Brain injury after single fetal demise in monochorionic twin pregnancies: an international multicentre retrospective cohort study
Abstract
Background: Single fetal demise (sFD) in monochorionic (MC) twins may lead to acute exsanguination through placental anastomoses and result in brain injury in initially surviving cotwins. We aimed to evaluate the prevalence, type, severity, and factors associated with brain injury in initially surviving cotwins after sFD.
Methods: In this international multicentre retrospective cohort study, all MC twin pregnancies complicated by sFD between 1 January 2000 and 1 January 2025 at 13 fetal therapy centres in Argentina, Belgium, Canada, Germany, Israel, Italy, the Netherlands, Spain, Sweden, and the United Kingdom were included. Pregnancies with sFD following laser surgery, selective feticide or twin anaemia-polycythaemia sequence were excluded. The primary outcome was severe brain injury in the initially surviving cotwin, assessed using all available fetal and/or neonatal neuroimaging. Severe brain injury was defined as cystic periventricular leukomalacia, multicystic encephalomalacia, migration disorders, severe ventriculomegaly or volume loss, acute hypoxic-ischaemic injury, arterial ischaemic infarction, high-grade intraventricular haemorrhage, non-punctate intraparenchymal or cerebellar haemorrhage.
Findings: A total of 395 MC pregnancies with sFD and available neuroimaging were included. Median gestational age at diagnosis of sFD was 22.7 (interquartile range [IQR] 19.3–27.1) weeks. Severe brain injury was detected in 18% (72/395) of initially surviving cotwins. The most common type was multicystic encephalomalacia in 32% (23/72). The presumed timing of severe brain injury was antenatal in 82% (59/72), perinatal in 5% (4/72), postnatal in 10% (7/72) and indeterminate in 3% (2/72) of cases. In multivariable analysis, later gestational age at sFD (adjusted odds ratio [aOR] 1.09 per week, 95% confidence interval [CI] 1.03–1.14; p = 0.001) and fetal anaemia (aOR 2.29, 95% CI 1.24–4.25; p = 0.009) were associated with severe brain injury. In liveborn infants, earlier gestational age at birth was associated with severe brain injury (p = 0.009).
Interpretation: Severe brain injury was diagnosed in one fifth of initially surviving cotwins in MC twin pregnancies after sFD and occurred predominantly antenatally, with imaging patterns consistent with hypoxic-ischaemic injury following acute exsanguination. Our findings support routine serial antenatal and postnatal neuroimaging after sFD. Earlier birth was associated with brain injury, but causality cannot be inferred because of confounding by indication. sFD alone should not prompt early delivery in clinically stable pregnancies. Prospective studies are needed to determine the optimal timing and modality of neuroimaging after sFD and evaluate management strategies including the use of intrauterine transfusion and optimal timing of delivery.
Funding: European Society for Paediatric Research (ESPR), Leids Universitair Fonds (LUF), and Gratama Stichting, Strong Babies, Honors College Leiden University Medical Center, Janivo Stichting, Gisela Thier Fonds, Raynor Cerebellar Initiatives and Vaillant Stichting.
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BibTeX
@article{rondagh2026brain,
title = {{Brain injury after single fetal demise in monochorionic twin pregnancies: an international multicentre retrospective cohort study}},
author = {Mathies Rondagh and Liesbeth Lewi and Michael Aertsen and Francesca Russo and Mariano Lanna and Daniela Casati and Andrea Righini and Shiri Shinar and Elka Miller and Laurence S. Carmant and Asma Khalil and Sara Sorrenti and Doaa Mohammed and Lotta Herling and Kajsa Bohlin and Yoav Yinon and Daphna Amitai Komem and Daniel Sanin-Ramirez and Paola Roca and Cesar H. Meller and Lucas Otaño and Javier U. Ortiz and Isabella Fabietti and Lotte C.M. Zwinkels and Femke Slaghekke and Monique C. Haak and Jeanine M.M. van Klink and Linda S. de Vries and Sophie G. Groene and Sylke J. Steggerda and Enrico Lopriore and Ana Alarcón and Mar Bennasar and Giana Izzo and Daniela Longo and Marcelo Pietrani and Borna Poljak and Sara Savelli and Irene Spektor and Federica Torracca},
journal = {eClinicalMedicine},
year = {2026},
month = oct,
doi = {10.1016/j.eclinm.2026.104290},
