Bettiol Alessandra, Avagliano Laura, Lombardi Niccolò, Crescioli Giada, Emmi Giacomo, Urban Maria Letizia, Virgili Gianni, Ravaldi Claudia, Vannacci Alfredo
Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
Department of Health Sciences, San Paolo Hospital Medical School, University of Milan, Milan, Italy.
Clin Pharmacol Ther. 2021 Jul;110(1):189-199. doi: 10.1002/cpt.2164. Epub 2021 Feb 26.
The prevention of fetal growth restriction (FGR) is challenging in clinical practice. To date, no meta-analysis summarized evidence on the relative benefits and harms of pharmacological interventions for FGR prevention. We performed a systematic review and network meta-analysis (NetMA), searching PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until November 2019. We included clinical trials and observational studies on singleton gestating women evaluating antiplatelet, anticoagulant, or other treatments, compared between each other or with controls (placebo or no treatment), and considering the pregnancy outcome FGR (primary outcome of the NetMA). Secondary efficacy outcomes included preterm birth, placental abruption, and fetal or neonatal death. Safety outcomes included bleeding and thrombocytopenia. Network meta-analyses using a frequentist framework were conducted to derive odds ratios (ORs) and 95% confidence intervals (CIs). Of 18,780 citations, we included 30 studies on 4,326 patients. Low molecular weight heparin (LMWH), alone or associated with low-dose aspirin (LDA), appeared more efficacious than controls in preventing FGR (OR 2.00, 95% CI 1.27-3.16 and OR 2.67, 95% CI 1.21-5.89 for controls vs. LMWH and LDA + LMWH, respectively). No difference between active treatments emerged in terms of FGR prevention, but estimates for treatments other than LMWH +/- LDA were imprecise. Only the confidence in the evidence regarding LMWH vs. controls was judged as moderate, according to the Confidence in Network Meta-Analysis framework. No treatment was associated with an increased risk of bleeding, although estimates were precise enough only for LMWH. These results should inform clinicians on the benefits of active pharmacological prophylaxis for FGR prevention.
在临床实践中，预防胎儿生长受限（FGR）具有挑战性。迄今为止，尚无荟萃分析总结药物干预预防FGR的相对益处和危害的证据。我们进行了一项系统评价和网状荟萃分析（NetMA），从数据库建立至2019年11月检索了PubMed、Embase、Cochrane图书馆和ClinicalTrials.gov。我们纳入了关于单胎妊娠妇女的临床试验和观察性研究，评估抗血小板药物、抗凝剂或其他治疗方法，相互之间或与对照组（安慰剂或不治疗）进行比较，并考虑妊娠结局FGR（NetMA的主要结局）。次要疗效结局包括早产、胎盘早剥以及胎儿或新生儿死亡。安全性结局包括出血和血小板减少症。使用频率学派框架进行网状荟萃分析以得出比值比（OR）和95%置信区间（CI）。在18780条引文中，我们纳入了30项针对4326例患者的研究。低分子量肝素（LMWH）单独使用或与低剂量阿司匹林（LDA）联合使用，在预防FGR方面似乎比对照组更有效（对照组与LMWH以及LDA + LMWH相比，OR分别为2.00，95%CI 1.27 - 3.16和OR 2.67，95%CI 1.21 - 5.89）。在预防FGR方面，活性治疗之间未出现差异，但LMWH +/- LDA以外的治疗估计值不精确。根据网状荟萃分析框架的信心评估，只有关于LMWH与对照组的证据信心被判定为中等。没有治疗与出血风险增加相关，尽管只有LMWH的估计足够精确。这些结果应为临床医生提供关于药物积极预防FGR的益处的信息。
