EARLY VITAMIN A SUPPLEMENTATION IMPROVES THE OUTCOME OF RETINOPATHY OF PREMATURITY IN EXTREMELY PRETERM INFANTS

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Abstract

This prospective, three-center, randomized study assessed the efficacy and safety of early vitamin A supplementation in improving the outcomes of retinopathy of prematurity in extremely preterm infants. Two hundred sixty-two extremely preterm infants were randomized to vitamin A and control groups. Vitamin A supplementation reduced its deficiency in these infants.

Abstract

Purpose:

This study assessed the efficacy and safety of early vitamin A (VA) supplementation to improve outcomes of retinopathy of prematurity in extremely preterm infants.

Methods:

A total of 262 eligible extremely preterm infants underwent randomization; of these, 132 were assigned to the VA group and 130 to the control group. The infants were administered a solution of VA (1,500 IU/day), added to their enteral feeds as soon as minimal feeding was introduced and continued for 28 days or until discharge.

Results:

With no adverse effects occurring, serum VA of the VA-supplemented infants on Days 14, 28, and postmenstrual 36 weeks was higher than that of the placebo group ( P < 0.001). No signs of VA toxicity or increased intracranial pressure were reported. The VA group had lower unadjusted rates of Type 1 retinopathy of prematurity (1.6 vs. 6.9%, P = 0.030) and bronchopulmonary dysplasia (18.9 vs. 33.8%, P = 0.008) than the control group. Regression analysis revealed an association between serum VA levels and risk of Type 1 retinopathy of prematurity (beta = −2.37).

Conclusion:

Vitamin A supplementation reduced VA deficiency in extremely preterm infants; it was associated with a decreased incidence of Type 1 retinopathy of prematurity and may also have a positive impact on reducing bronchopulmonary dysplasia.

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Most cited references 50

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Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial.

Early Treatment For Retinopathy Of Prematurity Cooperative Group (2003)

To determine whether earlier treatment using ablation of the avascular retina in high-risk prethreshold retinopathy of prematurity (ROP) results in improved grating visual acuity and retinal structural outcomes compared with conventional treatment. Infants with bilateral high-risk prethreshold ROP (n = 317) had one eye randomized to early treatment with the fellow eye managed conventionally (control eye). In asymmetric cases (n = 84), the eye with high-risk prethreshold ROP was randomized to early treatment or conventional management. High risk was determined using a model based on the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity natural history cohort. At a corrected age of 9 months, visual acuity was assessed by masked testers using the Teller acuity card procedure. At corrected ages of 6 and 9 months, eyes were examined for structural outcome. Outcomes for the 2 treatment groups of eyes were compared using chi2 analysis, combining data for bilateral and asymmetric cases. Grating acuity results showed a reduction in unfavorable visual acuity outcomes with earlier treatment, from 19.5% to 14.5% (P =.01). Unfavorable structural outcomes were reduced from 15.6% to 9.1% (P<.001) at 9 months. Further analysis supported retinal ablative therapy for eyes with type 1 ROP, defined as zone I, any stage ROP with plus disease (a degree of dilation and tortuosity of the posterior retinal blood vessels meeting or exceeding that of a standard photograph); zone I, stage 3 ROP without plus disease; or zone II, stage 2 or 3 ROP with plus disease. The analysis supported a wait-and-watch approach to type 2 ROP, defined as zone I, stage 1 or 2 ROP without plus disease or zone II, stage 3 ROP without plus disease. These eyes should be considered for treatment only if they progress to type 1 or threshold ROP. Early treatment of high-risk prethreshold ROP significantly reduced unfavorable outcomes to a clinically important degree. Additional analyses led to modified recommendations for the use of peripheral retinal ablation in eyes with ROP. Long-term follow-up is being conducted to learn whether the benefits noted in the first year after birth will persist into childhood.

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Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.

C Agostoni, G. Buonocore, VP Carnielli … (2010)

The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

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Impact of a physiologic definition on bronchopulmonary dysplasia rates.

