{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T06:40:45Z","timestamp":1764225645608,"version":"3.46.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Timely administration of antenatal corticosteroids improves preterm outcomes; however, in low- and middle-income countries (LMICs), multiple barriers often delay treatment. Whether exposure within 24 h before delivery confers benefits remains uncertain. We aimed to evaluate the association between antenatal dexamethasone-to-delivery intervals and preterm outcomes in an LMIC setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This single-center prospective cohort study was conducted at a tertiary neonatal intensive care unit in India from June 2023 to December 2024. The participants were preterm infants born at 24 0\/7\u201333 6\/7 week gestation. Exclusion criteria were major congenital anomalies, multiple courses of dexamethasone, administration-to-birth interval &amp;gt; 7 d, and interfacility transfer. The exposure variable was maternal first dexamethasone dose-to-delivery interval, categorized as \u2264 24 h (\n                      <jats:italic>n<\/jats:italic>\n                      = 167), &amp;gt; 24 h\u20137 d (\n                      <jats:italic>n<\/jats:italic>\n                      = 64), or no exposure (\n                      <jats:italic>n<\/jats:italic>\n                      = 101). The primary outcome was in-hospital mortality. Secondary outcomes included severe necrotizing enterocolitis (NEC), intraventricular hemorrhage, respiratory distress syndrome, and a composite of death or severe morbidity. Propensity scores from 10 covariates generated inverse-probability-of-treatment-weights (IPTW). Adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) were estimated using a doubly-robust, trimmed IPTW-modified Poisson model. Sensitivity analyses used doubly-robust overlap weighting and an entropy-balanced treatment-only model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 371 infants born during the study period, 332 met eligibility criteria (mean gestational age, 30.6 \u00b1 2.2 week; 60.5% male). Overall mortality was 7.8% (26\/332): 11.9% (12\/101) without dexamethasone, 6.6% (11\/167) with \u2264 24 h exposure, and 4.7% (3\/64) with &amp;gt; 24 h\u20137 d exposure. Mortality did not differ by dexamethasone timing intervalgroup: \u2264 24 h (aRR, 0.58; 95%CI 0.26\u20131.27) and &amp;gt; 24 h\u20137 d (aRR, 0.33; 95%CI, 0.10\u20131.12) vs. no dexamethasone. Wide CIs were observed, reflecting imprecision due to lower-than-expected mortality in the unexposed group. Severe NEC was lower with \u2264 24 h exposure (1.8% [3\/167] vs. 8.9% [9\/101]; aRR, 0.15; 95%CI 0.04\u20130.54), persisting in sensitivity analyses (aRR, 0.11; 95%CI 0.03\u20130.38) and after multiple-comparison adjustment. No other secondary outcomes differed significantly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dexamethasone administration within 24 h before delivery did not reduce mortality but significantly decreased the risk of severe NEC. Imprecise estimates due to lower-than-expected mortality, reduced statistical power, and potential residual confounding limit definitive conclusions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1712437","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T06:29:40Z","timestamp":1764224980000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of antenatal dexamethasone administration timing with outcomes in preterm infants in a low- and middle-income country"],"prefix":"10.3389","volume":"12","author":[{"given":"Vijay","family":"Kalrao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamta","family":"Benda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s12978-025-02033-x","article-title":"Born too soon: global epidemiology of preterm birth and drivers for change.","volume":"22","author":"Bradley","year":"2025","journal-title":"Reprod Health."},{"key":"B2","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1038\/jp.2016.183","article-title":"State of newborn health in India.","volume":"36","author":"Sankar","year":"2016","journal-title":"J Perinatol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1542\/peds.50.4.515","article-title":"A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants.","volume":"50","author":"Liggins","year":"1972","journal-title":"Pediatrics."