ArticleEClinicalMedicine2026
Gestational age references and trajectory of fetal haemoglobin in relation to outcome in neonates born before 30 weeks of gestation: a single-centre retrospective cohort study in The Netherlands.
Article in EClinicalMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Fetal haemoglobin (HbF) has a high oxygen affinity and predominates during fetal life. After birth, HbF is progressively replaced by adult haemoglobin (HbA). In preterm neonates, transfusion with HbA-containing red blood cells (RBCs) may accelerate this transition, increasing tissue oxygen exposure and oxidative stress, which have been associated with retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. We aimed to establish gestational age (GA)-specific reference values and examine postnatal HbF trajectories in relation to transfusion exposure and outcomes, focusing on neonates born before 30 weeks' gestation. Methods: In this single-centre retrospective cohort study, 856 neonates with HbF measurements (24-42 weeks' gestation) admitted to the ErasmusMC NICU, Rotterdam, the Netherlands (1 February 2020-1 February 2024) were included. GA-specific HbF reference values were derived from day 0 samples. Longitudinal HbF trajectories during NICU admission were analysed in 458 neonates born before 30 weeks' gestation using 9461 blood gas samples. Linear mixed-effects models assessed associations between HbF decline, transfusion exposure, and prematurity-related outcomes. Findings: HbF at birth remained high until approximately 35 weeks' gestation (median ≥0.85) and declined towards term. In neonates born before 30 weeks' gestation, HbF declined during the first postnatal weeks, with the steepest decline seen in babies born at 24-25 weeks' gestation. Neonates who received RBC transfusions showed a steeper HbF decline than those who did not (p < 0.001), as did neonates with prematurity-related outcomes compared with those without major morbidity or mortality (p < 0.001). Interpretation: RBC transfusions accelerate HbF decline in neonates born before 30 weeks' gestation. Its association with prematurity-related morbidity supports evaluation of HbF-preserving transfusion strategies. Future studies should incorporate the interval and frequency of successive transfusions through time-varying cumulative transfusion exposure or analyses centred on individual transfusion events to further refine the temporal dynamics of HbF decline and recovery. These studies should ultimately evaluate the optimal interval and frequency of transfusions and whether HbF-preserving transfusion strategies improve clinical outcomes in extremely preterm neonates. Funding: No funding was received for this work.
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