BACKGROUND: Postpartum haemorrhage (PPH) is the single leading cause of maternal mortality worldwide. Most of the deaths associated with PPH occur in resource-poor settings where effective methods of prevention and treatment - such as oxytocin - are not accessible because many births still occur at home, or in community settings, far from a health facility. Likewise, most of the evidence supporting oxytocin effectiveness comes from hospital settings in high-income countries, mainly because of the need of well-organised care for its administration and monitoring. Easier methods for oxytocin administration have been developed for use in resource-poor settings, but as far as we know, its effectiveness has not been assessed in a systematic review. OBJECTIVES: To assess the effectiveness and safety of oxytocin provided in non-facility birth settings by any way in the third stage of labour to prevent PPH. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov (12 November 2015), and reference lists of retrieved reports. SELECTION CRITERIA: All published, unpublished or ongoing randomised or quasi-randomised controlled trials comparing the administration of oxytocin with no intervention, or usual/standard care for the management of the third stage of labour in non-facility birth settings were considered for inclusion.Quasi-randomised controlled trials and randomised controlled trials published in abstract form only were eligible for inclusion but none were identified. Cross-over trials were not eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, assessed risk of bias and extracted the data using an agreed data extraction form. Data were checked for accuracy. MAIN RESULTS: We included one cluster-randomised trial conducted in four rural districts in Ghana that randomised 28 community health officers (CHOs) (serving 2404 potentially eligible pregnant women) to the intervention group and 26 CHOs (serving 3515 potentially eligible pregnant women) to the control group. Overall, the trial had a high risk of bias. CHOs delivered the intervention in the experimental group (injection of 10 IU (international units) of oxytocin in the thigh one minute following birth using a prefilled, auto-disposable syringe). In the control group, CHOs did not provide this prophylactic injection to the women they observed. CHOs had no midwifery skills and did not in any way manage the birth. All other CHO activities (outcome measurement, data collection, and early treatment and referral when necessary) were identical across the control and oxytocin CHOs.Although only one of the nine cases of severe PPH (blood loss greater or equal to 1000 mL) occurred in the oxytocin group, the effect estimate for this outcome was very imprecise and it is uncertain whether the intervention prevents severe PPH (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.02 to 1.30; 1570 women (very low-quality evidence)). Similarly, because of the lack of cases of severe maternal morbidity (e.g. uterine rupture) and maternal deaths, it was not possible to obtain effect estimates for those outcomes (both very low-quality evidence).Oxytocin compared with the control group decreased the incidence of PPH (> 500 mL) in both our unadjusted (RR 0.48, 95% CI 0.28 to 0.81; 1569 women) and adjusted (RR 0.49, 95% CI 0.27 to 0.90; 1174 women (both low-quality evidence)) analyses. There was little or no difference between the oxytocin and control groups on the rates of transfer or referral of the mother to a healthcare facility (RR 0.72, 95% CI 0.34 to 1.56; 1586 women (low-quality evidence)), stillbirths (RR 1.27, 95% CI 0.67 to 2.40; 2006 infants (low-quality evidence)); andearly infant deaths (0 to three days) (RR 1.03, 95% CI 0.35 to 3.07; 1969 infants (low-quality evidence)). There were no cases of needle-stick injury or any other maternal major or minor adverse event or unanticipated harmful event. There were no cases of oxytocin use during labour.There were no data reported for some of this review's secondary outcomes: manual removal of placenta, maternal anaemia, neonatal death within 28 days, neonatal transfer to health facility for advanced care, breastfeeding rates. Similarly, the women's or the provider's satisfaction with the intervention was not reported. AUTHORS' CONCLUSIONS: It is uncertain if oxytocin administered by CHO in non-facility settings compared with a control group reduces the incidence of severe PPH (>1000 mL), severe maternal morbidity or maternal deaths. However, the intervention probably decreases the incidence of PPH (> 500 mL).The quality of the one trial included in this review was limited because of the risk of attrition and recruitment biases related to limitations in the follow-up of pregnant women in both arms of the trials and some baseline imbalance on the size of babies at birth. Additionally, there was serious imprecision of the effect estimates for most of the primary outcomes mainly because of the size of the trial, very few or no events and CIs around both relative and absolute estimates of effect that include both appreciable benefit and appreciable harm.Although the trial presented data both for primary and secondary outcomes, it seemed to be underpowered to detect differences in the primary outcomes that are the ones more relevant for making judgments about the potential applicability of the intervention in other settings (especially severe PPH).Therefore, taking into account the extreme setting where the intervention was implemented, the limited role of the CHO in the trial and the lack of power for detecting effects on primary (relevant) outcomes, the applicability of the evidence found seems to be rather limited.Further well-executed and adequately-powered randomised controlled trials assessing the effects of using oxytocin in pre-filled injection devices or other new delivery systems (spray-dried ultrafine formulation of oxytocin) on severe PPH are urgently needed. Likewise, other important outcomes like possible adverse events and acceptability of the intervention by mothers and other community stakeholders should also be assessed.
