Environmental, Maternal and Placental Vascular Determinants of Foetal Growth Restriction: A Systematic Review and Meta-analysis of the Maternal–uteroplacental Microvascular Continuum

Abstract Background and Objective: Foetal growth restriction (FGR) is a major contributor to perinatal morbidity, yet its upstream determinants remain insufficiently integrated across maternal, uterine and placental domains. Emerging evidence suggests that FGR arises along a maternal–uteroplacental vascular continuum. This review aimed to synthesise current knowledge on maternal cardiovascular adaptation, uterine artery remodelling, environmental influences and placental microvascular pathology associated with FGR. Methodology: A systematic review was undertaken in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Searches of PubMed and PubMed Central identified studies examining maternal haemodynamics, uteroplacental circulation, environmental exposures and placental microvascular findings relevant to FGR. No date or language limits were applied other than the availability of an English abstract. Duplicates were removed, and studies were screened in two stages. Risk of bias was assessed using the risk of bias in systematic reviews. Data were synthesised narratively due to heterogeneity in study designs, populations and outcome measures. Results: A total of 612 records were identified; 39 studies met the predefined eligibility criteria. Across maternal studies, women who later developed FGR commonly demonstrated reduced cardiac output, increased systemic vascular resistance or impaired early gestational vascular adaptation. Uterine artery studies consistently reported incomplete spiral artery remodelling and elevated impedance. Environmental literature indicated additional vascular stress from endocrine-disrupting chemicals and microplastic exposure. Placental studies described recurring microvascular lesions, including maternal vascular malperfusion, distal villous hypoplasia and inflammatory injury. Diagnostic approaches combining maternal haemodynamics, Doppler indices and placental biomarkers performed better than single-modality assessments. Conclusions: Evidence across domains supports FGR as the downstream expression of a disrupted maternal–uteroplacental vascular continuum. Earlier risk stratification based on maternal cardiovascular phenotype, uteroplacental imaging and placental biomarkers may enable preventive strategies and shift clinical practice towards upstream intervention.