RT Journal Article
SR Electronic
T1 Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysis
JF BMJ Open
JO BMJ Open
FD British Medical Journal Publishing Group
SP e029467
DO 10.1136/bmjopen-2019-029467
VO 9
IS 7
A1 Alessandra Bettiol
A1 Niccolò Lombardi
A1 Giada Crescioli
A1 Laura Avagliano
A1 Alessandro Mugelli
A1 Claudia Ravaldi
A1 Alfredo Vannacci
YR 2019
UL http://bmjopen.bmj.com/content/9/7/e029467.abstract
AB Introduction 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.Methods and analysis 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.Ethics and dissemination Results will be disseminated through a peer-reviewed scientific journal, and by scientific congresses and meetings.PROSPERO registration number CRD42019122831.