Beyond Maximum Haemorrhage Grade: Serial Cranial Ultrasound Phenotyping Refines Developmental Risk Stratification...

Background/Objectives: In neonatal intensive care, intraventricular haemorrhage (IVH) is one of the most frequent brain morbidities in very preterm infants, but maximum IVH grade may not fully capture developmental risk. We assessed whether a serial cranial ultrasound (CUS) phenotype integrating IVH grade, associated parenchymal lesion visible on serial CUS (visible APL) and ventricular morbidity refined developmental risk stratification. Methods: We studied 2756 very preterm infants from a single-centre cohort of 3081 who had at least two protocolised CUS examinations. IVH was classified by maximum serial CUS grade. Visible APL, severe ventriculomegaly (VM), post-haemorrhagic hydrocephalus (PHH), cerebral palsy (CP), clinically classified school-age cognitive sequelae and sustained developmental/educational support were analysed. Results: Visible APL and ventricular morbidity increased with maximum IVH grade. Among infants with grade 3 IVH (IVH3), visible APL was present in 60.5%, severe VM in 40.8% and PHH in 21.7%. In the isolated-IVH analysis, CP occurred in 1.4% of the reference group (no IVH/no visible APL), 2.9% with isolated grade 1 IVH, 2.8% with isolated grade 2 IVH and 27.5% with IVH3. Isolated IVH3 was associated with CP (aOR 28.55, 95% CI 11.31-72.11), school-age cognitive sequelae and sustained support. After adding severe VM, the CP aOR for isolated IVH3 attenuated to 12.94, while severe VM remained associated with CP, cognitive sequelae and support. Conclusions: Our findings support interpreting IVH as a multidimensional serial CUS risk-stratification phenotype beyond maximum grade alone, with the potential to inform bedside counselling and targeted developmental follow-up in neonatal intensive care, pending external validation.