url = {https://linkinghub.elsevier.com/retrieve/pii/S2589537026005432},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Brain injury after single fetal demise in monochorionic twin pregnancies: an international multicentre retrospective cohort study
AU - Mathies Rondagh
AU - Liesbeth Lewi
AU - Michael Aertsen
AU - Francesca Russo
AU - Mariano Lanna
AU - Daniela Casati
AU - Andrea Righini
AU - Shiri Shinar
AU - Elka Miller
AU - Laurence S. Carmant
AU - Asma Khalil
AU - Sara Sorrenti
AU - Doaa Mohammed
AU - Lotta Herling
AU - Kajsa Bohlin
AU - Yoav Yinon
AU - Daphna Amitai Komem
AU - Daniel Sanin-Ramirez
AU - Paola Roca
AU - Cesar H. Meller
AU - Lucas Otaño
AU - Javier U. Ortiz
AU - Isabella Fabietti
AU - Lotte C.M. Zwinkels
AU - Femke Slaghekke
AU - Monique C. Haak
AU - Jeanine M.M. van Klink
AU - Linda S. de Vries
AU - Sophie G. Groene
AU - Sylke J. Steggerda
AU - Enrico Lopriore
AU - Ana Alarcón
AU - Mar Bennasar
AU - Giana Izzo
AU - Daniela Longo
AU - Marcelo Pietrani
AU - Borna Poljak
AU - Sara Savelli
AU - Irene Spektor
AU - Federica Torracca
PY - 2026
DA - 2026/10/28
JO - eClinicalMedicine
DO - 10.1016/j.eclinm.2026.104290
UR - https://linkinghub.elsevier.com/retrieve/pii/S2589537026005432
AB - Background: Single fetal demise (sFD) in monochorionic (MC) twins may lead to acute exsanguination through placental anastomoses and result in brain injury in initially surviving cotwins. We aimed to evaluate the prevalence, type, severity, and factors associated with brain injury in initially surviving cotwins after sFD. Methods: In this international multicentre retrospective cohort study, all MC twin pregnancies complicated by sFD between 1 January 2000 and 1 January 2025 at 13 fetal therapy centres in Argentina, Belgium, Canada, Germany, Israel, Italy, the Netherlands, Spain, Sweden, and the United Kingdom were included. Pregnancies with sFD following laser surgery, selective feticide or twin anaemia-polycythaemia sequence were excluded. The primary outcome was severe brain injury in the initially surviving cotwin, assessed using all available fetal and/or neonatal neuroimaging. Severe brain injury was defined as cystic periventricular leukomalacia, multicystic encephalomalacia, migration disorders, severe ventriculomegaly or volume loss, acute hypoxic-ischaemic injury, arterial ischaemic infarction, high-grade intraventricular haemorrhage, non-punctate intraparenchymal or cerebellar haemorrhage. Findings: A total of 395 MC pregnancies with sFD and available neuroimaging were included. Median gestational age at diagnosis of sFD was 22.7 (interquartile range [IQR] 19.3–27.1) weeks. Severe brain injury was detected in 18% (72/395) of initially surviving cotwins. The most common type was multicystic encephalomalacia in 32% (23/72). The presumed timing of severe brain injury was antenatal in 82% (59/72), perinatal in 5% (4/72), postnatal in 10% (7/72) and indeterminate in 3% (2/72) of cases. In multivariable analysis, later gestational age at sFD (adjusted odds ratio [aOR] 1.09 per week, 95% confidence interval [CI] 1.03–1.14; p = 0.001) and fetal anaemia (aOR 2.29, 95% CI 1.24–4.25; p = 0.009) were associated with severe brain injury. In liveborn infants, earlier gestational age at birth was associated with severe brain injury (p = 0.009). Interpretation: Severe brain injury was diagnosed in one fifth of initially surviving cotwins in MC twin pregnancies after sFD and occurred predominantly antenatally, with imaging patterns consistent with hypoxic-ischaemic injury following acute exsanguination. Our findings support routine serial antenatal and postnatal neuroimaging after sFD. Earlier birth was associated with brain injury, but causality cannot be inferred because of confounding by indication. sFD alone should not prompt early delivery in clinically stable pregnancies. Prospective studies are needed to determine the optimal timing and modality of neuroimaging after sFD and evaluate management strategies including the use of intrauterine transfusion and optimal timing of delivery. Funding: European Society for Paediatric Research (ESPR), Leids Universitair Fonds (LUF), and Gratama Stichting, Strong Babies, Honors College Leiden University Medical Center, Janivo Stichting, Gisela Thier Fonds, Raynor Cerebellar Initiatives and Vaillant Stichting.
SN - 2589-5370
ER -