Clinical trial NCT05133999: Iron and Retinopathy of Prematurity (ROP)
Official title: Iron, Transferrin and Retinopathy of Prematurity (ROP): Towards New Pathophysiological Mechanisms.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Retinopathy of Prematurity
Keywords: retinopathy
prematurity
ROP
Iron and transferrin
Preterm infants
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Fondation VISIO
name: Fondation Université de Paris
First posted: 2021-11-24
Enrollment: 175
Sex: ALL
Minimum age (years): 24
Maximum age (years): 31
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Preterm infants born at \<31 weeks' PMA or ≤1250 g of birth weight

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: ROP screening
timeFrame: From 31 to 45 weeks' post menstrual age (PMA) [= (term + 4 weeks of life)].
measure: Levels of transferrin saturation in plasma at 1 week of life
timeFrame: at 1 week of life
Secondary outcomes:
measure: Levels of iron
timeFrame: at birth, 2, 3, and 4 weeks of life
measure: Levels of transferrin
timeFrame: at birth, 2, 3, and 4 weeks of life
measure: Levels of ferritin
timeFrame: at birth, 2, 3, and 4 weeks of life
measure: ROP's highest stage
timeFrame: during follow-up about 5 months, up to 45 weeks' PMA
measure: Need of treatment for ROP
timeFrame: during follow-up about 5 months, up to 45 weeks' PMA
measure: Number of each intervention
timeFrame: during follow-up about 5 months, up to 45 weeks' PMA
measure: Death or presence of severe co-morbidities in preterm infant
timeFrame: At 36 weeks' PMA
Other outcomes:
Locations:
city: Paris
country: France
facility: Pediatrics and neonatal intensive care department - Cochin hospital - Port Royal Maternity
city: Paris
country: France
facility: Ophtalmology department _ Necker Enfants Malades Hospital
city: Paris
country: France
facility: Pediatrics and noenatal intensive care department - Necker-Enfants Malades Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Alejandra DARUICH, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Elsa KERMOVANT, MD, PhD
role: STUDY_CHAIR
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