Kleijnen Systematic Reviews Ltd, York, UK.
Health Technol Assess. 2013 Sep;17(40):1-138. doi: 10.3310/hta17400.
Premature birth is defined as birth of before 37 completed weeks' gestation. Not all pregnant women showing symptoms of preterm labour will go on to deliver before 37 weeks' gestation. Hence, addition of fetal fibronectin (fFN) testing to the diagnostic workup of women with suspected preterm labour may help to identify those women who do not require active management, and thus avoid unnecessary interventions, hospitalisations and associated costs.
To assess the clinical effectiveness and cost-effectiveness of rapid fFN testing in predicting preterm birth (PTB) in symptomatic women.
Bibliographic databases (including EMBASE, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials) were searched from 2000 to September/November 2011. Trial registers were also searched.
Systematic review methods followed published guidance; we assessed clinical effectiveness and updated a previous systematic review of test accuracy. Risk of bias was assessed using the Cochrane tool (randomised controlled trials; RCTs) and a modification of QUADAS-2 (diagnostic test accuracy studies; DTAs). Summary risk ratios or weighted mean difference were calculated using random-effects models. Summary sensitivity and specificity used a bivariate summary receiver operating characteristic model. Heterogeneity was investigated using subgroup and sensitivity analyses. Health economic analysis focused on cost consequences. The time horizon was hospital admission for observation. A main structural assumption was that, compared with usual care, fFN testing doesn't increase adverse events or negative pregnancy outcomes.
Five RCTs and 15 new DTAs were identified. No RCT reported significant effects of fFN testing on maternal or neonatal outcomes. One study reported a subgroup analysis of women with negative fFN test observed > 6 hours, which showed a reduction in length of hospital stay where results were known to clinicians. Combining data from new studies and the previous systematic review, the pooled estimates of sensitivity and specificity were: 76.7% and 82.7% for delivery within 7-10 days of testing; 69.1% and 84.4% for delivery < 34 weeks' gestation; and 60.8% and 82.3% for delivery < 37 weeks' gestation. Estimates were similar across all subgroups sensitivity analyses. The base-case cost analysis resulted in a cost saving of £23.87 for fFN testing compared with usual care. The fFN testing was cost-neutral at an approximate cost of £45. Probabilistic sensitivity analysis gave an incremental cost (saving) of -£25.59 (97.5% confidence interval -£304.96 to £240.06), indicating substantial uncertainty. Sensitivity analyses indicated that admission rate had the largest impact on results.
Fetal fibronectin testing has moderate accuracy for predicting PTB. The main potential role is likely to be reducing health-care resource usage by identifying women not requiring intervention. Evidence from RCTs suggests that fFN does not increase adverse outcomes and may reduce resource use. The base-case analysis showed a modest cost difference in favour of fFN testing, which is largely dependent on whether or not fFN testing reduces hospital admission. Currently, there are no high-quality studies and the existing trials were generally underpowered. Hence, there is a need for high-quality adequately powered trials using appropriate study designs to confirm the findings presented.
PROSPERO 2011:CRD42011001468. Available from www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42011001468.
The National Institute for Health Research Health Technology Assessment programme.
早产是指妊娠 37 周前分娩。并非所有出现早产症状的孕妇都会在 37 周前分娩。因此，在疑似早产的孕妇的诊断中添加胎儿纤维连接蛋白（fFN）检测可能有助于识别那些不需要积极管理的孕妇，从而避免不必要的干预、住院和相关费用。
评估快速 fFN 检测在预测有症状孕妇早产（PTB）中的临床有效性和成本效益。
从 2000 年到 2011 年 9 月/11 月，在文献数据库（包括 EMBASE、Cochrane 系统评价数据库和 Cochrane 对照试验中心注册库）中进行了检索。还对试验登记册进行了检索。
系统评价方法遵循已发布的指南；我们评估了临床有效性并更新了之前对检测准确性的系统评价。使用 Cochrane 工具（随机对照试验；RCTs）和 QUADAS-2 的修改版（诊断测试准确性研究；DTAs）评估偏倚风险。使用随机效应模型计算汇总风险比或加权均数差。使用双变量汇总受试者工作特征模型计算汇总敏感性和特异性。使用亚组和敏感性分析来研究异质性。卫生经济学分析侧重于成本后果。时间范围是入院观察。一个主要的结构假设是，与常规护理相比，fFN 检测不会增加不良事件或不良妊娠结局。
确定了 5 项 RCT 和 15 项新的 DTA。没有 RCT 报道 fFN 检测对母婴结局有显著影响。一项研究报告了对阴性 fFN 检测结果的妇女进行 >6 小时观察的亚组分析，结果表明，在医生知道结果的情况下，住院时间缩短。结合新研究和之前系统评价的数据，汇总的敏感性和特异性估计值为：检测后 7-10 天内分娩的为 76.7%和 82.7%；<34 周妊娠的为 69.1%和 84.4%；<37 周妊娠的为 60.8%和 82.3%。所有亚组敏感性分析的结果相似。基础成本分析结果表明，与常规护理相比，fFN 检测可节省 23.87 英镑。fFN 检测的成本接近 45 英镑，处于成本中性状态。概率敏感性分析给出了增量成本（节省）为 -25.59 英镑（97.5%置信区间 -304.96 至 240.06），表明存在很大的不确定性。敏感性分析表明，入院率对结果的影响最大。
胎儿纤维连接蛋白检测对预测早产具有中等准确性。主要潜在作用可能是通过识别不需要干预的妇女来减少医疗保健资源的使用。来自 RCTs 的证据表明，fFN 不会增加不良结局，并且可能减少资源使用。基础案例分析显示，fFN 检测具有适度的成本优势，这主要取决于 fFN 检测是否减少了住院。目前，没有高质量的研究，现有的试验通常缺乏足够的效力。因此，需要使用适当的研究设计进行高质量的、充分有力的试验，以证实所提出的发现。
PROSPERO 2011：CRD42011001468。可从 www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42011001468 获得。
国家卫生研究所卫生技术评估计划。
