Genetic Variants Linked to Suspected Neonatal Brain Injury from Lack of Oxygen

Kai Zucco^*
*Correspondence: Kai Zucco, Department of Cardiac Surgery, Capital Medical University, Beijing, China, Email:

Received: 02-Jan-2025, Manuscript No. ijdrt-25-163392; Editor assigned: 04-Jan-2025, Pre QC No. P-163392; Reviewed: 17-Jan-2025, QC No. Q-163392; Revised: 23-Jan-2025, Manuscript No. R-163392; Published: 31-Jan-2025, DOI: 10.37421/2277-1506.2025.14.485

Introduction

Neonatal Hypoxic-Ischemic Encephalopathy (HIE) is a serious condition caused by a lack of oxygen and blood flow to the brain during birth, leading to potential neurological damage or long-term disabilities. While birth complications are the primary cause, emerging research suggests that genetic factors may influence a newbornâ??s susceptibility to brain injury, response to oxygen deprivation, and recovery process. Understanding the genetic variants associated with suspected neonatal HIE can provide new insights into risk assessment, early diagnosis, and potential therapeutic strategies. This report explores the role of genetic factors in neonatal HIE, focusing on bioinformatics-driven studies that have identified relevant genetic variants and their potential impact on disease outcomes.

Description

Advancements in genomic research have made it possible to study the genetic predisposition to neonatal HIE using Whole-Genome Sequencing (WGS) and Whole-Exome Sequencing (WES). These technologies allow researchers to analyze millions of genetic variants in affected infants, uncovering potential genetic contributions to the severity and progression of brain injury. Studies have identified multiple gene variants linked to inflammation, oxidative stress, neuronal survival, and metabolic regulationâ??factors that play crucial roles in determining the extent of damage and recovery following hypoxia. One group of genes implicated in neonatal HIE includes those involved in the inflammatory response. Excessive inflammation following oxygen deprivation can worsen brain injury, and genetic variations in inflammatory cytokine genes may contribute to individual differences in the severity of the condition. For example, polymorphisms in the IL-6, TNF-α, and IL-1β genes have been associated with altered inflammatory responses. Variants in these genes may lead to either an exaggerated immune response that exacerbates neuronal damage or a suppressed response that affects the ability to clear damaged cells and initiate repair mechanisms. Genome-Wide Association Studies (GWAS) have identified specific Single Nucleotide Polymorphisms (SNPs) in these cytokine-related genes that correlate with increased risk or severity of neonatal HIE [1].

Oxidative stress also plays a significant role in neonatal HIE, as hypoxia leads to the overproduction of free radicals, causing cellular damage. Genetic variants in antioxidant defense genes, such as SOD2 (superoxide dismutase 2), GPX1 (glutathione peroxidase 1), and NQO1 (NAD(P)H quinone dehydrogenase 1), may influence the ability of brain cells to counteract oxidative stress. Variants that reduce the activity of these enzymes could lead to higher levels of oxidative damage in affected infants. Conversely, protective genetic variants may enhance antioxidant responses, reducing neuronal injury and improving outcomes. Neuronal survival and repair mechanisms are also genetically regulated, with several genes playing a role in neuroprotection and brain plasticity. Variants in the BDNF (brain-derived neurotrophic factor) gene, which is involved in neuronal survival and repair, have been associated with different recovery outcomes in neonatal HIE cases. Certain polymorphisms in BDNF may enhance neuroprotection, while others may impair the brainâ??s ability to recover from injury. Similarly, genes encoding heat shock proteins (HSP70, HSP27) have been investigated for their roles in protecting neurons from hypoxic damage. Variations in these genes may determine whether an infant has a stronger or weaker protective response against oxygen deprivation [2].

Metabolic genes have also been linked to neonatal HIE, as energy metabolism plays a crucial role in brain function and recovery. Mutations in genes related to mitochondrial function, such as MT-ND1, UQCRC2, and ATP5A1, can impact how efficiently cells produce energy under hypoxic conditions. Since brain cells are highly dependent on energy supply, variants that impair mitochondrial function can exacerbate neuronal injury and reduce the ability of cells to recover. This explains why some infants with similar birth complications may experience more severe neurological damage than others. One of the challenges in studying genetic variants associated with neonatal HIE is distinguishing between genetic predisposition and environmental factors. Birth complications such as placental insufficiency, umbilical cord accidents, and maternal infections play major roles in HIE occurrence, making it difficult to isolate genetic contributions. However, twin studies and familial case studies have provided valuable insights. Cases where one twin develops severe HIE while the other remains unaffected suggest that genetic factors may influence individual susceptibility. Additionally, familial clustering of neonatal HIE cases in certain populations supports the hypothesis that inherited genetic variations contribute to the risk of brain injury [3].

