Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysisBMJ 2016; 354 doi: https://doi.org/10.1136/bmj.i4353 (Published 06 September 2016) Cite this as: BMJ 2016;354:i4353
- Fiona Cheong-See, clinical research fellow1,
- Ewoud Schuit, postdoctoral research fellow2 3 4,
- David Arroyo-Manzano, biostatistician5,
- Asma Khalil, consultant obstetrician6,
- Jon Barrett, senior scientist7,
- K S Joseph, professor of obstetrics and gynaecology8,
- Elizabeth Asztalos, associate professor9,
- Karien Hack, MD and PhD, in obstetrics and gynaecology10,
- Liesbeth Lewi, assistant professor in obstetrics and gynaecology11 12,
- Arianne Lim, gynaecologist13,
- Sophie Liem, MD in obstetrics and gynaecology13,
- Jane E Norman, professor of maternal and fetal health14,
- John Morrison, professor of obstetrics and gynaecology and paediatrics15,
- C Andrew Combs, associate director of research16,
- Thomas J Garite, director of research and education, professor emeritus of obstetrics and gynaecology16 17,
- Kimberly Maurel, associate director16,
- Vicente Serra, professor of obstetrics and gynaecology18 19,
- Alfredo Perales, professor of obstetrics and gynaecology19 20,
- Line Rode, senior resident21,
- Katharina Worda, specialist in obstetrics and gynaecology22,
- Anwar Nassar, professor of obstetrics and gynaecology23,
- Mona Aboulghar, professor of obstetrics and gynaecology24,
- Dwight Rouse, principal investigator, professor of obstetrics and gynaecology25,
- Elizabeth Thom, research professor of biostatistics and epidemiology26,
- Fionnuala Breathnach, consultant obstetrician and gynaecologist, senior lecturer in maternal fetal medicine26,
- Soichiro Nakayama, assistant professor27,
- Francesca Maria Russo, MD in obstetrics and gynaecology28,
- Julian N Robinson, chief of obstetrics and associate professor29,
- Jodie M Dodd, professor of obstetrics and gynaecology30,
- Roger B Newman, professor and Maas chair for reproductive sciences31,
- Sohinee Bhattacharya, senior lecturer32,
- Selphee Tang, data analyst33,
- Ben Willem J Mol, professor of obstetrics and gynaecology34,
- Javier Zamora, senior lecturer, head of clinical biostatistics unit, director of clinical epidemiology research area35 36,
- Basky Thilaganathan, professor and director of fetal medicine6,
- Shakila Thangaratinam, professor of maternal and perinatal health1,
- A Global Obstetrics Network (GONet) Collaboration
- 1Women’s Health Research Unit, Barts and the London School of Medicine and Dentistry, Queen Mary University of London E1 2AB, UK
- 2Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands
- 3Department of Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, Netherlands
- 4Stanford Prevention Research Center, Stanford University, Palo Alto, Stanford, CA 94305, USA
- 5Clinical Biostatistics Unit, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
- 6Fetal Medicine Unit, St George’s Healthcare NHS Trust, London SW17 0QT, UK
- 7Evaluative Clinical Sciences, Women and Babies Research Program, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada
- 8Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC V6Z 2K5, Canada
- 9Department of Newborn and Developmental Paediatrics, Women and Babies Research Program, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada
- 10Department of Gynaecology and Obstetrics, Diakonessenhuis, 3582 KE Utrecht, Netherlands
- 11Department of Obstetrics-Gynaecology, University Hospitals, 3000 Leuven, Belgium
- 12Department of Development and Regeneration: Pregnancy, Fetus and Neonate, KU Leuven, Belgium
- 13Department of Obstetrics and Gynaecology, Academic Medical Centre, 1105 AZ Amsterdam, Netherlands
- 14University of Edinburgh MRC Centre for Reproductive Health, Queen’s Medical Research Institute, Edinburgh EH16 4TY, UK
- 15Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS, USA
- 16Obstetrix Collaborative Research Network, Center for Research, Education and Quality, Mednax National Medical Group, FL 33323, USA
- 17University of California Irvine, Irvine, CA 92697, USA
- 18Maternal-Fetal Medicine Unit, Instituto Valenciano de Infertilidad, University of Valencia, Spain
- 19Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Valencia, Jefe Servicio Obstetricia Hospital U P La FE, Torre F, Valencia, Espana
- 20Department of Obstetrics, University Hospital La Fe, Valencia, 46026 València, Spain
- 21Centre of Fetal Medicine, Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- 22Department of Obstetrics and Gynaecology, Medical University of Vienna, 1090 Wien, Austria
- 23Department of Obstetrics and Gynaecology, American University of Beirut Medical Centre, Riad El Solh, Beirut 1107 2020, Lebanon
- 24The Egyptian IVF Centre, Maadi and Department of Obstetrics and Gynaecology, Faculty of Medicine, Cairo University, Oula, Giza, Egypt
- 25Department of Obstetrics and Gynecology, Women and Infants Hospital, Brown University Women and Infants Hospital, Providence, RI 02905, USA
- 26Royal College of Surgeons in Ireland, Rotunda Hospital, Dublin, Republic of Ireland
- 27Department of Maternal Fetal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka 594-1101, Japan
- 28Department of Obstetrics and Gynecology, University of Milano-Bicocca, 20126 Milan, Italy
- 29Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- 30Robinson Research Institute, and Discipline of Obstetrics and Gynaecology, University of Adelaide, North Adelaide SA 5006, Australia
- 31Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC 29403, USA
- 32University of Aberdeen, Dugald Baird Centre for Research on Women’s Health, Aberdeen Maternity Hospital, Aberdeen AB25 2ZL, UK
- 33Department of Obstetrics and Gynecology, Alberta Health Services, Calgary, AB T2N 2T9, Canada
- 34Australian Research Centre for Health of Women and Babies, Robinson Institute, University of Adelaide, North Adelaide, SA 5006, Australia
- 35Clinical Biostatistics Unit, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain
- 36CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Correspondence to: J Zamora
- Accepted 6 August 2016
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; I2=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; I2=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; I2=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.
We thank Stephen Wood who contributed to the acquisition of data for the work, revisions of the draft, and analysis (as a peer reviewer).
Contributors: BT and STh are joint lead authors. Substantial contribution to conception and design, acquisition, analysis, and interpretation of data for work (BT); substantial contribution to conception and design, acquisition, analysis, and interpretation of data for work and developed the review protocol (STh); substantial contribution to acquisition, analysis, interpretation of data for work (FC-S, ES, JB, KSJ, EA); substantial contribution to analysis and interpretation of data for work (DA-M, JZ); substantial contribution to acquisition of data for work (AK, KH, LL, AL, SL, JEN, JM, CAC, TJG, KM, VS, AP, LR, KW, AN, MA, DR, ET, FB, FMR, JNR, JMD, RBN, SB, STa, BWJM); performing all statistical analyses (DA-M, JZ); writing of initial drafts and revisions (FC-S); contribution to initial and critical revisions of drafts (JZ); and writing of critical revision of drafts (ES, DA-M, AK, JB, KSJ, EA, KH, LL, AL, SL, JEN, JM, CAC, TJG, KM, VS, AP, LR, KW, AN, MA, DR, ET, FB, FMR, JNR, JMD, RBN, SB, STa, BWJM, BT, STh). All authors approved the final version and agree to be accountable for all aspects of work.
Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Competing interests: 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.
Ethical approval: Not required.
Data sharing: No additional data available.
Transparency: The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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