Planned Early Delivery Versus Expectant Management for Monoamniotic Twins (Review)

Planned early delivery versus expectant management for monoamniotic twins (Review)

Shub A, Walker SP

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2015, Issue 4 http://www.thecochranelibrary.com

Planned early delivery versus expectant management for monoamniotic twins (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER...... 1 ABSTRACT ...... 1 PLAINLANGUAGESUMMARY ...... 2 BACKGROUND ...... 2 OBJECTIVES ...... 3 METHODS ...... 3 RESULTS...... 5 DISCUSSION ...... 5 AUTHORS’CONCLUSIONS ...... 5 ACKNOWLEDGEMENTS ...... 5 REFERENCES ...... 6 DATAANDANALYSES...... 8 APPENDICES ...... 8 CONTRIBUTIONSOFAUTHORS ...... 11 DECLARATIONSOFINTEREST ...... 12 SOURCESOFSUPPORT ...... 12 DIFFERENCES BETWEEN PROTOCOL AND REVIEW ...... 12

Planned early delivery versus expectant management for monoamniotic twins (Review) i Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Review] Planned early delivery versus expectant management for monoamniotic twins

Alexis Shub1, Susan P Walker1

1Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia

Contact address: Alexis Shub, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia. [email protected]. [email protected].

Editorial group: Cochrane Pregnancy and Childbirth Group. Publication status and date: New, published in Issue 4, 2015. Review content assessed as up-to-date: 31 March 2015.

Citation: Shub A, Walker SP. Planned early delivery versus expectant management for monoamniotic twins. Cochrane Database of Systematic Reviews 2015, Issue 4. Art. No.: CD008820. DOI: 10.1002/14651858.CD008820.pub2.

ABSTRACT

Background Monoamniotic twin pregnancies are formed when a single egg is fertilised and the resulting inner cell mass splits to form twins sharing the same amniotic sac. This condition is rare and affects about one in 10,000 pregnancies overall. Monoamniotic twin pregnancies are susceptible to complications including cord entanglement, increased congenital anomalies, intrauterine growth restriction, twin-to- twin transfusion syndrome and increased perinatal mortality. All twin pregnancies also carry additional maternal risks including pre- eclampsia, anaemia, antepartum haemorrhage, postpartum haemorrhage and operative delivery. The optimal timing for the delivery of monoamniotic twins is not known. The options include ’planned early delivery’ between 32 and 34 weeks, or alternatively awaiting spontaneous labour at least up until the usual time of planned delivery for other monochorionic twins (approximately 36 to 38 weeks’ gestation), unless there is a speciﬁc indication for earlier delivery. Objectives To assess whether routine early delivery in monoamniotic twin pregnancies improves fetal, neonatal or maternal outcomes compared with ’expectant management’. Expectant management means awaiting spontaneous labour at least up until the usual time of planned delivery for other monochorionic twins (approximately 36 to 38 weeks’ gestation in many centres), unless a speciﬁc indication for delivery occurs in the meantime, e.g. for non-reassuring antenatal testing. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 March 2015). Selection criteria Published and unpublished randomised controlled trials (including cluster-randomised trials) comparing outcomes for women and infants who were randomised to planned early delivery of a monoamniotic twin pregnancy with outcomes for women and infants who were randomised to either planned term delivery or expectant management. However, we did not identify any trials for inclusion in this review. Quasi-randomised controlled trials, trials published in abstract form only, and trials using a cross-over design are not eligible for inclusion in this review.

No trials were identiﬁed by the search strategy.

Main results

No trials were identiﬁed by the search strategy.

Authors’ conclusions

Monoamniotic twins are rare, and there is insufﬁcient randomised controlled evidence on which to draw strong conclusions about the best management. In their absence, we can refer to historical case series and expert consensus. Management plans should take into consideration the availability of high-quality neonatal care if early delivery is chosen. Women and their families should be involved in the decision making about these high-risk pregnancies.

