title: Pregnancy-associated plasma protein-A is positively correlated with first-trimester skin microvascular reactivity.
abstract: OBJECTIVE
  To investigate the relationship between levels of circulating maternal pregnancy-associated plasma protein-A (PAPP-A) and first-trimester maternal vascular function.
  
  
  METHODS
  This was a cross-sectional study of 53 healthy, non-smoking, nulliparous pregnant women in Stockholm, Sweden. PAPP-A levels and vascular function were assessed during gestational weeks 11-14. Forearm skin microcirculation was investigated by laser Doppler perfusion imaging during iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess endothelium-dependent and -independent microvascular vasodilatation, respectively. Microvascular endothelial function index was calculated as peak ACh/peak SNP. Endothelium-dependent and -independent vasodilatation in the brachial artery was evaluated, respectively, by postischemic hyperemia-induced flow-mediated vasodilatation (FMD) and by response to sublingual intake of glyceryl trinitrate (GTN).
  
  
  RESULTS
  PAPP-A was correlated with skin microvascular endothelial function index (β = 1.008 (95% CI, 0.34-1.68), r2= 0.17, P = 0.004). PAPP-A also correlated inversely with FMD (β = -0.052 (95% CI, -0.094 to -0.011), r2= 0.13, P = 0.014) but did not relate to forearm endothelial function index (i.e. FMD/GTN). The results were retained in multivariate analyses including known confounding factors.
  
  
  CONCLUSIONS
  First-trimester endothelium-dependent skin microvascular reactivity was positively related to PAPP-A levels. If confirmed, these novel findings suggest that first-trimester skin microvascular reactivity could be a useful early pregnancy marker of placental function. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
authors.affiliation: Division of Obstetrics and Gynecology, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: C
authors.identifier: http://orcid.org/0000-0002-6092-7743
authors.initials: C
authors.lastname: Iacobaeus
authors.affiliation: Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Kahan
authors.affiliation: Division of Medicine, Microcirculation Laboratory, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Jörneskog
authors.affiliation: Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Bremme
authors.affiliation: Division of Obstetrics and Gynecology, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Andolf
authors.affiliation: Division of Obstetrics and Gynecology, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Thorsell
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001916:Brachial Artery / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D047109:Fetal Development; D005542:Forearm / Q000098:blood supply* / Q000502:physiology; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008137:Longitudinal Studies; D008833:Microcirculation / Q000502:physiology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000502:physiology; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D037841:Pregnant People; D012867:Skin / Q000098:blood supply*; D012879:Skin Physiological Phenomena; D013548:Sweden
chemical_list: D015415:Biomarkers; D011266:Pregnancy-Associated Plasma Protein-A
keywords: endothelium; first-trimester pregnancy; microcirculation; placental circulation; pregnancy-associated plasma protein-A; vascular