{"id":"2ba6c950-883b-5092-9d61-b57684719a44","stable_key":"e69ef6a0-0e23-5eac-aca1-cf333781b962:ino-preterm-2018-composite","predicate":"increases","statement":"Death or type 1 ROP occurred in 29% with myo-inositol versus 21% with placebo (adjusted RR 1.41, 95% CI 1.08–1.83).","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"0c52f2ed-779c-513c-a5d9-9047ace83fa3","mechanism_event_label":"The later larger neonatal trial did not reproduce the expected overall benefit.","subject":{"id":"50afe95c-f542-5511-ba8b-c2ff2b037977","slug":"myo-inositol","display_name":"Myo-inositol","entity_type_key":"small_molecule"},"object":{"id":"4a709040-fb8d-5672-a6da-e754276dfda4","slug":"preterm-death-or-rop","display_name":"Death or type 1 retinopathy of prematurity composite","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0c52f2ed-779c-513c-a5d9-9047ace83fa3","stable_key":"e69ef6a0-0e23-5eac-aca1-cf333781b962:ino-preterm-2018-composite-event","event_type":"observed_intervention","label":"The later larger neonatal trial did not reproduce the expected overall benefit.","description":"Death or type 1 ROP occurred in 29% with myo-inositol versus 21% with placebo (adjusted RR 1.41, 95% CI 1.08–1.83).","status":"provisional","compartment":null,"participants":[{"entity":{"id":"50afe95c-f542-5511-ba8b-c2ff2b037977","slug":"myo-inositol","display_name":"Myo-inositol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4a709040-fb8d-5672-a6da-e754276dfda4","slug":"preterm-death-or-rop","display_name":"Death or type 1 retinopathy of prematurity composite","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/inositol-research/30357297.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f\", \"start_char\": 0, \"end_char\": 2589, \"text_sha256\": \"b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Multicenter randomized neonatal trial stopped early","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Myo-inositol 40 mg/kg every 12 hours, initially IV then enteral, for up to 10 weeks versus placebo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Early termination limits estimates but does not remove the mortality signal. Different era, gestational ages, treatment duration and endpoints may contribute to divergence from early trials; the explanation remains unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Inositol research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"inositol","display_name":"Inositol (stereoisomer family)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The later larger neonatal trial did not reproduce the expected overall benefit.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ino-p30357297] Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial. (2018). https://pubmed.ncbi.nlm.nih.gov/30357297/ DOI: 10.1001/jama.2018.14996","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"638 infants born before 28 weeks at 18 US centers","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"db48ee37-38bc-57d7-ae1d-be8e82665c91","evidence_kind":"source_excerpt","locator":"Lines 1445-1456","start_line":1445,"end_line":1456,"excerpt":"### ino-preterm-2018-composite\nDeath or type 1 ROP occurred in 29% with myo-inositol versus 21% with placebo (adjusted RR 1.41, 95% CI 1.08–1.83).\nCondition category: normal\nnutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The later larger neonatal trial did not reproduce the expected overall benefit.\norganism: Homo sapiens\ntissue_or_cell_type: 638 infants born before 28 weeks at 18 US centers\nexperimental_model: Multicenter randomized neonatal trial stopped early\nlimitations: Early termination limits estimates but does not remove the mortality signal. Different era, gestational ages, treatment duration and endpoints may contribute to divergence from early trials; the explanation remains unresolved.\nexposure: Myo-inositol 40 mg/kg every 12 hours, initially IV then enteral, for up to 10 weeks versus placebo\nevidence_span: {\"source_cache\": \"artifacts/inositol-research/30357297.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f\", \"start_char\": 0, \"end_char\": 2589, \"text_sha256\": \"b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f\"}\n[ino-p30357297] Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial. (2018). https://pubmed.ncbi.nlm.nih.gov/30357297/ DOI: 10.1001/jama.2018.14996","model_system":"Multicenter randomized neonatal trial stopped early","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ino-p30357297] Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial. (2018). https://pubmed.ncbi.nlm.nih.gov/30357297/ DOI: 10.1001/jama.2018.14996","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"d590c659-b774-50e6-9f1d-aff61d5f7c9c","stable_key":"import-e69ef6a0-0e23-5eac-aca1-cf333781b962","title":"Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"f7adbcedad647d5f8a3cc9e46bfa515e83c508be9c2a4e9d59c5f5dfb0667d53","revision_id":"a82d187c-60fb-52d1-8482-eadb92860f33","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"dc0a00bd-56aa-504e-af34-079993d80963","title":"Early neonatal benefit was not reproduced in the larger trial, which found increased mortality","kind":"contradiction","status":"open","why":"The early randomized trial reported reduced retinopathy, motivating an expectation of neonatal benefit; the later larger randomized trial instead found more death or type 1 ROP and increased mortality. This is a genuine unresolved clinical evidence disagreement, not a correction of the ledger. Populations, care era, regimen duration and endpoints differ, so it is not an identical-experiment contradiction.","resolution":"Retain