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Metabolic changes accompanying gestational aging have been postulated as a determinant of birth timing, but specific nutrients, sensors, and messengers remain obscure. We report that placental nicotinamide adenine dinucleotide (NAD\n                    <jats:sup>+<\/jats:sup>\n                    ) dynamically tunes gestational length. Depletion of placental NAD\n                    <jats:sup>+<\/jats:sup>\n                    in mice provoked labor onset, mediated by the role of NAD\n                    <jats:sup>+<\/jats:sup>\n                    as a cofactor for 15-hydroxy prostaglandin dehydrogenase, an enzyme responsible for suppressing prostaglandin accumulation. Augmentation of placental NAD\n                    <jats:sup>+<\/jats:sup>\n                    prolonged gestation at baseline and in a model of preterm labor. These findings suggest a central role for metabolic exhaustion in provoking labor and reveal potential therapeutic avenues for preterm labor and the optimization of labor induction.\n                  <\/jats:p>","DOI":"10.1126\/science.adz1624","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T18:01:19Z","timestamp":1781200879000},"page":"1194-1199","update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Placental nicotinamide adenine dinucleotide modulates the timing of labor"],"prefix":"10.1126","volume":"392","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6153-1994","authenticated-orcid":true,"given":"Erin J.","family":"Ciampa","sequence":"first","affiliation":[{"name":"Department of Anesthesia, Beth Israel Deaconess Medical Center, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9455-4718","authenticated-orcid":true,"given":"Luana M.","family":"Machado","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Beth Israel Deaconess Medical Center, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Beth Israel Deaconess Medical Center, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6550-730X","authenticated-orcid":true,"given":"Amanda J.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center and Children\u2019s Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7439-1786","authenticated-orcid":true,"given":"Kyle Q.","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center and Children\u2019s Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7049-9284","authenticated-orcid":true,"given":"Nawal A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8521-7041","authenticated-orcid":true,"given":"Sarah","family":"Kispert","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Beth Israel Deaconess Medical Center, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0283-3772","authenticated-orcid":true,"given":"Samantha","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Beth Israel Deaconess Medical Center, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1399-5241","authenticated-orcid":true,"given":"Yunping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Beth Israel Deaconess Medical Center, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3890-151X","authenticated-orcid":true,"given":"Ginger L.","family":"Milne","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8863-4558","authenticated-orcid":true,"given":"Ashley","family":"Solmonson","sequence":"additional","affiliation":[{"name":"Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2281-6831","authenticated-orcid":true,"given":"S. Ananth","family":"Karumanchi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1038-981X","authenticated-orcid":true,"given":"Samir M.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA."},{"name":"Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.11.005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.11.043"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000301049"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00572-w"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0029-7"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251816"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.85597"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.11.037"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal0092"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.08.014"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.03.016"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.013988"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1704945114"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2007-0178"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2020.12.012"},{"key":"e_1_3_2_17_2","unstructured":"E. 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