Preterm Papers
1. Selvanathan T, Ufkes S, Guo T, Chau V, Branson HM, Ibrahim GM, Ly LG, Kelly E, Grunau RE, Miller SP. Pain exposure and brain connectivity in preterm infants. JAMA Netw Open. 2024 Mar 4;7(3). doi: 10.1001/jamanetworkopen.2024.2551. PubMed PMID: 38488791; PubMed Central PMCID: PMC10943417.
Researchers have found that the amount of pain very preterm infants experience shortly after birth can affect how their brains develop and their cognitive abilities at 18 months. This study looked at 193 infants born very prematurely, focusing on 150 who had brain scans and 123 whose development was assessed later.
They discovered that more pain from medical procedures was linked to slower brain development, especially in female infants. These brain changes were measured using MRI scans that showed how different parts of the brain are connected to each other. Infants with more pain exposure showed less efficient brain connections.
When the researchers checked the children’s development at 18 months, they found that those with less efficient brain connections tended to score lower on cognitive tests. This study highlights the importance of minimizing pain in preterm infants to support better brain development and cognitive outcomes.
2. Selvanathan T, Guo, T, Ufkes S, Chau V, Branson HM, Synnes AR, Linh LG, Kelly EN, Grunau RE, Miller SP. Size and location of preterm brain injury and associations with neurodevelopmental outcomes. Neurology. 2024 Apr 23;102(8). doi: 10.1212/WNL.0000000000209264. Epub 2024 Mar 25. PubMed PMID: 38527245.
This study explored how brain injuries in very preterm infants — those born before 32 weeks of pregnancy — affect their development by the time they are 18 months old. Researchers looked at 254 infants and used MRI scans to measure the size and location of brain injuries, such as white matter injury (WMI) and periventricular hemorrhagic infarction (PVHI). They also considered the mothers' education levels as a marker of socioeconomic status.
The study found that larger areas of brain injury were linked to poorer motor skills at 18 months. Specifically, injuries in the central and parietal areas of the brain were associated with lower motor scores. On the other hand, higher maternal education was associated with better cognitive outcomes, suggesting that socioeconomic factors also play a role in the child's development.
These findings emphasize that both the size and location of brain injuries can help predict which infants may face greater challenges with motor skills. However, these findings also highlight the importance of socioeconomic factors in promoting a child’s overall cognitive development.
3. Selvanathan T, Au-Young SH, Guo T, Chau V, Branson HM, Synnes AR, Ly LG, Kelly EN, Grunau RE, Miller SP. Major surgery, brain injury and neurodevelopmental outcomes in very preterm infants. Neurology. 2023 Nov; 101(21):952-957. PMID 37821234.
This study explored how major surgeries impact brain injury and development in very preterm infants. Researchers followed 294 infants who had early-life and term-equivalent age MRI scans to check for brain injury and assessed their development at 18 months.
They found that infants who underwent major surgery were more likely to have brain injury and poorer motor skills at 18 months. The study also revealed that brain injury worsened the effect of major surgery on motor skills, meaning infants who had both major surgery and brain injury had the lowest motor scores.
These findings suggest that very preterm infants who require major surgery are also at higher risk for brain injury and poorer motor development. The study recommends regular brain scans and close monitoring of development for these infants to better manage their care and outcomes.
4. Cayam-Rand, D., Guo, T., Grunau, R. E., Benavente-Fernández, I., Synnes, A., Chau, V., Branson, H., Latal, B., McQuillen, P., & Miller, S. P. (2019). Predicting developmental outcomes in preterm infants: A simple white matter injury imaging rule. Neurology, 93(13), e1231–e1240. doi.org/10.1212/WNL.0000000000008172
This study aimed to develop a straightforward method for predicting development in school-age children who were very preterm infants with brain white matter injury (WMI). Researchers used early brain scans from 68 preterm babies born between 24 and 32 weeks of pregnancy to assess the location of WMI. They found that the location of this injury in the brain could predict whether a child would have cognitive or motor difficulties at 4.5 years old.
The study showed that simply looking at where WMI is located in the brain could accurately predict 90% of cognitive outcomes and 85% of motor outcomes. Adding other clinical factors, such as bleeding in the brain, lung disease, and eye problems, improved the accuracy of these predictions even more.
The researchers validated their findings with another group of children, confirming that this imaging rule is a useful tool for predicting developmental outcomes in preterm infants. This method helps identify which children might need extra support early on, based on their early brain scans and clinical factors.
5. Cayam-Rand, D., Guo, T., Synnes, A., Chau, V., Mabbott, C., Benavente-Fernández, I., Grunau, R. E., & Miller, S. P. (2021). Interaction between Preterm White Matter Injury and Childhood Thalamic Growth. Annals of Neurology, 90(4), 584–594. doi.org/10.1002/ana.26201
This study investigated how brain injury in very preterm infants affects the growth of a key brain region called the thalamus and how this, in turn, impacts their development by age 8. Researchers followed 114 preterm children who had brain scans early in life and at 8 years old to track changes in thalamic volume and assess cognitive, motor, and visual-motor skills.
They found that the growth of the thalamus during early childhood was influenced by the extent of white matter injury (WMI) seen in preterm infants, as well as other factors like gestational age and sex. Children with more WMI tended to have smaller thalamic volumes by school age. Moreover, the interaction between WMI and the development of thalamic pathways (measured by fractional anisotropy) predicted cognitive and motor outcomes.
