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Meta-Analysis
. 2014 Feb 5;2014(2):CD010441.
doi: 10.1002/14651858.CD010441.pub2.

Hyaluronidase for reducing perineal trauma

Fan Zhou  1 , Xiao Dong Wang, Jing Li, Gui Qiong Huang, Bing Xin Gao
Affiliations
Meta-Analysis

Hyaluronidase for reducing perineal trauma

Fan Zhou et al. Cochrane Database Syst Rev. .

Update in

  • Hyaluronidase for reducing perineal trauma.
    Zhou F, Zhang J, Li Y, Huang GQ, Li J, Wang XD. Zhou F, et al. Cochrane Database Syst Rev. 2024 Nov 14;11(11):CD010441. doi: 10.1002/14651858.CD010441.pub3. Cochrane Database Syst Rev. 2024. PMID: 39540564

Abstract

Background: Perineal hyaluronidase (HAase) injection was widely used to reduce the occurrence of perineal trauma, pain and need for episiotomy in the 1950s to 1960s. Reports suggested that the administration of HAase was a simple, low risk, low cost and effective way to decrease perineal trauma without adverse effects.

Objectives: The objective of this review was to assess the effectiveness and safety of perineal HAase injection for reducing spontaneous perineal trauma, episiotomy and perineal pain in vaginal deliveries.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2013), the International Clinical Trials Registry Platform (ICTRP) and the Networked Digital Library of Theses and Dissertations (both on 1 April 2013), and reference lists of retrieved studies. We also contacted relevant organisations.

Selection criteria: Published and unpublished randomised and quasi-randomised controlled trials comparing perineal HAase injection with placebo injection or no intervention in vaginal deliveries.

Data collection and analysis: Two review authors independently assessed trials for inclusion, extracted data and evaluated methodological quality. Data were checked for accuracy.

Main results: The search strategy identified six potentially eligible studies. Two studies were excluded. We included four randomised controlled trials that randomised a total of 599 women (data were available for 595 women).Two trials (283 women) compared the effects of perineal HAase injection during the second stage of labour with placebo injection and were at low risk of bias. Three trials (one three-armed trial was analysed twice) (373 women) compared the effects of perineal HAase injection during second stage of labour with no intervention and two out of the three trials were at high risk of bias. Data from four trials involving 599 women suggested that perineal HAase injection during second stage of labour had a lower incidence of perineal trauma (average risk ratio (RR) 0.69, 95% confidence interval (CI) 0.50 to 0.95,Tau² = 0.08, I² = 82% compared with women in the control group, but there was no clear evidence of a reduction in the incidence of episiotomy (average RR 0.74, 95% CI 0.43 to 1.29, Tau² = 0.17, I² = 66%), first and second degree perineal lacerations (average RR 0.54, 95% CI 0.38 to 1.33, Tau² = 0.30 , I² = 85%) and third and fourth degree perineal lacerations (RR 0.12, 95% CI 0.01 to 2.13). Data from two trials involving 283 women indicated that there was no clear evidence of a reduction in the incidence of perineal trauma (RR 0.90, 95% CI 0.77 to 1.06, Tau²=1.07, I² = 7%), episiotomy (RR 0.77, 95% CI 0.32 to 1.89, Tau² = 0.27, I² = 54%), first and second degree perineal lacerations (RR 1.08, 95% CI 0.83 to 1.40, Tau² = 1.11, I² = 10%) and third and fourth degree perineal lacerations (RR 0.12, 95% CI 0.01 to 2.13) with perineal HAase injection. Data from three trials involving 373 women suggested that perineal HAase injection during second stage of labour had a lower incidence of perineal trauma (RR 0.61, 95% CI 0.42 to 0.88, Tau² = 0.08, I² = 78%) compared with no intervention, but had no clear effect on in the incidence of episiotomy (RR 0.79, 95% CI 0.44 to 1.42, Tau² = 0.16, I² = 70%) and first and second degree perineal lacerations (RR 0.58, 95% CI 0.31 to 1.10, Tau² = 0.18, I² = 59%). No side effects were reported in the included trials.No included trials reported on perineal pain and other pre-specified secondary outcomes: perineal trauma requiring suturing; blood loss; dyspareunia; urinary incontinence; faecal incontinence; assisted delivery rate; women's satisfaction; Apgar score less than seven at five minutes and need for admission to special care baby unit.

