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

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

Abstract

Background: Blood loss and adult blood transfusions are common during the neonatal period in preterm infants. The objective of the study was to clarify if degree of loss of fetal haemoglobin (HbF) was associated with later retinopathy of prematurity (ROP).

Methods: Retrospective observational cohort study. In total, 452 infants born <30 gestational weeks at a tertiary level neonatal intensive care unit in Sweden in 2009-2015 were included, 385 of whom had final ROP outcome. Mean fractions of HbF (%) during the first postnatal week were calculated from 11 861 arterial blood gas analyses. The relationship between fractions of HbF (%) and ROP was evaluated.

Results: The mean (SD) gestational age (GA) at birth was 26.4 (1.8) weeks. In total, 104 (27 %) infants developed ROP. Higher fraction of HbF (%) was associated with a lower prevalence of ROP, OR by a 10% increase 0.83 (95% CI: 0.71 to 0.97; p=0.019), following adjustment for GA at birth, small for GA and sex. Infants with HbF (%) in the lowest quartile had OR of 22.0 (95% CI: 8.1 to 59.2; p<0.001) for ROP development compared with those in the highest quartile. The predictive ability (area under the curve) of HbF (%) in the full model during the first week was 0.849 for ROP.

Conclusions: Early low fraction of HbF is independently associated with abnormal retinal neurovascular development in the very preterm infant. The potential benefit of minimising blood loss on development of ROP will be investigated in a multicenter randomised trial (NCT04239690).

Keywords: angiogenesis; diagnostic tests/Investigation; pathology; retina.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Mean fraction (%) of HbF during postnatal days 1–7 in relation to development of any ROP. Infants with no ROP (n=281) in blue; Infants with any ROP (n=104) in red. The bars represent 95% CI. HbF, fetal haemoglobin; ROP, retinopathy of prematurity.
Figure 2
Figure 2
Significantly higher fraction of HbF during postnatal week 1 in infants without ROP compared with infants developing any ROP, in a cohort consisting of 452 very preterm infants. ** Indicating p

Figure 3

(A, B) Estimated probability for…

Figure 3

(A, B) Estimated probability for any ROP in relation to HbF (A) and…

Figure 3
(A, B) Estimated probability for any ROP in relation to HbF (A) and GA at birth (B). Illustrated by linear function by mean HbF (%) in postnatal week 1 in the complete cohort for any ROP (A) and by GA at birth illustrated per quartile of HbF (%) in postnatal week 1 for any ROP (B). Q1 represents infants with a mean HbF% in the lowest quartile in B, and Q4 represent the infants with a mean HbF% in the highest quartile. Q4; HbF%>77.6%, Q3; 74%–77.6%, Q2; 58.8%–73.9% and Q1

Figure 4

ROC curve for any ROP…

Figure 4

ROC curve for any ROP (A) and adjusted fraction of HbF (%) during…

Figure 4
ROC curve for any ROP (A) and adjusted fraction of HbF (%) during postnatal week 1. HbF (%) adjusted for GA at birth, SGA and sex in the ROC curve. The AUC for HbF was 0.849. ROP, retinopathy of prematurity; HbF, fetal haemoglobin; GA, gestational age; SGA, small for gestational age; AUC, area under the curve.
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References
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Figure 3
Figure 3
(A, B) Estimated probability for any ROP in relation to HbF (A) and GA at birth (B). Illustrated by linear function by mean HbF (%) in postnatal week 1 in the complete cohort for any ROP (A) and by GA at birth illustrated per quartile of HbF (%) in postnatal week 1 for any ROP (B). Q1 represents infants with a mean HbF% in the lowest quartile in B, and Q4 represent the infants with a mean HbF% in the highest quartile. Q4; HbF%>77.6%, Q3; 74%–77.6%, Q2; 58.8%–73.9% and Q1

Figure 4

ROC curve for any ROP…

Figure 4

ROC curve for any ROP (A) and adjusted fraction of HbF (%) during…

Figure 4
ROC curve for any ROP (A) and adjusted fraction of HbF (%) during postnatal week 1. HbF (%) adjusted for GA at birth, SGA and sex in the ROC curve. The AUC for HbF was 0.849. ROP, retinopathy of prematurity; HbF, fetal haemoglobin; GA, gestational age; SGA, small for gestational age; AUC, area under the curve.
Figure 4
Figure 4
ROC curve for any ROP (A) and adjusted fraction of HbF (%) during postnatal week 1. HbF (%) adjusted for GA at birth, SGA and sex in the ROC curve. The AUC for HbF was 0.849. ROP, retinopathy of prematurity; HbF, fetal haemoglobin; GA, gestational age; SGA, small for gestational age; AUC, area under the curve.

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