BACKGROUND: Postpartum haemorrhage (PPH) is the single leading cause of maternal mortality worldwide. Most of the deaths associated with PPH occur in resource-poor settings where effective methods of prevention and treatment - such as oxytocin - are not accessible because many births still occur at home, or in community settings, far from a health facility. Likewise, most of the evidence supporting oxytocin effectiveness comes from hospital settings in high-income countries, mainly because of the need of well-organised care for its administration and monitoring. Easier methods for oxytocin administration have been developed for use in resource-poor settings, but as far as we know, its effectiveness has not been assessed in a systematic review. OBJECTIVES: To assess the effectiveness and safety of oxytocin provided in non-facility birth settings by any way in the third stage of labour to prevent PPH. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov (12 November 2015), and reference lists of retrieved reports. SELECTION CRITERIA: All published, unpublished or ongoing randomised or quasi-randomised controlled trials comparing the administration of oxytocin with no intervention, or usual/standard care for the management of the third stage of labour in non-facility birth settings were considered for inclusion.Quasi-randomised controlled trials and randomised controlled trials published in abstract form only were eligible for inclusion but none were identified. Cross-over trials were not eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, assessed risk of bias and extracted the data using an agreed data extraction form. Data were checked for accuracy. MAIN RESULTS: We included one cluster-randomised trial conducted in four rural districts in Ghana that randomised 28 community health officers (CHOs) (serving 2404 potentially eligible pregnant women) to the intervention group and 26 CHOs (serving 3515 potentially eligible pregnant women) to the control group. Overall, the trial had a high risk of bias. CHOs delivered the intervention in the experimental group (injection of 10 IU (international units) of oxytocin in the thigh one minute following birth using a prefilled, auto-disposable syringe). In the control group, CHOs did not provide this prophylactic injection to the women they observed. CHOs had no midwifery skills and did not in any way manage the birth. All other CHO activities (outcome measurement, data collection, and early treatment and referral when necessary) were identical across the control and oxytocin CHOs.Although only one of the nine cases of severe PPH (blood loss greater or equal to 1000 mL) occurred in the oxytocin group, the effect estimate for this outcome was very imprecise and it is uncertain whether the intervention prevents severe PPH (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.02 to 1.30; 1570 women (very low-quality evidence)). Similarly, because of the lack of cases of severe maternal morbidity (e.g. uterine rupture) and maternal deaths, it was not possible to obtain effect estimates for those outcomes (both very low-quality evidence).Oxytocin compared with the control