title: An optimal periconception maternal folate status for embryonic size: the Rotterdam Predict study.
abstract: OBJECTIVE
  To investigate the association between periconception maternal folate status and embryonic size.
  
  
  METHODS
  Prospective periconception cohort study.
  
  
  METHODS
  Erasmus University Medical Centre, Rotterdam, the Netherlands.
  
  
  METHODS
  Seventy-seven singleton pregnancies recruited in 2009 and 2010.
  
  
  METHODS
  We recruited women before 8 weeks of gestation and performed weekly three-dimensional ultrasound scans from enrolment up to 13 weeks of gestation. As a measure of embryonic growth, crown-rump length (CRL) measurements were performed using V-Scope software in the BARCO I-Space. Maternal blood was collected to determine first-trimester long-term red blood cell (RBC) folate status. Non-malformed live births were included in the analysis. We calculated quartiles of RBC folate, square root-transformed CRL data and performed multivariable linear mixed model analyses.
  
  
  METHODS
  Serial first-trimester CRL measurements.
  
  
  RESULTS
  In total, 484 ultrasound scans were performed in 77 women, in 440 (90.7%) of which CRLs could be measured. RBC folate in the third quartile (1513-1812 nmol/l) was significantly associated with an increased CRL compared with the first two quartiles (814-1512 nmol/l) and the upper quartile (1813-2936 nmol/l; P(overall) = 0.03; adjusted for gestational age, smoking, body mass index and fetal sex). Compared with the third quartile, embryos in the upper quartile were 24.2% smaller at 6(+0) weeks [4.1 mm (95% confidence interval 3.5, 4.7) versus 5.4 mm (95% confidence interval 4.8, 6.1)] and 7.6% smaller at 12(+0) weeks [55.1 mm (95% confidence interval 52.9, 57.3) versus 59.6 mm (95% confidence interval 57.4, 62.0)] of gestation.
  
  
  CONCLUSIONS
  This study suggests that a very high maternal periconception folate status is associated with reduced embryonic size. Whether these effects are beneficial or harmful requires further investigation.
authors: Department of Obstetrics and Gynaecology, Erasmus University Medical Centre, Rotterdam, the Netherlands.
authors: E M
authors: EM
authors: van Uitert
authors: S
authors: S
authors: van Ginkel
authors: S P
authors: SP
authors: Willemsen
authors: J
authors: J
authors: Lindemans
authors: A H J
authors: AH
authors: Koning
authors: P H C
authors: PH
authors: Eilers
authors: N
authors: N
authors: Exalto
authors: J S E
authors: JS
authors: Laven
authors: E A P
authors: EA
authors: Steegers
authors: R P M
authors: RP
authors: Steegers-Theunissen
mesh_terms: D000328:Adult; D018568:Crown-Rump Length; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006801:Humans; D009426:Netherlands; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D016216:Ultrasonography, Prenatal
chemical_list: D005492:Folic Acid
keywords: Crown-rump length; RBC folate; embryonic growth