Osteoprotegerin - Fetal Growth Retardation and Atherosclerosis in Newborns

Fetal growth restriction (FGR) is believed to occur in about 3–7% of pregnancies (1), making it a relatively common complication in pregnancy. FGR is linked to higher rates of perinatal morbidity and mortality. Early prenatal detection and appropriate intervention can enhance outcomes (2).

Understanding Fetal Growth Retardation

Osteoprotegerin – Fetal Growth Retardation and Atherosclerosis in Newborns

Fetal Growth Retardation (FGR) is a condition characterized by the inadequate growth of the fetus in utero, typically resulting from placental insufficiency, maternal health factors, or fetal anomalies. It is diagnosed when the fetus exhibits a growth trajectory below the 10th percentile for gestational age, often associated with compromised nutrient and oxygen delivery. FGR has been linked to adverse perinatal outcomes and may have long-term implications for cardiovascular and metabolic health, potentially mediated by alterations in vascular structure and function established during fetal development.

The Role of Osteoprotegerin

Osteoprotegerin (OPG) is a protein involved in bone metabolism and vascular health. Elevated levels of OPG have been associated with various cardiovascular conditions, including atherosclerosis and arterial stiffness (3, 4).

Exploring the Link Between Fetal Growth Retardation, Postnatal Osteoprotegerin Levels, and Aortic Health

A recent study titled “Association of Fetal Growth Retardation with Postnatal Osteoprotegerin Concentrations and Aortic Intima-Media Thickness.” sheds light on how early-life growth issues might influence cardiovascular health later in life.

Osteoprotegerin – Fetal Growth Retardation and Atherosclerosis in Newborns

Using the Biomedica Osteoprotegerin (OPG) ELISA assay (cat. no. BI-20403), scientists investigated how fetal growth issues might influence postnatal OPG serum levels and aortic intima-media thickness.

Key findings:

• The study examined the association between FGR and postnatal cardiovascular markers.
• Increased postnatal OPG levels were linked to FGR.
• FGR was also associated with increased Aortic Intima-Media Thickness, indicating early vascular changes.

The findings suggest that fetal growth issues might play a role in future cardiovascular health, highlighting the potential benefits of early detection and monitoring of at-risk infants for better long-term outcomes.

Osteoprotegerin (OPG) can reliably be measured with a conventional ELISA assay

 Biomedica OPG ELISA (cat. no. BI-20403)

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Association of Fetal Growth Retardation with Postnatal Osteoprotegerin Concentrations and Aortic Intima-Media Thickness. Diseases. Karatza AA, Kostopoulou E, Fouzas S, Antonakopoulos N, Sinopidis X, Kritikou D, Efthymiadou A, Dimitriou G, Chrysis D. 2026 Mar 8;14(3):100. doi: 10.3390/diseases14030100. PMID: 41892001; PMCID: PMC13025314.

Abstract

Background: Fetal Growth Retardation (FGR) is considered a risk factor for atherosclerosis and coronary artery disease in adulthood. Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor superfamily, is reported to be elevated in atherosclerosis.

Objectives: In this case-control study, we investigated whether FGR affects postnatal OPG serum concentrations and the possible association between OPG levels and aortic intima-media thickness (aIMT), an index of preclinical atherosclerosis.

Methods: We studied 30 infants with FGR and 30 appropriate for gestational age (AGA) infants matched for gestational age and sex. Quantitative determination of plasma OPG was performed via enzyme immunoassay on the second (DOL2) and fifth (DOL5) day of life. aIMT was measured in the distal abdominal aorta and adjusted for aortic lumen diameter.

Results: Infants with FGR had significantly higher OPG levels on both DOL2 and DOL5 as compared to controls (DOL2: 5.4 ± 1.0 pmol/L vs. 4.6 ± 1.0 pmol/L, p = 0.002 and DOL5: 5.1 ± 0.8 pmol/L vs. 3.9 ± 0.7 pmol/L, p < 0.001). Between DOL2 and DOL5, OPG concentrations did not change significantly in infants with FGR (difference 0.3 ± 0.2 pmol/L, p = 0.087) but decreased slightly in controls (difference 0.7 ± 0.3 pmol/L, p = 0.003). FGR was also associated with increased aIMT (0.11 ± 0.03 vs. 0.06 ± 0.02, p < 0.001). There was a positive correlation between OPG and aIMT on DOL2 (r = 0.494, p < 0.001), which became stronger on DOL5 (r = 0.791, p < 0.001).

Conclusions: We report significantly increased concentrations of OPG in infants with FGR and a positive correlation with aIMT. Follow-up studies with repeat OPG and aIMT measurements may be indicated to evaluate whether these findings represent a permanent effect of FGR on the offspring.

Literature

1. Genetic Background of Fetal Growth Restriction. Nowakowska BA, Pankiewicz K, Nowacka U, Niemiec M, Kozłowski S, Issat T. Int J Mol Sci. 2021 Dec 21;23(1):36. doi: 10.3390/ijms23010036. PMID: 35008459; PMCID: PMC8744929.
2. Clinical practice guidance for the management of fetal growth restriction: an expert review. Villalaín C, Herraiz I, Akolekar R, Figueras F, Crispi F, Rizzo G, Mappa I, Mendoza M, Del Moral T, Stampalija T, Ghi T, Galindo A. J Matern Fetal Neonatal Med. 2025 Dec;38(1):2526111. doi: 10.1080/14767058.2025.2526111. Epub 2025 Jul 7. PMID: 40623849.
3. Association of bone biomarkers with advanced atherosclerotic disease in people with overweight/obesity. Del Toro R, Cavallari I, Tramontana F, Park K, Strollo R, Valente L, De Pascalis M, Grigioni F, Pozzilli P, Buzzetti R, Napoli N, Maddaloni E. Endocrine. 2021 Aug;73(2):339-346. doi: 10.1007/s12020-021-02736-8. Epub 2021 May 4. PMID: 33948786.
4. Atherosclerosis and Bone Loss in Humans-Results From Deceased Donors and From Patients Submitted to Carotid Endarterectomy. Carmona-Fernandes D, Barreira SC, Leonardo N, Casimiro RI, Castro AM, Santos PO, Fernandes AN, Cortes-Figueiredo F, Gonçalves CA, Cruz R, Fernandes ML, Ivo M, Pedro LM, Canhão H, Fonseca JE, Santos MJ.Front Med (Lausanne). 2021 May 20;8:672496. doi: 10.3389/fmed.2021.672496. PMID: 34095177.