Cerebroplacental ratio in predicting adverse perinatal outcome: a meta-analysis of individual participant data

C. A. Vollgraff Heidweiller-Schreurs; I. R. van Osch; M. W. Heymans; W. Ganzevoort; L. J. Schoonmade; C. J. Bax; B. W.J. Mol; C. J.M. de Groot; P. M.M. Bossuyt; M. A. de Boer; CPR IPD Study Group

doi:10.1111/1471-0528.16287

Cerebroplacental ratio in predicting adverse perinatal outcome: a meta-analysis of individual participant data

C. A. Vollgraff Heidweiller-Schreurs^*, I. R. van Osch, M. W. Heymans, W. Ganzevoort, L. J. Schoonmade, C. J. Bax, B. W.J. Mol, C. J.M. de Groot, P. M.M. Bossuyt, M. A. de Boer, CPR IPD Study Group

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Objective: To investigate if cerebroplacental ratio (CPR) adds to the predictive value of umbilical artery pulsatility index (UA PI) alone – standard of practice – for adverse perinatal outcome in singleton pregnancies. Design and setting: Meta-analysis based on individual participant data (IPD). Population or sample: Ten centres provided 17 data sets for 21 661 participants, 18 731 of which could be included. Sample sizes per data set ranged from 207 to 9215 individuals. Patient populations varied from uncomplicated to complicated pregnancies. Methods: In a collaborative, pooled analysis, we compared the prognostic value of combining CPR with UA PI, versus UA PI only and CPR only, with a one-stage IPD approach. After multiple imputation of missing values, we used multilevel multivariable logistic regression to develop prediction models. We evaluated the classification performance of all models with receiver operating characteristics analysis. We performed subgroup analyses according to gestational age, birthweight centile and estimated fetal weight centile. Main outcome measures: Composite adverse perinatal outcome, defined as perinatal death, caesarean section for fetal distress or neonatal unit admission. Results: Adverse outcomes occurred in 3423 (18%) participants. The model with UA PI alone resulted in an area under the curve (AUC) of 0.775 (95% CI 0.709–0.828) and with CPR alone in an AUC of 0.778 (95% CI 0.715–0.831). Addition of CPR to the UA PI model resulted in an increase in the AUC of 0.003 points (0.778, 95% CI 0.714–0.831). These results were consistent across all subgroups. Conclusions: Cerebroplacental ratio added no predictive value for adverse perinatal outcome beyond UA PI, when assessing singleton pregnancies, irrespective of gestational age or fetal size. Tweetable abstract: Doppler measurement of cerebroplacental ratio in clinical practice has limited added predictive value to umbilical artery alone.

Original language	English
Pages (from-to)	226-235
Number of pages	11
Journal	BJOG: An International Journal of Obstetrics and Gynaecology
Volume	128
Issue number	2
Early online date	8 Jun 2020
DOIs	https://doi.org/10.1111/1471-0528.16287
Publication status	Published - 1 Jan 2021

Bibliographical note

Acknowledgement
We would like thank Dr F. Figueras, Prof. E. Gratacos, Dr F. Crispi and Dr J. Miranda for sharing data for this project.
The CPR IPD Study Group: Asma Khalil (Fetal Medi- cine Unit, St George’s Hospital Medical School and St George’s University of London, London, UK; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George’s University of London, Lon- don, UK), Basky Thilaganathan (Fetal Medicine Unit, St George’s Hospital Medical School and St George’s Univer- sity of London, London, UK; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George’s University of London, London, UK), Ozhan M Turan (Departments of Obstetrics, Gynecology and Repro- ductive Sciences, University of Maryland School of Medi- cine, Baltimore, MD, USA), Sarah Crimmins (Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA), Chris Harman (Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA), Alis- son M Shannon (Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA), Sailesh Kumar (School of Medicine, The University of Queensland, Brisbane, QLD, Australia; Mater Research Institute – University of Queensland, South Brisbane, QLD, Australia), Patrick Dicker (Department of Epidemiology and Public Health, Royal College of Surgeons in Ireland), Fergal Malone (Departments of Obstetrics and Gynaecology, Royal College of Surgeons in Ireland), Elizabeth C Tully (Departments of Obstetrics and Gynaecology, Royal College of Surgeons in Ireland), Julia Unterscheider (Department of Maternal Fetal Medicine, The Royal Women’s Hospital, Melbourne, VIC, Australia), Isabella Crippa (Department of Obstetrics and Gynaecology, University of Milano-Bicocca, Monza, Italy), Alessandro Ghidini (Department of Obstetrics and Gynae- cology, University of Milano-Bicocca, Monza, Italy), Nadia Roncaglia (Department of Obstetrics and Gynaecology, University of Milano-Bicocca, Monza, Italy), Patrizia Ver- gani (Department of Obstetrics and Gynaecology, Univer- sity of Milano-Bicocca, Monza, Italy), Amarnath Bhide (Fetal Medicine Unit, St George’s Hospital Medical School and St George’s University of London, London, UK), Fran- cesco D’Antonio (Fetal Medicine Unit, St George’s Hospital Medical School and St George’s University of London, London, UK), Gianluigi Pilu (Policlinico S. Orsola-Mal- pighi, University of Bologna, Bologna, Italy), Alberto Galindo (Fetal Medicine Unit-SAMID, Department of Obstetrics and Gynaecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Com- plutense University of Madrid, Madrid, Spain), Ignacio Herraiz (Fetal Medicine Unit-SAMID, Department of Obstetrics and Gynaecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Com- plutense University of Madrid, Madrid, Spain), Alicia Vazquez-Sarandeses(FetalMedicineUnit-SAMID,Depart- ment of Obstetrics and Gynaecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Complutense University of Madrid, Madrid, Spain), Cath- rine Ebbing (Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway), Synnøve L Johnsen (Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway), Henriette O Karlsen (Research Group for Pregnancy, Fetal Develop- ment and Birth, Department of Clinical Science, University of Bergen, Bergen, Norway).