Ongoing, multicentre audits of maternal and perinatal outcomes for monoamniotic twins are needed in order to inform families and clinicians about up-to-date perinatal outcomes with contemporary obstetric practice. Research should consider the social and economic implications of planned interventions, as well as the perinatal outcomes.

PLAIN LANGUAGE SUMMARY

Planned early delivery versus expectant management for twins who are in the same amniotic sac during pregnancy (monoamniotic twins)

Monoamniotic twin pregnancies are rare and affect about one in 10,000 pregnancies. These pregnancies are more susceptible to complications such as increased congenital abnormalities, intrauterine growth restriction, twin-to-twin transfusion syndrome, cord entanglement and possible occlusion, which may lead to an increased risk of fetal and infant death compared with other kinds of twin pregnancies. The optimal timing for the birth of monoamniotic twins is not known. Options include ’planned early delivery’ between 32 and 34 weeks, or alternatively awaiting spontaneous labour at least up until the usual time of planned delivery for other monochorionic twins (approximately 36 to 38 weeks’ gestation), unless there is a speciﬁc indication for earlier delivery.

We searched for randomised controlled studies comparing planned early delivery with waiting until 36 to 38 weeks of pregnancy. We did not identify any relevant trials for inclusion in this review. Consequently, decisions about the optimal timing of delivery for monoamniotic twins will be based on other information including from case series and based on expert opinion. Ongoing, multicentre audit of maternal and perinatal outcomes for monoamniotic twins should be performed in order to inform families and clinicians about up-to-date perinatal outcomes with contemporary obstetric practice. Research should consider the social and economic implications of planned interventions, as well as the perinatal outcomes. Women and their families should be involved in the decision making around these high-risk pregnancies.

BACKGROUND egg is fertilised and the resulting inner cell mass splits after day nine.Monoamniocity is a rare condition affecting about one in 10,000 pregnancies. The presence of both fetuses in the same amniotic sac commonly Description of the condition leads to cord entanglement and this may result in cord accidents Twin pregnancies make up about 1.4% of pregnancies. Twenty and fetal death. In addition, monoamniotic twins are susceptible per cent of these pregnancies consist of monochorionic twins to the complications faced by all monochorionic twins including (where the fetuses share a placenta) and 5% of monochorionic preterm birth, increased congenital anomalies, intrauterine growth twins are monoamniotic (where the fetuses are in the same am- restriction, twin-to-twin transfusion syndrome and increased peri- niotic sac). Monoamniotic pregnancies are formed when a single

