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OBJECTIVE: To evaluate the relative importance of ethnicity and socioeconomic deprivation in determining the likelihood and prevalence of placentally derived composite of adverse pregnancy outcomes (CAPO) and composite of severe adverse pregnancy outcomes (CAPO-S). METHODS: This was a single-center retrospective cohort study of data obtained in a tertiary maternity unit. Data regarding ethnicity and socioeconomic deprivation (as measured with indices of multiple deprivation) were collected for 13 165 singleton pregnancies screened routinely in the first trimester for pre-eclampsia using the Fetal Medicine Foundation combined risk-assessment algorithm. CAPO was defined as the presence of one or more interrelated outcomes associated with placental dysfunction, namely, hypertensive disorders of pregnancy, preterm birth, birth weight ≤ 10th centile and stillbirth. CAPO-S was defined as the presence of one or more of the following: hypertensive disorders of pregnancy at < 37 + 0 weeks, preterm birth at < 34 + 0 weeks, birth weight ≤ 5th centile and stillbirth at < 37 + 0 weeks. RESULTS: The prevalence of CAPO was 16.3% in white women, 29.3% in black women and 29.3% in South Asian women. However, half (51.7%) of all CAPO cases occurred in white women. There was a strong interaction between ethnicity and socioeconomic deprivation, with a correlation coefficient of -0.223. Both ethnicity and socioeconomic deprivation influenced the prevalence of CAPO and CAPO-S, with the contribution of ethnicity being the strongest. CONCLUSIONS: Black and Asian ethnicity, as well as socioeconomic deprivation, influence the prevalence of placenta-mediated adverse pregnancy outcomes. Despite this, most adverse pregnancy outcomes occur in white women, who represent the majority of the population and are also affected by socioeconomic deprivation. For these reasons, inclusion of socioeconomic deprivation should be considered in early pregnancy risk assessment for placenta-mediated CAPO. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Origen étnico materno y privación socioeconómica: influencia en los resultados adversos del embarazo OBJETIVO: Evaluar la importancia relativa de la etnia y la privación socioeconómica en la determinación de la probabilidad y la prevalencia de los resultados adversos compuestos del embarazo relacionados con la placenta (CAPO, por sus siglas en inglés) y los resultados adversos compuestos graves del embarazo (CAPOS). MÉTODOS: Se trata de un estudio de cohortes retrospectivo unicéntrico de datos obtenidos en una unidad de maternidad terciaria. Se recopilaron datos relativos al origen étnico y la privación socioeconómica (mediante índices de privación múltiple) de 13 165 embarazos únicos sometidos a cribado rutinario en el primer trimestre para detectar la preeclampsia mediante el algoritmo combinado de evaluación de riesgos de la Fetal Medicine Foundation. Los CAPO se definieron como la presencia de uno o más resultados interrelacionados asociados con una disfunción placentaria, como trastornos hipertensivos del embarazo, parto prematuro, peso al nacer ≤10° percentil y éxitus fetal. Los CAPOS se definieron como la presencia de uno o más de los siguientes: trastornos hipertensivos del embarazo <37+0 semanas, parto prematuro a <37+0 semanas, peso al nacer ≤5° percentil y éxitus fetal a <37+0 semanas. RESULTADOS: La prevalencia de los CAPO fue del 16,3% en las mujeres blancas, del 29,3% en las negras y del 29,3% en las sudasiáticas. Sin embargo, la mitad (51,7%) de todos los casos de CAPO se produjeron en mujeres blancas. Hubo una fuerte interacción entre etnia y privación socioeconómica, con un coeficiente de correlación de −0,223. Tanto la etnia como la privación socioeconómica influyeron en la prevalencia de los CAPO y CAPOS, siendo la contribución de la etnia la más fuerte. CONCLUSIONES: Las etnias negra y asiática, así como la privación socioeconómica, influyen en la prevalencia de resultados adversos del embarazo relacionados con la placenta. A pesar de ello, la mayoría de los resultados adversos del embarazo se producen en mujeres blancas, que representan la mayoría de la población y también se ven afectadas por la privación socioeconómica. Por estas razones, debe considerarse la inclusión de la privación socioeconómica en la evaluación temprana del riesgo de CAPO relacionados con la placenta durante el embarazo.
