Maternal Circulating Angiogenic Biomarkers for Predicting Fetal Growth Restriction and Small-for-Gestational-Age Birth Without Preeclampsia
- 1Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea
- 2Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul 06273, Republic of Korea
Abstract
Maternal circulating angiogenic factors are established biomarkers in preeclampsia, but their early profiles in fetal growth impairment without preeclampsia remain unclear. We quantitatively synthesized data from observational studies measuring maternal serum placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), or their ratio before 29 weeks and before clinical recognition of growth impairment in singleton pregnancies without preeclampsia, subsequently classified as fetal growth restriction (FGR), small for gestational age (SGA), or unaffected. PubMed, Embase, and the Cochrane Library were searched through April 2026; 22 studies were included. In random-effects meta-analysis, PlGF was lower in affected pregnancies (standardized mean difference [SMD] −0.38; 95% CI −0.63 to −0.13; I2 = 92.0%; 19 studies), whereas sFlt-1 did not differ (SMD 0.03; 95% CI −0.27 to 0.34; I2 = 79.5%; 12 studies) and the ratio was higher in the primary analysis (SMD 0.39; 95% CI 0.08 to 0.70; I2 = 80.0%; seven studies). This pattern suggests that the ratio signal was influenced largely by lower PlGF. Bivariate analysis of five PlGF accuracy studies yielded a summary sensitivity of 0.29 and specificity of 0.86. Despite substantial heterogeneity, reduced PlGF was the most consistent early angiogenic feature in pregnancies subsequently classified as FGR/SGA without preeclampsia. Its low sensitivity does not support its use as a stand-alone screening test, but these findings warrant further evaluation of PlGF within multimarker prediction models.
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BibTeX
@article{kim2026maternal,
title = {{Maternal Circulating Angiogenic Biomarkers for Predicting Fetal Growth Restriction and Small-for-Gestational-Age Birth Without Preeclampsia}},
author = {Min-A Kim and Eunju Lee and Hye Sun Lee and Ah-Young Choi},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209155},
url = {https://www.mdpi.com/1422-0067/27/20/9155},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Maternal Circulating Angiogenic Biomarkers for Predicting Fetal Growth Restriction and Small-for-Gestational-Age Birth Without Preeclampsia
AU - Min-A Kim
AU - Eunju Lee
AU - Hye Sun Lee
AU - Ah-Young Choi
PY - 2026
DA - 2026/10/15
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209155
UR - https://www.mdpi.com/1422-0067/27/20/9155
AB - Maternal circulating angiogenic factors are established biomarkers in preeclampsia, but their early profiles in fetal growth impairment without preeclampsia remain unclear. We quantitatively synthesized data from observational studies measuring maternal serum placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), or their ratio before 29 weeks and before clinical recognition of growth impairment in singleton pregnancies without preeclampsia, subsequently classified as fetal growth restriction (FGR), small for gestational age (SGA), or unaffected. PubMed, Embase, and the Cochrane Library were searched through April 2026; 22 studies were included. In random-effects meta-analysis, PlGF was lower in affected pregnancies (standardized mean difference [SMD] −0.38; 95% CI −0.63 to −0.13; I2 = 92.0%; 19 studies), whereas sFlt-1 did not differ (SMD 0.03; 95% CI −0.27 to 0.34; I2 = 79.5%; 12 studies) and the ratio was higher in the primary analysis (SMD 0.39; 95% CI 0.08 to 0.70; I2 = 80.0%; seven studies). This pattern suggests that the ratio signal was influenced largely by lower PlGF. Bivariate analysis of five PlGF accuracy studies yielded a summary sensitivity of 0.29 and specificity of 0.86. Despite substantial heterogeneity, reduced PlGF was the most consistent early angiogenic feature in pregnancies subsequently classified as FGR/SGA without preeclampsia. Its low sensitivity does not support its use as a stand-alone screening test, but these findings warrant further evaluation of PlGF within multimarker prediction models.
SN - 1422-0067
ER -