One-Month Blood Inflammation Markers Flag Retinopathy Risk in Very Preterm Infants

Infants born very preterm who go on to develop retinopathy of prematurity show a distinctive pattern of blood-based inflammation markers at one month of age, but not in the first days of life, according to a retrospective single-center cohort study published in BMC Pediatrics. The study analyzed 139 preterm infants born at 32 weeks of gestation or earlier who were admitted to the neonatal intensive care unit of Malatya Training and Research Hospital in Türkiye between May 2022 and December 2025. Its central question was whether simple indices calculated from routine complete blood count results could discriminate between infants who developed retinopathy of prematurity and those who did not, and whether that ability depended on gestational age at birth.

The researchers calculated a panel of markers from standard complete blood count measurements: the neutrophil-to-lymphocyte ratio, the platelet-to-lymphocyte ratio, the lymphocyte-to-monocyte ratio, the systemic immune-inflammation index, the systemic inflammation response index, and the aggregate index of systemic inflammation. They also computed the hemoglobin–albumin–lymphocyte–platelet score, known as the HALP score, which combines hemoglobin, albumin, lymphocyte, and platelet values into a single measure. Blood parameters were analyzed from samples taken during the early postnatal period, on days 2 to 4 of life, and, when available, again at postnatal month 1, on days 28 to 32. Infants were stratified into two groups: those born at 30 weeks of gestation or earlier and those born between 30 and 32 weeks, with comparisons performed according to retinopathy status within each stratum.

Retinopathy of prematurity developed in 30 of the 139 infants, or 21.6 percent of the cohort, and 10 of those infants required treatment. The group born at 30 weeks of gestation or earlier had a higher incidence of the disease than the 30-to-32-week group. The early postnatal measurements told a clear negative story: none of the inflammatory indices measured in the first days of life were associated with later retinopathy of prematurity. The picture changed substantially at postnatal month 1. Among infants born at 30 weeks or earlier, those who went on to develop the disease had lower albumin values and lower lymphocyte-to-monocyte ratios, together with higher values of the systemic immune-inflammation index, the systemic inflammation response index, the aggregate index of systemic inflammation, and the neutrophil-to-lymphocyte ratio. Receiver operating characteristic analysis, which measures how well a marker separates affected from unaffected individuals, yielded area under the curve values ranging from 0.73 to 0.82 for these month-1 indices.

To test whether these associations held independently of gestational maturity and birth size, the researchers ran logistic regression models adjusted for gestational age and birth weight. This analysis included all infants with available month-1 data, a subset of 86 infants in whom 30 retinopathy events occurred. After adjustment, significant associations with retinopathy of prematurity persisted for the systemic immune-inflammation index, the systemic inflammation response index, the neutrophil-to-lymphocyte ratio, the lymphocyte-to-monocyte ratio, and the neutrophil count itself. In contrast, the HALP score and the platelet-to-lymphocyte ratio demonstrated limited discriminative performance, indicating that not all composite blood indices carried the same signal in this cohort. The month-1 findings were strongest and most interpretable in the group born at 30 weeks or earlier; for the 30-to-32-week group, interpretation was limited by substantial missing follow-up data, so the authors could not draw firm conclusions about whether the same marker pattern applies to more mature preterm infants.

The authors conclude that, in this cohort, complete blood count-derived inflammatory indices measured at postnatal month 1 were more discriminative than early postnatal measurements, particularly among infants born at 30 weeks of gestation or earlier, and they suggest these indices may serve as adjunctive biomarkers for retinopathy of prematurity risk assessment in very preterm infants. They explicitly state that external validation in larger prospective multicenter studies is required before any clinical implementation. As a retrospective, single-center cohort study, the design cannot establish causation, and the moderate area under the curve values reflect the discriminative limits of the markers observed here.

Subject of Research: Complete blood count-derived inflammatory indices and the HALP score as biomarkers for retinopathy of prematurity in very preterm infants

Article Title: Gestational age–stratified analysis of HALP score and complete blood count–derived inflammatory indices in retinopathy of prematurity

Article References: Ekici Gök, Z., Melekoğlu, N. A., & Yaşar, Ş. (2026). Gestational age–stratified analysis of HALP score and complete blood count–derived inflammatory indices in retinopathy of prematurity. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07786-3

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07786-3

Keywords: retinopathy of prematurity, preterm infants, HALP score, complete blood count, inflammatory indices, systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, neonatal intensive care, gestational age, biomarkers, retrospective cohort study, BMC Pediatrics