group decreased the incidence of PPH (> 500 mL) in both our unadjusted (RR 0.48, 95% CI 0.28 to 0.81; 1569 women) and adjusted (RR 0.49, 95% CI 0.27 to 0.90; 1174 women (both low-quality evidence)) analyses. There was little or no difference between the oxytocin and control groups on the rates of transfer or referral of the mother to a healthcare facility (RR 0.72, 95% CI 0.34 to 1.56; 1586 women (low-quality evidence)), stillbirths (RR 1.27, 95% CI 0.67 to 2.40; 2006 infants (low-quality evidence)); andearly infant deaths (0 to three days) (RR 1.03, 95% CI 0.35 to 3.07; 1969 infants (low-quality evidence)). There were no cases of needle-stick injury or any other maternal major or minor adverse event or unanticipated harmful event. There were no cases of oxytocin use during labour.There were no data reported for some of this review's secondary outcomes: manual removal of placenta, maternal anaemia, neonatal death within 28 days, neonatal transfer to health facility for advanced care, breastfeeding rates. Similarly, the women's or the provider's satisfaction with the intervention was not reported. AUTHORS' CONCLUSIONS: It is uncertain if oxytocin administered by CHO in non-facility settings compared with a control group reduces the incidence of severe PPH (>1000 mL), severe maternal morbidity or maternal deaths. However, the intervention probably decreases the incidence of PPH (> 500 mL).The quality of the one trial included in this review was limited because of the risk of attrition and recruitment biases related to limitations in the follow-up of pregnant women in both arms of the trials and some baseline imbalance on the size of babies at birth. Additionally, there was serious imprecision of the effect estimates for most of the primary outcomes mainly because of the size of the trial, very few or no events and CIs around both relative and absolute estimates of effect that include both appreciable benefit and appreciable harm.Although the trial presented data both for primary and secondary outcomes, it seemed to be underpowered to detect differences in the primary outcomes that are the ones more relevant for making judgments about the potential applicability of the intervention in other settings (especially severe PPH).Therefore, taking into account the extreme setting where the intervention was implemented, the limited role of the CHO in the trial and the lack of power for detecting effects on primary (relevant) outcomes, the applicability of the evidence found seems to be rather limited.Further well-executed and adequately-powered randomised controlled trials assessing the effects of using oxytocin in pre-filled injection devices or other new delivery systems (spray-dried ultrafine formulation of oxytocin) on severe PPH are urgently needed. Likewise, other important outcomes like possible adverse events and acceptability of the intervention by mothers and other community stakeholders should also be assessed.