Planned early delivery versus expectant management for monoamniotic twins (Review) 2 Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. natal mortality. All twin pregnancies also carry additional maternal stated that this risk is minimal after 32 weeks’ gestation because risks including pre-eclampsia, anaemia, antepartum haemorrhage, less fetal movement occurs with increasing fetal size and relatively postpartum haemorrhage and operative delivery. decreased amniotic fluid (Tessen 1991). It has also been stated Monoamniotic twin pregnancies in the current era are associated that early detection of impending fetal death is possible by detec- with a perinatal mortality of approximately 15% in pregnancies af- tion of cardiotocographic changes present when cord compression ter 20 weeks’ gestation (Allen 2001; Hack 2009; Morikawa 2012), occurs (Rodis 1997). These potential benefits of reducing fetal although previously this has been reported to be as high as 70% death by early delivery must be balanced against the neonatal risks (Beasley 1999). Overall perinatal mortality for all monochorionic of prematurity; the medical, psychological, social and financial twins is approximately 8% (Ortibus 2009) and much of the excess implications for the mother of intensive inpatient or outpatient perinatal mortality for monoamniotic twins is thought to be due to surveillance regimens; and cost implications for the health service. cord entanglement (Su 2002). All twin pregnancies are associated Consideration of the neonatal risks must include not only mortal- with a higher maternal and fetal complication rate than singleton ity, but short- and long-term morbidity. Increasing evidence sug- pregnancies, but none more so than monoamniotic twins. gests that even late preterm birth has important long-term health and neurodevelopmental risks for the child (Boyle 2012; Quigley 2012). Description of the intervention This review attempts to answer the question regarding the optimal Why it is important to do this review timing of delivery of monoamniotic twins. The options for management include delivering all monoamni- Monoamniotic twin pregnancies are uncommon, and are associ- otic twins at a predetermined gestation, such as 32 or 34 weeks, ated with high rates of poor outcomes. Individual centres and clin- ’planned early delivery’ or alternatively ’expectant management’. icians are unlikely to care for enough women to gain experience in Expectant management means waiting for spontaneous labour at the best form of management of these complicated pregnancies. least up until the usual time of planned delivery for other mono- Much of the literature regarding monoamniotic twin pregnancy chorionic twins (approximately 36 to 38 weeks’ gestation in many and optimal management is based on small case series, often col- centres), unless there is a specific indication for delivery in the lected over a lengthy period of time, with changing obstetric and meantime, e.g. for non-reassuring antenatal testing. neonatal practices, and the potential problems of both positive Although the review discusses timing of delivery, it is also im- and negative publication bias. The interventions that are proposed portant to note that the standard practice for the management to reduce perinatal mortality may carry a high rate of perinatal of monoamniotic twins is widely variable with regard to ante- and maternal risks, and so it is important to base management natal ultrasound and cardiotocography (CTG) surveillance regi- decisions on high-quality evidence. mens. These factors may also have an independent role to play in maternal and neonatal outcomes. Published regimens for antenatal surveillance of monoamniotic twins vary from ultrasound and CTG testing every two weeks to prolonged admission to hospital OBJECTIVES from as early as 26 weeks’ gestation with CTG testing up to three times each day (Heyborne 2005; Van Mieghem 2014). Most cen- To assess whether routine early delivery in monoamniotic twin tres plan to deliver all monoamniotic twins by caesarean section; pregnancies improves fetal, neonatal or maternal outcomes com- however, this is not universal, and some centres deliver selected pared with ’expectant management’. monoamniotic twins vaginally. We aim to determine whether a policy of planned delivery at a predetermined, premature gestation results in improved maternal METHODS and perinatal outcomes compared to a policy of ’expectant management’ as defined above. Criteria for considering studies for this review

How the intervention might work Many authors have commented that early delivery will reduce the Types of studies perinatal risks of monoamniotic twins, by delivering the babies All published and unpublished randomised controlled trials, in- before a catastrophic event such as cord occlusion associated with cluding cluster-randomised trials, that compare outcomes for entanglement, with consequent death of one or both babies, oc- women and infants who were randomised to planned early deliv- curs (Dickinson 2005; Pasquini 2006; Roque 2003). Others have ery of a monoamniotic twin pregnancy with outcomes for women

Planned early delivery versus expectant management for monoamniotic twins (Review) 3 Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. and infants who were randomised to either planned term delivery Short-term maternal outcomes or expectant management. We did not plan to include quasi-ran- 1. Postpartum haemorrhage, as defined by the trial authors. domised trials, cross-over trials or trials published only as abstracts. 2. Blood transfusion. 3. Prolonged hospital stay. 4. Venous thromboembolus. Types of participants 5. Woman not satisfied with care. Women with an antenatally diagnosed monoamniotic twin pregnancy, excluding women with other serious twin complications Longer-term maternal outcomes (at one to six months) (twin-to-twin transfusion syndrome, twin reversed arterial perfu- 1. Postnatal depression, as defined by trial authors. sion, serious fetal anomaly, conjoined twins, intrauterine growth restriction) or higher order multiples. Health services 1. Cost. Types of interventions Planned early delivery before 34 completed weeks’ gestation compared with other types of care. Search methods for identification of studies The following methods section of this review is based on a standard template used by the Cochrane Pregnancy and Childbirth Group. Types of outcome measures