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Etnicidad , Resultado del Embarazo , Factores Socioeconómicos , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Adulto , Resultado del Embarazo/etnología , Resultado del Embarazo/epidemiología , Etnicidad/estadística & datos numéricos , Nacimiento Prematuro/etnología , Nacimiento Prematuro/epidemiología , Prevalencia , Mortinato/epidemiología , Mortinato/etnología , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/etnología , Preeclampsia/epidemiología , Preeclampsia/etnología , Recién Nacido , Población Blanca/estadística & datos numéricos , Medición de Riesgo/estadística & datos numéricosRESUMEN
OBJECTIVE: Antenatal growth assessment using ultrasound aims to identify small fetuses that are at higher risk of perinatal morbidity and mortality. This study explored whether the association between suboptimal fetal growth and adverse perinatal outcome varies with different definitions of fetal growth restriction (FGR) and different weight charts/standards. METHODS: This was a retrospective cohort study of 17 261 singleton non-anomalous pregnancies at ≥ 24 + 0 weeks' gestation that underwent routine ultrasound at a tertiary referral hospital. Estimated fetal weight (EFW) and Doppler indices were converted into percentiles using a reference standard (INTERGROWTH-21st (IG-21)) and various reference charts (Hadlock, Fetal Medicine Foundation (FMF) and Swedish). Test characteristics were assessed using the consensus definition, Society for Maternal-Fetal Medicine (SMFM) definition and Swedish criteria for FGR. Adverse perinatal outcome was defined as perinatal death, admission to the neonatal intensive care unit at term, 5-min Apgar score < 7 and therapeutic cooling for neonatal encephalopathy. The association between FGR according to each definition and adverse perinatal outcome was compared. Multivariate logistic regression analysis was used to test the strength of association between ultrasound parameters and adverse perinatal outcome. Ultrasound parameters were also tested for correlation. RESULTS: IG-21, Hadlock and FMF fetal size references classified as growth-restricted 1.5%, 3.6% and 4.6% of fetuses, respectively, using the consensus definition and 2.9%, 8.8% and 10.6% of fetuses, respectively, using the SMFM definition. The sensitivity of the definition/chart combinations for adverse perinatal outcome varied from 4.4% (consensus definition with IG-21 charts) to 13.2% (SMFM definition with FMF charts). Specificity varied from 89.4% (SMFM definition with FMF charts) to 98.6% (consensus definition with IG-21 charts). The consensus definition and Swedish criteria showed the highest specificity, positive predictive value and positive likelihood ratio in detecting adverse outcome, irrespective of the reference chart/standard used. Conversely, the SMFM definition had the highest sensitivity across all investigated growth charts. Low EFW, abnormal mean uterine artery pulsatility index (UtA-PI) and abnormal cerebroplacental ratio were significantly associated with adverse perinatal outcome and there was a positive correlation between the covariates. Multivariate logistic regression showed that UtA-PI > 95th percentile and EFW < 5th percentile were the only parameters consistently associated with adverse outcome, irrespective of the definitions or fetal growth chart/standard used. CONCLUSIONS: The apparent prevalence of FGR varies according to the definition and fetal size reference chart/standard used. Irrespective of the method of classification, the sensitivity for the identification of adverse perinatal outcome remains low. EFW, UtA-PI and fetal Doppler parameters are significant predictors of adverse perinatal outcome. As these indices are correlated with one other, a prediction algorithm is advocated to overcome the limitations of using these parameters in isolation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Retardo del Crecimiento Fetal , Peso Fetal , Ultrasonografía Prenatal , Humanos , Retardo del Crecimiento Fetal/diagnóstico por imagen , Retardo del Crecimiento Fetal/diagnóstico , Femenino , Embarazo , Estudios Retrospectivos , Adulto , Recién Nacido , Edad Gestacional , Resultado del Embarazo , Valor Predictivo de las PruebasAsunto(s)
Cardiotocografía , Frecuencia Cardíaca Fetal , Embarazo , Femenino , Humanos , Cardiotocografía/métodos , Edad GestacionalRESUMEN
OBJECTIVES: To establish the correlation between phase-rectified signal averaging (PRSA) outputs obtained from a novel self-applicable non-invasive fetal electrocardiography (NIFECG) monitor with those from computerized cardiotocography (cCTG). A secondary objective was to evaluate the potential for remote assessment of fetal wellbeing by determining the relationship between PRSA and short-term variation (STV). METHODS: This was a prospective observational study of women with a singleton pregnancy over 28 + 0 weeks' gestation attending a London teaching hospital for cCTG assessment. Participants underwent concurrent cCTG and NIFECG monitoring for up to 60 min. Averaged accelerative (AAC) and decelerative (ADC) capacities and STV were derived by postprocessing and filtration of signals, generating fully (F) and partially (P) filtered results. Linear correlation and accuracy and precision analysis were performed to assess the relationship between PRSA outputs from cCTG and NIFECG, using varying anchor thresholds, and their association with STV. RESULTS: A total of 306 concurrent cCTG and NIFECG traces were collected from 285 women. F-filtered NIFECG PRSA (eAAC/eADC) results were generated from 65% of traces, whereas