Authors: Nicholas J Kassebaum; Amelia Bertozzi-Villa; Megan S Coggeshall; Katya A Shackelford; Caitlyn Steiner; Kyle R Heuton; Diego Gonzalez-Medina; Ryan Barber; Chantal Huynh; Daniel Dicker; Tara Templin; Timothy M Wolock; Ayse Abbasoglu Ozgoren; Foad Abd-Allah; Semaw Ferede Abera; Ibrahim Abubakar; Tom Achoki; Ademola Adelekan; Zanfina Ademi; Arsène Kouablan Adou; José C Adsuar; Emilie E Agardh; Dickens Akena; Deena Alasfoor; Zewdie Aderaw Alemu; Rafael Alfonso-Cristancho; Samia Alhabib; Raghib Ali; Mazin J Al Kahbouri; François Alla; Peter J Allen; Mohammad A AlMazroa; Ubai Alsharif; Elena Alvarez; Nelson Alvis-Guzmán; Adansi A Amankwaa; Azmeraw T Amare; Hassan Amini; Walid Ammar; Carl A T Antonio; Palwasha Anwari; Johan Arnlöv; Valentina S Arsic Arsenijevic; Ali Artaman; Majed Masoud Asad; Rana J Asghar; Reza Assadi; Lydia S Atkins; Alaa Badawi; Kalpana Balakrishnan; Arindam Basu; Sanjay Basu; Justin Beardsley; Neeraj Bedi; Tolesa Bekele; Michelle L Bell; Eduardo Bernabe; Tariku J Beyene; Zulfiqar Bhutta; Aref Bin Abdulhak; Jed D Blore; Berrak Bora Basara; Dipan Bose; Nicholas Breitborde; Rosario Cárdenas; Carlos A Castañeda-Orjuela; Ruben Estanislao Castro; Ferrán Catalá-López; Alanur Cavlin; Jung-Chen Chang; Xuan Che; Costas A Christophi; Sumeet S Chugh; Massimo Cirillo; Samantha M Colquhoun; Leslie Trumbull Cooper; Cyrus Cooper; Iuri da Costa Leite; Lalit Dandona; Rakhi Dandona; Adrian Davis; Anand Dayama; Louisa Degenhardt; Diego De Leo; Borja del Pozo-Cruz; Kebede Deribe; Muluken Dessalegn; Gabrielle A deVeber; Samath D Dharmaratne; Uğur Dilmen; Eric L Ding; Rob E Dorrington; Tim R Driscoll; Sergei Petrovich Ermakov; Alireza Esteghamati; Emerito Jose A Faraon; Farshad Farzadfar; Manuela Mendonca Felicio; Seyed-Mohammad Fereshtehnejad; Graça Maria Ferreira de Lima; Mohammad H Forouzanfar; Elisabeth B França; Lynne Gaffikin; Ketevan Gambashidze; Fortuné Gbètoho Gankpé; Ana C Garcia; Johanna M Geleijnse; Katherine B Gibney; Maurice Giroud; Elizabeth L Glaser; Ketevan Goginashvili; Philimon Gona; Dinorah González-Castell; Atsushi Goto; Hebe N Gouda; Harish Chander Gugnani; Rahul Gupta; Rajeev Gupta; Nima Hafezi-Nejad; Randah Ribhi Hamadeh; Mouhanad Hammami; Graeme J Hankey; Hilda L Harb; Rasmus Havmoeller; Simon I Hay; Ileana B Heredia Pi; Hans W Hoek; H Dean Hosgood; Damian G Hoy; Abdullatif Husseini; Bulat T Idrisov; Kaire Innos; Manami Inoue; Kathryn H Jacobsen; Eiman Jahangir; Sun Ha Jee; Paul N Jensen; Vivekanand Jha; Guohong Jiang; Jost B Jonas; Knud Juel; Edmond Kato Kabagambe; Haidong Kan; Nadim E Karam; André Karch; Corine Kakizi Karema; Anil Kaul; Norito Kawakami; Konstantin Kazanjan; Dhruv S Kazi; Andrew H Kemp; Andre Pascal Kengne; Maia Kereselidze; Yousef Saleh Khader; Shams Eldin Ali Hassan Khalifa; Ejaz Ahmed Khan; Young-Ho Khang; Luke Knibbs; Yoshihiro Kokubo; Soewarta Kosen; Barthelemy Kuate Defo; Chanda Kulkarni; Veena S Kulkarni; G Anil Kumar; Kaushalendra Kumar; Ravi B Kumar; Gene Kwan; Taavi Lai; Ratilal Lalloo; Hilton Lam; Van C Lansingh; Anders Larsson; Jong-Tae Lee; James Leigh; Mall Leinsalu; Ricky Leung; Xiaohong Li; Yichong Li; Yongmei Li; Juan Liang; Xiaofeng Liang; Stephen S Lim; Hsien-Ho Lin; Steven E Lipshultz; Shiwei Liu; Yang Liu; Belinda K Lloyd; Stephanie J London; Paulo A Lotufo; Jixiang Ma; Stefan Ma; Vasco Manuel Pedro Machado; Nana Kwaku Mainoo; Marek Majdan; Christopher