},{"key":"B4","doi-asserted-by":"publisher","first-page":"CD004454","DOI":"10.1002\/14651858.CD004454.pub3","article-title":"Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.","volume":"3","author":"Roberts","year":"2017","journal-title":"Cochrane Database Syst Rev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"CD004454","DOI":"10.1002\/14651858.CD004454.pub4","article-title":"Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.","volume":"12","author":"McGoldrick","year":"2020","journal-title":"Cochrane Database Syst Rev."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e102","DOI":"10.1097\/AOG.0000000000002237","article-title":"Committee opinion No. 713: antenatal corticosteroid therapy for fetal maturation.","volume":"130","year":"2017","journal-title":"Obstet Gynecol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e1707","DOI":"10.1016\/S2214-109X(22)00434-X","article-title":"Updated WHO recommendations on antenatal corticosteroids and tocolytic therapy for improving preterm birth outcomes.","volume":"10","author":"Vogel","year":"2022","journal-title":"Lancet Glob Health."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1097\/AOG.0000000000000840","article-title":"Association between antenatal corticosteroid administration-to-birth interval and outcomes of preterm neonates.","volume":"125","author":"Melamed","year":"2015","journal-title":"Obstet Gynecol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1111\/1471-0528.14545","article-title":"Timing of antenatal corticosteroid administration and survival in extremely preterm infants: a national population-based cohort study.","volume":"124","author":"Norberg","year":"2017","journal-title":"BJOG."},{"key":"B10","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1002\/ijgo.13836","article-title":"FIGO good practice recommendations on the use of prenatal corticosteroids to improve outcomes and minimize harm in babies born preterm.","volume":"155","author":"Norman","year":"2021","journal-title":"Int J Gynaecol Obstet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"101916","DOI":"10.1016\/j.eclinm.2023.101916","article-title":"Effect of antenatal corticosteroid administration-to-birth interval on maternal and newborn outcomes: a systematic review.","volume":"58","author":"McDougall","year":"2023","journal-title":"EClinicalMedicine."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e000398","DOI":"10.1136\/bmjgh-2017-000398","article-title":"Antenatal corticosteroids for women at risk of imminent preterm birth in low-resource countries: the case for equipoise and the need for efficacy trials.","volume":"2","author":"Vogel","year":"2017","journal-title":"BMJ Glob Health."},{"key":"B13","doi-asserted-by":"publisher","first-page":"575","DOI":"10.9745\/GHSP-D-20-00716","article-title":"Readiness to provide antenatal corticosteroids for threatened preterm birth in public health facilities in Northern India.","volume":"9","author":"Kankaria","year":"2021","journal-title":"Glob Health Sci Pract."},{"key":"B14","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1001\/jamapediatrics.2017.0602","article-title":"Association of short antenatal corticosteroid administration-to-birth intervals with survival and morbidity among very preterm infants: results from the EPICE cohort.","volume":"171","author":"Norman","year":"2017","journal-title":"JAMA Pediatr."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e2461312","DOI":"10.1001\/jamanetworkopen.2024.61312","article-title":"Short duration of antenatal corticosteroid exposure and outcomes in extremely preterm infants.","volume":"8","author":"Chawla","year":"2025","journal-title":"JAMA Netw Open."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e2511315","DOI":"10.1001\/jamanetworkopen.2025.11315","article-title":"Timing of antenatal corticosteroid administration and neonatal outcomes.","volume":"8","author":"Melamed","year":"2025","journal-title":"JAMA Netw Open."},{"key":"B17","doi-asserted-by":"publisher","first-page":"101744","DOI":"10.1016\/j.eclinm.2022.101744","article-title":"Effect of dexamethasone on newborn survival at different administration-to-birth intervals: a secondary analysis of the WHO ACTION (Antenatal CorticosTeroids for improving outcomes in preterm newborn)-I trial.","volume":"53","year":"2022","journal-title":"EClinicalMedicine."},{"key":"B18","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.tips.2018.11.002","article-title":"Non-genomic effects of glucocorticoids: an updated view.","volume":"40","author":"Panettieri","year":"2019","journal-title":"Trends Pharmacol Sci."