Perinatal outcome of monochorionic twin pregnancy complicated by selective fetal growth restriction according to management: systematic review and meta‐analysis

IntroductionFetal growth restriction (FGR) is a relevant research and clinical concern since it is related to higher risks of adverse outcomes at any period of life. Current predictive tools in pregnancy (clinical factors, ultrasound scan, placenta-related biomarkers) fail to identify the true growth-restricted fetus. However, technologies based on metabolomics have generated interesting findings and seem promising. In this systematic review, we will address diagnostic accuracy of metabolomics analyses in predicting FGR.Methods and analysisOur primary outcome is small for gestational age infant, as a surrogate for FGR, defined as birth weight below the 10th centile by customised or population-based curves for gestational age. A detailed systematic literature search will be carried in electronic databases and conference abstracts, using the keywords ‘fetal growth retardation’, ‘metabolomics’, ‘pregnancy’ and ‘screening’ (and their variations). We will include original peer-reviewed articles published from 1998 to 2018, involving pregnancies of fetuses without congenital malformations; sample collection must have been performed before clinical recognition of growth impairment. If additional information is required, authors will be contacted. Reviews, case reports, cross-sectional studies, non-human research and commentaries papers will be excluded. Sample characteristics and the diagnostic accuracy data will be retrieved and analysed. If data allows, we will perform a meta-analysis.Ethics and disseminationAs this is a systematic review, no ethical approval is necessary. This protocol will be publicised in our institutional websites and results will be submitted for publication in a peer-reviewed journal.PROSPERO registration numberCRD42018089985.

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Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-029467 ◽

2019 ◽

Vol 9 (7) ◽

pp. e029467 ◽

Cited By ~ 2

Author(s):

Alessandra Bettiol ◽

Niccolò Lombardi ◽

Giada Crescioli ◽

Laura Avagliano ◽

Alessandro Mugelli ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Meta Analysis ◽

Scientific Journal ◽

Antiplatelet Agents ◽

Growth Restriction ◽

Pharmacological Management ◽

Safety Outcome

IntroductionFetal 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 analysisWe 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 disseminationResults will be disseminated through a peer-reviewed scientific journal, and by scientific congresses and meetings.PROSPERO registration numberCRD42019122831.

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The ability of late pregnancy maternal tests to predict adverse pregnancy outcomes associated with placental dysfunction (specifically fetal growth restriction and pre-eclampsia): a protocol for a systematic review and meta-analysis of prognostic accuracy studies

Systematic Reviews ◽

10.1186/s13643-020-01334-5 ◽

2020 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Melanie Griffin ◽

Alexander E. P. Heazell ◽

Lucy C. Chappell ◽

Jian Zhao ◽

Deborah A. Lawlor

Keyword(s):

Systematic Review ◽

Fetal Growth ◽

Pregnancy Outcomes ◽

Fetal Growth Restriction ◽

Meta Analysis ◽

Late Pregnancy ◽

Growth Restriction ◽

Placental Dysfunction ◽

Prognostic Accuracy ◽

Adverse Pregnancy

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The effect of phosphodiesterase-5 inhibitors on uteroplacental and fetal cerebral perfusion in pregnancies with fetal growth restriction: a systematic review and meta-analysis

European Journal of Obstetrics & Gynecology and Reproductive Biology ◽

10.1016/j.ejogrb.2021.10.032 ◽

2021 ◽

Author(s):

Kamran Hessami ◽

Mauro Cozzolino ◽

Alireza A. Shamshirsaz

Keyword(s):

Systematic Review ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Cerebral Perfusion ◽

Meta Analysis ◽

Growth Restriction ◽

Phosphodiesterase 5 Inhibitors ◽

Phosphodiesterase 5

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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

Systematic Reviews ◽

10.1186/s13643-021-01849-5 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Jessica Liauw ◽

Katie Groom ◽

Wessel Ganzevoort ◽

Christian Gluud ◽

Christopher J. D. McKinlay ◽

...

Keyword(s):

Systematic Review ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Early Onset ◽

Sequential Analysis ◽

Meta Analysis ◽

Growth Restriction ◽

Trial Sequential Analysis ◽

Individual Participant Data ◽

Individual Participant

Abstract 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).

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