title: Longitudinal trends in fetoplacental biochemical markers, uterine artery pulsatility index and maternal blood pressure during the first trimester of pregnancy.
abstract: OBJECTIVE
  To assess trends in levels of biochemical markers, uterine artery (UtA) pulsatility index (PI) and maternal blood pressure changes over time and study their relationships in uncomplicated first-trimester pregnancies.
  
  
  METHODS
  The study population comprised 86 women with singleton pregnancies. In each woman, a blood sample was collected at 6-7, 8-9, 10-11 and 12-13 weeks' gestation. At the same visit blood pressure was measured and ultrasound examination was performed to measure the crown-rump length and Doppler flow velocity waveform patterns of both UtAs. Serum concentrations of pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (β-hCG), A disintegrin and metalloprotease domain-containing protein-12 (ADAM-12), placental protein-13 (PP-13) and placental growth factor (PlGF) levels were measured in thawed specimens using an automated time-resolved fluorescence assay. Summary curves were created to describe normal ranges and trends over time. The data were analyzed with a linear mixed model with the log-transformed marker values as dependent variables. This allowed for flexible modeling of patterns over time.
  
  
  RESULTS
  Sixty-eight pregnancies had an uneventful outcome, with the birth of an appropriate-for-gestational-age (AGA) infant. In these pregnancies serum PAPP-A, ADAM-12, PP-13 and PlGF levels increased with gestational age. The UtA-PI decreased and the mean arterial blood pressure remained constant. There were no significant correlations between maternal age, birth-weight percentile, gender and blood pressure and any of the biochemical markers. The serum markers were highly correlated with each other except for β-hCG. A negative correlation was found between most biomarkers and UtA-PI, especially from 10 weeks onwards. Serum concentrations of ADAM-12 and PP-13 were lower in a small-for-gestational-age (SGA) subgroup born at term (n = 6), the former statistically significantly (P = 0.031), the latter non-significantly (P = 0.054), whereas UtA-PI was significantly higher (P = 0.02). Biomarker concentrations in 12 women delivering a large-for-gestational age infant did not differ from those delivering AGA neonates.
  
  
  CONCLUSIONS
  There is a relationship between biochemical markers of early placentation and downstream resistance to flow in the UtAs in low-risk uncomplicated pregnancies, indicating differences in placentation. In a small series of SGA infants born at term we could demonstrate differences as compared to normal pregnancies, with potential value for screening.
authors.affiliation: Department of Obstetrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, The Netherlands. E.Wortelboer@umcutrecht.nl
authors.forename: E J
authors.initials: EJ
authors.lastname: Wortelboer
authors.forename: M P H
authors.initials: MP
authors.lastname: Koster
authors.forename: S
authors.initials: S
authors.lastname: Kuc
authors.forename: M J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.forename: C M
authors.initials: CM
authors.lastname: Bilardo
authors.forename: P C J I
authors.initials: PC
authors.lastname: Schielen
authors.forename: G H A
authors.initials: GH
authors.lastname: Visser
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D015992:Body Mass Index; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008423:Maternal Age; D048208:Nuchal Translucency Measurement; D021041:Placental Circulation / Q000502:physiology; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D014469:Umbilical Arteries / Q000502:physiology
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A