Keywords

Cerebroplacental ratio
Doppler
fetal growth restriction
individual participant data
meta-analysis
middle cerebral artery
prognostic accuracy

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Vollgraff Heidweiller-Schreurs, C. A., van Osch, I. R., Heymans, M. W., Ganzevoort, W., Schoonmade, L. J., Bax, C. J., Mol, B. W. J., de Groot, C. J. M., Bossuyt, P. M. M., de Boer, M. A., & CPR IPD Study Group (2021). Cerebroplacental ratio in predicting adverse perinatal outcome: a meta-analysis of individual participant data. BJOG: An International Journal of Obstetrics and Gynaecology, 128(2), 226-235. https://doi.org/10.1111/1471-0528.16287

Vollgraff Heidweiller-Schreurs, CA, van Osch, IR, Heymans, MW, Ganzevoort, W, Schoonmade, LJ, Bax, CJ, Mol, BWJ, de Groot, CJM, Bossuyt, PMM, de Boer, MA & CPR IPD Study Group 2021, 'Cerebroplacental ratio in predicting adverse perinatal outcome: a meta-analysis of individual participant data', BJOG: An International Journal of Obstetrics and Gynaecology, vol. 128, no. 2, pp. 226-235. https://doi.org/10.1111/1471-0528.16287

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title = "Cerebroplacental ratio in predicting adverse perinatal outcome: a meta-analysis of individual participant data",

abstract = "Objective: To investigate if cerebroplacental ratio (CPR) adds to the predictive value of umbilical artery pulsatility index (UA PI) alone – standard of practice – for adverse perinatal outcome in singleton pregnancies. Design and setting: Meta-analysis based on individual participant data (IPD). Population or sample: Ten centres provided 17 data sets for 21 661 participants, 18 731 of which could be included. Sample sizes per data set ranged from 207 to 9215 individuals. Patient populations varied from uncomplicated to complicated pregnancies. Methods: In a collaborative, pooled analysis, we compared the prognostic value of combining CPR with UA PI, versus UA PI only and CPR only, with a one-stage IPD approach. After multiple imputation of missing values, we used multilevel multivariable logistic regression to develop prediction models. We evaluated the classification performance of all models with receiver operating characteristics analysis. We performed subgroup analyses according to gestational age, birthweight centile and estimated fetal weight centile. Main outcome measures: Composite adverse perinatal outcome, defined as perinatal death, caesarean section for fetal distress or neonatal unit admission. Results: Adverse outcomes occurred in 3423 (18%) participants. The model with UA PI alone resulted in an area under the curve (AUC) of 0.775 (95% CI 0.709–0.828) and with CPR alone in an AUC of 0.778 (95% CI 0.715–0.831). Addition of CPR to the UA PI model resulted in an increase in the AUC of 0.003 points (0.778, 95% CI 0.714–0.831). These results were consistent across all subgroups. Conclusions: Cerebroplacental ratio added no predictive value for adverse perinatal outcome beyond UA PI, when assessing singleton pregnancies, irrespective of gestational age or fetal size. Tweetable abstract: Doppler measurement of cerebroplacental ratio in clinical practice has limited added predictive value to umbilical artery alone.",

