{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:45:29Z","timestamp":1790685929937,"version":"4.1.0"},"reference-count":30,"publisher":"Georg Thieme Verlag KG","issue":"S 01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Perinatol"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:p>\n            Objective\u2003Animal literature has suggested that the impact of antenatal corticosteroids (ACS) may vary by infant sex. Our objective was to assess the impact of infant sex on the use of multiple courses versus a single course of ACS and perinatal outcomes.<\/jats:p><jats:p>\n            Study Design\u2003We conducted a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth trial, which randomly allocated pregnant people to multiple courses versus a single course of ACS. Our primary outcome was a composite of perinatal mortality or clinically significant neonatal morbidity (including neonatal death, stillbirth, severe respiratory distress syndrome, intraventricular hemorrhage [grade III or IV], cystic periventricular leukomalacia, and necrotizing enterocolitis [stage II or III]). Secondary outcomes included individual components of the primary outcome as well as anthropometric measures. Baseline characteristics were compared between participants who received multiple courses versus a single course of ACS. An interaction between exposure to ACS and infant sex was assessed for significance and multivariable regression analyses were conducted with adjustment for predefined covariates, when feasible.<\/jats:p><jats:p>\n            Results\u2003Data on 2,300 infants were analyzed. The interaction term between treatment status (multiple courses vs. a single course of ACS) and infant sex was not significant for the primary outcome (p\u2009=\u20090.86), nor for any of the secondary outcomes (p\u2009&gt;\u20090.05).<\/jats:p><jats:p>\n            Conclusion\u2003Infant sex did not modify the association between exposure to ACS and perinatal outcomes including perinatal mortality or neonatal morbidity or anthropometric outcomes. However, animal literature indicates that sex-specific differences after exposure to ACS may emerge over time and thus investigating long-term sex-specific outcomes warrants further attention.<\/jats:p><jats:p>\n            Key Points\n          <\/jats:p>","DOI":"10.1055\/s-0043-1776348","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:05:26Z","timestamp":1699401926000},"page":"e2919-e2926","source":"Crossref","is-referenced-by-count":1,"special_numbering":"S","title":["The Impact of Infant Sex on Multiple Courses versus a Single Course of Antenatal Corticosteroids: A Secondary Analysis of a Randomized Controlled Trial"],"prefix":"10.1055","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8085-6751","authenticated-orcid":false,"given":"Kiran","family":"Ninan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kellie E.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9468-2860","authenticated-orcid":false,"given":"Elizabeth V.","family":"Asztalos","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Biostatistics Research Unit, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella","family":"Huszti","sequence":"additional","affiliation":[{"name":"Biostatistics Research Unit, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen G.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasqualina","family":"Santaguida","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Mukerji","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, McMaster University, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4461-2178","authenticated-orcid":false,"given":"Sarah D.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Radiology, McMaster University, Hamilton, Ontario, Canada"},{"name":"Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"e102","DOI":"10.1097\/AOG.0000000000002237","article-title":"Committee opinion no. 713: antenatal corticosteroid therapy for fetal maturation","volume":"130","author":"Committee on Obstetric Practice","year":"2017","journal-title":"Obstet Gynecol"},{"issue":"09","key":"ref2","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.jogc.2018.04.018","article-title":"No. 364-antenatal corticosteroid therapy for improving neonatal outcomes","volume":"40","author":"A Skoll","year":"2018","journal-title":"J Obstet Gynaecol Can"},{"issue":"12","key":"ref3","first-page":"CD004454","article-title":"Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth","volume":"12","author":"E McGoldrick","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"issue":"06","key":"ref5","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1203\/00006450-199712000-00027","article-title":"Postnatal lung function after prenatal steroid treatment in sheep: effect of gender","volume":"42","author":"K E Willet","year":"1997","journal-title":"Pediatr Res"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3109\/01902148.2013.858197","article-title":"Does lung development differ in male and female fetuses?","volume":"40","author":"N Ishak","year":"2014","journal-title":"Exp Lung Res"},{"issue":"02","key":"ref7","first-page":"240","article-title":"The clinical use of corticosteroids in pregnancy","volume":"22","author":"M W Kemp","year":"2016","journal-title":"Hum Reprod Update"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1210\/en.2017-00896","article-title":"Prenatal stress, glucocorticoids, and developmental programming of the stress response","volume":"159","author":"P O McGowan","year":"2018","journal-title":"Endocrinology"},{"issue":"01","key":"ref9","doi-asserted-by":"crossref","first-page":"11814","DOI":"10.1038\/s41598-017-11635-w","article-title":"Prenatal glucocorticoid exposure modifies endocrine function and behaviour for 3 generations following maternal and paternal transmission","volume":"7","author":"V G Moisiadis","year":"2017","journal-title":"Sci Rep"},{"issue":"03","key":"ref10","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/j.1365-2826.2006.01517.x","article-title":"Prenatal glucocorticoid exposure alters hypothalamic-pituitary-adrenal function in juvenile guinea pigs","volume":"19","author":"D Owen","year":"2007","journal-title":"J Neuroendocrinol"},{"issue":"05","key":"ref11","doi-asserted-by":"crossref","first-page":"E729","DOI":"10.1152\/ajpendo.2001.280.5.E729","article-title":"Maternal glucocorticoid treatment programs HPA regulation in adult offspring: sex-specific effects","volume":"280","author":"L