Please cite this paper as: Conde‐Agudelo A, Papageorghiou A, Kennedy S, Villar J. Novel biomarkers for the prediction of the spontaneous preterm birth phenotype: a systematic review and ...meta‐analysis. BJOG 2011;118:1042–1054.
Background Being able to predict preterm birth is important, as it may allow a high‐risk population to be selected for future interventional studies and help in understanding the pathways that lead to preterm birth.
Objective To investigate the accuracy of novel biomarkers to predict spontaneous preterm birth in women with singleton pregnancies and no symptoms of preterm labour.
Search strategy Electronic searches in PubMed, Embase, Cinahl, Lilacs, and Medion, references of retrieved articles, and conference proceedings. No language restrictions were applied.
Selection criteria Observational studies that evaluated the accuracy of biomarkers proposed in the last decade to predict spontaneous preterm birth in asymptomatic women. We excluded studies in which biomarkers were evaluated in women with preterm labour.
Data collection and analysis Two reviewers independently extracted data on study characteristics, quality, and accuracy. Data were arranged in 2 × 2 contingency tables and synthesised separately for spontaneous preterm birth before 32, 34, and 37 weeks of gestation. We used bivariate meta‐analysis to estimate pooled sensitivities and specificities, and calculated likelihood ratios (LRs).
Main results A total of 72 studies, including 89 786 women and evaluating 30 novel biomarkers, met the inclusion criteria. Only three biomarkers (proteome profile and prolactin in cervicovaginal fluid, and matrix metalloproteinase‐8 in amniotic fluid) had positive LRs > 10. However, each of these biomarkers was evaluated in only one small study. Four biomarkers had a moderate predictive accuracy (interleukin‐6 and angiogenin, in amniotic fluid; human chorionic gonadotrophin and phosphorylated insulin‐like growth factor binding protein‐1, in cervicovaginal fluid). The remaining biomarkers had low predictive accuracies.
Conclusions None of the biomarkers evaluated in this review meet the criteria to be considered a clinically useful test to predict spontaneous preterm birth. Further large, prospective cohort studies are needed to evaluate promising biomarkers such as a proteome profile in cervicovaginal fluid.
Background
Several biomarkers for predicting intrauterine growth restriction (IUGR) have been proposed in recent years. However, the predictive performance of these biomarkers has not been ...systematically evaluated.
Objective
To determine the predictive accuracy of novel biomarkers for IUGR in women with singleton gestations.
Search strategy
Electronic databases, reference list checking and conference proceedings.
Selection criteria
Observational studies that evaluated the accuracy of novel biomarkers proposed for predicting IUGR.
Data collection and analysis
Data were extracted on characteristics, quality and predictive accuracy from each study to construct 2 × 2 tables. Summary receiver operating characteristic curves, sensitivities, specificities and likelihood ratios (LRs) were generated.
Main results
A total of 53 studies, including 39 974 women and evaluating 37 novel biomarkers, fulfilled the inclusion criteria. Overall, the predictive accuracy of angiogenic factors for IUGR was minimal (median pooled positive and negative LRs of 1.7, range 1.0–19.8; and 0.8, range 0.0–1.0, respectively). Two small case–control studies reported high predictive values for placental growth factor and angiopoietin‐2 only when IUGR was defined as birthweight centile with clinical or pathological evidence of fetal growth restriction. Biomarkers related to endothelial function/oxidative stress, placental protein/hormone, and others such as serum levels of vitamin D, urinary albumin : creatinine ratio, thyroid function tests and metabolomic profile had low predictive accuracy.
Conclusions
None of the novel biomarkers evaluated in this review are sufficiently accurate to recommend their use as predictors of IUGR in routine clinical practice. However, the use of biomarkers in combination with biophysical parameters and maternal characteristics could be more useful and merits further research.
Please cite this paper as: Ioannou C, Talbot K, Ohuma E, Sarris I, Villar J, Conde‐Agudelo A, Papageorghiou A. Systematic review of methodology used in ultrasound studies aimed at creating charts of ...fetal size. BJOG 2012;119:1425–1439.
Background Reliable ultrasound charts are necessary for the prenatal assessment of fetal size, yet there is a wide variation of methodologies for the creation of such charts.
Objective To evaluate the methodological quality of studies of fetal biometry using a set of predefined quality criteria of study design, statistical analysis and reporting methods.
Search strategy Electronic searches in MEDLINE, EMBASE and CINAHL, and references of retrieved articles.
Selection criteria Observational studies whose primary aim was to create ultrasound size charts for bi‐parietal diameter, head circumference, abdominal circumference and femur length in fetuses from singleton pregnancies.
Data collection and analysis Studies were scored against a predefined set of independently agreed methodological criteria and an overall quality score was given to each study. Multiple regression analysis between quality scores and study characteristics was performed.
Main results Eighty‐three studies met the inclusion criteria. The highest potential for bias was noted in the following fields: ‘Inclusion/exclusion criteria’, as none of the studies defined a rigorous set of antenatal or fetal conditions which should be excluded from analysis; ‘Ultrasound quality control measures’, as no study demonstrated a comprehensive quality assurance strategy; and ‘Sample size calculation’, which was apparent in six studies only. On multiple regression analysis, there was a positive correlation between quality scores and year of publication: quality has improved with time, yet considerable heterogeneity in study methodology is still observed today.
