An optimal periconception maternal folate status for embryonic size: the Rotterdam Predict study

ObjectiveTo investigate the association between periconception maternal folate status and embryonic size. DesignProspective periconception cohort study. SettingErasmus University Medical Centre, Rotterdam, the Netherlands. PopulationSeventy-seven singleton pregnancies recruited in 2009 and 2010. MethodsWe recruited women before 8weeks of gestation and performed weekly three-dimensional ultrasound scans from enrolment up to 13weeks 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 measuresSerial first-trimester CRL measurements. ResultsIn 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 (1513-1812nmol/l) was significantly associated with an increased CRL compared with the first two quartiles (814-1512nmol/l) and the upper quartile (1813-2936nmol/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 [4.1mm (95% confidence interval 3.5, 4.7) versus 5.4mm (95% confidence interval 4.8, 6.1)] and 7.6% smaller at 12(+0)weeks [55.1mm (95% confidence interval 52.9, 57.3) versus 59.6mm (95% confidence interval 57.4, 62.0)] of gestation. ConclusionsThis 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.