Objective To investigate the association between periconception maternal folate status and embryonic size. Design Prospective periconception cohort study. Setting Erasmus University Medical Centre, Rotterdam, the Netherlands. Population 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. Main outcome measures 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; 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. 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.

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doi.org/10.1111/1471-0528.12592, hdl.handle.net/1765/67791
BJOG: An International Journal of Obstetrics and Gynaecology
Department of Bioinformatics

van Uitert, E. M., van Ginkel, S., Willemsen, S., Lindemans, J., Koning, A., Eilers, P., … Steegers-Theunissen, R. (2014). An optimal periconception maternal folate status for embryonic size: The Rotterdam Predict study. BJOG: An International Journal of Obstetrics and Gynaecology, 121(7), 821–829. doi:10.1111/1471-0528.12592