Clinical and Economic Evaluation after Adopting Contingent Cell-Free DNA Screening for Fetal Trisomies in South Spain.

Contingent cell-free (cf) DNA screening on the basis of the first-trimester combined test (FCT) results has emerged as a cost-effective strategy for screening of trisomy 21 (T21). Objectives: To assess performance, patients’ uptake, and cost of contingent cfDNA screening and to compare them with those of the established FCT. Methods: This is a prospective cohort study including all singleton pregnancies attending to their FCT for screening of T21 at 2 university hospitals in South Spain. When the FCT risk was ≥1:50, there were major fetal malformations, or the nuchal translucency was ≥3.5 mm, women were recommended invasive testing (IT); if the risk was between 1:50 and 1:270, women were recommended cfDNA testing; and for risks bellow 1:270, no further testing was recommended. Detection rate (DR), false-positive rate (FPR), patients’ uptake, and associated costs were evaluated. Results: We analyzed 10,541 women, including 46 T21 cases. DR of our contingent strategy was 89.1% (41/46) at 1.4% (146/10,541) FPR. Uptake of cfDNA testing was 91.2% (340/373), and overall IT rate was 2.0%. The total cost of our strategy was €1,462,895.7, similar to €1,446,525.7 had cfDNA testing not been available. Conclusions: Contingent cfDNA screening shows high DR, low IT rate, and high uptake at a similar cost than traditional screening.pre-print133 K

Perfil clínico de los pacientes tratados con evolocumab en unidades hospitalarias de nefrología en España

Describir las características clínicas de los pacientes tratados con evolocumab, las razones del inicio de la terapia y los efectos del tratamiento en la fase inicial de disponibilidad de evolocumab en las unidades de nefrología de España

Obstetric outcomes of sars-cov-2 infection in asymptomatic pregnant women

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER)Around two percent of asymptomatic women in labor test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain. Families and care providers face childbirth with uncertainty. We determined if SARS-CoV-2 infection at delivery among asymptomatic mothers had different obstetric outcomes compared to negative patients. This was a multicenter prospective study based on universal antenatal screening for SARS-CoV-2 infection. A total of 42 hospitals tested women admitted for delivery using polymerase chain reaction, from March to May 2020. We included positive mothers and a sample of negative mothers asymptomatic throughout the antenatal period, with 6-week postpartum follow-up. Association between SARS-CoV-2 and obstetric outcomes was evaluated by multivariate logistic regression analyses. In total, 174 asymptomatic SARS-CoV-2 positive pregnancies were compared with 430 asymptomatic negative pregnancies. No differences were observed between both groups in key maternal and neonatal outcomes at delivery and follow-up, with the exception of prelabor rupture of membranes at term (adjusted odds ratio 1.88, 95% confidence interval 1.13-3.11; p = 0.015). Asymptomatic SARS-CoV-2 positive mothers have higher odds of prelabor rupture of membranes at term, without an increase in perinatal complications, compared to negative mothers. Pregnant women testing positive for SARS-CoV-2 at admission for delivery should be reassured by their healthcare workers in the absence of symptoms

Análisis genético e identificación de una nueva deleción en el gen de la fibrosis quística

Tesis doctoral inédita leída en la: Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 10 de Julio de 1991

Does a High-Risk (>1/50) Result for First-Trimester Combined Screening Always Entail Invasive Testing? Which Patients from This Group Might Benefit from cfDNA Testing?

Currently, cell-free DNA (cfDNA) is offered as part of a contingent screening for patients with a first-trimester combined test (FCT) risk between 1/50 and 1/250. However, most aneuploidies are within the group of patients with a risk above 1/10. An observational, retrospective, and multi-centric study was carried out, to evaluate the theorical performance of lowering the cut-off point for the high-risk group from 1/50 to 1/10. Out of the 25,920 patients included, 25,374 (97.9%) consented to the cfDNA contingent screening for aneuploidies. With the proposed strategy, knowing that the detection rate (DR) of cfDNA testing for trisomy 21 is 99.7%, the DR for trisomy 21 would have stayed in a 93.2%, just as it was with the current strategy. In this instance, 267 (1.1%) invasive tests would have been performed, while the current strategy had a total of 307 (1.2%). The false positive rate (FPR) rate would have stayed at 5.2% in both scenarios. In conclusion, the contingent screening of aneuploidies based in the result of the FCT, offering the analysis of cfDNA to patients with an intermediate risk after lowering the cut-off point from 1/50 to 1/10, is a valid alternative that might maintain the current detection rates and avoid the complications associated with invasive testing

Contingent prenatal screening for frequent aneuploidies with cell-free fetal DNA analysis.

To analyze the results of contingent screening for common aneuploidies at our center from June 2017 to June 2019. Traditional screening tests were performed using a combination of biochemical markers and ultrasound measurements in the first and second trimesters to assess the risk of trisomies 21 (T21), 18 (T18) and 13 (T13). Cell-free DNA (cf-DNA) testing was offered (Harmony test) to pregnant women at high risk (>1/280 for T21 and > 1/150 for T13 and T18) and a normal early morphology scan. In positive cases, prenatal sampling was strongly recommended to confirm the results by gold standard methods (QF-PCR and karyotyping). Newborns' phenotypes were corroborated after birth in all cases. In this prospective study, 8153 pregnant women were enrolled, resulting in 390 at high risk according to traditional screening tests. cfDNA testing was offered to 383 women. Traditional screening tests showed a false negative rate of 9.68% for T21. Traditional test sensitivity for T21 was 90.3%, for a false positive rate of 4.17% and a positive predictive value of 7.6%. The positive and negative predictive value for cfDNA testing was 100%. The approach used avoided invasive procedures in 91.3% of women at high risk. The prevalence of chromosomal abnormalities in the population analyzed was 1 in 164, and 1 in 210 for T21. Our results show that offering cf-DNA testing to women at high risk in traditional tests (including those with risks >1 in 50) significantly reduces false positives and, therefore, the number of invasive tests. Extending the use of cf-DNA testing to intermediate risk categories may be cost effective