Challenging the paradigm that neonatal uterine bleeding represents the first menstrual episode

Abstract Neonatal uterine bleeding (NUB) has been hypothesized as a relatively common early-life event potentially linked to the later development of endometriosis through retrograde menstruation. However, its true prevalence and biological nature remain uncertain. This study aimed to determine the prevalence, biological features, and maternal–neonatal correlates of reddish diaper staining in newborns, and to evaluate its purported association with endometriosis. A prospective cross-sectional study was conducted between September 2023 and March 2024 at a tertiary obstetric center with postpartum outpatient follow-up. A total of 638 pregnant women with singleton pregnancies (530 female and 108 male fetuses) were enrolled. Participants completed prenatal questionnaires, and neonatal outcomes, including diaper staining, were assessed during follow-up. Diapers with reddish staining were collected and analyzed using light microscopy and biochemical assays to identify the presence and origin of blood. Umbilical cord blood samples from female newborns were analyzed for steroid hormone concentrations. Reddish diaper staining was observed in 22% of female and 13% of male neonates. Only two female samples (2.5%) tested positive for menstrual blood. Most of the reddish diapers contained urate crystals rather than blood. Maternal characteristics, exposure to endocrine-disrupting factors, and cord blood steroid hormone levels did not differ significantly between female neonates with and without reddish diaper staining. These findings indicate that reddish diaper staining in neonates is predominantly due to urate crystal excretion rather than true NUB. By identifying a major and previously unrecognized confounder, this study calls into question a long-standing biological assumption and reshapes current understanding of NUB and its supposed link to endometriosis. Our results provide a substantial paradigm shift in the interpretation of this phenomenon, redefining its clinical and biological significance and opening new perspectives for research in early-life determinants of reproductive health. Similar content being viewed by others Funding This research was funded by the Italian Ministry of Health (ENDO-2021-12371933) following peer review in the competitive grant “Bando Endometriosi 2021”. Author information Authors and Affiliations Corresponding author Ethics declarations Competing interests P.Ve. is a member of the Editorial Board of Human Reproduction Open, the Journal of Obstetrics and Gynaecology Canada, and of the International Editorial Board of Acta Obstetricia et Gynecologica Scandinavica; has received royalties from Wolters Kluwer for chapters on endometriosis management in the clinical decision support resource UpToDate; and maintains both a public and private gynaecological practice. E.S. is Editor-in-Chief of Human Reproduction Open; discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures; and maintains both a public and private gynaecological practice. P.Vi. is Co-Editor-in-Chief of Journal of Endometriosis and Uterine Disorders. M.O. became a member of the Editorial Board of Scientific Reports after the submission of this manuscript. All other authors declare they have no conflict of interest. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Fornelli, G., Mondini, I., Reschini, M. et al. Challenging the paradigm that neonatal uterine bleeding represents the first menstrual episode. Sci Rep (2026). https://doi.org/10.1038/s41598-026-52360-7 Received: Accepted: Published: DOI: https://doi.org/10.1038/s41598-026-52360-7