Impact of early versus delayed cord clamping on oxidative stress in neonates with intrauterine growth restriction: a prospective randomized controlled trial.

BACKGROUND: Oxidative stress is a key contributor to the pathophysiology of intrauterine growth restriction (IUGR). Evidence regarding the influence of umbilical cord clamping timing on neonatal oxidative balance remains limited. This study evaluated the effect of delayed cord clamping (DCC) on oxidative stress biomarkers in IUGR and appropriate-for-gestational-age (AGA) neonates. METHODS: This single-center, prospective randomized controlled trial included 90 neonates born at ≥ 29 weeks of gestation. Participants were randomized into four subgroups: IUGR-DCC (n = 25), IUGR-ECC (early cord clamping)(n = 32), AGA-DCC (n = 17), and AGA-ECC (n = 16). DCC was defined as clamping at 120 ± 30 s and ECC within 60 s after birth. Umbilical cord blood was analyzed for total antioxidant status (TAS), total oxidant status (TOS), catalase activity, and oxidative stress index (OSI). RESULTS: In IUGR infants, DCC was associated with higher TAS (2.01 ± 0.20 vs. 1.69 ± 0.22 mmol/L, p < 0.001) and catalase activity (74.5 ± 13.7 vs. 63.8 ± 11.1 kU/L, p = 0.004), and lower TOS (31.8 ± 6.2 vs. 42.7 ± 7.5 µmol/L, p < 0.001) and OSI (15.8 ± 3.2 vs. 25.4 ± 4.8, p < 0.001) compared with ECC. Similar differences were found among AGA infants: TAS (2.12 ± 0.18 vs. 1.87 ± 0.20, p < 0.001), catalase (78.1 ± 10.6 vs. 69.3 ± 12.6, p = 0.006), TOS (26.2 ± 5.2 vs. 36.1 ± 6.7, p < 0.001), and OSI (12.5 ± 2.7 vs. 19.1 ± 3.6, p < 0.001). Multivariate analysis confirmed DCC as an independent predictor of improved oxidative markers. CONCLUSIONS: Delayed cord clamping improved oxidative stress profiles in both IUGR and AGA neonates, with greater benefit in growth-restricted infants. These results provide biochemical support for DCC, though larger multicenter trials are required to determine long-term clinical relevance. TRIAL REGISTRATION: This study was prospectively registered at ClinicalTrials.gov under registration number NCT07031583 on 13 June 2025.