Animal models of postpartum hemorrhage.

Postpartum hemorrhage (PPH)-heavy bleeding following childbirth-is a leading cause of morbidity and mortality worldwide. PPH can affect individuals regardless of risks factors and its incidence has been increasing in high-income countries including the United States. The high incidence and severity of this childbirth complication has propelled research into advanced treatments and alternative solutions for patients facing PPH; however, the development of novel treatments is limited by the absence of a common, well-established and well-validated animal model of PPH. A variety of animals have been used for in vivo studies of novel therapeutic materials; however, each of these animals differs considerably from the anatomy and physiology of a postpartum woman, and the methods used for achieving a postpartum hemorrhagic condition vary widely. Here we critically evaluate the various animal models of PPH presented in the literature and propose additional and alternative methods for modeling PPH in in vivo studies. We highlight how current animal models successfully or unsuccessfully mimic the anatomy and physiology of a postpartum woman and how this may impact treatment development. We aim to equip researchers with the necessary background information to select appropriate animal models for their research related to PPH solutions, while supporting the goals of refinement, reduction and replacement (3Rs) in preclinical animal studies.