Authors' conclusions: Perineal HAase injection during second stage of labour had a lower incidence of perineal trauma compared with control or no intervention, but there was no clear evidence of benefit compared with placebo injection. The difference in incidence of perineal trauma may probably be due to bias and confounding in the non-placebo controlled comparison, this result should be interpreted cautiously. The potential use of perineal HAase injection as a method to reduce perineal trauma were yet to be determined as there was no appropriate established dose for HAase, no evidence of follow up, and the number of high-quality trials and outcomes reported were 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.

PubMed Disclaimer

Conflict of interest statement

We certify that we have no affiliations or involvement in any organisation or entity with a direct financial interest in the subject matter of the review (e.g. employment, consultancy, stock ownership, honoraria, expert testimony).

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 HAase injection versus control, Outcome 1 Incidence of perineal trauma.
1.2
1.2. Analysis
Comparison 1 HAase injection versus control, Outcome 2 Incidence of episiotomy.
1.3
1.3. Analysis
Comparison 1 HAase injection versus control, Outcome 3 Incidence of first and second degree perineal lacerations.
1.4
1.4. Analysis
Comparison 1 HAase injection versus control, Outcome 4 Incidence of third and fourth degree perineal lacerations.
2.1
2.1. Analysis
Comparison 2 HAase injection versus placebo injection, Outcome 1 Incidence of perineal trauma.
2.2
2.2. Analysis
Comparison 2 HAase injection versus placebo injection, Outcome 2 Incidence of episiotomy.
2.3
2.3. Analysis
Comparison 2 HAase injection versus placebo injection, Outcome 3 Incidence of first and second degree perineal lacerations.
2.4
2.4. Analysis
Comparison 2 HAase injection versus placebo injection, Outcome 4 Incidence of third and fourth degree perineal trauma.
3.1
3.1. Analysis
Comparison 3 HAase injection versus no intervention, Outcome 1 Incidence of perineal trauma.
3.2
3.2. Analysis
Comparison 3 HAase injection versus no intervention, Outcome 2 Incidence of episiotomy.
3.3
3.3. Analysis
Comparison 3 HAase injection versus no intervention, Outcome 3 Incidence of first and second degree perineal lacerations.
3.4
3.4. Analysis
Comparison 3 HAase injection versus no intervention, Outcome 4 Incidence of third and fourth degree perineal trauma.
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References

References to studies included in this review

Chatfield 1966 {published data only}
    1. Chatfield WR, Moir DD. The effect of hyaluronidase on the perineum. A controlled trial of 200 primigravid patients in labour. Journal of Obstetrics and Gynaecology of the British Commonwealth 1966;73:670‐1. - PubMed
Colacioppo 2011 {published data only}
    1. Colacioppo PM, Gonzalez Riesco ML, Koiffman MD. Use of hyaluronidase to prevent perineal trauma during spontaneous births: a randomized, placebo‐controlled, double‐blind, clinical trial. Journal of Midwifery & Women's Health 2011;56(5):436‐45. - PubMed
O'Leary 1965 {published data only}
    1. O'Leary JA, Erez S. Hyaluronidase as an adjuvant to episiotomy. Obstetrics & Gynecology 1965;26(1):66‐9.
Scarabotto 2008 {published data only}
    1. Scarabotto LB, Riesco ML. Use of hyaluronidase to prevent perineal trauma during spontaneous delivery: a pilot study. Journal of Midwifery & Women's Health 2008;53(4):353‐61. - PubMed

References to studies excluded from this review

Giri 1969 {published data only}
    1. Giri AK, Sarkar A, Banerjee P. Use of hyaluronidase with lignocaine hydrochloride for local infiltration during episiotomy. Journal of Obstetrics and Gynaecology of India 1969;19(6):705‐9.
Nashar 2011 {published data only}
    1. Nashar S, Nikolov A, Atanasova M, Garnizov T. [Efficiency of Cikatridina spray for healing of episiotomy and perineal ruptures]. [Bulgarian]. Akusherstvo i Ginekologiia 2011;50(3):20‐5. - PubMed