Electronic searches

Primary outcomes We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register by contacting the Trials Search Co-ordinator (31 • Perinatal death or serious neonatal morbidity (e.g. severe March 2015). birth asphyxia, seizures, neonatal encephalopathy, serious birth The Cochrane Pregnancy and Childbirth Group’s Trials Register trauma, severe respiratory distress syndrome, prolonged neonatal is maintained by the Trials Search Co-ordinator and contains trials intensive care unit admission; or as defined by trial authors). identified from: 1. monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL); Secondary outcomes 2. weekly searches of MEDLINE (Ovid); 3. weekly searches of Embase (Ovid); 4. monthly searches of CINAHL (EBSCO); Short-term perinatal/neonatal morbidity 5. handsearches of 30 journals and the proceedings of major conferences; 1. Fetal death. 6. weekly current awareness alerts for a further 44 journals 2. Neonatal death. plus monthly BioMed Central email alerts. 3. Arterial cord blood pH less than 7.0. Details of the search strategies for CENTRAL, MEDLINE, Em- 4. Neonatal intensive care unit admission. base and CINAHL, the list of handsearched journals and confer- 5. Prolonged hospital admission, as defined by trial authors. ence proceedings, and the list of journals reviewed via the current 6. Neonatal encephalopathy, as defined by trial authors. awareness service can be found in the ‘Specialized Register’ section 7. Intraventricular haemorrhage: grade III or IV. within the editorial information about the Cochrane Pregnancy 8. Cystic periventricular leukomalacia. and Childbirth Group. 9. Septicaemia. Trials identified through the searching activities described above 10. Necrotising enterocolitis. are each assigned to a review topic (or topics). The Trials Search 11. Assisted ventilation 24 hours or more. Co-ordinator searches the register for each review using the topic 12. Breast fed at hospital discharge. list rather than keywords.

Long-term infant outcomes Searching other resources 1. Cerebral palsy. We planned to search reference lists of retrieved studies. 2. Intellectual disability. We did not apply any date or language restrictions to the search.

Planned early delivery versus expectant management for monoamniotic twins (Review) 4 Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Data collection and analysis 2014). Other experts, based on published case series, and a survey of maternal fetal medicine specialists in the USA, suggest delivery In this version of the review no relevant trials were identiﬁed by should take place between 32 and 34 weeks’ gestation (DeFalco the search strategy. If relevant trials are identiﬁed in the future we 2006; Desai 2012; Dickinson 2005; Ezra 2005; Roque 2003). will use the methods set out in Appendix 1 for assessing eligibility, data extraction, assessment of risk of bias and data analysis.

AUTHORS’ CONCLUSIONS

Implications for practice RESULTS There are no randomised controlled trial data available to guide decision making as to whether routine early delivery in monoamniotic twin pregnancies improves fetal, neonatal or maternal out- Description of studies comes compared with ’expectant management’. In their absence, we can refer to historical case series and expert consensus. Man- agement plans should take into consideration the availability of Results of the search high-quality neonatal care if early delivery is chosen. Women and There were no trial reports in the Pregnancy and Childbirth their families should be involved in the decision making about Group’s Trials Register. these high-risk pregnancies

Implications for research Risk of bias in included studies Due to the difficulties of performing good quality randomised controlled trials in this group of pregnant women, further research No trials were identified for inclusion in the review. should be by other methods. Ongoing, multicentre audit of maternal and perinatal outcomes for monoamniotic twins should be performed in order to inform families and clinicians about up- Effects of interventions to-date perinatal outcomes with contemporary obstetric practice. No trials were identified for inclusion in the review. Research should consider the social and economic implications of planned interventions, as well as the perinatal outcomes. National or international registries may be the most appropriate method to facilitate comprehensive audit. DISCUSSION This review did not identify any trials for inclusion. ACKNOWLEDGEMENTS While there is insufficient good quality randomised controlled trial evidence to guide the timing of birth for monoamniotic twins, Therese Dowswell (Cochrane Pregnancy and Childbirth Group) there is a body of expert opinion to draw on. The largest pub- assisted with the review, she is supported by a grant from the lished series of monoamniotic twins specifically addresses the is- National Institute for Health Research (NIHR), UK (NIHR sue of timing of delivery and significant neonatal complication, Cochrane Programme Grant Project: 13/89/05 - Pregnancy and and recommends delivery at 33 weeks’ gestation (Van Mieghem childbirth systematic reviews to support clinical guidelines).