cCTG PRSA (cAAC/cADC) outputs were generated from all. Strong correlations were observed between cAAC and F-filtered eAAC (r = 0.879, P < 0.001) and between cADC and F-filtered eADC (r = 0.895, P < 0.001). NIFECG anchor detection decreased significantly with increasing signal loss, and NIFECG PRSA indices showed considerable deviation from those of cCTG when derived from traces in which fewer than 100 anchors were detected. Removing anchor filters from NIFECG traces to generate P-filtered PRSA outputs weakened the correlation (AAC: r = 0.505, P < 0.001; ADC: r = 0.560, P < 0.001). Lowering the anchor threshold to 100 increased the yield of eAAC and eADC outputs to approximately 74%, whilst maintaining strong correlation with cAAC (r = 0.839, P < 0.001) and cADC (r = 0.815, P < 0.001), respectively. Both cAAC and cADC showed a very strong linear relationship with cCTG STV (r = 0.928, P < 0.001 and r = 0.911, P < 0.001, respectively). Similar findings were observed with eAAC (r = 0.825, P < 0.001) and eADC (r = 0.827, P < 0.001). CONCLUSIONS: PRSA appears to be a method of fetal assessment equivalent to STV, but, due to its innate ability to eliminate artifacts, it generates interpretable NIFECG traces with high accuracy at a higher rate. These findings raise the possibility of self-applied at-home or remote fetal heart-rate monitoring with automated reporting, thus enabling increased surveillance in high-risk women without impacting on service demand. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Monitoreo Fetal , Frecuencia Cardíaca Fetal , Embarazo , Humanos , Femenino , Frecuencia Cardíaca Fetal/fisiología , Cardiotocografía/métodos , Estudios Prospectivos , Atención PrenatalRESUMEN
OBJECTIVES: To compare short-term variation (STV) outputs from a novel self-applied non-invasive fetal electrocardiography (NIFECG) device with those obtained on computerized cardiotocography (cCTG). Technological and algorithmic limitations and mitigation strategies were also evaluated. METHODS: This was a prospective cohort study of women with a singleton pregnancy over 28 + 0 weeks' gestation attending a tertiary London hospital for cCTG assessment between June 2021 and June 2022. Women underwent concurrent monitoring with both NIFECG and cCTG for up to 1 h. Postprocessing of NIFECG data using various filtering methods produced NIFECG-STV (eSTV) values, which were compared with cCTG-STV (cSTV) outputs. Linear correlation, mean bias, precision and limits of agreement were assessed for STV derived by the different methods of computation and mathematical correction. RESULTS: Overall, 306 concurrent NIFECG and cCTG traces were collected from 285 women. Fully filtered eSTV was correlated very strongly with cSTV (r = 0.911, P < 0.001), but generated results only in 142/306 (46.4%) 1-h traces owing to the removal of traces with lower-quality signals. Partial filtering generated more eSTV data (98.4%), but with a weak correlation with cSTV (r = 0.337, P < 0.001). The difference in STV between the monitors (eSTV - cSTV) increased with signal loss; in traces with > 60% signal loss, the values became highly discrepant. Removal of traces with > 60% signal loss resulted in a stronger correlation with cSTV, while still generating eSTV results for 65% of traces. Correcting these remaining eSTV values for signal loss using linear regression analysis further improved correlation with cSTV (r = 0.839, P < 0.001). CONCLUSIONS: The discrepancy between STV computed by NIFECG and cCTG necessitates signal filtering, exclusion of poor-quality traces and eSTV correction. This study demonstrates that, with such correction, NIFECG is able to produce STV values that are strongly correlated with those of cCTG. This evidence base for NIFECG monitoring and interpretation is a promising step forward in the development of safe and effective at-home fetal heart-rate monitoring. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Cardiotocografía , Monitoreo Fetal , Embarazo , Humanos , Femenino , Cardiotocografía/métodos , Estudios Prospectivos , Feto , Electrocardiografía , Frecuencia Cardíaca FetalAsunto(s)
Cardiotocografía , Frecuencia Cardíaca Fetal , Embarazo , Femenino , Humanos , Edad GestacionalRESUMEN
OBJECTIVES: To evaluate the prenatal ultrasound features associated with operative complications and to assess the interobserver agreement of prenatal ultrasound assessment with histopathologic confirmation of placenta accreta spectrum (PAS) in a cohort of high-risk patients with detailed intraoperative and histopathologic data. METHODS: This was a retrospective multicenter cohort study of patients at high risk of PAS referred for specialist perinatal care and management between January 2019 and May 2022. Deidentified ultrasound images were reviewed independently by two experienced operators blinded to clinical details, intraoperative features, outcome and histopathologic findings. The diagnosis of PAS was confirmed by failure of detachment of one or more placental cotyledons from the uterine wall at delivery, and the absence of decidua with distortion of the uteroplacental interface by fibrinoid deposition on histologic examination of the accretic areas obtained by guided sampling of partial myometrial resection or hysterectomy specimens. Patients were categorized as having a low or high likelihood of PAS at birth. Interobserver agreement of prenatal ultrasound assessment with histopathologic confirmation of PAS was assessed using the kappa statistic. Primary outcome was major operative morbidity (blood loss ≥ 2000 mL, unintentional injury to the viscera, admission to intensive care