Uterine atony and postpartum haemorrhage: predisposing genetic factors and postmortem findings.

Abstract: Uterine atony (UA) represents a serious medical condition characterized by ineffective contraction of the uterine muscle after placenta delivery and is responsible for up to 80% of postpartum hemorrhages (PPH) worldwide. UA onset prediction before delivery is still an ongoing challenge, even if many risk factors for UA onset have been identified almost 50% of atonic PPH occur in women without identifiable antepartum risks, making high vigilance during labor essential for all the healthcare providers involved in labor assistance. To prevent the onset of UA in high-risk women, prophylactic measures such as active management of third stage of labor, presence of intravenous access during labor, and presence of cross-matched blood available are recommended. If UA occurs, a conservative management based on uterotonic drugs, tranexamic acid and intrauterine tamponade should be preferred while surgical methods such as arteries ligation or hysterectomy should be considered as a last resort. Finally, the influence of genetic factors on predisposing to the onset, severity, and variable responses to treatment of this pathology was analyzed. Among these genetic factors, it has been observed that mutations affecting the genes encoding for the oxytocin receptor (OXTRs), but also for "uterine contraction-associated proteins" (CAPs) such as connexin43, prostaglandin-endoperoxide synthase 2 (Ptgs2), Gap junction protein alpha 1 (Gja1) and COX-2 - determining an abnormal response to hypoxia - may be responsible for the development of postpartum haemorrhage (PPH) due to uterine atony (UA).