Additional references Morikawa 2012 Morikawa M, Yamada T, Yamada T, Sato S, Minakami H. Allen 2001 Prospective risk of intrauterine fetal death in monoamniotic Allen VM, Windrim R, Barret J, Ohlsson A. Management twin pregnancies. Twin Research and Human Genetics 2012; of monoamniotic twin pregnancies: a case series and 15(4):522–6. systematic review of the literature. BJOG: an international Ortibus 2009 journal of obstetrics and gynaecology 2001;108:931–6. Ortibus E, Lopriore E, Deprest J, Vandenbussche FP, Beasley 1999 Walther FJ, Diemert A, et al. The pregnancy and long-term Beasley E, Megerian G, Gerson A, Roberts NS. neurodevelopmental outcome of monochorionic diamniotic Monoamniotic twins: case series and proposal for antenatal twin gestations: a multicenter prospective cohort study from management. Obstetrics and Gynecology 1999;93(1):130–4. the first trimester onward. American Journal of Obstetrics [PUBMED: 9916970] and Gynecology 2009;200(5):494.e1–494.e8. [PUBMED: Boyle 2012 19375567] Boyle EM, Poulsen G, Field DJ, Kurinczuk JJ, Wolke D, Pasquini 2006 Alfirevic Z, et al. Effects of gestational age at birth on health Pasquini L, Wimalasundera RC, Fichera A, Barigye outcomes at 3 and 5 years of age: population based cohort O, Chappell L, Fisk NM. High perinatal survival in study. BMJ 2012;344:e896. [DOI: 10.1136/bmj.e896.] monoamniotic twins managed by prophylactic sulindac, DeFalco 2006 intensive ultrasound surveillance, and cesarean delivery at DeFalco LM, Sciscione AC, Megerian G, Tolosa J, Macones 32 weeks’ gestation. Ultrasound in Obstetrics and Gynecology G, O’Shea A, et al. Inpatient versus outpatient management 2006;28(5):681–7. [PUBMED: 17001748] of monoamniotic twins and outcomes. American Journal of Quigley 2012 Perinatology 2006;23(4):205–11. [PUBMED: 16596486] Quigley MA, Poulsen G, Boyle E, Wolke D, Field D, Desai 2012 Alfirevic Z, et al. Early term and late preterm birth are Desai N, Lewis D, Sunday S, Rochelson B. Current associated with poorer school performance at age 5 years: antenatal management of monoamniotic twins: a survey of a cohort study. Archives of Disease in Childhood. Fetal and maternal-fetal medicine specialists. Journal of Maternal-Fetal Neonatal Edition 2012;97(3):F167–F173. [PUBMED: Medicine 2012;25(10):1913–6. [PUBMED: 22385411] 22215800] Dickinson 2005 RevMan 2014 Dickinson JE. Monoamniotic twin pregnancy: a review The Nordic Cochrane Centre, The Cochrane Collaboration. of contemporary practice. Australian and New Zealand Review Manager (RevMan). 5.3. Copenhagen: The Nordic Journal of Obstetrics and Gynaecology 2005;45(6):474–8. Cochrane Centre, The Cochrane Collaboration, 2014. [PUBMED: 16401210] Rodis 1997 Ezra 2005 Rodis JF, McIlveen PF, Egan JF, Borgida AF, Turner GW, Ezra Y, Shveiky D, Ophir E, Nadjari M, Eisenberg VH, Campbell WA. Monoamniotic twins: improved perinatal Samueloff A, et al. Intensive management and early survival with accurate prenatal diagnosis and antenatal fetal delivery reduce antenatal mortality in monoamniotic twin surveillance. American Journal of Obstetrics and Gynecology pregnancies. Acta Obstetricia et Gynecologica Scandinavica 1997;177(5):1046–9. [PUBMED: 9396891] 2005;84(5):432–5. [PUBMED: 15842206] Roque 2003 Hack 2009 Roque H, Gillen-Goldstein J, Funai E, Young BK, Hack KE, Derks JB, Schaap AH, Lopriore E, Elias SG, Lockwood CJ. Perinatal outcomes in monoamniotic Arabin B, et al. Perinatal outcome of monoamniotic twin gestations. Journal of Maternal-Fetal and Neonatal Medicine pregnancies. Obstetrics & Gynecology 2009;113:353–60. 2003;13(6):414–21. [PUBMED: 12962268] Heyborne 2005 Su 2002 Heyborne KD, Porreco RP, Garite TJ, Phair K, Abril Su LL. Monoamniotic twins: diagnosis and management. D. Improved perinatal survival of monoamniotic twins Acta Obstetricia et Gynecologica Scandinavica 2002;81(11): with intensive inpatient monitoring. American Journal 995–1000. [PUBMED: 12421165] of Obstetrics and Gynecology 2005;192(1):96–101. Tessen 1991 [PUBMED: 15672009] Tessen JA, Zlatnik FJ. Monoamniotic twins: a retrospective Higgins 2011 controlled study. Obstetrics & Gynecology 1991;77(6): Higgins JPT, Green S, editors. Cochrane Handbook for 832–4. [PUBMED: 2030852] Systematic Reviews of Interventions Version 5.1.0 [updated Van Mieghem 2014 March 2011]. The Cochrane Collaboration, 2011. Van Mieghem T, De Heus R, Lewi L, Klaritsch P,Kollmann Available from www.cochrane-handbook.org. M, Baud D, et al. Prenatal management of monoamniotic

