Monday, May 6, 2024
Immediately after birth, premature babies are at risk of developing sepsis. It is crucial to treat this condition promptly. A more accurate and early diagnosis is vital for survival. Manchu Thangavelu (Leiden University, co-supervised by Erasmus MC), a PhD candidate from the scientific program Medical Delta Institute of Fetal & Neonatal Care, aims to provide vulnerable newborns with a chance for a healthier start through her research on metabolic diagnostics.
This interview is the fourteenth in a series of interviews with PhD candidates and postdoctoral researchers funded by Medical Delta. Manchu's research is funded by the Medical Delta Institute of Fetal & Neonatal Care program.
What is your research about, and how did you come to focus on this topic?
“I have always had diverse interests, which led me to study various disciplines. I started with my bachelor's in electrical engineering and gained work experience in information technology, where I developed programming and software skills. My passion for biology ultimately led me to pursue a master's in biomedical engineering. It was my interest in healthcare that motivated me to pursue a PhD as part of the Medical Delta Institute of Fetal & Neonatal Care program, in a joint project between Leiden University and Erasmus MC.
At the moment, I am in the final year of my PhD, focusing on the theme of 'survival of the littlest,' to improve the lives of premature babies. Specifically, my focus is on neonatal sepsis, a life-threatening condition caused by a dysregulated immune response to an infection. Neonatal sepsis poses a serious risk, as the health of the baby can deteriorate rapidly within just a few hours if left untreated.
Neonatal sepsis poses a serious risk, as the health of the baby can deteriorate rapidly within just a few hours if left untreated
Therefore, a rapid and accurate diagnosis is crucial, but it poses a challenge for clinicians because the symptoms of neonatal sepsis often resemble those of other non-infectious inflammatory conditions. One diagnostic method is blood culture, but unfortunately, the small volume of blood samples that can be obtained from premature babies often leads to inaccurate results and culturing of pathogens takes too long for a rapid diagnosis.
Given the severity of sepsis and the time required for blood culture results, clinicians often opt to administer antibiotics to all babies suspected of having sepsis under the guise of better safe than sorry. However, this practice leads to unnecessary antibiotic use, contributing to future antibiotic resistance and other neonatal consequences such as a higher risk of obesity, allergy, or asthma.
Therefore, my research focuses on identifying biomarkers. These biomarkers may potentially aid in diagnosing neonatal sepsis in premature babies, differentiating between non-infectious inflammation and sepsis. In addition, they may provide a better understanding of the physiological processes of inflammation and sepsis, and can guide choice of drugs and prediction of treatment outcome.”
Photo: Guido Benschop
What motivates you, and what have you learned?
“The realization that my research has the potential to significantly improve the lives of the most vulnerable members of our population - premature babies - is what motivates me. The idea that my efforts, from sampling to analysis, can lead to innovative diagnostic tools and treatments for these babies, gives me a tremendous sense of motivation. It's the feeling of responsibility and purpose that keeps me driven during my research process, and I have already obtained promising results.
Using metabolomics, which involves studying small biological molecules that reflect the body's health status, I investigate plasma samples from three different groups of babies: a control group without suspicion of neonatal sepsis, a group with non-infectious inflammation, and a group diagnosed and treated for sepsis.
The initial findings appear promising: some metabolites were exclusively dysregulated in the sepsis group, allowing for early differentiation between sepsis and non-infectious inflammation. Additionally, I discovered that male and female babies seem to respond differently to neonatal sepsis, with females recovering faster and males manifesting more severe consequences. This suggests the need for gender-specific treatment approaches.
We have demonstrated the potential of metabolomics in diagnosing sepsis, laying a solid foundation for future researchers to build upon
However, the research is still in its early stages. Clinicians cannot yet utilize this technique because most sepsis analyses are conducted on adults, and that data cannot be extrapolated to this research due to the vastly different immune responses of infants. Therefore, further analysis and validation of neonates with and without sepsis are necessary before this research can be implemented in clinical practice.
Nonetheless, we have demonstrated the potential of metabolomics in diagnosing sepsis, laying a solid foundation for future researchers to build upon, and our colleagues at Erasmus MC are already collecting samples for a validation.”
What have you learned from your collaborations within the Medical Delta program?
“I have gained valuable insights and experiences. With my diverse interests, the Medical Delta environment has been particularly conducive to my growth. The conferences and meetings organized for PhD candidates and postdocs have connected me with fellow Medical Delta researchers like Chantal Eenkhoorn, who is also part of the same program. The mutual support has been invaluable; knowing that others face similar challenges fosters a sense of camaraderie. It's a two-way street - I can seek advice or opinions from my colleagues and, in return, offer assistance with tasks such as data analysis.
Furthermore, I have learned to embrace change and remain flexible within the twists and turns of a PhD research journey. Research progress is rarely linear, and setbacks are inevitable. Developing the mental resilience to accept setbacks and adapt to changing circumstances has been crucial. It was through this mindset that I discovered the potential of metabolomics, which turned out to be a significant breakthrough in my research.”
The mutual support has been invaluable; knowing that others face similar challenges fosters a sense of camaraderie
The last Interviewee, Chiara Carboni asks: are there any perspectives that were overlooked which could have led to broader interdisciplinary contributions?
“It would have been helpful to involve someone with expertise in both metabolomics and clinical practice at an early stage. This would have guided me on where to focus my research efforts, making my research direction clearer sooner. As a result, I wouldn't have needed to explore as many options to obtain meaningful results, and the link between my research findings and clinical observations could have been established more effectively.”
