{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T17:34:12Z","timestamp":1755797652614,"version":"3.44.0"},"reference-count":41,"publisher":"Georg Thieme Verlag KG","issue":"12","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH grants","award":["R01HL153429"],"award-info":[{"award-number":["R01HL153429"]}]},{"name":"NIH grants","award":["RO1GM142112"],"award-info":[{"award-number":["RO1GM142112"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Perinatol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Extremely premature infants are treated with acetaminophen (APAP) for pain and patent ductus arteriosus. High doses of APAP in adults are toxic, and a recent study found an association between APAP metabolite levels in mothers' breast milk and both bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) in their premature infants. In this study, we determined levels of APAP metabolites in the urine of infants at high risk for BPD and ROP.<\/jats:p><jats:p>Biorepository urine samples from 314 infants &lt;29 weeks' gestation in the multicenter TOLSURF and PROP studies were analyzed by untargeted UHPLC:MS\/MS (Metabolon, Inc.). We performed multivariate logistic regression and meta-analysis to examine associations between APAP metabolite levels and clinical outcomes.<\/jats:p><jats:p>4-APAP sulfate was the most abundant of eight detected APAP metabolites and was present in 95% of urines. There were high correlations between levels of 4-APAP sulfate and the other APAP metabolites. In longitudinal studies on a subgroup of infants (day 6\u201356), periods of elevated 4-APAP sulfate occurred in 24\/28 infants and were of longer duration (10.5 vs. 4.2 days, p\u2009=\u20090.001) with higher levels (13.3 vs. 5.6, p\u2009=\u20090.01) in infants after transition to enteral from total parenteral nutrition. Episodes of elevated metabolite did not differ by BPD status. On both days 10 and 28 there were no significant associations between levels of APAP metabolites and either BPD or ROP for all infants or for infants exclusively on parenteral or enteral nutrition.<\/jats:p><jats:p>In two cohorts of extremely premature infants, levels of urinary APAP metabolites were not associated with increased risk for two adverse clinical outcomes.<\/jats:p>","DOI":"10.1055\/a-2512-9387","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T19:27:39Z","timestamp":1736450859000},"page":"1576-1587","source":"Crossref","is-referenced-by-count":0,"title":["Urinary Acetaminophen Metabolites and Clinical Outcomes in Extremely Premature Infants"],"prefix":"10.1055","volume":"42","author":[{"given":"Miguel","family":"Guardado","sequence":"additional","affiliation":[{"name":"Department of Biological and Medical Informatics, University of California, San Francisco, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dara","family":"Torgerson","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl","family":"Chapin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Francisco, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azuka","family":"Atum","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan D.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Clyman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Francisco, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Simmons","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Parry","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip L.","family":"Ballard","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San 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