Additional references

Aasheim 2011
    1. Aasheim V, Nilsen ABV, Lukasse M, Reinar LM. Perineal techniques during the second stage of labour for reducing perineal trauma. Cochrane Database of Systematic Reviews 2011, Issue 12. [DOI: 10.1002/14651858.CD006672.pub2] - DOI - PMC - PubMed
Albers 2005
    1. Albers LL, Sedler KD, Bedrick EJ, Teaf D, Peralta P. Midwifery care measures in the second stage of labor and reduction of genital tract trauma at birth: a randomized trial. Journal of Midwifery & Womens Health 2005;50(5):365‐72. - PMC - PubMed
Albers 2006
    1. Albers LL, Sedler KD, Bedrick EJ, Teaf D, Peralta P. Factors related to genital trauma in normal spontaneous vaginal births. Birth 2006;33(2):94‐100. - PubMed
Altman 2007
    1. Altman D, Ragnar I, Ekstrom A, Tyden T, Olsson SE. Anal sphincter lacerations and upright delivery postures ‐ a risk analysis from a randomized controlled trial. International Urogynecology Journal 2007;18(2):141‐6. - PubMed
Andrews 2006
    1. Andrews V, Sultan AH, Thakar R, Jones PW. Risk factors for obstetric anal sphincter injury: a prospective study. Birth 2006;33(2):117‐22. - PubMed
Andrews 2007
    1. Andrews V, Thakar R, Sultan AH, Jones PW. Evaluation of postpartum perineal pain and dyspareunia ‐ a prospective study. European Journal of Obstetrics, Gynecology and Reproductive Biology 2007;137:152‐6. - PubMed
Attarha 2009
    1. Attarha M, Vakilian K, Akbari Torkestani N, Heydari T, Bayatian Y. Effect of perineal massage during second phase of labor on episiotomy and laceration rates among nulliparous women. HAYAT 2009;15(3):15‐22.
Barrett 2000
    1. Barrett G, Pendry E, Peacock J, Victor C, Thakar R, Manyonda I. Women's sexual health after childbirth. BJOG: an international journal of obstetrics and gynaecology 2000;107(2):186‐95. - PubMed
Beckmann 2013
    1. Beckmann MM, Stock OM. Antenatal perineal massage for reducing perineal trauma. Cochrane Database of Systematic Reviews 2013, Issue 4. [DOI: 10.1002/14651858.CD005123.pub3] - DOI - PMC - PubMed
Boyles 2009
    1. Boyles SH, Li H, Mori T. Effect of mode of delivery on the incidence of urinary incontinence in primiparous women. Obstetrics and Gynecology 2009;113(1):134‐41. - PubMed
Brement 2007
    1. Brement S, Mossan S, Belery A, Racinet C. Delivery in lateral position. Randomized clinical trial comparing the maternal positions in lateral position and dorsal position for the second stage of labour. Gynecologie, Obstetrique and Fertilite 2007;35:637‐44. - PubMed
Byrd 2005
    1. Byrd LM, Hobbiss J, Tasker M. Is it possible to predict or prevent third degree tears?. Colorectal Disease 2005;7(4):311‐8. - PubMed
Carroli 2009
    1. Carroli G, Mignini L. Episiotomy for vaginal birth. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858.CD000081.pub2] - DOI - PMC - PubMed
Carroll 2003
    1. Carroll TG, Engelken M, Mosier MC, Nazir N. Epidural analgesia and severe perineal laceration in a community‐based obstetric practice. Journal of the American Board of Family Practice 2003;16(1):1‐6. - PubMed
Christianson 2003
    1. Christianson LM, Bovbjerg VE, McDavitt EC, Hullfish KL. Risk factors for perineal injury during delivery. American Journal of Obstetrics and Gynecology 2003;189(1):255‐60. - PubMed
Dahlen 2007
    1. Dahlen HG, Homer CSE, Cooke M, Upton AM, Nunn R, Brodrick B. Perineal outcomes and maternal comfort related to the application of perineal warm packs in the second stage of labor: a randomized controlled trial. Birth 2007;34(4):282‐90. - PubMed
Dahlen 2009
    1. Dahlen HG, Homer CS, Cooke M, Upton AM, Nunn RA, Brodrick BS. 'Soothing the ring of fire': Australian women's and midwives' experiences of using perineal warm packs in the second stage of labour. Midwifery 2009;25(2):39‐48. - PubMed
Dannecker 2004
    1. Dannecker C, Hillemanns P, Strauss A, Hasbargen U, Hepp H, Anthuber C. Episiotomy and perineal tears presumed to be imminent: randomized controlled trial. Acta Obstetricia et Gynecologica Scandinavica 2004;83(4):364‐8. - PubMed
Davidson 2000
    1. Davidson K, Jacoby S, Brown MS. Prenatal perineal massage: preventing lacerations during delivery. Journal of Obstetric, Gynecologic and Neonatal Nursing 2000;29(5):474‐9. - PubMed
