磷酸二酯酶 5 抑制剂治疗胎儿生长受限的短期结局：一项系统评价的研究方案，包含个体参与者数据荟萃分析、汇总荟萃分析和试验序贯分析。
Short-term outcomes of phosphodiesterase type 5 inhibitors for fetal growth restriction: a study protocol for a systematic review with individual participant data meta-analysis, aggregate meta-analysis, and trial sequential analysis.
机构信息
Department of Obstetrics and Gynaecology, University of British Columbia, Room C420-4500 Oak Street, Vancouver, British Columbia, V6H 3N1, Canada.
Liggins Institute, University of Auckland, Auckland, New Zealand.
出版信息
Syst Rev. 2021 Dec 3;10(1):305. doi: 10.1186/s13643-021-01849-5.
BACKGROUND
Early onset fetal growth restriction secondary to placental insufficiency can lead to severe maternal and neonatal morbidity and mortality. Pre-clinical studies and a few small randomised clinical trials have suggested that phosphodiesterase type 5 (PDE-5) inhibitors may have protective effects against placental insufficiency in this context; however, robust evidence is lacking. The STRIDER Consortium conducted four randomised trials to investigate the use of a PDE-5 inhibitor, sildenafil, for the treatment of early onset fetal growth restriction. We present a protocol for the pre-planned systematic review with individual participant data meta-analysis, aggregate meta-analysis, and trial sequential analysis of these and other eligible trials. The main objective of this study will be to evaluate the effects of PDE-5 inhibitors on neonatal morbidity compared with placebo or no intervention among pregnancies with fetal growth restriction.
METHODS
We will search the following electronic databases with no language or date restrictions: OVID MEDLINE, OVID EMBASE, the Cochrane Controlled Register of Trials (CENTRAL), and the clinical trial registers Clinicaltrials.gov and World Health Organisation International Clinical Trials Registry Platform (ICTRP). We will identify randomised trials of PDE-5 inhibitors in singleton pregnancies with growth restriction. Two reviewers will independently screen all citations, full-text articles, and abstract data. Our primary outcome will be infant survival without evidence of serious adverse neonatal outcome. Secondary outcomes will include gestational age at birth and birth weight z-scores. We will assess bias using the Cochrane Risk of Bias 2 tool. We will conduct aggregate meta-analysis using fixed and random effects models, Trial Sequential Analysis, and individual participant data meta-analysis using one- and two-stage approaches. The certainty of evidence will be assessed with GRADE.
DISCUSSION
This pre-defined protocol will minimise bias during analysis and interpretation of results, toward the goal of providing robust evidence regarding the use of PDE-5 inhibitors for the treatment of early onset fetal growth restriction.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42017069688).
背景
胎盘功能不全导致的早期胎儿生长受限可导致严重的母婴发病率和死亡率。临床前研究和一些小型随机临床试验表明，磷酸二酯酶 5（PDE-5）抑制剂在这种情况下可能对胎盘功能不全具有保护作用；然而，缺乏确凿的证据。STRIDER 联合会进行了四项随机试验，以研究 PDE-5 抑制剂西地那非治疗早期胎儿生长受限的作用。我们提出了一项方案，对这些试验和其他符合条件的试验进行预先计划的系统评价，包括个体参与者数据荟萃分析、汇总荟萃分析和试验序贯分析。本研究的主要目的将是评估 PDE-5 抑制剂与安慰剂或无干预相比，在胎儿生长受限的妊娠中对新生儿发病率的影响。
方法
我们将在没有语言或日期限制的情况下搜索以下电子数据库：OVID MEDLINE、OVID EMBASE、Cochrane 对照试验登记册（CENTRAL）以及临床试验登记处 Clinicaltrials.gov 和世界卫生组织国际临床试验注册平台（ICTRP）。我们将确定 PDE-5 抑制剂在胎儿生长受限的单胎妊娠中的随机试验。两名评审员将独立筛选所有引用、全文文章和摘要数据。我们的主要结局将是无严重不良新生儿结局的婴儿存活率。次要结局将包括出生时的胎龄和出生体重 z 评分。我们将使用 Cochrane 偏倚风险 2 工具评估偏倚。我们将使用固定和随机效应模型进行汇总荟萃分析，使用单阶段和两阶段方法进行试验序贯分析和个体参与者数据荟萃分析。证据的确定性将使用 GRADE 进行评估。
讨论
本预先定义的方案将最大限度地减少分析和解释结果中的偏倚，旨在为 PDE-5 抑制剂治疗早期胎儿生长受限的应用提供有力的证据。
系统评价注册
PROSPERO（CRD42017069688）。
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