title: Periconceptional maternal biomarkers of one-carbon metabolism and embryonic growth trajectories: the Rotterdam Periconceptional Cohort (Predict Study).
abstract: OBJECTIVE
  To study the associations between the periconceptional maternal biomarkers of one-carbon metabolism and embryonic growth.
  
  
  METHODS
  Prospective, periconceptional hospital-based birth cohort.
  
  
  METHODS
  Tertiary medical care center.
  
  
  METHODS
  Between 2010 and 2014, 236 women with early singleton ongoing pregnancies that resulted in 139 strictly dated spontaneous pregnancies and 97 pregnancies conceived after assisted reproductive technology.
  
  
  METHODS
  None.
  
  
  METHODS
  Maternal serum vitamin B12and plasma total homocysteine (tHcy) assessed at enrollment, and longitudinal first-trimester crown-rump length (CRL), embryonic volume (EV), and absolute growth rates obtained via three-dimensional ultrasound (3D-US) and virtual reality.
  
  
  RESULTS
  In early pregnancy, we performed a median of five 3D-US scans (range: 1-7). Vitamin B12concentrations were positively associated with CRL and EV measurements in the total population (CRL: β 5ˆ10-4(1ˆ10-4to 9ˆ10-4) √mm; EV: β 2ˆ10-4(0ˆ10-4to 4ˆ10-4)3√cm3) and in the strictly dated spontaneous pregnancy subgroup. The tHcy concentration was negatively associated with embryonic growth in all study groups. High tHcy concentrations (+2 standard deviation [SD], 10.3 μmol/L) were associated with a 1.7 mm smaller CRL (-13.4%) at 7 weeks and a 3.6-mm smaller CRL (-7.1%) at 11 weeks compared with -2 SD tHcy (-3.0 μmol/L). A high tHcy concentration was also associated with a 0.10 cm3smaller EV (-33.3%) at 7 weeks and a 1.65 cm3smaller EV (-16.1%) at 11 weeks. The embryonic growth rate was positively associated with vitamin B12and negatively associated with tHcy.
  
  
  CONCLUSIONS
  Minor variations in periconceptional maternal concentrations of one-carbon metabolism biomarkers are associated with human embryonic growth.
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.
authors.forename: Francesca
authors.initials: F
authors.lastname: Parisi
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.
authors.forename: Melek
authors.initials: M
authors.lastname: Rousian
authors.affiliation: Department of Bioinformatics, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.
authors.forename: Anton H J
authors.initials: AH
authors.lastname: Koning
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands; Department of Biostatistics, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.
authors.forename: Sten P
authors.initials: SP
authors.lastname: Willemsen
authors.affiliation: Centre for Fetal Research Giorgio Pardi, Department of Biomedical and Clinical Sciences, Hospital Luigi Sacco, Università degli Studi di Milano, Milan, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Cetin
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands; Department of Pediatrics, Division of Neonatology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands. Electronic address: r.steegers@erasmusmc.nl.
authors.forename: Régine P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002244:Carbon / Q000378:metabolism*; D018568:Crown-Rump Length; D047108:Embryonic Development; D005260:Female; D005298:Fertility; D006710:Homocysteine / Q000097:blood; D006801:Humans; D021621:Imaging, Three-Dimensional; D007246:Infertility / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D009426:Netherlands; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011379:Prognosis; D011446:Prospective Studies; D027724:Reproductive Techniques, Assisted; D062606:Tertiary Care Centers; D016216:Ultrasonography, Prenatal / Q000379:methods; D014805:Vitamin B 12 / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D002244:Carbon; D014805:Vitamin B 12
keywords: Crown-rump length; embryonic volume; homocysteine; maternal one-carbon metabolism; virtual reality