Planned early delivery versus expectant management for monoamniotic twins (Review) 6 Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. twin pregnancies. Obstetrics & Gynecology 2014;124(3): 498–506. References to other published versions of this review

Shub 2010 Shub A, Walker S. Planned early delivery versus expectant management for monoamniotic twins. Cochrane Database of Systematic Reviews 2010, Issue 11. [DOI: 10.1002/ 14651858.CD008820] ∗ Indicates the major publication for the study

This review has no analyses.

APPENDICES

Appendix 1. Methods to be used in updates if relevant trials are identiﬁed In future updates we will use the following methods based on a standard template used by the Cochrane Pregnancy and Childbirth Group.

Searching other resources We will look for additional studies in the reference lists of the studies identiﬁed. We will not apply any language or date restrictions.

Data collection and analysis

Selection of studies Two review authors will independently assess for inclusion all the potential studies identiﬁed as a result of the search strategy. We will resolve any disagreement through discussion or, if required, we will consult a third person.

Data extraction and management We will design a form to extract data. For eligible studies, two review authors will extract the data using the agreed form. We will resolve discrepancies through discussion or, if required, we will consult a third person. Data will be entered into Review Manager software (RevMan 2014) and checked for accuracy. When information regarding any of the above is unclear, we plan to contact the authors of the original reports to provide further details.

Assessment of risk of bias in included studies Two review authors will independently assess risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Any disagreement will be resolved by discussion or by involving a third assessor.

(1) Random sequence generation (checking for possible selection bias) We will describe for each included study the method used to generate the allocation sequence in sufﬁcient detail to allow an assessment of whether it should produce comparable groups. We will assess the method as: • low risk of bias (any truly random process, e.g. random number table; computer random number generator); • high risk of bias (any non-random process, e.g. odd or even date of birth; hospital or clinic record number); • unclear risk of bias.

Planned early delivery versus expectant management for monoamniotic twins (Review) 8 Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. (2) Allocation concealment (checking for possible selection bias) We will describe for each included study the method used to conceal allocation to interventions prior to assignment and will assess whether intervention allocation could have been foreseen in advance of, or during recruitment, or changed after assignment. We will assess the methods as: • low risk of bias (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes); • high risk of bias (open random allocation; unsealed or non-opaque envelopes, alternation; date of birth); • unclear risk of bias.

