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Purpose: Hyaluronidase (HAase) has many uses in medicine, and reports suggest that it affects perineal tissue during fetal passagethrough the vaginal canal. However, its potential use for preventing perineal trauma has yet to be determined. This study sought toevaluate the efficacy and safety of perineal HAase injections in reducing perineal trauma during vaginal delivery. Materials and Methods: A multi-center, double-blind, placebo-controlled, randomized study was conducted from January 2016 toMarch 2017. Nulliparous women who planned to undergo vaginal delivery were recruited, and the enrolled women were randomlyassigned to the HAase injection group (HAase injection, 5000 IU, n=75) or the control group (normal saline injection, n=73). Thedegree of perineal laceration, rate of episiotomy, and grade of perineal edema at 1 hour and 24 hours after spontaneous vaginal deliverywere compared between the two groups. Results: A total of 148 women who underwent vaginal delivery were recruited. No significant differences were observed betweenthe HAase injection and control groups in the rates of perineal laceration (p=0.422). Perineal edema significantly decreased 24hours after delivery in the women treated with perineal HAase injections, compared to women in the control group (p=0.008). Theoverall incidences of adverse events, such as redness of the injection site, infection, and wound dehiscence, were similar betweenthe two groups. Conclusion: HAase injections in nulliparous women afforded no reductions in the rates of perineal lacerations and episiotomy. However, the use of perineal HAase injections did reduce perineal edema without severe adverse events.