Iron and Retinopathy of Prematurity (ROP)

NCT ID: NCT05133999

Last Updated: 2025-11-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

175 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-04-28

Study Completion Date

2025-08-18

Brief Summary

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The purpose of this study is to determine whether increased transferrin saturation in plasma (that reflects iron overload and/or low transferrin) is an independent risk factor for ROP development and severity.

Preterm infants born at \<31 week's post-menstrual age (PMA) or ≤1250g of birth weight will be included. Iron parameters in plasma will be measured during the first month of life. Retinopathy of prematurity (ROP) will be screened as currently recommended. The relationship between plasma iron parameters and ROP development and/or severity will be established.

Detailed Description

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The incidence of ROP, the main cause of vision impairment in children, is increasing parallel to the recent changes in practices targeting higher oxygen saturation in preterm babies in many countries following the publication of five trials that showed higher rates of death with lower oxygen saturations. The main risk factor for ROP development is oxygen excess. Oxygen contributes to the formation of reactive oxygen species and to lipid peroxidation which leads to vasoconstriction, vascular cytotoxicity, and arrest of vascular development causing ischemia of retinal neurons, thereby promoting the development of ROP.

90% of extremely low birth weight infants need red blood cell transfusions (RBCT) due to their immature erythropoiesis, frequent blood sampling and small circulating blood volume. RBCT are a major source of iron overload and ferritin plasma levels may remain elevated for several weeks after transfusions. It has been shown that blood transfusion is a risk factor of ROP in preterm infants. However, whether this relationship is mediated by an increased iron load remains controversial.

Only two studies, conducted before the 2000s, identified plasma iron overload as a risk factor for ROP. These studies with a limited number of patients, showed contradictory results, failing to draw a conclusion.

Excess iron worsens oxidative stress. Iron catalyzes the Fenton reaction which leads to the formation of reactive oxygen species. In addition a transferrin deficiency (the main iron chelator) has been suggested in premature infants. The oxidative stress observed in ROP could therefore be the consequence not only of oxygen therapy but also of iron overload.

The main objective of this study is to determine whether increased transferrin saturation in plasma (that reflects iron overload and/or low transferrin) is an independent risk factor for ROP development and severity.

The secondary aims/objectives are :

* Determine whether low transferrin level in plasma is an independent risk factor for ROP development and severity.
* Determine whether iron parameters imbalance in plasma are a risk factor for other comorbidities in Preterm infants i.e.:
* 1\) sepsis
* 2\) severe bronchopulmonary dysplasia
* 3\) necrotizing enterocolitis (stage 2 or 3)
* 4\) cystic periventricular leukomalacia
* 5\) grade III or IV intraventricular haemorrhage

Study duration will be 29 months, with an inclusion period of 24 months and a last visit for ROP evaluation at 45 week's post-menstrual age (PMA).

A total of 175 patients should be included: 35 with ROP and 140 without ROP.

Conditions

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Retinopathy of Prematurity

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Preterm infants

infants born at \<31 week's post-menstrual age (PMA) or ≤1250g of birth weight

Plasma determination of iron, transferrin and ferritin

Intervention Type BIOLOGICAL

Iron, transferrin and ferritin levels in plasma

Fundus Examination by wide field digital imaging camera (PanocamTM camera)

Intervention Type OTHER

ROP screening using wide field digital retinal imaging according to current recommendations.

Interventions

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Plasma determination of iron, transferrin and ferritin

Iron, transferrin and ferritin levels in plasma

Intervention Type BIOLOGICAL

Fundus Examination by wide field digital imaging camera (PanocamTM camera)

ROP screening using wide field digital retinal imaging according to current recommendations.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* All infants born at \<31 week's post-menstrual age (PMA) or ≤1250g of birthweight
* Admitted at two neonatology departments (level III) from birth
* With non-opposition consent of two parents

Exclusion Criteria

* Congenital malformation
* Life-threatening condition (not expected to survive more than a few days)
* Absence of health care protection.
Minimum Eligible Age

24 Weeks

Maximum Eligible Age

31 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondation VISIO

UNKNOWN

Sponsor Role collaborator

Fondation Université de Paris

UNKNOWN

Sponsor Role collaborator

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alejandra DARUICH, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Elsa KERMOVANT, MD, PhD

Role: STUDY_CHAIR

Assistance Publique - Hôpitaux de Paris

Locations

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Pediatrics and neonatal intensive care department - Cochin hospital - Port Royal Maternity

Paris, , France

Site Status

Ophtalmology department _ Necker Enfants Malades Hospital

Paris, , France

Site Status

Pediatrics and noenatal intensive care department - Necker-Enfants Malades Hospital

Paris, , France

Site Status

Countries

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France

References

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de Verdier K, Ulla E, Lofgren S, Fernell E. Children with blindness - major causes, developmental outcomes and implications for habilitation and educational support: a two-decade, Swedish population-based study. Acta Ophthalmol. 2018 May;96(3):295-300. doi: 10.1111/aos.13631. Epub 2017 Nov 23.

