@article {1580480, title = {Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity: A Randomized Clinical Trial}, journal = {JAMA Pediatr}, volume = {175}, number = {4}, year = {2021}, month = {2021 Apr 01}, pages = {359-367}, abstract = {Importance: Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP). Objective: To determine whether enteral supplementation with fatty acids from birth to 40 weeks{\textquoteright} postmenstrual age reduces ROP in extremely preterm infants. Design, Setting, and Participants: The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 28 weeks{\textquoteright} gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020. Interventions: Infants received either supplementation with an enteral oil providing AA (100 mg/kg/d) and DHA (50 mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks{\textquoteright} postmenstrual age. Main Outcomes and Measures: The primary outcome was severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth. Results: A total of 101 infants (58 boys [57.4\%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2\%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8\%] in the AA:DHA group vs 35 of 105 [33.3\%] in the control group; adjusted relative risk, 0.50 [95\% CI, 0.28-0.91]; P = .02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol\% [95\% CI, 0.46-1.18 mol\%]; P \< .001; overall mean difference in control group, 0.13 mol\% [95\% CI, 0.01-0.24 mol\%]; P = .03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5\%] vs 48 of 105 [45.7\%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6\%] vs 42 of 105 [40.0\%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6\%) and 53 of 105 infants (50.5\%), serious adverse events occurred in 26 of 101 infants (25.7\%) and 26 of 105 infants (24.8\%), and 16 of 101 infants (15.8\%) and 13 of 106 infants (12.3\%) died. Conclusions and Relevance: This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50\% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants. Trial Registration: ClinicalTrials.gov Identifier: NCT03201588.}, issn = {2168-6211}, doi = {10.1001/jamapediatrics.2020.5653}, author = {Hellstr{\"o}m, Ann and Nilsson, Anders K and Wackernagel, Dirk and Pivodic, Aldina and Vanpee, Mireille and Sj{\"o}bom, Ulrika and Hellgren, Gunnel and Hallberg, Boubou and Domell{\"o}f, Magnus and Klevebro, Susanna and Hellstr{\"o}m, William and Andersson, Mats and Lund, Anna-My and L{\"o}fqvist, Chatarina and Elfvin, Anders and S{\"a}vman, Karin and Hansen-Pupp, Ingrid and H{\r a}rd, Anna-Lena and Smith, Lois E H and Ley, David} }