Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
Department of Health Sciences, San Paolo Hospital Medical School, Università degli Studi di Milano, Milano, Italy.
BMJ Open. 2019 Jul 26;9(7):e029467. doi: 10.1136/bmjopen-2019-029467.
Fetal growth restriction (FGR) includes different conditions in which a fetus fails to reach the own full growth, and accounts for 28%-45% of non-anomalous stillbirths. The management of FGR is based on the prolongation of pregnancy long enough for fetal organs to mature while preventing starvation. As for pharmacological management, most guidelines recommend treatment with low-dose aspirin and/or with heparin, although this approach is still controversial and innovative promising therapies are under investigation. As no firm evidence exists to guide clinicians towards the most effective therapeutic intervention, this protocol describes methods for a systematic review and network meta-analysis (NetMA) of pharmacological treatments for FGR prevention.
We will search MEDLINE and Embase for clinical trials and observational studies performed on gestating women with clinically diagnosed risk of FGR. Experimental interventions will include heparin and low-molecular-weight heparin, acetylsalicylic acid, antiplatelet agents, phosphodiesterase type 3 and 5 inhibitors, maternal vascular endothelial growth factor gene therapy, nanoparticles, microRNA, statins, nitric oxide donors, hydrogen sulphide, proton pump inhibitors, melatonin, creatine and N-acetylcysteine, and insulin-like growth factors, compared between each other or to placebo or no treatment. Primary efficacy outcome is FGR. Secondary efficacy outcomes will be preterm birth, fetal or neonatal death and neonatal complications. For the safety outcome, all adverse events reported in included studies and experienced by either mothers, fetuses or newborns will be considered. Two review authors will independently screen title, abstract and full paper text, and will independently extract data from included studies. Where possible and appropriate, for primary and secondary efficacy outcomes, a NetMA will be performed using a random-effects model within a frequentist framework. Adverse events will be narratively described.
Results will be disseminated through a peer-reviewed scientific journal, and by scientific congresses and meetings.
CRD42019122831.
胎儿生长受限（FGR）包括胎儿未能充分生长的不同情况，占非畸形性死胎的 28%-45%。FGR 的管理基于延长妊娠时间，以使胎儿器官成熟，同时防止饥饿。在药物治疗方面，大多数指南建议使用低剂量阿司匹林和/或肝素治疗，尽管这种方法仍存在争议，正在研究创新的有前途的治疗方法。由于没有确凿的证据指导临床医生采取最有效的治疗干预措施，因此本方案描述了一种用于预防胎儿生长受限的药物治疗的系统评价和网络荟萃分析（NetMA）的方法。
我们将在 MEDLINE 和 Embase 中搜索针对临床诊断为胎儿生长受限风险的孕妇进行的临床试验和观察性研究。实验性干预措施将包括肝素和低分子量肝素、乙酰水杨酸、抗血小板药物、磷酸二酯酶 3 和 5 抑制剂、母血管内皮生长因子基因治疗、纳米颗粒、microRNA、他汀类药物、一氧化氮供体、硫化氢、质子泵抑制剂、褪黑素、肌酸和 N-乙酰半胱氨酸、以及胰岛素样生长因子，将彼此之间以及与安慰剂或不治疗进行比较。主要疗效结局是胎儿生长受限。次要疗效结局将是早产、胎儿或新生儿死亡和新生儿并发症。对于安全性结局，将考虑纳入研究中报告的所有不良事件以及母亲、胎儿或新生儿经历的不良事件。两名综述作者将独立筛选标题、摘要和全文文本，并独立从纳入研究中提取数据。在可能和适当的情况下，对于主要和次要疗效结局，将在频繁主义框架内使用随机效应模型进行 NetMA。不良事件将进行叙述性描述。
结果将通过同行评议的科学期刊、科学大会和会议传播。
PROSPERO 注册号：CRD42019122831。
