{"doi":"10.1111/apa.15406","title":"Association between low fatty acid levels and platelet count in infants with Retinopathy of Prematurity","abstract":"Numerous factors are involved in retinopathy of prematurity (ROP) and these differ between preterm infants and fetuses. Sight-threatening pathological retinal neovascularisation may occur during the second phase, due to increased expression of pro-angiogenic factors like vascular endothelial growth factor-A (VEGF-A). Low platelet counts and thrombocytopenia are independent risk factors for ROP. Experimental mice studies have suggested that platelets release stimuli that cause downregulation of retinal VEGF-A and supress neovascularisation.1 Low levels of long-chain polyunsaturated fatty acids (LC-PUFAs), like docosahexaenoic acid (DHA) and arachidonic acid (AA), have been associated with ROP.2 LC-PUFAs have enhanced platelet formation from mature megakaryocytes in vitro.3 Low platelet counts and low levels of LC-PUFAs have been associated with ROP, but their inter-relationship has not been evaluated. This was a prospective study of 78 infants born at Sahlgrenska University Hospital, Gothenburg, Sweden, before 28 weeks of gestation in 2013˗2015. We assessed their longitudinal postnatal platelet counts and serum phospholipid-bound fractions of DHA and AA4 in relation to ROP. Blood samples for LC-PUFA analysis and platelet counts were taken from birth until 40 weeks of postmenstrual age (PMA). Thrombocytopenia was any platelet count <100 × 109/L. LC-PUFA levels and platelet counts were used to calculate weekly Pearson correlations for PMAs from 28 to 40 weeks. Two-tailed tests were used and .05 was significant. The analyses were performed using SAS software, version 9.4 (SAS Institute Inc.). Table 1 shows the infants' characteristics and the correlations between DHA, AA and platelet counts. Of these, 28% developed severe ROP requiring treatment at a median PMA of 36.8 (interquartile range 35.4-38.9) weeks and exhibited thrombocytopenia more frequently (82% versus 36%, P < .001) than those with no, or less severe, ROP. Detailed data about their serum fractions of AA and DHA have previously been published.4 Briefly, DHA decreased by 1.14 (95% confidence interval 0.93-1.36, P < .0001) mol% and AA decreased by 7.5 (6.8-8.1, P < .0001) mol% during the first postnatal week. DHA then increased slowly and AA remained low. The associations between DHA, AA and the predicted platelet counts were r = .32 (range 0.23-0.43, P = .0008) and r = 0.23 (0.16-0.34, P = .0045) respectively. They were markedly higher in infants with severe ROP (Table 1), particularly for DHA between 32 and 36 weeks of PMA (range 0.59-0.66), when neovascularisation may occur (Table 1, Figure S1). AA presented an overall weaker association than DHA. We believe that no associations between platelet counts and LC-PUFAs have previously been reported for extremely preterm infants. However, in the 1970s, Freidman et al reported thrombocytopenia in infants with essential fatty acid deficiency and long-time parenteral nutrition.5 We hypothesised that low LC-PUFA would interact negatively with platelet formation. Consequently, platelet derived anti-angiogenic stimuli were decreased which may have contributed to neovascularisation in the second ROP phase. Retinal vascularisation involves a complex interaction and timing of pro-angiogenic or anti-angiogenic factors. In ROP, pathological neovascularisation occurs when retinal expression of VEGF-A is upregulated to meet the demands of the maturing neural retina. An ROP mouse model indicated that platelet alpha-granules released anti-angiogenic stimuli, causing downregulation of retinal VEGF-A transcripts and suppressed neovascularisation during the second ROP phase.1 Platelets are released from mature megakaryocytes in bone marrow through a series of events. Our positive association between LC-PUFAs and platelets was not surprising, as in vitro studies have shown that DHA and AA in culture media improved megakaryocyte migration, maintained platelet membrane structure and affected platelet survival.3 Postnatal LC-PUFA deficiency app","journal":"Acta Paediatrica","year":2020,"id":111079,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":527423,"name":"Anders Nilsson","orcid":"0000-0003-3631-0783","position":1,"is_corresponding":false},{"id":527424,"name":"Gunnel Hellgren","orcid":"0000-0001-7287-7598","position":2,"is_corresponding":false},{"id":454653,"name":"Aldina Pivodic","orcid":"0000-0002-2224-3236","position":3,"is_corresponding":false},{"id":90501,"name":"Lois E. H. Smith","orcid":"0000-0001-7644-6410","position":4,"is_corresponding":false},{"id":290714,"name":"Ann Hellström","orcid":"0000-0002-9259-1244","position":5,"is_corresponding":false},{"id":527422,"name":"Pia Lundgren","orcid":"0000-0002-7731-1988","position":0,"is_corresponding":true}],"reference_count":5,"raw_metadata":null,"created_at":"2026-07-18T23:13:01.914939Z","pmid":"32521072","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}