Digonnet 1952
    1. Digonnet L, Cahn J, Roy J, Boucet J. Effect of local injection of hyaluronidase on perineal distension in labor in primiparas. Therapie 1952;7:388‐91. - PubMed
Downe 2003
    1. Downes S. Transition and the second stage of labour. Myles Textbook for Midwives. Edinburgh: Churchill Livingstone, 2003.
Eason 2002
    1. Eason E, Labrecque M, Marcoux S, Mondor M. Anal incontinence after childbirth. Canadian Medical Association Journal 2001;166(3):326‐30. - PMC - PubMed
Edwards 2006
    1. EdwardsH, Grotegut C, Harmanli OH, Rapkin D. Is severe perineal damage increased in women with prior anal sphincter injury?. Journal of Maternal‐fetal and Neonatal Medicine 2006;19(11):723‐7. - PubMed
Ekeus 2008
    1. Ekeus C, Nilsson E, Gottvall K. Increasing incidence of anal sphincter tears among primiparas in Sweden: a population based register study. Acta Obstetricia et Gynecologica Scandinavica 2008;87(5):564‐73. [DOI: 10.1080/00016340802030629] - DOI - PubMed
Eskandar 2009
    1. Eskandar O, Shet D. Risk factors for 3rd and 4th degree perineal tear. Journal of Obstetrics and Gynaecology 2009;29(2):119‐22. - PubMed
Fenner 2003
    1. Fenner DE, Genberg B, Brahma P, Marek L, DeLancey JO. Fecal and urinary incontinence after vaginal delivery with anal sphincter disruption in an obstetrics unit in the United States. American Journal of Obstetrics and Gynecology 2003;189(6):1543‐9. - PubMed
Fitzpatrick 2003
    1. Fitzpatrick M, Behan M, O'Connell PR, O'Herlihy C. Randomised clinical trial to assess anal sphincter function following forceps or vacuum assisted vaginal delivery. BJOG: an international journal of obstetrics and gynaecology 2003;110(4):424‐9. - PubMed
Girish 2007
    1. Girish KS, Kemparaju K. The magic glue hyaluronan and its eraser hyaluronidase: a biological overview. Life Sciences 2007;80(21):1921‐43. - PubMed
Goldberg 2003
    1. GoldbergJ, Hyslop T, Tolosa JE, Sultana C. Racial differences in severe perineal lacerations after vaginal delivery. American Journal of Obstetrics and Gynecology 2003;188(4):1063‐7. - PubMed
Graham 2005
    1. Graham ID, Carroli G, Davies C, Medves JM. Episiotomy rates around the world: an update. Birth 2005;32(3):219‐23. - PubMed
Hartman 2005
    1. Hartman K, Viswanathan M, Palmieri R, Gartlehner G, Thorp J Jr, Lohr KN. Outcomes of routine episiotomy: a systematic review. JAMA 2005;293(17):2141‐8. - PubMed
Higgins 2011
    1. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Hirayama 2012
    1. Hirayama F, Koyanagi A, Mori R, Zhang J, Souza JP, Gulmezoglu AM. Prevalence and risk factors for third‐ and fourth‐ degree perineal lacerations during vaginal delivery: a multi‐country study. BJOG: an international journal of obstetrics and gynaecology 2012;119(3):340‐7. - PubMed
Kalichman 2008
    1. Kalichman L. Perineal massage to prevent perineal trauma in childbirth. Israel Medical Association Journal 2008;10(7):531‐3. - PubMed
Kudish 2008
    1. KudishB, Sokol RJ, Kruger M. Trends in major modifiable risk factors for severe perineal trauma, 1996‐2006. BJOG: an international journal of obstetrics and gynaecology 2008;102(2):165‐70. - PMC - PubMed
Lowder 2007
    1. Lowder JL, Burrows LJ, Krohn MA, Weber AM. Risk factors for primary and subsequent anal sphincter lacerations: a comparison of cohorts by parity and prior mode of delivery. American Journal of Obstetrics and Gynecology 2007;196:344e1‐344e5. - PubMed
Macarthur 2004
    1. Macarthur AJ, Macarthur C. Incidence, severity, and determinants of perineal pain after vaginal delivery: a prospective cohort study. American Journal of Obstetrics and Gynecology 2004;191(4):1199‐204. - PubMed
Mayerhofer 2002
    1. Mayerhofer K, Bodner‐Adler B, Bodner K, Rabl M, Kaider A, Wagenbichler P, et al. Traditional care of the perineum during birth. A prospective, randomized, multicenter study of 1,076 women. Journal of Reproductive Medicine 2002;47(6):477‐82. - PubMed
McCandlish 1998
    1. McCandlish R, Bowler U, van Asten H, Berridge G, Winter C, Sames L, et al. A randomized controlled trial of care of the perineum during second stage of normal labor. British Journal of Obstetrics and Gynaecology 1998;105(12):1262‐72. - PubMed
