Perinatal Redox Dysregulation in Gestational Tobacco Exposure: Compartment-Specific Composite Indices and Their Association with Birth Outcomes-A Prospective Cohort Study.

BACKGROUND

Gestational tobacco exposure is a major modifiable risk factor for adverse pregnancy outcomes; how smoking-induced redox perturbations transmit across the placental barrier to the fetal compartment, and mediate neonatal outcomes, remains incompletely understood.

METHODS

In a prospective cohort of 66 maternal-neonatal dyads (24 smokers, 42 non-smokers) from Târgu-Mures, six redox biomarkers (nitrite, nitrate, malondialdehyde, reduced, oxidized glutathione (GSH, GSSG) and GSH/GSSG ratio) were quantified in paired maternal and cord blood and converted to SI units, and pathway-specific composite indices (oxidative and nitrosative stress index-OSI, NSI, global redox index-GRI) were derived via standardized Z-scores of natural-log-transformed concentrations. Associations with preterm birth (PTB) and low birth weight (LBW) were assessed via multivariable regression. Benjamini-Hochberg false discovery rate (FDR) correction was applied within predefined test families.

RESULTS

Tobacco exposure was associated with nominally significant depletion of the Neonatal NSI (mean difference = -0.842; 95% CI: -1.567 to -0.117; p = 0.024; FDR-adjusted p = 0.142), while maternal indices showed no significant group differences. Lower Maternal GRI and Neonatal NSI were independently associated with lower birth weight and higher odds of preterm birth (aOR = 0.35 and 0.52, respectively; both p < 0.05). Maternal and neonatal nitrite concentrations were positively correlated (FDR-adjusted p = 0.002) and oxidized glutathione showed an inverse maternal-neonatal correlation (FDR-adjusted p = 0.001), whereas the maternal and neonatal NSI was not significant after FDR-correction (FDR-adjusted p = 0.078)

Conclusions

Gestational tobacco exposure was associated with depletion of the neonatal nitrosative stress index. Independently, lower maternal and neonatal composite redox indices were associated with lower birth weight and higher odds of preterm birth. Composite indices may offer an integrated assessment of perinatal redox status, but without external validation warrant confirmation in larger cohorts.