Miguel Guardado, Dara Torgerson, Cheryl Chapin, Azuka Atum, Ryan D Hernandez, Ronald Clyman, Rebecca Simmons, Samuel Parry, Philip L Ballard
{"title":"尿对乙酰氨基酚代谢物与极早产儿的临床结局。","authors":"Miguel Guardado, Dara Torgerson, Cheryl Chapin, Azuka Atum, Ryan D Hernandez, Ronald Clyman, Rebecca Simmons, Samuel Parry, Philip L Ballard","doi":"10.1055/a-2512-9387","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong> 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.</p><p><strong>Study design: </strong> Biorepository urine samples from 314 infants <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.</p><p><strong>Results: </strong> 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 6-56), periods of elevated 4-APAP sulfate occurred in 24/28 infants and were of longer duration (10.5 vs. 4.2 days, <i>p</i> = 0.001) with higher levels (13.3 vs. 5.6, <i>p</i> = 0.01) 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.</p><p><strong>Conclusion: </strong> In two cohorts of extremely premature infants, levels of urinary APAP metabolites were not associated with increased risk for two adverse clinical outcomes.</p><p><strong>Key points: </strong>· Safety of acetaminophen (APAP) in extremely premature infants has not been established.. · The major urinary APAP metabolite was detected in the majority of urine samples.. · No association was found between APAP levels and either bronchopulmonary dysplasia or retinopathy of prematurity..</p>","PeriodicalId":7584,"journal":{"name":"American journal of perinatology","volume":" ","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Urinary Acetaminophen Metabolites and Clinical Outcomes in Extremely Premature Infants.\",\"authors\":\"Miguel Guardado, Dara Torgerson, Cheryl Chapin, Azuka Atum, Ryan D Hernandez, Ronald Clyman, Rebecca Simmons, Samuel Parry, Philip L Ballard\",\"doi\":\"10.1055/a-2512-9387\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong> 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.</p><p><strong>Study design: </strong> Biorepository urine samples from 314 infants <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.</p><p><strong>Results: </strong> 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 6-56), periods of elevated 4-APAP sulfate occurred in 24/28 infants and were of longer duration (10.5 vs. 4.2 days, <i>p</i> = 0.001) with higher levels (13.3 vs. 5.6, <i>p</i> = 0.01) 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.</p><p><strong>Conclusion: </strong> In two cohorts of extremely premature infants, levels of urinary APAP metabolites were not associated with increased risk for two adverse clinical outcomes.</p><p><strong>Key points: </strong>· Safety of acetaminophen (APAP) in extremely premature infants has not been established.. · The major urinary APAP metabolite was detected in the majority of urine samples.. · No association was found between APAP levels and either bronchopulmonary dysplasia or retinopathy of prematurity..</p>\",\"PeriodicalId\":7584,\"journal\":{\"name\":\"American journal of perinatology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2025-01-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of perinatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1055/a-2512-9387\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of perinatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1055/a-2512-9387","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
Urinary Acetaminophen Metabolites and Clinical Outcomes in Extremely Premature Infants.
Objective: 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.
Study design: Biorepository urine samples from 314 infants <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.
Results: 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 6-56), periods of elevated 4-APAP sulfate occurred in 24/28 infants and were of longer duration (10.5 vs. 4.2 days, p = 0.001) with higher levels (13.3 vs. 5.6, p = 0.01) 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.
Conclusion: In two cohorts of extremely premature infants, levels of urinary APAP metabolites were not associated with increased risk for two adverse clinical outcomes.
Key points: · Safety of acetaminophen (APAP) in extremely premature infants has not been established.. · The major urinary APAP metabolite was detected in the majority of urine samples.. · No association was found between APAP levels and either bronchopulmonary dysplasia or retinopathy of prematurity..
期刊介绍：
The American Journal of Perinatology is an international, peer-reviewed, and indexed journal publishing 14 issues a year dealing with original research and topical reviews. It is the definitive forum for specialists in obstetrics, neonatology, perinatology, and maternal/fetal medicine, with emphasis on bridging the different fields.
The focus is primarily on clinical and translational research, clinical and technical advances in diagnosis, monitoring, and treatment as well as evidence-based reviews. Topics of interest include epidemiology, diagnosis, prevention, and management of maternal, fetal, and neonatal diseases. Manuscripts on new technology, NICU set-ups, and nursing topics are published to provide a broad survey of important issues in this field.
All articles undergo rigorous peer review, with web-based submission, expedited turn-around, and availability of electronic publication.
The American Journal of Perinatology is accompanied by AJP Reports - an Open Access journal for case reports in neonatology and maternal/fetal medicine.
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