keywords = "Cerebroplacental ratio, Doppler, fetal growth restriction, individual participant data, meta-analysis, middle cerebral artery, prognostic accuracy",

author = "{Vollgraff Heidweiller-Schreurs}, {C. A.} and {van Osch}, {I. R.} and Heymans, {M. W.} and W. Ganzevoort and Schoonmade, {L. J.} and Bax, {C. J.} and Mol, {B. W.J.} and {de Groot}, {C. J.M.} and Bossuyt, {P. M.M.} and {de Boer}, {M. A.} and Asma Khalil and Basky Thilaganathan and Turan, {Ozhan M.} and Sarah Crimmins and Chris Harman and Shannon, {Alisson M.} and Sailesh Kumar and Patrick Dicker and Fergal Malone and Tully, {Elizabeth C.} and Julia Unterscheider and Isabella Crippa and Alessandro Ghidini and Nadia Roncaglia and Patrizia Vergani and Amarnath Bhide and Francesco D'Antonio and Gianluigi Pilu and Alberto Galindo and Ignacio Herraiz and Alicia V{\'a}zquez-Sarandeses and Cathrine Ebbing and Johnsen, {Synn{\o}ve L.} and Karlsen, {Henriette O.} and {CPR IPD Study Group}",

note = "Acknowledgement We would like thank Dr F. Figueras, Prof. E. Gratacos, Dr F. Crispi and Dr J. Miranda for sharing data for this project. The CPR IPD Study Group: Asma Khalil (Fetal Medi- cine Unit, St George{\textquoteright}s Hospital Medical School and St George{\textquoteright}s University of London, London, UK; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George{\textquoteright}s University of London, Lon- don, UK), Basky Thilaganathan (Fetal Medicine Unit, St George{\textquoteright}s Hospital Medical School and St George{\textquoteright}s Univer- sity of London, London, UK; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George{\textquoteright}s University of London, London, UK), Ozhan M Turan (Departments of Obstetrics, Gynecology and Repro- ductive Sciences, University of Maryland School of Medi- cine, Baltimore, MD, USA), Sarah Crimmins (Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA), Chris Harman (Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA), Alis- son M Shannon (Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA), Sailesh Kumar (School of Medicine, The University of Queensland, Brisbane, QLD, Australia; Mater Research Institute – University of Queensland, South Brisbane, QLD, Australia), Patrick Dicker (Department of Epidemiology and Public Health, Royal College of Surgeons in Ireland), Fergal Malone (Departments of Obstetrics and Gynaecology, Royal College of Surgeons in Ireland), Elizabeth C Tully (Departments of Obstetrics and Gynaecology, Royal College of Surgeons in Ireland), Julia Unterscheider (Department of Maternal Fetal Medicine, The Royal Women{\textquoteright}s Hospital, Melbourne, VIC, Australia), Isabella Crippa (Department of Obstetrics and Gynaecology, University of Milano-Bicocca, Monza, Italy), Alessandro Ghidini (Department of Obstetrics and Gynae- cology, University of Milano-Bicocca, Monza, Italy), Nadia Roncaglia (Department of Obstetrics and Gynaecology, University of Milano-Bicocca, Monza, Italy), Patrizia Ver- gani (Department of Obstetrics and Gynaecology, Univer- sity of Milano-Bicocca, Monza, Italy), Amarnath Bhide (Fetal Medicine Unit, St George{\textquoteright}s Hospital Medical School and St George{\textquoteright}s University of London, London, UK), Fran- cesco D{\textquoteright}Antonio (Fetal Medicine Unit, St George{\textquoteright}s Hospital Medical School and St George{\textquoteright}s University of London, London, UK), Gianluigi Pilu (Policlinico S. Orsola-Mal- pighi, University of Bologna, Bologna, Italy), Alberto Galindo (Fetal Medicine Unit-SAMID, Department of Obstetrics and Gynaecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Com- plutense University of Madrid, Madrid, Spain), Ignacio Herraiz (Fetal Medicine Unit-SAMID, Department of Obstetrics and Gynaecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Com- plutense University of Madrid, Madrid, Spain), Alicia Vazquez-Sarandeses(FetalMedicineUnit-SAMID,Depart- ment of Obstetrics and Gynaecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Complutense University of Madrid, Madrid, Spain), Cath- rine Ebbing (Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway), Synn{\o}ve L Johnsen (Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway), Henriette O Karlsen (Research Group for Pregnancy, Fetal Develop- ment and Birth, Department of Clinical Science, University of Bergen, Bergen, Norway).",

year = "2021",

month = jan,

day = "1",

doi = "10.1111/1471-0528.16287",

language = "English",

volume = "128",

pages = "226--235",

journal = "BJOG: An International Journal of Obstetrics and Gynaecology",

issn = "1470-0328",

publisher = "John Wiley & Sons, Ltd (10.1111)",

number = "2",

}

TY - JOUR

T1 - Cerebroplacental ratio in predicting adverse perinatal outcome

T2 - a meta-analysis of individual participant data

AU - Vollgraff Heidweiller-Schreurs, C. A.