Kathy Auten, N Newman, … (2004)

Bronchopulmonary dysplasia (BPD) is the endpoint of many intervention trials in neonatology, yet the outcome measure when based solely on oxygen administration may be confounded by differing criteria for oxygen administration between physicians. We previously reported a technique to standardize the definition of BPD between sites by using a timed room-air challenge in selected infants. We hypothesized that a physiologic definition of BPD would reduce the variation in observed rates of BPD among different neonatal centers. Methodology. A total of 1598 consecutive inborn premature infants (501-1249 g birth weight) who remained hospitalized at 36 weeks' postmenstrual age were prospectively assessed and assigned an outcome with both a clinical definition and physiologic definition of BPD. The clinical definition of BPD was oxygen supplementation at exactly 36 weeks' postmenstrual age. The physiologic definition of BPD was assigned at 36 +/- 1 weeks' postmenstrual age and included 2 distinct subpopulations. First, neonates on positive pressure support or receiving >30% supplemental oxygen with saturations between 90% and 96% were assigned the outcome BPD and not tested further. Second, those receiving 30% with saturations >96% underwent a room-air challenge with continuous observation and oxygen-saturation monitoring. Outcomes of the room-air challenge were "no BPD" (saturations > or =90% during weaning and in room air for 30 minutes) or "BPD" (saturation <90%). At the conclusion of the room-air challenge, all infants were returned to their baseline oxygen levels. Safety (apnea, bradycardia, increased oxygen use) and outcomes of the physiologic definition versus the clinical definition were assessed. A total of 560 (35.0%) neonates were diagnosed with BPD by the clinical definition of oxygen use at 36 weeks' postmenstrual age. The physiologic definition diagnosed BPD in 398 (25.0%) neonates in the cohort. All infants were safely studied. There were marked differences in the impact of the definition on BPD rates between centers (mean reduction: 10%; range: 0-44%). Sixteen centers had a decrease in their BPD rate, and 1 center had no change in their rate. The physiologic definition of BPD reduced the overall rate of BPD and reduced the variation among centers. Significant center differences in the impact of the physiologic definition were seen, and differences remained even with the use of this standardized definition. The magnitude of the change in BPD rate is comparable to the magnitude of treatment effects seen in some clinical trials in BPD. The physiologic definition of BPD facilitates the measurement of BPD as an outcome in clinical trials and the comparison between and within centers over time.

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Author and article information

Journal

Journal ID (nlm-ta): Retina

Journal ID (iso-abbrev): Retina (Philadelphia, Pa.)

Journal ID (publisher-id): retina

Title: Retina (Philadelphia, Pa.)

Publisher: Retina

ISSN (Print): 0275-004X

ISSN (Electronic): 1539-2864

Publication date (Print): June 2020

Publication date (Electronic): 05 April 2019

Volume: 40

Issue: 6

Pages: 1176-1184

Affiliations

Departments of [* ]Neonatology, and

[† ]Ophthalmology, Children's Hospital affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China;

[‡ ]Department of Neonatology, Children's Hospital of Nanjing Medical University, Nanjing, China; and

[§ ]Department of Neonatology, Shangqiu People's Hospital, Shangqiu, China.

Author notes

Reprint requests: Huiqing Sun, PhD, Department of Neonatology, Children's Hospital affiliated to Zhengzhou University, 33 Longhuwaihuan Road, Zhengzhou 450018, China; e-mail: s_huiqing@ 123456sina.com

Article

Publisher ID: Retina-218-1788 Accession ID: 00023

DOI: 10.1097/IAE.0000000000002543

PMC ID: 7242171

PubMed ID: 30964778

SO-VID: d03bffff-8801-4a23-961c-a40c1d7244b4

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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Keywords: early,extremely,infants,preterm,retinopathy of prematurity,supplementation,vitamin a

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Keywords: early, extremely, infants, preterm, retinopathy of prematurity, supplementation, vitamin a

EARLY VITAMIN A SUPPLEMENTATION IMPROVES THE OUTCOME OF RETINOPATHY OF PREMATURITY IN EXTREMELY PRETERM INFANTS

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Most cited references 50

Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial.

Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.

Impact of a physiologic definition on bronchopulmonary dysplasia rates.

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