Pharmacological interventions for the prevention of foetal growth restriction: systematic review and network meta-analysis.

Pharmacological interventions for the prevention of foetal growth restriction: systematic review and network meta-analysis.

Alfredo Vannacci (1,2), Alessandra Bettiol (1), Niccolò Lombardi (1), Giada Crescioli (1), Laura Avagliano (3), Claudia Ravaldi (1,3)

(1) Department of Neurosciences, Psychology, Drug Research and Child Health, Florence, Italy; (2) CiaoLapo, Charity for Healthy Pregnancy, Stillbirth and Perinatal Loss Support, Prato, Italy; (3) Department of Health Sciences, San Paolo Hospital Medical School, University of Milan, Milan, Italy; (4) Department of Health Sciences, University of Florence, Florence, Italy

Background:
Foetal growth restriction (FGR) includes different conditions in which a foetus 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 foetal organs to mature, while preventing starvation. As no firm evidence exists to guide clinicians towards the most effective therapeutic intervention, we performed a systematic review and network meta-analysis of available literature.

Methods:
We searched MEDLINE and Embase for clinical trials and observational studies performed on gestating women with clinically-diagnosed risk of FGR. All experimental interventions were included. Studied outcomes were birth of small for gestational age (SGA) babies, stillbirth or neonatal death, and pre-eclampsia.

Results:
Systematic review and network meta-analysis are still undergoing. Final results will be presented in the communication. Here we report preliminary results. A total of 16772 records were identified, after 8-step screening 11 studies were included in the meta-analysis. Nine studies were randomised controlled trial, 2 were observational studies. Among the outcomes, seven studies evaluated pre-eclampsia, 6 SGA, 9 foetal or neonatal death. Quality assessment of the studies is still undergoing. With regard to preeclampsia, aspirin showed a protective effect with respect to placebo or no treatment (direct comparison OR 2.93 [1.40-6.12] – mixed comparison OR 4.21 (1.37-12.97)]), and aspirin + LMWH was superior to placebo/no treatment (OR 4.18 [1.70-10.28]) and sildenafil [OR 5.03 (1.46-17.33)]. With regard to the outcomes SGA and stillbirth or neonatal death, no significant association was found.

Conclusion:
Although data are still preliminary, aspirin alone or associated with LMWH seems to be significantly more effective than placebo or no treatment in preventing pre-eclampsia in women with FGR, while no significant preventive effect was found regarding birth of SGA or stillbirth/neonatal death.

Ethics statement:
No subject was recruited for the research. Before starting the systematic review and network meta-analysis, the protocol was registered with PROSPERO (registration number CRD42019122831).

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