Extrauterine Growth Restriction Followed by Catch-Up Growth Reveals Adverse Effects on Aorta Microstructure: An Animal-Based Experimental Study

Abstract

Background: Preterm birth is a major global concern, often leading to extrauterine growth restriction (EUGR) and later need for catch-up growth. Excessive catch-up growth may predispose to long-term cardiovascular risk. The objective of this study was to investigate the histological alterations in the aortic microstructure of Wistar rats exposed to extrauterine growth restriction followed by varying degrees of catch-up growth. 
Methods: This animal-based experimental study was conducted on 120 neonatal Wistar rats using a rodent litter-size manipulation model that mimics human extrauterine growth restriction (EUGR) and catch-up growth. Initially, 30 pups were fed normally (Group N), while 90 were undernourished (Group R) to simulate EUGR. From days 11 to 21, the undernourished rats were separated into two subgroups: normal growth (RN, n = 30) and catch-up growth (RC, n = 60). The RC subgroup was further subdivided into accelerated (RCA) and slow (RCS) catch-up growth based on growth velocity. On day 60, microscopic aortic parameters (lumen and wall areas, wall-to-lumen ratio, and collagen & elastin content) were assessed after euthanasia and compared using ANOVA with post hoc Tukey tests.
Results: Both RCA and RCS groups showed significantly reduced aortic luminal area and increased vessel wall area and wall-to-lumen ratio compared with RN and N groups (p<0.001). No significant difference was observed between RCA and RCS (p>0.05). Collagen and elastin contents of the tunica media did not differ significantly among groups (p>0.05).
Conclusion: Catch-up growth after extra-uterine growth restriction led to aortic wall changes, supporting the need for balanced rather than rapid catch-up growth in preterm infants.