Early Hum Dev. 2026 Oct 7;224:106693. doi: 10.1016/j.earlhumdev.2026.106693. Online ahead of print.
ABSTRACT
Survival among children with congenital heart disease (CHD) has improved substantially with advances in prenatal screening, perioperative care and cardiac surgery. However, neurodevelopmental, cognitive-behavioural and health-related quality-of-life outcomes remain major determinants of long-term morbidity. Recent work using fetal magnetic resonance imaging (MRI), fetal cardiovascular magnetic resonance (CMR), Doppler haemodynamic assessment and placental studies suggests that CHD-related alterations in brain development do not arise solely after postnatal surgery or intensive care, but may already be present before birth. In normal fetal circulation, finely tuned coupling between the placenta, heart and brain preferentially directs oxygen-rich blood towards the cerebral and coronary circulations. Complex CHD can disrupt this streaming physiology, leading to reduced cerebral perfusion, oxygenation and metabolism. Placental dysfunction, genetic variation, inflammation and oxidative stress may further amplify heart-brain imbalance, making reduced brain volume, delayed white-matter maturation and abnormal brain-network development important intermediate phenotypes for later neurodevelopmental risk. This review discusses the normal physiology of the fetal heart-brain axis, mechanisms of fetal heart-brain-axis disruption in CHD, links with long-term outcomes, prenatal assessment tools and potential intervention strategies. We also identify key knowledge gaps and emphasise the need for multicentre longitudinal cohorts and multimodal prediction models, with the aim of shifting CHD care from cardiac repair alone towards continuous neuroprotection before and after birth.
PMID:42858691 | DOI:10.1016/j.earlhumdev.2026.106693