# The role of proteinuria on a simple urinalysis in neonatal hypoxic–ischemic encephalopathy: association with clinical and neurodevelopmental outcomes

**Authors:** Ya-Chun Hu, Ji-Nan Sheu, Inn-Chi Lee

PMC · DOI: 10.3389/fneur.2025.1451346 · 2025-03-18

## TL;DR

High urine protein levels in newborns with brain injury from lack of oxygen are linked to worse outcomes and can predict long-term development issues.

## Contribution

This study identifies urine protein levels as a novel early predictor of neurodevelopmental outcomes in neonatal hypoxic-ischemic encephalopathy.

## Key findings

- Elevated urine protein levels correlate with serum lactic acid levels and clinical staging of HIE.
- Higher urine protein levels are strongly associated with worse neurodevelopmental outcomes at one year of age.
- Group 4 patients (≥300 mg/dL urine protein) had high predictive value and specificity for moderate-to-severe HIE.

## Abstract

Early diagnosis and initiation of hypothermia therapy for neonatal hypoxic–ischemic encephalopathy (HIE) are critical within the first 6 h after birth. Collecting urine, especially from neonates with HIE, can be challenging and time-consuming post-birth due to the likelihood of renal injury.

We assessed whether urine protein levels, measured via a simple urinalysis on the first day, could correlate with the outcomes of neonatal HIE.

We conducted urine analyses of patients with neonatal HIE on the first day to establish a correlation between the severity of HIE and neurodevelopmental outcomes at ≥1 year of age. Eighty-three patients were enrolled, encompassing cases of mild (n = 37), moderate (n = 30), and severe (n = 16) HIE. Three cases were excluded due to mortality caused by severe HIE with associated auria. Based on urine protein levels, patients were grouped as 0 to 30 mg/dL (group 1), 30 to 100 mg/dL (group 2), 100 to 300 mg/dL (group 3), and ≥ 300 mg (group 4).

Urine protein levels were correlated with serum lactic acid levels [p = 0.006; r (81) = 0.304; n = 83], clinical staging [p = 0.001; r (81) = 0.36], and neurodevelopmental outcomes at ≥1 year of age [X2 (3, n = 83) = 11.35; p = 0.009]. The odds ratio for moderate-to-severe HIE in group 4 patients was 7.66 [p = 0.010; 95% confidence interval (CI), 1.61–36.33] compared with those in groups 1–3. Those in group 4 had a high positive predictive value (87.50%) and high specificity (94.59%).

Elevated urine protein levels observed in the first urinalysis conducted on the day after birth were found to be associated with serum lactic acid levels, clinical staging, and neurodevelopmental outcomes at ≥1 year of age.

## Linked entities

- **Diseases:** HIE (MONDO:0006663)

## Full-text entities

- **Diseases:** renal injury (MESH:D007674), hypothermia (MESH:D007035), HIE (MESH:D020925), proteinuria (MESH:D011507)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11958179/full.md

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Source: https://tomesphere.com/paper/PMC11958179