TY - JOUR
T1 - The role of vitamin D deficiency in fetal growth restriction
T2 - a systematic review
AU - Octavia, Leony
AU - Nabila, Putri
AU - Panjarwanto, Dwi Andhika
AU - Geany, Putri Lenggo
AU - Kosen, Yosua Darmadi
AU - Rahman, Aldo Aulia
AU - Yora, Vallexa Septina
AU - Javier, R. Mohamad
AU - Haekal, Mohammad
AU - Sutanto, Lucky
AU - Tandayu, Arthur Peter
AU - Varsha, Srigita
AU - Putra, Muhamad Dwi Eka
AU - Cita, Angela Anjelina
AU - Maharani, Brilliant Sofia
AU - Nuruddin, Muhammad Falah Ghani
AU - Salsabila, Savira
AU - Friska, Dwi Fitri Handayani
N1 - Publisher Copyright:
Copyright © 2026 Octavia, Nabila, Panjarwanto, Geany, Kosen, Rahman, Yora, Javier, Haekal, Sutanto, Tandayu, Varsha, Putra, Cita, Maharani, Nuruddin, Salsabila and Friska.
PY - 2026
Y1 - 2026
N2 - 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.
AB - 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.
KW - birthweight
KW - fetal growth restriction
KW - placental angiogenesis
KW - pregnancy outcomes
KW - preterm birth
KW - small-for-gestational-age
KW - vitamin D deficiency
UR - https://www.scopus.com/pages/publications/105029036140
U2 - 10.3389/fmed.2025.1725177
DO - 10.3389/fmed.2025.1725177
M3 - Review article
AN - SCOPUS:105029036140
SN - 2296-858X
VL - 12
JO - Frontiers in Medicine
JF - Frontiers in Medicine
M1 - 1725177
ER -