Associations of serum biomarkers with blood pressure in ex-preterm children and adolescents

Objective: Preterm birth is considered a risk factor for the development of hypertension throughout life course. The aims of the present study were to assess the levels of serum biomarkers in ex-preterm children and adolescents compared to healthy controls and to examine for associations with office, ambulatory BP parameters, and pulse wave velocity. Design and method: The study population included 52 preterm and 26 term born children and adolescents who underwent office, ambulatory BP monitoring, and assessment of pulse wave velocity. Serum biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), and matrix metalloproteinase-2, -9 (MMP-2, -9) were measured using double-antibody sandwich enzyme-linked Immunosorbent assay. Results: Thirty-five % of the study population presented office hypertension, 38.5% of the ex-preterm and 28% of the term children. Seventeen % of the ex-preterm group presented ABP hypertension. None of the controls had ABP hypertension. Half of the ex-preterm children had white-coat hypertension. Serum NGAL and MMP-2 and -9 levels did not differ between ex-preterm and term groups. NGAL and MMP-9 presented significant correlations with office systolic BP z score (r = 0.33, p<0.005, and r = 0.30, p<0.05, respectively) and day systolic BP z score (r = 0.29, p<0.01, and r = 0.23, p<0.05, respectively). The above associations were also observed in the ex-preterm, but not in the term group. There was no association between any biomarker and PWV. In univariate analysis NGAL presented significant correlations with office (B = 0.009, 95%CI 0.001-0.017, p<0.05) and day systolic BP z-score (B = 0.009, 95%CI 0.001-0.017, p< 0.05) in the ex-preterm group after adjustment for age, sex, birth weight and gestational age. The receiver operating characteristic (ROC) curve analysis showed that NGAL predicted hypertension in ex-preterm children with area under the curve (AUC) 0.713, 95% CI 0.57-0.85, p = 0.010. Conclusions: In ex-preterm children and adolescents NGAL and MMP-9 presented significant associations with systolic BP. The associations for NGAL persisted after adjustment for birth parameters, age and sex suggesting that NGAL should be further investigated as it could serve as early biomarker of hypertension evolution in ex-preterm children and adolescents.