Visual outcome at 2.5 years of age in ω-3 and ω-6 long-chain polyunsaturated fatty acid supplemented preterm infants: a follow-up of a randomized controlled trial

Pia Lundgren; Lena Jacobson; Lotta Gränse; Anna-Lena Hård; Karin Sävman; Ingrid Hansen-Pupp; David Ley; Anders K Nilsson; Aldina Pivodic; Lois E Smith; Ann Hellström

doi:10.1016/j.lanepe.2023.100696

Visual outcome at 2.5 years of age in ω-3 and ω-6 long-chain polyunsaturated fatty acid supplemented preterm infants: a follow-up of a randomized controlled trial

Lancet Reg Health Eur. 2023 Aug 24:32:100696. doi: 10.1016/j.lanepe.2023.100696. eCollection 2023 Sep.

Authors

Pia Lundgren¹, Lena Jacobson^{1

2}, Lotta Gränse³, Anna-Lena Hård¹, Karin Sävman^{4

5}, Ingrid Hansen-Pupp⁶, David Ley⁶, Anders K Nilsson¹, Aldina Pivodic¹, Lois E Smith⁷, Ann Hellström¹

Affiliations

¹ The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Department of Clinical Neuroscience, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
³ Department of Clinical Sciences, Ophthalmology, Skåne University Hospital, Lund University, Lund, Sweden.
⁴ Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵ Region Västra Götaland, Department of Neonatology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁶ Department of Clinical Sciences Lund, Pediatrics, Lund University, Skåne University Hospital, Lund, Sweden.
⁷ The Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Background: We investigated ophthalmological outcomes at 2.5 years of corrected age in children born extremely preterm (EPT) to evaluate the effects of postnatal enteral supplementation with ω-3 and ω-6 long-chain polyunsaturated fatty acids.

Methods: In the Mega Donna Mega clinical trial, EPT infants born at less than 28 weeks of gestation were randomized to receive an enteral supplementation of docosahexaenoic acid (DHA) and arachidonic acid (AA) from birth to 40 weeks postmenstrual age. In this exploratory follow-up at 2.5 years of corrected age, we assessed visual acuity (VA), refraction, manifest strabismus, and nystagmus. Satisfactory VA was defined as ≥20/63. Multiple imputation (MI) was used to address the issue of missing data.

Findings: Of 178 children in the trial, 115 (with median gestational age (GA) of 25 + 4/7 weeks and median birth weights of 790 g) were ophthalmologically assessed at a median corrected age of 2.7 years (range 2.0-3.9 years). VA assessment was missing in 42.1% (75/178), in 41.7% (35/84) of the AA/DHA supplemented infants, and in 42.6% (40/94) of the control infants. After MI and adjustments for GA, study center, plurality, and corrected age at VA exam, no significant effect of AA/DHA supplementation was detected in VA outcome (≥20/63) (odds ratio 2.16, confidence interval 95% 0.99-4.69, p = 0.053).

Interpretation: In this randomized controlled trial follow-up, postnatal supplementation with enteral AA/DHA to EPT children did not significantly alter VA at 2.5 years of corrected age. Due to the high loss to follow-up rate and the limited statistical power, additional studies are needed.

Funding: The Swedish Medical Research Council #2020-01092, The Gothenburg Medical Society, Government grants under the ALF agreement ALFGBG-717971 and ALFGBG-971188, De Blindas Vänner, Knut and Alice Wallenberg Foundation - Wallenberg Clinical Scholars, NIHEY017017, EY030904BCHIDDRC (1U54HD090255 Massachusetts Lions Eye Foundation) supported the study.

Keywords: Arachidonic acid; Docosahexaenoic acid; Fatty acid supplementation; Ophthalmological outcome; Preterm infant.

Abstract

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