unit or death). RESULTS: A total of 102 women at high risk of PAS were referred, of whom 66 had evidence of PAS at birth and 36 did not. When blinded to other clinical details, the examiners agreed on the low or high probability of PAS, according to ultrasound features, in 75/102 cases (73.5%). The kappa statistic was 0.47 (95% CI, 0.28-0.66), showing moderate agreement. Morbidity was twice as common with concordant prenatal diagnosis of PAS vs concordant diagnosis of not PAS. Concordant assessment of high probability of PAS was associated with the highest morbidity (66.6%) and a very high (97.6%) likelihood of histopathologic confirmation. CONCLUSIONS: The probability of histopathologic confirmation is very high with concordant prenatal assessment suggestive of PAS. The interobserver agreement for preoperative assessment with histopathologic confirmation of PAS is only moderate. Morbidity is associated with both histopathologic diagnosis and concordant antenatal assessment of PAS. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Placenta Accreta , Placenta Previa , Femenino , Humanos , Recién Nacido , Embarazo , Estudios de Cohortes , Placenta/diagnóstico por imagen , Placenta/patología , Placenta Accreta/diagnóstico por imagen , Placenta Accreta/patología , Placenta Previa/patología , Estudios Retrospectivos , Ultrasonografía PrenatalRESUMEN
OBJECTIVE: To determine, by expert consensus through a modified Delphi process, the role of standardized and new ultrasound signs in the prenatal evaluation of patients at high risk of placenta accreta spectrum (PAS). METHODS: A systematic review of articles providing information on ultrasound imaging signs or markers associated with PAS was performed before the development of questionnaires for the first round of the Delphi process. Only peer-reviewed original research studies in the English language describing one or more new ultrasound sign(s) for the prenatal evaluation of PAS were included. A three-round consensus-building Delphi method was then conducted under the guidance of a steering group, which included nine experts who invited an international panel of experts in obstetric ultrasound imaging in the evaluation of patients at high risk for PAS. Consensus was defined as agreement of ≥ 70% between participants. RESULTS: The systematic review identified 15 articles describing eight new ultrasound signs for the prenatal evaluation of PAS. A total of 35 external experts were approached, of whom 31 agreed and participated in the first round. Thirty external experts (97%) and seven experts from the steering group completed all three Delphi rounds. A consensus was reached that a prior history of at least one Cesarean delivery, myomectomy or PAS should be an indication for detailed PAS ultrasound assessment. The panelists also reached a consensus that seven of the 11 conventional signs of PAS should be included in the examination of high-risk patients and the routine mid-gestation scan report: (1) loss of the 'clear zone', (2) myometrial thinning, (3) bladder-wall interruption, (4) placental bulge, (5) uterovesical hypervascularity, (6) placental lacunae and (7) bridging vessels. A consensus was not reached for any of the eight new signs identified by the systematic review. With respect to other ultrasound features that are not specific to PAS but increase the probability of PAS at birth, the panelists reached a consensus for the finding of anterior placenta previa or placenta previa with cervical involvement. The experts were also asked to determine which PAS signs should be quantified and consensus was reached only for the quantification of placental lacunae using an existing score. For predicting surgical outcome in patients with a high probability of PAS at delivery, a consensus was obtained for loss of the clear zone, bladder-wall interruption, presence of placental lacunae and presence of placenta previa involving the cervix. CONCLUSIONS: We have confirmed the continued importance of seven established standardized ultrasound signs of PAS, highlighted the role of transvaginal ultrasound in evaluating the placental position and anatomy of the cervix, and identified new ultrasound signs that may become useful in the future prenatal evaluation and management of patients at high risk for PAS at birth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Placenta Accreta , Placenta Previa , Recién Nacido , Embarazo , Femenino , Humanos , Placenta Accreta/diagnóstico por imagen , Placenta/diagnóstico por imagen , Técnica Delphi , Ultrasonografía , Ultrasonografía Prenatal , Estudios RetrospectivosRESUMEN
PURPOSE: To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). MATERIALS AND METHODS: A prospective European multicenter observational study included women with a singleton pregnancy, 32+â0-36+â6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] <â10th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of >â40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (<â0.9) or abnormal (≥â0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. RESULTS: 856 women had 2770 measurements; 696 (81â%) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7â%) a UCR ≥â0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30â% vs. 9â%, relative risk 3.2; 95â%CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67â% (95â%CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6â% (95â%CI 5-7â%). The risk of composite adverse outcome was similar using the first or subsequent UCR values. CONCLUSION: An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7â% when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.