both trials and prioritize the later mortality signal when presenting neonatal use. Do not claim inositol prevents ROP in preterm infants. Differences in gestational age, duration, care and competing mortality require explanation, not an assumed mechanism; proposed explanations belong in the discussion until supported.","created_at":"2026-09-17 17:44:25","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/dc0a00bd-56aa-504e-af34-079993d80963","sides":[{"conflict_id":"dc0a00bd-56aa-504e-af34-079993d80963","ordinal":0,"label":"An early neonatal trial reported fewer severe eye complications.","revision_id":"a82d187c-60fb-52d1-8482-eadb92860f33","start_line":1432,"end_line":1443,"quote":"### ino-preterm-1992-rop\nThe 1992 trial reported ROP in 13% of inositol-treated infants versus 26% of placebo recipients, and stage 4 ROP in 0% versus 9%.\nCondition category: normal\nnutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: An early neonatal trial reported fewer severe eye complications.\norganism: Homo sapiens\ntissue_or_cell_type: 221 infants at 24–32 weeks gestation with respiratory distress\nexperimental_model: Randomized double-blind neonatal trial\nlimitations: Early-era neonatal care and short exposure. The indexed abstract has inconsistent BPD count/percentage arithmetic; that endpoint is not numerically reproduced here. ROP findings are retained with the later adverse trial.\nexposure: Inositol 80 mg/kg/day for the first five days during parenteral nutrition\nevidence_span: {\"source_cache\": \"artifacts/inositol-research/1560798.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"6ece5de763b822dca6ca1a93b5f7a61a2d94be9af29755ffd9379f16a983027e\", \"start_char\": 0, \"end_char\": 2123, \"text_sha256\": \"6ece5de763b822dca6ca1a93b5f7a61a2d94be9af29755ffd9379f16a983027e\"}\n[ino-p1560798] Inositol supplementation in premature infants with respiratory distress syndrome. (1992). https://pubmed.ncbi.nlm.nih.gov/1560798/ DOI: 10.1056/nejm199205073261901","source_key":"import-e69ef6a0-0e23-5eac-aca1-cf333781b962","source_title":"Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17)","claim_ids":["741c7c0e-309b-5f89-9646-103d64cc6e8b"]},{"conflict_id":"dc0a00bd-56aa-504e-af34-079993d80963","ordinal":1,"label":"The later larger neonatal trial did not reproduce the expected overall benefit.","revision_id":"a82d187c-60fb-52d1-8482-eadb92860f33","start_line":1445,"end_line":1456,"quote":"### ino-preterm-2018-composite\nDeath or type 1 ROP occurred in 29% with myo-inositol versus 21% with placebo (adjusted RR 1.41, 95% CI 1.08–1.83).\nCondition category: normal\nnutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The later larger neonatal trial did not reproduce the expected overall benefit.\norganism: Homo sapiens\ntissue_or_cell_type: 638 infants born before 28 weeks at 18 US centers\nexperimental_model: Multicenter randomized neonatal trial stopped early\nlimitations: Early termination limits estimates but does not remove the mortality signal. Different era, gestational ages, treatment duration and endpoints may contribute to divergence from early trials; the explanation remains unresolved.\nexposure: Myo-inositol 40 mg/kg every 12 hours, initially IV then enteral, for up to 10 weeks versus placebo\nevidence_span: {\"source_cache\": \"artifacts/inositol-research/30357297.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f\", \"start_char\": 0, \"end_char\": 2589, \"text_sha256\": \"b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f\"}\n[ino-p30357297] Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial. (2018). https://pubmed.ncbi.nlm.nih.gov/30357297/ DOI: 10.1001/jama.2018.14996","source_key":"import-e69ef6a0-0e23-5eac-aca1-cf333781b962","source_title":"Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17)","claim_ids":["2ba6c950-883b-5092-9d61-b57684719a44"]},{"conflict_id":"dc0a00bd-56aa-504e-af34-079993d80963","ordinal":2,"label":"The increased deaths are essential evidence and cannot be hidden behind the earlier positive findings.","revision_id":"a82d187c-60fb-52d1-8482-eadb92860f33","start_line":1458,"end_line":1469,"quote":"### ino-preterm-2018-mortality\nMortality before 55 weeks postmenstrual age was 18% versus 11% (adjusted RR 1.66, 95% CI 1.14–2.43), prompting early trial termination.\nCondition category: normal\nnutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The increased deaths are essential evidence and cannot be hidden behind the earlier positive findings.\norganism: Homo sapiens\ntissue_or_cell_type: 638 infants born before 28 weeks at 18 US centers\nexperimental_model: Multicenter randomized neonatal trial stopped early\nlimitations: Early termination limits estimates but does not remove the mortality signal. Different era, gestational ages, treatment duration and endpoints may contribute to divergence from early trials; the explanation remains unresolved.\nexposure: Myo-inositol 40 mg/kg every 12 hours, initially IV then enteral, for up to 10 weeks versus placebo\nevidence_span: {\"source_cache\": \"artifacts/inositol-research/30357297.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f\", \"start_char\": 0, \"end_char\": 2589, \"text_sha256\": \"b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f\"}\n[ino-p30357297] Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial. (2018). https://pubmed.ncbi.nlm.nih.gov/30357297/ DOI: 10.1001/jama.2018.14996","source_key":"import-e69ef6a0-0e23-5eac-aca1-cf333781b962","source_title":"Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17)","claim_ids":["3caacf20-c0a2-5580-a2f4-c5cdc29d2974"]}]}],"corrections":[],"research":null}