(3.1) Blinding of participants and personnel (checking for possible performance bias) We will describe for each included study the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We will consider that studies are at low risk of bias if they were blinded, or if we judge that the lack of blinding unlikely to affect results. We will assess blinding separately for different outcomes or classes of outcomes. We will assess the methods as: • low, high or unclear risk of bias for participants; • low, high or unclear risk of bias for personnel.

(3.2) Blinding of outcome assessment (checking for possible detection bias) We will describe for each included study the methods used, if any, to blind outcome assessors from knowledge of which intervention a participant received. We will assess blinding separately for different outcomes or classes of outcomes. We will assess methods used to blind outcome assessment as: • low, high or unclear risk of bias.

(4) Incomplete outcome data (checking for possible attrition bias due to the amount, nature and handling of incomplete outcome data) We will describe for each included study, and for each outcome or class of outcomes, the completeness of data including attrition and exclusions from the analysis. We will state whether attrition and exclusions were reported and the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. Where sufﬁcient information is reported, or is supplied by the trial authors, we plan to re-include missing data in the analyses which we undertake. We will assess methods as: • low risk of bias (e.g. no missing outcome data; missing outcome data balanced across groups); • high risk of bias (e.g. numbers or reasons for missing data imbalanced across groups; ‘as treated’ analysis done with substantial departure of intervention received from that assigned at randomisation); • unclear risk of bias.

(5) Selective reporting (checking for reporting bias) We will describe for each included study how we have investigated the possibility of selective outcome reporting bias and what we found. We will assess the methods as: • low risk of bias (where it is clear that all of the study’s pre-specified outcomes and all expected outcomes of interest to the review have been reported); • high risk of bias (where not all the study’s pre-specified outcomes have been reported; one or more reported primary outcomes were not pre-specified; outcomes of interest are reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported); • unclear risk of bias.

(6) Other bias (checking for bias due to problems not covered by (1) to (5) above) We will describe for each included study any important concerns we had about other possible sources of bias.

Planned early delivery versus expectant management for monoamniotic twins (Review) 9 Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. (7) Overall risk of bias We will make explicit judgements about whether studies are at high risk of bias, according to the criteria given in the Handbook (Higgins 2011). With reference to (1) to (6) above, we plan to assess the likely magnitude and direction of the bias and whether we consider it is likely to impact on the ﬁndings. We will explore the impact of the level of bias through undertaking sensitivity analyses - see Sensitivity analysis.

Measures of treatment effect

Dichotomous data For dichotomous data, we will present results as summary risk ratio with 95% conﬁdence intervals.

Continuous data We will use the mean difference if outcomes are measured in the same way between trials. We will use the standardised mean difference to combine trials that measure the same outcome, but use different methods.

Unit of analysis issues

Cluster-randomised trials We will include cluster-randomised trials in the analyses along with individually-randomised trials. We will adjust their sample sizes using the methods described in the Handbook using an estimate of the intracluster correlation co-efﬁcient (ICC) derived from the trial (if possible), from a similar trial or from a study of a similar population. If we use ICCs from other sources, we will report this and conduct sensitivity analyses to investigate the effect of variation in the ICC. If we identify both cluster-randomised trials and individually-randomised trials, we plan to synthesise the relevant information. We will consider it reasonable to combine the results from both if there is little heterogeneity between the study designs and the interaction between the effect of intervention and the choice of randomisation unit is considered to be unlikely. We will also acknowledge heterogeneity in the randomisation unit and perform a subgroup analysis to investigate the effects of the randomisation unit.

Cross-over trials Cros-over trials are not a relevant design for this type of intervention.

Other unit of analysis issues For the neonatal data, we will seek statistical advice to correct the conﬁdence intervals to allow for the cluster effect of randomisation of the babies in pairs.

