Brain injury after single fetal demise in monochorionic twin pregnancies: an international multicentre retrospective cohort study

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.