• Crown–rump length;
  • embryonic growth;
  • RBC folate


To investigate the association between periconception maternal folate status and embryonic size.


Prospective periconception cohort study.


Erasmus University Medical Centre, Rotterdam, the Netherlands.


Seventy-seven singleton pregnancies recruited in 2009 and 2010.


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.

Main outcome measures

Serial first-trimester CRL measurements.


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; Poverall = 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.


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.