Year: 2026
Type: review
Study design: Systematic Review
Abstract: Background: Fetal Growth Restriction (FGR) and Small-for-Gestational-Age (SGA) are major contributors to perinatal morbidity and mortality. Maternal vitamin D deficiency has been proposed to impair placental development and fetal growth through mechanisms involving angiogenesis, immune regulation, and oxidative stress. Increasing evidence suggests that maternal 25-hydroxyvitamin D [25(OH)D] status may play a significant role in the pathogenesis of impaired fetal growth. Objective: To synthesize evidence on the association between maternal 25-hydroxyvitamin D [25(OH)D] concentrations and the risk of FGR and SGA, and to evaluate the impact of vitamin D supplementation on fetal growth outcomes. Methods: A systematic search of PubMed, Cochrane Library, Springer, ScienceDirect, and DOAJ was performed following PRISMA 2020 guidelines. Observational studies and randomized controlled trials examining maternal vitamin D status and fetal growth outcomes were included. Results: The 48 included studies showed consistent evidence linking low maternal 25(OH)D concentrations with increased risk of FGR and SGA, with several analyses demonstrating dose-response patterns at lower vitamin D thresholds. Associations with preterm birth were directionally similar but less consistent. Findings from intervention trials assessing vitamin D supplementation were heterogeneous, influenced by variations in dosage, timing of initiation, baseline vitamin D status, adherence, and co-nutrient exposures. Experimental and mechanistic studies further supported biological plausibility, demonstrating vitamin D-mediated effects on placental angiogenesis, immune modulation, endocrine signaling, and oxidative stress pathways. Conclusion: Maternal vitamin D deficiency is consistently associated with impaired fetal growth, although findings from supplementation trials remain variable. Standardized dosing strategies, harmonized diagnostic cut-offs, and better-controlled interventions are needed to clarify the optimal role of vitamin D in preventing FGR and SGA. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024622395.
Source: Frontiers in Medicine
Authors: Leony Octavia, Putri Nabila, Dwi Andhika Panjarwanto, Putri Lenggo Geany, Yosua Darmadi Kosen, Aldo Aulia Rahman, Vallexa Septina Yora, R. Mohamad Javier, Mohammad Haekal, Lucky Sutanto, Arthur Peter Tandayu, Srigita Varsha, Muhamad Dwi Eka Putra, Angela Anjelina Cita, Brilliant Sofia Maharani, Muhammad Falah Ghani Nuruddin, Savira Salsabila, Dwi Fitri Handayani Friska
Institutions: Hasanuddin University, Pelita Harapan University, University of Brawijaya, Diponegoro University, Maranatha Christian University, Sriwijaya University, Fatmawati Hospital, Universitas Muhammadiyah Malang, Padjadjaran University, Universitas Jember, Duta Wacana Christian University, Sultan Agung Islamic University, Islamic University of Indonesia, Riau University
Language: English
Topic: Vitamin D Research Studies
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7123942380