},{"key":"B19","unstructured":"India\u2019s Newborn Action Plan (INAP).\n          \n          2014"},{"key":"B20","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1080\/01621459.2016.1260466","article-title":"Balancing covariates via propensity score weighting.","volume":"113","author":"Li","year":"2017","journal-title":"J Am Stat Assoc."},{"key":"B21","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1023\/a:1020363010465","article-title":"Using propensity scores to help design observational studies: application to the tobacco litigation.","volume":"2","author":"Rubin","year":"2001","journal-title":"Health Serv Outcomes Res Methodol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1093\/aje\/kwq439","article-title":"Doubly robust estimation of causal effects.","volume":"173","author":"Funk","year":"2011","journal-title":"Am J Epidemiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e017638","DOI":"10.1136\/bmjopen-2017-017638","article-title":"Benefits of probiotics in preterm neonates in low-income and medium-income countries: a systematic review of randomised controlled trials.","volume":"7","author":"Deshpande","year":"2017","journal-title":"BMJ Open."},{"key":"B24","first-page":"229","article-title":"Necrotizing enterocolitis\u2014an unconquered disease.","volume":"39","author":"Singh","year":"2002","journal-title":"Indian Pediatr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1007\/s00404-022-06411-9","article-title":"Is there a benefit of antenatal corticosteroid when given < 48 h before delivery?","volume":"306","author":"Siegler","year":"2022","journal-title":"Arch Gynecol Obstet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"247","DOI":"10.12891\/ceog3469.2017","article-title":"Neonatal outcomes based on antenatal corticosteroid exposure time for infants delivered between 23 and 34 weeks gestation.","volume":"44","author":"Borgida","year":"2017","journal-title":"Clin Exp Obstet Gynecol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"100077","DOI":"10.1016\/j.ajogmf.2019.100077","article-title":"Optimal timing of antenatal corticosteroid administration and preterm neonatal and early childhood outcomes.","volume":"2","author":"Battarbee","year":"2020","journal-title":"Am J Obstet Gynecol MFM."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e1523","DOI":"10.1016\/S2214-109X(22)00340-0","article-title":"Antenatal dexamethasone for improving preterm newborn outcomes in low-resource countries: a cost-effectiveness analysis of the WHO ACTION-I trial.","volume":"10","year":"2022","journal-title":"Lancet Glob Health."},{"key":"B29","doi-asserted-by":"publisher","first-page":"CD006764","DOI":"10.1002\/14651858.CD006764.pub4","article-title":"Different corticosteroids and regimens for accelerating fetal lung maturation for babies at risk of preterm birth.","volume":"8","author":"Williams","year":"2022","journal-title":"Cochrane Database Syst Rev."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1016\/j.jfma.2019.11.002","article-title":"The gestational effect of antenatal corticosteroids on respiratory distress syndrome in very low birth weight infants: a population-based study.","volume":"119","author":"Liu","year":"2020","journal-title":"J Formos Med Assoc."},{"key":"B31","doi-asserted-by":"publisher","first-page":"130.e1","DOI":"10.1016\/j.ajog.2017.11.554","article-title":"Mortality and pulmonary outcomes of extremely preterm infants exposed to antenatal corticosteroids.","volume":"218","author":"Travers","year":"2018","journal-title":"Am J Obstet Gynecol."},{"key":"B32","first-page":"989","article-title":"Cost of neonatal intensive care in a tertiary care center.","volume":"42","author":"Narang","year":"2005","journal-title":"Indian Pediatr."},{"key":"B33","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1007\/s13312-013-0234-y","article-title":"Cost of neonatal intensive care delivered through district level public hospitals in India.","volume":"50","author":"Prinja","year":"2013","journal-title":"Indian Pediatr."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1712437\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T06:29:42Z","timestamp":1764224982000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1712437\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":33,"alternative-id":["10.3389\/fmed.2025.1712437"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1712437","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,27]]},"article-number":"1712437"}}