In summary, the study revealed that both early brain injury and thalamic growth are important for understanding long-term developmental outcomes. It suggests that evaluating multiple aspects of brain injury and growth can provide a better picture of how preterm birth affects a child's future development.
6. Duerden, E. G., Guo, T., Chau, C., Chau, V., Synnes, A., Grunau, R. E., & Miller, S. P. (2023). Association of Neonatal Midazolam Exposure With Hippocampal Growth and Working Memory Performance in Children Born Preterm. Neurology, 101(19), e1863–e1872. doi.org/10.1212/WNL.0000000000207817
This study investigated the impact of early exposure to midazolam, a commonly used sedative in neonatal intensive care, on brain development and memory in preterm children. The researchers focused on the hippocampus, a brain region crucial for learning and memory.
The study included 140 preterm children who were 8 years old. Of these, 25 had been given midazolam shortly after birth. The researchers used MRI scans to measure the size of the hippocampus and its subfields and assessed the children's cognitive abilities using intelligence tests.
They found that children exposed to midazolam had smaller hippocampal volumes at age 8 compared to those who were not exposed. This effect was particularly pronounced in boys and was linked to lower working memory scores. The study also found that higher doses of midazolam were associated with smaller volumes in the subiculum, a part of the hippocampus involved in memory.
These findings suggest that early exposure to midazolam may negatively impact hippocampal development and memory skills, especially in boys. The study highlights the need for careful consideration of sedation practices in neonatal care to mitigate potential long-term effects on brain development.
Cardiac Papers
1. Lee FT, Sun L, van Amerom JFP, Portnoy S, Marini D, Saini A, Milligan N, Lim JM, Saini B, Selvanathan T, Kazazian V, Sananes R, Jaeggi E, Kingdom JC, Macgowan CK, Ly L, Chau V, Miller SP, Seed M. Fetal Hemodynamics, Early Survival, and Neurodevelopment in Patients With Cyanotic Congenital Heart Disease. J Am Coll Cardiol. 2024 Apr 2;83(13):1225-1239. doi: 10.1016/j.jacc.2024.02.005. Epub 2024 Mar 25. PMID: 38538202.
This study explored how blood flow and oxygen levels in fetuses with the most serious forms of (cyanotic) congenital heart disease (CHD) impact their survival and development. Researchers used advanced imaging techniques to measure blood flow and oxygen in the fetuses and tracked their outcomes up to 18 months after birth.
They found that fetuses with lower blood flow and oxygen delivery in the brain were more likely to die or have developmental challenges. Specifically, reduced blood flow in the superior vena cava (SVC), a major vein that carries blood to the heart, was strongly linked to poorer cognitive, language, and motor skills at 18 months. This measure of blood flow was more accurate in predicting developmental delays than other methods.
The study highlights the importance of using fetal imaging to assess blood flow and oxygen levels, as this can help identify which babies are at higher risk for poor outcomes and may need more intensive monitoring and care.
2. Peyvandi S, Xu D, Barkovich AJ, Gano D, Chau V, Reddy VM, Selvanathan T, Guo T, Gaynor JW, Seed M, Miller SP, McQuillen P. Declining Incidence of Postoperative Neonatal Brain Injury in Congenital Heart Disease. J Am Coll Cardiol. 2023 Jan 24;81(3):253-266. doi: 10.1016/j.jacc.2022.10.029. PMID: 36653093; PMCID: PMC10548869.
This study looked at how brain injuries in newborns with complex congenital heart disease (CHD) have changed over the past 20 years. Researchers analyzed brain scans from 270 newborns who underwent heart surgery between 2001 and 2021.
They found that while the rate of brain injury before surgery remained steady, the incidence of new brain injuries after surgery has decreased significantly. Specifically, the likelihood of developing new brain injury after surgery dropped from 24% to 6% over the study period. This improvement is likely due to better management of blood pressure in the first 24 hours after surgery, which helps maintain healthy blood flow to the brain.
These findings highlight the progress made in reducing brain injuries in newborns with CHD and suggest that maintaining optimal blood pressure after surgery is crucial for protecting brain health.
3. Selvanathan T, Mabbott C, Au-Young SH, Seed M, Miller SP, Chau V; PCNR Study Group. Antenatal diagnosis, neonatal brain volumes, and neurodevelopment in transposition of the great arteries. Dev Med Child Neurol. 2024 Jan; 10.1111/dmcn.15840.
This study investigated how diagnosing a serious heart condition called transposition of the great arteries (TGA) before birth affects brain development and cognitive outcomes in children by 18 months old. Researchers looked at 139 children with TGA, comparing those diagnosed before birth to those diagnosed after birth. They measured brain volumes using MRI scans before and after heart surgery and assessed cognitive development at 18 months.
They found that children diagnosed before birth generally had better cognitive outcomes. Specifically, smaller brain volumes were linked to lower cognitive scores in children diagnosed after birth, but this link was weaker in children who were diagnosed before birth. This suggests that an early diagnosis of TGA might help protect brain development, potentially due to better pre-surgery care.
The study highlights the importance of early diagnosis in improving outcomes for children with TGA and suggests that improving antenatal diagnosis rates could be beneficial for their brain health and development.