AU - van Osch, I. R.

AU - Heymans, M. W.

AU - Ganzevoort, W.

AU - Schoonmade, L. J.

AU - Bax, C. J.

AU - Mol, B. W.J.

AU - de Groot, C. J.M.

AU - Bossuyt, P. M.M.

AU - de Boer, M. A.

AU - Khalil, Asma

AU - Thilaganathan, Basky

AU - Turan, Ozhan M.

AU - Crimmins, Sarah

AU - Harman, Chris

AU - Shannon, Alisson M.

AU - Kumar, Sailesh

AU - Dicker, Patrick

AU - Malone, Fergal

AU - Tully, Elizabeth C.

AU - Unterscheider, Julia

AU - Crippa, Isabella

AU - Ghidini, Alessandro

AU - Roncaglia, Nadia

AU - Vergani, Patrizia

AU - Bhide, Amarnath

AU - D'Antonio, Francesco

AU - Pilu, Gianluigi

AU - Galindo, Alberto

AU - Herraiz, Ignacio

AU - Vázquez-Sarandeses, Alicia

AU - Ebbing, Cathrine

AU - Johnsen, Synnøve L.

AU - Karlsen, Henriette O.

AU - CPR IPD Study Group

N1 - Acknowledgement We would like thank Dr F. Figueras, Prof. E. Gratacos, Dr F. Crispi and Dr J. Miranda for sharing data for this project. The CPR IPD Study Group: Asma Khalil (Fetal Medi- cine Unit, St George’s Hospital Medical School and St George’s University of London, London, UK; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George’s University of London, Lon- don, UK), Basky Thilaganathan (Fetal Medicine Unit, St George’s Hospital Medical School and St George’s Univer- sity of London, London, UK; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George’s University of London, London, UK), Ozhan M Turan (Departments of Obstetrics, Gynecology and Repro- ductive Sciences, University of Maryland School of Medi- cine, Baltimore, MD, USA), Sarah Crimmins (Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA), Chris Harman (Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA), Alis- son M Shannon (Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA), Sailesh Kumar (School of Medicine, The University of Queensland, Brisbane, QLD, Australia; Mater Research Institute – University of Queensland, South Brisbane, QLD, Australia), Patrick Dicker (Department of Epidemiology and Public Health, Royal College of Surgeons in Ireland), Fergal Malone (Departments of Obstetrics and Gynaecology, Royal College of Surgeons in Ireland), Elizabeth C Tully (Departments of Obstetrics and Gynaecology, Royal College of Surgeons in Ireland), Julia Unterscheider (Department of Maternal Fetal Medicine, The Royal Women’s Hospital, Melbourne, VIC, Australia), Isabella Crippa (Department of Obstetrics and Gynaecology, University of Milano-Bicocca, Monza, Italy), Alessandro Ghidini (Department of Obstetrics and Gynae- cology, University of Milano-Bicocca, Monza, Italy), Nadia Roncaglia (Department of Obstetrics and Gynaecology, University of Milano-Bicocca, Monza, Italy), Patrizia Ver- gani (Department of Obstetrics and Gynaecology, Univer- sity of Milano-Bicocca, Monza, Italy), Amarnath Bhide (Fetal Medicine Unit, St George’s Hospital Medical School and St George’s University of London, London, UK), Fran- cesco D’Antonio (Fetal Medicine Unit, St George’s Hospital Medical School and St George’s University of London, London, UK), Gianluigi Pilu (Policlinico S. Orsola-Mal- pighi, University of Bologna, Bologna, Italy), Alberto Galindo (Fetal Medicine Unit-SAMID, Department of Obstetrics and Gynaecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Com- plutense University of Madrid, Madrid, Spain), Ignacio Herraiz (Fetal Medicine Unit-SAMID, Department of Obstetrics and Gynaecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Com- plutense University of Madrid, Madrid, Spain), Alicia Vazquez-Sarandeses(FetalMedicineUnit-SAMID,Depart- ment of Obstetrics and Gynaecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Complutense University of Madrid, Madrid, Spain), Cath- rine Ebbing (Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway), Synnøve L Johnsen (Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway), Henriette O Karlsen (Research Group for Pregnancy, Fetal Develop- ment and Birth, Department of Clinical Science, University of Bergen, Bergen, Norway).

