Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis.
OBJECTIVE
To determine the risks of stillbirth and neonatal complications by gestational age in uncomplicated monochorionic and dichorionic twin pregnancies.


METHODS
Systematic review and meta-analysis.


METHODS
Medline, Embase, and Cochrane databases (until December 2015).


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.


BACKGROUND
PROSPERO CRD42014007538.
Women's Health Research Unit, Barts and the London School of Medicine and Dentistry, Queen Mary University of London E1 2AB, UK.
Fiona
F
Cheong-See
Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands Department of Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, Netherlands Stanford Prevention Research Center, Stanford University, Palo Alto, Stanford, CA 94305, USA.
Ewoud
E
Schuit
Clinical Biostatistics Unit, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
David
D
Arroyo-Manzano
Fetal Medicine Unit, St George's Healthcare NHS Trust, London SW17 0QT, UK.
Asma
A
Khalil
Evaluative Clinical Sciences, Women and Babies Research Program, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
Jon
J
Barrett
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC V6Z 2K5, Canada.
K S
KS
Joseph
Department of Newborn and Developmental Paediatrics, Women and Babies Research Program, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.
Elizabeth
E
Asztalos
Department of Gynaecology and Obstetrics, Diakonessenhuis, 3582 KE Utrecht, Netherlands.
Karien
K
Hack
Department of Obstetrics-Gynaecology, University Hospitals, 3000 Leuven, Belgium Department of Development and Regeneration: Pregnancy, Fetus and Neonate, KU Leuven, Belgium.
Liesbeth
L
Lewi
Department of Obstetrics and Gynaecology, Academic Medical Centre, 1105 AZ Amsterdam, Netherlands.
Arianne
A
Lim
Department of Obstetrics and Gynaecology, Academic Medical Centre, 1105 AZ Amsterdam, Netherlands.
Sophie
S
Liem
University of Edinburgh MRC Centre for Reproductive Health, Queen's Medical Research Institute, Edinburgh EH16 4TY, UK.
Jane E
JE
Norman
Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS, USA.
John
J
Morrison
Obstetrix Collaborative Research Network, Center for Research, Education and Quality, Mednax National Medical Group, FL 33323, USA.
C Andrew
CA
Combs
Obstetrix Collaborative Research Network, Center for Research, Education and Quality, Mednax National Medical Group, FL 33323, USA University of California Irvine, Irvine, CA 92697, USA.
Thomas J
TJ
Garite
Obstetrix Collaborative Research Network, Center for Research, Education and Quality, Mednax National Medical Group, FL 33323, USA.
Kimberly
K
Maurel
Maternal-Fetal Medicine Unit, Instituto Valenciano de Infertilidad, University of Valencia, Spain Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Valencia, Jefe Servicio Obstetricia Hospital U P La FE, Torre F, Valencia, Espana.
Vicente
V
Serra
Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Valencia, Jefe Servicio Obstetricia Hospital U P La FE, Torre F, Valencia, Espana Department of Obstetrics, University Hospital La Fe, Valencia, 46026 València, Spain.
Alfredo
A
Perales
Centre of Fetal Medicine, Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Line
L
Rode
Department of Obstetrics and Gynaecology, Medical University of Vienna, 1090 Wien, Austria.
Katharina
K
Worda
Department of Obstetrics and Gynaecology, American University of Beirut Medical Centre, Riad El Solh, Beirut 1107 2020, Lebanon.
Anwar
A
Nassar
The Egyptian IVF Centre, Maadi and Department of Obstetrics and Gynaecology, Faculty of Medicine, Cairo University, Oula, Giza, Egypt.
Mona
M
Aboulghar
Department of Obstetrics and Gynecology, Women and Infants Hospital, Brown University Women and Infants Hospital, Providence, RI 02905, USA.
Dwight
D
Rouse
Royal College of Surgeons in Ireland, Rotunda Hospital, Dublin, Republic of Ireland.
Elizabeth
E
Thom
Royal College of Surgeons in Ireland, Rotunda Hospital, Dublin, Republic of Ireland.
Fionnuala
F
Breathnach
Department of Maternal Fetal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka 594-1101, Japan.
Soichiro
S
Nakayama
Department of Obstetrics and Gynecology, University of Milano-Bicocca, 20126 Milan, Italy.
Francesca Maria
FM
Russo
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Julian N
JN
Robinson
Robinson Research Institute, and Discipline of Obstetrics and Gynaecology, University of Adelaide, North Adelaide SA 5006, Australia.
Jodie M
JM
Dodd
Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC 29403, USA.
Roger B
RB
Newman
University of Aberdeen, Dugald Baird Centre for Research on Women's Health, Aberdeen Maternity Hospital, Aberdeen AB25 2ZL, UK.
Sohinee
S
Bhattacharya
Department of Obstetrics and Gynecology, Alberta Health Services, Calgary, AB T2N 2T9, Canada.
Selphee
S
Tang
Australian Research Centre for Health of Women and Babies, Robinson Institute, University of Adelaide, North Adelaide, SA 5006, Australia.
Ben Willem J
BW
Mol
Clinical Biostatistics Unit, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain javier.zamora@hrc.es.
Javier
J
Zamora
Fetal Medicine Unit, St George's Healthcare NHS Trust, London SW17 0QT, UK.
Basky
B
Thilaganathan
Women's Health Research Unit, Barts and the London School of Medicine and Dentistry, Queen Mary University of London E1 2AB, UK.
Shakila
S
Thangaratinam
D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000453:epidemiology*; D015931:Intensive Care, Neonatal / Q000706:statistics & numerical data; D066087:Perinatal Death / Q000209:etiology*; D011247:Pregnancy; D059285:Pregnancy, Twin / Q000706:statistics & numerical data*; D011446:Prospective Studies; D012307:Risk Factors; D050497:Stillbirth / Q000453:epidemiology*; D014429:Twins, Dizygotic / Q000706:statistics & numerical data; D014430:Twins, Monozygotic / Q000706:statistics & numerical data