Machine learning and bioinformatics tools are increasingly being used to analyze large datasets of genetic information, helping researchers identify patterns that link specific variants to disease outcomes. By integrating genomic data with clinical records, researchers can develop predictive models that estimate an infantâ??s risk of severe HIE based on their genetic profile. These models could potentially be used in neonatal care settings to guide early interventions, such as targeted neuroprotective therapies or personalized treatment plans. Recent research has also explored the role of epigenetic modifications in neonatal HIE. Unlike genetic mutations, which involve permanent changes in DNA sequence, epigenetic changes such as DNA methylation and histone modifications can alter gene expression without changing the underlying DNA sequence. Studies have shown that hypoxic stress can trigger epigenetic changes in key genes involved in inflammation, oxidative stress, and neuronal survival. Understanding these epigenetic mechanisms could open new avenues for treatment, including drugs that modify gene expression to enhance brain protection and repair [4].

Despite these advancements, there are still limitations in the study of genetic variants associated with neonatal HIE. One major challenge is the genetic diversity among different populations, as many genomic studies are conducted on specific ethnic groups, limiting the generalizability of findings. More diverse studies are needed to ensure that genetic risk factors identified are relevant across different populations. Additionally, while genetic studies provide valuable insights, they cannot yet fully predict which infants will develop severe HIE, as environmental and maternal factors also play critical roles. Future research in this field aims to integrate multi-omics approaches, combining genomics, transcriptomics, proteomics, and metabolomics to gain a more comprehensive understanding of neonatal HIE. Advances in CRISPR-based gene editing may also provide potential therapeutic strategies for correcting harmful genetic variants before birth. As precision medicine continues to evolve, the hope is that genetic insights will lead to improved screening, early detection, and personalized treatment options for infants at risk of HIE [5].

Conclusion

In conclusion, genetic variants play a significant role in determining susceptibility, severity, and recovery outcomes in neonatal hypoxic-ischemic encephalopathy. While birth complications remain the primary cause, differences in genetic makeup influence how an infant responds to oxygen deprivation and whether they can effectively recover from brain injury. Advances in bioinformatics and genomic research have identified key genes involved in inflammation, oxidative stress, neuronal survival, and metabolism, shedding light on the complex interplay between genetics and neonatal brain injury. As research progresses, integrating genetic knowledge into neonatal care could lead to improved diagnosis, targeted therapies, and better long-term outcomes for affected infants.

Acknowledgement

None.

Conflict of Interest

None.

References

1. McIntyre, S., K. B. Nelson, Sarah B. Mulkey and M. Lechpammer, et al. "Neonatal encephalopathy: Focus on epidemiology and underexplored aspects of etiology." Semin Fetal Neonatal Med 26 (2021): p. 101265.

Google Scholar Cross Ref Indexed at

2. Aslam, Saima, Tammy Strickland and Eleanor J. Molloy. "Neonatal encephalopathy: Need for recognition of multiple etiologies for optimal management." Front pediatr 7 (2019): 142.

Google Scholar Cross Ref Indexed at

3. Nelson, Karin B. "Is it HIE? And why that matters." Acta Paediatr 96 (2007): 1113-1114.

Google Scholar Cross Ref Indexed at

4. Douglas-Escobar, Martha and Michael D. Weiss. "Hypoxic-ischemic encephalopathy: A review for the clinician." JAMA Pediatr 169 (2015): 397-403.

Google Scholar Cross Ref Indexed at

5. Horn, Alan R., George H. Swingler, Landon Myer and Michael C. Harrison, et al. "Defining hypoxic ischemic encephalopathy in newborn infants: Benchmarking in a South African population." J Perinat Med 41 (2013): 211-217.

Google Scholar Cross Ref Indexed at