Reference Type BACKGROUND
PMID: 29168313 (View on PubMed)

Manley BJ, Kuschel CA, Elder JE, Doyle LW, Davis PG. Higher Rates of Retinopathy of Prematurity after Increasing Oxygen Saturation Targets for Very Preterm Infants: Experience in a Single Center. J Pediatr. 2016 Jan;168:242-244. doi: 10.1016/j.jpeds.2015.10.005. Epub 2015 Nov 6.

Reference Type BACKGROUND
PMID: 26548746 (View on PubMed)

BOOST II United Kingdom Collaborative Group; BOOST II Australia Collaborative Group; BOOST II New Zealand Collaborative Group; Stenson BJ, Tarnow-Mordi WO, Darlow BA, Simes J, Juszczak E, Askie L, Battin M, Bowler U, Broadbent R, Cairns P, Davis PG, Deshpande S, Donoghoe M, Doyle L, Fleck BW, Ghadge A, Hague W, Halliday HL, Hewson M, King A, Kirby A, Marlow N, Meyer M, Morley C, Simmer K, Tin W, Wardle SP, Brocklehurst P. Oxygen saturation and outcomes in preterm infants. N Engl J Med. 2013 May 30;368(22):2094-104. doi: 10.1056/NEJMoa1302298. Epub 2013 May 5.

Reference Type BACKGROUND
PMID: 23642047 (View on PubMed)

Sapieha P, Joyal JS, Rivera JC, Kermorvant-Duchemin E, Sennlaub F, Hardy P, Lachapelle P, Chemtob S. Retinopathy of prematurity: understanding ischemic retinal vasculopathies at an extreme of life. J Clin Invest. 2010 Sep;120(9):3022-32. doi: 10.1172/JCI42142. Epub 2010 Sep 1.

Reference Type BACKGROUND
PMID: 20811158 (View on PubMed)

Howarth C, Banerjee J, Aladangady N. Red Blood Cell Transfusion in Preterm Infants: Current Evidence and Controversies. Neonatology. 2018;114(1):7-16. doi: 10.1159/000486584. Epub 2018 Mar 16.

Reference Type BACKGROUND
PMID: 29550819 (View on PubMed)

Hesse L, Eberl W, Schlaud M, Poets CF. Blood transfusion. Iron load and retinopathy of prematurity. Eur J Pediatr. 1997 Jun;156(6):465-70. doi: 10.1007/s004310050641.

Reference Type BACKGROUND
PMID: 9208245 (View on PubMed)

Dani C, Reali MF, Bertini G, Martelli E, Pezzati M, Rubaltelli FF. The role of blood transfusions and iron intake on retinopathy of prematurity. Early Hum Dev. 2001 Apr;62(1):57-63. doi: 10.1016/s0378-3782(01)00115-3.

Reference Type BACKGROUND
PMID: 11245995 (View on PubMed)

Inder TE, Clemett RS, Austin NC, Graham P, Darlow BA. High iron status in very low birth weight infants is associated with an increased risk of retinopathy of prematurity. J Pediatr. 1997 Oct;131(4):541-4. doi: 10.1016/s0022-3476(97)70058-1.

Reference Type BACKGROUND
PMID: 9386655 (View on PubMed)

Hirano K, Morinobu T, Kim H, Hiroi M, Ban R, Ogawa S, Ogihara H, Tamai H, Ogihara T. Blood transfusion increases radical promoting non-transferrin bound iron in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2001 May;84(3):F188-93. doi: 10.1136/fn.84.3.f188.

Reference Type BACKGROUND
PMID: 11320046 (View on PubMed)

Daruich A, Le Rouzic Q, Jonet L, Naud MC, Kowalczuk L, Pournaras JA, Boatright JH, Thomas A, Turck N, Moulin A, Behar-Cohen F, Picard E. Iron is neurotoxic in retinal detachment and transferrin confers neuroprotection. Sci Adv. 2019 Jan 9;5(1):eaau9940. doi: 10.1126/sciadv.aau9940. eCollection 2019 Jan.

Reference Type BACKGROUND
PMID: 30662950 (View on PubMed)

Hellstrom A, Engstrom E, Hard AL, Albertsson-Wikland K, Carlsson B, Niklasson A, Lofqvist C, Svensson E, Holm S, Ewald U, Holmstrom G, Smith LE. Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth. Pediatrics. 2003 Nov;112(5):1016-20. doi: 10.1542/peds.112.5.1016.

Reference Type BACKGROUND
PMID: 14595040 (View on PubMed)

Luo XQ, Zhang CY, Zhang JW, Jiang JB, Yin AH, Guo L, Nie C, Lu XZ, Deng H, Zhang L. Identification of Iron Homeostasis Genes Dysregulation Potentially Involved in Retinopathy of Prematurity Pathogenicity by Microarray Analysis. J Ophthalmol. 2015;2015:584854. doi: 10.1155/2015/584854. Epub 2015 Oct 18.

Reference Type BACKGROUND
PMID: 26557385 (View on PubMed)

Other Identifiers

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2021-A02182

Identifier Type: OTHER

Identifier Source: secondary_id

APHP211233

Identifier Type: -

Identifier Source: org_study_id

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