Liu","year":"2001","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"04","key":"ref12","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1067\/mob.2002.121624","article-title":"Repeated doses of antenatal corticosteroids in animals: a systematic review","volume":"186","author":"F Aghajafari","year":"2002","journal-title":"Am J Obstet Gynecol"},{"issue":"07","key":"ref13","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/s41390-019-0712-1","article-title":"Long-term neuropathological and\/or neurobehavioral effects of antenatal corticosteroid therapy in animal models: a systematic review","volume":"87","author":"J L van der Merwe","year":"2020","journal-title":"Pediatr Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"115","DOI":"10.12688\/f1000research.7224.1","article-title":"The critical importance of the fetal hypothalamus-pituitary-adrenal axis","volume":"5","author":"C E Wood","year":"2016","journal-title":"F1000 Res"},{"issue":"07","key":"ref15","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nrendo.2014.73","article-title":"Glucocorticoids and fetal programming part 1: outcomes","volume":"10","author":"V G Moisiadis","year":"2014","journal-title":"Nat Rev Endocrinol"},{"issue":"9656","key":"ref16","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1016\/S0140-6736(08)61929-7","article-title":"Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial","volume":"372","author":"K E Murphy","year":"2008","journal-title":"Lancet"},{"issue":"06","key":"ref17","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1093\/aje\/kwk052","article-title":"Relaxing the rule of ten events per variable in logistic and Cox regression","volume":"165","author":"E Vittinghoff","year":"2007","journal-title":"Am J Epidemiol"},{"issue":"02","key":"ref18","first-page":"65","article-title":"A simple sequentially rejective multiple test procedure","volume":"6","author":"S Holm","year":"1979","journal-title":"Scand J Stat"},{"issue":"18","key":"ref20","doi-asserted-by":"crossref","first-page":"3438","DOI":"10.1080\/14767058.2020.1819977","article-title":"Antenatal corticosteroids and the influence of sex on morbidity and mortality of preterm infants","volume":"35","author":"C Ramos-Navarro","year":"2022","journal-title":"J Matern Fetal Neonatal Med"},{"issue":"12","key":"ref21","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1055\/s-0039-1683886","article-title":"Sex-specific differences in late preterm neonatal outcomes","volume":"36","author":"A N Battarbee","year":"2019","journal-title":"Am J Perinatol"},{"issue":"03","key":"ref22","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/S1701-2163(16)34822-8","article-title":"Role of fetal sex in the outcome of antenatal glucocorticoid treatment to prevent respiratory distress syndrome: systematic review and meta-analysis","volume":"33","author":"S Roberge","year":"2011","journal-title":"J Obstet Gynaecol Can"},{"issue":"03","key":"ref23","doi-asserted-by":"crossref","first-page":"e164396","DOI":"10.1001\/jamapediatrics.2016.4396","article-title":"Variation in performance of neonatal intensive care units in the United States","volume":"171","author":"J D Horbar","year":"2017","journal-title":"JAMA Pediatr"},{"issue":"01","key":"ref24","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1186\/1471-2393-14-272","article-title":"Association between gestational age at birth, antenatal corticosteroids, and outcomes at 5 years: multiple courses of antenatal corticosteroids for preterm birth study at 5 years of age (MACS-5)","volume":"14","author":"E Asztalos","year":"2014","journal-title":"BMC Pregnancy Childbirth"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1016\/j.placenta.2009.11.010","article-title":"Review: sex and the human placenta: mediating differential strategies of fetal growth and survival","volume":"31","author":"V L Clifton","year":"2010","journal-title":"Placenta"},{"issue":"04","key":"ref26","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.yhbeh.2009.07.003","article-title":"Direct and dam-mediated effects of prenatal dexamethasone on emotionality, cognition and HPA axis in adult Wistar rats","volume":"56","author":"J Hauser","year":"2009","journal-title":"Horm Behav"},{"issue":"01","key":"ref27","doi-asserted-by":"crossref","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":"A N Battarbee","year":"2020","journal-title":"Am J Obstet Gynecol MFM"},{"issue":"10","key":"ref28","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1111\/1471-0528.14636","article-title":"Antenatal corticosteroids: it's all about timing","volume":"124","author":"C Gyamfi-Bannerman","year":"2017","journal-title":"BJOG"},{"issue":"02","key":"ref29","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/s41390-020-01249-w","article-title":"Antenatal corticosteroids: a reappraisal of the drug formulation and dose","volume":"89","author":"A H Jobe","year":"2021","journal-title":"Pediatr Res"},{"issue":"06","key":"ref30","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/dgd.12376","article-title":"Prenatal exposure to dexamethasone in the mouse induces sex-specific differences in placental gene expression","volume":"59","author":"J Y Lee","year":"2017","journal-title":"Dev Growth Differ"},{"issue":"05","key":"ref31","doi-asserted-by":"crossref","first-page":"233","DOI":"10.21037\/atm.2019.12.156","article-title":"Prenatal dexamethasone exposure exerts sex-specific effect on placental oxygen and nutrient transport ascribed to the differential expression of IGF2","volume":"8","author":"J Guo","year":"2020","journal-title":"Ann Transl Med"},{"issue":"01","key":"ref32","doi-asserted-by":"crossref","first-page":"E109","DOI":"10.1152\/ajpendo.00551.2018","article-title":"Sex-specific regulation of stress-induced fetal glucocorticoid surge by the mouse placenta","volume":"317","author":"A Wieczorek","year":"2019","journal-title":"Am J Physiol Endocrinol Metab"}],"container-title":["American Journal of Perinatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0043-1776348.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T13:45:07Z","timestamp":1730814307000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-1776348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,7]]},"references-count":30,"journal-issue":{"issue":"S 01","published-online":{"date-parts":[[2024,5,13]]},"published-print":{"date-parts":[[2024,5]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0043-1776348","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0735-1631","1098-8785"],"issn-type":[{"value":"0735-1631","type":"print"},{"value":"1098-8785","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,7]]}}}