467 - Longitudinal Cardiovascular and Renal Biomarker Profiles in Extremely Preterm Infants: Influence of gestational age and PDA shunt burden

Publication Number: 3452.467

Adrianne R. Bischoff, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States; Lyndsay Harshman, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States; Brynna Van Wyk, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States; Timothy Boly, University of Iowa, Iowa City, IA, United States; Jennifer Bermick, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States; Patrick McNamara, University of Iowa, Iowa city, IA, United States

Background: Patent ductus arteriosus (PDA) can reduce systemic blood pressure (BP), with prolonged exposure altering normal physiological adaptations. Chronic PDA-attributable renal under perfusion may upregulate the renin-angiotensin-aldosterone system, normalizing BP overtime. The temporal evolution of cardiovascular and renal biomarkers in this context remains under explored.

Objective: Establish normative longitudinal data for cardiovascular and renal biomarkers in extremely preterm infants and evaluate their relationship with gestational age (GA) and postnatal age. The secondary objective was to evaluate biomarkers patterns in neonates with low versus high PDA shunt burden.

Design/Methods: Prospective cohort of infants born < 27 weeks gestation at the University of Iowa Stead Family Children's Hospital (04/22-11/24). Eligible infants underwent targeted neonatal echocardiography on days 1 and 7±2. Exclusion criteria: right-to-left or bidirectional PDA on day 7 and major congenital/genetic anomalies. Blood samples were obtained at 4 timepoints (7-14, 21-28, 35-42 days, and term-corrected GA); urine was obtained at the same timepoints plus < 48h after birth. Patients were classified as a) low shunt burden (≤1 medical course) or b) high shunt burden (≥2 medical courses and/or definitive PDA closure). Biomarkers included urinary neutrophil gelatinase-associated lipocalin (uNGAL), renin, aldosterone, brain natriuretic peptide (BNP) and troponin. Associations were assessed using mixed-effect models and groups were compared with standard statistics. The study was approved by the University of Iowa IRB.

Results: Fifty patients were enrolled (mean±SD GA 24.7±1.3 weeks; birth weight 668±157 grams). Figure 1 depicts the longitudinal biomarker trajectories. Both gestational age and postnatal week were independently associated with uNGAL concentrations (Table 1). BNP levels were significantly higher among infants with high shunt burden at 7-14 days (p=0.004) and 21-28 days (p < 0.001), while renin concentrations were elevated at 35-42 days (p=0.018) (Table 2). BNP and renin were similar between the groups at term-corrected GA.

Conclusion(s): Cardiovascular and renal biomarkers in extremely preterm infants evolve dynamically with both gestational and postnatal maturation. Higher BNP and renin concentrations among infants with greater PDA shunt burden suggest progressive myocardial and RAAS activation with prolonged exposure. These preliminary findings are hypothesis-generating and warrant future mechanistic and longitudinal investigations exploring biomarker changes in relation to the timing and severity of PDA shunt physiology.

Figure 1
Longitudinal trends of cardiovascular and renal biomarkers (uNGAL, renin, aldosterone, BNP and troponin) across postnatal age in extremely preterm infants.

Table 1
PAS table 1.pdfMixed-effects model evaluating associations between gestational and postnatal age with urinary NGAL concentrations.

Table 2
PAS table 2.pdfDemographic and biomarker comparisons between infants with low and high PDA shunt burden.