RESUMEN
BACKGROUND AND AIM OF THE STUDY: Scientific Societies do not recommend the use of cell-free DNA (cfDNA) testing as a first-tier screening for microdeletion and microduplication syndromes (MMs). The aim of this study was to review the current available literature on the performance of cell-free DNA as a screening for MMs. METHODS: Medline, Embase and the Cochrane Library were searched electronically from 2000 to January 2020 and articles reporting the diagnostic performance of cfDNA screening for MMs in large (>5000 cases) series were included. Between-study heterogeneity and random effect model for screen positive rate (SPR), false positive rate (FPR) and positive predictive value (PPV) were calculated. RESULTS: We identified 42 papers, seven included, for a total of 474,189 pregnancies and 210 cases of MMs. Diagnostic verification of positive cases was available overall in 486 (71.68 %) of 678 cases. The weighted pooled SPR, FPR and PPV were 0.19% (95% CI = 0.09-0.33), 0.07 (95% CI = 0.02-0.15) and 44.1 (95% CI = 31.49-63.07). In conclusion, the pooled PPV of cfDNA testing in screening for MMs was about 40%, ranging from 29% to 91%, for an overall FPR <0.1%. CONCLUSIONS: No confirmatory analysis was available in cases that did not undergo invasive testing, which were the vast majority of cases with a negative test, and therefore, the DR and the negative predictive value cannot be determined.
Asunto(s)
Ácidos Nucleicos Libres de Células/análisis , Pruebas de Detección del Suero Materno/enfermería , Madres/clasificación , Adulto , Ácidos Nucleicos Libres de Células/sangre , Femenino , Humanos , Pruebas de Detección del Suero Materno/métodos , EmbarazoAsunto(s)
Anomalías Múltiples/genética , Dosificación de Gen/genética , Predisposición Genética a la Enfermedad , Hernia Diafragmática/genética , Proteínas de Dominio T Box/genética , Anomalías Múltiples/mortalidad , Anomalías Múltiples/patología , Feto Abortado/anomalías , Femenino , Hernia Diafragmática/mortalidad , Hernia Diafragmática/patología , Humanos , Masculino , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To examine the incidence and type of chromosomal abnormalities in fetuses with first trimester ultrasound anomalies and a low-risk cfDNA test for common trisomies. METHODS: In 486 singleton pregnancies undergoing invasive testing after combined screening, a detailed first trimester ultrasound assessment was carried out and a maternal blood sample was sent for cfDNA analysis. Ultrasound and cfDNA data were analyzed in relation to fetal karyotype. RESULTS: Invasive testing demonstrated a chromosomal abnormality in 157 (32.3%) of 486 fetuses. In 348 cases with a low-risk cfDNA test for common trisomies, NT ≥ 3.5 mm and/or a major structural defect were observed in 92 (26.4%) fetuses. A chromosomal abnormality was found in 17 (18.5%; 95%CI 10.55-26.41) of these pregnancies, including 1 (1.1%) case of trisomy 21 and 16 (17.4%) fetuses with abnormalities different from common trisomies. The respective incidence in the 256 cases with a low-risk cfDNA test result and no ultrasound anomalies was 2.3% (95% CI 0.49-4.20; n = 6). CONCLUSIONS: In fetuses with first trimester ultrasound anomalies and a low-risk cfDNA result for trisomy 21, 18 and 13, diagnostic testing should be offered with the main objective to detect chromosomal abnormalities beyond common trisomies.
Asunto(s)
Aberraciones Cromosómicas/estadística & datos numéricos , Anomalías Congénitas/genética , Medida de Translucencia Nucal , Adulto , Ácidos Nucleicos Libres de Células/análisis , Anomalías Congénitas/diagnóstico por imagen , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Primer Trimestre del Embarazo , Estudios Prospectivos , Trisomía/diagnóstico , Adulto JovenRESUMEN
Hypertensive disorders are common complications during pregnancy (HDP) with substantial public health impact. Acute and chronic particulate matter (PM) exposure during pregnancy increases the risk of HDP, although the underlying molecular mechanisms remain unclear. Extracellular vesicles (EVs) may be the ideal candidates for mediating the effects of PM exposure in pregnancy as they are released in response to environmental stimuli. The INSIDE project aims to investigate this mechanism in pregnancy outcomes. The study population is enrolled at the Fetal Medicine Unit of Fondazione IRCCS Ca'Granda-Ospedale Maggiore Policlinico at 10-14 weeks of gestation. Exposure to PM10 and PM2.5 is assessed using the flexible air quality regional model (FARM) and Bayesian geostatistical models. Each woman provides a blood sample for EV analysis and circulating biomarker assessment. Moreover, a subgroup of recruited women (n = 85) is asked to participate in a cardiovascular screening program including a standard clinical evaluation, a non-invasive assessment of right ventricular function, and pulmonary circulation at rest and during exercise. These subjects are also asked to wear a personal particulate sampler, to measure PM10, PM2.5, and PM1. The INSIDE study is expected to identify the health impacts of PM exposure on pregnancy outcomes.
Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Vesículas Extracelulares , Hipertensión Inducida en el Embarazo/etiología , Material Particulado/efectos adversos , Adulto , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Estudios Transversales , Exposición a Riesgos Ambientales/análisis , Femenino , Humanos , Hipertensión Inducida en el Embarazo/epidemiología , Material Particulado/análisis , EmbarazoRESUMEN
OBJECTIVE: The objective of the study is to examine the incidence of chromosomal or genetic abnormalities in pregnancies complicated by polyhydramnios and to assess the value of prenatal ultrasound findings in the prediction of cases associated with such disorders. METHODS: We searched the prenatal records of all patients delivered in our hospital with a diagnosis of polyhydramnios during pregnancy. For each case, maternal characteristics, ultrasound findings, and genetic testing results were recorded. A postnatal follow-up program of at least 6 months, including a clinical assessment by a clinical geneticist, was carried out in all cases. RESULTS: On a total of 195 cases, genetic testing and clinical examination identified a chromosomal or genetic disease in 26 (13.3%) cases. Multivariate analysis demonstrated that significant predictors of a genetic disorder were a deepest vertical pocket of amniotic fluid of ≥13.0 cm (OR 4.306, 95%CI: 1.535-12.079) and reduced fetal movements (OR 25.084, 95%CI: 4.577-137.461), but not the presence of a structural defect. CONCLUSION: A postnatal clinical follow-up program can reveal chromosomal or genetic disorders in about 13% of neonates with a prenatal diagnosis of polyhydramnios. The severity of polyhydramnios and the reduction of fetal movements are independently associated with the presence of such diseases. © 2016 John Wiley & Sons, Ltd.
Asunto(s)
Líquido Amniótico/diagnóstico por imagen , Trastornos de los Cromosomas/epidemiología , Anomalías Congénitas/epidemiología , Enfermedades Genéticas Congénitas/epidemiología , Polihidramnios/epidemiología , Adulto , Anomalías Congénitas/diagnóstico por imagen , Femenino , Movimiento Fetal , Estudios de Seguimiento , Pruebas Genéticas , Humanos , Incidencia , Recién Nacido , Análisis Multivariante , Polihidramnios/diagnóstico por imagen , Embarazo , Estudios Retrospectivos , Ultrasonografía PrenatalRESUMEN
OBJECTIVE: The objective of this study was to investigate a strategy for clinical implementation of cell-free DNA (cfDNA) testing in high-risk pregnancies after first-trimester combined screening. METHODS: In 259 singleton pregnancies undergoing invasive testing after first-trimester combined screening, a maternal blood sample was sent to the laboratory Natera for cfDNA testing using a single-nucleotide polymorphism-based methodology. RESULTS: The cfDNA test provided a result in 249 (96.1%) pregnancies and, among these, identified as being at high risk 35 of 36 cases of trisomy 21, 13 of 13 with trisomy 18, five of five with trisomy 13 and three of four with sex chromosome aneuploidies. A policy of performing an invasive test in women with a combined risk of ≥1 in 10 or NT ≥4 mm and offering cfDNA testing to the remaining cases would detect all cases of trisomy 21, 18 or 13, 80% of sex aneuploidies and 62.5% of other defects and would avoid an invasive procedure in 82.4% of euploid fetuses. CONCLUSION: In high-risk pregnancies after combined screening, a policy of selecting a subgroup for invasive testing and another for cfDNA testing would substantially reduce the number of invasive procedures and retain the ability to diagnose most of the observed aneuploidies.