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Retardo del Crecimiento Fetal , Nacimiento Prematuro , Embarazo , Recién Nacido , Femenino , Humanos , Estudios Prospectivos , Ultrasonografía Prenatal , Recién Nacido Pequeño para la Edad Gestacional , Ultrasonografía Doppler , Peso Fetal , Edad Gestacional , Arterias Umbilicales/diagnóstico por imagenRESUMEN
OBJECTIVE: To evaluate the impact of a first-trimester combined screening program for pre-eclampsia, based on the Fetal Medicine Foundation (FMF) algorithm, on the rate of small-for-gestational age (SGA) at birth and adverse pregnancy outcome. METHODS: This was a retrospective cohort study of data obtained from a London tertiary hospital between January 2017 and March 2019. The data were derived from a secondary analysis of the cohort evaluated in a clinical-effectiveness study on the implementation of a first-trimester screening program for pre-eclampsia. The cohort included 7720 women screened according to the UK National Institute for Health and Care Excellence (NICE) risk-based approach and 4841 women screened by the FMF multimodal approach, which combines maternal risk factors, blood pressure, pregnancy-associated plasma protein-A and uterine artery Doppler indices. The care package for the FMF-screened group included 150-mg aspirin prophylaxis, ultrasound scans at 28 and 36 weeks' gestation and scheduled delivery at 40 weeks. Outcome measures included the rates of SGA neonates at birth, admission to the neonatal unit, intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy assessed by interrupted time series analysis (ITSA). RESULTS: There was no significant difference in the rates of intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy between the FMF-screened and NICE-screened cohorts. ITSA showed a significant reduction in the rate of term SGA birth < 10th percentile at 21 months following implementation of the FMF screening program, with a relative effect reduction of 45.1% (P = 0.004). However, there was no significant relative effect reduction in term SGA birth < 5th or < 3rd percentile. CONCLUSIONS: First-trimester combined screening for pre-eclampsia based on the FMF algorithm accompanied by a care package including serial ultrasound scans for growth evaluation and elective birth from 40 weeks' gestation resulted in a significant 45% relative effect reduction in term SGA birth < 10th percentile but did not affect term SGA birth < 5th or < 3rd percentile. Further screening strategies to detect and improve the outcome of cases with SGA birth < 5th percentile need to be considered. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
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Retardo del Crecimiento Fetal/diagnóstico , Recién Nacido Pequeño para la Edad Gestacional , Preeclampsia/diagnóstico , Resultado del Embarazo/epidemiología , Diagnóstico Prenatal/estadística & datos numéricos , Medición de Riesgo/métodos , Adulto , Algoritmos , Femenino , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Análisis de Series de Tiempo Interrumpido , Admisión del Paciente/estadística & datos numéricos , Perinatología/normas , Valor Predictivo de las Pruebas , Embarazo , Primer Trimestre del Embarazo , Diagnóstico Prenatal/métodos , Estudios Retrospectivos , Medición de Riesgo/normas , Reino Unido/epidemiologíaRESUMEN
PURPOSE: To predict if developing human embryos are permissive to multiple coronaviruses. METHOD: We analyzed publicly available single-cell RNA-seq datasets of human embryos for the known canonical and non-canonical receptors and spike protein cleavage enzymes for multiple coronaviruses like SARS-CoV, SARS-CoV-2, MERS-CoV, hCoV-229E, and hCoV-NL63. We also analyzed the expression of host genes involved in viral replication, host proteins involved in viral endosomal sorting complexes required for transport (ESCRT), genes of host proteins that physically interact with proteins of SARS-CoV-2, and the host genes essential for coronavirus infectivity. RESULTS: Of the known receptors of SARS viruses, ACE2, BSG, GOLGA7, and ZDHHC5 were expressed in different proportions in the zygote, 4-cell, 8-cell, morula, and blastocysts including the trophectoderm. The MERS-CoV receptor, DPP4, and hCoV-229E receptor, ANPEP, were expressed mainly from the compact morula to the blastocyst stages. Transcripts of the MERS-CoV alternate receptor LGALS1 were detected in most cells at all stages of development. TMPRSS2 transcripts were detected in the epiblast, primitive endoderm, and trophectoderm, while transcripts of the endosomal proteases CTSL, CTSB, and FURIN were expressed in most cells at all stages of development. ACE2 and TMPRSS2 were co-expressed in a proportion of epiblast and trophectoderm cells. The embryonic cells expressed genes involved in ESCRT, viral replication, SARS-CoV-2 interactions, and coronavirus infectivity. The ACE2 and TMPRSS2 co-expressing cells were enriched in genes associated with lipid metabolism, lysosome, peroxisome, and oxidative phosphorylation pathways. CONCLUSION: Preimplantation and implantation stage human embryos could be permissive to multiple hCoVs.
