Background: Two risk factors for severe retinopathy of prematurity (ROP) in extremely preterm infants are thrombocytopenia and low levels of arachidonic acid (AA) and docosahexaenoic acid (DHA). To date, these risk factors have not been linked.

Method: Infants born < 28 weeks gestational age (GA) from 2016 to 2019 were randomized to postnatal enteral AA/DHA supplementation or standard care (controls). Levels of AA and DHA, platelet counts ( < 100 × 10 9 /L defined as thrombocytopenia) and platelet-related proteins in the infants’ first four weeks of life were evaluated for their association with severe ROP.

Results: The mean birthweight of 178 included infants was 806 ± 200 grams, and the mean GA was 25.6 ± 1.4 weeks. During the first four postnatal weeks, 20.2% of AA/DHA-supplemented infants had thrombocytopenia versus 27.7% of controls ( p  = 0.29). In infants with thrombocytopenia, fewer AA/DHA-supplemented infants developed severe ROP than non-supplemented controls, 29.4% (5/17) versus 65.4% (17/26) ( p  = 0.031). Thrombocytopenia and serum levels of AA and DHA correlated with several platelet-related proteins involved in angiogenesis and ROP, such as platelet-derived growth factor subunits A and B and vascular endothelial growth factor.

Conclusions: AA and DHA supplementation is associated with less severe ROP in thrombocytopenic infants, possibly by modulating platelet activation and function.

Impact: Postnatal enteral supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) to extremely preterm infants reduces the risk of severe retinopathy of prematurity (ROP) in infants with thrombocytopenia. The impact of AA and DHA might be, at least in part, mediated through altered platelet activation. We found that AA and DHA may reduce the risk of severe ROP, possibly by modulating platelet-related proteins involved in angiogenesis. Our findings strongly support that supplementing AA and DHA to extremely preterm infants is crucial and can significantly impact their health. Postnatal enteral supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) to extremely preterm infants reduces the risk of severe retinopathy of prematurity (ROP) in infants with thrombocytopenia. The impact of AA and DHA might be, at least in part, mediated through altered platelet activation.We found that AA and DHA may reduce the risk of severe ROP, possibly by modulating platelet-related proteins involved in angiogenesis.Our findings strongly support that supplementing AA and DHA to extremely preterm infants is crucial and can significantly impact their health.