Loss of tight association between epidermis and dermis underlies several blistering disorders and is frequently caused by impaired function of extracellular matrix (ECM) proteins. Here we describe a new protein in mouse, Fras1, that is specifically detected in a linear fashion underlying the epidermis and the basal surface of other epithelia in embryos. Loss of Fras1 function results in the formation of subepidermal hemorrhagic blisters as well as unilateral or bilateral renal agenesis during mouse embryogenesis. Postnatally, homozygous Fras1 mutants have fusion of the eyelids and digits and unilateral renal agenesis or dysplasia. The defects observed in Fras1-/- mice phenocopy those of the existing bl (blebbed) mouse mutants, which have been considered a model for the human genetic disorder Fraser syndrome. We show that bl/bl homozygous embryos are devoid of Fras1 protein, consistent with the finding that Fras1 is mutated in these mice. In sum, our data suggest that perturbations in the composition of the extracellular space underlying epithelia could account for the onset of the blebbed phenotype in mouse and Fraser syndrome manifestation in human.

BackgroundEndometriosis is a common disease occurring in 1–2% of all women of reproductive age. Although there is increasing evidence on the association between endometriosis and adverse perinatal outcomes, little is known about the effect of pre-pregnancy treatments for endometriosis on subsequent perinatal outcomes. Thus, this study aimed to evaluate maternal and neonatal outcomes in pregnant women with endometriosis and to investigate whether pre-pregnancy surgical treatment would affect these outcomes.MethodsThis case-control study included 2769 patients who gave birth at Nagoya University Hospital located in Japan between 2010 and 2017. Maternal and neonatal outcomes were compared between the endometriosis group (n = 80) and the control group (n = 2689). The endometriosis group was further divided into two groups: patients with a history of surgical treatment such as cystectomy for ovarian endometriosis, ablation or excision of endometriotic implants, or adhesiolysis (surgical treatment group, n = 49) and those treated with only medications or without any treatment (non-surgical treatment group, n = 31).ResultsIn the univariate analysis, placenta previa and postpartum hemorrhage were significantly increased in the endometriosis group compared to the control group (12.5% vs. 4.1%, p <  0.01 and 27.5% vs. 18.2%, p = 0.04, respectively). In the multivariate analysis, endometriosis significantly increased the odds ratio (OR) for placenta previa (adjusted OR, 3.19; 95% confidence interval [CI], 1.56–6.50, p <  0.01) but not for postpartum hemorrhage (adjusted OR, 1.14; 95% CI, 0.66–1.98, p = 0.64). Other maternal and neonatal outcomes were similar between the two groups. In patients with endometriosis, patients in the surgical treatment group were significantly associated with an increased risk of placenta previa (OR. 4.62; 95% CI, 2.11–10.10, p <  0.01); however, patients in the non-surgical treatment group were not associated with a high risk (OR, 1.63; 95% CI, 0.19–6.59, p = 0.36). Additionally, other maternal and neonatal outcomes were similar between the two groups.ConclusionWomen who have had surgical treatment for their endometriosis appear to have a higher risk for placenta previa. This may be due to the more severe stage of endometriosis often found in these patients. However, clinicians should be alert to this potential increased risk and manage these patients accordingly.

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Introduction: Shock index (SI), calculated by dividing heart rate by systolic blood pressure, is used to detect hemodynamic instability and hypovolemia. In obstetric practice, limited evidence is available regarding its usefulness in detecting postpartum hemorrhage (PPH). We aimed to evaluate the usefulness of SI in detecting PPH in vaginal deliveries using clinical data from 12 primary maternity care units in Japan. Material and methods: In this multicenter retrospective study, a total of 30,820 women who delivered vaginally at term at 12 primary maternity care units from January 2012 to December 2018 were included. Systolic and diastolic blood pressures and heart rate were measured at five different time points from admission to postpartum 2 h, and postpartum blood loss was measured. We evaluated the trend of average SI and the performance of each vital sign for detection of PPH. Results: The trend of average SI during labor and the immediate postpartum period was approximately 0.7 in women with blood loss of <500 mL. SI from the time of delivery of the placenta increased with an increase in blood loss. SI had the highest area under the receiver operating characteristic curve of 0.699 [95% confidence interval (CI), 0.682-0.716] and 0.758 (95% CI, 0.729-0.788) for PPH of !1,000 and !1,500 mL, respectively. However, both sensitivity of SI (1.0) for PPH (!1,000 mL; 29.9%, and !1,500 mL; 40.5%, respectively) and correlation between maximum SI and blood loss (coefficient of correlation, 0.263) were low. Conclusions: SI is a better parameter for PPH detection in vaginal deliveries than other vital signs. However, clinical judgment must incorporate other vital signs and symptoms associated with hypovolemic shock due to the low sensitivity of SI.

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