Study protocol of the Speech of children After Neonatal Encephalopathy (SANE): a single-centre prospective cohort study
Dora Luca Bodocs, Anett Ragó, Nelli Farkas, Andrea Lakatos, Bence Kas, Ágnes Lukács, Agnes Jermendy, Márk Hernádfői, Emma Lökkös, Norbert Kiss, János Major, Péter Hegyi, Miklós Szabó, Zsuzsanna Varga, András BánvölgyiIntroduction
Language development is a key determinant of academic achievement and psychosocial outcome. Due to the therapeutic hypothermia procedure, 75% of children diagnosed with moderate to severe neonatal encephalopathy (E) survive without serious neurological sequelae. Several studies have already revealed the overall cognitive deficits of these infants; however, their long-term language developmental specificities and their attendant neonatal risk markers remain under-investigated.
Methods and analyses
In our single-centre prospective cohort study (n≈128), we will include only those children with perinatal asphyxia who meet the stepwise criteria of the Total Body Hypothermia (TOBY) study and who survive NE without functional motor deficits and moderate/severe overall cognitive deficits at the second-year follow-up examination. The NE survivors included and cared for in the Level III Neonatal Intensive Care Unit of the Pediatric Center, Semmelweis University, Budapest, Hungary, were born between 2017 and 2022. Clinical, laboratory, electrographic and neuroimaging data will be extracted from their medical records and will be evaluated retrospectively. Patients will be followed up to assess overall cognitive and language development between 4 and 8 years. The association between neonatal biomarkers and developmental language disorder (DLD) will be analysed with binary logistic regression models. Machine learning techniques will be used to develop predictive models for DLD. For modelling the longitudinal changes between early (2 years) and later (4–8 years) cognitive and language status, mixed effects models will be applied.
Ethics and dissemination
The protocol was approved by the National Centre for Public Health and Pharmacy (NNGYK/24844-9/2025) on 21 May 2025. Results of this study will be disseminated through multiple channels. We will publish the findings in international peer-reviewed scientific journals and present them at national and international conferences.
Trial registration number