Hyaluronidase for reducing perineal trauma.

Background: Perineal trauma after vaginal birth is common and can be associated with short- and long-term health problems. Perineal hyaluronidase (HAase) injection has been widely used to reduce perineal trauma, perineal pain and the need for episiotomy since the 1950s. The administration of HAase is considered to be a simple, low risk, low cost and effective way to decrease perineal trauma without causing adverse effects.

Objectives: To assess the effectiveness and safety of perineal HAase injection for reducing perineal trauma, episiotomy and perineal pain during vaginal delivery.

Search methods: To identify studies for inclusion in this review, we searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase, CINAHL (EBSCOhost), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) in November 2023.

Selection criteria: Randomised and quasi-randomised controlled trials comparing women giving birth to their first baby receiving perineal HAase injection compared to placebo injection or no intervention during vaginal delivery of a single foetus with vertex foetal presentation (foetus with head engaging the maternal pelvis).

Data collection and analysis: We used standard methodological procedures expected by Cochrane. Two review authors independently assessed trials for inclusion, extracted and checked data, and evaluated the risk of bias in the studies. Our primary outcomes were perineal trauma (tears or episiotomy, or both), episiotomy and perineal pain. Our secondary outcomes were first and second degree perineal lacerations, third and fourth degree perineal lacerations, perineal oedema 1 hour after vaginal delivery, perineal oedema 24 hours after vaginal delivery and neonatal Apgar scores of less than 7 at five minutes after birth (Apgar score is a measure of the health status of a newborn). We assessed the certainty of the evidence using the GRADE approach.

Main results: We included five randomised controlled trials involving a total of 747 women (data were available for 743 women). The dosage of HAase used in the perineal injection varied from 750 turbidity-reducing units to 5000 international units. The certainty of the evidence was largely low (ranging from very low to moderate). Perineal HAase injection versus placebo injection Data from three trials involving 426 women provided low-certainty evidence that there may be no difference between the HAase and placebo groups in the incidence of perineal trauma (tears or episiotomy, or both) (RR 0.94, 95% CI 0.87 to 1.03; 426 participants, 3 studies), episiotomy (RR 0.91, 95% CI 0.71 to 1.15; 427 participants, 3 studies), first and second degree perineal lacerations (RR 1.02, 95% CI 0.87 to 1.18; 341 participants, 3 studies), third and fourth degree perineal lacerations (RR 0.46, 95% CI 0.11 to 2.05; 426 participants, 3 studies), and perineal oedema one hour after vaginal delivery (RR 0.99, 95% CI 0.78 to 1.25; 303 participants, 2 studies). Moreover, perineal HAase injection during the second stage of labour likely resulted in a reduction in incidence of perineal oedema 24 hours after vaginal delivery compared with placebo injection (RR 0.42, 95% CI 0.26 to 0.70; 303 participants, 2 studies; moderate-certainty evidence). There may be no difference between groups in Apgar scores less than 7 at five minutes (RR 5.00, 95% CI 0.24 to 105.95; 148 participants, 1 study; low-certainty evidence). Perineal HAase injection versus no intervention Data from three trials involving 373 women suggested that perineal HAase injection during the second stage of labour may result in a lower incidence of perineal trauma (tears or episiotomy, or both) (RR 0.61, 95% CI 0.42 to 0.88; 373 participants, 3 studies; low-certainty evidence) compared with no intervention. The evidence is very uncertain for episiotomy (RR 0.79, 95% CI 0.44 to 1.42; 373 participants, 3 studies), first and second degree perineal lacerations (RR 0.59, 95% CI 0.30 to 1.18; 373 participants, 3 studies) and perineal oedema one hour after vaginal delivery (RR 0.32, 95% CI 0.01 to 7.71; 139 participants, 1 study), all very low certainty evidence. No third and fourth degree perineal lacerations, perineal oedema 24 hours after vaginal delivery or Apgar scores less than 7 at five minutes were reported in these three trials. No side effects were reported in the included trials.

Authors' conclusions: Perineal HAase injection during the second stage of labour may result in a lower incidence of perineal trauma (tears or episiotomy, or both) compared with no intervention, but not compared with placebo injection, in women having a vaginal delivery. Meanwhile, perineal HAase injection likely reduces the incidence of perineal oedema 24 hours after vaginal delivery compared with placebo injection. The potential use of perineal HAase injection as a method to reduce perineal trauma and perineal oedema remains to be determined as the number of high-quality trials and outcomes reported was too limited to draw conclusions on its effectiveness and safety. Further rigorous randomised controlled trials are required to evaluate the role of perineal HAase injection in vaginal deliveries, including evaluating whether there is any differential effect based on the dose, frequency and positioning of HAase injection.