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

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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.

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Most cited references 45

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Jose Ceriani Cernadas (1979)

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WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity

Pallavi Latthe, Manish Latthe, Lale Say … (2006)

Background Health care planning for chronic pelvic pain (CPP), an important cause of morbidity amongst women is hampered due to lack of clear collated summaries of its basic epidemiological data. We systematically reviewed worldwide literature on the prevalence of different types of CPP to assess the geographical distribution of data, and to explore sources of variation in its estimates. Methods We identified data available from Medline (1966 to 2004), Embase (1980 to 2004), PsycINFO (1887 to 2003), LILACS (1982 to 2004), Science Citation index, CINAHL (January 1980 to 2004) and hand searching of reference lists. Two reviewers extracted data independently, using a piloted form, on participants' characteristics, study quality and rates of CPP. We considered a study to be of high quality (valid) if had at least three of the following features: prospective design, validated measurement tool, adequate sampling method, sample size estimation and response rate >80%. We performed both univariate and multivariate meta-regression analysis to explore heterogeneity of results across studies. Results There were 178 studies (459975 participants) in 148 articles. Of these, 106 studies were (124259 participants) on dysmenorrhoea, 54 (35973 participants) on dyspareunia and 18 (301756 participants) on noncyclical pain. There were only 19/95 (20%) less developed and 1/45 (2.2%) least developed countries with relevant data in contrast to 22/43 (51.2%) developed countries. Meta-regression analysis showed that rates of pain varied according to study quality features. There were 40 (22.5%) high quality studies with representative samples. Amongst them, the rate of dysmenorrhoea was 16.8 to 81%, that of dyspareunia was 8 to 21.8%, and that for noncyclical pain was 2.1 to 24%. Conclusion There were few valid population based estimates of disease burden due to CPP from less developed countries. The variation in rates of CPP worldwide was due to variable study quality. Where valid data were available, a high disease burden of all types of pelvic pain was found.

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Stillbirths: recall to action in high-income countries.

Vicki Flenady, Aleena M. Wojcieszek, Philippa Middleton … (2016)

Variation in stillbirth rates across high-income countries and large equity gaps within high-income countries persist. If all high-income countries achieved stillbirth rates equal to the best performing countries, 19,439 late gestation (28 weeks or more) stillbirths could have been avoided in 2015. The proportion of unexplained stillbirths is high and can be addressed through improvements in data collection, investigation, and classification, and with a better understanding of causal pathways. Substandard care contributes to 20-30% of all stillbirths and the contribution is even higher for late gestation intrapartum stillbirths. National perinatal mortality audit programmes need to be implemented in all high-income countries. The need to reduce stigma and fatalism related to stillbirth and to improve bereavement care are also clear, persisting priorities for action. In high-income countries, a woman living under adverse socioeconomic circumstances has twice the risk of having a stillborn child when compared to her more advantaged counterparts. Programmes at community and country level need to improve health in disadvantaged families to address these inequities.

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Author and article information

Contributors

Fiona Cheong-See: Role: clinical research fellow

Ewoud Schuit: Role: postdoctoral research fellow

David Arroyo-Manzano: Role: biostatistician

Asma Khalil: Role: consultant obstetrician

Jon Barrett: Role: senior scientist

K S Joseph: Role: professor of obstetrics and gynaecology

Elizabeth Asztalos: Role: associate professor

Karien Hack: Role: in obstetrics and gynaecology

Liesbeth Lewi: Role: assistant professor in obstetrics and gynaecology

Arianne Lim: Role: gynaecologist

Sophie Liem: Role: MD in obstetrics and gynaecology

Jane E Norman: Role: professor of maternal and fetal health

John Morrison: Role: professor of obstetrics and gynaecology and paediatrics

C Andrew Combs: Role: associate director of research

Thomas J Garite: Role: director of research and education, professor emeritus of obstetrics and gynaecology

Kimberly Maurel: Role: associate director

Vicente Serra: Role: professor of obstetrics and gynaecology

Alfredo Perales: Role: professor of obstetrics and gynaecology

Line Rode: Role: senior resident

Katharina Worda: Role: specialist in obstetrics and gynaecology

Anwar Nassar: Role: professor of obstetrics and gynaecology

Mona Aboulghar: Role: professor of obstetrics and gynaecology

Dwight Rouse: Role: principal investigatorRole: professor of obstetrics and gynaecology

Elizabeth Thom: Role: research professor of biostatistics and epidemiology

Fionnuala Breathnach: Role: consultant obstetrician and gynaecologist, senior lecturer in maternal fetal medicine

Soichiro Nakayama: Role: assistant professor

Francesca Maria Russo: Role: MD in obstetrics and gynaecology

Julian N Robinson: Role: chief of obstetrics and associate professor

Jodie M Dodd: Role: professor of obstetrics and gynaecology

Roger B Newman: Role: professor and Maas chair for reproductive sciences

Sohinee Bhattacharya: Role: senior lecturer

Selphee Tang: Role: data analyst

Ben Willem J Mol: Role: professor of obstetrics and gynaecology

Javier Zamora: Role: senior lecturer, head of clinical biostatistics unit, director of clinical epidemiology research area

Basky Thilaganathan: Role: professor and director of fetal medicine

Shakila Thangaratinam: Role: professor of maternal and perinatal health

Journal

Journal ID (nlm-ta): BMJ

Journal ID (iso-abbrev): BMJ

Journal ID (publisher-id): bmj

Title: The BMJ

Publisher: BMJ Publishing Group Ltd.