Menzel 1998
    1. Menzel EJ, Farr C. Hyaluronidase and its substrate hyaluronan: biochemistry, biological activities and therapeutic uses. Cancer Letters 1998;131(1):3‐11. - PubMed
Mink 1955
    1. Mink E. Experience with the softening effect of hyaluronidase on high and rigid perineum in primiparous. Geburtshilfe Frauenheilkd 1955;15(3):246‐58. - PubMed
Nakai 2006
    1. Nakai A, Yoshida A, Yamaguchi S, Kawabata I, Hayashi M, Yokota A, et al. Incidence and risk factors for severe perineal laceration after vaginal delivery in Japanese patients. Archives of Gynecology 2006;274(4):222‐6. - PubMed
Patrini 1956
    1. Patrini G. Usefulness of hyaluronidase in labor as protector of the perineum. Rivista di Ostetricia e Ginecologia 1956;38:710‐4. - PubMed
Radestad 2008
    1. Radestad I, Olsson A, Nissen E, Rubertsson C. Tears in the vagina, perineum, sphincter ani, and rectum and first sexual intercourse after childbirth: a nationwide follow‐up. Birth 2008;35(2):98‐106. - PubMed
Raisanen 2009
    1. Raisanen S, Vehvilainen‐Julkunen K, Gissler M, Heinonen S. The increased incidence of obstetric anal sphincter rupture? an emerging trend in Finland. Preventive Medicine 2009;49(6):535‐40. - PubMed
RCOG 2007
    1. Fernando RJ, Williams AA, Adams EJ. The Management of Third and Fourth‐Degree Perineal Tears. RCOG Green‐top Guidelines. No 29. London: RCOG, 2007.
RevMan 2012 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Rodriguez 2008
    1. Rodriguez A, Arenas EA, Osorio AL, Mendez O, Zuleta JJ. Selective vs routine midline episiotomy for the prevention of third or fourth‐degree lacerations in nulliparous women. American Journal of Obstetrics and Gynecology 2008;198(258):e1‐4. - PubMed
Samarasekera 2009
    1. Samarasekera DN, Bekhit MT, Preston JP, Speakman CT. Risk factors for anal sphincter disruption during child birth. Langenbecks Archives of Surgery 2009;394(3):535‐8. - PubMed
Sanders 2005
    1. Sanders J, Peters T, Campbell R. Techniques to reduce perineal pain during spontaneous vaginal delivery and perineal suturing: a UK survey of midwifery practice. Midwifery 2005;21(2):154‐60. - PubMed
Schaub 2008
    1. Schaub AF, Litschgi M, Hoesli I, Holzgreve W, Bleul U, Geissbuhler V. Obstetric gel shortens second stage of labor and prevents perineal trauma in nulliparous women: a randomized controlled trial on labor facilitation. Journal of Perinatal Medicine 2008;36(2):129‐35. - PubMed
Soong 2005
    1. Soong B, Barnes M. Maternal position at midwife‐attended birth and perineal trauma: is there an association?. Birth 2005;32(3):164‐9. - PubMed
Spallicci 2007
    1. Spallicci MD, Chiea MA, Singer JM, Albuquerque PB, Bittar RE, Zugaib M. Use of hyaluronidase for cervical ripening: a randomized trial. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2007;130(1):46‐50. - PubMed
Sultan 2002
    1. Sultan AH, Thakar R. Lower genital tract and anal sphincter trauma. Best Practice and Research in Clinical Obstetrics and Gynaecology 2002;16(1):99‐115. - PubMed
Thies‐Lagergren 2011
    1. Thies‐Lagergren L, Kvist LJ, Christensson K, Hildingsson I. Maternal outcomes in nulliparous women who gave vaginal birth on a birth seat or in any other position: Results of a randomised controlled trial in Sweden. Journal of Paediatrics and Child Health 2011;47 (Suppl 1):36‐7.
Voldner 2009
    1. Voldner N, Froslie KF, Haakstad LAH, Bo K, Henriksen T. Birth complications, overweight, and physical inactivity. Acta Obstetricia et Gynecologica Scandinavica 2009;88(5):550‐5. - PubMed
Weerasekera 2002
    1. Weerasekera DS, Premaratne S. A randomised prospective trial of the obstetric forceps versus vacuum extraction using defined criteria. Journal of Obstetrics and Gynaecology 2002;22:344‐5. - PubMed
Williams 2007
    1. Williams A, Herron‐Marx S, Carolyn H. The prevalence of enduring postnatal perineal morbidity and its relationship to perineal trauma. Midwifery 2007;23(4):392‐403. - PubMed
Williams 2011
    1. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Rouse DJ, Spong CY. Williams Obstetrics. The McGraw‐Hill Companies, 2011.

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