyotype due to chromosomal mosaicism. Therefore, a positive NIPT result should always be confirmed with invasive testing, preferably amniocentesis, in order to investigate the fetal karyotype. However, since this invasive test can only be safely performed after 15.5 weeks of gestation while NIPT can be done from the 10th week of gestation, this potentially means an unacceptable long waiting time for the prospective parents to receive a definitive result. Based on our experience with cytogenetic investigations in CV and the literature, we determined whether CV sampling may be appropriate for confirmation of an abnormal NIPT result. 相似文献
ObjectiveWe present prenatal diagnosis of pseudomosaicism for trisomy 20 at amniocentesis with a negative non-invasive prenatal testing (NIPT) result in a pregnancy with a favorable outcome.Case reportA 33-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation, which revealed a karyotype of 47,XX,+20[8]/46,XX[31]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1–22,X) × 2, consistent with no genomic imbalance. She was referred to the hospital for repeat amniocentesis at 23 weeks of gestation. At repeat amniocentesis, cultured amniocytes had a karyotype of 47,XX,+20[2]/46,XX[33]. The parental karyotypes were normal. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes using SurePrint G3 Unrestricted CGH ISCA v2, 8 × 60 K (Agilent Technologies, Santa Clara, CA, USA) revealed no genomic imbalance, or arr (1–22,X) × 2, Y × 0. Interphase fluorescence in situ hybridization (FISH) analysis using the bacterial artificial chromosome (BAC) probes of RP11-266K16 [20q13.33; fluorescein isothiocyanate (FITC), spectrum green] and RP11-348I14 (20q11.1-q11.21; Texas Red, spectrum red) detected trisomy 20 signals in 4/104 uncultured amniocytes (3.8%), compared with 0/100 in the normal control. Polymorphic DNA marker analysis using the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy 20. NIPT analysis on maternal blood revealed a negative result without gene dosage increase in chromosome 20. The pregnancy was carried to term, and a healthy 2830-g female baby was delivered with no phenotypic abnormality. Both cord blood and placenta had a karyotype of 46,XX.ConclusionNIPT is useful for rapid differential diagnosis of pseudomosaicism from true mosaicism in case of mosaic trisomy 20 at amniocentesis. 相似文献
Introduction: Biological factors are known to influence the fetal fraction (FF) of cell-free DNA and may also influence the accuracy of non-invasive prenatal testing.
Material and methods: NIPT from 5267 mixed risk women across three specialist clinics in Australia were analyzed. Multivariable regression analysis was used to determine whether maternal characteristics, ultrasound, and placental biomarkers affect FF and test accuracy.
Results: FF ranged from 4% to 37% (mean 11.6%). Body mass index (BMI), gestation, and placental biomarkers were found to be significant factors associated with FF. For each unit increase in BMI, the logarithmically transformed FF, (lnFF), mean value decreased by 0.027. Each week increases in gestation, lnFF increased by 0.023. Each unit increase in free BhCG, PAPPA, and PlGF, the lnFF increased by 0.065, 0.050, and 0.17, respectively. There was no significant association between FF with either maternal age or nuchal translucency. The false-positive cases and one false-negative case did not have lower FF than the true-positive cases.
Discussion: The fetal fraction in maternal plasma cfDNA increased with gestational age, serum pregnancy-associated plasma protein A (PAPP-A), β-hCG, and PlGF and decreased with increasing maternal BMI. There was no significant correlation between low FF and test accuracy, when FF was above 4%. 相似文献
Objective: The aim of this study was to evaluate clinical use of NIPT at gestational ages of 23 weeks and above.Methods: A cohort of 5579 clinical patients with singleton gestations of 23 weeks or greater submitting a blood sample for NIPT in an 18-month period were selected for this study. Clinical outcomes were requested for samples with NIPT results indicating fetal aneuploidy and compared with NIPT findings to confirm concordance or discordance.Results: A review of clinical indications revealed that a significantly (p?0.0001) larger proportion of late-gestation samples indicated abnormal ultrasound findings with or without other indications, 6.2% and 42.1%, compared with early-gestation samples, 1.8% and 6.0%, respectively. Of 5372 reported late-gestation samples, 151 (2.8%) were reported as aneuploidy detected or suspected. In late-gestation samples, the overall observed positive predictive value (PPV) for NIPT was 64.7%, with an observed PPV of 100% in the subset of cases with multiple clinical indications including abnormal ultrasound findings.Conclusions: NIPT is a highly accurate prenatal screening option for women after 23 weeks of gestation. Women who presented for NIPT in the latter stages of pregnancy more frequently specified clinical indications of abnormal ultrasound findings than women who entered screening earlier in pregnancy. 相似文献
AbstractObjective: Noninvasive prenatal testing (NIPT) for fetal aneuploidies has been widely adopted in developed countries. Despite the sharp decrease in the cost of massively parallel sequencing, the technical know-how and skilled personnel are still one of the major limiting factors for applying this technology to NIPT in low-income settings. Here, we present the establishment and validation of our NIPT procedure called triSure for detection of fetal aneuploidies.Methods: We established the triSure algorithm based on the difference in proportion of fetal and maternal fragments from the target chromosome to all chromosomes. Our algorithm was validated using a published data set and an in-house data set obtained from high-risk pregnant women in Vietnam who have undergone amniotic testing. Several other aneuploidy calling methods were also applied to the same data set to benchmark triSure performance.Results: The triSure algorithm showed similar accuracy to size-based method when comparing them using published data set. Using our in-house data set from 130 consecutive samples, we showed that triSure correctly identified the most samples (overall sensitivity and specificity of 0.983 and 0.986, respectively) compared to other methods tested including count-based, sized-based, RAPIDR and NIPTeR.Conclusions: We have demonstrated that our triSure NIPT procedure can be applied to pregnant women in low-income settings such as Vietnam, providing low-risk screening option to reduce the need for invasive diagnostic tests. 相似文献