title: Longer time-to-pregnancy in spontaneously conceived pregnancies is associated with lower PAPP-A and free β-hCG in first trimester screening for Down syndrome.
abstract: OBJECTIVE
  The aim of this study was to investigate whether subfertility, measured as longer time-to-pregnancy (TTP) in spontaneously conceived pregnancies, affects the first trimester levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotrophin (β-hCG) and hence the risk estimates in Down syndrome screening.
  
  
  METHODS
  The study included a cohort of 10 469 singleton pregnant women who underwent first trimester combined screening and responded to a questionnaire regarding TTP. PAPP-A and free β-hCG levels were measured between gestational week 8 + 0 and 13 + 6 and were related to TTP.
  
  
  RESULTS
  The median PAPP-A and free β-hCG MoMs were significantly lower in women with a TTP ≥24 months compared with the reference group with a TTP <6 months (PAPP-A: 0.96 vs 1.06 MoM, p = 0.003; free β-hCG: 1.04 vs 1.12 MoM, p = 0.03). This led to an increased odds for trisomy 21 risk ≥1 : 300 for TTP ≥24 months compared with TTP <6 months, but when adjusting for potential confounders, the odds ratio (OR) lost significance (OR 1.4, 95% confidence interval; 0.8-2.4).
  
  
  CONCLUSIONS
  Time-to-pregnancy ≥24 months in spontaneously conceived pregnancies is associated with decreased levels of PAPP-A and free β-hCG.
authors: Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark.
authors: I
authors: I
authors: Kirkegaard
authors: N
authors: N
authors: Uldbjerg
authors: A
authors: A
authors: Tabor
authors: T B
authors: TB
authors: Henriksen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D015331:Cohort Studies; D004314:Down Syndrome / Q000175:diagnosis; D005260:Female; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D061685:Time-to-Pregnancy
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human