Low Plasma Protein Levels at Birth Are Associated with Poor Cardiovascular Adaptation and Serious Adverse Outcome in Infants with Gestational Age <32 Weeks: The ProHémie Study

Abstract

Background: Retrospective studies suggest that early hypoproteinemia has prognostic value for adverse outcome in preemies, but the underlying pathophysiology is unknown. We hypothesized that the prognostic relevance of hypoproteinemia could be related to its association with impaired cardiovascular function and organ perfusion during transition.

Objectives: To describe the plasma protein status and the measures of cardiovascular function according to the outcome in infants <32 weeks' gestation.

Methods: One hundred and twenty-eight infants were prospectively included from birth to discharge. During the first 24 h of life, we assessed the cardiovascular function and systemic and organ blood flow by Doppler ultrasound, and monitored cerebral and renal regional oxygen saturation (cRSO2, rRSO2) using near-infrared spectroscopy. These measures were analyzed in relationship to hypoproteinemia (total plasma protein level <40 g/L at 12 h of life) and severe adverse outcome (death or survival with severe neurological injury).

Results: Hypoproteinemia was associated with a higher risk of a severe adverse outcome after adjustment of confounding variables (adjusted OR = 6.8; 95% CI 1.3-34). Compared to normoproteinemic infants and after adjustment for gestational age, hypoproteinemic ones had more significantly: hypotension (7 vs. 13%, p = 0.03), abnormal capillary refilling time (20 vs. 36%, p < 0.001), abnormal renal blood flow (resistive index 0.78 ± 0.11 vs. 0.85 ± 0.09, p = 0.04), lower rRSO2 (82.9 ± 9.2 vs. 73.6 ± 10.5%, p = 0.04), and lower systemic vascular resistance (0.155 ± 0.058 vs. 0.108 ± 0.037 mm Hg/L/kg; p = 0.04). The cRSO2 patterns were significantly decreased in infants with severe adverse outcome and independent from protein status.

Conclusion: Hypoproteinemia is associated with impaired cardiovascular function. Further studies are required to elucidate the interplay between changes in protein levels, postnatal hemodynamics and clinical outcome.

Keywords: Albumin; Arterial blood pressure; Neonatal intensive care; Neurological outcome; Peripheral circulation; Postnatal adaptation; Prognosis; Renal function; Very-low-birth-weight infants.