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Survival of the littlest: improving preterm outcomes through metabolomics and microsampling
Preterm birth is a major contributor to neonatal morbidity and mortality and is associated with both acute complications and long-term health consequences. In perinatal medicine, clinicians often make treatment decisions under diagnostic uncertainty, such as during threatened preterm labor or suspected sepsis. Due to the lack of accurate diagnostic tools, interventions, including antenatal corticosteroids and empirical antibiotics, are frequently administered on suspicion. Although potentially life-saving, unnecessary exposure may influence developmental outcomes.
This thesis aimed to elucidate biological mechanisms underlying spontaneous preterm birth and late-onset sepsis in preterm babies to support more accurate and timely diagnosis. Using targeted metabolomics, inflammatory signaling molecules were investigated in pregnant women and preterm infants. Urine samples collected during threatened preterm birth and blood samples from infants with suspected sepsis revealed...
Show morePreterm birth is a major contributor to neonatal morbidity and mortality and is associated with both acute complications and long-term health consequences. In perinatal medicine, clinicians often make treatment decisions under diagnostic uncertainty, such as during threatened preterm labor or suspected sepsis. Due to the lack of accurate diagnostic tools, interventions, including antenatal corticosteroids and empirical antibiotics, are frequently administered on suspicion. Although potentially life-saving, unnecessary exposure may influence developmental outcomes.
This thesis aimed to elucidate biological mechanisms underlying spontaneous preterm birth and late-onset sepsis in preterm babies to support more accurate and timely diagnosis. Using targeted metabolomics, inflammatory signaling molecules were investigated in pregnant women and preterm infants. Urine samples collected during threatened preterm birth and blood samples from infants with suspected sepsis revealed distinct molecular signatures corresponding to different pathological processes.
Further, given the extremely limited circulating blood volume of preterm neonates, sampling approaches must accommodate stringent volume limitations while minimizing invasiveness and preserving analytical integrity. Therefore, a comprehensive review of existing microsampling techniques was conducted, and the feasibility of Volumetric Absorptive Microsampling for metabolomic analysis was evaluated. Together, these findings contribute to improving diagnostic precision while promoting scientifically rigorous and ethically responsible research in this vulnerable population.
Show less- All authors
- Thangavelu, M.U.
- Supervisor
- Hankemeier, T.; Reiss, I.K.M.
- Co-supervisor
- Wouters, B.
- Committee
- Eck, M. van; Lange, E.C.M. de; Knibbe, C.A.J.; Aerts, J.M.F.G.; Hilgendorff, A.; Kleinsmann, M.S.
- Qualification
- Doctor (dr.)
- Awarding Institution
- Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University
- Date
- 2026-02-26
- ISBN (print)
- 9789464965391