ISSN (Print): 0959-8138

ISSN (Electronic): 1756-1833

Publication date Collection: 2016

Publication date (Electronic): 6 September 2016

Volume: 354

Electronic Location Identifier: i4353

Affiliations

[1 ]Women’s Health Research Unit, Barts and the London School of Medicine and Dentistry, Queen Mary University of London E1 2AB, UK

[2 ]Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands

[3 ]Department of Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, Netherlands

[4 ]Stanford Prevention Research Center, Stanford University, Palo Alto, Stanford, CA 94305, USA

[5 ]Clinical Biostatistics Unit, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain

[6 ]Fetal Medicine Unit, St George’s Healthcare NHS Trust, London SW17 0QT, UK

[7 ]Evaluative Clinical Sciences, Women and Babies Research Program, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada

[8 ]Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC V6Z 2K5, Canada

[9 ]Department of Newborn and Developmental Paediatrics, Women and Babies Research Program, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada

[10 ]Department of Gynaecology and Obstetrics, Diakonessenhuis, 3582 KE Utrecht, Netherlands

[11 ]Department of Obstetrics-Gynaecology, University Hospitals, 3000 Leuven, Belgium

[12 ]Department of Development and Regeneration: Pregnancy, Fetus and Neonate, KU Leuven, Belgium

[13 ]Department of Obstetrics and Gynaecology, Academic Medical Centre, 1105 AZ Amsterdam, Netherlands

[14 ]University of Edinburgh MRC Centre for Reproductive Health, Queen’s Medical Research Institute, Edinburgh EH16 4TY, UK

[15 ]Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS, USA

[16 ]Obstetrix Collaborative Research Network, Center for Research, Education and Quality, Mednax National Medical Group, FL 33323, USA

[17 ]University of California Irvine, Irvine, CA 92697, USA

[18 ]Maternal-Fetal Medicine Unit, Instituto Valenciano de Infertilidad, University of Valencia, Spain

[19 ]Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Valencia, Jefe Servicio Obstetricia Hospital U P La FE, Torre F, Valencia, Espana

[20 ]Department of Obstetrics, University Hospital La Fe, Valencia, 46026 València, Spain

[21 ]Centre of Fetal Medicine, Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

[22 ]Department of Obstetrics and Gynaecology, Medical University of Vienna, 1090 Wien, Austria

[23 ]Department of Obstetrics and Gynaecology, American University of Beirut Medical Centre, Riad El Solh, Beirut 1107 2020, Lebanon

[24 ]The Egyptian IVF Centre, Maadi and Department of Obstetrics and Gynaecology, Faculty of Medicine, Cairo University, Oula, Giza, Egypt

[25 ]Department of Obstetrics and Gynecology, Women and Infants Hospital, Brown University Women and Infants Hospital, Providence, RI 02905, USA

[26 ]Royal College of Surgeons in Ireland, Rotunda Hospital, Dublin, Republic of Ireland

[27 ]Department of Maternal Fetal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka 594-1101, Japan

[28 ]Department of Obstetrics and Gynecology, University of Milano-Bicocca, 20126 Milan, Italy

[29 ]Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

[30 ]Robinson Research Institute, and Discipline of Obstetrics and Gynaecology, University of Adelaide, North Adelaide SA 5006, Australia

[31 ]Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC 29403, USA

[32 ]University of Aberdeen, Dugald Baird Centre for Research on Women’s Health, Aberdeen Maternity Hospital, Aberdeen AB25 2ZL, UK

[33 ]Department of Obstetrics and Gynecology, Alberta Health Services, Calgary, AB T2N 2T9, Canada

[34 ]Australian Research Centre for Health of Women and Babies, Robinson Institute, University of Adelaide, North Adelaide, SA 5006, Australia

[35 ]Clinical Biostatistics Unit, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain

[36 ]CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain

Author notes

Correspondence to: J Zamora javier.zamora@ 123456hrc.es

Article

Publisher ID: chef027508

DOI: 10.1136/bmj.i4353

PMC ID: 5013231

PubMed ID: 27599496

SO-VID: 1cec9d07-d003-4cf3-b9a2-b0deaeaa620f

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This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

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

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Pediatric Pulse: Advancing Neonatal and Child Health

Most cited references 45

PEDIATRICS

WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity

Stillbirths: recall to action in high-income countries.

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