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Enzima Convertidora de Angiotensina 2/metabolismo , Blastocisto/metabolismo , Infecciones por Coronavirus/metabolismo , Embrión de Mamíferos/metabolismo , Serina Endopeptidasas/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Replicación Viral , Enzima Convertidora de Angiotensina 2/genética , Blastocisto/patología , Blastocisto/virología , Coronavirus/fisiología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Implantación del Embrión , Embrión de Mamíferos/patología , Embrión de Mamíferos/virología , Complejos de Clasificación Endosomal Requeridos para el Transporte , Humanos , Serina Endopeptidasas/genética , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
OBJECTIVES: Maternal mortality related to placenta accreta spectrum (PAS) disorders remains substantial when diagnosed unexpectedly at delivery. The aim of this study was to evaluate the effectiveness of a routine contingent ultrasound screening program for PAS. METHODS: This was a retrospective study of data obtained between 2009 and 2019, involving two groups: a screening cohort of unselected women attending for routine mid-trimester ultrasound assessment and a diagnostic cohort consisting of women referred to the PAS diagnostic service with a suspected diagnosis of PAS. In the screening cohort, women with a low-lying placenta at the mid-trimester assessment were followed up in the third trimester, and those with a persistent low-lying placenta (i.e. placenta previa) and previous uterine surgery were referred to the PAS diagnostic service. Ultrasound assessment by the PAS diagnostic service consisted of two-dimensional grayscale and color Doppler ultrasonography, and women with a diagnosis of PAS were usually managed with conservative myometrial resection. The final diagnosis of PAS was based on a combination of intraoperative clinical findings and histopathological examination of the surgical specimen. RESULTS: In total, 57 179 women underwent routine mid-trimester fetal anatomy assessment, of whom 220 (0.4%) had a third-trimester diagnosis of placenta previa. Seventy-five of these women were referred to the PAS diagnostic service because of a history of uterine surgery, and 21 of 22 cases of PAS were diagnosed correctly (sensitivity, 95.45% (95% CI, 77.16-99.88%) and specificity, 100% (95% CI, 99.07-100%)). Univariate analysis demonstrated that parity ≥ 2 (odds ratio (OR), 35.50 (95% CI, 6.90-649.00)), two or more previous Cesarean sections (OR, 94.20 (95% CI, 22.00-656.00)) and placenta previa (OR, 20.50 (95% CI, 4.22-369.00)) were the strongest risk factors for PAS. In the diagnostic cohort, there were 173 referrals, with one false-positive and three false-negative diagnoses, resulting in a sensitivity of 96.63% (95% CI, 90.46-99.30%) and a specificity of 98.81% (95% CI, 93.54-99.97%). CONCLUSIONS: A contingent screening strategy for PAS is both feasible and effective in a routine healthcare setting. When linked to a PAS diagnostic and surgical management service, adoption of such a screening strategy has the potential to reduce the maternal morbidity and mortality associated with this condition. However, larger prospective studies are necessary before implementing this screening strategy into routine clinical practice. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Eficacia de la detección contingente para los trastornos del espectro de la placenta acreta a partir de la placenta baja persistente y en la cirugía uterina previa OBJETIVOS: La mortalidad materna relacionada con los trastornos de la gama espectral de la placenta acreta (EPA) sigue siendo considerable cuando se diagnostica de forma inesperada en el momento del parto. El objetivo de este estudio fue evaluar la efectividad de un programa rutinario de detección contingente mediante ecografía para el EPA. MÉTODOS: Este fue un estudio retrospectivo de datos obtenidos entre 2009 y 2019, en el que participaron dos grupos: una cohorte de detección de mujeres no seleccionadas que acudieron a la evaluación ecográfica rutinaria de mitad de trimestre y una cohorte de diagnóstico, integrada por mujeres remitidas al servicio de diagnóstico del EPA con un presunto diagnóstico del EPA. En la cohorte de detección, a las mujeres con una placenta baja en la evaluación de mitad de trimestre se les hizo un seguimiento en el tercer trimestre, y a aquellas con una placenta baja persistente (es decir, placenta previa) que habían tenido cirugía uterina previa se las remitió al servicio de diagnóstico del EPA. La evaluación ecográfica por el servicio de diagnóstico del EPA consistió en una ecografía Doppler bidimensional en escala de grises y en color, y a las mujeres con diagnóstico del EPA se las trató habitualmente con una resección conservadora del miometrio. El diagnóstico final del EPA se basó en una combinación de indicadores clínicos intraoperatorios y el examen histopatológico de la muestra quirúrgica. RESULTADOS: En total, 57179 mujeres se sometieron a una evaluación rutinaria de la anatomía fetal a mitad del trimestre, de las cuales a 220 (0,4%) se les diagnosticó con placenta previa en el tercer trimestre. Setenta y cinco de estas mujeres fueron remitidas al servicio de diagnóstico del EPA, debido a su historial de cirugía uterina, y 21 de los 22 casos de EPA fueron diagnosticados correctamente (sensibilidad, 95,45% (IC 95%, 77,16-99,88%) y especificidad, 100% (IC 95%, 99,07-100%)). El análisis univariante demostró que la paridad ≥2 (razón de momios (RM), 35,50 (IC 95%, 6,90-649,00)), dos o más cesáreas previas (RM, 94,20 (IC 95%, 22,00-656,00)) y la placenta previa (RM, 20,50 (IC 95%, 4,22-369,00)) fueron los factores de riesgo más fuertes para el EPA. En la cohorte de diagnóstico, se remitió a 173 mujeres, entre las cuáles hubo un diagnóstico de falso-positivo y tres diagnósticos de falsos-negativos, lo que dio como resultado una sensibilidad del 96,63% (IC 95%, 90,46-99,30%) y una especificidad del 98,81% (IC 95%, 93,54-99,97%). CONCLUSIONES: La adopción de una estrategia de detección contingente para el EPA es tanto factible como eficaz en un entorno de atención sanitaria rutinaria. Cuando se asocia a un servicio de diagnóstico y gestión quirúrgica del EPA, la adopción de esa estrategia de detección podría reducir la morbilidad y la mortalidad maternas asociadas a esta afección. Sin embargo, se necesitan estudios prospectivos más amplios antes de aplicar esta estrategia de detección en la práctica clínica habitual. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Asunto(s)
