Neurodevelopmental outcomes following fetal laser therapy in twin reversed arterial perfusion sequence: a current review and critical analysis

Abstract Twin reversed arterial perfusion (TRAP) sequence is one of the rarest and most complex complications of monochorionic twin pregnancies, where the pump twin perfuses an acardiac, and non-viable cotwin through artery-to-artery anastomosis. While the survival of the pump twin has traditionally been the main therapeutic goal, long-term neurodevelopmental integrity is now recognized as the true measure of success. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines to evaluate survival and neurodevelopmental outcomes after fetal intervention, with a focus on fetoscopic intrafetal laser (IFL) therapy. Extensive searches of MEDLINE, Embase, Scopus, Web of Science, Cochrane CENTRAL, and clinical trial registries were performed from 2000 through May 2025, supplemented by reference screening. Inclusion criteria included case series, cohort studies, and randomized or non-randomized trials reporting TRAP management with survival or neurodevelopmental outcomes of the pump twin. Two reviewers independently screened studies, extracted data, and assessed risk of-bias using validated tools (Not Otherwise Specified, A Measurement Tool to Assess Systematic Reviews, Version 2, Risk of Bias in Systematic reviews). Of 520 records identified, 35 studies met the eligibility criteria, of which 20 were designated as core literature for synthesis. Fetoscopic IFL consistently demonstrated high pump twin survival and showed emerging evidence of neuroprotective benefits compared with cord occlusion techniques. Radiofrequency ablation provided the most comprehensive long-term follow-up, while microwave ablation and high-intensity focused ultrasound remain exploratory. Despite encouraging results, existing neurodevelopmental data are heterogeneous and methodologically limited, underscoring the urgent need for standardized neurodevelopmental assessments, international registries, and prospective comparative trials to identify the optimal intervention strategy for the TRAP sequence.