{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:14:01Z","timestamp":1790115241759,"version":"4.0.1"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1123498"],"award-info":[{"award-number":["APP1123498"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Obstet Gynecol Scand"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Melatonin has been suggested to have a biological role in the onset and progress of labor. We tested the hypothesis that the addition of melatonin during an induction of labor will reduce the need for a cesarean birth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>This trial underwent protocol amendments that are detailed in the main text of the article. This trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12616000311459). At a multi\u2010center health service including secondary and tertiary obstetric hospitals, we performed a randomized, double\u2010blind, placebo\u2010controlled trial in women with a singleton cephalic pregnancy, free of significant maternal or perinatal complications who were undergoing induction of labor (with or without cervical ripening). Women were randomized to 10\u2009mg melatonin vs placebo, with cervical ripening as required, and then 6\u2010h during their induction of labor to a maximum of four doses or until birth. The primary outcome was cesarean birth. Secondary outcomes included labor, maternal, and neonatal outcomes. Data were analyzed using intention to treat. Sub\u2010group analyses based on mode of ripening and parity were also performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Between 2019 and 2021 we randomized 189 women (103 to melatonin and 86 to placebo). The study was prematurely terminated due to logistical complications resulting from the COVID\u201019 pandemic. Cesarean rates were 28\/103 (27.2%) in the melatonin group vs 20\/84 (23.3%) in the placebo group (RR 1.17 95% CI 0.71\u20131.92). There were no significant differences in rate of cesarean birth between the melatonin and placebo groups for failure to progress (13.4% and 9.3%, respectively, RR 1.46; 95% CI 0.64\u20133.32) or suspected fetal distress (10.7% and 10.5%, respectively, RR 1.02; 95% CI 0.44\u20132.34). The melatonin group had significantly lower rates of spontaneous vaginal birth within 24\u2009h (35.0% vs. 50.0%; RR 0.70 95% CI 0.50\u20130.98). The rates of secondary outcomes such as total length of labor, rate of postpartum hemorrhage, and instrumental birth were comparable. Babies born in the melatonin group were more likely to need admission to the special care nursery, namely for hypoglycemic monitoring (18.5% vs. 8.1% RR 2.26; 95% CI 1.00\u20135.10).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In women undergoing induction of labor, melatonin does not reduce the cesarean section rate. Melatonin use intrapartum may also be associated with neonatal hypoglycemia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aogs.14951","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T16:39:28Z","timestamp":1729787968000},"page":"2442-2454","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A double\u2010blind, randomized, placebo\u2010controlled trial of melatonin as an adjuvant agent for induction of labor: The\u00a0<scp>MILO<\/scp> trial"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2638-209X","authenticated-orcid":false,"given":"Diane","family":"Quach","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Monash Women's, Monash Health  Clayton Victoria Australia"},{"name":"Department of Obstetrics and Gynecology Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8337-550X","authenticated-orcid":false,"given":"Ben W.","family":"Mol","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Monash University  Clayton Victoria Australia"},{"name":"Aberdeen Centre for Women's Health Research, School of Medicine, Medical Sciences and Nutrition University of Aberdeen  Aberdeen UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Springer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Monash Women's, Monash Health  Clayton Victoria Australia"},{"name":"Department of Obstetrics and Gynecology Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Tully","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Monash Women's, Monash Health  Clayton Victoria Australia"},{"name":"Department of Obstetrics and Gynecology Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Higgins","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Monash Women's, Monash Health  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Monash Women's, Monash Health  Clayton Victoria Australia"},{"name":"Department of Obstetrics and Gynecology Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hennes","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Monash Women's, Monash Health  Clayton Victoria Australia"},{"name":"Department of Obstetrics and Gynecology Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen","family":"Pham","sequence":"additional","affiliation":[{"name":"The Ritchie Centre Hudson Institute of Medical Research  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamala","family":"Swarnamani","sequence":"additional","affiliation":[{"name":"The Ritchie Centre Hudson Institute of Medical Research  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Monash Women's, Monash Health  Clayton Victoria Australia"},{"name":"Department of Obstetrics and Gynecology Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1918-5538","authenticated-orcid":false,"given":"Miranda","family":"Davies\u2010Tuck","sequence":"additional","affiliation":[{"name":"The Ritchie Centre Hudson Institute of Medical Research  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"Welfare AIoHa.Australia's mothers and babies 2022 2022.https:\/\/www.aihw.gov.au\/reports\/mothers\u2010babies\/australias\u2010mothers\u2010babies\/contents\/summary"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800566"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2015.11.014"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4755-12-S2-S10"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-015-0518-z"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.2991\/jegh.k.200813.001"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00616"},{"key":"e_1_2_13_9_1","first-page":"43","article-title":"The hour of birth; a study of the distribution of times of onset of labor and of delivery throughout the 24\u2010hour period","volume":"7","author":"Charles E","year":"1953","journal-title":"Br J Prev Soc Med"},{"key":"e_1_2_13_10_1","first-page":"594","article-title":"Circadian rhythms during pregnancy","volume":"14","author":"Seron\u2010Ferre M","year":"1993","journal-title":"Endocr Rev"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-2243(94)90038-8"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719112442244"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1723"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12566"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2008.02102.x"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2001.310409.x"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2008.00649.x"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-015-0368-5"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.075655"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-2243(93)90099-X"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.1998.tb00550.x"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12508"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12121"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-032480"},{"key":"e_1_2_13_25_1","unstructured":"WormerK BauerA WillifordA.Bishop Score 2024.https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470368\/#:~:text=The%20most%20common%20modification%20to than%205%20is%20considered%20favorable."},{"key":"e_1_2_13_26_1","unstructured":"Promotion OoDPaH. Healthy people targets 2020\u2014maternal infant and child health ODPHD 2024.https:\/\/wayback.archive\u2010it.org\/5774\/20220414032744\/https:\/\/www.healthypeople.gov\/2020\/topics\u2010objectives\/topic\/maternal\u2010infant\u2010and\u2010child\u2010health\/objectives"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2021.01.034"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2014.46"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-017-4418-5"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-09-3691"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2014.06.020"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/01443619750112411"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-020-00537-z"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-00071"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/07420528.2020.1863975"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-022-00850-0"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12565"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-028243"},{"key":"e_1_2_13_39_1","unstructured":"Registry ANZCT. Melatonin supplementation effect on induction of labor rates in first time mothers: the MyTIME trial. Australian New Zealand Clinical Trials Registry 2024.https:\/\/www.anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?id=385355&isReview=true"},{"key":"e_1_2_13_40_1","first-page":"3252","article-title":"The role of melatonin in pregnancy and the health benefits for the newborn","volume":"10","author":"Verteramo R","year":"2022","journal-title":"Biomedicine"}],"container-title":["Acta Obstetricia et Gynecologica Scandinavica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aogs.14951","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T12:40:44Z","timestamp":1748349644000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1111\/aogs.14951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,24]]},"references-count":39,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/aogs.14951"],"URL":"https:\/\/doi.org\/10.1111\/aogs.14951","archive":["Portico"],"relation":{},"ISSN":["0001-6349","1600-0412"],"issn-type":[{"value":"0001-6349","type":"print"},{"value":"1600-0412","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,24]]},"assertion":[{"value":"2024-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}