Periconceptional maternal biomarkers of one-carbon metabolism and embryonic growth trajectories: the Rotterdam Periconceptional Cohort (Predict Study)

Objective: To study the associations between the periconceptional maternal biomarkers of one-carbon metabolism and embryonic growth. Design: Prospective, periconceptional hospital-based birth cohort. Setting: Tertiary medical care center. Patient(s): 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. Intervention(s): None. Main Outcome Measure(s): Maternal serum vitamin B-12 and 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. Result(s): In early pregnancy, we performed a median of five 3D-US scans (range: 1-7). Vitamin B1, concentrations were positively associated with CRL and EV measurements in the total population (CRL: beta 5(boolean AND)10(-4) (1(boolean AND)10(-4) to 9(boolean AND)10(-4)) root mm; EV: beta 2(boolean AND)10(-4) (0(boolean AND)10(-4) to 4(boolean AND)10(-4)) 3 root cm(3)) 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 gmol/L) were associated with a 1.7 mm smaller CRL (-13.4 parts per thousand) at 7 weeks and a 3.6-mm smaller CRL (-7.1 /a) at 11 weeks compared with 2 SD tHcy (-3.0 Amol/L). A high tHcy concentration was also associated with a 0.10 cm(3) smaller EV (-33.3 parts per thousand) at 7 weeks and a 1.65 cm(3) smaller EV (-16.1 parts per thousand) at 11 weeks. The embryonic growth rate was positively associated with vitamin B-12 and negatively associated with tHcy. Conclusion(s): Minor variations in periconceptional maternal concentrations of one-carbon metabolism biomarkers are associated with human embryonic growth. (C) 2016 by American Society for Reproductive Medicine.)