Comparative effectiveness of pharmacological treatments for fetal growth restriction: a network meta-analysis

Background: Fetal growth restriction (FGR) is a common pregnancy complication associated with adverse maternal and fetal outcomes. Effective pharmacological interventions are essential for enhancing fetal growth and mitigating related complications. This study aimed to evaluate and compare the efficacy of various pharmacological treatments for FGR using a network meta-analysis (NMA). Objective: To systematically evaluate and compare the effectiveness of different pharmacological interventions for FGR via a network meta-analysis (NMA). Strategy: A comprehensive literature search was performed in PubMed, Medline, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials, and Web of Science. The search was updated through 31 January 2026, to ensure the inclusion of the most recent evidence. Selection Criteria: Eligible studies included singleton pregnancies at high risk of FGR. Studies were excluded if they involved multiple pregnancies, fetal genetic abnormalities, or maternal comorbidities such as drug or alcohol abuse. Data Collection and Analysis: A systematic review and network meta-analysis were conducted in strict accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to ensure methodological rigor. Main Results: Compared with the control group and low-dose aspirin (LDA) alone, low-molecular-weight heparin (LMWH) and the combination of LMWH + LDA significantly reduced the incidence of intrauterine growth restriction (IUGR) (odds ratio [OR] = 0.40, 95% confidence interval [CI] = 0.26-0.62; OR = 0.37, 95% CI = 0.15-0.93, respectively). Additionally, LMWH monotherapy significantly decreased the risk of several pregnancy complications, including preeclampsia (OR = 0.21, 95% CI = 0.05-0.93), preterm birth (OR = 0.61, 95% CI = 0.45-0.81), miscarriage (OR = 0.42, 95% CI = 0.19-0.91), and cesarean section (OR = 0.34, 95% CI = 0.18-0.67). The combination of LMWH + LDA significantly improved the live birth rate (OR = 7.08, 95% CI = 2.16-23.22) and reduced the incidence of preeclampsia (OR = 0.22, 95% CI = 0.08-0.59). Conclusion: LMWH and LMWH combined with LDA are effective in reducing IUGR, preventing preeclampsia, and improving live birth rates in high-risk pregnancies complicated by FGR. These findings provide robust evidence supporting the use of LMWH and LMWH + LDA as promising therapeutic options for the management of FGR. Clinical Trial Registration: PROSPERO registration: CRD420251142968.