Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis

Fiona Cheong-See, Ewoud Schuit, David Arroyo-Manzano, Asma Khalil, Jon Barrett, K S Joseph, Elizabeth Asztalos, Karien Hack, Liesbeth Lewi, Arianne Lim, Sophie Liem, Jane E Norman, John Morrison, C Andrew Combs, Thomas J Garite, Kimberly Maurel, Vicente Serra, Alfredo Perales, Line Rode, Katharina Worda, Anwar Nassar, Mona Aboulghar, Dwight Rouse, Elizabeth Thom, Fionnuala Breathnach, Soichiro Nakayama, Francesca Maria Russo, Julian N Robinson, Jodie M Dodd, Roger B Newman, Sohinee Bhattacharya, Selphee Tang, Ben Willem J Mol, Javier Zamora, Basky Thilaganathan, Shakila Thangaratinam, Global Obstetrics Network (GONet) Collaboration, Fiona Cheong-See, Ewoud Schuit, David Arroyo-Manzano, Asma Khalil, Jon Barrett, K S Joseph, Elizabeth Asztalos, Karien Hack, Liesbeth Lewi, Arianne Lim, Sophie Liem, Jane E Norman, John Morrison, C Andrew Combs, Thomas J Garite, Kimberly Maurel, Vicente Serra, Alfredo Perales, Line Rode, Katharina Worda, Anwar Nassar, Mona Aboulghar, Dwight Rouse, Elizabeth Thom, Fionnuala Breathnach, Soichiro Nakayama, Francesca Maria Russo, Julian N Robinson, Jodie M Dodd, Roger B Newman, Sohinee Bhattacharya, Selphee Tang, Ben Willem J Mol, Javier Zamora, Basky Thilaganathan, Shakila Thangaratinam, Global Obstetrics Network (GONet) Collaboration

Abstract

Objective: To determine the risks of stillbirth and neonatal complications by gestational age in uncomplicated monochorionic and dichorionic twin pregnancies.

Design: Systematic review and meta-analysis.

Data sources: Medline, Embase, and Cochrane databases (until December 2015).

Review methods: Databases were searched without language restrictions for studies of women with uncomplicated twin pregnancies that reported rates of stillbirth and neonatal outcomes at various gestational ages. Pregnancies with unclear chorionicity, monoamnionicity, and twin to twin transfusion syndrome were excluded. Meta-analyses of observational studies and cohorts nested within randomised studies were undertaken. Prospective risk of stillbirth was computed for each study at a given week of gestation and compared with the risk of neonatal death among deliveries in the same week. Gestational age specific differences in risk were estimated for stillbirths and neonatal deaths in monochorionic and dichorionic twin pregnancies after 34 weeks' gestation.

Results: 32 studies (29 685 dichorionic, 5486 monochorionic pregnancies) were included. In dichorionic twin pregnancies beyond 34 weeks (15 studies, 17 830 pregnancies), the prospective weekly risk of stillbirths from expectant management and the risk of neonatal death from delivery were balanced at 37 weeks' gestation (risk difference 1.2/1000, 95% confidence interval -1.3 to 3.6; I(2)=0%). Delay in delivery by a week (to 38 weeks) led to an additional 8.8 perinatal deaths per 1000 pregnancies (95% confidence interval 3.6 to 14.0/1000; I(2)=0%) compared with the previous week. In monochorionic pregnancies beyond 34 weeks (13 studies, 2149 pregnancies), there was a trend towards an increase in stillbirths compared with neonatal deaths after 36 weeks, with an additional 2.5 per 1000 perinatal deaths, which was not significant (-12.4 to 17.4/1000; I(2)=0%). The rates of neonatal morbidity showed a consistent reduction with increasing gestational age in monochorionic and dichorionic pregnancies, and admission to the neonatal intensive care unit was the commonest neonatal complication. The actual risk of stillbirth near term might be higher than reported estimates because of the policy of planned delivery in twin pregnancies.

Conclusions: To minimise perinatal deaths, in uncomplicated dichorionic twin pregnancies delivery should be considered at 37 weeks' gestation; in monochorionic pregnancies delivery should be considered at 36 weeks.

Systematic review registration: PROSPERO CRD42014007538.

Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5013231/bin/chef027508.f1_default.jpg
Fig 1 Study selection process in systematic review on prospective risk of stillbirth and neonatal complications in uncomplicated twin pregnancies (TTTT=twin to twin transfusion syndrome)
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5013231/bin/chef027508.f2_default.jpg
Fig 2 Risk of bias in studies included in systematic review on prospective risk of stillbirth and neonatal complications in uncomplicated twin pregnancies
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5013231/bin/chef027508.f3_default.jpg
Fig 3 Prospective risks of stillbirths from expectant management compared with risks of neonatal mortality from delivery at weekly intervals from 34 weeks’ gestation in twin pregnancies

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