Chabila Mapoma; Wagner Marcenes; Melvin Barrientos Marzan; Amanda J Mason-Jones; Man Mohan Mehndiratta; Fabiola Mejia-Rodriguez; Ziad A Memish; Walter Mendoza; Ted R Miller; Edward J Mills; Ali H Mokdad; Glen Liddell Mola; Lorenzo Monasta; Jonathan de la Cruz Monis; Julio Cesar Montañez Hernandez; Ami R Moore; Maziar Moradi-Lakeh; Rintaro Mori; Ulrich O Mueller; Mitsuru Mukaigawara; Aliya Naheed; Kovin S Naidoo; Devina Nand; Vinay Nangia; Denis Nash; Chakib Nejjari; Robert G Nelson; Sudan Prasad Neupane; Charles R Newton; Marie Ng; Mark J Nieuwenhuijsen; Muhammad Imran Nisar; Sandra Nolte; Ole F Norheim; Luke Nyakarahuka; In-Hwan Oh; Takayoshi Ohkubo; Bolajoko O Olusanya; Saad B Omer; John Nelson Opio; Orish Ebere Orisakwe; Jeyaraj D Pandian; Christina Papachristou; Jae-Hyun Park; Angel J Paternina Caicedo; Scott B Patten; Vinod K Paul; Boris Igor Pavlin; Neil Pearce; David M Pereira; Konrad Pesudovs; Max Petzold; Dan Poenaru; Guilherme V Polanczyk; Suzanne Polinder; Dan Pope; Farshad Pourmalek; Dima Qato; D Alex Quistberg; Anwar Rafay; Kazem Rahimi; Vafa Rahimi-Movaghar; Sajjad ur Rahman; Murugesan Raju; Saleem M Rana; Amany Refaat; Luca Ronfani; Nobhojit Roy; Tania Georgina Sánchez Pimienta; Mohammad Ali Sahraian; Joshua A Salomon; Uchechukwu Sampson; Itamar S Santos; Monika Sawhney; Felix Sayinzoga; Ione J C Schneider; Austin Schumacher; David C Schwebel; Soraya Seedat; Sadaf G Sepanlou; Edson E Servan-Mori; Marina Shakh-Nazarova; Sara Sheikhbahaei; Kenji Shibuya; Hwashin Hyun Shin; Ivy Shiue; Inga Dora Sigfusdottir; Donald H Silberberg; Andrea P Silva; Jasvinder A Singh; Vegard Skirbekk; Karen Sliwa; Sergey S Soshnikov; Luciano A Sposato; Chandrashekhar T Sreeramareddy; Konstantinos Stroumpoulis; Lela Sturua; Bryan L Sykes; Karen M Tabb; Roberto Tchio Talongwa; Feng Tan; Carolina Maria Teixeira; Eric Yeboah Tenkorang; Abdullah Sulieman Terkawi; Andrew L Thorne-Lyman; David L Tirschwell; Jeffrey A Towbin; Bach X Tran; Miltiadis Tsilimbaris; Uche S Uchendu; Kingsley N Ukwaja; Eduardo A Undurraga; Selen Begüm Uzun; Andrew J Vallely; Coen H van Gool; Tommi J Vasankari; Monica S Vavilala; N Venketasubramanian; Salvador Villalpando; Francesco S Violante; Vasiliy Victorovich Vlassov; Theo Vos; Stephen Waller; Haidong Wang; Linhong Wang; XiaoRong Wang; Yanping Wang; Scott Weichenthal; Elisabete Weiderpass; Robert G Weintraub; Ronny Westerman; James D Wilkinson; Solomon Meseret Woldeyohannes; John Q Wong; Muluemebet Abera Wordofa; Gelin Xu; Yang C Yang; Yuichiro Yano; Gokalp Kadri Yentur; Paul Yip; Naohiro Yonemoto; Seok-Jun Yoon; Mustafa Z Younis; Chuanhua Yu; Kim Yun Jin; Maysaa El Sayed Zaki; Yong Zhao; Yingfeng Zheng; Maigeng Zhou; Jun Zhu; Xiao Nong Zou; Alan D Lopez; Mohsen Naghavi; Christopher J L Murray; Rafael Lozano Journal: Lancet Date: 2014-05-02 Impact factor: 79.321
Authors: Cynthia K Stanton; Samuel Newton; Luke C Mullany; Patience Cofie; Charlotte Tawiah Agyemang; Edward Adiibokah; Niamh Darcy; Sadaf Khan; Alice Levisay; John Gyapong; Deborah Armbruster; Seth Owusu-Agyei Journal: BMC Pregnancy Childbirth Date: 2012-06-07 Impact factor: 3.007
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