Tamizaje Masivo/métodos , Placenta Accreta/diagnóstico por imagen , Placenta Previa/diagnóstico por imagen , Adulto , Cesárea/efectos adversos , Femenino , Humanos , Placenta Accreta/epidemiología , Placenta Previa/epidemiología , Embarazo , Tercer Trimestre del Embarazo , Estudios Retrospectivos , Factores de Riesgo , Ultrasonografía Doppler en Color , Ultrasonografía PrenatalRESUMEN
OBJECTIVES: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. METHODS: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored. RESULTS: The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n = 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33 weeks and 1.0 at 34-36 weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association. CONCLUSION: In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
Asunto(s)
Desarrollo Fetal , Retardo del Crecimiento Fetal/diagnóstico por imagen , Reología , Ultrasonografía Doppler , Ultrasonografía Prenatal , Adulto , Peso al Nacer , Europa (Continente) , Femenino , Retardo del Crecimiento Fetal/fisiopatología , Peso Fetal , Feto/irrigación sanguínea , Feto/diagnóstico por imagen , Feto/fisiopatología , Edad Gestacional , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Nacimiento Vivo , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/embriología , Embarazo , Estudios Prospectivos , Flujo Pulsátil , Valores de Referencia , Mortinato , Arterias Umbilicales/diagnóstico por imagen , Arterias Umbilicales/embriología , Circunferencia de la CinturaAsunto(s)
Mola Hidatiforme , Embarazo Gemelar , Neoplasias Uterinas , Femenino , Feto , Humanos , EmbarazoRESUMEN
OBJECTIVE: There has been an unprecedented fall in the rate of stillbirth in twin pregnancy in the UK. It is contested whether implementation of the National Institute for Health and Care Excellence (NICE) guidance on the antenatal management of uncomplicated twin pregnancies has contributed to this change. The aim of this study was to investigate whether the implementation of NICE guidance was associated with a reduction in the rate of stillbirth in twin pregnancies delivered in a large UK hospital. METHODS: This was a retrospective cohort study including all twin pregnancies delivered at St George's Hospital, London, UK, between 2000 and 2018. Data were analyzed according to two time periods: before implementation of the NICE guidance on twins (before June 2013; pre-NICE) and after its implementation (after June 2013; post-NICE). The exclusion criteria were higher-order multiple gestations, pregnancies of unknown chorionicity, pregnancies complicated by miscarriage, those that underwent termination and those diagnosed with vanishing twin. The main outcome was stillbirth. Other outcomes included neonatal death (NND), admission to the neonatal intensive care unit (NICU) and emergency Cesarean section. We planned a priori a sensitivity analysis according to chorionicity. The chi-square test and Mann-Whitney U-test were used to compare outcomes between the study groups. RESULTS: We included in the analysis 1666 twin pregnancies (3332 fetuses), of which 1114 pregnancies (2228 fetuses) were delivered before and 552 pregnancies (1104 fetuses) after June 2013. Of those, 1299 were dichorionic and 354 were monochorionic diamniotic. The incidence of stillbirth was significantly lower in the post-NICE than in the pre-NICE group (3.6 per 1000 births vs 13.5 per 1000 births; P = 0.008). The reduction in stillbirth rate was from 8.5 to 3.6 per 1000 births (P = 0.161) in dichorionic and from 33.6 to 3.8 per 1000 births (P = 0.011) in monochorionic diamniotic twin pregnancies. There was no significant difference in the rates of NND (P = 0.625), NICU admission (P = 0.506) or emergency Cesarean section (P = 0.820) between the two groups. The median gestational age at delivery was significantly lower in the post-NICE than in the pre-NICE group (median 36.3 vs 36.9 weeks; P < 0.001), as a consequence of a significant increase in preterm birth between 34 and 37 weeks' gestation (39.3% vs 27.0%; P = 0.002), but not before 34 weeks (P = 0.473). CONCLUSIONS: A significant reduction of > 70% in the stillbirth rate in twin pregnancies was noted after implementation of the NICE guidance. This reduction was statistically significant in monochorionic, but not dichorionic, twin pregnancies. The improvement in twin pregnancy outcome was achieved without a concomitant increase in NND, admission to the NICU or emergency Cesarean section. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
Asunto(s)
Parto Obstétrico/estadística & datos numéricos , Implementación de Plan de Salud/estadística & datos numéricos , Embarazo Gemelar/estadística & datos numéricos , Atención Prenatal/normas , Mortinato/epidemiología , Adulto , Cesárea/estadística & datos numéricos , Distribución de Chi-Cuadrado , Femenino , Edad Gestacional , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Admisión del Paciente/estadística & datos numéricos , Muerte Perinatal , Embarazo , Resultado del Embarazo , Nacimiento Prematuro/epidemiología , Estudios Retrospectivos , Estadísticas no Paramétricas , Reino Unido/epidemiologíaRESUMEN
