title: The impact of early- and late-onset preeclampsia on umbilical cord blood cell populations.
abstract: Pregnancies complicated by preeclampsia (PE) are characterised by an enhanced maternal and fetal inflammatory response with increased numbers of leukocytes in maternal peripheral blood. The impact of PE on newborn umbilical cord blood cell (UCBC) populations however, has been scarcely studied. We hypothesise that PE deranges fetal haematopoiesis and subsequently UCBC populations. Therefore, the objective of this study was to investigate newborn umbilical cord blood cell populations in early- (EOPE) and late-onset PE (LOPE). A secondary cohort analysis in The Rotterdam Periconceptional Cohort was conducted comprising 23 PE cases, including 11 EOPE and 12 LOPE, and 195 controls, including 153 uncomplicated and 23 fetal growth restriction- and 19 preterm birth complicated controls. UCBC counts and differentials were quantified by flow cytometry and analysed as main outcome measures. Multivariable regression analysis revealed associations of EOPE with decreased leucocyte- (monocytes, neutrophils, eosinophils, immature granulocytes) and thrombocyte counts and increased NRBC counts (all p<0.05). EOPE remained associated with neutrophil- (β-0.92, 95%CI -1.27,-0.57, p<0.001) and NRBC counts (β1.11, 95%CI 0.27,1.95, p=0.010) after adjustment for gestational age and birth weight. LOPE did not reveal any significant association. We conclude that derangements of fetal haematopoiesis, in particular of neutrophil- and NRBC counts, are associated with EOPE only, with a potential impact for future health of the offspring. This heterogeneity in UCBC should be considered as confounder in epigenetic association studies examining EOPE.
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: e.herzog@erasmusmc.nl.
authors.forename: Emilie M
authors.initials: EM
authors.lastname: Herzog
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: a.eggink@erasmusmc.nl.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Eggink
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: m.vanderzee@erasmusmc.nl.
authors.forename: Marten
authors.initials: M
authors.lastname: van der Zee
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: j.lagendijk.2@erasmusmc.nl.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lagendijk
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands; Department of Biostatistics, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: s.willemsen@erasmusmc.nl.
authors.forename: Sten P
authors.initials: SP
authors.lastname: Willemsen
authors.affiliation: Department of Clinical Chemistry, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: r.dejonge@erasmusmc.nl.
authors.forename: Robert
authors.initials: R
authors.lastname: de Jonge
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: e.a.p.steegers@erasmusmc.nl.
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands; Department of Paediatrics, division of Neonatology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: r.steegers@erasmusmc.nl.
authors.forename: Regine P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000473:pathology*; D002469:Cell Separation; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D047109:Fetal Development; D005434:Flow Cytometry; D005865:Gestational Age; D006410:Hematopoiesis; D006801:Humans; D007231:Infant, Newborn; D007962:Leukocytes / Q000473:pathology*; D011225:Pre-Eclampsia / Q000276:immunology* / Q000473:pathology; D011247:Pregnancy; D014470:Umbilical Cord / Q000166:cytology; D055815:Young Adult
keywords: Fetal haematopoiesis; Gestational age; Neutrophils; Nucleated red blood cells; White blood cell count