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

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.