Conclusions There is considerable methodological heterogeneity in studies of fetal biometry. Standardisation of methodologies is necessary in order to make correct interpretations and comparisons between different charts. A checklist of recommended methodologies is proposed.
RESUMEN
Pautas de práctica de ISUOG: la función del ultrasonido en la detección y seguimiento de la preeclampsia
Introducción
La hipertensión en el embarazo afecta hasta el 10% de las mujeres ...embarazadas y la incidencia global combinada de la preeclampsia (PE) es de aproximadamente el 3%. Las diferencias significativas entre los países desarrollados y en desarrollo pueden atribuirse a diferencias reales o a diferencias derivadas de la adquisición de datos. La PE y sus complicaciones contribuyen en gran medida a la morbilidad y mortalidad materna y perinatal en todo el mundo. Dado que la atención oportuna y efectiva puede mejorar los resultados de la PE, el desarrollo de estrategias eficaces de predicción y prevención ha sido uno de los principales objetivos de la atención prenatal y de la investigación.
La PE es una enfermedad multisistémica de origen multifactorial: está relacionada con placentación defectuosa, estrés oxidativo, autoinmunidad, activación de plaquetas y trombina, inflamación intravascular, disfunción endotelial, desequilibrio en la angiogénesis y mala adaptación cardíaca materna. La invasión defectuosa de la placenta está fuertemente asociada con la mayoría de los casos de PE temprana y grave. En contraste, la placentación defectuosa parece ser menos importante para el desarrollo de la PE que se manifiesta más tarde en el embarazo, por ejemplo después de las 34 semanas. En comparación con los embarazos afectados por la enfermedad de aparición temprana, en aquellos complicados con PE a término o cerca de este, la frecuencia de anomalías histológicas de las placentas es significativamente menor, y los factores maternos (p. ej. el síndrome metabólico o la hipertensión crónica) tienen una importancia relativamente mayor. También se observan diferencias entre la PE de aparición temprana y la de aparición tardía en los factores de riesgo, la capacidad de respuesta vascular materna, el rendimiento del cribado y la eficacia de la prevención.
El conocimiento cada vez mayor sobre la fisiopatología de la PE se refleja en las estrategias de cribado actuales, que se basan en el historial, la demografía, los biomarcadores (como la presión arterial) y el Doppler de la arteria uterina.
Actualmente hay más de 10 000 artículos de PubMed relacionados con la detección de la PE, lo que indica el gran interés en este tema. Menos de una quinta parte de estos se refieren a la detección temprana, lo que constituye un avance de la última década. El objetivo de estas Pautas es revisar la evidencia más reciente y, en lo posible, proporcionar recomendaciones basadas en la evidencia con respecto a la función del ultrasonido en el cribado y seguimiento de la PE. Las Pautas se centran en los aspectos técnicos y clínicos del cribado, sin incluir los aspectos económicos y políticos de la salud, como la conveniencia y la rentabilidad del cribado. Además, estas Pautas se elaboraron partiendo del supuesto de que se dispone de los recursos necesarios para la realización del cribado y el seguimiento (equipo, examinadores y conocimientos especializados). Los pasos y procedimientos descritos en estas Pautas no tienen la intención de constituir un estándar legal para el servicio clínico.
摘要
ISUOG实践指南:超声在子痫前期筛查和随访中的作用
前言
妊娠期高血压疾病累及多达10%的孕妇,子痫前期(pre‐eclampsia,PE)总的全球发病率约为3%。发达国家和发展中国家存在明显差异,可能是真实差异或是数据采集造成的差异所致。PE及其并发症是影响全球孕产妇围产期发病率和死亡率的一个重要因素。及时、有效的治疗能够改善PE结局,因此发展有效的预测和预防方法已经成为产前保健和研究的一个主要目标。
PE是一种多因素导致的多系统疾病:包括胎盘形成障碍、氧化应激、自身免疫、血小板和凝血酶激活、血管内炎症、内皮功能障碍、血管生成失衡、孕产妇心脏不适应。胎盘植入障碍与大多数早发型重度PE呈强相关。相反,胎盘形成障碍似乎对晚发型PE(如孕34周后)的发生影响不大。与早发型PE孕产妇相比,足月或接近足月时发生PE的孕产妇其胎盘组织学异常的发生率明显较低,母亲因素(如代谢综合征或长期高血压)具有较大意义。早发型和晚发型PE相比,危险因素、母亲血管反应、筛查能力和预防效能也存在差异。
目前的筛查方法反映了对PE病理生理学的了解逐渐加深,筛查方法是基于病史、流行病学、生物标志物(包括血压)和子宫动脉多普勒检查。
目前PubMed中收录了10 000多篇有关PE筛查的文章,表明人们非常关注这一问题。其中不到五分之一的文章探讨了早期筛查,这是过去十年取得的进展。本指南的目的是回顾最新的证据,如果可能,为超声在PE筛查和随访中的作用提供循证推荐。本指南关注筛查的技术和临床方面,并未扩展到卫生经济学和政策问题,包括筛查的可行性和成本—效益。而且指南的制定是假设能够获得筛查和随访所需的资源(设备、检查人员、专家)。本指南中所描述的步骤和程序并不是作为临床服务的法律标准。
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