Low fraction of fetal haemoglobin is associated with retinopathy of prematurity in the very preterm infant

Hellström, William; Martinsson, Tobias; Morsing, Eva; Gränse, Lotta; Ley, David; Hellström, Ann

doi:10.1136/bjophthalmol-2020-318293

Cited by 21 publications

(21 citation statements)

References 28 publications

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“…The authors found that in comparison with neonates without ROP, the 104 neonates developing any stage of ROP had equivalent HbF at birth but lower HbF levels in the first postnatal week. The probability for developing any ROP was about 60% in neonates with a mean HbF value of 40% in the first week of life, compared with only a 10% probability in those with a mean HbF value of 90% ( 31 ). Considering that the GA of enrolled patients was 26.4 ± 1.7 weeks, these findings strongly suggest that low-HbF-related causal mechanisms of ROP operate at a PMA lower than 31 weeks, in contrast to what Lust et al suggested ( 27 ).…”

Section: Discussionmentioning

confidence: 97%

“…The association between repeated transfusions and ROP is supported by robust scientific evidence ( 7 – 9 , 16 , 25 – 28 ). The risk for developing ROP seems to be higher if RBC transfusions are administered at an early period of life ( 27 , 29 – 31 ). In this regard, the findings emerging in the present study highlight two main points.…”

Section: Discussionmentioning

confidence: 99%

“…However, only three neonates with severe ROP were included in this study; no information related to transfusions was provided. Finally, Hellström et al retrospectively evaluated HbF data collected at birth and in the first seven postnatal days in 385 infants ( 31 ). The authors found that in comparison with neonates without ROP, the 104 neonates developing any stage of ROP had equivalent HbF at birth but lower HbF levels in the first postnatal week.…”

Section: Discussionmentioning

confidence: 99%

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Transfusion-Free Survival Predicts Severe Retinopathy in Preterm Neonates

Teofili¹,

Papacci

Bartolo³

et al. 2022

Front. Pediatr.

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Repeated red blood cell (RBC) transfusions are thought to increase the risk for retinopathy of prematurity (ROP), likely due to a critical fetal hemoglobin (HbF) reduction. In this study, we investigated if the postmenstrual age (PMA) of neonates at transfusion influences the risk for ROP. We estimated the cumulative transfusion-free survival (TFS) in a series of 100 preterm neonates receiving one or more RBC units. TFS was calculated by censoring patients at first transfusion and expressing the time between birth and transfusion as either PMA or postnatal day. Then, we investigated if TFS predicted the occurrence of severe ROP, defined as ROP stage 3 or higher. We found that neonates with severe ROP displayed a significantly shorter TFS expressed according to their PMA (p = 0.001), with similar TFS according to postnatal days. At receiver operating characteristic (ROC) curve analysis, receiving an RBC unit before week 28 of PMA predicted severe ROP with a sensitivity of 64% and a specificity of 78%. In addition, receiving a second RBC unit before the PMA of 29 weeks predicted severe ROP with a sensitivity of 75% and a specificity of 69%. At multivariate analysis, PMA at the second transfusion was even more informative than at first transfusion and outperformed all other variables in predicting severe ROP, with an odds ratio of 4.554 (95% CI 1.332–15.573, p = 0.016). Since HbF decrease is greater after multiple RBC transfusions, it is conceivable that neonates receiving more than one unit before the PMA of 29 weeks may be exposed to a greater disturbance of retinal vascularization. Any strategy aimed at preventing the critical HbF decrease at this low age might potentially reduce the risk for severe ROP.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Transfusion-Free Survival Predicts Severe Retinopathy in Preterm Neonates

Teofili¹,

Papacci

Bartolo³

et al. 2022

Front. Pediatr.

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“…23 Hellström et al (retrospectively study including 385 infants born at GA ≤ 30 weeks) found that neonates developing any stage of ROP had equivalent HbF at birth but lower HbF levels in the rst postnatal week. 24 The probability of ROP was about 60% in neonates with a mean HbF value of 40%, compared to only 10% probability in those with a mean HbF value of 90%. 24 RBC transfusions represent the mainstay for treating prematurity anemia and are unavoidable for most patients.…”

Section: Introductionmentioning

confidence: 93%

BORN study: a multicenter randomized trial investigating cord blood RBC transfusions to reduce the ROP severity in extremely low gestational age neonates.

Teofili

Papacci

Orlando

et al. 2022

Preprint

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Background. Extremely low gestational age neonates (ELGAN, i.e., neonates born before 28 weeks of gestation), are at high risk of developing retinopathy of prematurity (ROP), with potential long-life visual impairment. Due to concomitant anemia, ELGANs need repeated red blood cell (RBC) transfusions. These produce a progressive replacement of fetal hemoglobin (HbF) by adult hemoglobin (HbA). Furthermore, a close association exists between low levels of HbF and severe ROP, suggesting that a perturbation of the HbF-mediated oxygen release may derange retinal angiogenesis and promote ROP. Methods/design. BORN (umBilical blOod to tRansfuse preterm Neonates) is a multicenter double-blinded randomized controlled trial in ELGANs, to assess the effect of allogeneic cord blood RBC transfusions (CB-RBCs) on severe ROP development. Recruitment, consent and randomization take place at 10 Neonatology Intensive Care Units (NICUs) of 8 Italian tertiary Hospitals. ELGANs with gestational age at birth comprised between 24 + 0 and 27 + 6 weeks are randomly allocated into two groups: 1) standard RBC transfusions (adult-RBCs) (control arm); 2) CB-RBCs (intervention arm). In case of transfusion need, enrolled patients receive transfusions according to the allocation arm, unless an ABO/RhD CB-RBC is unavailable. Nine Italian public CB banks cooperate to make available a suitable amount of CB-RBC units for all participating NICUs. The primary outcome is the incidence of severe ROP (stage 3 or higher) at discharge or 40 weeks of post-menstrual age, which occurs first. Discussion. BORN is a ground-breaking trial, pioneering a new transfusion approach dedicated to ELGANs at high risk for severe ROP. In previous non-randomized trials, this transfusion approach was proven feasible and able to prevent the HbF decrease in patients requiring multiple transfusions. Should the BORN trial confirm the efficacy of CB-RBCs in reducing ROP severity, this transfusion strategy would became the preferential blood product to be used in severely preterm neonates. Trial registration: ClinicalTrials.gov Identifier: NCT05100212

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“…Therefore, using UCB for transfusions instead of blood from adult donors could be an alternative to reduce anemia and the risk for hyperoxemia and fluctuating oxygenation which are prominent risk factors for neonatal morbidities. In accordance, frequent diagnostic blood sampling in combination with blood transfusions in very preterm infants has been associated with an increased risk for neonatal morbidities such as bronchopulmonary dysplasia (BPD) and rethinopathy of prematurity (ROP) [21,22]. ROP is a leading cause of childhood blindness worldwide; 1.2 percent of premature infants (year 2010) developed ROP [23,24].…”

Section: Introductionmentioning

confidence: 99%