Dealing with missing data For included studies we will note levels of attrition and if there are several studies included, the impact of including studies with high levels of missing data in the overall assessment of treatment effect will be explored by using sensitivity analysis. For all outcomes, analyses will be carried out, as far as possible, on an intention-to-treat basis, i.e. we will attempt to include all participants randomised to each group in the analyses. The denominator for each outcome in each trial being the number randomised minus any participants whose outcomes are known to be missing.

Planned early delivery versus expectant management for monoamniotic twins (Review) 10 Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Assessment of heterogeneity We will assess statistical heterogeneity in each meta-analysis using the Tau², I² and Chi² statistics. We will regard heterogeneity as substantial if an I² is greater than 30% and either a Tau² is greater than zero, or there is a low P value (less than 0.10) in the Chi² test for heterogeneity. If we identify substantial heterogeneity (above 30%), we plan to explore it by pre-speciﬁed subgroup analysis.

Assessment of reporting biases If there are 10 or more studies in the meta-analysis, we will investigate reporting biases (such as publication bias) using funnel plots. We will assess funnel plot asymmetry visually. If asymmetry is suggested by a visual assessment, we will perform exploratory analyses to investigate it.

Data synthesis We will carry out statistical analysis using the Review Manager software (RevMan 2014). We will use fixed-effect meta-analysis for combining data where it is reasonable to assume that studies are estimating the same underlying treatment effect: i.e. where trials examine the same intervention, and the trials’ populations and methods are judged sufficiently similar. If there is clinical heterogeneity sufficient to expect that the underlying treatment effects differ between trials, or if substantial statistical heterogeneity is detected, we will use random-effects meta-analysis to produce an overall summary, if an average treatment effect across trials is considered clinically meaningful. The random-effects summary will be treated as the average range of possible treatment effects and we will discuss the clinical implications of treatment effects differing between trials. If the average treatment effect is not clinically meaningful, we will not combine trials. If we use random-effects analyses, the results will be presented as the average treatment effect with 95% confidence intervals, and estimates of Tau² and I².

Subgroup analysis and investigation of heterogeneity If we identify substantial heterogeneity, we will investigated it using subgroup analyses. We plan to carry out the following subgroup analyses: 1. planned delivery before 32 completed weeks’ gestation versus other form of care; 2. intensive surveillance versus routine surveillance. We will use the following outcome in subgroup analysis: • perinatal death (excluding fatal anomalies) or serious neonatal morbidity (e.g. severe birth asphyxia, seizures, neonatal encephalopathy, serious birth trauma, severe respiratory distress syndrome, prolonged neonatal intensive care unit admission; or as deﬁned by trial authors). We will assess differences between subgroups by interaction tests available within RevMan (RevMan 2014). We will report the results of subgroup analyses quoting the Chi² statistic and P value, and the interaction test I² value.

Sensitivity analysis We plan to carry out sensitivity analyses to explore the effect of trial quality assessed by concealment of allocation, high attrition rates, or both, with poor quality studies being excluded from the analyses in order to assess whether this makes any difference to the overall result.

Planned early delivery versus expectant management for monoamniotic twins (Review) 11 Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. CONTRIBUTIONSOFAUTHORS SP Walker reviewed the topic and contributed to the protocol and review development. A Shub prepared a ﬁrst draft of the review and is the guarantor for the review.

DECLARATIONSOFINTEREST None known.

SOURCES OF SUPPORT

Internal sources • No sources of support supplied

External sources • National Institute for Health Research (NIHR), UK. NIHR Cochrane Programme Grant Project: 13/89/05 - Pregnancy and childbirth systematic reviews to support clinical guidelines

DIFFERENCESBETWEENPROTOCOLANDREVIEW The methods text has been updated in line with the most recent standard methods text used by the Cochrane Pregnancy and Childbirth Group. We have edited the secondary outcome ’Prolonged hospital admission’ to ’Prolonged hospital admission, as deﬁned by the trial authors’.