OBJECTIVE: Fetal hydrops is associated with increased perinatal morbidity and mortality. The etiology and outcome of fetal hydrops may differ according to the gestational age at diagnosis. The aim of this study was to evaluate the cause, evolution and outcome of non-immune fetal hydrops (NIFH), according to the gestational age at diagnosis. METHODS: This was a retrospective cohort study of all singleton pregnancies complicated by NIFH, at the Fetal Medicine Unit at St George's University Hospital, London, UK, between 2000 and 2018. All fetuses had detailed anomaly and cardiac ultrasound scans, karyotyping and infection screening. Prenatal diagnostic and therapeutic intervention, gestational age at diagnosis and delivery, as well as pregnancy outcome, were recorded. Regression analysis was used to test for potential association between possible risk factors and perinatal mortality. RESULTS: We included 273 fetuses with NIFH. The etiology of the condition varied significantly in the three trimesters. Excluding 30 women who declined invasive testing, the cause of NIFH was defined as unknown in 62 of the remaining 243 cases (25.5%). Chromosomal aneuploidy was the most common cause of NIFH in the first trimester. It continued to be a significant etiologic factor in the second trimester, along with congenital infection. In the third trimester, the most common etiology was cardiovascular abnormality. Among the 152 (55.7%) women continuing the pregnancy, 48 (31.6%) underwent fetal intervention, including the insertion of pleuroamniotic shunts, fetal blood transfusion and thoracentesis. Fetal intervention was associated significantly with lower perinatal mortality (odds ratio (OR), 0.30 (95% CI, 0.14-0.61); P < 0.001); this association remained significant after excluding cases with a diagnosis of anemia or infection (OR, 0.29 (95% CI, 0.13-0.66); P = 0.003). In 104 fetuses not undergoing active fetal intervention, the gestational age at diagnosis was the only parameter that was significantly associated with the risk of perinatal mortality (OR, 0.92 (95% CI, 0.85-0.99); P = 0.035), while the affected body cavity and polyhydramnios were not (P > 0.05). CONCLUSIONS: An earlier gestational age at diagnosis of NIFH was associated with an increased risk of aneuploidy and worse pregnancy outcome, including a higher risk of perinatal loss. Fetal therapy was associated significantly with lower perinatal mortality. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Asunto(s)
Hidropesía Fetal/mortalidad , Diagnóstico Prenatal , Adulto , Inglaterra/epidemiología , Femenino , Edad Gestacional , Humanos , Hidropesía Fetal/diagnóstico , Hidropesía Fetal/etiología , Embarazo , Resultado del Embarazo , Trimestres del Embarazo , Análisis de Regresión , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVES: To evaluate the natural history and outcome of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancy, according to gestational age at onset and various reported diagnostic criteria, and to quantify the risk of superimposed twin-to-twin transfusion syndrome (TTTS). METHODS: This was a cohort study of MCDA twin pregnancies that had their routine antenatal care from the first trimester at St George's Hospital, London, UK. Pregnancies had ultrasound examinations every 2 weeks at 16-24 weeks and then every 2-3 weeks until delivery. The diagnostic criteria for sFGR were estimated fetal weight (EFW) of one twin < 10th centile and intertwin EFW discordance ≥ 25%. We also applied other diagnostic criteria reported in a recent Delphi consensus. Pregnancies in which the diagnosis of TTTS was made before that of sFGR were not included in the analysis. Pregnancies that underwent fetal intervention for sFGR were excluded. The incidence of sFGR was compared between the different diagnostic criteria, overall and according to gestational age at onset. In all subsequent analyses, cases of sFGR included those diagnosed according to any of the criteria. The Gratacós classification of sFGR was applied (Type I, II or III). Pregnancy outcomes included miscarriage, intrauterine death, neonatal death and admission to the neonatal unit. Comparisons between groups were carried out using the Mann-Whitney U-test for continuous variables and the chi-square or Fisher's exact test for categorical variables. RESULTS: The analysis included 287 MCDA twin pregnancies. According to the International Society of Ultrasound in Obstetrics and Gynecology diagnostic criteria, the incidence of early (< 24 weeks) sFGR was 4.9%, while that of late sFGR was 3.8%. When applying the various diagnostic criteria, the incidence of early sFGR varied from 1.7% to 9.1% and that of late sFGR varied from 1.1% to 5.9%. In early-onset cases, the incidence of Type I sFGR was 80.8%, that of Type II was 15.4% and that of Type III was 3.8%. The corresponding figures in late-onset cases were 94.4%, 5.6% and 0%. The incidence of superimposed TTTS was 26.9% in cases affected by early-onset sFGR and 5.6% in those affected by late-onset sFGR. The incidence of perinatal death was 8.0% in early-onset sFGR and 5.6% in late-onset sFGR (P = 0.661). Admission to the neonatal unit occurred in 61.0% and 52.9% of cases, respectively (P = 0.484). CONCLUSIONS: In MCDA twin pregnancies, early-onset sFGR is slightly more common than is late-onset sFGR, although this difference was not significant, and is associated with worse perinatal outcome. The incidence of Types II and III sFGR is higher in early-onset sFGR. The incidence also varies according to the diagnostic criteria used, which supports the use of standardized international diagnostic criteria. Superimposed TTTS is more common in early- than in late-onset sFGR. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.