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Free thiols in maternal serum and urine for detection of fetal growth restriction

(2017) Sissingh, N.J.

Background: Oxidative stress plays a pivotal role in the pathogenesis of pregnancy complications as fetal growth restriction (FGR) and preeclampsia (PE) The level of oxidative stress can be determined by measuring free thiols, as they readily oxidize when exposed to reactive species. As the diagnostic criteria of FGR remain uncertain due to the scarcity of accurate biomarkers, the aim of this study is to assess the utility of serum and urinary free thiols to come to a non-invasive biomarker for FGR.
Methods: Free thiols were detected in patients from two case-control cohorts. In the first cohort, serum, 24-hour urine and first morning urine were derived from nine patients with FGR, eleven patients with FGR+PE, four patients with SGA and fourteen patients with a healthy grown fetus. In the second cohort, we included serum samples from ten PE patients with no FGR and fourteen matched controls. The concentrations of free thiols (μM) were determined using the Ellman’s method.
Results: The main result was that we found significantly lower concentration of serum free thiols in patients with FGR+PE as well in PE patients with no FGR, when compared to healthy controls (p=0.001, p=0.000). Patients with solely FGR had no significant depletion (p=1.000). Moreover, no significant differences were demonstrated in 24-hour urine (p=0.128) and first morning urine (p=0.481) among all groups.
Conclusion: This pilot study observed an association between PE, irrespective the presence of FGR, and lower levels of serum free thiols. This finding merits further investigations in larger cohorts, in which we recommend serum samples as the best representative. As free thiols were not aberrant in FGR, the search for early predictive biomarkers must continue.





ID 3839
Moeder ID 3463
Volgorde SissinghNJ
Naam SissinghNJ
Publiceren yes
OAI-naam Student_thesis
Path root/geneeskunde/2017/SissinghNJ/
Gemaakt op: 2018-11-23 13:19:34
Gemodificeerd op: 2018-11-23 13:19:34
Digitaal ID 5bf7fe6610e35
Afstudeerrichting opleiding/afstudeerrichting 1
Studierichting Studierichting 1
Titel Free thiols in maternal serum and urine for detection of fetal growth restriction
Ruilverkeer mogelijk no
Printen in opdracht no
Aantal pagina's 36
Publicatiejaar 2017
Taal en
Engelse samenvatting Background: Oxidative stress plays a pivotal role in the pathogenesis of pregnancy complications as fetal growth restriction (FGR) and preeclampsia (PE) The level of oxidative stress can be determined by measuring free thiols, as they readily oxidize when exposed to reactive species. As the diagnostic criteria of FGR remain uncertain due to the scarcity of accurate biomarkers, the aim of this study is to assess the utility of serum and urinary free thiols to come to a non-invasive biomarker for FGR.
Methods: Free thiols were detected in patients from two case-control cohorts. In the first cohort, serum, 24-hour urine and first morning urine were derived from nine patients with FGR, eleven patients with FGR+PE, four patients with SGA and fourteen patients with a healthy grown fetus. In the second cohort, we included serum samples from ten PE patients with no FGR and fourteen matched controls. The concentrations of free thiols (μM) were determined using the Ellman’s method.
Results: The main result was that we found significantly lower concentration of serum free thiols in patients with FGR+PE as well in PE patients with no FGR, when compared to healthy controls (p=0.001, p=0.000). Patients with solely FGR had no significant depletion (p=1.000). Moreover, no significant differences were demonstrated in 24-hour urine (p=0.128) and first morning urine (p=0.481) among all groups.
Conclusion: This pilot study observed an association between PE, irrespective the presence of FGR, and lower levels of serum free thiols. This finding merits further investigations in larger cohorts, in which we recommend serum samples as the best representative. As free thiols were not aberrant in FGR, the search for early predictive biomarkers must continue.
Nederlandse samenvatting Introductie: Oxidatieve stress speelt een cruciale rol in de pathogenese van de zwangerschapscomplicaties foetale groeirestrictie (FGR) en preeclampsie (PE). De mate van oxidatieve stress kan worden bepaald door het meten van vrije thiolen, omdat vrije thiolen gemakkelijk oxideren tijdens blootstelling aan vrije radicalen. Door het gebrek van goede biomarkers voor FGR, zijn de criteria om FGR te diagnosticeren momenteel onduidelijk. Het doel van de huidige studie is het beoordelen van de bruikbaarheid van vrije thiolen in urine en serum om tot een non-invasieve biomarker voor FGR te komen.
Methode: Vrije thiolen werden gemeten bij patiënten uit twee case-control cohorten. In het eerste cohort werd serum, 24-uurs urine en ochtendurine verzameld van negen patiënten met FGR, elf patiënten met FGR+PE, vier patiënten met SGA en veertien patiënten met een gezonde zwangerschap. In het tweede cohort werden serummonsters geïncludeerd van tien PE-patiënten zonder FGR en veertien gematchte controle patiënten. De vrije thiolen concentraties (μM) werden bepaald met behulp van de Ellman’s methode.
Resultaten: De belangrijkste bevinding is dat patiënten met zowel FGR+PE als patiënten met PE zonder FGR een significant lagere concentratie van serum vrije thiolen hadden in vergelijking met de controle patiënten (p=0.001, p=0.000). In patiënten met alléén FGR werd geen significante afname van vrije thiolen waargenomen (p=1.000). Ook werd geen significant verschil aangetoond in de 24-uurs urine (p=0.128) en de ochtendurine (p=0.481) tussen alle groepen.
Conclusie: In deze pilotstudie werd een associatie gevonden tussen PE en lagere concentraties van serum vrije thiolen, ongeacht de aanwezigheid van FGR. Deze bevinding verdient verder onderzoek, waarin wij serum samples van een grotere patiëntenpopulatie aanbevelen. Aangezien vrije thiolen niet afwijkend waren in FGR, moet de zoektocht naar vroeg voorspellende biomarkers voor FGR worden voortgezet.
Onderwijsinstelling Medical Sciences
Type embargo abstract openbaar, scriptie op aanvraag
Auteur(s) Sissingh, N.J.
UMCG begeleider(s) GordijnDr. S.J. , ¹; Goor,Prof. dr. H. van ²; Department:; ¹Department of Obstetrics and Gynaecology; ²Department of Pathology; University Medical Centre Groningen; University of Groningen
Auteur(s) Sissingh, N.J.
UMCG begeleider(s) GordijnDr. S.J. , ¹; Goor,Prof. dr. H. van ²; Department:; ¹Department of Obstetrics and Gynaecology; ²Department of Pathology; University Medical Centre Groningen; University of Groningen


 
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