PY - 2021/1/1

Y1 - 2021/1/1

N2 - Objective: To investigate if cerebroplacental ratio (CPR) adds to the predictive value of umbilical artery pulsatility index (UA PI) alone – standard of practice – for adverse perinatal outcome in singleton pregnancies. Design and setting: Meta-analysis based on individual participant data (IPD). Population or sample: Ten centres provided 17 data sets for 21 661 participants, 18 731 of which could be included. Sample sizes per data set ranged from 207 to 9215 individuals. Patient populations varied from uncomplicated to complicated pregnancies. Methods: In a collaborative, pooled analysis, we compared the prognostic value of combining CPR with UA PI, versus UA PI only and CPR only, with a one-stage IPD approach. After multiple imputation of missing values, we used multilevel multivariable logistic regression to develop prediction models. We evaluated the classification performance of all models with receiver operating characteristics analysis. We performed subgroup analyses according to gestational age, birthweight centile and estimated fetal weight centile. Main outcome measures: Composite adverse perinatal outcome, defined as perinatal death, caesarean section for fetal distress or neonatal unit admission. Results: Adverse outcomes occurred in 3423 (18%) participants. The model with UA PI alone resulted in an area under the curve (AUC) of 0.775 (95% CI 0.709–0.828) and with CPR alone in an AUC of 0.778 (95% CI 0.715–0.831). Addition of CPR to the UA PI model resulted in an increase in the AUC of 0.003 points (0.778, 95% CI 0.714–0.831). These results were consistent across all subgroups. Conclusions: Cerebroplacental ratio added no predictive value for adverse perinatal outcome beyond UA PI, when assessing singleton pregnancies, irrespective of gestational age or fetal size. Tweetable abstract: Doppler measurement of cerebroplacental ratio in clinical practice has limited added predictive value to umbilical artery alone.

AB - Objective: To investigate if cerebroplacental ratio (CPR) adds to the predictive value of umbilical artery pulsatility index (UA PI) alone – standard of practice – for adverse perinatal outcome in singleton pregnancies. Design and setting: Meta-analysis based on individual participant data (IPD). Population or sample: Ten centres provided 17 data sets for 21 661 participants, 18 731 of which could be included. Sample sizes per data set ranged from 207 to 9215 individuals. Patient populations varied from uncomplicated to complicated pregnancies. Methods: In a collaborative, pooled analysis, we compared the prognostic value of combining CPR with UA PI, versus UA PI only and CPR only, with a one-stage IPD approach. After multiple imputation of missing values, we used multilevel multivariable logistic regression to develop prediction models. We evaluated the classification performance of all models with receiver operating characteristics analysis. We performed subgroup analyses according to gestational age, birthweight centile and estimated fetal weight centile. Main outcome measures: Composite adverse perinatal outcome, defined as perinatal death, caesarean section for fetal distress or neonatal unit admission. Results: Adverse outcomes occurred in 3423 (18%) participants. The model with UA PI alone resulted in an area under the curve (AUC) of 0.775 (95% CI 0.709–0.828) and with CPR alone in an AUC of 0.778 (95% CI 0.715–0.831). Addition of CPR to the UA PI model resulted in an increase in the AUC of 0.003 points (0.778, 95% CI 0.714–0.831). These results were consistent across all subgroups. Conclusions: Cerebroplacental ratio added no predictive value for adverse perinatal outcome beyond UA PI, when assessing singleton pregnancies, irrespective of gestational age or fetal size. Tweetable abstract: Doppler measurement of cerebroplacental ratio in clinical practice has limited added predictive value to umbilical artery alone.

KW - Cerebroplacental ratio

KW - Doppler

KW - fetal growth restriction

KW - individual participant data

KW - meta-analysis

KW - middle cerebral artery

KW - prognostic accuracy

UR - http://www.scopus.com/inward/record.url?scp=85086119614&partnerID=8YFLogxK

U2 - 10.1111/1471-0528.16287

DO - 10.1111/1471-0528.16287

M3 - Article

C2 - 32363701

AN - SCOPUS:85086119614

SN - 1470-0328

VL - 128

SP - 226

EP - 235

JO - BJOG: An International Journal of Obstetrics and Gynaecology

JF - BJOG: An International Journal of Obstetrics and Gynaecology

IS - 2

ER -

Cerebroplacental ratio in predicting adverse perinatal outcome: a meta-analysis of individual participant data

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