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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Nándor Gábor Than, Semmelweis University, Hungary
- Second opponent: Assistant Professor Janne Rossen, Sørlandet Hospital Trust, Norway
- Third member and chair of the evaluation committee: Professor Leiv Arne Rosseland, University of Oslo
Chair of the Defence
Associate Professor Tina Tellum, University of Oslo
Principal Supervisor
Professor II Meryam Sugulle, University of Oslo
Summary
Placental dysfunction is the underlying cause of major pregnancy complications, including preeclampsia, gestational hypertension, fetal growth restriction, and preterm birth. It is characterized by syncytiotrophoblast stress, which leads to dysregulated release of the angiogenic biomarkers placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) into the maternal circulation. Maternal factors, such as hyperglycemia in gestational diabetes mellitus, may further exacerbate these mechanisms.
The aim of this thesis was to investigate whether placental dysfunction, measured as levels of PlGF and sFlt-1 in the maternal circulation, is modified by fetal sex and how it relates to maternal circulating inflammatory markers linked to neutrophil extracellular traps (NETs) and deoxyribonuclease (DNase). NETs are complexes of DNA and proteins released from activated neutrophils, and DNase is an enzyme that degrades NETs. Analyses were based on two large Norwegian cohorts: 2511 pregnancies recruited at midpregnancy from the population-based PreventADALL study and 1664 pregnancies recruited prior to delivery from the Oslo Pregnancy Biobank.
The results show that pregnancies with a female fetus had lower midpregnancy PlGF and higher sFlt-1 than those with a male fetus. However, fetal sex did not influence the association between low midpregnancy maternal PlGF or sFlt-1 levels and the subsequent risk of pregnancy complications. Furthermore, the results show that levels of NETs and DNase in the maternal circulation were reduced in preeclampsia, and that NETs levels were also reduced in gestational diabetes mellitus. Lower NETs levels were associated only with placental dysfunction, measured as PlGF and sFlt-1, elevated maternal blood pressure, and reduced fetal birth weight in preeclampsia. These findings suggest a role for NETs in the placental and vascular dysfunction characteristic of preeclampsia.
Additional information
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