In children with a severe congenital heart defect, delayed brain development can begin as early as pregnancy and continues after birth until the heart surgery. That is one of the conclusions of the PhD research conducted by Maaike Nijman, a pediatric resident and researcher at UMC Utrecht, for which she was awarded her PhD on 12 June.
A severe congenital heart defect is also known as critical congenital heart disease (CCHD). Children with a severe congenital heart defect will not survive without heart surgery or cardiac catheterisation in the first few weeks of their lives. Thanks to improvements in diagnostics, surgery and intensive care, their chances of survival have increased significantly. As a result, there is also growing attention being paid to the long-term consequences.
Many children with CCHD go on to develop problems with learning, behaviour, cognitive and learning abilities, with consequences for school, social participation and quality of life. According to Maaike Nijman, these problems can arise even before birth. “We see that brain development can already be abnormal during pregnancy and that this delay increases further around the time of birth and heart surgery.”
For her research, led by Prof. Manon Benders and dr. Hans Breur, Nijman followed hundreds of children with various serious congenital heart defects. Gynaecologist and obstetrician Mireille Bekker and paediatrician Nathalie Claessens are also closely involved as co-supervisors. MRI-scans were used to map brain development during pregnancy, before surgery and after surgery. The results were compared with those of healthy children.
Researchers Maaike Nijman and Inge van Ooijen observed that brain growth in children with a severe congenital heart defect differs from that of healthy children. The differences were visible in several brain regions, including the cerebral cortex, white matter and cerebellum. The nature and severity of the growth delay varied depending on the type of heart defect.
Children with transposition of the great arteries – a condition in which the aorta and pulmonary artery are reversed – already had smaller brain volumes than healthy peers at around 30 weeks’ gestation. Abnormal growth patterns were also found in other types of severe congenital heart defects.
The final months of pregnancy and the early postnatal period are crucial for brain development. During this phase, the brain grows rapidly and key connections are formed. According to Nijman, a reduced supply of oxygen and nutrients to the brain during this period could be a key explanation for the differences observed.
The results provide important starting points for better preventing brain damage and developmental problems in this vulnerable group of children. By gaining a better understanding of when and how brain development is disrupted, doctors can take a more targeted approach to identifying protective measures during pregnancy, around the time of birth and during the treatment of the heart defect.
The thesis shows that brain development in children with severe congenital heart defects is not affected at a single point in time, but over a longer period. The researchers therefore argue that attention must be paid to the entire process: from pregnancy through to the post-operative period.
Scientists at the academic hospitals in Utrecht, Rotterdam, Nijmegen and Groningen are collaborating to investigate whether the drug Allopurinol can limit brain damage in babies with a severe congenital heart defect. This study is called the CRUCIAL trial, funded by UMC Utrecht & Wilhelmina Kinderziekenhuis Foundation. The treatment is administered immediately after birth and around the time of heart surgery, to better protect the brain against oxygen deprivation. This study started in 2020 and will run until 2027.
Maaike’s research was funded by ZonMw and carried out as part of the CHD LifeSpan programme at the Wilhelmina Children’s Hospital and UMC Utrecht. Within this programme, children with a severe congenital heart defect are monitored from pregnancy onwards, including MRI-scans of the brain and long-term developmental assessments. The aim is to better understand how heart defects influence brain development and how neurological damage can be prevented.
