The Analysis of Association of Retinopathy of Prematurity, Gut Microbiome Profile, and Systemic Inflammation

Study Aims

1. Understanding the gut microbiome profile in very low birth weight infants with or without ROP. The onset and aggravation of ROP and their relationship with gut microbiome will be examined.
2. Understanding the serum inflammatory cytokine profile in these infants and its relationship with the onset and progression of ROP. Their changes and association with the other systemic disorders such as NEC or RDS or sepsis will be explored.
3. Examiningthe associations amongmicrobiome profile and serum inflammatory cytokines and their relationship with ROP clinical features (prematurity without ROP, ROP without treatment, and ROP with treatment) in the study participant

Study Overview

• Status: Enrolling by invitation
• Conditions: Retinopathy of Prematurity; Microbiome
• Intervention / Treatment: Procedure: intravitreal injection of anti VEGF; Procedure: laser photocoagulation

Detailed Description

Background In recent decades, severeretinopathy of prematurity (ROP) and the proportion of ROP needing treatment is increasing. These conditions are due to the fact that more premature infants now could surviveowing to the improvement in neonatology. Since ROP isa leading cause of blindness in children, how to deal with these severely affected eyes becomes a major challenge.

In recent years, growing evidence support that exposure to infection and inflammation increases risk of ROP and these exposures are considered key contributors to the pathogenesis of ROP. These exposures, which are modifiable, have gained interest among researchers.

The microbiome are symbiotic organisms living inside human bodies. They are most abundant in human gastrointestinal tracts and play a fundamental role in host inflammatory and immunity physiology. The gut microbiome is most extensively studied, and reports showed that they play a role not only in gastrointestinal inflammatory diseases, but also in extra-gastrointestinal conditions.

Recent data have shown that microbiome changes may involve in the pathogenesisof ophthalmic diseasessuch as uveitis, but its role in ROP has not been explored. Since ROP is closely related to inflammation, and that the gut microbiome has a significant role in the modulation of both systemic and ocular inflammatory pathways, we are interested to know whether there is association between ROP, microbiome, and systemic inflammation. Whether the microbiome profile is different in ROP and no-ROP neonates is worth exploring. Also, it is important to see whether the onset of ROP is related to the systemic inflammation status. To the best of our knowledge, there are no report on such topic, therefore our current study is designed to answer this question.

Methods Very low birth weight preterm infantsborn in our hospital from August 2020to July 2023 will be enrolled into study. Infants who has major or congenital GI anomaly will be excluded. ROP screening protocol and categorization will follow the international standards. DNA will be extracted from the stool samples and underwent microbiome profiling either by 16S rRNA or shotgun metagenomic sequencing. Blood samples from the routine blood examinations will beanalyzed by an immunoassay to reveal the level of systemic inflammation (IL-1 alpha/beta, IL-10, IL-13 and so on). Statistical analysis will be performed and the associations among ROP features, gut microbiome, and serum inflammatory cytokines will be explored.

Study Aims

1. Understanding the gut microbiome profile in very low birth weight infants with or without ROP. The onset and aggravation of ROP and their relationship with gut microbiome will be examined.
2. Understanding the serum inflammatory cytokine profile in these infants and its relationship with the onset and progression of ROP. Their changes and association with the other systemic disorders such as NEC or RDS or sepsis will be explored.
3. Examiningthe associations amongmicrobiome profile and serum inflammatory cytokines and their relationship with ROP clinical features (prematurity without ROP, ROP without treatment, and ROP with treatment) in the study participant

• Study Type: Observational
• Enrollment (Anticipated): 240

Contacts and Locations

Study Locations

• Taiwan
  • Linkou
    • Taoyuan, Linkou, Taiwan, 33305
      • Department of Ophthalmology, Chang Gung Memorial Hospital.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 1 week (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

All GA<37 weeks preterm infants with birth weight (BW) between 500 and 1500 grams born in Linkou of Chung Gung Memorial Hospital from August 2020 to July 2023 will be enrolled into study after obtaining informed consent from their parent within 1-week-of-age.

Description

Inclusion Criteria:

• All GA<37 weeks preterm infants with birth weight (BW) between 500 and 1500 grams born in Linkou of Chung Gung Memorial Hospital from August 2020 to July 2023 will be enrolled into study after obtaining informed consent from their parent within 1-week-of-age.

Exclusion Criteria:

• Preterm infants who has major or congenital gastrointestional (GI) anomaly (eg. trisomy 13, trisomy 18, esophageal or intestinal atresia, GI obstruction, meconium peritonitis with prenatal bowel perforation, etc.).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
premature baby without ROP (Group 1); ROP: retinopathy of prematurity
ROP without treatment (Group 2); ROP: retinopathy of prematurity
ROP with anti-VEGF treatment (Group 3); ROP: retinopathy of prematurity	Procedure: intravitreal injection of anti VEGF; The treatment for ROP was either primary intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF).
ROP with laser photocoagulation treatment (Group 4); ROP: retinopathy of prematurity	Procedure: laser photocoagulation; The treatment for ROP was either primary laser photocoagulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut Microbiome	Understanding the gut microbiome profile in very low birth weight infants with or without ROP. The onset and aggravation of ROP and their relationship with gut microbiome will be examined.	2020-2023
Serum Inflammatory Cytokine	Understanding the serum inflammatory cytokine profile in these high-risk infants and its relationship with the onset and progression of ROP. Their changes and association with the other systemic disorders such as NEC or RDS or sepsis will be explored.	2020-2023
Microbiome Profile And Serum Inflammatory Cytokines And Their Relationship with ROP	Examining the associations among microbiome profile and serum inflammatory cytokines and their relationship with ROP clinical features in the study participants (patients with prematurity without ROP, patients with ROP without treatment, and patients with ROP and treatment).	2020-2023

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Wu WeiChi, M.D., PhD., Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2020
• Primary Completion (Anticipated): July 31, 2023
• Study Completion (Anticipated): July 31, 2023

Study Registration Dates

• First Submitted: November 22, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): December 3, 2021

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: microbiome; inflammatory cytokine; Retinopathy of prematurity; very low birth weight
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Infant, Premature, Diseases; Inflammation; Retinal Diseases; Premature Birth; Retinopathy of Prematurity
• Other Study ID Numbers: 201902088A3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No